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Ward 86 Management Recommendations

Ward 86 Approach to HIV/HCV Coinfection Screening, Evaluation, and Treatment

Contributors: Monika Roy, MD
Catherine Koss, MD
Annie Luetkemeyer, MD

Approximately 25% of all HIV patients in the United States and 80% of those who inject drugs are coinfected with hepatitis C virus (HCV). HIV coinfection more than triples the risk of liver failure and liver-related mortality from HCV. Hence, screening for HCV coinfection and treating coinfected patients has become a high priority in HIV medical care. Combinations of new, direct-acting antiviral agents (DAAs) that target specific steps in the HCV replicative cycle have become standard of care for treatment of chronic, active HCV infection in the United States. Though expensive, these new DAA regimens are far more effective (>95% sustained virologic cure rates) at much shorter durations of treatment (8-12 weeks) and are better tolerated than the interferon-alfa/ribavirin regimens that were the mainstay of HCV treatment until 2014. Of note, even patients with cirrhosis benefit from HCV treatment. In fact, more than half of patients with liver fibrosis have regression of fibrosis after a sustained virologic response,(1) although the effect of fibrosis regression on the risk of hepatocellular carcinoma remains unknown. Importantly, DAA regimens are as effective in HIV/HCV-coinfected patients as in those with HCV monoinfection and can be coadministered with many commonly used antiretroviral regimens.

Because the field of DAA treatment continues to evolve rapidly, we refer readers to the regularly updated consensus guidelines of the American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA) for specific treatment recommendations. However, we strongly recommend DAA treatment for all HCV patients with evidence of chronic, active HCV infection who have a life expectancy of >12 months, regardless of the extent of liver fibrosis.

Screening

  • All HIV patients should be screened when entering medical care for the presence of serum anti-HCV antibodies.

  • Those with ongoing risk of HCV infection (ie, MSM who have condomless anal sex and injection drug users) should have HCV antibody testing and transaminase evaluation repeated every 6-12 months.

  • HIV patients who are HCV antibody negative but have otherwise unexplained elevations in serum ALT should be tested for the presence of HCV RNA in blood. Observational studies have reported that 5% of HIV patients with chronic active HCV infection remain HCV antibody negative at 1 year or longer after primary HCV infection,(2,3) particularly in the setting of CD4 counts <200 cells/µL.

  • Patients at risk of HCV acquisition who present with newly elevated transaminases and/or symptoms of acute hepatitis (including fatigue, jaundice, right upper quadrant abdominal pain) should be evaluated for the presence of acute HCV infection with both HCV RNA and HCV antibody.

Evaluation

  • All patients who are HCV antibody positive should be tested for the presence of HCV RNA in serum to confirm ongoing infection. Those who are antibody positive but RNA negative may have spontaneously cleared active HCV infection; a subsequent HCV RNA test after 3-6 months is recommended to confirm the absence of HCV viremia.

  • Patients who are positive for HCV RNA are likely to be in the first year of HCV infection if they had: a) a self-limited clinical hepatitis-like syndrome with symptoms and elevated ALT levels within the last year, b) a negative HCV antibody at the time of the first positive HCV RNA result, which occurred in the last year, or c) a negative HCV antibody result within the last year preceding positive HCV RNA testing. Patients with recent or acute HCV infection should be monitored for 3-6 months after the initial HCV diagnosis to see if they spontaneously clear HCV viremia without treatment.(4) Individuals whose HCV RNA becomes undetectable during the 3- to 6-month follow-up period should have HCV RNA testing repeated in several months to confirm viral clearance, because HCV viral loads can fluctuate substantially during the first year of infection, and sometimes briefly drop to undetectable levels only to rebound upward. (Spontaneous clearance is more likely to occur in patients who have clinically apparent hepatitis, particularly jaundice, at the time of primary infection.)

  • Patients who fail to clear HCV viremia or who have been known to be HCV antibody positive for >6 months and continue to have HCV viremia should be evaluated for treatment as follows:

    • Send a serum sample for HCV genotype analysis, as HCV genotype influences the choice and duration of HCV treatment.

