Raymond D'Souza

Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis c and in the response to antiviral therapy

OBJECTIVES:To assess whether insulin resistance is associated with liver fibrosis in a group of patients with chronic hepatitis C virus (HCV) infection and whether there were any differences in insulin resistance between Asians and the indigenous Caucasian population. Secondly, to assess whether insulin resistance is associated with sustained virological response to antiviral therapy.METHODS:We determined insulin resistance in 59 (30 Caucasians; 29 Asians) consecutive patients with HCV prior to starting antiviral therapy. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). The relationship between insulin resistance and biochemical, virological, and histological data together with response to antiviral therapy was assessed.RESULTS:In multivariable analyses, insulin resistance as measured using the HOMA-IR model correlated positively with the stage of fibrosis, with higher degrees of insulin resistance in those with greater degrees of fibrosis (p < 0.001). This significant relationship remained even after excluding cirrhotic patients, or after adjusting for other factors associated with fibrosis in univariable analyses. Insulin resistance was significantly higher in Asians than Caucasians (p= 0.004). Around half (55.6%) of patients completing a course of antiviral treatment had a sustained virological response. Multivariable logistic regression identified HCV genotype 3, lower fasting glucose levels, and lower aspartate transaminase (AST) levels as being associated with a higher odds of a sustained virological response. After adjusting for these variables, Asian ethnicity, higher fasting insulin levels, and higher HOMA-IR levels were all associated with a poorer virological response to therapy.CONCLUSIONS:Insulin resistance contributes to liver fibrosis in chronic HCV infection; this relationship is not genotypic specific. Asian patients had higher insulin resistance than Caucasians. Insulin resistance is also an important predictor of sustained response to antiviral therapy.

An unusual form of autoimmune hepatitis in young Somalian men.

Background: Significant diversity in disease severity has been identified for autoimmune disorders among different ethnic groups. Current knowledge of both the natural history and management of autoimmune hepatitis (AIH) has been derived from European or Japanese patients, and there is limited information about the disease in patients from other ethnic groups.

Prevalence of Hepatitis C–Related Cirrhosis in Elderly Asian Patients Infected in Childhood

BACKGROUND & AIMS Approximately 20% of hepatitis C virus (HCV) patients develop cirrhosis from infection after about 20 years. The proportion of patients developing cirrhosis for longer than 30 years after infection is unknown. Our objectives were to determine the prevalence of HCV-related cirrhosis in a population of Asian patients who were infected in childhood 20 to 80 years ago and compare this with the prevalence of cirrhosis in Caucasian patients referred to the same hospitals. METHODS Retrospective analyses were performed of all patients who had detectable HCV-RNA levels and who attended local hospitals in northeast London between 1992 and 2003. Factors implicated in the development of cirrhosis were examined by multivariable analysis. RESULTS A total of 143 adult Asian patients who had been infected with HCV for many decades were compared with 239 Caucasian patients. The prevalence of cirrhosis increased with age. Of Asian patients aged 61-80 years (n = 55) 78% had cirrhosis, whereas 25% of Caucasian patients aged 61-80 years (n = 55) had cirrhosis. Multivariable linear analysis revealed that fibrosis progression and age were similar in both groups and the difference in the prevalence of cirrhosis was not explained by any unique Asian characteristic other than prolonged infection. CONCLUSIONS The prevalence of cirrhosis in patients with chronic HCV increases with increasing duration of infection. In Asian patients infected at birth, infection for over 60 years causes cirrhosis in 71% of infected individuals. Because relationship between the severity of fibrosis and age in Asian patients is similar to that seen in Caucasian patients it is likely that similar rates of cirrhosis will be seen in other patients who are infected for more than 60 years.

Relationship between serum ferritin, hepatic iron staining, diabetes mellitus and fibrosis progression in patients with chronic hepatitis C.

Background : Chronic infection with the hepatitis C virus affects over 170 million individuals worldwide and 20% of patients develop cirrhosis after 20 years. Increased iron stores and hepatic iron content have been suggested to be important in fibrosis progression. The increased prevalence of diabetes mellitus has been associated with increased iron deposits in patients with chronic hepatitis C.

Improving hepatitis C services across the UK: response to a walk-in HCV testing service

The Department of Health (DH) estimates that approximately 0.4% of the UK population are chronically infected with hepatitis C virus (HCV) (that is, 200 000 people). As few as 10% of these individuals, who are at risk of end stage liver disease, are thought to be aware of their infection. Clearly action is required to identify and treat these patients with current drugs (pegylated interferons …

Discontinuation of pegylated interferon plus ribavirin in patients who are not responding to therapy -- patients' views of early cessation of therapy.

Background : Current therapy for chronic hepatitis C infection involves a course of pegylated interferon and ribavirin. Patients who do not show a virological response after 12 weeks of therapy have a low probability of sustained virological response and it is therefore recommended that such patients stop treatment.