Chapter 25 Hepatobiliary complications of HIV
1 Approximately 10% of human immunodeficiency virus (HIV)–infected persons worldwide are chronically infected with hepatitis B virus. The choice of antiviral therapy depends on the need for HIV treatment.
2 Approximately 30% of HIV-infected persons are chronically coinfected with hepatitis C virus (HCV). Antiretroviral therapy may improve hepatic outcomes and survival among coinfected patients. Pegylated interferon alpha plus weight-based ribavirin can achieve sustained virologic response in up to 72% of HIV-infected patients infected with HCV genotype 2 or 3 and up to 35% of those infected with HCV genotype 1 or 4. The role of protease inhibitors active against HCV in this population is under study.
3 Infiltrative infections (mainly disseminated bacterial and fungal processes) may lead to hepatocellular necrosis or granulomatous inflammation in HIV-infected patients with advanced immunosuppression. Mycobacterium avium complex infection is most common.
4 Macrovesicular hepatic steatosis is identified in 40% to 69% of liver biopsy specimens in patients coinfected with both HIV and HCV, and steatosis is associated with more advanced hepatic fibrosis.
5 Virtually every antiretroviral medication has been associated with hepatotoxicity. In the setting of suspected hepatotoxicity, discontinuation of antiretroviral medications should be considered if (1) serum aminotransferase levels exceed 10 times the upper limit of normal, (2) overt jaundice is identified, (3) symptomatic hepatitis develops, or (4) findings consistent with drug hypersensitivity (e.g., rash, fever, eosinophilia) are observed.
Viral Hepatitis and Other Viral Infections
Hepatitis A virus
1. Seroprevalence of antibody to hepatitis A virus (HAV) is high among HIV-infected persons, with a range of 40% to 70%.
2. The annual cumulative incidence of HAV infection is reported to be 5.8% per year among HIV-positive persons.
3. HAV viremia is prolonged in HIV-infected persons, and the level of HAV viremia is higher compared with those without HIV infection, even with relatively high CD4+ T lymphocyte counts.
4. No evidence indicates that antiretroviral therapy (ART) has a detrimental effect on the course of HAV infection.
Hepatitis B and D viruses
2. HIV adversely affects the natural history of HBV infection. Compared with those infected with HBV alone, HIV-coinfected persons have a higher rate of progression from acute to chronic HBV, higher HBV DNA levels, lower rates of spontaneous hepatitis B e antigen (HBeAg) to antibody to HBeAg (anti-HBe) seroconversion, increased frequency of reactivation episodes, faster progression to hepatic cirrhosis, and earlier development of and more aggressive hepatocellular carcinomas.
4. All HIV/HBV-coinfected patients with active HBV replication should be considered for HBV antiviral therapy, which can potentially prevent development of liver-related complications and reduce HBV transmission.
5. The goals of HBV treatment in HIV-infected persons are suppression of HBV DNA to an undetectable level (as for persons without HIV infection), return of serum aminotransferase levels to normal, HBeAg seroconversion (not applicable to HBeAg negative–pre-core/core promoter mutant states [see Chapters 3 and 4]), and improvement in liver histology.
6. As of 2011, seven antiviral medications have been approved in the United States for chronic HBV treatment, and three of these have also been approved for HIV treatment (Table 25.1). The choice of therapy for HBV infection depends on the need for HIV treatment.
7. When both HIV and HBV infections meet criteria for treatment, combination oral nucleoside/nucleotide analogue therapy with tenofovir 300 mg daily plus either emtricitabine 200 mg daily or lamivudine 300 mg daily is preferred. Because replication of both viruses depends on reverse transcription, dual HIV/HBV therapy can use the same reverse transcriptase-inhibiting agents to treat both viruses.
8. When HBV infection requires treatment but HIV infection does not, treatment options include the following:
Medications with no capacity to induce HIV-resistance mutations, such as subcutaneous peginterferon alfa-2a or oral adefovir (10 mg daily), can be used.
