Cirrhosis, hepatocellular carcinoma, and liver transplantation are among the most serious potential sequelae of hepatitis C, a viral illness that affects more than 3 million US adults. Often asymptomatic until the disease converts to chronic form, HCV is diagnosed through lab studies that include an HCV antibody screen, an HCV RNA assay, and genotyping. Currently available treatments make it possible to eradicate the disease in many patients, and promising new developments are being investigated. Primary care providers play an important role in managing patients with HCV throughout testing, treatment, and follow-up.
The hepatitis C virus (HCV) is estimated to affect 180 million people worldwide, and the CDC estimates that approximately 3.2 million persons in the United States are chronically infected with HCV.1,2 In recent years, reported HCV-related deaths have outnumbered those attributed to HIV infection.3 Clinicians in almost any practice area are likely to encounter patients affected by HCV.
Infection with HCV is a major risk factor for cirrhosis, a disease associated with significant morbidity and mortality; HCV-associated cirrhosis is considered the leading cause of liver transplantation.4
Screening for HCV is important in patients with known risk factors for the disease1 (see Table 11,2,5). Of note, however, the CDC is in the process of expanding its recommendations to one-time screening for all Americans born between 1945 and 1965—an age-group that accounts for more than 75% of cases of HCV infection among US adults.6 (Clinicians interested in viewing the draft document for public comment can refer to www.regulations.gov, docket #CDC-2-12-0005.)
PATIENT PRESENTATION/ PATIENT HISTORY
Most patients with hepatitis C present without signs or symptoms of their illness. If symptoms are present, they may include fatigue, pruritus, abdominal pain/ discomfort, arthralgias, or anorexia; results on routine liver function tests may be abnormal.1,7-9 Liver function may appear normal in patients with HCV, although 30% of patients with a normal alanine aminotransferase (ALT) level may have significant fibrosis.10 Lichen planus is commonly associated with HCV infection,9-11 and patients with this condition should be screened for HCV.
HCV infection most commonly presents between the fourth and sixth decades of life. Many patients have had the disease for as long as 20 years by the time they present for treatment—often after abnormal laboratory findings are discovered7 (but see "Can Some Patients Defer Treatment?"7,10,12).
Patients with acute HCV infection usually do not appear jaundiced or exhibit other signs of acute hepatitis. Symptomatic illness occurs in only 20% to 40% of patients with acute hepatitis C.7 Patients who present with acute illness (15% to 25% of patients with HCV) typically have an improved prognosis and are less likely to convert to chronicity if they survive the initial symptoms (ie, malaise, weakness, anorexia, jaundice).2,7 In many such patients, the body appears to mount a full immune response, and patients are often virus-free within weeks.
For 75% to 85% of patients, however, it is believed that the immune system fails to overcome the virus, and chronic infection, with progressive damage to the liver tissue, ensues.7 In chronic HCV infection, the rate of progression varies, depending on the HCV genotype, the infected host's genetic factors and lifestyle (including level of alcohol consumption), the extent of liver injury, and possible coinfection (as with HIV or hepatitis B virus [HBV]).1,7
Cirrhosis and Hepatocellular Carcinoma
Complications of cirrhosis include portal hypertension, ascites, hepatic encephalopathy, esophageal varices, and hepatocellular carcinoma (HCC).13 In patients with HCV-related cirrhosis, HCC develops at a rate of 1% to 4% per year, with a twofold to fourfold increased risk among black patients and Asian patients, respectively, compared with whites.7 The risk for HCC appears to be reduced in patients who undergo treatment leading to a sustained virologic response (ie, a viral load that is no longer detectable); and the risk is increased in patients with diabetes mellitus and those with HCV genotypes 1b and 3.14-16
HCC is difficult to treat unless detected in its early stages. It often results in death.13
PHYSICAL EXAMINATION
An appropriate physical exam is critical in detecting sequelae of chronic liver disease, which may reflect complications of long-term HCV infection. The patient should be evaluated for the presence of spider angiomas, palmar erythema, scleral icterus, ascites, caput medusae, and evidence of umbilical hernias—all possible signs of advanced liver disease.8,9
The initial physical exam is also an appropriate time to screen and treat patients for hypertension and diabetes, and to identify disorders that may make them poor candidates for HCV treatment. These conditions include coronary heart disease, untreated cancers or thyroid disease, kidney or autoimmune diseases, and psychiatric illness.1,17
Evaluation of the skin for "track marks," tattoos or body piercings that may have been applied in prisons, homes, or other nonsterile settings, or nonhealing lesions that may indicate immune compromise or diabetes is important.5,8 Visual acuity testing and fundoscopic exams are critical to establish a baseline, because treatment with pegylated interferon has the potential to cause visual changes and retinopathy.18
Laboratory Work-up
Initial testing for HCV includes an HCV antibody test. This serum test is commonly performed as part of a hepatitis panel—testing for hepatitis A virus (HAV), HBV, and HCV. Testing for hepatitis D and E is not routinely recommended unless the patient routinely travels to the Mediterranean Basin, the Middle East, Central Asia, or West Africa (where hepatitis D is most prevalent19) or the patient is pregnant (because during the third trimester, hepatitis E infection carries a mortality rate of 20% and can be transmitted to the fetus20).
