October 21, 2001
Dr. Reinus, Head of the Hepatology Section at Albert Einstein College of Medicine in Bronx, New York, discussed the clinical aspects of liver disease in patients with AIDS. The approach to the patient with AIDS and liver disease must consider diagnostic possibilities in three broad categories:
Which of these diagnostic categories is most likely in a given individual depends on the stage of their HIV disease. Those patients presenting with liver disease who have early HIV infection, adequate CD4 counts and are not on antiretroviral therapy likely have one of the common causes of liver disease, such as viral hepatitis or alcoholic liver disease. In contrast, opportunistic liver and biliary tree infections should be considered as the likely cause of liver disease in those patients with advanced HIV infection and low CD4 counts.
The introduction of highly active antiretroviral therapy (HAART) in 1996 greatly changed the type of liver disease presenting in HIV patients. Prior to 1995, 29.4/100 person-years had a CD4 count of <100 cells/mm3. In contrast, in 1997, only 8.8/100 person-years had a CD4 cell count of <100/mm3. Thus, opportunistic infections as the cause of liver disease have become much less prevalent since the introduction of HAART, and common diseases such as hepatitis C infection much more prevalent.
According to Dr. Reinus, hepatitis C infection is one of the most common liver diseases encountered in HIV-infected individuals. It is estimated that 40% of HIV patients are infected with HCV; this translates to approximately 400,000 individuals co-infected with HIV and HCV in the U.S. Because HIV and HCV share common risk factors, epidemiologic studies have shown that most co-infected people become infected with both viruses at about the same time. Prior to HAART therapy, most co-infected patients died of HIV disease before the hepatitis C virus could cause severe liver damage. Now that patients receiving HAART therapy can live for many years, more and more patients are developing complications from hepatitis C infection which can lead to premature deaths.
If we assume that 85% of the 400,000 people co-infected with HIV and HCV will develop chronic hepatitis C: 68,000 patients are at risk of progressing to cirrhosis after 20 years of infection, and 16,000 will die from advanced liver disease after 30 years of hepatitis C infection if no therapy is offered. These numbers are likely an underestimate, as epidemiologic evidence suggests that the natural course of hepatitis C infection is more aggressive in HIV-positive individuals, potentially leading to death from advanced liver disease in less than 30 years.
According to Dr. Reinus, several unanswered questions regarding HIV and HCV co-infection remain. We know that in non-HIV patients, much of the injury to the liver is caused by the immune system. In HIV patients, however, the decreased immune response allows for rapid viral replication and high viral load. It is not known if, at high viral loads, the virus itself becomes cytopathic and is responsible for most of the damage to the liver. Another unanswered question is whether HIV-associated immunosuppression decreases inflammation and damage to the liver. It is also unknown if immune reconstitution using HAART therapy will affect the natural history of hepatitis C infection. Finally the role that other factors such as alcohol use and the use of potentially hepatotoxic medications play in the natural history of liver disease in HIV is unknown.
Given the extended life expectancy of patients with effectively treated HIV, patients with hepatitis C coinfection should be evaluated in the same manner as other individuals with hepatitis C infection. Treatment should be offered to patients thought to have severe enough liver disease to be a potential cause of future morbidity and mortality. According to Dr. Reinus, HIV-infected individuals with a CD4 count of >200 cells/mm3, who have <20,000 copies of HIV per ml of serum and who have no objective evidence of clinical deterioration due to HIV infection are adequate candidates for HCV antiviral therapy.
When properly selected according to the above guidelines, Dr. Reinus stated that the response to HCV treatment in patients with HIV coinfection appears to be similar to that in persons with hepatitis C alone. Co-infected patients that are most likely to clear the virus are those with a CD4 count >500 cells/mm3 at the time of antiviral therapy.
Dr. Reinus also discussed liver injury caused by HAART therapy or other medications commonly used in patients with HIV infection. Three antibiotics commonly used in HIV patients account for most cases of drug-induced liver injury: trimethoprim-sulfamethoxazole, isoniazid and rifampin. Medications used as part of HAART may be responsible for liver damage. HAART-related liver toxicity usually develops after months of receiving HAART therapy and presents with jaundice or elevated liver enzymes. Among the medications used as part of the HAART regimen, ritonavir and didanosine are best known for causing possible liver damage.
In summary, the approach to the patient coinfected with HIV and HCV has drastically changed since HAART was introduced. The life expectancy of HIV patients has increased dramatically, allowing HCV infection to progress and result in premature deaths in these patients. In some instances, the presence of HCV infection increases the risk of drug-induced liver injury preventing patients from receiving the benefit of HAART. In those instances, the treatment of hepatitis C infection may allow for institution of HAART and prolongation of the patient's life span. In general, patients with HCV infection and stable HIV infection (CD4 count >200 and low HIV viral load) should be aggressively treated using antiretroviral therapy against hepatitis C infection.
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