Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission

Shiv K. Sarin, Manoj Kumar, Mohammed Eslam, Jacob George, Mamun Al Mahtab, Sheikh M.Fazle Akbar, Jidong Jia, Qiuju Tian, Rakesh Aggarwal, David H. Muljono, Masao Omata, Yoshihiko Ooka, Kwang Hyub Han, Hye W. Lee, Wasim Jafri, Amna S. Butt, Chern H. Chong, Seng G. Lim, Raoh Fang Pwu, Ding Shinn Chen

Research output: Contribution to journalReview articlepeer-review

23 Citations (Scopus)

Abstract

The Asia-Pacific region is home to more than half of the global population and accounted for 62·6% of global deaths due to liver diseases in 2015. 54·3% of global deaths due to cirrhosis, 72·7% of global deaths due to hepatocellular carcinoma, and more than two-thirds of the global burden of acute viral hepatitis occurred in this region in 2015. Chronic hepatitis B virus (HBV) infection caused more than half of the deaths due to cirrhosis in the region, followed by alcohol consumption (20·8%), non-alcoholic fatty liver disease (NAFLD; 12·1%), and chronic infection with hepatitis C virus (HCV; 15·7%). In 2015, HBV accounted for about half the cases of hepatocellular carcinoma in the region. Preventive strategies for viral hepatitis-related liver disease include increasing access to clean drinking water and sanitation. HBV vaccination programmes for neonates have been implemented by all countries, although birth-dose coverage is extremely suboptimal in some. Availability of screening tests for blood and tissue, donor recall policies, and harm reduction strategies are in their initial stages in most countries. Many governments have put HBV and HCV drugs on their essential medicines lists and the availability of generic versions of these drugs has reduced costs. Efforts to eliminate viral hepatitis as a public health threat, together with the rapid increase in per-capita alcohol consumption in countries and the epidemic of obesity, are expected to change the spectrum of liver diseases in the Asia-Pacific region in the near future. The increasing burden of alcohol-related liver diseases can be contained through government policies to limit consumption and promote less harmful patterns of alcohol use, which are in place in some countries but need to be enforced more strictly. Steps are needed to control obesity and NAFLD, including policies to promote healthy lifestyles and regulate the food industry. Inadequate infrastructure and insufficient health-care personnel trained in liver diseases are issues that also need to be addressed in the Asia-Pacific region. The policy response of most governments to liver diseases has thus far been inadequate and poorly funded. There must be a renewed focus on prevention, early detection, timely referral, and research into the best means to introduce and improve health interventions to reduce the burden of liver diseases in the Asia-Pacific region.

Original languageEnglish
Pages (from-to)167-228
Number of pages62
JournalThe Lancet Gastroenterology and Hepatology
Volume5
Issue number2
DOIs
Publication statusPublished - 2020 Feb

Bibliographical note

Funding Information:
DHM thanks Pretty Multiharina Sasono, Wiendra Waworuntu, Naning Nugrahini, Sedya Dwisangka, and all staff of Sub-directorate of Hepatitis and Gastrointestinal Infection, Directorate General of Communicable Diseases, Ministry of Health, Indonesia, for providing data and discussions. SGL thanks Benjamin Ong, for reviewing the manuscript. ME and JG are supported by the Robert W Storr bequest to the Sydney Medical Foundation (University of Sydney, Sydney, Australia) and National Health and Medical Research Council of Australia (NHMRC) programme grant (1053206) and project grants (APP1107178 and APP1108422). MK and SKS thank Guresh Kumar (Institute of Liver and Biliary Sciences, New Delhi, India) for help in statistical analysis and figures. Editorial note: The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations.

Funding Information:
According to World Bank data, 241 the Chinese economy is the second largest in the world in nominal terms, might be the largest by purchasing power parity (PPP) as of 2013, and was the sixth fastest-growing major economy in the world, with a growth rate of 6·7% in 2016. 242 The per-capita gross national income (GNI) in 2012 was US$ 10 890 in PPP terms. 243 The country's health-care expenditure (about 5·55% of gross domestic product [GDP] in 2014) compares well with other similarly-placed countries. 244 In 2009, the Government launched an ambitious health-care reform initiative and by 2015, 95% of the population had health insurance. 245 Antiviral drugs for HBV, including conventional and pegylated interferons, entecavir, tenofovir, lamivudine, adefovir, and telbivudine, have been on the national reimbursement list since early 2017 (see for the status of policies and interventions against viral hepatitis in China). Direct-acting antiviral drugs against HCV, such as simeprevir, asunaprevir, daclatasvir, sofosbuvir, velpatasvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir, elbasvir, and grazoprevir have been approved and are already on the reimbursement lists in some provinces. table 3 The public health system of mainland China consists of national and local Centers for Disease Control and Prevention and has functioned well in the prevention of viral hepatitis, with current coverage and timely free universal vaccination of infants against HBV exceeding 90%. China has released national action plans for control of viral hepatitis that set clear targets on prevention. However, a specific, large-scale, test-and-treat financed programme for patients with chronic hepatitis B or C is still to be established. Guidelines for prevention and control of hepatitis B and hepatitis C have been published and are regularly updated, with most recommendations in line with the major international guidelines. 246,247 To facilitate clinical research and evidence-based decision making for clinical practice and public health, a nationwide hospital-based registry for patients with chronic hepatitis B was initiated in 2012, which might prove to be essential to investigate disease burden and long-term outcomes in patients with chronic hepatitis B in a real-world setting. 248 Many aspects of alcohol policy are weaker in China than in its neighbouring countries ( ). For example, China has no enforceable legal drinking age and does not regulate when or where alcoholic products are sold. An advertising regulation on alcoholic beverages was issued in 1995, but its enforcement has also been weak. Moreover, taxation in China has not been used to improve public health. Few treatment programmes are available in China for people with alcohol use disorders. Although some psychiatric hospitals in China have special addiction units for the treatment of patients with alcohol-related mental disorders, most of these units, which were established in the 1990s, are in major cities. table 4 181 In an effort to tackle obesity and NAFLD from an early age, the Chinese Government has launched several public health campaigns, including Happy 10 Minutes, which encourages schoolchildren to have daily 10-min breaks for exercise ( ). However, these strategies have paid seemingly little, if any, attention to diet. The Chinese Government's attempts to tackle obesity are being supported by several large multinational food companies, including the Coca-Cola Company, PepsiCo, and Nestlé. table 5 249 These companies fund a non-profit research organisation, the International Life Sciences Institute (ILSI), originally established in the USA in 1978 by a Coca-Cola executive. For several decades, ILSI–China has led public health initiatives emphasising the importance of exercise and physical activity—rather than nutrition—as key to solving the obesity problem. By focusing more on physical activity than on a healthy diet, attention has been diverted away from highly processed food and calorie-dense snacks and drinks. Dietary policies advocated by the WHO, such as taxing sugary drinks and restricting food advertising to children, are missing. 249 The Indian economy was the fastest-growing major economy in the world in 2016, with a growth rate of 7·1%. 2 Its per-capita GNI in 2016 was $1680 ($6500 in PPP terms). The country's health-care expenditure (about 4% of GDP) compares well with other similarly placed countries. More than 70% of the population uses private health-care facilities 250 that have high costs, 251 often out of necessity rather than by choice. India launched a National Viral Hepatitis Control Program in 2018, 252 which aims to provide testing and treatment with antivirals to patients infected with hepatitis B and C and their sequelae of chronic liver diseases. With large-scale procurement, the current cost of a 12-week HCV treatment regimen of sofosbuvir and daclatasvir is $70 and is expected to decrease (Sarin S K, Institute of Liver and Biliary Sciences, New Delhi, India, personal communication). This is one of the most comprehensive hepatitis control programmes globally, on the basis that it incorporates the sequelae of hepatitis infection together with hepatitis infection itself, and intends to reach out to primary health centres in a phased manner. It also features surveillance for acute hepatitis, including hepatitis A and E. Some ongoing related programmes are hepatitis B immunisation for infants, safe blood transfusion, policies on injection safety, safe disposal of biomedical waste, food safety, and, most recently, treatment of hepatitis C. India does not currently have a national alcohol policy, but it has several policies and interventions aimed at reducing the harmful effects of alcohol ( table 4 ). The Ministry of Social Justice and Empowerment also has reduction and prevention policies on alcohol and drugs . Alcohol is a subject in the State List under the Seventh Schedule of the Constitution of India, which defines the exclusive legislative powers of state governments. Therefore, the laws governing alcohol, such as the legal drinking age in India and the laws that regulate its sale and consumption, vary from state to state. In India, consumption of alcohol is prohibited in the states of Bihar Gujarat, and Nagaland, as well as the union territory of Lakshadweep. There is a partial ban on alcohol in some districts of Manipur. All other Indian states permit alcohol consumption but have various legal drinking ages. In some states, the legal drinking age can be different for different types of alcoholic beverages. Current policies in India largely do not focus directly on overweight, obesity, and NAFLD ( table 5 ). However, in the context of ameliorating the burden of non-communicable diseases, certain government initiatives have been undertaken. The GBD statistics 253 and the projected prevalence of death and disability due to non-communicable diseases (obesity being the major risk factor) led the Indian Ministry of Health and Family Welfare to reduce the overweight diagnostic threshold for BMI to 23 kg/m 2 (from 25), and the standard waist circumference indicative of abdominal obesity to 90 cm in men and 80 cm in women (internationally accepted waist circumference thresholds for abdominal obesity are 102 cm in men and 88 cm in women). These standards have been published in the ministry's Consensus Guidelines for the Prevention and Management of Obesity and Metabolic Syndrome, which were released jointly with the Diabetes Foundation of India, the All-India Institute of Medical Science, the Indian Council of Medical Research, the National Institute of Nutrition, and 20 other health organisations. 