Insulin resistance is independently associated with significant hepatic fibrosis in Asian chronic hepatitis C genotype 2 or 3 patients

Keyur Patel, Alexander J. Thompson, Wan Long Chuang, Chuan Mo Lee, Chen Yuan Peng, Ganesananthan Shanmuganathan, Satawat Thongsawat, Tawesak Tanwandee, Varocha Mahachai, Chutima Pramoolsinsap, Mong Cho, KwangHyub Han, Samir R. Shah, Graham R. Foster, Paul J. Clark, Erik Pulkstenis, G. Mani Subramanian, John G. Mchutchison

Research output: Contribution to journalArticle

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Abstract

Background and Aim: The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian-region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC genotype 2/3 patients. Methods: A total of 303 treatment-naïve Asian-region patients with CHC genotype 2/3 were enrolled in a multicenter phase 3 study of albinterferon alfa-2b plus ribavirin for 24weeks. IR was defined as Homeostasis Model for Assessment of IR (HOMA-IR)>2. Baseline liver biopsy was evaluated by a single expert histopathologist. Post hoc subgroup logistic regression modeling selected for independent variables associated with significant fibrosis (METAVIR stage F2-F4). Results: Insulin resistance was available in 263 non-diabetic Asian-region patients (hepatitis C virus-2 [HCV-2]=171, HCV-3=92), and 433 non-Asian region patients (407 "Caucasian"); METAVIR fibrosis prevalence F0-F1 (minimal fibrosis)=201 (77%) and F2-F4 (significant fibrosis)=59 (23%), and steatosis prevalence of grade 0=169 (65%), grade 1=64 (25%), grade 2/3=27 (10%). Median HOMA-IR was 1.8 (interquartile range: 1.2-2.7); 100 (38%) patients had HOMA-IR>2. Factors independently associated with significant fibrosis included HOMA-IR (odds ratio [OR]=8.42), necro-inflammatory grade (OR=3.17), age (OR=1.07) and serum total cholesterol levels (OR=0.008). This was similar to non-Asian region patients, but steatosis was not associated with significant fibrosis in either cohort. Conclusions: In this subgroup study of Asian-region HCV genotype 2 or 3 patients, insulin resistance, along with age, cholesterol levels and necro-inflammation, but not steatosis may be associated with significant hepatic fibrosis.

Original languageEnglish
Pages (from-to)1182-1188
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume26
Issue number7
DOIs
Publication statusPublished - 2011 Jan 1

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Chronic Hepatitis C
Insulin Resistance
Fibrosis
Genotype
Liver
Homeostasis
Odds Ratio
Infection
Cholesterol
Ribavirin
Hepacivirus
Logistic Models
Inflammation
Biopsy
Serum
Population

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Patel, Keyur ; Thompson, Alexander J. ; Chuang, Wan Long ; Lee, Chuan Mo ; Peng, Chen Yuan ; Shanmuganathan, Ganesananthan ; Thongsawat, Satawat ; Tanwandee, Tawesak ; Mahachai, Varocha ; Pramoolsinsap, Chutima ; Cho, Mong ; Han, KwangHyub ; Shah, Samir R. ; Foster, Graham R. ; Clark, Paul J. ; Pulkstenis, Erik ; Subramanian, G. Mani ; Mchutchison, John G. / Insulin resistance is independently associated with significant hepatic fibrosis in Asian chronic hepatitis C genotype 2 or 3 patients. In: Journal of Gastroenterology and Hepatology (Australia). 2011 ; Vol. 26, No. 7. pp. 1182-1188.
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abstract = "Background and Aim: The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian-region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC genotype 2/3 patients. Methods: A total of 303 treatment-na{\"i}ve Asian-region patients with CHC genotype 2/3 were enrolled in a multicenter phase 3 study of albinterferon alfa-2b plus ribavirin for 24weeks. IR was defined as Homeostasis Model for Assessment of IR (HOMA-IR)>2. Baseline liver biopsy was evaluated by a single expert histopathologist. Post hoc subgroup logistic regression modeling selected for independent variables associated with significant fibrosis (METAVIR stage F2-F4). Results: Insulin resistance was available in 263 non-diabetic Asian-region patients (hepatitis C virus-2 [HCV-2]=171, HCV-3=92), and 433 non-Asian region patients (407 {"}Caucasian{"}); METAVIR fibrosis prevalence F0-F1 (minimal fibrosis)=201 (77{\%}) and F2-F4 (significant fibrosis)=59 (23{\%}), and steatosis prevalence of grade 0=169 (65{\%}), grade 1=64 (25{\%}), grade 2/3=27 (10{\%}). Median HOMA-IR was 1.8 (interquartile range: 1.2-2.7); 100 (38{\%}) patients had HOMA-IR>2. Factors independently associated with significant fibrosis included HOMA-IR (odds ratio [OR]=8.42), necro-inflammatory grade (OR=3.17), age (OR=1.07) and serum total cholesterol levels (OR=0.008). This was similar to non-Asian region patients, but steatosis was not associated with significant fibrosis in either cohort. Conclusions: In this subgroup study of Asian-region HCV genotype 2 or 3 patients, insulin resistance, along with age, cholesterol levels and necro-inflammation, but not steatosis may be associated with significant hepatic fibrosis.",
author = "Keyur Patel and Thompson, {Alexander J.} and Chuang, {Wan Long} and Lee, {Chuan Mo} and Peng, {Chen Yuan} and Ganesananthan Shanmuganathan and Satawat Thongsawat and Tawesak Tanwandee and Varocha Mahachai and Chutima Pramoolsinsap and Mong Cho and KwangHyub Han and Shah, {Samir R.} and Foster, {Graham R.} and Clark, {Paul J.} and Erik Pulkstenis and Subramanian, {G. Mani} and Mchutchison, {John G.}",
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Patel, K, Thompson, AJ, Chuang, WL, Lee, CM, Peng, CY, Shanmuganathan, G, Thongsawat, S, Tanwandee, T, Mahachai, V, Pramoolsinsap, C, Cho, M, Han, K, Shah, SR, Foster, GR, Clark, PJ, Pulkstenis, E, Subramanian, GM & Mchutchison, JG 2011, 'Insulin resistance is independently associated with significant hepatic fibrosis in Asian chronic hepatitis C genotype 2 or 3 patients', Journal of Gastroenterology and Hepatology (Australia), vol. 26, no. 7, pp. 1182-1188. https://doi.org/10.1111/j.1440-1746.2011.06722.x

