Hepatitis C and Steatosis

Hepatitis C infection and non-alcohol-related hepatic steatosis are the most common liver dieases worldwide, and both conditions often co-exist in the same patient. Hepatitis C virus (HCV) genotype 3 directly induces development of steatosis, whereas in patients with non-genotype 3 chronic hepatitis C infection, insulin resistance plays a key role in the pathophysiology of steatosis. Insulin resistance and its clinical components including obesity, hyperglycemia, hypertriglyceridemia, increased blood pressure, and low HDL-cholesterol levels are often seen in patients with chronic hepatitis C infection. Both increased adipocity and presence of steatosis may increase the risk of fibrosis progression, and both have been associated with a decreased rate of response to antiviral treatment. Hence, liver steatosis in the setting of HCV infection is a distinct condition with specific clinical and prognostic implications. Accumulating evidence suggests that weight management may lead not only to a decrease in steatosis but also improvement in fibrosis severity. However, further studies are necessary to determine whether weight reduction improves response to antiviral therapy.

Introduction

Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. According to the most recent WHO estimate the prevalence of HCV is approximately 2.2%, affecting approximately 123 million people in the world (1). Hepatic steatosis refers to excessive fat accumulation in the liver, which also is very common in the general population. Hepatic steatosis is the most common cause of elevated aminotransferases and probably the most common cause of chronic liver disease worldwide (2). Over the last decade it has become apparent that liver steatosis in the setting of HCV infection is a distinct condition with specific clinical and prognostic features 3, 4, 5, 6, 7, 8.

Several epidemiological studies have shown that hepatic steatosis among people who do not drink alcohol, or drink only small amounts of alcohol—nonalcoholic fatty liver disease (NAFLD)—affects a substantial proportion of the general population from different countries (2). NAFLD is considered to be the liver component of the metabolic syndrome 2, 9, 10, 11, 12, a cluster of abnormalities related to insulin resistance including central obesity, high blood pressure, increased triglyceride levels, low HDL-cholesterol, and hyperglycemia. The estimated prevalence of NAFLD reported to date depends on the methodology used and the type of population studied. In a recent study using magnetic resonance spectroscopy, hepatic steatosis was observed in an adjusted 34% of the general adult population in Dallas, TX (13). Similarly, a total of 33% of individuals undergoing evaluation for potential live liver donors in the U.S. were found to have liver steatosis on a liver biospy (14). Population-based studies in Italy, China, and Japan have reported a prevalence of NAFLD of 23% (15), 15% (16), and 14% (17), respectively. NAFLD is the most common explanation of chronically elevated aminotransferases among patients undergoing a liver biopsy 18, 19, 20, 21. With an increase in prevalence of obesity and type II diabetes mellitus in the Western world 22, 23, the incidence and prevalence of NAFLD is probably increasing in parallel over time.

The occurrence of NAFLD in patients with HCV is in most cases due to concomitant features of the metabolic syndrome or due to infection with genotype 3 of HCV 3, 4, 5, 6, 7, 8 or presence of both the metabolic syndrome and genotype 3. The presence of steatosis in patients with HVC has prognostic implications, as it is associated with a more rapid progression of fibrosis and a poorer response to treatment as detailed below.