254 Considering the increasing burden of non-communicable diseases and the risk factors common among the major non-communicable chronic conditions, the Government of India initiated the integrated National Programme for Prevention and Control of Diabetes, Cardiovascular Disease, and Stroke. 255 The programme focuses on health promotion and prevention, strengthening infrastructure and human resources, early diagnosis and management, and integration with the primary health-care system through non-communicable-disease cells at different levels for optimal operational synergies. 255 Consumption of junk food has also increased rampantly in India over the past two decades, and the industry primarily targets children. Although the Indian Government has not yet established a policy to ban junk food in schools and their close perimeters, the state governments of Delhi and Uttar Pradesh have instructed schools not to allow the sale of junk food in their canteens. In India, no specific laws or guidelines regulate the advertising or marketing of junk foods, but provisions under laws in other policy areas and some guidelines issued by the self-governing Advertising Standards Council of India could be used to regulate their advertising. The Food Safety and Standards Authority of India (FSSAI) has also produced the Guidelines–Code of Self-Regulation in Food Advertisement to control the objectivity and accuracy of food advertisements. 256 However, all of these measures are recommendations rather than mandatory. 257 Amendments regarding packaging and labelling of food under part VII of the Prevention of Food Adulteration Rules of 1955 mandate the disclosure of health claims alongside nutritional labeling. 258 However, stricter policies are required to prevent misleading information. For example, most packaged junk food in India does not mention trans fat because that is not required by the law. In 2010, the FSSAI expert group formulated guidelines that recommend less than 10% trans fats in food products. 259 Indonesia has the largest economy in southeast Asia and is one of the emerging market economies of the world, according to 2016 World Bank estimates. Its GDP per capita, however, ranks below the world average, making Indonesia a lower-middle-income country with a GNI per capita of $3440 and PPP per capita of $10 680 in 2015. 260 In 2015, Indonesia spent 3·6% of its GDP on health-care, which is less than its neighbouring countries such as Singapore (5·8%), Malaysia (4·3%), and Thailand (4·2%). 260 This expenditure covered 40% of the country's total health-care costs, whereas the remaining 60% were covered by private firms or out-of-pocket expenses, but by 2020 it is expected that public and private expenditure will contribute equally. 244 A serious effort to address hepatitis infection began in 1991 with a WHO-sponsored neonatal hepatitis B vaccination project in Lombok. In 1992, the Indonesian Red Cross started programmes for safe blood. These efforts—and more recent active harm reduction measures from 2010—were considered to support the decreasing incidence of HBV and HCV. 261 In 1997, hepatitis B immunisation for infants was launched as a national programme and upscaled in 1999 by the introduction of birth-dose vaccination. 262 A Hepatitis Control Program within the Ministry of Health was launched in 2012. 263 The Indonesian Government issued a decree on the National Control of Viral Hepatitis in 2015, supported by a national budget, 263 followed by a decree in 2017 for the Triple Elimination of Mother-to-Child Transmission of HIV, Syphilis, and Hepatitis B by integrating HIV, syphilis, and hepatitis B antenatal screening, prevention, and treatment interventions into Mother-and-Child Health Care services. 264 A government assistance programme began in 2017 that provides free testing and direct-acting antiviral drugs for 6000 patients with chronic hepatitis C infection who cannot afford diagnosis and treatment. 36 Meanwhile, efforts are made to include these drugs in the Essential Medical List to be used through the public health-care insurance system. Sofosbuvir, simeprevir, daclastavir, and one fixed-combination (elbasvir–grazoprevir) drug are the currently registered direct-acting antivirals in Indonesia. Currently, there are no alcohol bans being enforced in Indonesia, with the exception of Aceh province (Sumatra; table 4 ). In 2015, the Government began to restrict the availability of alcohol by banning sales from mini-marts and groceries. In a bid to prevent the prevalence of overweight and obesity, the Health Ministry has set the improvement of public health and nutrition as a top priority in the National Long-Term Development Plan ( table 5 ). 265 In November, 2016, the Indonesian Government launched a programme to improve public health called Healthy Living Community Movement (GERMAS). 266 One of the key elements included in the programme was the Isi Piringku (My Plate) campaign, 267 which describes the proportion of carbohydrates, protein, vegetables, and fruit each meal should contain. The scheme aims to drive change using a cost-effective model targeting individuals and the community by harnessing their motivations (eg, improved appearance, social acceptance, overall wellbeing) to improve health. School settings are recognised as an ideal and crucial starting point, to help children to acquire basic knowledge in the areas of nutrition and health, which would persist through adulthood, and to actively improve their diets through the provision of fruits and vegetables in their school meals. According to the World Bank's income classification, Pakistan is a lower-middle-income country, with GNI per capita of $5560 in PPP terms in 2016. Pakistan is developing and is one of the 11 countries identified as having high potential of becoming one of the world's largest economies in the 21st century. 268 The current policies and national action plan that track liver diseases, such as food, nutrition, alcohol, and HBV policies, have largely not been acted on or adequately popularised. These policies need to be updated with result-oriented strategies that aim to improve accountability and effectiveness by clearly defining expected outcomes, facilitating monitoring and evaluation, and reflecting improvements resulting from performance assessment processes. For example, in 1997, Pakistan introduced a National Health Policy targeting non-communicable diseases, and in 2003, it introduced an integrated national plan for action on four major non-communicable diseases and their risk factors, injuries, and mental health. Both the Policy and plan could not be implemented properly because of a change in government. 269 In Pakistan, vaccination against HBV was incorporated into WHO's Expanded Programme on Immunisation in 2002, providing the first vaccine dose at the age of 6 weeks; however, coverage for all three doses has reached 75% according to WHO-UNICEF estimates in 2018. 270 National guidelines on treatment and surveillance, provision of screening kits, injection safety equipment, training for preventive measures, and campaigns to increase mass awareness and financial support for treatment have also been developed. 271 The National Programme for Hepatitis Prevention and Control was launched in 2005, after which provincial implementation units were also set up. 272 The Programme focused on screening and treatment for HCV infection and did not establish laboratory-based viral hepatitis surveillance. At the time, hepatitis surveillance in Pakistan was syndromic, not providing laboratory confirmation of infection or information on the type of virus, and not collecting information on risk factors. In 2009, to monitor the effectiveness of the Programme's activities and guide the implementation of evidence-based preventative interventions, the Pakistan Field Epidemiology and Laboratory Training Programme (under the akistani Centres for Disease Control and Prevention and the Ministry of Health) launched a hepatitis sentinel-site surveillance system ( appendix p 3 ). The sites were located in five public tertiary care hospitals in four provincial headquarters (Lahore, Peshawar, Karachi, and Quetta) and in Islamabad. To engage Sindh province to implement strategies, the United States Agency for International Development further supported the Pakistani Centres for Disease Control and Prevention toward expansion of the surveillance sites. 273,274 A National Hepatitis Strategic Framework for viral hepatitis (2017–21) 274,275 has been launched to eliminate viral hepatitis C by 2030, reduce hepatitis B and C by 10% reduction by 2021, and reduce new cases of hepatitis B, C, and D by 30% by 2021. So far, the measures implemented by the Government of Pakistan include HBV vaccination for children and adults and providing antiviral therapy for patients with HBV and HCV through various programmes and public awareness campaigns. The national essential medicines list, subsidised by the government, includes antiviral therapy for HBV (interferon alpha, pegylated interferon, entecavir, tenofovir, and lamuvidine) and HCV (interferon alpha, pegylated interferon, ribavirin, sofosbuvir, daclatasvir, and velpatsavir). After its independence in 1947, Pakistani law was fairly liberal regarding alcohol ( table 4 ). Major cities had a culture of drinking, and alcohol was readily available until the mid-1970s when the Government introduced prohibition. As a result of the prohibition, the consumption of alcohol in the country has been very low, but mostly unrecorded. Many nutritional programmes (eg, School Health Programme, Micronutrient Initiative, National Programme for Family Planning and Primary Health Care, and Tawana Pakistan Project) have been initiated by governmental and nongovernmental organisations ( table 5 ). 