day 1 - viral hepatitis Flashcards
what is hepatitis A and how is it transmitted
Hepatitis A virus (HAV) is a single stranded RNA virus with an incubation period of approximately 2 to 6 weeks. HAV has a world-wide distribution, but is especially common in the tropics.
HAV is transmitted via the faecal-oral route following faecal contamination of food and water. Raw or poorly cooked shellfish are often implicated. Epidemics occur. Sexual transmission may occur through oro-anal intercourse and there is an increased frequency of infection amongst homosexual men in the UK.
HAV is maintained in human populations by case to case transmission. HAV enters the body via GI tract. Primary multiplication probably occurs in the gut. The virus then spreads to the liver where it multiplies in the hepatocytes. Virus is present in the faeces for about two weeks before the onset of jaundice, but usually only for a few days after the onset of symptoms. HAV has recently been transmitted by high purity clotting factor concentrates.
clinical features of hepatitis A (HAV)
Prodromal symptoms consisting of malaise, anorexia, nausea; aversion to fatty foods and cigarettes may be present. The severity of the icteric phase of the illness is age related with adults more likely to suffer a symptomatic infection. The overall mortality is less than 0.1%. Most acute HAV infections resolve over a period of weeks. However, the hepatitis may relapse within a few weeks of apparent recovery. There is no carrier state.
diagnosis of HAV infection
This is made serologically by the detection of HAV-specific IgM or by demonstrating seroconversion for antibody.
treatment of HAV
This is conservative with complete resolution in most cases.
prophylaxis for HAV
HAV infection may be prevented by either passive immunisation with human normal immunoglobulin or active immunisation with HAV vaccine. This is a killed whole virus vaccine prepared from tissue cultured HAV.
what is HBV and how is it transmitted
Hepatitis B (HBV) is a double stranded DNA virus with an incubation period of 2 to 6 months. The virus itself, the Dane particle, has a distinctive morphology and was first visualised in this medical school. HBV may be transmitted sexually, from mother to child or by parenteral inoculation. Sexual transmission of HBV is common. HBV is usually maintained in populations by infectious carriers rather than by acute case to case transmission. It is common in the tropics. Blood and blood products, in spite of screening, may transmit infection. Hospital staff are at risk of infection through needlestick exposure, they may also pass HBV to their patients.
The site of early replication is not known but may be the Küpffer cell. HBV spreads through the liver and expression of HBcAg can be seen in hepatocyte nuclei with HBsAg and HBeAg in the cytoplasm. Virus and viral antigens are shed into the blood. HBV is not cytopathic and the liver damage is immune mediated.
clinical features of HBV
A prodrome of malaise, anorexia, arthralgia and arthritis may be present. The acute infection is often subclinical, particularly in children. The mortality associated with an acute infection is less than 1%. Approximately 5-10% of acutely infected adults will become HBV carriers. Acute infections which present with jaundice virtually never leads to chronic carriage. A history of jaundice in the remote past does not indicate a risk of HBV carriage. HBV infections in neonates and immunosuppressed patients are likely to persist. These patients are termed carriers and this carrier state may persist for life.
Carriers may develop chronic liver disease, cirrhosis and primary liver cell cancer. Some HBV carriers may also develop extra-hepatic disease, for example glomerulonephritis in children and polyarteritis nodosa. HBV carriers are classified as high infectivity and low infectivity carrier on the basis of their hepatitis B e antigen status (see below). Initially carriers are of high infectivity with their serum containing high levels of HBsAg, HBeAg and virions. Sometimes referred to as ‘supercarriers’ they represent the principal reservoir of infection. After time, the infection becomes partially suppressed. HBsAg remains in the serum but HBeAg is replaced by anti- HBe and virions virtually disappear from the circulation. Such carriers are far less infectious and are often referred to as ‘simple carriers’.
diagnosis of HBV
The diagnosis of a current or past HBV infection or immunisation with HBV vaccine is usually made serologically based on presence of various HBV antigens and antibodies to these.
eg
acute infection - HBV surface antigen usually present, anti-HBV surface antigen is not. anti-HBc IgM present.
past infection/immunisation - HBV surface antigen not present, Antibody to hepatitis B surface antigen is.
treatment of HBV
Management of the acute infection is usually conservative.
