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 classified as acute or chronic (lasting > 6 months) and may progress to fulminant liver failure, cirrhosis, and, in some cases, hepatocellular carcinoma. Hepatitis may result from infectious (e.g., bacterial, viral, parasitic or fungal) and noninfectious causes (e.g., drugs, metabolic diseases, alcohol, autoimmune diseases). The most common causes in the United States are alcohol abuse and viral infection.

Viral hepatitis is most commonly caused by hepatitis viruses (especially hepatitis A, hepatitis B, and hepatitis C) and herpes viruses (cytomegalovirus, Epstein-Barr virus, varicella-zoster virus, herpes simplex virus).

Common symptoms include fever, nausea, vomiting, fatigue, jaundice, right-upper-quadrant abdominal tenderness, and dark urine and pale stools.[1] Extrahepatic manifestations may occur, particularly with chronic hepatitis. These include amenorrhea, arthritis, skin rash, vasculitis, thyroiditis, gynecomastia, glomerulonephritis, polyarteritis nodosa, and Sjögren’s syndrome. Complications of chronic hepatitis include cirrhosis, progressive liver failure, and development of hepatocellular carcinoma.

Hepatitis A (HAV) 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, with symptoms present in 70% of patients,[1] starting abruptly and last from 6-24 weeks. However, fulminant liver failure may occur in patients with underlying liver disease.[2]

Hepatitis B (HBV) generally causes a mild or subclinical acute hepatitis but may result in chronic hepatitis or an asymptomatic carrier state. Most symptoms last 1-3 months, although fatigue can last longer. Progression to chronic hepatitis is most common in perinatal infections and young children. Transmission occurs via blood and body fluids (e.g., unprotected sex, intravenous drug use, blood transfusions, tattoos, and body piercing). Sexual contact and IV drug use are the most common modes of transmission in the United States,[3] ,[4] whereas perinatal transmission is more common in developing countries and areas with high HBV prevalence.[5]

Hepatitis C (HCV) is the most common cause of chronic hepatitis in the United States and most common indication for liver transplantation. Acute hepatitis is usually asymptomatic, but many cases do progress to chronic hepatitis. Hepatitis C patients usually do well for 20-25 years before developing cirrhosis, which occurs in about 20%-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.[6] 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 (HDV) 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.[7] Transmission occurs via blood and body fluids.

Hepatitis E (HEV) 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%.[8] The virus is most commonly spread by fecal-oral route in endemic areas,[9] usually from contaminated water sources. It can also be transmitted by blood transfusions[10] or after organ transplants.[11]

Risk Factors

Hepatitis A. Contact with an infected person (either living in close contact or sexual contact), poor hygiene, traveling to areas with inadequate sanitation and illicit drug use.[12]

Hepatitis B. Exposure to blood or body fluids (e.g., Intravenous drug use, high-risk sexual activity, blood transfusion and/or organ transplant, occupational needle stick exposure).[13]

Hepatitis C. Same as HBV, with IV drug use being the greatest risk factor.[14]

Hepatitis D. Same as HBV. Patients with HDV are always positive for HBV as well, making HBV infection a risk factor on its own.[15]

Hepatitis E. Poor hygiene and inadequate sanitation.

Underlying liver disease. Patients with underlying liver disease (e.g., 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

A complete history and physical examination is important for assessing exposures and risk factors. Blood tests are essential for a proper diagnosis. Abnormal liver function tests are common in viral hepatitis patients, especially during the acute phases of infection. Serum transaminases (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: Anti-hepatitis A virus IgM reflects acute infection. IgG, in patients with no acute clinical symptoms, 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. In patients who have received immunization, only surface antibody is present, whereas core antibody and surface antibody are present in patients with past exposure who have recovered. Elevation of ALT for a period longer than six months indicates chronic infection. It is important to test for superinfection with hepatitis D virus.

Hepatitis C: Testing includes serology, PCR, and genotyping. Hepatitis C antibodies are usually present and indicate chronic infection. PCR indicates viral replication and active disease. Chronic HCV is diagnosed if RNA via PCR remains positive for more than 6 months.

