Approximately 40 million people worldwide are now infected with HIV, while 370 million are infected with hepatitis B virus (HBV), and 180 million are infected with hepatitis C virus (HCV).

Hepatitis is a nonspecific inflammation of the liver. The causes of hepatitis include drug or alcohol use and viral, parasitic or infiltrative infections. The route of transmission varies according to the underlying cause of hepatitis. The initial clinical presentation of the acute phase of hepatitis, regardless of the underlying cause, may be asymptomatic or at the other extreme: severe fatigue, jaundice, nausea, vomiting and diarrhea.

All hepatitis patients whose laboratory values are monitored show increased transaminase levels. In some cases these levels are quite high, with aspartame transaminase (AST) and alanine transaminase (ALT) ranging into the thousands.

Patients who are co-infected with human immunodeficiency virus (HIV) can complicate the course of hepatitis, and the drugs used to treat HIV infection may actually increase the risk of drug-induced hepatitis.

This article provides information about the pathophysiology, causes, sequelae and treatments for hepatitis A (HAV), HBV, HCV, hepatitis D (HDV), hepatitis E (HEV), hepatitis G (HGV) and drug-induced hepatitis.

Several studies show that hepatitis and HIV infection transmission may occur simultaneously, and that patients who present with acute hepatitis should be screened for acute HIV infection. HIV is transmitted through body-fluid contact.^1,2 The virus infects the macrophages, monocytes and the CD4 T-cells, causing a reduction in the overall number and function of the cells responsible for immune response to infection. In many people living with HIV, a co-infection with hepatitis may increase morbidity and mortality. People co-infected with HIV and viral hepatitis are more likely to develop chronic hepatitis that progresses to liver failure or have an increased risk of hepatic carcinoma. Several published reports have documented increases in poor outcomes among HIV patients who are co-infected with HBV or HCV.^3-5

Pathophysiology

The liver is located in the right upper quadrant of the abdomen, underneath the ribs. When the liver is enlarged (hepa-tomegaly), it can protrude below the rib cage and may be palpable and tender. The liver is considered part of the digestive system and acts as a detoxifier by processing potentially harmful agents into safe chemicals. The liver is also responsible for glucose metabolism and manufactures and controls the release of bile, an important enzyme that breaks down fats and starches, the sources of cellular energy. The liver is capable of some degree of regeneration and can continue to function despite considerable damage.

Hepatitis can be diagnosed when blood samples show an elevation in transaminases (ALT and AST). Normal values for transaminases may vary from laboratory to laboratory but should be less than 60 IU/L. Elevated transaminases do not render a diagnosis and only indicate that inflammation is present. To determine a diagnosis, liver biopsies must be performed. Since a liver biopsy may be difficult to obtain and is associated with morbidity or mortality, most acute hepatitis is a presumptive diagnosis based on clinical indicators and laboratory markers.

Hepatitis A

HAV is transmitted through oral-fecal contact. Acute HAV usually has an acute phase that lasts from 4 to 6 weeks with or without jaundice, fatigue and hepatomegaly. During this time, HAV IgM is detectable (acute phase) but will be replaced by IgG. During this acute phase, patients with a co-infection of HIV may have a considerable drop in T-cell counts that will rebound 6 to 12 weeks after acute infection. HAV is generally cleared from the body after 6 weeks. It may take several months to fully recover from an acute episode of HAV. In general, an acute HAV infection will not produce any sequelae, but a co-infection with HIV may lead to permanent liver damage and an increase in HIV viral replication.^6,7

The impact of hepatitis A on HIV patients may include disruption of their antiretroviral therapy, increases in viral replication and, sometimes, a dramatic decrease in CD4 T-cell counts. In a segment of patients who acquire acute HAV infections, CD4 T-cells decrease enough (below 200 cells/mm3) that the patient may be reclassified as having AIDS. But generally, the CD4 T-cells rebound back to baseline once the patient has completed the acute phase. Viral replication will also return to baseline once the patient is able to resume antiretroviral therapy.

Treatment for HAV is usually supportive care with rest and discontinuation of drug therapy until the acute phase is completed, at which time therapies may be restarted. Maintaining hydration, bed rest, no contact sports and good nutrition are all essential for a complete recovery.

