HEPATITIS B

This form of the disease is responsible for almost 80% of primary hepatocellular carcinoma cases. Approximately 400 million people worldwide are infected with HBV; an estimated 1.2 million live in the United States.3 The highest incidence is in those aged 20-40.4 Each year, about 6,000 Americans die from HBV infection and its complications.

Although the virus can be found in virtually all of an infected patient’s body fluids, including blood, semen, saliva, and urine, transmission requires either direct inoculation or intimate personal contact. The most common routes of transmission are contact with infected blood or unprotected sex with an infected person. Vertical transmission occurs when a pregnant woman passes the virus to her fetus. Individuals at high risk of contracting HBV include those with multiple sex partners, men who have sex with men, IV drug users, infants born to infected mothers, those on hemodialysis, hemophiliacs, and health-care workers.


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Symptoms


Incubation is relatively long at 45-180 days. Most patients are asymptomatic during acute infection. The virus will then be cleared by the immune system, or the patient will enter a chronic carrier state (5%-10% of cases3). Very few patients progress to fulminant hepatic failure. Some will develop a flulike illness several weeks to months after infection, with such symptoms as fevers, chills, malaise, anorexia, and nausea. Jaundice and hepatomegaly may also be present. Similar to HAV infection, constitutional symptoms resolve with the onset of jaundice. 

Most patients with chronic hepatitis B do not demonstrate any abnormal findings on examination. Those with advanced disease, such as cirrhosis, may exhibit jaundice, confusion, ascites, splenomegaly, edema, gynecomastia, palmar erythema, spider angiomas, muscle wasting, testicular atrophy, and asterixis. Extrahepatic manifestations, such as polyarteritis nodosa, glomerular disease, and nonspecific rashes and arthralgias, occur in 10%-20% of patients with chronic infection.5

Diagnosis


HBV serology is often the most difficult of all hepatitis viruses to interpret. Several tests are needed to distinguish among acute or chronic infection, immunity secondary to a previous HBV infection, or vaccine-induced immunity

The hepatitis B surface antigen (HBsAg) is the first test to be abnormal. A positive result indicates active acute or chronic infection. HBsAg levels usually increase two to six weeks after exposure but before symptom onset. Levels then decrease and become undetectable one to three months after the initial peak. Persistence of HBsAg indicates chronic infection. 

The hepatitis B surface antibody (anti-HBs or HBsAb) test is a marker for HBV immunity; sensitivity and specificity is >98%. A positive anti-HBs indicates immunity through previous infection or immunization. Antibodies can appear two weeks to a few months after cessation of symptoms or after disappearance of HBsAg; they usually remain elevated for life. 

The hepatitis B core antibody total (anti-HBc total or HBcAb total) is a nonspecific marker of acute, chronic, or resolved HBV infection. This test is often broken down into subclasses, anti-HBc IgM and anti-HBc IgG. IgM typically appears in conjunction with clinical symptoms; its presence indicates acute or recent infection. IgG is found in all patients infected with HBV, past or present. Although levels are often undetectable after three to six months, they can persist for up to two years after initial infection. 

A positive anti-HBc total indicates either chronic infection or resolved infection. Diagnosis is determined by HBsAg and anti-HBs results. A positive HBsAg indicates chronic infection; a  positive anti-HBs indicates a resolved infection.

Infectivity in chronic carriers is measured by persistence of the hepatitis B envelope antigen (HBeAg). This marker generally develops three to five days after the appearance of HBsAg and disappears two to four weeks after initial infection. 

The hepatitis B envelope antibody (anti-HBe or HBeAb) appears shortly after HBeAg resolves and indicates the end of the acute phase of infection. This marker can be detected for up to six years after acute infection. It is seen in infected patients as well as in those with immunity caused by resolved infection. The likelihood of infectivity is greatly reduced when this antibody is present.

Viral replication, which also correlates with infectivity, can be assessed with the HBV DNA test, or HBV viral load test. This test is also used to help monitor the treatment of those with chronic HBV.

Treatment


Treating HBV infections is often difficult, and therapy can be complicated by patient age; stage of disease; pattern of liver disease; coinfection with HCV, HDV, or HIV; presence of comorbid conditions; adverse medication effects; and the willingness of the patient to be treated. The goal of treatment is seropositivity for anti-HBe with undetectable HBe antigen and HBV DNA. This decreases the risk of cirrhosis and its complications. 

Before initiating therapy, liver function should be monitored for at least six months to assess the pattern of disease. Enzymes are usually elevated with acute infection. In this phase, levels of alanine aminotransferase (ALT) and aspartate aminotranferase (AST) can number in the thousands of units per milliliter, alkaline phosphatase levels may be doubled, bilirubin is elevated, and prothrombin time may be elevated up to 5 seconds longer than normal. Chronic carriers may demonstrate normal liver enzyme levels, with occasional mild elevation in the aminotransferases, mainly ALT. 

Treatment candidates are patients with ALT elevations greater than twice the upper level of normal, HBV DNA levels >10,000/mL, or evidence of moderate-to-severe chronic hepatitis on liver biopsy.6 Treatment differs for HBeAb-positive and -negative patients, so status should be determined. Patients with decompensated liver disease should be referred to an experienced hepatologist at a liver transplant center. 

Interferon is the first-line treatment for chronic active hepatitis B. Patients at this stage exhibit positive HBV DNA and HBeAg, elevated aminotransferase levels, and signs of liver dysfunction, such as decreased albumin levels. Several factors increase the likelihood for successful treatment, including female gender, elevated aminotransferases, negative HIV status, and low HBV DNA viral load.6

Interferon works by directly suppressing the virus while activating a cytotoxic T-lymphocyte response. Therapeutic advantages include a defined period of administration, lack of drug resistance, and a durable response, if attained. A loss of HBeAg and gain of anti-HBe suggests treatment success. 

Antiviral drugs have also been used to treat HBV infection. Lamivudine, or 3TC, is often effective in patients resistant to interferon therapy. The best candidates for 3TC therapy are patients who are HIV-positive, are infected with mutant viruses, or have normal aminotransferase levels.6 While a 12-week course of therapy is usually effective,6 DNA levels can rebound after treatment cessation. Also, viral resistance has developed to lamivudine and can lead to exacerbations of HBV.