Management of Special Groups: Obesity and HCV Infection
KEY POINTS
  • Steatosis is common in patients with HCV infection; obesity, alcohol use, and genotype 3 are the factors most commonly associated with it.
  • Superimposed steatohepatitis is often associated with advanced liver disease.
  • Response to therapy in HCV-infected patients is inversely related to body mass index.
  • Weight-based dosing of ribavirin is important in patients with genotype 1 infection.
Obesity and its complications have reached epidemic proportions in the Western world. Obesity affects HCV in two different ways. First, obese patients with HCV may have a second form of liver disease, nonalcoholic fatty liver disease, and its subtype of nonalcoholic steatohepatitis (NASH). HCV-infected patients who also have histologic evidence for superimposed NASH seem to have more advanced liver disease.151,152 Second, obese patients with HCV seem to have lower rates of sustained virologic response to IFN/ribavirin-containing regimens.153

In one study, Bressler et al conducted a retrospective analysis of factors associated with treatment response over the past decade at a single treatment center in Toronto.154 One of their findings was that a poor response to therapy was associated with a body mass index (BMI) greater than 30 kg/m2. The poorer response could not be attributed to steatosis in liver biopsy specimens.154 At the same time, lower BMIs were associated with better treatment outcomes in two large studies of PEG-IFN plus ribavirin.49,50 And in an earlier study, Lam et al found that IFN blood levels and 2´,5´-oligoadenylate synthetase induction were diminished in obese patients after they had taken a single 10 million IU dose of IFN alfa-2b.155 In addition, Hickman et al found that ALT values, liver steatosis, and histologic activity improved in HCV-infected patients following a 3-month period of weight loss.156

Notably, steatosis is a common finding in patients with chronic hepatitis C. Alcohol use is a well-known cause of hepatic steatosis and steatohepatitis. Although HCV genotype 3 is independently associated with hepatic steatosis (virus-related steatosis), patients who have non-genotype 3 HCV and steatosis seem to have conditions typically associated with metabolic syndrome (obesity, type 2 diabetes, hyperlipidemia). In patients with genotype 3, steatosis seems to improve with sustained virologic response to antiviral therapy. On the other hand, in patients with non-genotype 3 infection, improvement in steatosis may be related to improvement in obesity.153,157

A number of mechanisms have been proposed to explain the impact of obesity on response to therapy for HCV infection. First, the lower rate of response may be related to lower relative doses of ribavirin in obese patients, since patients with an elevated BMI may have a larger distribution volume and lower serum antiviral drug concentrations. As mentioned earlier, an optimal, weight-based dose of ribavirin seems to be important for sustained virologic response in patients with HCV genotype 1. Second, the presence of hepatic steatosis related to obesity may decrease the contact between the antiviral drug and the infected hepatocytes. Third, leptin resistance, which is commonly seen in obese patients, may diminish the immune response of obese HCV-infected patients to antiviral therapy.157 Despite these interesting possibilities, the interactions between obesity, nonalcoholic fatty liver disease, and HCV remain important areas for future research.