Hepatitis C Infection

According to the 2002 guidelines of the United States Public Health Service and the Infectious Diseases Society of America, all HIV-infected patients should be tested for anti-HCV antibodies using the enzyme immunoassay (EIA) test. HCV EIA tests are sometimes falsely negative in HIV-infected patients, although the third version of the test is highly sensitive and specific; it is also the least expensive screening test currently available. HIV-infected people who test positive on the EIA should be tested to determine whether they have circulating virus (ie, detectable HCV RNA). Falsely negative HCV viral load testing is uncommon.

Genotyping of HCV is helpful in assessing the likelihood of response to therapy. Patients with genotype 1 have much lower rates of response to treatment than do patients with genotype 2 or 3. Some specialists use the genotype to determine the type and duration of treatment, whereas others treat all HIV/HCV-coinfected patients similarly.

Monitoring of ALT is used to assess liver inflammation, although levels may be low in patients with advanced liver disease.

Ultrasonography can be performed to screen for cirrhosis or mass lesions. Computed tomography (CT), magnetic resonance imaging (MRI), and single-photon emission computed tomography (SPECT) are more expensive and are generally reserved for evaluation of liver masses. Some specialists recommend screening for HCC every 6 months.

Liver biopsy is used to stage the degree of inflammation and fibrosis to determine the need for HCV treatment. Biopsy should be considered in patients who are candidates for HCV treatment, after education about HCV therapy (including the expected success rates given the genotype, potential adverse effects, and the duration and logistics of treatment). Recently, blood tests have been used as noninvasive markers of hepatic fibrosis and have shown reasonable ability to identify patients with either mild or advanced liver fibrosis (currently about 40% of patients with HCV), allowing them to avoid liver biopsies.

The recommendations of the National Institutes of Health (NIH) from June 2002 suggest that current alcohol users, pregnant women, patients with untreated depression, patients with renal disease, and patients with advanced cirrhosis are not candidates for HCV treatment. However, more recent data suggest that patients in several of these "special groups" can be treated on a case-by-case basis. Although pregnant women and persons with active alcohol use should not receive HCV treatment, certain individuals with renal disease, depression, injection drug use, and lower degrees of hepatic fibrosis (ie, Child-Pugh class A) should be considered for HCV treatment. These comorbid conditions should, of course, be treated to the degree possible.

HIV-infected patients with low CD4 counts should not be excluded from HCV treatment on the basis of CD4 count alone. Some studies do not support an association between absolute CD4 cell counts and treatment response.

Patients with a high risk of progression to cirrhosis should receive higher priority for treatment. Risk is indicated by portal or bridging cirrhosis, moderate inflammation and necrosis, measurable HCV RNA levels, or persistently elevated ALT levels. However, because ALT levels do not correlate with liver damage and some patients with normal ALT levels have abnormal liver biopsies, many experts treat patients who have normal ALT levels. For patients with minimal findings on liver biopsy and minimal ALT elevations, therapy should be deferred and the patients should be monitored. Patients with decompensated liver disease generally should not receive HCV treatment; appropriate candidates can be considered for clinical studies of liver transplantation in HIV/HCV-coinfected patients.

The most effective treatment for HCV in patients with or without HIV is combination therapy with pegylated interferon-alfa (PEG-IFN) plus ribavirin. Among HIV-uninfected patients, approximately 50% with genotype 1 achieve HCV viral clearance using this combination. HCV/HIV-coinfected patients with genotype 1 have a 22% rate of sustained virologic response to PEG-IFN plus ribavirin if treated for 48 weeks, whereas patients with other genotypes have approximately a 55% rate of sustained virologic response. Data suggest that early virologic response (EVR), defined as a ≥2 log₁₀ decrease in HCV viral load 12 weeks into treatment, predicts sustained virologic response to treatment; treatment may be stopped if patients do not demonstrate EVR. The recommended duration of treatment in patients with genotype 1 HCV and EVR is 48 weeks. For genotype 2 or 3, the optimal duration of treatment is not clear; some specialists treat for 24 weeks, whereas others treat for 48 weeks.

Adverse effects of treatment

HCV therapy may cause significant adverse effects. IFN reduces total white blood cell counts, and can cause neutropenia. It also decreases CD4 cell counts, although the CD4 percentage usually does not change. IFN can reduce HIV RNA somewhat (approximately a 0.5 log10 decrease). IFN may also produce flulike symptoms, depression, peripheral neuropathy, and other symptoms. Ribavirin can cause anemia and other adverse effects. Zidovudine and didanosine should be avoided, if possible, in patients taking HCV treatment. HCV treatment should not be given during pregnancy, and women receiving HCV treatment should avoid pregnancy. Ribavirin is teratogenic, and both women and men must use contraception consistently during treatment with ribavirin and for 6 months after treatment. IFN may cause fetal growth abnormalities, and is abortifacient in animals.

Treatment of acute HCV is associated with a much higher response rate than treatment during the chronic phase. However, delaying therapy for 12 weeks to ascertain whether spontaneous clearance will occur does not affect treatment response rates. Treatment with PEG-IFN monotherapy has been associated with viral eradication in >90% of patients. Treatment for 24 weeks appears to be sufficient to clear HCV.

The decision of whether and when to treat HCV among people infected with HIV must be determined individually. When coinfected patients require treatment for both infections, some experts begin with HIV treatment in hope that by improving CD4 counts, they may enhance the response to HCV therapy, even though CD4 cell counts by themselves are not firmly associated with an increased likelihood of a sustained virologic response. Other experts choose to treat HCV before initiating ARV therapy (ART) in those with high CD4 counts and low HIV viral loads to simplify treatment and improve the tolerability of ART. Consult with an HCV treatment expert to determine the appropriateness and timing of HCV treatment.

Some patients with HCV will experience worsening of hepatic function during ART, and liver function tests should be monitored closely. Some ARV medications are hepatotoxic and should be avoided or used cautiously; these include nevirapine, tipranavir, and high-dose ritonavir. Numerous other medications (eg, fluconazole and isoniazid) are hepatotoxic and can pose problems for people with impaired liver function.