276 Some of these programmes focus on raising awareness in the general public, and others focus on directly supplying food or fortified nutrition to communities. A national action plan for prevention and control of non-communicable diseases and health promotion 277 has been devised but has not been implemented. The Ministry of Planning and Development and Reform, in collaboration with the UN Food and Agriculture Organization, launched the Pakistan dietary guidelines for better nutrition in December, 2018. 278 Bangladesh is a lower-middle-income economy which grew by 7·1% in 2016–17. 2 The per-capita GNI in 2016 was $1330 ($3790 in PPP terms). According to the latest Bangladesh national health accounts, the country spends $2·3 billion on health or $16·20 per person per year, of which 64% comes through out-of-pocket payments. 279 Health insurance initiatives cover a very small proportion of the total population. Hepatitis B vaccination was introduced in Bangladesh in phases during 2003–05 under the Expanded Program on Immunization 280 and since 2007, more than 95% of infants younger than 1 year have been vaccinated against HBV. 281 The coverage in 2016 was reported to be as high as 97% by WHO and UNICEF. HBV prevalence appears to have declined in Bangladesh, from 5·5% in 2008 and from 6·4% in 1997 to 0·7% in 2010. 58,59 Local generics are available for tenofovir, entecavir, adefovir, lamivudine, and pegylated interferon at reduced costs. However, eliminating HBV remains a challenge because of factors such as an increase in HBeAg-negative infections, lack of adequate numbers of hepatologists, insufficient availability of laboratory facilities for viral load estimation, social taboos, lack of public awareness about hepatitis B and its preventability, and misconceptions about the mode of transmission and consequences of HBV infection. Regarding HCV, local generic direct-acting antiviral drugs such as sofosbuvir, ledipasvir, daclatasvir, and velpatasvir are available at low cost, offering HCV treatment of good quality. However, the challenges in the management of transmission resemble those for HBV. Harm reduction interventions, particularly a needle syringe programme for people who inject drugs, have been implemented in Bangladesh since 1998. Opioid substitution therapy commenced in 2010 but only covers 2·9% of the total estimated people who inject drugs in the country. 63 The Government is allocating funds and staff for the national Nohep programme for viral hepatitis. This strategy for elimination of HBV, HCV, and HEV has been drafted and is now in the final stage of approval. Advocacy programmes on viral hepatitis and validated training modules for training health-care personnel have been developed. More than 3000 physicians serving the Health Cadre of the Bangladesh Civil Service have already received training about hepatitis and its management strategies. The status of various policies and interventions to reduce the harmful use of alcohol in Bangladesh is shown in table 4 . In 1990, the Ministry of Home Affairs in Bangladesh published the Narcotic Control Act, 282 which outlines national policies on alcohol tax rates, selling and serving of alcohol, alcohol advertisements, legal blood alcohol concentration when driving, and alcohol licensures. Although the Act restricts alcohol use, enforcement of its policies is minimal, so alcohol is still widely used in Bangladesh. Non-Muslim residents and foreign visitors are not affected by such restrictions, as long as they consume alcohol in private. The Bangladesh National Plan for Action on Nutrition was started in 1997, 283 with a focus on targeting undernutrition ( table 5 ). Dietary guidelines for Bangladesh were introduced in 2013 that describe population goals for intake of various nutrients, including saturated fats, trans fats, and sugars, which represent the average nutrient intake needed to maintain a healthy population. Bangladesh also endorsed a second National Plan of Action for Nutrition for 2016–25 in March, 2017. 284 Its goal is to improve the nutritional status of all citizens and reduce all forms of malnutrition, with a focus on children, adolescent girls, and pregnant and lactating women. The only strategies that discuss overnutrition in depth as a development challenge are the National Urban Health Strategy 2011 285 and the Strategic Plan for Surveillance and Prevention of Non-Communicable Diseases in Bangladesh 2011–15. 286 The Health, Nutrition, and Population Sector Program, 287 which began in 2011, also recognises overnutrition and obesity as development challenges. The programme is particularly focused at early intervention to address obesity and its risk factors, but trains front-line fieldworkers on prevention of all risk factors related to non-communicable diseases. 288 According to the World Bank's income classification, Japan is a high-income country with GNI per capita of $43 630 in PPP terms in 2016. Japan's health-care system is largely successful because of its wide availability, effectiveness, and efficiency. 289 The Japanese population has the longest life expectancy of all members of the Organisation for Economic Co-operation and Development (OECD), 290 and its health-care expenditure as a share of GDP is lower than most of the developed OECD countries. In 2013, health expenditure in Japan was 10·3% of GDP, compared with an OECD average of 8·9%. 291 Health insurance is mandatory in principle, but there is no penalty for the 10% of individuals who evade the compulsory insurance premium contribution, making it optional in practice. 292 Health insurance can be either national or provided by the employer. In 1958, a new citizens' health insurance law formally committed Japan to universal health coverage by making enrolment in governmental insurance systems mandatory for people not covered by employee-based plans, and by 1961 all municipalities had established insurance programmes with near-complete coverage. 52 The Japanese Government has been providing free hepatitis testing since 2002 for all citizens aged 40–70 years as part of routine health examinations. In 2007, patient management was strengthened by the establishment of a community hepatitis care network that links primary care physicians with specialised regional centres to co-manage patients with liver disease. Treatment for hepatitis was expensive, so the Government introduced a subsidy programme in 2008 to reduce the burden of out-of-pocket expenses. 293 The cost of subsidies is borne by the national and local governments. People living with hepatitis currently pay ¥10 000–20 000 (approximately The cost of subsidies is borne by the national and local governments. People living with hepatitis currently pay ¥10 000–20 000 (approximately $100–200) per month on the basis of their income to cover the cost of drugs, medical appointments, and laboratory tests.00–200) per month on the basis of their income to cover the cost of drugs, medical appointments, and laboratory tests. In 1985, Japan implemented public programmes for mandatory HBsAg tests for pregnant women to prevent mother-to-child HBV transmission. Infants who were born to HBsAg-positive mothers began receiving HBV vaccination plus IgG therapy in 1986. Further, the Japanese Red Cross implemented nucleic acid screening programmes for HBV and HCV in 1999. These national efforts markedly reduced the prevalence of childhood HBV infections. Nevertheless, about 200 new, primarily adult infections of acute HBV are reported annually. 48 The distribution of HBV genotypes also appears to have changed on the basis of an observed increase of chronic infections but without obvious household transmission, which makes controlling infection challenging. 294 The Japanese Ministry of Health, Labour and Welfare implemented routine immunisation of children for HBV in 2016 to prevent horizontal HBV transmission and to eradicate infection incidence, in line with WHO's target of eliminating the public health threat of viral hepatitis by 2030. 294 Because of the universal health insurance system and the subsidy programme, the economic barrier to HCV eradication is very low in Japan, with all patients with HCV having access to direct-acting antiviral drugs (sofosbufir, sofosbufir–ledipasvir, ombitasvir, paritaprevir–ritonavir, daclatasvir, elbasvir–grazoprevir, and sofosbufir–velpatasvir). In a 5-year retrospective cohort study between 2008 and 2013 that estimated HCV in blood donors from their medical records, the incidence of HCV infection was 0·40 per 100 000 person-years (95% CI 0·27–0·57) on the basis of viral RNA seroconversion. 295 Incidence was as low as that reported between 1994 and 2004 (1·9 per 100 000 person-years, 95% CI 1·1–3·0). 296 Additionally, the incidence of HCV infection is very low, and HCV is nearly eradicated. As discussed, deaths due to hepatocellular carcinoma plateaued in 2002–04 and have declined since. Access to medical examinations is easy, so patients with high risk of hepatocellular carcinoma can be regularly monitored and many cases are treatable because they are detected at an early stage. The production and off-premise sale of all alcoholic beverages based on the Liquor Tax Law requires a Government licence ( table 4 ). This licensing system has been strictly imposed over time and almost no home-brewed alcohol has been available on the market for the past 30 years. However, there is virtually no restriction on off-premise sales in Japan and there are no restrictions on the advertising alcoholic beverages. Encouraging weight loss is a central aim of Healthy Japan 21, a series of 10-year public-health goals devised at the start of the millennium ( table 5 ). 297 This reduction of overweight is to be achieved through public education campaigns on healthy eating and increased physical activity. 298 Japan's school lunches programme has helped to slow the rise of child obesity in Japan. Lunches tend to be planned by a nutritionist, include locally grown and fresh ingredients, and tend to be dominated by rice, vegetables, soups, and fish. Childhood obesity has increased in Japan since the 1970s, but that increase has happened more slowly than in other economically developed countries. The Government has established healthy waistline thresholds for adults aged 40–74 years with the metabo law, which came into effect in 2008, and these are measured at annual checkups. 