HIV and Hepatitis C Co-infection: Guideline and Commentary

Douglas G. Fish, MD


January 05, 2011

In This Article

Evaluation and Initial Management of Confirmed Hepatitis C Infection

Recommendations. As part of the baseline evaluation of HIV/HCV co-infected patients, clinicians should (AII):

  • Obtain laboratory measurements, including a complete blood count, serum aspartate aminotransferase (AST) and ALT, bilirubin, prothrombin time, and serum albumin

  • Determine the patient’s HCV genotype

  • Assess for signs and symptoms of liver disease

  • Assess for alcohol and substance use

  • Screen for immunity to hepatitis A (HAV) and B (HBV) viruses

Laboratory Measurements

Higher serum ALT and AST levels are, to some degree, predictive of more rapid disease progression; however, significant liver disease may occur even in the presence of persistently normal levels.[28] Bilirubin, albumin, and prothrombin time are useful tests for evaluation of advanced liver disease. For HCV RNA, the same laboratory should be used for subsequent testing because of the interlaboratory variation of quantitative HCV RNA assay results.

Genotypic Testing. Because patients with HCV genotypes 1 and 4 are known to have a poorer response to interferon-based therapy than genotypes 2 and 3, genotypic testing can guide treatment considerations, such as likelihood of treatment response and dose and length of treatment.

Key Point

HCV genotypic testing is not necessary for patients in whom HCV treatment is contraindicated due to nonmodifiable contraindications, such as hypersensitivity to interferon or ribavirin, hemoglobinopathies (eg, thalassemia major and sickle cell anemia), unstable angina, unstable cardiac arrhythmias, and hepatic decompensation.

Assessment for Fibrosis, Cirrhosis, and Hepatocellular Carcinoma


Liver biopsy is the most specific test for defining the extent of liver pathology induced by HCV infection. It may be used to predict an individual’s long-term prognosis. Typically, liver biopsy reports will describe the degrees of inflammation and fibrosis. Several indices have been developed and validated to describe inflammation and fibrosis. The Batts-Ludwig scoring system[29] assesses the degrees of inflammation (grade) and fibrosis (stage) on a scale of 1 to 4 and is commonly used in the clinical setting. The Ishak or Metavir scoring system is also valid and is used in many of the clinical trials that study liver biopsy material.

The decision to treat HIV/HCV co-infected patients is often based on biopsy, particularly for patients with genotype 1 or 4; however, it is not required to treat HCV and, in some cases, may not be preferred. For example, patients with hemophilia require transjugular liver biopsies, and either the patient or the provider may not wish to proceed with this intervention. A patient’s decision to decline liver biopsy should not preclude treatment for HCV when it is otherwise indicated.

Key Point

Liver biopsy is used primarily to guide the decision to treat but may not be necessary in patients who are not being considered for treatment or who will be treated regardless of biopsy result.


Ultrasound of the liver can sometimes detect cirrhosis and steatosis. Liver stiffness measurements and calculations of a fibrosis score from noninvasive tests, such as FibroTest and FibroSure, are available in the United States. These tests use a combination of serum biochemical markers to predict the degree of hepatic fibrosis.[30] The AST/platelet ratio index is an easily calculated index used as a predictor of the presence or absence of significant fibrosis on liver biopsy in patients with chronic HCV. In one study, this index accurately distinguished significant from insignificant fibrosis in 60% of patients.[31,32] A technique used for calculating liver stiffness, known as elastography (FibroScan), has been studied for its potential as a sonography-based method for detecting liver fibrosis and cirrhosis.[33]

Hepatocellular Carcinoma

Screening for HCC in persons with cirrhosis is most commonly performed with regular imaging by ultrasonography or computed tomography (CT) scan, as well as with determination of serum α-fetoprotein (AFP). HCC is rare in HCV unless the patient has advanced fibrosis or cirrhosis. AFP testing alone has relatively low sensitivity and specificity for HCC, and the optimal interval for screening remains undetermined. However, evidence suggests that biannual AFP coupled with annual ultrasonography may be cost-effective in HCV-infected patients with cirrhosis.[34]If AFP is elevated, then a screening examination is no longer appropriate, and a diagnostic test is indicated. Both triple-phase CT scans and liver magnetic resonance imaging (MRI) offer greater sensitivity in finding and distinguishing among liver abnormalities.

