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Hepatitis

Hepatitis A

• Epidemiology
  • Hepatitis A is a picornavirus that is resistant to environmental factors (eg, temperature, certain chemicals).
• Transmission
  • Hepatitis A exists in highest concentration in the faeces of infected individuals; the greatest faecal viral load tends to occur near the end of the incubation period of hepatitis A.
  • Most commonly, the virus spreads from person to person via the faecal-oral route. Contaminated water and food, including shellfish collected from sewage-contaminated water, hepatitis Ae also resulted in epidemics of hepatitis A.
  • Finally, the virus may also spread via infected serum.
  • Infection with hepatitis A occurs throughout the world. However, risk of infection is greatest in developing countries, areas of low socioeconomic status, and areas without sufficient sanitation. Higher infection rates also exist in settings where faecal-oral spread is likely, such as day care centres.
  • Other groups at high risk for hepatitis A infection include international travellers, users of injected drugs, military personnel stationed abroad, and homosexual men. Maternal-neonatal transmission is not established.
  • Close contacts of infected individuals are also at risk. The secondary infection rate for hepatitis A in household contacts of patients with acute hepatitis A infection is around 20%. Thus, secondary infection plays a significant role in the maintenance of hepatitis A outbreaks.
• Clinical course
  • The incubation period of hepatitis A is 2-7 weeks, with an average of 28 days. Clinical symptoms then develop, often with a presentation similar to that of gastroenteritis or a viral respiratory infection.
  • Most common signs and symptoms include fatigue, nausea, vomiting, fever, hepatomegaly, jaundice, dark urine, anorexia, and rash.
  • Hepatitis A infection usually occurs as a mild self-limited disease and confers lifelong immunity to hepatitis A. Chronic infection with hepatitis A does not occur.
• Morbidity and death
  • Although hepatitis A usually causes mild disease, the older the patient, the more severe the disease is likely to be. While icteric disease occurs in fewer than 10% of children younger than 6 years with hepatitis A, it occurs in 40-50% of older children and in 70-80% of adults with hepatitis A. Other complications can include acute liver failure, cholestatic hepatitis, and relapsing hepatitis.
  • The overall mortality rate for hepatitis A is approximately 0.01%. Children younger than 5 years and adults older than 50 years hepatitis Ae the highest case-fatality rates.

 