298 The threshold for men is 33·5 inches or less and women, it is 35·4 inches. People who exceed those norms are required to attend counselling and support sessions. Companies are required to measure the waistlines of at least 80% of their employees along with their families, and of retired employees. Furthermore, at the time of introduction, companies were required to help 10% of those who were above the thresholds to lose weight by 2012, and 25% by 2015. Companies and local governments that failed to meet specific targets were liable for financial penalties, potentially as high as The threshold for men is 33·5 inches or less and women, it is 35·4 inches. People who exceed those norms are required to attend counselling and support sessions. Companies are required to measure the waistlines of at least 80% of their employees along with their families, and of retired employees. Furthermore, at the time of introduction, companies were required to help 10% of those who were above the thresholds to lose weight by 2012, and 25% by 2015. Companies and local governments that failed to meet specific targets were liable for financial penalties, potentially as high as $19 million.9 million. 298 The targets have not been updated, but companies are now required to increase their contributions to their welfare fund by 10% if they do not perform well. Men and women who exceed the waistline measurement threshold during their annual medical examinations are enrolled in diet programmes, fitness classes, or are asked to see a doctor. The long-term effectiveness of this controversial stringent approach are yet to be clarified. 299 South Korea is a high-income country with nominal GNI per capita of $28 380 and annual GDP growth of 3·1%. 2 By contrast with most OECD countries, health spending in South Korea has been growing continuously since the 1970s at a rate above the OECD average. Total health expenditure as a proportion of GDP was 7·1% in 2014. 300 Although the public sector is the main source of health funding in nearly all OECD countries, the private sector has a much more important role in South Korea and only 56% of health spending was funded by public sources in 2013, well below the average of 73% in OECD countries. 300 Out-of-pocket spending is also an important component of overall health expenditure in South Korea. At 37% of health spending, its share is almost twice the overall OECD average (19·5%). 300 South Korea achieved universal health coverage in 1989. The national health insurance covers about 97% of the population, and the remaining 3% are covered by the Medical Aid Program, a tax-funded programme for health-care access of citizens with low incomes. By contrast with public health financing, health-care delivery relies heavily on the private sector, although some public health facilities provide medical services at the central, regional, and municipal levels. As of 2012, almost all clinics and about 94% of hospitals were privately owned. 301 For hepatitis B in South Korea, the use of oral antiviral drugs is done according to the reimbursement guidelines of the national health insurance programme. Pegylated interferon can also be used. For HCV, the use of pegylated interferon and ribavirin has been covered by the national health insurance programme. Coverage is not complete for direct-acting antiviral drugs but is improving and the following drugs have been approved by the South Korean Ministry of Food and Drug Safety for the treatment of HCV: sofosbuvir–ledipasvir, sofosbuvir, daclatasvir, asunaprevir, ombitasvir/paritaprevir/ritonavir plus dasabuvir, elbasvir–grazoprevir, and glecaprevir–pibrentasvir. South Korea has implemented a minimum age for purchasing alcohol, but other legally binding policies (eg, regulating promotion of the sales of alcoholic beverages or sale restriction in petrol stations and to intoxicated individuals) do not exist ( table 4 ). South Korean ministries, especially the Ministry of Health and Welfare and the Ministry of Education, have introduced many interventions to improve diets and increase physical activity ( table 5 ). For example, the Ministry of Health and Welfare provides budget support to local governments' obesity programmes, develops educational materials and publicises them, and provides vouchers for management services of physical activity and diets for obese children. The National School Lunch Act, introduced in 1981, has provisions on school dietitians, nutritional requirements, and dietary consultation. In July, 2018, the South Korean Government set a goal to keep the population's obesity prevalence lower than 35% by implementing measures on nutrition, exercise, obesity treatment, and improved awareness. Surgical procedures to treat obesity are covered by public health insurance. Starting in 2020, medical consultations and dietary training will also be eligible for partial coverage under the national insurance plan. Additionally, the Government will finance outdoor activities for students so that children will have access to activities outside their school gyms such as swimming, skating, bowling, climbing, and baseball. The Government plans to create a monitoring system for television programmes and advertisements that promote overeating; however, because of widespread critique, these plans have not yet been implemented. 302 The economy of Australia is a large mixed-market economy, with a GDP of $1·43 trillion as of 2017. In 2018, Australia became the country with the largest median wealth per adult. 303 According to the World Bank's income classification, it is classified as a high-income country, with GNI per capita of $45 210 in PPP terms in 2016. Health care in Australia is delivered as a mixed system via universal health care (public), which predominates, and private providers (insurance), who make a small contribution. Australia's universal health care is primarily funded by Medicare, a financing system that covers most costs of health services, including those in public hospitals. Medicare is funded partly by a 2% Medicare income levy (with exceptions for people with low incomes), with any shortfall being met by the Government from its general revenue. 304 The proportion of Australia's health expenditure of GDP (9·5%) for 2011–12 was slightly above average compared with other OECD countries. 305 In Australia, a universal hepatitis B vaccination programme for all infants was introduced in 2000. 306 It was preceded by various programmes implemented in the late 1980s that targeted individuals at increased risk of HBV infection. Catch-up vaccination programmes against hepatitis B for adolescents have been implemented at different times, settings, and jurisdictions since 1997. 71 However, health inequity between Indigenous and non-Indigenous Australians regarding HBV infection is still substantial. Vaccination coverage of Indigenous Australian adults needs to be increased through a state-funded vaccination catch-up programme. In 2017, an estimated 149 746 people living with chronic hepatitis B in Australia had been diagnosed, representing 68% of the total estimated population living with chronic hepatitis B and a modest increase from the 63% estimate in 2011. 307 The first National Hepatitis B Strategy 2010–13 308 sought to reduce disease transmission and the morbidity and mortality associated with hepatitis B. Furthermore, the introduction of highly effective HBV antiviral therapy in Australia with entecavir in 2005 and tenofovir in 2007 was accompanied by considerable increases in treatment uptake. During 2017, 19 358 people were administered drugs for hepatitis B, representing 8·7% of those estimated to be living with chronic hepatitis B. Modeled trends between 2011 and 2017 show an ongoing modest increase (average 0·93% per year) in this proportion. 307 At the population-level, only a few people with chronic HBV infections (possibly 10–15%) would be recommended for treatment on the basis of national and international consensus guidelines. 309,310 These vaccination efforts are collectively reflected in the fact that Australia was recognised by WHO as meeting the regional control target of hepatitis B, which is a prevalence of less than 1% in children younger than 5 years. 311 Australia implemented its Third National Hepatitis B Strategy for 2018–22 to achieve and maintain 95% vaccination coverage against hepatitis B in infants, increase the proportion of diagnosed people with chronic hepatitis B infection to 80%, increase the proportion of those receiving care to 50% and those receiving antiviral treatment to 20%, and reduce mortality related to chronic hepatitis B by 30%. 312 Estimates from modelling studies indicate that 75–85% of Australians with HCV are diagnosed, one of the highest proportions of diagnosed individuals globally. 313 Despite this estimate, treatment uptake was low (2000–4000 people per year, or 1–2% of the infected population) in the era of interferon-based regimens. 313 However, uptake has substantially increased following the Pharmaceutical Benefits Scheme, which, since March 1, 2016, has listed interferon-free, all-oral regimens of direct-acting antiviral drugs with no restrictions on the basis of the stage of liver disease or drug and alcohol intake. 314 4400 incident patients were treated per month during the first four months of listing. 315 By December, 2017, the number of patients starting therapy with direct-acting antiviral drugs had stabilised to about 1280 patients per month. 315 Over the first 2 years of listing, 2016–18, 56 356 patients had been supplied with medication, and as of April 30, 2018, this number of patients was 58 941. 315 The Australian Government has allocated The Australian Government has allocated $0·6 billion to fund this scheme over the subsequent 5 years. This treatment increase suggests that Australia could eliminate hepatitis C within the next 10–15 years if the current trend continues.·6 billion to fund this scheme over the subsequent 5 years. This treatment increase suggests that Australia could eliminate hepatitis C within the next 10–15 years if the current trend continues. 316 The 2009 Australian Guidelines to Reduce Health Risks from Drinking Alcohol have led to some recommendations on reducing alcohol-related liver harms and on broader health aspects ( table 4 ). 317 Subsequent estimates suggest that Australians were drinking less alcohol in 2013–14 than in 1960, 50 years earlier. 