Evaluation of Hepatitis A and B Status

Recommendations. As part of the baseline assessment, clinicians should ask HIV-infected patients about their HAV and hepatitis B virus (HBV) vaccination history and should:

  • Obtain HBV serologies: HBsAg, HBsAb, and HBcAb (IgG or total) (AII)

  • Obtain hepatitis A IgG (AII)

  • Vaccinate those who are not immune to hepatitis A and/or B viruses (see Hepatitis A Virus and Hepatitis B Virus) (AII)

Although HAV does not progress to a chronic infection, severe disease may develop in patients with underlying HCV. HIV/HCV/HBV tri-infection confers the risk for serious complications. Accordingly, HAV and HBV screening and vaccination should be performed according to current guidelines.

Other Disease Screening

If clinically suspected, screening for the following diseases may be indicated in HIV/HCV co-infected patients (AII):

  • Hemochromatosis: obtain percentage iron saturation with ferritin (uncommon in patients of African descent)

  • Primary biliary cirrhosis: obtain antimitochondrial antibody

  • Autoimmune hepatitis: obtain antinuclear antibody and anti-smooth muscle antibody

  • α-1 antitrypsin deficiency: obtain α-1 antitrypsin level

  • Wilson’s disease: obtain ceruloplasmin level

  • Steatohepatitis: assess with liver biopsy (see Section 5: Evaluation and Initial Management of Confirmed Hepatitis C Infection)

Assessment for Mental Health Disorders

Recommendations. Clinicians should perform the following:

Screening for mental health disorders in HIV/HCV co-infected patients should be performed according to standard guidelines for all HIV-infected patients, regardless of whether or not the patient will receive anti-HCV therapy. Numerous studies have documented the association between interferon alfa and depression, with an estimated incidence between 20% and 40%; however, the prevalence of mental health disorders, and depression in particular, is increased in patients infected with HCV. The rate of depression in untreated HCV-infected patients may be as high as 25%,[35] demonstrating that HCV itself may also be a risk factor for depression. HCV commonly presents with symptoms of fatigue and malaise, which may mimic depression and complicate its diagnosis.

At present, insufficient data exist to determine the risk factors for developing depression during interferon treatment. Patients with a history of mental health disorders are at particular risk for mood alterations due to anti-HCV therapy.

Key Point

A history of mental health disorders, such as depression, should not be regarded as a contraindication to therapy. However, clinicians who prescribe interferon alfa should consult with a psychiatrist when treating patients with a history of mental health disorders.

Assessment for Alcohol and Substance Use

Recommendations. Clinicians should obtain an alcohol and substance use history for HIV/HCV co-infected patients. Patients with alcohol abuse or dependence should be referred for alcohol-dependency treatment. (AII)

Clinicians should educate HIV/HCV co-infected patients about the effects of alcohol, tobacco, and cannabis on the course of HCV infection. Patients who have other underlying liver disease should be advised to abstain from alcohol. (AII)

Numerous studies indicate that patients with HCV and heavy alcohol intake have increased progression of hepatic fibrosis and increased risk for cirrhosis, HCC, and death.[36,37] Although some studies suggest that light to moderate consumption may contribute to progression, this has not been clearly shown.[38] The National Institute on Alcohol Abuse and Alcoholism defines moderate alcohol use for most adults as up to 2 drinks per day for men and 1 drink per day for women and older people. One drink equals one 12-ounce bottle of beer or wine cooler, one 5-ounce glass of wine, or 1.5 ounces of 80-proof distilled spirits. For more information regarding alcohol dependence in HIV-infected patients, see Clinical Management of Alcohol Use and Abuse in HIV-Infected Patients .

Most hepatologists recommend abstinence from alcohol in patients who are infected with HCV. All patients with HCV infection who use alcohol should be educated about the effects of alcohol on the course of HCV infection. Abstinence in heavy drinkers with HCV is associated with improvement in chemical markers, as well as decreased HCV RNA levels.[39,40] Patients with alcohol abuse or dependence should be referred for alcohol-dependency treatment.

Smoking tobacco is a risk factor for hepatoma and is a predictor for the progression of fibrosis in persons with HCV.[41] Daily cannabis use may increase the risk for progression to moderate to severe fibrosis by up to 7-fold compared with nondaily use in HCV-infected patients.[42] However, weekly or monthly cannabis use does not significantly increase risk for progression of fibrosis compared with rare or no use.

Methamphetamine use promotes HCV replication in hepatic cells and, therefore, may contribute to HCV disease progression.[43] As with alcohol, abstinence from smoking and regular cannabis use, as well as abstinence from other substances, is recommended in individuals who are infected with HCV.

For more information regarding management of alcohol and substance use in HIV-infected patients, refer to the Substance Use Guidelines .


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