Severity of HCV-Induced Liver Damage Alters Glucose Homeostasis in Noncirrhotic Patients with Chronic HCV Infection

Abstract

Background/Aims: To investigate the link between hepatitis C infection and glucose intolerance, we measured insulin sensitivity, glucose effectiveness and β-cell secretion in noncirrhotic HCV-infected patients with normal glucose tolerance according to WHO criteria as assessed by oral glucose tolerance tests. Methods: Glucose, insulin and C-peptide data from frequently sampled intravenous glucose tolerance tests were analyzed using the minimal modeling technique for glucose and C-peptide to determine insulin sensitivity, glucose effectiveness, first and second phase insulin secretion in noncirrhotic HCV-infected patients (n = 10) and in healthy control subjects (n = 10). Histological activity index (HAI) as well as the extent of fibrosis were evaluated by scoring liver biopsies. Results: Insulin sensitivity (2.72 ± 1.63 vs. 6.84 ± 1.20 10^–4 min^–1 per µU/ml, p < 0.01) and glucose effectiveness (2.29 ± 0.45 vs. 2.89 ± 0.39 10^–2 min^–1, p < 0.05) ere significantly lower in patients with HCV-induced liver disease. Insulin sensitivity was negatively related to serum alanine aminotransferase (r = –0.47, p < 0.05) and aspartate aminotransferase concentrations (r = –0.65, p < 0.05). Multiple linear regression analysis revealed a strong relation of insulin sensitivity with fibrosis score and HAI (r = –0.82, p < 0.02 for both). Second phase insulin secretion was significantly enhanced in HCV-infected patients (14.30 ± 2.04 vs. 8.29 ± 1.65 min^–1, p < 0.05). Conclusions: HCV-infected patients with normal glucose tolerance are insulin and glucose resistant. The impairment of glucose tolerance appears to be closely related with the severity of HCV-induced liver damage.

Insulin resistance and insulin secretion in chronic hepatitis C virus infection

“…HCV has been identified in bile ducts within the liver [35], and HCV RNA was detected in pancreatic tissue harvested from patients with acquired immune deficiency syndrome [36]. The production of cytokines during HCV-induced inflammatory processes in liver tissue could explain the progressive impairment of b-cell function with increasing liver damage [12].…”

“…Konrad et al [12] suggested that insulin resistance in patients with CH due to HCV infection (CHC) is caused by the liver disease itself. In contrast, Petit et al [13] demonstrated that insulin resistance in nondiabetic HCV-infected patients correlates with the staging of liver fibrosis but may occur at an early stage in the course of HCV infection, even in nondiabetic patients.…”

Glucose Abnormalities in Patients with Hepatitis C Virus Infection

“…the fasting insulin and a decrease in insulin sensitivity have been observed in HCV-infected subjects with a moderate or severe degree of hepatic fibrosis (75,134,135). However, HCV-infected patients without fibrosis (fibrosis stage 0) also present higher insulin resistance than patients with primary biliary cirrhosis with different degrees of hepatic fibrosis (fibrosis stages 1-3) and healthy individuals (36).…”

“…Alternatively, insulin resistance has been described as an independent factor in predicting the presence of hepatic fibrosis in HCV-infected patients (36). In fact, several studies have reported that both insulin resistance and diabetes can adversely affect the course of chronic hepatitis C leading to enhanced steatosis and liver fibrosis (24,28,95,96,100,101,134) and even increase the risk of hepatocellular carcinoma (136,137). Notably, Romero-Gó mez et al (138) and D'Souza et al (139), have recently shown that insulin resistance is an independent predictor of a poor response to antiviral therapy in chronic hepatitis C infection.…”

Fat, diabetes, and liver injury in chronic hepatitis C

“…For example, HCVinduced cirrhosis could increase the occurrence of diabetes merely by an alteration in glucose homeostasis [17]. Consequently, studies have confirmed the association between HCV and type 2 diabetes, even after excluding cirrhotic patients [8][9][10]. Moreover, in population-based cohort studies, undiagnosed end-stage liver disease is highly improbable.…”