318 In 2014–15, 65·3% of Australians aged at least 15 years had sedentary lives or exercised rarely. This proportion comprises 33·8% sedentary people and 31·5% people with low levels of exercise below the “sufficiently active” threshold, defined as at least 30 min of moderate-intensity physical activity on most, preferably all, days. 319 During the past two decades, frequent campaigns run by Federal and State agencies in Australia to promote healthy food intake and physical activity have been successful on the basis of improved general awareness about obesity, increased physical activity, and modification of dietary patterns ( table 5 ). 320,321 New Zealand's Government is applying a nationwide wellbeing approach to policy and budget decision making. General wellbeing in the country is high, as reflected by OECD's economic health survey. 322 According to the World Bank's income classification, New Zealand is a high-income country with GNI per capita of $37 190 in PPP terms in 2016. New Zealand's health system is predominantly tax-funded and provides universal coverage. Health expenditure as a proportion of GDP increased from 6·8% in 1990 to 10·1% in 2010 (slightly above the OECD average of 9·5%). The population has a high health status overall but health inequalities are substantial in Pacific peoples and Māori. In New Zealand, a hepatitis B vaccination programme started in 1985 and was first intended for infected expecting and lactating mothers. Universal vaccination of infants against hepatitis B was introduced in 1988. Lamivudine treatment was approved and funded for the management of patients with chronic hepatitis B in 2000 and, until 2015, almost 2500 patients had been treated. Adefovir was introduced in early 2003 and, subsequently, entecavir and tenofovir were also introduced. 85 New Zealand has also implemented screening programmes for blood products and needle exchange programmes for intravenous drug users. The Pharmaceutical Management Agency (known as Pharmac) announced funding for direct-acting antiviral drug therapies for patients with HCV on June 9, 2016. From Oct 1, 2016, all prescribers including general practitioners were able to prescribe these drugs. 316 Until February, 2019, an estimated 3000 patients with HCV have been treated with direct-acting antiviral drugs funded by Pharmac and another 2000 have been treated with such drugs provided through clinical trials. 323 General practitioners in New Zealand are the primary health-care professionals responsible for monitoring patients for liver cancer, typically with a liver ultrasound. If cancer is suspected, a patient is referred for specialist care and further management. However, there are no data to indicate the quality of surveillance practices, even in specialist settings. Although a national registry would deal with this issue and improve surveillance, currently there is no political will to implement such a policy. Several approaches are being taken to prevent and reduce hazardous drinking in New Zealand, including strengthening regulation through the Sale and Supply of Alcohol Act 2012 ( table 4 ). This Act introduced a limit on alcohol vending hours, strengthened restrictions around irresponsible promotion of alcohol, and stricter laws on the supply of alcohol. It also increased the ability of communities to control alcohol licensing in their local area, run national social marketing campaigns to raise awareness about alcohol harms, expand school-based health services to improve early identification and treatment referrals for young people with an alcohol problem, provide self-help tools such as the Alcohol Drug Helpline , and support people to address their alcohol issues through primary care and specialist services. 325 A Childhood Obesity Plan was launched in New Zealand in October, 2015, with three focus areas comprising 22 initiatives ( table 5 ). 326 These initiatives either expanded on already existing recommendations or were new, such as targeted interventions for obese individuals, increased support for people at risk of becoming obese, and broad approaches to make healthier choices easier for all New Zealanders. The focus of the plan is on food, the environment, and physical activity at each life stage, starting from pregnancy. The plan brings together initiatives across government agencies, the private sector, communities, schools, families, and whānau (Māori for extended family or community co-inhabiting an area as an economic unit). There have been many initiatives that encourage healthy eating, physical activity, and adequate sleep, such as Eating and Activity Guidelines for New Zealand Adults, 327 Physical Activity guidelines, 328 Clinical Guidelines for Weight Management for Adults, 329 Clinical Guidelines for Weight Management for Children and Young People, 330 Fruit in Schools, 331 Green Prescriptions, 332 and Active Families. 333 The Fruit in Schools programme provides a piece of fruit each day to children from communities with low socioeconomic status. The Green Prescriptions initiative provides individual support for increased physical activity after a referral from a general practitioner or a practice. The Active Families initiative comprises community-based health initiatives designed to increase physical activity and improve nutrition in children and young people aged 5–18 years and in their whānau . 325 The World Bank classifies Singapore as a high-income country, with GNI per capita of $85 050 in PPP terms in 2016. Singapore was ranked as the world's most competitive economy, according to the International Institute for Management Development's World Competitiveness Rankings for 2019 . Although Government health-care spending as a proportion of GDP is relatively low, Singapore is among the 25 countries with the highest per-capita health-care spending. In 2015, Singapore's Government spent 2·1% of GDP or $6·3 billion on health. Health-care financing is based on Singapore's 3M framework: MediSave (a compulsory national health savings account), MediShield Life (a government-funded universal health insurance plan), and MediFund (an endowment fund set up by the government to help Singaporeans who are unable to pay for their medical expenses). 334 Under MediShield Life, even people with pre-existing conditions will be covered. The national health-care plan covers the entire population and ensures that all Singaporeans have access to medical care. Although public hospitals provide 80% of expensive tertiary care services, private sector practitioners account for 80% of primary health care, with government polyclinics that operate under the Ministry of Health accounting for the other 20%. 334 Currently there is no national action plan for liver diseases in Singapore. Chronic hepatitis B is the most common cause of liver diseases and is primarily addressed the National Childhood Immunisation Programme implemented in 1987. Infant vaccination is given at birth followed by the second dose at 1 month of age and the third dose 6 months later. Hepatitis B serology is routinely tested as part of antenatal assessments. For surveillance, only acute hepatitis B and C are notifiable diseases to the Ministry of Health. Singapore's hepatitis B guidelines, which include chronic hepatitis B management, were introduced by the Ministry of Health in 2011. 93 The Government also setup a Medication Assistance Fund to help eligible patients to pay for expensive drugs that are not in Singapore's standard drug list but have been assessed to be clinically cost-effective. Patients receive drug subsidies and assistance on the basis of their subsidy and means-test status and the scheme under which the drug is covered (ie, standard drug list vs Medication Assistance Fund). For patients with chronic hepatitis B, adefovir and lamivudine are the only drugs listed under the standard drug list. Entecavir and tenofovir are listed under the Medication Assistance Fund. Drug subsidies are provided for patients with HCV, including for pegylated interferon, ribavirin, and sofosbufir–velpatasvir. 335 MediSave's list of chronic diseases for which patients can make claims does not include liver diseases. For MediShield Life, claims cover mainly expensive hospital procedures and inpatient treatment for liver disease. Outpatient claims for immunosuppression therapy for organ transplants is also covered. Singapore's Liquor Control (Supply and Consumption) Act 2015 came into force on April 1, 2015 ( table 4 ). 336 The Act regulates the supply and consumption of alcoholic beverages in public places to minimise public disorder and disamenities arising from drinking in public, and prohibits the consumption of alcohol in public spaces from 2230 h to 0700 h every day. There are also restrictions on the sale, supply, and delivery of liquor. Policies and programmes on obesity and NAFLD have been customised for different parts of the population and implemented in various settings in Singapore (ie, schools, workplaces, health-care institutions, and communities; table 5 ). There have been many initiatives to raise awareness through health education and communication including official dietary 337 and physical activity 338 guidelines by the Health Promotion Board; the Championing Efforts Resulting in Improved School Health (CHERISH) award for primary and secondary schools, junior colleges, and centralised academic institutions; 339 workplace health promotion programmes (Healthier Canteen Certification Programme); 340 the Singapore Helping Employees Achieve Lifetime Health (HEALTH) award for companies; 341 various programmes in schools (model school tuck shop programme, 342 Trim and Fit programme); 343 and various community-wide programmes that promote healthy eating and physical activity (Healthier Hawker Program, Healthier Dining Programme, Lose to Win Programme). 344,345 Taiwan is included in the group of advanced economies by the International Monetary Fund. It is a high-income economy according to the World Bank, with GNI per capita of $45 582 in PPP terms in 2015. It is ranked 15th in the world by the Global Competitiveness Report of the World Economic Forum, is 22nd largest in the world in terms of PPP, and ranks as 18th by GDP at PPP per capita. Taiwan's national health expenditure accounted for 6·1% of GDP in 2015. The national health insurance system in Taiwan was launched in 1995 and currently provides coverage of about 99·7% of the population. As of June, 2016, 20 759 hospitals and health-care providers, or 93·0% of all health-care facilities in the country, were contracted by the national health insurance system. Taiwan's National Health Insurance Administration first started to reimburse treatment for chronic hepatitis B and C in 2003. Coverage of oral drug treatments for patients with hepatitis C has been approved since January, 2017. 