Hepatitis C virus (HCV), a member of the Flaviviridae family, consists of at least 6 genotypes and more than 50 subtypes. Genotype 1 is the most common in the United States and genotypes 2 and 3 are the most common in Europe and Asia. An estimated 3.8 million individuals in the United States, 1.8% of the population, have been exposed to HCV, and 2.7 million of these individuals have detectable HCV RNA indicating chronic viral infection. The virus causes approximately 10,000 deaths each year. HCV has infected an estimated 170 million individuals worldwide, about 3% of the world's entire population, and the virus is the leading cause of liver transplantation. In comparison, HIV has an estimated prevalence of 800,000-900,000 in the United States. It appears that many with chronic HCV alone do not progress to complications, a reasonable percentage with HCV alone may eventually die for reasons completely unrelated to HCV. The risk of cirrhosis in patients with chronic HCV infection is approximately 20% within 20 years and 30% within 30 years ,and this condition carries a mortality rate of approximately 2% to 5% a year. For example, the risk of dying 3 years after developing cirrhosis is 6%- 15%. Treatment with interferon can stabilize (slow or stop) fibrosis progression despite little or no viral load reduction. Further, HCV-related cirrhosis (HCC) is the leading predisposing cause for primary liver cancer, and following the development of cirrhosis HCC occurs at a rate of approximately 3-10% per year. So, 3 years after developing cirrhosis the risk for HCC is 9%-30%.

Based on estimates and projections from Gary Davis (Hepatology 1998;28), K.Rajender Reddy (University of Miami) suggested at DDW (Spring 2001) that the disease burden from HCV is likely to rise considerably over the next 10-20 years. His estimates/projections are that the increase in the number of patients with cirrhosis over the next 8 to 10 years could be in the order of 500%, which could cause increasing demands on liver transplantation. The cost of health care is also likely to rise significantly. I presume these estimates do not factor in therapy with pegylated interferon/ribavirin. See section on Liver Transplantation.

HCV can be more of a problem when coinfection with HIV is present. Although more studies are needed to better understand the affect of HIV on HCV progression over the longer term and the effect of HAART on liver disease progression, a number of studies show that HIV can accelerate liver disease progression. Liver disease progression can lead to cirrhosis and liver cancer, and acceleration may lead to progression in a shorter period of time. Studies are mixed on the affect of HAART on HCV progression. As you will see later in this report several studies appear to show HAART having a negative impact on liver disease, while other studies suggest HAART may not have such an affect or may slow progression. Perhaps all may be true and it may depend on the patient's situation, health, and history. Recent studies suggest that, in the era of potent antiretroviral therapy, the number of deaths due to liver disease in HIV-1infected individuals has been increasing. In a cohort of about 4,000 individuals, liver disease was the primary cause of non-AIDS death. In a recently published study that retrospectively examined the causes of death between 1991 and 1998 in HIV-1 seropositive individuals, end-stage liver disease was found to be the leading cause among hospitalized HIV-seropositive individuals. Most of these individuals were HCV-positive.

The prevalence of coinfection appears staggering as it s been estimated that about 30% or more of HIV infected may also have HCV. Perhaps as many as 60-90% HIV-infected persons in the United States and Western Europe who acquired HIV through intravenous drugs are also infected with HCV, since HCV is transmitted by blood just like HIV. In fact, HCV may be more easily transmitted than HIV. It s been estimated that most IVDUs get HCV in their first year of IVDU and therefore are likely to have had HCV for longer than they have had HIV. Considering the percentages of HIV+IVDUs who are African-American and Latino, coinfection in these communities appears to be a major challenge.