Update on chronic hepatitis C

The burden of chronic hepatitis C infection remains significant in the United States and worldwide. Increased knowledge regarding the natural history of acute and chronic infection and the key factors responsible for disease progression, risk for cirrhosis, and risk for hepatocellular carcinoma are critical in guiding secondary and tertiary prevention measures. The past decade has been substantial improvement of antiviral therapy for chronic hepatitis C virus with an increasing number of individuals achieving viral eradication. Decisions regarding whom, when, and how to use antiviral therapy have become more complex and change as new studies become available.

There are an estimated 170 million individuals worldwide with chronic hepatitis C virus (HCV) infection. In the United States, the incidence of HCV has decreased since the late 1980s, but models based on known prevalent cases and the increased risk for cirrhosis and hepatocellular carcinoma with longer duration of infection predict that the rate of liver-related complications of chronic infection is dependent on identification of infected individuals, modification of factors that negatively influence disease progression (eg. alcohol use), and treatment of infection and complications of chronic liver disease will be prevented most effectively by the development of a vaccine for HCV.

Epidemiology and natural history

Risk factors for HCV acquisition in the United States has changed over time, with a decrease in the number of infections attributable to blood transfusion and increased proportion attributed to sexual contact. Sharing of contaminated needles and paraphernalia among injection drug users remain the most common mode of HCV transmission, both past and present.

Screening for HCV infection is targeted toward risk groups with an HCV prevalence rate greater than that of the general population, including all patients with a history of transfusion of clotting factor before 1987, patients who received blood products or an organ transplant before 1992, patients with a history of injection drug use, chronic dialysis recipients, infants born to HCV-positive mothers, all human immunodeficiency virus (HIV)-infected persons, and any patient with clinical evidence of liver disease. The identification of infected individuals is dependent on health care providers recognizing persons at risk and offering testing. Although knowledge of HCV screening guidelines is high, physicians do not inquire consistently regarding HCV risk factors nor do they always screen those identified with risk factors. The absence of increased liver enzymes may be one factor influencing screening in persons with recognized risk factors, but the primary barrier to identifying infected individuals is the lack of inquiry into current and past risk factors for HCV acquisition.

The natural history of HCV is quite variable. After exposure to HCV, 55%-80% of persons become chronically infected. The age of infection is linked with risk for chronicity and rate of disease progression. Among children and young adults, spontaneous clearance of infection occurs in approximately 40%-45% and cirrhosis develops in 2%-4% after 20 years of infection. In contrast, older individuals clear virus spontaneously less often (-20%), and 20%-30% progress to cirrhosis after 20 years or more. Among those with cirrhosis, risks for liver decomposition are estimated to be 3%-4% annually and liver cancer occurs at an annual incidence of 1.4%-6.9%. The prevention of liver-related complications, including cirrhosis and hepatocellular carcinoma, is an important goal of antiviral therapy.

The risk-benefit of antiviral therapy required an understanding of the natural history of infection and the anticipated future risk for liver complications. Factors most consistently linked with a higher risk for developing cirrhosis are older age at infection, long duration of infection, male sex, heavy alcohol use, and HIV co-infection. Other immuno-compromised populations, including transplant recipients, are at a higher risk for progressive liver disease than non-immunocompromised populations. Steatosis and possibly race are additional factors influencing fibrosis progression. Recent studies suggest African Americans may have less severe histologic disease compared with Caucasians, but appear to have higher rates of hepatocellular carcinoma.

Initial evaluation of the  anti-hepatitis C virus-positive patient

The initial evaluation of an anti-HCV-positive individual serves to determine the following: (1) if chronic infection is present or whether spontaneous viral clearance has occurred, (2) exclusion of concomitant causes of liver disease, (3) the severity of liver disease, and (4) suitability for antiviral therapy. Identification of risk factors for acquisition of infection may help to estimate the duration of infection. Counseling regarding prevention of transmission to others and lifestyle modifications to reduce the risk for disease progression are required. Alcohol and drug dependency are important comorbidities to identify and treat. Review of systems focuses on hepatic and extrahepatic manifestation of HCV infection, and relevant comorbid medical and psychiatric conditions.

In all anti-HCV-positive individuals, the persistence of infection should be confirmed by detections of HCV-RNA in serum using a sensitive qualitative assay. The confirmation of viremia also is necessary before initiation genotype or viral load and disease severity, but these virologic parameters have great relevance in the determination of treatment duration, ribavirin dose, and likelihood of response.

Therefore, quantitative HCV-RNA levels and genotyping should be measured in those being considered for antiviral therapy. Other causes of liver disease should be ruled out if liver enzyme levels are increased. In general, a baseline abdominal ultrasound is used to assess for radiologic signs of cirrhosis and portal hypertension, especially if the duration of infection is unknown or estimated to be in excess of 20 years.