346 The Alternative Therapies programme for drug addiction, subsidised by Taiwan's Ministry of Health and Welfare, was introduced in 2006, and the Ministry's needle exchange programme was implemented in 2005. 347 At the end of 2016, 179 institutions throughout Taiwan were providing alternative therapy for drug use. The Ministry of Health and Welfare also subsidised health institutions to provide treatment for drug and alcohol addiction in correctional facilities. In 2016, four health institutions offered services at five correctional facilities. In 1984, the Taiwanese Government introduced the first control programme for viral hepatitis in infants globally. 102 Initially, the programme focused on prevention of hepatitis B through immunisation, public education to avoid transmission, encouraging the use of disposable syringes, and blood safety. Only babies born to HBsAg-positive mothers were vaccinated because of high costs but, as of 1986, all infants weighing 2500 g or more were eligible. In the late 1980s, the programme was extended to preschool children, medical personnel, and elementary-school children, and from 1992 onward, unvaccinated teenagers and adults have been encouraged to be vaccinated on a fee-for-service basis. Around 2000, because of the availability of effective treatments for hepatitis B and C, treatment of chronic viral hepatitis was added to the programme. In 2003, treatment for chronic hepatitis B and C was reimbursed by the national health insurance, which has had a tremendous impact on the outcomes of patients with chronic hepatitis. A 2010 analysis showed a steady and substantial decrease of the mortality of patients with end-stage liver disease and hepatocellular carcinoma in Taiwan. 348 In 2017, some of the direct-acting antivirals against HCV infection were covered by the national health insurance for the treatment of patients with chronic hepatitis C. Although health insurance has been introduced in most countries of Asia-Pacific, overall coverage remains low in countries like India, Pakistan, and Bangladesh, with consequent high out-of-pocket expenditure. HBV vaccination programmes for infants have been implemented by all countries. The administration of a birth dose of HBV vaccine is still inadequate in many countries, especially in low-income and rural settings. Policies regarding mandatory screening of blood and blood products for HBV and HCV and safe injection practices are available in all countries (although nucleic-acid amplification testing is not mandatory in a few countries). Most countries have put HBV and HCV drugs on essential medicines lists. The costs of antiviral drugs have been brought down considerably by the availability of generic versions. Except in Muslim-majority countries, alcoholic liver disease is a major public health issue, especially in China and India. Although many countries have policies on alcohol, major sociocultural and behavioural changes will be needed at the societal level to reduce overall consumption of alcohol. Changes in patterns of obesity, physical inactivity, and diets is driving an increase in NAFLD across countries, irrespective of their income status. National food and nutrition policies in lower-middle-income countries has historically focused on combating undernutrition. Anti-obesity policies have been developed and implemented by some countries such as China, South Korea, Japan, Singapore, Australia, and New Zealand. Chinese anti-obesity policies, under the influence of large multinational food companies, have focused mainly on promoting physical activity, and less on nutritional measures.

Funding Information:
Liver diseases are increasingly recognised as a major health challenge in developing countries, especially those in the Asia-Pacific region. Although viral hepatitis is a major cause of morbidity and mortality, the contribution of alcohol-related liver disease and NAFLD to the liver disease burden is rapidly increasing. Viral hepatitis A and E are major causes of morbidity and mortality related to acute hepatitis in countries of the Asia-Pacific that have medium and high HDIs and whose populations have low access to clean drinking water and sanitation facilities (see for a list of priority areas for liver diseases related to viral hepatitis). Of all deaths due to acute hepatitis in the region, 89% occur in medium-HDI countries, 9% in high-HDI countries, and 2% in countries with very high HDIs ( ). 95% of deaths related to acute HAV and HEV in the region occur in medium-HDI countries ( ). The SDGs, as part of the UN's 2030 Agenda for Sustainable Development, have ambitious goals in this regard. Goal 6 is to ensure availability and sustainable management of water and sanitation for all by 2030. Goal 6.1 calls to achieve universal and equitable access to safe and affordable drinking water for all, and Goal 6.2 aspires to achieve access to adequate and equitable sanitation and hygiene for all, as well as the end of open defecation. panel 1 figure 6 figure 7 404 In the past decade, much progress has been made to increase access to drinking water and sanitation but still too many people lack access to a safe, sustainable water supply and sanitation services. Hepatitis B and C are still responsible for a considerable fraction of morbidity and mortality due to liver diseases in almost all countries of the Asia-Pacific, although Taiwan has shown great success with HBV vaccination and reducing the burden of HBV in the past two decades. Overall, 86% of deaths related to acute HBV occur in medium-HDI countries ( ). ). figure 7 ). 1 Of all deaths due to cirrhosis in the Asia-Pacific, 66% occur in medium-HDI countries, 30% in high-HDI countries, and 4% in countries with very high HDIs ( figure 6 ). 1 63% of deaths due to HBV-related cirrhosis and 77% of deaths due to HCV-related cirrhosis occur in medium-HDI countries ( figure 8 1 Of all deaths due to liver cancer in the Asia-Pacific, 74% occur in high-HDI countries, 18% in medium-HDI countries, and 8% in countries with very high HDIs ( figure 6 ). 79% of those due to HBV-related liver cancer and 32% of those due to HCV-related liver cancer occur in high-HDI countries ( figure 9 1 Preventing transmission of HBV and HCV is entirely achievable. HBV vaccination programmes for infants have been implemented by all countries. The administration of a birth dose of the HBV vaccine is still inadequate in many countries, especially in low-income and rural settings. Implementing policies on mandatory screening of blood and blood products for HBV and HCV and safe injection practices is still a challenge in many countries (eg, India and Pakistan). We strongly recommend a focus on harm reduction strategies that target people who inject drugs in all countries of the Asia-Pacific where these practices are prevalent. There has been progress in improving access to generic medications and reducing costs. The governments of many countries have put HBV and HCV drugs on their lists of essential medicines. There is an urgent need to make generic drugs available in all countries of the region and bring the costs of hepatitis C drugs to less than a dollar a day, following India's example. Since only a small proportion of patients with hepatitis B and C are ever diagnosed, the importance of screening and diagnostics need to be better emphasised. New approaches and tools are required for point-of-care diagnostics that are suitable for high-burden, low-resource countries. The 2018 establishment of a WHO Essential Diagnostics List 426 is a welcome recognition of this importance. A greater focus is now needed on prequalification (ie, evaluating diagnostic tests with standardised protocols for their quality, performance, and safety to guide procurement decisions by actors such as WHO Member States or UN agencies) to ensure provision of high-quality diagnostics and clinical evidence for simplified management algorithms in settings where diagnostics are not available. 4 We believe that governments should widely engage with all stakeholders, including individuals and organisations representing at-risk groups (eg, people who inject drugs, prisoners, and individuals with HIV), and also be liberal in approving and implementing new diagnostic devices. International organisations have a key part in supporting national progress and they need to ensure that viral hepatitis is part of their remit, equal to other major infectious diseases such as tuberculosis, malaria, and HIV. Some organisations have led in this regard—notably WHO, Unitaid, and Clinton Health Access Initiative—but more can be done. There are several areas that organisations can prioritise to support viral hepatitis elimination efforts. Some are specific to viral hepatitis, for example the need to support the scale-up of birth-dose vaccination, which should be included in the remit of Gavi, the Vaccine Alliance, for support. Several other areas can leverage existing mechanisms that support other disease responses, notably HIV, to improve access to care and treatment for patients with viral hepatitis. 4 We believe that governments should be increasingly accountable and take timely measures toward national viral hepatitis elimination strategies. Adequate enforcement of policies is also needed. Funding bodies should ask for evidence of the outcomes of their investments to improve accountability. Data on progress of achieving elimination targets should be regularly reported by WHO and other funders but more attention needs to be paid to each country's performance relative to others. Countries need to develop new fiscal spaces to accelerate the elimination of viral hepatitis, which will require innovative means of financing. 4 Sponsoring the scale-up of blood testing is a key challenge and sustaining progress will require not only financing but also strong political will and unrelenting advocacy. In 2015, WHO issued a draft Global Health Sector Strategy on Viral Hepatitis 2016–21, calling on all countries to aim to reach concrete targets towards the elimination of viral hepatitis. 404 The policy response to viral hepatitis until now has been inadequate and considerable challenges exist, particularly in low-income and middle-income countries, which bear most of the burden of viral hepatitis ( table 3 ). The Asia-Pacific region experiences a greater challenge from HBV and HCV infection than any other global region, having half of the 20 most heavily burdened countries. 427 Countries in the Asia-Pacific with a high burden of viral hepatitis span the economic spectrum and there is a negative correlation between GNI and the prevalence of both HBV and HCV, with a greater burden in low-income countries. 