Hepatitis C, Acute

Essentials of Diagnosis

• Often asymptomatic

• Prodrome of anorexia, nausea, vomiting, malaise, aversion to smoking

• Fever, enlarged and tender liver, jaundice

• Markedly elevated aminotransferases early in the course

• Liver biopsy shows hepatocellular necrosis and mononuclear infiltrate

• Source of infection is unknown in many

General Considerations

• The hepatitis C virus (HCV) is a single-stranded RNA virus (hepacivirus) with properties similar to those of flavivirus

• Seven major genotypes of HCV have been identified

• Coinfection is found in at least 30% of persons infected with HIV

• HIV leads to more rapid progression of chronic hepatitis C to cirrhosis

• Anti-HCV is not protective; in patients with acute or chronic hepatitis, its presence in serum generally signifies that HCV is the cause

Demographics

• In the past, HCV caused over 90% of cases of posttransfusion hepatitis, yet only 4% of cases of hepatitis C were attributable to blood transfusions

• Over 50% of cases are transmitted by injection drug use

• Body piercing, tattoos, and hemodialysis may be risk factors

• The risk of sexual and maternal-neonatal transmission is low and may be greatest in those with high circulating levels of HCV RNA

  • Multiple sexual partners may increase the risk of HCV infection

  • Transmission via breast-feeding has not been documented

• Hospital-acquired transmission may occur between patients on a liver unit or via

  • Multidose vials of saline

  • Reuse of disposable syringes

  • Contamination of shared saline, radiopharmaceutical, and sclerosant vials

Symptoms and Signs

• The incubation period averages 6–7 weeks

• Clinical illness

  • Often mild

  • Usually asymptomatic

  • Characterized by waxing and waning aminotransferase elevations and a high rate (> 80%) of chronic hepatitis

• In patients with the CC genotype,

  • Spontaneous clearance of HCV following acute infection is more common (64%)

  • Jaundice is more likely to develop during the course of acute hepatitis C

Differential Diagnosis

• Hepatitis A, B, D, E virus

• Hepatitis G virus (HGV) rarely, if ever, causes frank hepatitis

• TT virus (TTV)

  • Found in up to 7.5% of blood donors

  • Readily transmitted by blood transfusions

  • However, an association between this virus and liver disease has not been established

• A related virus known as SEN-V has been found in 2% of US blood donors

  • Is transmitted by transfusion

  • May account for some cases of transfusion-associated non-ABCDE hepatitis

• Cytomegalovirus, Epstein-Barr virus, and herpes simplex virus, particularly in immunocompromised hosts

Laboratory Tests

• Antibodies to HCV (Figure 16–3)

  • The immunoassay has moderate sensitivity (false-negatives) for the diagnosis early in the course and in healthy blood donors and has low specificity (false-positives) in persons with elevated γ-globulin levels

  • In these situations, a diagnosis of hepatitis C may be confirmed by use of an assay for HCV RNA

• Occasional persons are found to have anti-HCV in serum without HCV RNA in serum, suggesting recovery from HCV infection in the past

• In pregnant patients, serum aminotransferase levels frequently normalize despite persistence of viremia, only to increase again after delivery

• The white blood cell count is normal to low, especially in the preicteric phase

• Large atypical lymphocytes may occasionally be seen

• Mild proteinuria is common, and bilirubinuria often precedes the appearance of jaundice

• Elevated serum aspartate or alanine aminotransferase levels occur early, followed by elevations of bilirubin and alkaline phosphatase; in a small number of patients, the latter persist after aminotransferase levels have normalized

Medications

• If nausea and vomiting are pronounced or if oral intake is substantially decreased, 10% intravenous glucose is indicated

• Small doses of oxazepam are safe, as metabolism is not hepatic; morphine sulfate is to be avoided

• Oral direct-acting agents have supplanted interferon-based therapy (see Table 16–6)

• Treatment with interferon alfa or peginterferon can be considered when HCV RNA has not cleared from serum in 3–4 months (doses as for chronic hepatitis C)

• If HCV RNA has not cleared after 3 months of therapy, ribavirin can be added, but some authorities recommend using ribavirin with peginterferon from the start of therapy

Therapeutic Procedures

• Bed rest is recommended only if symptoms are marked

• Dietary management consists of palatable meals as tolerated, without overfeeding; breakfast is usually best tolerated

• Strenuous physical exertion, alcohol, and hepatotoxic agents are avoided

Complications

• Mixed cryoglobulinemia

• Membranoproliferative glomerulonephritis

• Lichen planus

• Autoimmune thyroiditis

• Lymphocytic sialadenitis

• Idiopathic pulmonary fibrosis

• Sporadic porphyria cutanea tarda

• Monoclonal gammopathies

• Non-Hodgkin lymphoma

Prognosis

• In most patients, clinical recovery is complete in 3–6 months

• Liver tests return to normal, though serum aminotransferase elevations persist in most patients in whom chronic hepatitis C ensues

• The mortality rate is < 1%, but the rate is higher in older people

• Acute liver failure due to hepatitis C is rare in the United States

• Chronic hepatitis develops in as many as 80% of all persons with acute hepatitis C, which in many cases progresses very slowly

• Cirrhosis develops in up to 30% of those with chronic hepatitis C; the risk of cirrhosis and hepatic decompensation is higher in patients coinfected with both HCV and HBV or with HCV and HIV

• Patients with cirrhosis are at risk for hepatocellular carcinoma at a rate of 3–5% per year

Prevention

• Strict isolation of patients is not necessary, but hand washing after bowel movements is required

• Thorough hand washing by anyone who may contact contaminated utensils, bedding, or clothing is essential

• Testing blood for HCV has helped reduce the risk of transfusion-associated hepatitis C

• Birth cohort screening of persons born between 1945 and 1965 ("baby boomers") for HCV infection is recommended by the CDC and the United States Preventive Services Task Force and could identify over 900,000 new cases