Improved detection of hepatocellular carcinoma by dynamic computed tomography in cirrhotic patients with chronic hepatitis B: A multicenter study

Ji Hyun Kim, Seong Hee Kang, Minjong Lee, Hoon Sung Choi, Baek Gyu Jun, Tae Suk Kim, Dae Hee Choi, Ki Tae Suk, Moon Young Kim, Young Don Kim, Gab Jin Cheon, Soon Koo Baik, Dong Joon Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Aims: Current guidelines for chronic hepatitis B (CHB) patients are to undergo surveillance for hepatocellular carcinoma (HCC) with 6-monthly ultrasonography (US). However, sensitivities of US to detect early-stage HCC in cirrhotic patients are suboptimal. We aimed to compare overall survival and detection rates of very-early-stage HCC in two groups: group A, undergoing 6-monthly US versus group B, undergoing 6-monthly US alternating with dynamic computed tomography (CT). Methods: This retrospective multicenter study assessed 1235 cirrhotic patients with CHB under entecavir/tenofovir therapy from 2007 to 2016. The primary endpoint was overall survival rates between the two groups. The Cox proportional hazards model and propensity score matching analyses were used to assess the effect of surveillance modalities on overall survival and detection of Barcelona Clinic Liver Cancer stage 0 HCC after balancing. Results: During a median follow-up of 4.5 years, 10-year cumulative HCC incidence rates of 16.3% were significantly higher in group B (n = 576) than 13.7% in group A (n = 659; P < 0.001). However, in patients with HCC, 10-year overall survival rates of 85.1% were significantly higher in group B than 65.6% in group A (P = 0.001 by log-rank test). CT exam alternating with US was independently associated with reduced overall mortality (hazard ratio 0.47, P = 0.02). Cumulative incidence of Barcelona Clinic Liver Cancer stage 0 HCC was significantly higher in group B than in group A (hazard ratio 2.82, P < 0.001). Conclusion: In cirrhotic patients with CHB, dynamic CT exam alternating with US led to higher detection rates of very-early-stage HCC and benefit of overall survival than did US exams.

Original languageEnglish
Pages (from-to)1795-1803
Number of pages9
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume35
Issue number10
DOIs
Publication statusPublished - 2020 Oct 1

Bibliographical note

Funding Information:
This was a retrospective cohort study that included 1235 consecutively registered cirrhotic patients with CHB under ETV and/or TDF therapy at four tertiary hospitals in Korea (Kangwon National University Hospital, Gangneung Asan Hospital, Wonju Severance Christian Hospital, and Chuncheon Sacred Heart Hospital) from 2007 to 2016. Patients were included if they were aged???18?years, had inadequate quality of US due to cirrhosis, and had received treatment with ETV and/or TDF. Patients na?ve to or previously treated with other nucleos(t)ide analogs were also included. Because the accuracy of US alone may be improved with addition of measurement of serum alpha fetoprotein (AFP) levels, we enrolled patients who underwent both measurement of serum AFP levels and image surveillance on a regular basis. Patients were excluded for any of the following criteria: non-cirrhotic patients; HCC diagnosed before the initiation of ETV/TDF treatment; received one exam of CT every 2?years on a regular basis; Eastern Cooperative Oncology Group performance status?>?2; co-infected with hepatitis D, hepatitis C, or human immunodeficiency virus; Child?Pugh class C; active alcoholism; history of liver transplantation; and lost during follow-up. We excluded noncompliant patients during follow-up periods in this study. All of patients who visited outpatient clinics on a regular basis were included. We consecutively enrolled cirrhotic patients who underwent US exams or US with alternating CT exams and showed good compliance: patients who did not follow image surveillance regularly were excluded through meticulous review of medical records. The Institutional Review Board of each hospital approving this study must comply with acceptable international standards (Declaration of Helsinki 2013). This was a retrospective cohort study that included 1235 consecutively registered cirrhotic patients with CHB under ETV and/or TDF therapy at four tertiary hospitals in Korea (Kangwon National University Hospital, Gangneung Asan Hospital, Wonju Severance Christian Hospital, and Chuncheon Sacred Heart Hospital) from 2007 to 2016. Patients were included if they were aged???18?years, had inadequate quality of US due to cirrhosis, and had received treatment with ETV and/or TDF. Patients na?ve to or previously treated with other nucleos(t)ide analogs were also included. Because the accuracy of US alone may be improved with addition of measurement of serum alpha fetoprotein (AFP) levels, we enrolled patients who underwent both measurement of serum AFP levels and image surveillance on a regular basis. Patients were excluded for any of the following criteria: non-cirrhotic patients; HCC diagnosed before the initiation of ETV/TDF treatment; received one exam of CT every 2?years on a regular basis; Eastern Cooperative Oncology Group performance status?>?2; co-infected with hepatitis D, hepatitis C, or human immunodeficiency virus; Child?Pugh class C; active alcoholism; history of liver transplantation; and lost during follow-up. We excluded noncompliant patients during follow-up periods in this study. All of patients who visited outpatient clinics on a regular basis were included. We consecutively enrolled cirrhotic patients who underwent US exams or US with alternating CT exams and showed good compliance: patients who did not follow image surveillance regularly were excluded through meticulous review of medical records. The Institutional Review Board of each hospital approving this study must comply with acceptable international standards (Declaration of Helsinki 2013). Chronic hepatitis B and HCC were diagnosed according to previous literatures (Data S1).5,16,17 All patients were treated with ETV and/or TDF and followed up according to clinical practice guidelines.18 The two groups of patients were compared. Group A patients underwent US every 6?months (?1?month). When patients in the group A received one-time additional CT exam (a recall test) to confirm the suspicious nodules detected by US or find hidden lesions as increase of serum AFP levels above normal without any suspicious findings on US exams, the patients were regarded as group A: continuous US exams thereafter. Group B patients underwent US with alternating CT every 6?months (?1?month): CT exams should be performed at least two times every 2?years on a regular basis. Given the lack of accepted quality benchmarks for US exam adequacy, US quality for HCC surveillance was defined based on the previous literature.19 Inadequate quality of US exam was defined based on combination of visual unclarity of the liver parenchyma including heterogeneity, nodularity and coarse liver echotexture from cirrhosis, anatomical coverage less than two thirds of shrunken liver visualized, and any other exam limitations such as ascites from cirrhosis, ribs, or bowel gas. The primary endpoint was overall survival rates compared between two groups. The secondary endpoints were detection rates of very-early-stage HCC (Barcelona Clinic Liver Cancer [BCLC] 0). The index date was defined as the date of the initiation of ETV/TDF treatment. Follow-up was considered to be the time interval between the index date and the last available clinical information: the date of diagnosis of HCC or the end of follow-up in the absence of HCC development up to January 2017. Regarding cumulative risk of HCC at specific stages such as BCLC 0, A, B, and C stages, patients who had other-stage HCC during follow-up were censored. The cumulative probabilities of overall survival and HCC development were estimated by the Kaplan?Meier method and compared with those of the log-rank test. Multivariable Cox regression models were used to estimate the effect of various variables on the probability of overall survival and early detection of HCC. A P value?<?0.05 was considered to be statistically significant. Propensity score (PS)-matching analysis and competing risk analysis were described in Data S2.

Publisher Copyright:
© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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