Free Shipping on All Orders $75 Or More!

Your Trusted Brand for Over 35 Years

Health Protocols

Hepatitis B

Development and Progression of HBV Infection

HBV Biology. The hepatitis B virus infects humans and higher primates, entering and replicating within liver cells (hepatocytes), and secreting new virus particles into circulation (WHO 2009; Gish 2012). HBV is extremely effective at targeting hepatocytes; less than 10 individual virus particles are sufficient to establish an infection (Protzer 2012). Upon infection, HBV DNA enters the nucleus of the hepatocyte, where it serves as the reservoir for formation of virus particles for the lifetime of the cell and makes treatment of HBV challenging (Wilson 2009; Nebbia 2012). Replication of HBV requires the activity of a viral reverse transcriptase enzyme, which is prone to introducing mutations into the viral genome and potentially allowing the virus to become resistant to some treatments (Liaw 2009; Nebbia 2012).

Following an incubation period of 1-4 months, acute symptomatic hepatitis occurs in about one-third of infected adults, 10% of young children, and rarely in infants (Nebbia 2012). Acute hepatitis B resolves on its own in over 95% of adult cases (Liaw 2009). The acute infection is considered resolved when hepatitis B surface antigen (HBsAg) can no longer be detected in the blood within 6 months of infection (Nebbia 2012). HBsAg, a lipoprotein that forms part of the protective coating of the virus particle, is a marker for disease progression. Many individuals with HBV infection (7–40%) who are HBsAg-positive may also carry the hepatitis B e-antigen (HBeAg), a viral protein associated with high infectivity (WHO 2009). After resolution of an acute infection, an individual generally develops lifelong immunity against HBV-associated hepatitis, although the virus itself is not cleared from the liver (Nebbia 2012). Small amounts of viral DNA can be detected in blood years after recovery from acute hepatitis B (Liaw 2009). Thus, immunosuppression (eg, corticosteroid therapy) has the potential to reactivate an HBV infection.

There are several genetic strains of HBV (genotypes A-H), which vary in geographic distribution, response to treatment, and risk of progression to advanced liver disease (Liaw 2009; Tanwar 2012). In the United States, HBV genotypes A and D are more common in African-Americans and Caucasians, whereas HBV genotypes B and C are more common among persons of Asian ancestry (El-Serag 2012). Severe liver disease and hepatocellular carcinoma is more likely from infection with genotypes C and D. Response to interferon treatment (a conventional therapy; see below) is greater in genotypes A and B (than C or D), and thymosin treatment (see below) is twice as effective in genotype B than C (Chien 2006; Tanwar 2012). Although not yet standard for HBV treatment, genotyping could enable clinicians to identify and provide appropriate therapy for those at increased risk of disease progression (Tanwar 2012).

Transmission and Infectivity. HBV is transmitted through the skin (eg, injection) or via mucosal exposure to infected blood or other body fluids, mainly semen or vaginal fluid (WHO 2009). In geographic areas with low HBV prevalence (such as the United States), sexual transmission and use of contaminated needles by illicit drug users are major risk factors for infection (Daniels 2009).

In areas of high HBV prevalence (such as the Asia Pacific region), the virus is most commonly spread from infected mother to child at birth or child to child during early childhood. About 90% of mothers with high viral load will infect their babies with HBV (Liaw 2009). HBV can also infect sperm, enabling possible transmission from infected father to embryo during conception (Kang 2012). The likelihood of parent-to-child transmission can be reduced by vaccination (Lee 2006) (see below).

Individuals with acute or chronic HBV infection should be considered infectious any time HBsAg is present in the blood. HBsAg can be found in blood and bodily fluids for 1–2 months before and after the onset of symptoms. HBsAg can be identified in serum 30 to 60 days after exposure to HBV. Other markers of infectivity include HBeAg (hepatitis B e antigen) and HBV DNA (Hepatitis B DNA). HBeAg is a viral protein that indicates ongoing viral replication and increased infectivity. HBV DNA is a marker of viral replication; higher viral loads correlate with greater infectivity (CDC 1990, WHO 2009, Byrd 2012).

Outcomes of HBV Infection:

Asymptomatic or acute HBV infection. Acute HBV infection is asymptomatic in most individuals (symptomatic acute hepatitis B occurs in only about one-third of infected adults, 10% of children, and rarely in infants) (Nebbia 2012). Symptoms are similar to other viral hepatitis’ and include loss of appetite, fatigue, nausea, vomiting, abdominal pain, joint pain, mild fever, dark urine, and jaundice (yellowing of the skin and eyes due to accumulation of bilirubin secondary to liver dysfunction) (Merck 2007). The majority of acute hepatitis cases resolve, and the infected person eventually develops immunity to the virus (Liaw 2009; Nebbia 2012).

Chronic HBV infection. Some acutely infected individuals will progress to chronic HBV infection. Chronic HBV carriers are identified by the presence of hepatitis B surface antigen (HBsAg) in their blood for over 6 months, a HBV DNA blood level of 2000-20 000 IU/ml, and persistent or intermittent increases in liver enzymes. People with viral DNA loads of less than 2000 IU/ml are considered inactive carriers (Chevaliez 2012).

Age of infection has a significant effect on persistence of HBV (WHO 2009; Nebbia 2012); 90% of children infected at birth will develop chronic HBV, compared to 20-30% of children aged 1-5 and 1-5% of adults (Nebbia 2012). Chronic HBV infection increases the risk of serious liver disease, including cirrhosis and hepatocellular carcinoma (El-Serag 2012). Dysbiosis (detrimental changes in intestinal flora) is also possible (Xu 2012).

Cirrhosis. Cirrhosis, the end stage of any chronic liver disease (Garcia-Tsao 2009), involves functional liver tissue being replaced by fibrous tissue and scarring. Ascites (buildup of fluid in the abdomen), hepatic encephalopathy (depressed brain function due to accumulation of toxins in the brain), bacterial infection of the abdomen, and cancer are complications of cirrhosis (Garcia-Tsao 2009; Mayo Clinic 2011a). Cirrhosis is generally irreversible, although studies suggest that some HBV-mediated cirrhosis may be reversible with treatment (Scaglione 2012).

Hepatocellular carcinoma. Liver cancer is the fifth most common cancer in men and seventh most common in women worldwide. Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Approximately 80% of HCC cases are associated with chronic HBV or HCV infection (El-Serag 2012). HCC risk increases with viral load. In the REVEAL-HBV study of liver disease in chronic HBV patients, individuals with the highest viral loads at study entry (over 1 million copies of HBV DNA per ml in blood) had almost 11 times the risk of HCC than those with viral loads of less than 10 000 copies/ml of blood (Chen 2006).

Fulminant Hepatitis. Fulminant hepatitis is an acute hepatitis leading to acute liver failure and hepatic encephalopathy within a rapid period of time (less than 8 weeks after the onset of jaundice) (Ichai 2011). Between 7 and 33.7% of fulminant hepatitis cases stem from HBV infection (Ichai 2011). Fulminant hepatitis is rare in HBV-infected children, and develops in 0.1-0.6% of acute hepatitis cases in adults (Nebbia 2012). HBV-mediated fulminant hepatitis has a mortality rate of about 70% (WHO 2009).