Hepatitis B

• Epidemiology
  • A major cause of infectious hepatitis worldwide, hepatitis B belongs to the class of hepadna viruses.
  • Estimates suggest that 400 to 500 million people worldwide are hepatitis B carriers. The virus leads to 1 million deaths annually as a result of viral hepatitis–induced liver disease.
  • The incidence of childhood hepatitis B infection is not well established because more than 90% of hepatitis B infections in this age group are asymptomatic.
• Transmission
  • The major reservoir of hepatitis B is people with chronic hepatitis B infection. In this group, those with hepatitis B e antigen (HBeAg) in their serum tend to hepatitis have higher viral titres and thus greater infectivity.
  • Hepatitis B transmits both parenterally and sexually, most often by mucous membrane exposure or percutaneous exposure to infectious body fluids. Saliva, serum, and semen all have been determined to be infectious.
  • Percutaneous exposures leading to the transmission of hepatitis B include transfusion of blood or blood products, injection drug use with shared needles, haemodialysis, and needlesticks (or other wounds caused by sharp implements) in health care workers.
  • Another significant mode of transmission is perinatal transmission. The greatest risk of perinatal transmission occurs in infants of HBeAg-positive women. By age 6 months, these children have a 70-90% risk of infection and, of those, about 90% will go on to develop chronic infection with hepatitis B.
  • For infants born to HBeAg-negative women, risk of infection approximates 10-40%, with a chronic infection rate of 40-70%. Even if transmission does not occur in the perinatal period, these children still have a significant risk of developing infection during early childhood.
  • High-risk groups for infection with hepatitis B include intravenous drug users, persons born in endemic areas, and men who are homosexually active.
  • Other groups at risk include health care workers with exposure to infected blood or bodily fluids, recipients of multiple blood transfusions, patients undergoing haemodialysis, heterosexual persons with multiple partners or a history of sexually transmitted disease, institutionalized persons including prisoners, people who are developmentally disabled, and household contacts or sexual partners of hepatitis B carriers.
• Clinical course
  • The incubation period for hepatitis B varies from 30-180 days, with the average approximately 75 days. Patients then enter the prodromal or preicteric phase, developing gradual onset of anorexia, malaise, and fatigue. During this phase, as the liver becomes inflamed, liver enzymes start to elevate, and the patient may experience right upper quadrant pain. Fifteen percent of patients develop an illness resembling serum sickness. These patients may experience fever, arthritis, arthralgias, or an urticarial rash.
  • As the disease progresses to the icteric phase, the liver becomes tender, and jaundice develops. Patients may note that their urine darkens and that their stools lighten in color. Other symptoms in this stage include nausea, vomiting, and pruritus.
  • From this point on, patients may have quite a variable course. Some experience fairly rapid improvements in their symptoms, while others go on to a prolonged disease course with slow resolution. Still others may have symptoms that periodically improve, only to worsen later (relapsing hepatitis).
  • A subset of patients suffers rapid progression of their disease to the point of fulminant hepatic failure. This may occur over days to weeks.
• Complications
  • One of the major complications of hepatitis B infection is the development of chronic infection. Patients with chronic hepatitis B infection are at risk of later developing chronic active hepatitis, cirrhosis of the liver, and eventual hepatocellular cancer.
  • Patients infected at an early age have the greatest risk of developing chronic hepatitis B infection. While 90% of those infected at birth develop chronic hepatitis B, only 5-10% of older children or adults go on to develop chronic infection. The risk of chronic infection is also higher in patients who are immunocompromised.
  • Patients with chronic hepatitis B infection have a significantly increased risk of developing hepatocellular cancer. In fact, hepatocellular cancer is the leading cause of cancer-related deaths in areas where hepatitis B is endemic. The cancer is believed to result from repeated bouts of chronic inflammation and cellular regeneration. Hepatocellular cancer develops an average of 25-30 years after initial infection.
  • Another major complication of hepatitis B infection is development of fulminant hepatic failure. In approximately 0.5-1% of hepatitis B-infected patients, the disease progresses to fulminant hepatic failure, with coagulopathy, encephalopathy, and cerebral oedema. The case-fatality rate for these patients approaches 80%.

 

Hepatitis C

• Epidemiology
  • Hepatitis C is a single-stranded ribonucleic acid (RNA) virus that is the most frequent cause of parenteral non-A, non-B hepatitis worldwide. Estimates suggest that 170 million people are chronically infected with HCV. In the United States, approximately 4 million people are infected with HCV; of those, nearly 3 million have chronic infection.
  • HCV causes approximately 17-20% of acute hepatitis cases in the United States, and the CDC estimates that 150,000 new cases of HCV occur annually. Highest rates of disease prevalence are found in patients with haemophilia and in injection drug users. Before the newer universal plasma screening measures, HCV accounted for 90% of post transfusion hepatitis cases.
  • HCV is the most common cause of chronic viral hepatitis in the United States. About 80% of people infected progress to chronic HCV infection.
• Transmission
  • HCV can be transmitted parenterally, perinatally, and sexually. HCV is transmitted most reliably through transfusion of infected blood or blood products, transplantation of organs from infected donors, and sharing contaminated needles among intravenous drug users.
  • Needlestick injuries among health care workers place them at significant risk of infection. Incidence of HCV infection in health care workers with history of needlestick exposure to infected blood approaches 10%. Even more concerning is the 0.4-1% chance of developing irreversible liver injury from a needlestick infection in this setting.
• Clinical course
  • Incubation period for HCV runs 15-150 days, with symptoms developing anywhere from 5-12 weeks after exposure.
  • During acute infection with HCV, symptoms may appear similar to those of hepatitis B infection. In up to 80% of cases, however, patients are asymptomatic and do not develop icterus.
• Complications
  • Acute infection with HCV may cause fulminant hepatic failure and is associated with aplastic anaemia.
  • Approximately 50-85% of patients with HCV become chronically infected with HCV; of those, 29-76% later develop chronic active hepatitis or cirrhosis. In fact, HCV is a leading cause of chronic hepatitis and cirrhosis worldwide.
  • In the United States and Europe, chronic HCV infection is the leading indication for liver transplant. Moreover, chronic HCV infection causes 10,000 deaths per year in the United States.
  • Chronic HCV infection is also strongly linked to the development of hepatocellular cancer, which usually develops after 30 years in patients who are chronically infected and have cirrhosis.