4 Countries need to define target screening populations, improve awareness among health-care workers regarding treatment options, subsidise the costs of drugs, and enhance access to them. Emulating Egypt and Georgia in managing HCV could be useful for countries in the Asia-Pacific region. 428,429 Infant HBV vaccination programmes have been implemented by all countries but often fall short of administering birth doses; Taiwan can be a positive example for HBV vaccination. Although policies on mandatory screening of blood and blood products for HBV and HCV are in place in all countries in the Asia-Pacific region (although nucleic-acid amplification testing is not mandatory in all), as are policies on safe injection practices, the lack of strong political commitment and effective regulations in low-to-middle income countries, especially in southeast Asia, limits the outcomes. Reuse of contaminated needles continues to cause outbreaks of hepatitis B and C in southeast Asia. 46,398 Harm reduction strategies targeting people who inject drugs need to be implemented, as has been done in Malaysia using the “Support. Don't punish” philosophy. 430 The WHO's Global Health Sector Strategy 404 on viral hepatitis called for elimination of viral hepatitis as a major public health threat by 2030 (ie, 90% reduction in incidence and 65% in mortality). Various targets have been proposed to achieve this, including three-dose coverage of hepatitis B vaccination in infancy (90%), receiving a timely birth dose (90%), blood safety (100%), injection safety (unsafe injections target of 0%), harm reduction (target for syringe and needle per person who injects drugs per year of 300), awareness of status of people infected with HBV and HCV (90%), and awareness of the status of infected people who were on HBV treatment or had started HCV treatment (80%). All countries in the Asia-Pacific should work towards achieving these targets in a time-bound manner. Mortality in the Asia-Pacific region from alcohol-related cirrhosis correlates with per-capita alcohol consumption. Commensurate with an increase in mean incomes, per-capita alcohol consumption has increased in countries of the Asia-Pacific, such as China and India, which will increase their burden of alcohol-related liver disease. Overall, 65% of deaths due to alcohol-related cirrhosis occur in medium-HDI countries and 80% of deaths due to alcohol-related liver cancer occur in high-HDI countries ( figure 8, 9 ). A systematic review 182 reported that DALYs attributable to alcohol use have increased by more than 25% over 1990–2016 globally, driven primarily by increased consumption in south, southeast, and central Asia, in both men and women. The largest increases in exposure have been in countries in the low-middle quintile of the SDI. 182 In 2016, alcohol use accounted for 4·0% (3·4–4·6) of age-standardised DALYs in southeast Asia. 182 Unlike tobacco or drugs, governments have been discouraged from efforts to limit the availability of alcohol by trade agreements and disputes. Alcohol use is ranked as one of the leading risk factors, surpassing cholesterol, for total DALYs globally since 2010 compared with previous iterations of the GBD Study. 182 The increasing burden of alcohol-related liver diseases can be ameliorated through government policies to control consumption and promote less harmful patterns of alcohol use ( table 4 ). Alcohol policies can exist at the global, regional, international, national, or subnational levels. Effective alcohol strategies incorporate a multilevel, multicomponent approach, targeting multiple determinants of drinking and alcohol-related harms, such as availability, price, marketing, and criminalisation of drink-driving. We believe that these policies must be well implemented, enforced, and evaluated to be effective. We recommend that countries should develop their own capacities and set up national monitoring systems to complement national surveys and provide crucial information that allows them to evaluate alcohol policies and track alcohol consumption trends over time. Mongolia is a good example, where the President initiated the Alcohol Free Mongolia programme by advocating drinking a glass of milk instead of alcohol. 431 SDG 3 aims to ensure healthy lives and promote wellbeing for all at all ages by 2030, and SDG 3.5 calls for strengthening the prevention and treatment of substance abuse, including narcotic drug use and harmful alcohol consumption. Although it is difficult to control alcohol use, several countries have added additional taxes on alcohol. The Global Strategy to Reduce the Harmful Use of Alcohol, 432 negotiated and agreed by WHO Member States in 2010, represents international consensus that reducing the harmful use of alcohol and its associated health and social burden is a public health priority. The strategy provides guidance for action at all levels, including ten recommended target areas for policy and interventions for national action to reduce the harmful use of alcohol, and the main components for global action to support and complement activities at the country level. 165 Given the magnitude and the complexity of the problem of reducing overall alcohol consumption in communities, concerted global and regional efforts must be in place to support countries and communities to reduce their harmful use of alcohol. International coordination and collaboration can create the necessary synergies and provide increased leverage for states to implement evidence-based measures. Local, national, and international monitoring and surveillance frameworks are needed to track the magnitude and trends of alcohol consumption and related harm, as well as monitor policy responses and analyse trends in alcohol consumption and its related disease burden. Such frameworks would be crucial to strengthen advocacy, adjust policy, and programme responses to the trends in alcohol-related harms and assess the effect of interventions. The ultimate goal of monitoring and surveillance is to provide, in a timely manner, relevant and reliable information to policy makers and decision makers for the effective prioritisation, implementation, and evaluation of policy options and interventions to reduce the harmful use of alcohol. WHO's Global Information System on Alcohol and Health serves that purpose and enables these processes. 165 The UN's 2011 Political Declaration of the High-Level Meeting of the General Assembly on the Prevention and Control of Non-Communicable Diseases mandated the development of a global monitoring framework, including indicators, and a set of voluntary global targets for the prevention and control of non-communicable diseases. 433 This work yielded one voluntary target related to alcohol use: including at least a 10% relative reduction, as appropriate within the national context, in the harmful use of alcohol by 2025. Obesity and NAFLD, although traditionally thought of as diseases of high-income countries, are increasingly recognised and have become epidemic in all countries of the Asia-Pacific region, irrespective of income status. Overall, 68% of deaths in Asia-Pacific due to NAFLD-related cirrhosis occur in medium-HDI countries, and 74% of deaths due to NAFLD-related liver cancer occur in high-HDI countries ( ). The high frequency of metabolic comorbidities in patients with NAFLD indicates that management of the increasing number of these patients might increase the strain on health systems. Furthermore, many patients with NAFLD develop progressive liver disease, which creates challenges for screening. figure 8, 9 ). Changing lifestyles and diet have contributed to the obesity and NAFLD epidemic in the Asia-Pacific. A systematic review and meta-analysis assessing the prevalence, incidence, and outcome of NAFLD disease in Asia found that even in people without obesity, the prevalence of NAFLD was 11·76%. 240 A 2018 study suggested that so-called lean patients with NAFLD are more likely to develop progressive liver disease and die from causes related to liver disease than those with obesity-associated NAFLD, indicating that NAFLD is not a benign condition. 434 Therefore, when a patient without obesity has abnormal anthropometric and laboratory measurements, and as the environment in Asia-Pacific continues to change, such awareness might become even more prudent. 240 The prevalence of NAFLD in the Asia-Pacific is following similar trends to the prevalence reported in high-income countries, indicating that NAFLD is a global disease warranting the attention of primary care physicians, specialists, and health policy makers ( panel 2 240 Various steps need to be taken to promote healthy lifestyles to avoid overweight or obesity by increasing physical activity in schools and offices and regulating the food industry (eg, restricting the marketing of unhealthy foods and sugar-sweetened beverages, increasing taxation on unhealthy foods and beverages, labelling food with nutritional information and health facts, regulating the advertising of unhealthy foods, and promoting healthy foods; table 5 ). SDG 3.4 calls to reduce premature mortality from non-communicable diseases by a third through prevention and treatment by 2030. The 2011 UN high-level political declaration on non-communicable diseases 433 included two voluntary targets potentially related to NAFLD, a 10% relative reduction, as appropriate nationally, in prevalence of insufficient physical activity and halting the increase of diabetes and obesity by 2025. Actions and interventions against NAFLD need to be urgently incorporated into WHO's Global Action Plan on non-communicable diseases, 435 including public awareness (under Objective 1 of the Plan); screening for NAFLD; using simple, non-invasive biochemical markers to detect fibrosis in patients with NAFLD; early detection and weight management strategies including lifestyle modifications (dietary and physical activity); and interventions to prevent progression of NAFLD to cirrhosis and hepatocellular carcinoma. The primary responsibility to prevent and control obesity and NAFLD lies with governments, although the engagement of all sectors of society, international collaboration, and cooperation are essential for success. Effective prevention and control of non-communicable diseases (including NAFLD) require leadership, coordinated multistakeholder engagement, and multisectoral action for health, both at the government level and at actor level. Such efforts would include health-in-all-policies and whole-of-government