Vaccination for HAV should be considered as preventive therapy for patients with chronic terminal infections such as HIV and patients who are not HAV IgG-positive at the time of hepatitis diagnosis. This may prevent potential infections in patients who may be immunocompromised. The cost of the vaccination varies, and in some research facilities or in states with the AIDS Drug Assistance Program (ADAP), the HAV vaccine may be free to HIV patients.

Hepatitis B

HBV infection remains a considerable health problem worldwide and a significant cause of liver disease and liver cancer in humans.⁸ HBV is readily transmitted via parenteral and sexual routes, and as such, it is common in patients who are co-infected with HIV-1. For an immunocompromised host, a frequent outcome of HBV is the development of a chronic carrier state that does not spontaneously resolve over time. Approximately 20 percent of patients are unable to clear the virus, and the infection may continue to develop, leading to hepatomegaly, cirrhosis or primary hepatocellular carcinoma.⁹

All blood and body fluids are considered potentially infectious. In infected patients, HBV particles may be present in saliva, semen and cervical secretions; thus, it is potentially transmitted via percutaneous and nonpercutaneous (usually sexual) routes.

Common modes of transmission include accidental puncture of the skin with an infected needle, blood splashed in the eye, or sharing of unsterilized needles. Other modes include exposure to instruments while receiving tattoos, ear piercing or acupuncture, as well as sharing razors or toothbrushes. Aerosolized blood in the vicinity of centrifuges and dental drills may also play a role in transmission.¹⁰

HBV can present in any age group, with certain populations considered at high risk for HBV infection (Alaskan Eskimos, Pacific Islanders and infants born to women who are first-generation immigrants from endemic regions). The usual incubation period is 28 to 160 days. Patients may present with insidious symptoms such as arthralgias, rash, nausea, vomiting and, less commonly, jaundice.

Laboratory diagnosis is made via HBsAg, which will be positive or reactive. It represents both a current and chronic infection and is presumed to be infectious. The anti-HBc-positive will also be positive during a current and chronic infection with HBV. This finding may also represent a past infection, but is not diagnostic for an acute infection unless the patient is also positive for anti-HBc IgM. A positive laboratory anti-HBs indicates immunity. If HBcAb is positive, natural immunity is present; if negative, the patient will need vaccination.

HBV DNA is currently the most accurate test to assess current disease and infectivity. It will not be present if the patient is HBV-negative or has had the vaccination series. Patients who have not cleared HBV from their blood within 6 months are considered chronic carriers of hepatitis B and require regular monitoring. These patients should be vaccinated with HAV if they are HAV antibody-negative, to protect the liver from further potential damage.

Currently, few pharmacologic solutions are available for patients who are co-infected with HIV and HBV. Several clinical studies have assessed the efficacy of medications such as lamivudine (3TC, Epivir), famcyclovir (Famvir) and adefovir (Preveon) and provided significantly promising results. Clinically, patients may continue on lamivudine after a vRNA rebound indicating virologic failure to lamivudine, with the hope that the patient who is co-infected may still benefit from lamivudine. Available data suggest that lamivudine shows promise as an effective treatment for chronic HBV. In studies, serum HBV DNA by liquid hybridization decreased in all patients and was undetectable at the end of the treatment in seven of 12 (58 percent, 25 mg), 13 of 14 (93 percent, 100 mg), and 14 of 16 (88 percent, 300 mg) patients with decreases in abnormal ALT.^11,12 Most data about chronic HBV response to lamivudine have been gathered from HIV-negative patients. Little data are available from patients who are co-infected with HIV and chronic HBV.

Several studies have documented early resistance to lamivudine in patients not infected with HIV. Data from a study of immunocompromised adults with chronic HBV showed a high incidence of lamivudine resistance, which may have implications for the concept of long-term virus-suppressive therapy of chronic HBV with lamivudine monotherapy.¹³

Although adefovir is not cleared by the FDA for use as an antiretroviral, it has demonstrated activity against HBV along with its daughter compound, tenofovir, which may become available this year.

Prevention is still most desirable, and all patients should have a baseline HBV screening as new patients and receive the vaccine, which consists of a series of three injections. The initial injection is at baseline, followed by a second in 1 month and the third 6 months after the initial injection. At 5 years post-vaccination, approximately 80 percent of people remain anti-HBs positive. In HIV-infected patients, this number generally falls to response levels of only 30 percent to 50 percent.