Overview

Hepatitis is an inflammation of the liver that results in diffuse hepatic cell death and may lead to areas of liver necrosis. It can be acute or chronic (lasting > 6 months) and may progress to fulminant liver failure, cirrhosis, and/or hepatocellular carcinoma. The most common causes of hepatitis in the United States are alcohol abuse and viral infection.

Viral hepatitis can be caused by dozens of viral infections, most commonly the hepatitis viruses (especially hepatitis A, hepatitis B, and hepatitis C) and the herpes viruses (cytomegalovirus, Epstein-Barr virus, varicella-zoster virus, herpes simplex virus).

Most cases are subclinical and asymptomatic. In clinically apparent disease, common symptoms include fever, nausea, vomiting, fatigue, jaundice, right-upper-quadrant abdominal tenderness, and dark urine and pale stools. Extrahepatic manifestations may occur, particularly with chronic hepatitis, and include amenorrhea, arthritis, skin rash, vasculitis, thyroiditis, gynecomastia, glomerulonephritis, polyarteritis nodosa, and Sjogren's syndrome. Complications of chronic hepatitis include cirrhosis, progressive liver failure, and hepatocellular carcinoma.

Hepatitis A is a self-limited cause of acute hepatitis and does not result in a carrier state or chronic disease. Transmission occurs via the fecal-oral route and most commonly results from poor hygienic practices and inadequate sanitation. Disease is usually mild and self-limited, and patients may be asymptomatic. However, fulminant liver failure may occur in patients with underlying liver disease, especially hepatitis C.

Hepatitis B generally causes a mild or subclinical acute hepatitis, but may result in chronic hepatitis or an asymptomatic carrier state. Progression to chronic hepatitis is most common in perinatal infections and young children. Transmission occurs via blood and body fluids (eg, unprotected sex, intravenous drug use, blood transfusions, tattoo and body piercing). Sexual contact is the most common mode of transmission in the United States, whereas perinatal transmission is common in developing countries.

Hepatitis C is the most common cause of chronic hepatitis in the United States and is the most common indication for liver transplantation. Acute hepatitis is usually asymptomatic, but more than 50% of cases will progress to chronic hepatitis. Hepatitis C patients usually do well for 20 to 25 years before developing cirrhosis, which occurs in about 20% to 30% of chronic cases. Although transmission can occur via blood products, this route is much less common since universal blood screening for hepatitis was initiated in 1990. Intravenous drug use in adults and vertical transmission in infants are the most common causes of hepatitis C today. Transmission rate is higher in patients with concomitant HIV.

Hepatitis D is dependent on co-infection with the hepatitis B virus. If hepatitis D is acquired at the same time as hepatitis B, complete recovery can be expected. However, hepatitis D occurring as a superinfection in a hepatitis B patient can cause a syndrome of accelerated hepatitis, with progression to chronic hepatitis within weeks. Transmission occurs via blood and body fluids.

Hepatitis E usually causes a self-limited and mild acute hepatitis. However, the disease may be severe in pregnant women, in whom it may progress to acute onset of liver failure, with mortality as high as 25%. The virus is most commonly spread by fecally contaminated water in endemic areas. No chronic disease state exists for hepatitis E.

Risk Factors and Diagnosis

Risk Factors

Exposure to blood or body fluids (eg, intravenous drug use, high-risk sexual intercourse, tattoos, body piercing, blood transfusion, occupational needlestick exposure). Transmission via blood transfusion is now rare due to universal screening.

Contact with an infected person (hepatitis A).

Poor hygiene and inadequate sanitation (hepatitis A and hepatitis E).

Underlying liver disease. Patients with underlying liver disease (eg, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency) are at increased risk of developing symptomatic hepatitis.

Alcohol use, smoking, HIV infection, and fatty liver are risk factors for progression of hepatitis.

Diagnosis

Abnormal liver function tests are common in viral hepatitis patients. Transaminases such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), bilirubin, and alkaline phosphatase are generally elevated. Coagulation studies, such as prothrombin time (PT) and partial thromboplastin time (PTT), and albumin are often normal, except in severe disease.

Hepatitis Virus Serology

• Hepatitis A: Antihepatitis A virus IgM reflects acute infection. IgG reflects past exposure or vaccination and confers lifelong immunity.
• Hepatitis B: Surface antigen and core antibody reflect acute infection. Hepatitis B envelope antigen indicates high infectivity. Be sure to test for superinfection with hepatitis D virus.
• Hepatitis C: Testing includes serology, PCR, and genotyping.
• Hepatitis D: Antihepatitis D virus IgM or IgG is consistent with infection.
• Hepatitis E: Antihepatitis E virus IgM or IgG is consistent with infection.

Biopsy may be indicated to evaluate for etiology and staging of disease.

Right-upper-quadrant ultrasound is usually indicated to evaluate the biliary system and rule out cholelithiasis and biliary obstruction.

Xray, CT scan, MRI, and/or endoscopic retrograde cholangiopancreatography (ERCP) may be necessary to rule out other abdominal pathology (eg, pancreatitis, cholecystitis, malignancy).

