HBV, a double-stranded DNA virus, belongs to the family of hepadnaviruses. HBV infection is a global public health problem. Perinatal transmission and occasionally horizontal transmission early in life are most common in high prevalence areas. Sexual contact and percutaneous transmission also contribute to the transmission of HBV.
The spectrum of clinical manifestations of HBV infection varies in both acute and chronic disease. During the acute phase, manifestations range from subclinical or anicteric hepatitis to icteric hepatitis and, in some cases, fulminant hepatitis. The incubation period for HBV varies from 30-180 days. In chronic phase, manifestations range from an asymptomatic carrier state to chronic hepatitis, cirrhosis, and HCC. Extra-hepatic manifestations can also occur with both acute and chronic infection.
Approximately 70 percent of patients with acute HBV infection have subclinical or anicteric hepatitis, while 30 percent develop icteric hepatitis. The disease may be more severe in patients co-infected with other hepatitis viruses or with underlying liver disease. Fulminant hepatitis B is unusual, occurring in approximately 0.1 to 0.5 percent of patients; it is believed to be due to massive immune-mediated lysis of infected hepatocytes.
A serum sickness-like syndrome may develop during the prodromal period, followed by constitutional symptoms, anorexia, nausea, jaundice, and right upper quadrant discomfort.
The symptoms and jaundice generally disappear after one to three months, but some patients have prolonged fatigue even after normalization of serum aminotransferase concentrations.
A history of acute hepatitis is elicited in only a small percentage of patients with chronic HBV infection. In low or intermediate prevalence areas, approximately 30 to 50 percent of patients with chronic HBV infection have a past history of acute hepatitis; such a history is lacking in the remaining patients in these areas and in the majority of patients in high prevalence areas (predominantly perinatal infection).
Many patients with chronic HBV are asymptomatic (unless they have decompensated cirrhosis or have extra hepatic manifestations), while others have nonspecific symptoms such as fatigue. Some patients experience exacerbations of the infection which may be asymptomatic, mimic acute hepatitis, or manifest as hepatic failure.
Physical examination may be normal, or there may be stigmata of chronic liver disease. Jaundice, splenomegaly, ascites, peripheral edema, upper gastrointestinal bleed and encephalopathy may be present in patients with decompensated cirrhosis. Laboratory tests may be normal, but most patients have a mild to moderate elevation in serum AST and ALT.
During exacerbations, the serum ALT concentration may be as high as 50 times the upper limit of normal, and alfa-fetoprotein (AFP) concentrations as high as 1000 ng/mL may be seen. A progression to cirrhosis is suspected when there is evidence of hypersplenism (decreased hemoglobin, white blood cell and/ or platelet counts) or impaired hepatic synthetic function (hypoalbuminemia and/or prolonged prothrombin time/ international normalized ratio (INR).
Natural Course and Phases of Chronic Hepatitis B Infection
The natural course of chronic HBV infection is determined by the interplay between virus replication and the host immune response. Other factors that may play a role in the progression of HBV-related liver disease include gender, alcohol consumption, and concomitant infection with other hepatitis virus (es). The outcome of chronic HBV infection depends upon the severity of liver disease at the time HBV replication is arrested.
Laboratory testing during the acute phase reveals elevations in the concentration of alanine and aspartate aminotransferase levels (ALT and AST); values up to 1000 to 2000 international units/L are typically seen during the acute phase with ALT being higher than AST. The serum bilirubin concentration may be normal in patients with anicteric hepatitis.
The prothrombin time is the best indicator of prognosis. In patients who recover, the normalization of serum aminotransferases usually occurs within one to four months. A persistent elevation of serum ALT for more than six months indicates a progression to chronic hepatitis.
Management of HBV
As a priority, all adults, adolescents and children with CHB and evidence of compensated or decompensated cirrhosis should be treated, regardless of ALT levels, HBeAg status or HBV DNA levels/
Antiviral therapy is not recommended and can be deferred in persons without evidence of cirrhosis, and with persistently normal ALT levels and low levels of HBV replication (HBV DNA below 2000 IU/mL), regardless of HBeAg status or age.
• Where HBV DNA testing is not available: Treatment can be deferred in HBeAg-positive persons aged 30 years or less and persistently normal ALT levels. Treatment is recommended for adults with CHB who do not have evidence of cirrhosis, but are aged more than 30 years (in particular), and have persistently abnormal ALT levels and evidence of high-level HBV replication (HBV DNA less than 20000 IU/mL), regardless of HBeAg status.
Continued monitoring is necessary in all persons with CHB, but in particular those who do not currently meet the recommended criteria for whom to treat or not treat, to determine if antiviral therapy may be indicated in the future to prevent progressive liver disease. These include persons without cirrhosis aged 30 years or less, with HBV DNA levels greater than 20000 IU/mL but persistently normal ALT.