The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C

Abstract

SUMMARY AimsTo assess whether host metabolic factors influence the degree of hepatic steatosis and fibrosis in patients infected with hepatitis C virus, and to evaluate the impact of anti-viral therapy on insulin resistance and serum levels of adipocytokines. MethodsClinical and biochemical features, anthropometrical characteristics, and levels of fasting insulin, leptin, adiponectin and resistin were measured in 'naïve' patients with chronic hepatitis C, before, during and after therapy with Peg-Interferon-alpha 2a plus Ribavirin. ResultsForty-eight patients were included (M/F 28/20; mean age 50.0 AE 12.6 years; 62.5% genotype-1). Body mass index was 26.4 AE 4.0 kg/m 2 , and visceral obesity was present in 24 patients. At multivariate analysis (RR; 95% CI), steatosis was associated to older age (1.08; 1-1.18), necroinflammatory activity (17.67; 1.6-194.46), and raised insulin levels (1.39; 1.1-1.77). Fibrosis was related to necroinflammatory activity (25.73; 2.54-261.11), and steatosis (6.47; 1.09-38.29). Sustained viral response was achieved by 62.5% of patients and was associated with younger age (0.92; 0.85-0.99), genotype non-1 (10.61; 1.52-73.76) and absence of visceral obesity (13.78; 2.36-80.29). At the end of follow-up, insulin and the homeostasis model assesment for insulin resistance were reduced and adiponectin increased when compared with baseline, all unrelated to the outcome of treatment. ConclusionsVisceral obesity correlates with the degree of steatosis and fibrosis, and it negatively affects treatment response. Significant changes of insulin resistance and adipocytokines occur under treatment, irrespective of virological outcome.

Serum leptin and plasma ghrelin concentrations in patients with chronic hepatitis C virus with steatosis: Their effect on the response to antiviral therapy

“…Although, many studies were demonstrated profibrogenic role of leptin [24,25], others did not reveal any role of leptin in determining severity of steatosis and fibrosis in patients with HCV [26]. Similarly to other investigators [18,24], we found high serum leptin concentrations and high insulin resistance at base line in patients with HCV compared to healthy controls.…”

Hepatitis C virus and type 2 diabetes

“…Only TNF-levels seemed to correlate with severity of portal and periportal inflammation, but none of the cytokines considered in this study were correlated with liver fibrosis. Several other studies have failed to pinpoint a clear correlation between the severity of fibrosis and serum levels of leptin [94,[104][105][106] , with only one positive report [107] . The role of adiponectin is quite controversial [103] .…”

Risk factors for cytomegalovirus reactivation after liver transplantation: Can pre‐transplant cytomegalovirus antibody titers predict outcome?

“…An association between a higher BMI and an increased risk of other viral infection such as influenza A and hepatitis C has been reported. 21,22 The secretion of cytokines from adipose tissue in obese patients may dysregulate the immune system, although the true mechanism remains unclear. 23,24 A prolonged cold ischemia time has been shown to increase the risk of ischemic cholangiopathy and subsequent allograft rejection.…”

“…23,24 A prolonged cold ischemia time has been shown to increase the risk of ischemic cholangiopathy and subsequent allograft rejection. 22 This event may predispose these patients to more aggressive immunosuppression and thus lead to an increased risk of CMV infection. We also found an increased risk of CMV infection in patients who received IL2RA for induction therapy, and this has not been identified in previous studies.…”

“…The median age was 57 years (IQR, 47-62 years), and the sex distribution was almost equal. The median MELD score was 25 (IQR, [18][19][20][21][22][23][24][25][26][27][28][29]. The majority of patients were Caucasian (85%).…”