Hepatitis C

HCV is a single-stranded RNA virus (hepacivirus) with properties similar to

those of flaviviruses. Six major genotypes of HCV have been identified. In the past,
HCV was responsible for 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, and both reinfection and superinfection of HCV are
common in people who actively inject drugs. Body piercing, tattoos, and hemodialysis
are risk factors.
The risk of sexual and maternal–neonatal transmission is low and may be
greatest in a subset of patients with high circulating levels of HCV RNA. Having
multiple sexual partners may increase the risk of HCV infection, and HIV coinfection,
unprotected receptive anal intercourse with ejaculation, and sex while high on
methamphetamine increase the risk of HCV transmission in men who have sex with
men. Transmission via breastfeeding has not been documented. An outbreak of
hepatitis C in patients with immune deficiencies has occurred in some recipients of
intravenous immune globulin. Hospital- and outpatient facility-acquired transmission
has occurred via multidose vials of saline used to flush Portacaths; through reuse of
disposable syringes (including drug “diversion” by an infected health care worker);
through contamination of shared saline, radiopharmaceutical, and sclerosant vials; via
inadequately disinfected endoscopy equipment; and between hospitalized patients on a
liver unit. In the developing world, unsafe medical practices lead to a substantial
number of cases of HCV infection. Covert transmission during bloody fisticuffs has
even been reported, and incarceration in prison is a risk factor, with a frequency of
26% in the United States. In many patients, the source of infection is unknown.
Coinfection with HCV is found in at least 30% of HIV-infected persons. HIV
infection leads to an increased risk of acute liver failure and more rapid progression of
chronic hepatitis C to cirrhosis; in addition, HCV increases the hepatotoxicity of
highly active antiretroviral therapy. There are about 3.2 million HCV carriers in the
United States (and 184 million worldwide) and another 1.3 million previously exposed
persons who have cleared the virus. The incidence of new cases of acute, symptomatic
hepatitis C declined from 1992 to 2005, but an increase was observed in persons aged
15 to 24 from 2002 to 2006, as a result of injection drug use.

Symptoms and Signs:

The incubation period for hepatitis C averages 6–7 weeks, and clinical illness is
often mild, usually asymptomatic, and characterized by waxing and waning
aminotransferase elevations and a high rate (> 80%) of chronic hepatitis. Spontaneous
clearance of HCV following acute infection is more common (64%) in persons with
the CC genotype of the IL28B gene (which encodes interferon lambda-3 on
chromosome 19) than in those with the CT or TT genotype (24% and 6%,
respectively). In persons with the CC genotype, jaundice is more likely to develop
during the course of acute hepatitis C. Patients with the CC genotype and chronic
hepatitis C are more likely to respond to therapy with pegylated interferon (see
Chronic Viral Hepatitis, below). Polymorphisms of genes encoding the killer cell
immunoglobulin-like receptors (KIR) and their HLA class-I ligands (HLA-C1) and
near genes for HLA class II are also associated with spontaneous resolution of viremia
following HCV exposure. In pregnant patients with chronic hepatitis C, serum
aminotransferase levels frequently normalize despite persistence of viremia, only to
increase again after delivery.

Laboratory Findings:
Diagnosis of hepatitis C is based on an enzyme immunoassay (EIA) that detects
antibodies to HCV. Anti-HCV is not protective, and in patients with acute or chronic
hepatitis, its presence in serum generally signifies that HCV is the cause. Limitations
of the EIA include moderate sensitivity (false-negatives) for the diagnosis of acute
hepatitis C early in the course and low specificity (false-positives) in some persons
with elevated gamma-globulin levels. In these situations, a diagnosis of hepatitis C
may be confirmed by using 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.

Prevention:
Testing donated blood for HCV has helped reduce the risk of transfusion-
associated hepatitis C from 10% in 1990 to about 1 case per 2 million units in 2011.
Birth cohort screening of persons born between 1945 and 1965 (“baby boomers”) for
HCV infection has been recommended by the CDC and the US Preventive Services
Task Force. HCV infected persons should practice safe sex, but there is little evidence
that HCV is spread easily by sexual contact or perinatally, and no specific preventive
measures are recommended for persons in a monogamous relationship or for pregnant
women. Vaccination against HAV (after prescreening for prior immunity) and HBV is
recommended for patients with chronic hepatitis C, and vaccination against HAV is
also recommended for patients with chronic hepatitis B, although the cost-
effectiveness of vaccination has been questioned.

Treatment:
Treatment of patients with acute hepatitis C with peginterferon for 6–24 weeks
appreciably decreases the risk of chronic hepatitis. In general, patients infected with
HCV genotype 1 requires a 24-week course of treatment, but a 12-week course is
adequate if HCV RNA is undetectable in serum by 4 weeks. Those infected with
genotypes 2, 3, or 4 generally require 8–12 weeks of therapy. Because 20% of patients
with acute hepatitis C, particularly those who are symptomatic, clear the virus without
such treatment, reserving treatment for patients in whom serum HCV RNA levels fail
to clear after 3 months may be advisable. Ribavirin may be added if HCV RNA fails
to clear after 3 months of peginterferon, but some authorities recommend using
ribavirin with peginterferon from the start of therapy.