approaches across sectors such as health, agriculture, communication, education, employment, energy, environment, finance, food, foreign affairs, housing, justice and security, legislature, social welfare, social and economic development, sports, tax and revenue, trade and industry, transport, urban planning, and youth affairs, and partnership with relevant civil society and private sector entities. Opportunities to prevent and control NAFLD and its risk factors occur at multiple stages of life and interventions in early life often offer the best chance for primary prevention. People and communities should be empowered and involved in activities for prevention and control, including advocacy, policy, planning, legislation, service provision, education and training, monitoring, and research and evaluation of the effects of measures for the control and prevention of NAFLD. We believe that prevention is always better than cure; now is the time to push for prevention of NAFLD before its burden becomes overwhelming. Other aspects that need urgent attention are inadequate infrastructure and facilities for liver transplantation and health-care personnel poorly trained in the management of liver diseases, including preventive aspects, especially in low-and-middle-income countries. The focus must be on early detection of liver diseases with timely referral and access to appropriate care by trained multidisciplinary teams. In this regard, SDG 3.9c calls to substantially increase health financing and the recruitment, development, training, and retention of the health workforce in developing countries. Access to health insurance, affordable health care, and affordable essential medicines are also important issues in low-and-middle-income countries in the Asia-Pacific. SDG 3.8 aims to achieve universal health coverage, including protection from financial risk, access to good-quality, essential health-care services, and access to safe, effective, good-quality, and affordable essential medicines and vaccines for all by 2030. SDG 3.9b calls for the provision of access to affordable essential medicines and vaccines, in accordance with the Doha Declaration on the TRIPS agreement and public health, ). 436 which affirms the right of developing countries to fully use the provisions of the TRIPS agreement to provide access to medicines for all by 2030. To this end, health-financing systems should not only seek to raise sufficient funds for health provision but should also do so in a way that allows people to use services without risk of severe financial hardship or impoverishment. 437 Three interrelated areas could bring health financing closer to universal health coverage: raising funds for health, reducing financial barriers to health-care access through prepayment and subsequent pooling of funds instead of direct out-of-pocket payments, and allocating or using funds in a way that promotes efficiency and equity. Public health systems and public–private partnerships need to be strengthened to face the challenges that an increasing burden of liver diseases could create, and measuring progress is an inherent part of any prevention and treatment strategy. We suggest a set of metrics to monitor the implementation of the various aspects of such a strategy ( table 6 Implementation of the recommendations of this Commission will depend less on technical capabilities and more on leadership and political will. Nevertheless, even when there is strong leadership and political will, the availability of finances, application of funds, and health-system capabilities will determine the magnitude and speed of the response. At the country level, public financing for health (as for any sector) is determined by the fiscal space available to the government. The fiscal space depends on the sources of finance available from improved economic growth that creates favourable macroeconomic conditions, such as revenues generated from new taxation or strengthened tax administration, borrowing from domestic and international sources, reprioritisation of health within the existing government budget, more effective and efficient allocation of available health resources, and innovative domestic and international financing. 438 The high-level Taskforce on Innovative International Financing for Health Systems was set up in 2008. 439 It recommended the creation of a common funding platform to strengthen health systems across the three global-scale innovative financing mechanisms—ie, the Global Fund, Gavi, and the World Bank. These innovative financing mechanisms link different elements of the financing value chain to mobilise funding from multiple sources (eg, governments, foundations, and the private sector), pool finances, and channel and allocate funds to health programmes through organisations and governments in low-income and middle-income countries. Outsourcing of services, such as diagnostic tests or management systems for health-care data, to non-government providers and encouraging the use of advanced market commitments (eg, vaccine purchases) can also be used to secure investment in health-care services from the private sector. 439 The opportunity to link revenue generation to a global redistributive and environmental agenda should be sought via taxes on carbon, luxury items, or capital flow, and leveraging an increased domestic return on the natural resources and primary commodities of poor countries. 440 Other financing mechanisms including global health bonds, debt-conversion instruments, market commitment instruments, social and development impact bonds, and global solidarity taxes and levies need to be invoked. Opportunity can be seized in the current political momentum within the G20 countries that is in favour of increased levies on currency transactions and additional financial transaction taxes that could be used to regulate the global financial system. 440 The agenda of expanding the domestic resource base of low-income countries is also important for generating finances for health-care programmes. Many low-income countries could increase domestic public finance by reducing capital flight, promoting more effective tax policy, and improving their tax collection systems. Such an agenda would have the added benefit of focusing attention on the broad challenges of economic development and improving democratic and accountable governance. High-income countries should adhere to their responsibility to allocate 0·7% of their GNI to development aid. Principles and mechanisms need to be established for a systematic transfer of resources from high-income to low-income countries. 440 There are some limitations to our analysis. First is the paucity and patchiness of data on liver diseases in the Asia-Pacific region. We did not include any countries with low HDI and thus our analysis is not wholly representative. Second, the tools for collecting, analysing, and reporting data in different countries are not homogenous. Therefore, it is possible that there are additional demands and concerns about staffing and financing needs and the requirements and timelines to reduce the burden of liver diseases. Despite these limitations, the Commission defines the unmet gaps and lays the foundation for collective thinking to eliminate viral hepatitis and control other liver disaeses, including NAFLD and alcohol-related disease, in the countries of the Asia-Pacific region. In summary, this Commission provides an insight into the burden of liver diseases in the Asia-Pacific region and identifies potential causes of change in their underlying epidemiology and aetiology. Although viral hepatitis (both acute and chronic) is still a major cause of morbidity and mortality related to liver diseases in the Asia-Pacific region, efforts towards its elimination as a public health threat by 2030 should reduce this burden. Nevertheless, mortality from alcohol-related liver diseases remains high in mostly non-Muslim countries, especially China and India, and is expected to increase. Similarly, obesity and NAFLD-related liver diseases are common in all countries, irrespective of HDI, and are also expected to increase. We hope that the Commission provides an opportunity for countries to learn from each other to tackle the changing landscape of the burden of liver disease in the Asia-Pacific region and to achieve the targets set by the Sustainable Development Goals. For e-Stat see https://www.e-stat.go.jp/en Contributors SKS, MK, and RA wrote the sections on India. ME and JG wrote the sections on Australia and New Zealand. MAM and SMFA wrote the sections on Bangladesh. JJ and QT wrote the sections on China. DHM wrote the sections on Indonesia. MO and YO wrote the sections on Japan. K-HH and HWL wrote the sections on South Korea. WJ and ASB wrote the sections on Pakistan. CHC and SGL wrote the sections on Singapore. R-FP and D-SC wrote the sections on Taiwan. The Discussion and Introduction were written by SKS and MK. Declaration of interests MO reports grants from Bayer, Sumitomo Dainippon Pharma, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, EA Pharma, Eisai, Bristol-Myers Squibb, Japan Bio Products, Ono Pharmaceutical, Boehringer Ingelheim, GE Healthcare Japan, and Medtronic, outside the submitted work. SGL reports grants, personal fees, honorariums for advisory board membership, and speakers' fees from Gilead Sciences, Merck, Abbott Diagnostics, and Roche; personal fees, honorariums for advisory board membership, and speakers' fees from AbbVie and Spring Bank Pharmaceuticals; and personal fees from Dicerna Pharmaceuticals, outside the submitted work. All other authors declare no competing interests. Acknowledgments DHM thanks Pretty Multiharina Sasono, Wiendra Waworuntu, Naning Nugrahini, Sedya Dwisangka, and all staff of Sub-directorate of Hepatitis and Gastrointestinal Infection, Directorate General of Communicable Diseases, Ministry of Health, Indonesia, for providing data and discussions. SGL thanks Benjamin Ong, for reviewing the manuscript. ME and JG are supported by the Robert W Storr bequest to the Sydney Medical Foundation (University of Sydney, Sydney, Australia) and National Health and Medical Research Council of Australia (NHMRC) programme grant ( 1053206 ) and project grants (APP1107178 and APP1108422). MK and SKS thank Guresh Kumar (Institute of Liver and Biliary Sciences, New Delhi, India) for help in statistical analysis and figures. Editorial note: The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations.

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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