Treatment

Initial treatment includes supportive fluids and electrolyte management, monitoring of nutrition status, and avoidance of hepatotoxic substances (eg, alcohol, acetaminophen, statins). Abstinence from alcohol is mandatory, as noted below.

In addition to the above measures, treatment targets the underlying hepatitis virus as follows:

• Hepatitis A: Most cases are self-limited. Hepatitis A immunoglobin may be given.  
• Hepatitis B: Hepatitis B immunoglobin is given for postexposure prophylaxis. Chronic hepatitis B is treated with interferon alpha. Lamivudine and ribavirin may also be used.
• Hepatitis C: Chronic disease is treated with interferon alpha and ribavirin for 6 months to 1 year.
• Hepatitis D: Interferon alpha is given for at least 1 year.
• Hepatitis E: The disease is usually self-limited. Prevention via clean water sources is essential.

Vaccination is available for hepatitis A and hepatitis B. All patients with chronic hepatitis B should be vaccinated for hepatitis A, and patients with hepatitis C should be vaccinated for both hepatitis A and hepatitis B.

Acute complications of liver failure are treated as necessary (eg, lactulose to reduce serum ammonia concentration in patients with hepatic encephalopathy, fresh-frozen plasma for coagulopathy).

End-stage liver failure may require liver transplantation.

Nutritional Considerations

The following nutrition considerations apply to prevention and treatment of viral hepatitis:

Hygiene and sanitation. Persons who travel internationally or who are in areas of the United States where contamination occurs should be aware of an increased risk for hepatitis A. Uncooked food, water, and ice can increase the risk for hepatitis A transmission. Drinking bottled water, making sure food is prepared hygienically, and careful washing of hands and dishes can help prevent virus spread.¹

Shellfish risk. Shellfish are often harvested from wastewater-polluted areas of the sea, and can concentrate the microbial pathogens in the seawater. An estimated 4 million cases of infectious hepatitis A and E occur each year globally as a result of consumption of raw or partially cooked filter-feeding shellfish/mollusks taken from polluted coastal waters.²

Alcohol abstinence. In persons with hepatitis C, alcohol appears to have undesirable effects on immune function, viral replication, and hepatic regeneration, while contributing to increased hepatic iron content and negating the effects of drug (ie, interferon) treatment. Alcohol and the hepatitis C virus also act in an additive and possibly synergistic fashion to promote the development and progression of liver damage.³ A review of studies indicates significantly worse outcomes for alcohol users who have hepatitis C.⁴

High-antioxidant diet. An imbalance between diet-derived and endogenously produced antioxidants and the generation of oxidants triggered by viral infection causes oxidative stress in patients with viral hepatitis; this process results in liver damage that ranges from random apoptosis to sporadic or massive cell necrosis.⁵ Limited preliminary evidence indicates that certain antioxidants may improve the effectiveness of antiviral treatments, but clinical trials have not yet established their benefit.

Iron-restricted diet. Iron-induced oxidative stress may contribute to the pathogenesis of chronic hepatitis C,⁶ and iron depletion by phlebotomy consistently reduces serum aminotransferases.⁷ The benefit of effecting a change in iron status has not yet been proven to affect disease outcome. Nevertheless, the American Liver Foundation suggests that chronic hepatitis C patients with an elevated serum iron level or cirrhosis avoid iron-containing supplements and restrict intake of high-iron foods (eg, meats, liver, and iron-fortified foods).⁸

Orders

See Basic Diet Orders.

What to Tell the Family

Viral hepatitis may be relatively mild and self-limiting, or it may become chronic, depending on the virus involved and success of treatment. In cases of hepatitis A, family members may protect themselves by avoiding direct contact with the affected member and by practicing safe hygiene. In patients with chronic hepatitis B or the more common hepatitis C, the family can help keep the patient well-nourished, which should strengthen the effectiveness of antiviral treatment.

References

1. Wilson TR. The ABCs of hepatitis. Nurse Pract. 2005;30:12-21.

2. Shuval H. Estimating the global burden of thalassogenic diseases: human infectious diseases caused by wastewater pollution of the marine environment.
J Water Health. 2003;1:53-64.

3. Riley TR III, Bhatti AM. Preventive strategies in chronic liver disease: part I. Alcohol, vaccines, toxic medications and supplements, diet and exercise. Am Fam Physician. 2001;64:1555-1560.

4. Hutchinson SJ, Bird SM, Goldberg DJ. Influence of alcohol on the progression of hepatitis C virus infection: a meta-analysis. Clin Gastroenterol Hepatol. 2005;3:1150-1159.

5. Stehbens WE. Oxidative stress in viral hepatitis and AIDS. Exp Mol Pathol. 2004;77:121-132.

6. Safdar K, Schiff ER. Alcohol and hepatitis C. Semin Liver Dis. 2004;24:305-315.

7. Ioannou GN, Tung BY, Kowdley KV. Iron in hepatitis C: villain or innocent bystander? Semin Gastrointest Dis. 2002;13:95-108.

8. American Liver Foundation. Hepatitis C: An Information Resource. Available at: http://www.liverfoundation.org/db/articles/1084. Accessed September 19, 2005.