Hepatitis B

Hepatitis B is an infectious illness caused by hepatitis B virus (HBV) which infects the liver of hominoidea, including humans, and causes an inflammation called hepatitis. Originally known as "serum hepatitis", the disease has caused epidemics in parts of Asia and Africa, and it is endemic in China. About a quarter of the world's population, more than 2 billion people, have been infected with the hepatitis B virus. This includes 350 million chronic carriers of the virus. Transmission of hepatitis B virus results from exposure to infectious blood or body fluids such as semen and vaginal fluids, while viral DNA has been detected in the saliva, tears, and urine of chronic carriers with high titer DNA in serum. Perinatal infection is a major route of infection in endemic (mainly developing) countries. Other risk factors for developing HBV infection include working in a health care setting, transfusions, and dialysis, acupuncture, tattooing, extended overseas travel and residence in an institution. However, Hepatitis B viruses cannot be spread by casual contact, such as holding hands, sharing eating utensils or drinking glasses, breast-feeding, kissing, hugging, coughing, or sneezing.

The acute illness causes liver inflammation, vomiting, jaundice and rarely, death. Chronic hepatitis B may eventually cause liver cirrhosis and liver cancer—a fatal disease with very poor response to current chemotherapy. The infection is preventable by vaccination.

Hepatitis B virus is an hepadnavirus—hepa from hepatotrophic and dna because it is a DNA virus^[11]—and it has a circular genome composed of partially double-stranded DNA. The viruses replicate through an RNA intermediate form by reverse transcription, and in this respect they are similar to retroviruses. Although replication takes place in the liver, the virus spreads to the blood where virus-specific proteins and their corresponding antibodies are found in infected people. Blood tests for these proteins and antibodies are used to diagnose the infection. 

Signs and symptoms

Acute infection with hepatitis B virus is associated with acute viral hepatitis – an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, dark urine, and then progresses to development of jaundice. It has been noted that itchy skin has been an indication as a possible symptom of all hepatitis virus types. The illness lasts for a few weeks and then gradually improves in most affected people. A few patients may have more severe liver disease (fulminant hepatic failure), and may die as a result of it. The infection may be entirely asymptomatic and may go unrecognized.

Chronic infection with hepatitis B virus may be either asymptomatic or may be associated with a chronic inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years. This type of infection dramatically increases the incidence of hepatocellular carcinoma (liver cancer). Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and liver cancer. Hepatitis B virus has been linked to the development of Membranous glomerulonephritis (MGN). 

Hepatitis B virus replication.

Prevention

Several vaccines have been developed for the prevention of hepatitis B virus infection. These rely on the use of one of the viral envelope proteins (hepatitis B surface antigen or HBsAg). The vaccine was originally prepared from plasma obtained from patients who had long-standing hepatitis B virus infection. However, currently, it is made using a synthetic recombinant DNA technology that does not contain blood products. One cannot be infected with hepatitis B from this vaccine.

The risk of vertical transmission to the newborn can be drastically reduced from 20%-90% to 5%-10% by administering to the newborn hepatitis B vaccine (HBV 1) and hepatitis B immune globulin (HBIG) within 12 hours of birth, followed by a second dose of hepatitis B vaccine (HBV 2) at 1-2 months and a third dose at and no earlier than 6 months (24 weeks). Since 2% of infants vaccinated will not develop immunity after the first three dose series, infants born to hepatitis B positive mothers are tested at 9 months for hepatitis B surface antigen (HBsAg) and the antibody to the hepatitis B surface antigen (anti-HBs); if post-vaccination test results indicate that the child is still susceptible, a second three dose series at (0, 1 and 6 months) is administered. If the child is still susceptible after the second series, a third series is not recommended.

Following vaccination, hepatitis B surface antigen may be detected in serum for several days; this is known as vaccine antigenaemia. The vaccine is administered in either two-, three-, or four-dose schedules into infants and adults, which provides protection for 85–90% of individuals. Protection has been observed to last 12 years in individuals who show adequate initial response to the primary course of vaccinations, and that immunity is predicted to last at least 25 years.

Unlike hepatitis A, hepatitis B does not generally spread through water and food. Instead, it is transmitted through body fluids; prevention is thus the avoidance of such transmission: unprotected sexual contact, blood transfusions, re-use of contaminated needles and syringes, and vertical transmission during child birth. Infants may be vaccinated at birth.

Shi, et al. showed that besides the WHO recommended joint immunoprophylaxis starting from the newborn, multiple injections of small doses of hepatitis B immune globulin (HBIg, 200–400 IU per month), or oral lamivudine (100 mg per day) in HBV carrier mothers with a high degree of infectiousness (>10⁶ copies/ml) in late pregnancy (the last three months of pregnancy), effectively and safely prevent HBV intrauterine transmission, which provide new insight into prevention of HBV at the earliest stage.

Treatment

Acute hepatitis B infection does not usually require treatment because most adults clear the infection spontaneously. Early antiviral treatment may only be required in fewer than 1% of patients, whose infection takes a very aggressive course (fulminant hepatitis) or who are immunocompromised. On the other hand, treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Chronically infected individuals with persistently elevated serum alanine aminotransferase, a marker of liver damage, and HBV DNA levels are candidates for therapy.

Although none of the available drugs can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. Currently, there are seven medications licensed for treatment of hepatitis B infection in the United States. These include antiviral drugs lamivudine (Epivir), adefovir (Hepsera), tenofovir (Viread), telbivudine (Tyzeka) and entecavir (Baraclude) and the two immune system modulators interferon alpha-2a and PEGylated interferon alpha-2a (Pegasys). The use of interferon, which requires injections daily or thrice weekly, has been supplanted by long-acting PEGylated interferon, which is injected only once weekly. However, some individuals are much more likely to respond than others and this might be because of the genotype of the infecting virus or the patient's heredity. The treatment reduces viral replication in the liver, thereby reducing the viral load (the amount of virus particles as measured in the blood).

Infants born to mothers known to carry hepatitis B can be treated with antibodies to the hepatitis B virus (HBIg). When given with the vaccine within twelve hours of birth, the risk of acquiring hepatitis B is reduced 90%. This treatment allows a mother to safely breastfeed her child.

Response to treatment differs between the genotypes. Interferon treatment may produce an e antigen seroconversion rate of 37% in genotype A but only a 6% seroconversion in type D. Genotype B has similar seroconversion rates to type A while type C seroconverts only in 15% of cases. Sustained e antigen loss after treatment is ~45% in types A and B but only 25–30% in types C and D.

In July 2005, researchers identified an association between a host-derived DNA-binding protein and the amount of HBV replication in the liver. Controlling the level of production of this protein could be used to treat hepatitis B.

Treatment lasts from 6 months to a year, depending on medication and genotype.