Viral hepatitis is acute or chronic symptomatic or even sometimes asymptomatic inflammation of the liver. Usually the infection is self-limiting and clears within 12 weeks, but in immunocompromised patients it can pose serious complications and development of systemic problems. All viral hepatitities can lead to liver cirrhosis if untreated. There are important serological markers involving different proteins of the virus that can tell us whether or not the infection is acute or chronic and whether or not the virus is actively replicating or not. The viruses replicate one week before detection and two weeks post-detectable levels. The most common types of hepatitis are A, B and C. Although Hep A and B are on the decline as vaccination campaigns have been more successful. Hep C is gradually declining, but as of recently there has been an increase in incidence. It should be noted that as of now there is no currently FDA approved vaccination for Hep C. There are some more less common Hep virus like E, and D, but the incidence is low and clinically not very relevant. One important distinction to point out is that a person much have Hep B to acquire Hep D. Hep D requires the viral envelope protein from Hep B to survive.
Hep A is a +ssRNA picornavirus. It is non-enveloped which means when it is shedding and replicating it causes lysis of the hepatocytes in the liver. The disease is spread by fecal/oral route and the virus is exceptionally hardy. It is very hard to inactivate and can survive in water or on surfaces for an extended period of time. The incubation period is 20-40 days and the disease itself is mild in nature. Clinical presentation includes variable prodromal symptoms usually fever, malaise, weakness, nausea, loss of appetite, and myalgia. Jaundice may or may not be present. The virus usually presents as asymptomatic, especially at a younger age as the immune system is able to hold it in check. Symptoms can actually be a good thing as it means that the immune system is recognizing the virus and trying to rid of it. Risk groups include those who have direct contact with persons who have Hep A such as a healthcare worker, travelers to endemic countries are at high risk even when good hygiene and sanitation measures are being applied. Less commonly users of injection and non-injection drugs, and people with clotting factor disorders. Diagnostic workout includes serologically workup and liver enzyme panel as well as bilirubin levels.
Hep B is a dsDNA-RT enveloped hepadnavirus. The Hep B genome is unique in that it virally replicates using an RNA intermediate and uses its reverse transcriptase mechanism to complete its DNA replication making the life cycle very complex. Transmission is through body fluids or sexually and is considered a sexually transmitted disease (STD). Activities involving percutaneous or mucosal contact such as heterosexual contact, injection drug-use with sharing of needles, birth to an infected mother or contact with blood or sores of an infected person. Medical professionals should take care to avoid any needle sticks or other exposures to those infected. Its estimated that 400 million people worldwide are infected with Hep B. The clinical presentation often presents with very generalized symptoms similar to Hep A with the addition of joint pain, jaundice, dark urine or clay-colored bowel movements. Chronic Hep B infection is not commonly talked about as Hep C is primarily dubbed as the chronic hepatitis infection, but 5% of adults become chronically infected with Hep B. They can live asymptomatically or they can display a spectrum of disease ranging from chronic hepatitis flares to cirrhosis or hepatocellular carcinoma.
The Hep B diagnosis is largely reliant on serology. The Hep B surface antigen (HBsAg) is a protein on the surface of HBV. It can be detected in high levels in the serum during acute or chronic HBV infection. It should be noted that individuals typically lose the expression of the HBsAg after 12 weeks when chronically infected. The presence of HBsAg means that person is infectious. Hep B surface antibody (Anti-HBs) present means that the person is recovering from an infection and that they now have immunity to the HBV. Anti-HBs also is developed when an individual is vaccinated against Hep B. IgM antibody to Hep B core antigen (IgM-Anti-HBc) indicates that an individual has an acute Hep B infection or has had an infection within the last 6 months. IgG-Anti-HBc indicates previous infection with Hep B and immunity towards the virus. The core antibody persists for life. Its important to note that when you run labs looking for hepatitis if the Anti-HBs antibody is present, but the Anti-HBc antibody is NOT present this indicates the individual has been vaccinated, not previously infected. The core antibody will not develop during vaccination. The Hep B (e) antigen is a secreted product of the nucleocapsid of HBV that is found in the serum during actively replicating infection. This indicates that the individual has an incredibly high viral burden. Anti-HBe antibody produced is an indicator of seroconversion and is used as a predictor of clearance of the Hep B virus for individuals undergoing treatment. Acute Hep B is usually not treated and the individual receives supportive therapy if needed. Chronic Hep B is treated using interferon or five different antiviral nucleoside analogs. The treatment is not curative, and only has a 20-50% response rate, but improves prognostic markers. Hep B is HIGHLY infective, 50-100x more infectious than HIV and 10x more infectious as HCV.
Hep C is a +ssRNA enveloped flavivirus. Typical transmission is through exposure to infectious blood. This can either be through injection drug use of shared needles or through recipient of donated blood, or organs, or neonatal birth to an HCV infected mother. Sexual transmission can still occur, but not at the rate that Hep B is transmitted. Acute infection usually is asymptomatic or presents with only mild symptoms similar to that of HAV and HBV. The incubation period is 4-12 weeks. Chronic HCV is generally asymptomatic while some individuals present with mild chronic liver disease and others with cirrhosis or hepatocellular carcinoma. 15-25% of individuals who develop Hep C will be able to clear the disease. Of the 75-85% that develop chronic HCV 60-70% will develop chronic liver disease, 5-20% will develop cirrhosis, and 1-5% will develop HCC. Hep D diagnosis is dependent on screening tests for the HCV antibody. These screening methods include enzyme immunoassay (EIA) or enhanced chemiluminescence immunoassay (CIA). There are PCR tests that detect the HCV RNA and also that quantify the viral RNA to determine the disease burden. A diagnosis based solely on elevation of liver enzymes AST, ALT is not acceptable. There is no currently accepted vaccine, but there is research ongoing. Previous infection does not grant immunity for subsequent infections like one would think likely due to high rte of viral mutation. There are 3 characteristic classes of drugs for treatment of Hep C and one novel advancement of one. HCV protease, polymerase inhibitors and interferon are most commonly used. A new novel treatment called direct acting antivirals (DAA) is a combination therapy that is shown to be highly effective at suppressing viral replication and can actually result in a cure in as short as 12 weeks of treatment. The cure rate is 95%. This novel treatment protocol is showing unprecedented success, but it comes as cost. A cost that no insurance company wants to pay for and that most people can’t afford.
Chronic HBV and HCV are associated with an increased incidence of HCC. This is due to the continuous cycles of viral replication, the immune-mediated killing of the hepatocytes and inflammation. Inflammation induces oxidative damage and altered cellular metabolism. This creates an unhealthy environment in the liver.