Medications with no capacity to induce HIV-resistance mutations, such as subcutaneous peginterferon alfa-2a or oral adefovir (10 mg daily), can be used.
9. Frequent toxicities and low rates of therapeutic success have limited peginterferon alfa-2a use as HBV therapy in HIV-infected persons, but it may be effective for HBeAg-positive persons with elevated serum aminotransferase levels and low HBV DNA levels.
10. Because lamivudine resistance occurs at a rate of 15% to 25% per year, lamivudine resistance may be present in HIV-infected patients who previously received lamivudine as part of an ART regimen. However, tenofovir remains active in patients with lamivudine-resistant HBV infection and can suppress HBV DNA to undetectable levels, because of the potency of tenofovir and the lack of cross-resistance between lamivudine and tenofovir.
11. For patients receiving combination tenofovir plus emtricitabine (or lamivudine) who fail to suppress HBV DNA by 24 to 48 weeks, adding entecavir 1 mg daily may be considered.
12. Because hepatocellular carcinoma can occur at any stage of chronic HBV infection, screening with abdominal ultrasonography and alpha fetoprotein testing is recommended every 6 to 12 months (see Chapter 27).
13. HBV vaccination is recommended in all HIV-positive/HBV surface antibody (anti-HBs) –negative persons. The presence in serum of isolated hepatitis B core antibody (anti-HBc) with no other HBV markers most likely reflects previous exposure and recovery, rather than a false-positive test, but not necessarily.
14. Anti-HBs titers should be evaluated after HBV vaccination in HIV-infected persons. Immune reactivity to the HBV vaccine is frequently suboptimal in these persons in terms of rate of response, antibody titers, and durability. A CD4+ count higher than 500 cells/mm3 and an HIV viral load lower than 1000 copies/mL promote optimal vaccine responses. Revaccination should be instituted if the anti-HBs titer is less than 10 IU/L.
TABLE 25.1 Antiviral medications for chronic hepatitis B
| Interferon alfa-2b |
| Peginterferon alfa-2a |
| Lamivudine∗ |
| Adefovir |
| Entecavir |
| Telbivudine |
| Tenofovir∗ |
∗ Also approved to treat HIV infection. Tenofovir is also available in combination with emtricitabine (Truvada®).
Hepatitis C virus
2. The natural history of HCV infection is adversely influenced by HIV coinfection. Compared with persons infected with HCV alone, HIV-coinfected persons more commonly progress to chronic HCV; have higher HCV RNA levels; are at higher risk of cirrhosis, hepatic decompensation, and liver-related death; and have a shorter survival once end-stage liver disease develops.
4. HIV/HCV coinfection increases the risk of hepatocellular carcinoma compared with HIV monoinfection persons but not HCV monoinfection.
5. Available data suggest that ART favorably affects the course of HIV disease in HIV-infected patients, decreases mortality from liver disease, and should not be withheld from HIV/HCV-coinfected persons on account of potential toxicity.
6. The stage of hepatic fibrosis can help guide HCV treatment decisions in HIV/HCV patients. The incidence rate of hepatic decompensation events or death is higher in coinfected patients with more advanced fibrosis at the time of staging.
7. The timing of HCV therapy depends on the need for HIV treatment. HCV treatment should be considered first if liver disease is advanced and HIV infection is at an early stage. If HIV infection requires treatment, ART should be initiated first, and once the HIV infection is controlled, HCV therapy can be considered.
8. Given accelerated progression to end-stage liver disease among HIV/HCV-infected patients, treatment of chronic HCV infection should be considered in all coinfected patients who do not have decompensated cirrhosis or other contraindications. Peginterferon alfa-2a plus ribavirin for 48 weeks (regardless of HCV genotype) is the standard of care for treating chronic HCV infection in the setting of HIV infection. The main goals of treatment are viral eradication (i.e., sustained virologic response) and reduction in the risk of liver-related complications (see Chapter 4).
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