Conventional interferon alpha, pegylated interferon alpha and nucleos(t)ide analogues such as lamivudine, adefovir, entecavir, telbivudine and tenofovir have been used in chronic carriers in attempts to switch the patient from being supercarriers (HBeAg) to simple carriers (anti-HBe).
Treatment may be monitored by using quantitative real-time PCR to measure the circulating ‘viral load’. The long- term effects, safety and tolerability of these drugs is uncertain and the development of drug resistance remains a significant problem.
The treatment of an acute HBV infection is
conservative with most patients being managed on an out-patient basis. The patient’s liver function, coagulation profile (prothrombin time) and HBV status (HBsAg, HBeAg, anti-HBe and anti-HBs) should be monitored into convalescence. The patient should be advised not to drink alcohol and to avoid other potentially hepatotoxic drugs until the hepatitis has resolved.
prophylaxis for HBV
Prophylaxis is given either by passive immunisation with hyperimmune hepatitis B immunoglobulin (HBIG) and/or by active immunisation with hepatitis B vaccine. Originally made from human plasma, this is now produced as a recombinant protein in yeast. Care with handling blood and sharp instruments in hospitals will reduce exposure. Nowadays all staff (including medical students!) should be immunised.
Staff conducting exposure-prone procedures (EPPs), i.e. those most likely to lead to accidental inoculation, are now screened for infection if not found to be immune. HBeAg carriers will not be allowed to perform EPPs.
HCV features and transmission
Hepatitis C virus (HCV) is a single stranded RNA virus with an incubation period of 2- 3 months. Prior to the introduction of blood donor screening for antibody to HCV (anti-HCV) this was the most important cause of post-transfusion non-A, non-B hepatitis. HCV infection can also be acquired through needlestick injuries in health care workers or via shared needles among intravenous drug users.
Carriers represent the most significant reservoir of infection by which HCV is maintained in the population.
Transmission from mother to child has also been documented. HCV may occasionally be transmitted sexually.
Six different genotypes are described and the virus is genetically quite diverse.
HCV clinical features
Most acute infections will be subclinical. When symptoms present they are usually mild (lethargy and anorexia). Jaundice is uncommon, occurring in only about 10% of cases. The majority of acute infections (over 70%) will develop into chronic persistent infections.
Chronic HCV infection is associated with the development of chronic liver disease including chronic hepatitis, cirrhosis and primary liver cell cancer. A chronic HCV infection may also act as a trigger factor for the development of autoimmune liver disease, mixed essential cryoglobulinaemia and porphyria cutanea tarda.
HCV diagnosis
Serology. Seroconversion for antibody to HCV (anti-HCV) may be delayed for several months after an acute HCV infection. Serology is therefore useful to diagnose a chronic, but not an acute, HCV infection.
Detection of HCV RNA. HCV RNA can be detected in the serum of an HCV-infected patient following amplification of serum viral RNA by RT-PCR. Detection of HCV- RNA may be used to diagnose acute infections. HCV antigen detection assays have recently become available and are being evaluated.
treatment of HCV
Chronic hepatitis carries a significant morbidity. Early studies with interferon alone lead to eradication of infection in less than 25% of carriers. Combined interferon and ribavirin treatment is more effective resulting in viral eradication in approximately 40% of cases. The use of pegylated interferon in combination with ribavirin has further improved the efficacy of treatment (~50% viral eradication), although the response rate in patients infected with genotypes 1 and 4 remains disappointing.
Determination of IL28B polymorphisms may be useful to identify a patient’s likelihood of response to treatment with pegylated interferon alpha and ribavirin; however, the predictive value is relatively low. Several protease inhibitors have been shown to be effective in clinical trials and two of these (telaprevir and boceprevir) are about to be introduced in the UK. Inhibitors of the RNA-dependent RNA-polymerase NS5B, as well as compounds that directly inhibit HCV replication through interaction with host cell proteins (e.g. cyclophilin) are also being investigated in clinical trials.
HCV treatment may be monitored by using quantitative real-time RT-PCR to measure the circulating ‘viral load’.
HCV prophylaxis
At present there is no prophylaxis other than care to prevent exposure to infection. Experimental vaccines are under development but there is no vaccine currently available.