    • Check baseline complete blood count with platelets and white blood cell differential, liver function tests, albumin, international normalized ratio (INR), and creatinine.

    • Screen for other viral hepatitis coinfections: hepatitis A total antibody, hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody; vaccinate for HAV and HBV if indicated.

    • Evaluate all patients for the presence of cirrhosis by:

      • Clinical examination

      • Serologic evaluation, including calculation of Fib-4 or APRI score (see Note, below) or by a commercial fibrosis blood test such as Fibrosure

      • Imaging (sonogram, CT, or MRI) or transient elastography (Fibroscan)

  • Patients with cirrhosis may need endoscopy to check for varices and should have follow-up imaging surveillance for hepatocellular carcinoma every 6-12 months.

Preparation for Anti-HCV Treatment

  • There are now many DAA regimens that are compatible with commonly used ART regimens. However, some DAAs have important drug interactions with specific antiretroviral drugs; thus, a careful review of all patient medications including ART and over-the-counter medications for possible drug interaction with DAA medications is warranted. See the AASLD/IDSA guidelines section on Unique Patient Populations as well as the University of Liverpool's Hepatitis Drug Interactions Checker for specific guidance and for evaluation of ART/DAA drug interactions.

  • For patients not already on ART, start ART with a regimen that will be compatible with the planned anti-HCV regimen. For patients on ART, modify ART, if needed, to be compatible with the planned anti-HCV regimen. For both groups, verify that HIV RNA is undetectable on the ARV regimen before initiating anti-HCV treatmrent.

  • Counsel patients to reduce or discontinue alcohol use, which is another driver of hepatic disease.

  • Vaccinate for hepatitis B and hepatitis A if not previously done and not already immune.

  • Counsel patients on the risk of reinfection after successful cure of HCV and how to reduce the risk of parenteral and sexually transmitted reinfection.

  • Recommended initial anti-HCV regimens are updated regularly at the AASLD/IDSA guidelines website. Advice for the approach to monitoring patients on anti-HCV treatment and for approaches to treating patients who have failed to achieve a sustained virologic response to prior anti-HCV therapy also can be found on this website.

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Note:
Severity of liver fibrosis can be estimated by a number of serologic tests, including the APRI and Fib-4. Serum tests for fibrosis have a high negative predictive value to exclude cirrhosis but only a moderate positive predictive value, so these must be evaluated in the context of all available data. The APRI (aspartate aminotransferase [AST]-to-platelet ratio index) score can be calculated as follows:

APRI = 100 x [AST/upper limit of normal]/platelet count (109/L)

The AST upper limit of normal varies from 30 to 40 international units in most clinical laboratories and is higher for men than for women. The range of normal platelet counts usually is 150-450 x 109/L. An APRI value >0.7 suggests the presence of clinically significant fibrosis, and a value >1.0 suggests cirrhosis with a sensitivity of 76%, a specificity of 72%, and a high negative predictive value. A simple-to-use calculator for determining APRI scores can be found here.

References

  1. ANRS CO13 HEPAVIH Cohort. Regression of liver stiffness after sustained hepatitis C virus (HCV) virological responses among HIV/HCV-coinfected patients. AIDS. 2015 Sep 10;29(14):1821-30.
  2. Thomson EC, Nastouli E, Main J, et al. Delayed anti-HCV antibody response in HIV-positive men acutely infected with HCV. AIDS. 2009 Jan 2;23(1):89-93.
  3. Bonacini M, Lin HJ, Hollinger FB. Effect of coexisting HIV-1 infection on the diagnosis and evaluation of hepatitis C virus. J Acquir Immune Defic Syndr. 2001 Apr 1;26(4):340-4.
  4. Vispo E, Barreiro P, Plaza Z, et al. Spontaneous hepatitis C virus clearance in HIV patients with chronic hepatitis C bearing IL28B-CC alleles using antiretroviral therapy. AIDS. 2014 Jun 19;28(10):1473-8.