The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance

Abstract

(2017) The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance, Virulence, 8:7, 1255-1264, DOI: 10.1080/21505594.2017 ABSTRACT Background: The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation. Methods: A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri-and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center. Results: Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy. In patients with a sustained virological response (SVR; n D 455), at 24 weeks post-therapy, sex, BMI, aspartate aminotransferase to platelet ratio index (APRI), HOMA-IR and steatosis were associated with adiponectin levels, and IFNL3 genotype was associated with HOMA-IR levels. GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels. Compared with pre-therapy levels, adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients, regardless of baseline insulin resistance (IR). However, HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR. Compared with controls, immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis. Conclusions: During HCV infection, adiponectin may affect insulin sensitivity through triglycerides. After viral clearance, adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis; with a link to the IFNL3 genotype, insulin sensitivity improved only in patients with baseline IR.

Systematic review: chronic viral hepatitis and metabolic derangement

“…A few studies reported the changes of adiponectin levels upon antiviral treatment. A lower adiponectin level was a negative predictive factor of achieving SVR in interferon‐based therapy . A decrease in adiponectin level is observed only in CHC patients who have achieved SVR.…”

“…These results were confirmed by Aksõz et al, in which chronic HCV infection did not affect adiponectin concentration in the absence of metabolic disorders . Moreover, adiponectin levels are not associated with HCV RNA levels, suggesting the impact of HCV infection on adiponectin levels may not be directly caused by virus itself but by metabolic or hepatic alterations after HCV infection …”

“…178 Moreover, adiponectin levels are not associated with HCV RNA levels, suggesting the impact of HCV infection on adiponectin levels may not be directly caused by virus itself but by metabolic or hepatic alterations after HCV infection. 179,180 The reduced expression level of adiponectin in CHC patients with steatosis may relate to tumour necrosis factor alpha. 181,182 This finding was confirmed by a study by Zografos et al, showing that low adiponectin and high tumour necrosis factor alpha levels were associated with hepatic steatosis.…”

Hepatitis C virus infection is associated with hepatic and adipose tissue insulin resistance that improves after viral cure

“…Hepatitis C virus replicates within hepatocytes in the liver and yet the sites of insulin resistance in patients with CHC remain elusive, with some studies reporting the liver as the primary site and others suggest extra‐hepatic sites, namely adipose tissue and skeletal muscle . Most of the current evidence studying insulin resistance in CHC is based on homoeostatic model assessment of insulin resistance (HOMA‐IR) which cannot distinguish sites of IR. Hepatic steatosis and insulin resistance can limit treatment response to interferon‐based therapies .…”

Adiponectin serum level changes and its dynamic relationship with hepatitis C during viral clearance

“…12 The study include 747 consecutive CHC patients and 546 of these complete anti-HCV therapy cycle with weight-based pegylated interferon-a-2b and ribavirin, 407 (54.5%) and 295 (39.5%) patients were respectively infected by HCV genotype 1 and 2. The Authors found the association between adiponectin values and sex, triglycerides serum levels and hepatic steatosis, and interferon λ3 (IFNL3) genotype with IR assessed by homeostasis model assessment-estimated insulin resistance (HOMA-IR), before anti-HCV therapy.…”