 

Hepatitis D

• Epidemiology
  • HDV, an incomplete virus, requires the presence of hepatitis B to replicate; therefore, HDV infection develops only in patients who are positive for the hepatitis B surface antigen (HBsAg).
  • Patients may acquire HDV as a co-infection (at the same time that they contract hepatitis B), or the HDV may superinfect patients who are chronic hepatitis B carriers.
  • Although HDV is not a reportable disease, the CDC estimates that it results in 7500 infections each year. Approximately 4% of cases of acute hepatitis B are thought to involve co-infection with HDV.
• Transmission
  • Modes of transmission for HDV are similar to those for hepatitis B, although perinatal transmission rarely occurs and has not been documented in the United States.
• Clinical course
  • The incubation period of HDV is approximately 35 days. Patients co-infected with hepatitis B and HDV tend to have a more severe disease course than those infected with hepatitis B alone. As many as one third of those with co-infection go on to develop fulminant hepatitis.
  • Chronic hepatitis B carriers superinfected with HDV usually also develop chronic HDV infection. Chronic co-infection often leads to rapidly progressive subacute or chronic hepatitis, resulting in a more rapid progression to cirrhosis.
  • Over the long term, as many as 70-80% of these patients have evidence of chronic liver disease with cirrhosis, compared to only 15-30% of patients with chronic hepatitis B alone.

 

Hepatitis E

• Epidemiology
  • Hepatitis E virus is the primary cause of enterically transmitted non-A, non-B hepatitis; most outbreaks occur in developing countries.
  • Until 1997, HEV transmission was undocumented in the United States. All previously documented HEV cases occurred in travelers from countries where HEV is endemic. In 1997, a case report was published of a US patient with no history of travel who developed hepatitis caused by HEV.
• Transmission
  • HEV is transmitted primarily by the faecal-oral route, with faecally contaminated water providing the most common means of transmission.
  • Transmission by person-to-person contact is undocumented.
• Clinical course
  • The incubation period is 2-9 weeks with an average of 45 days.
  • HEV usually causes an acute self-limited disease similar to hepatitis A. Fulminant disease does occur in about 10% of cases. In women who are pregnant, HEV infection has a case fatality rate of 15-20%. No reports of chronic infection with HEV exist.

 

Other types of viral hepatitis

• Other proposed agents of viral hepatitis (now referred to as non-ABCDE viral hepatitis) are currently under investigation, since researchers suspect that other forms of parenterally transmitted hepatitis may exist.
• Hepatitis F is proposed as another enterically transmitted hepatitis virus. A small number of cases have been documented in France.
• Hepatitis G virus, characterized in 1996, is associated with acute and chronic liver disease, but studies have not clearly implicated HGV as an etiologic agent of hepatitis.
• Other known viruses (eg, cytomegalovirus, Epstein-Barr virus, herpes simplex, varicella-zoster) may also cause inflammation of the liver.

Principal source: Emedicine  

• Brad Cheek: last updated Jan 2009
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