Insulin resistance is independently associated with significant hepatic fibrosis in Asian chronic hepatitis C genotype 2 or 3 patients. / Patel, Keyur; Thompson, Alexander J.; Chuang, Wan Long; Lee, Chuan Mo; Peng, Chen Yuan; Shanmuganathan, Ganesananthan; Thongsawat, Satawat; Tanwandee, Tawesak; Mahachai, Varocha; Pramoolsinsap, Chutima; Cho, Mong; Han, KwangHyub; Shah, Samir R.; Foster, Graham R.; Clark, Paul J.; Pulkstenis, Erik; Subramanian, G. Mani; Mchutchison, John G.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 26, No. 7, 01.01.2011, p. 1182-1188.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Insulin resistance is independently associated with significant hepatic fibrosis in Asian chronic hepatitis C genotype 2 or 3 patients

AU - Patel, Keyur

AU - Thompson, Alexander J.

AU - Chuang, Wan Long

AU - Lee, Chuan Mo

AU - Peng, Chen Yuan

AU - Shanmuganathan, Ganesananthan

AU - Thongsawat, Satawat

AU - Tanwandee, Tawesak

AU - Mahachai, Varocha

AU - Pramoolsinsap, Chutima

AU - Cho, Mong

AU - Han, KwangHyub

AU - Shah, Samir R.

AU - Foster, Graham R.

AU - Clark, Paul J.

AU - Pulkstenis, Erik

AU - Subramanian, G. Mani

AU - Mchutchison, John G.

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Background and Aim: The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian-region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC genotype 2/3 patients. Methods: A total of 303 treatment-naïve Asian-region patients with CHC genotype 2/3 were enrolled in a multicenter phase 3 study of albinterferon alfa-2b plus ribavirin for 24weeks. IR was defined as Homeostasis Model for Assessment of IR (HOMA-IR)>2. Baseline liver biopsy was evaluated by a single expert histopathologist. Post hoc subgroup logistic regression modeling selected for independent variables associated with significant fibrosis (METAVIR stage F2-F4). Results: Insulin resistance was available in 263 non-diabetic Asian-region patients (hepatitis C virus-2 [HCV-2]=171, HCV-3=92), and 433 non-Asian region patients (407 "Caucasian"); METAVIR fibrosis prevalence F0-F1 (minimal fibrosis)=201 (77%) and F2-F4 (significant fibrosis)=59 (23%), and steatosis prevalence of grade 0=169 (65%), grade 1=64 (25%), grade 2/3=27 (10%). Median HOMA-IR was 1.8 (interquartile range: 1.2-2.7); 100 (38%) patients had HOMA-IR>2. Factors independently associated with significant fibrosis included HOMA-IR (odds ratio [OR]=8.42), necro-inflammatory grade (OR=3.17), age (OR=1.07) and serum total cholesterol levels (OR=0.008). This was similar to non-Asian region patients, but steatosis was not associated with significant fibrosis in either cohort. Conclusions: In this subgroup study of Asian-region HCV genotype 2 or 3 patients, insulin resistance, along with age, cholesterol levels and necro-inflammation, but not steatosis may be associated with significant hepatic fibrosis.

AB - Background and Aim: The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian-region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC genotype 2/3 patients. Methods: A total of 303 treatment-naïve Asian-region patients with CHC genotype 2/3 were enrolled in a multicenter phase 3 study of albinterferon alfa-2b plus ribavirin for 24weeks. IR was defined as Homeostasis Model for Assessment of IR (HOMA-IR)>2. Baseline liver biopsy was evaluated by a single expert histopathologist. Post hoc subgroup logistic regression modeling selected for independent variables associated with significant fibrosis (METAVIR stage F2-F4). Results: Insulin resistance was available in 263 non-diabetic Asian-region patients (hepatitis C virus-2 [HCV-2]=171, HCV-3=92), and 433 non-Asian region patients (407 "Caucasian"); METAVIR fibrosis prevalence F0-F1 (minimal fibrosis)=201 (77%) and F2-F4 (significant fibrosis)=59 (23%), and steatosis prevalence of grade 0=169 (65%), grade 1=64 (25%), grade 2/3=27 (10%). Median HOMA-IR was 1.8 (interquartile range: 1.2-2.7); 100 (38%) patients had HOMA-IR>2. Factors independently associated with significant fibrosis included HOMA-IR (odds ratio [OR]=8.42), necro-inflammatory grade (OR=3.17), age (OR=1.07) and serum total cholesterol levels (OR=0.008). This was similar to non-Asian region patients, but steatosis was not associated with significant fibrosis in either cohort. Conclusions: In this subgroup study of Asian-region HCV genotype 2 or 3 patients, insulin resistance, along with age, cholesterol levels and necro-inflammation, but not steatosis may be associated with significant hepatic fibrosis.

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