Hepatitis D: Antihepatitis D virus IgM or IgG is consistent with infection. Serology differentiates between acute HBC/HDV coinfection, acute HDV superinfection with HBV, or chronic HDV.

Hepatitis E: Antihepatitis E virus IgM or IgG is consistent with infection. HEV can also be detected by PCR in serum or stool.

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.

X-ray, CT scan, MRI, and/or endoscopic retrograde cholangiopancreatography (ERCP) may be necessary to rule out other abdominal pathology (e.g., pancreatitis, cholecystitis, malignancy).

Treatment

Initial treatment includes supportive care with fluids and electrolyte management, monitoring of nutrition status, and avoidance of hepatotoxic substances (e.g., alcohol, acetaminophen, statins). Abstinence from alcohol is mandatory (see Nutritional Considerations below).

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

Hepatitis A: Most cases are self-limited, and in most cases, there is complete resolution of symptoms by 6 months.[16] Hepatitis A immunoglobulin may be given.

Hepatitis B: There is no treatment for acute HBV other than supportive care and taking precautions to prevent further transmission to others. Hepatitis B immunoglobulin is given for postexposure prophylaxis. Chronic hepatitis B is treated with lamivudine, adefovir, entecavir or tenofovir as monotherapy. Interferon is usually avoided due to greater risk of side effects.

Hepatitis C: Acute HCV usually clears on its own. When pharmacologic treatment is necessary, both acute and chronic disease can be treated with polymerase inhibitor such as sofosbuvir or grazoprevir, in combination with a protease inhibitor such as elbasvir, valpatasvir, or lepidasvir.

Hepatitis D: The only approved treatment is interferon alpha, given for at least 1 year. Many drugs are being studied, but further research is needed.

Hepatitis E: The disease is usually self-limited in immunocompetent patients. In organ transplant patients, interferon[17] and ribavirin[18] have been used. Prevention via clean water sources is essential.

Vaccination is available for hepatitis A[19] 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. Hepatitis E vaccines are being developed.[20]

Acute complications of liver failure are treated as necessary (e.g., 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 are at higher risk for hepatitis A ( HAV) through the consumption or handling of contaminated uncooked fruits and vegetables. Boiling or cooking food and water for ≥ 1 minute to 85°C (185° F) is necessary to inactivate HAV.[21]

Avoiding contaminated shellfish and game meats. Most acute HAV infections are due to contaminated shellfish consumption.[21] Shellfish are often taken from wastewater-polluted areas of the sea and can concentrate the microbial pathogens in seawater. Those taken from near the shoreline (e.g., clams and oysters) are particularly likely to be pathogenic. Hepatitis E (HEV) has been identified in contaminated shellfish and produce, as well as animal meats, particularly wild game.[22]

Avoiding high-iron foods and iron supplements. Hepatitis C progression occurs in patients as a result of accelerated hepatic iron uptake and the oxidative stress caused by iron-catalyzed free radical production. Along with phlebotomy, a low-iron diet helps lower the risk for hepatocellular carcinoma (HCC) in these patients.[23]

Nutritional supplementation may be required. Treatment with interferon (IFN) can cause digestive complaints with a subsequent reduction in appetite and food intake and has been reported to result in weight loss in 11%-29% of treated patients.[23]

A low-fat, low-cholesterol diet may be helpful. Chronic hepatitis C (CHC) infection increases the risk for hepatic steatosis. 23,[24] A higher intake of dietary cholesterol contributes to this problem and is associated with the progression of hepatitis C-related liver disease. Individuals on a dietary regimen that is reduced in fat (23% of calories) and cholesterol (185 mg/d) experienced a reduction in liver enzyme elevations and a improvement in immunological abnormalities (TH17/Treg balance) known to contribute to liver inflammation in patients with CHC patients.[25]

Adequate vitamin D status. Vitamin D deficiency is common in patients with chronic liver disease, and these patients may have a reduced ability to convert vitamin D to its active form.[26] An inverse relationship seems to exist between vitamin D concentrations and viral load in patients with CHC. Deficiency significantly lowers the chance for a sustained virological response to pegylated interferon and ribavirin, and vitamin D supplementation improves the probability of response to treatment.[26],[27]

Avoidance of extremes in B12 status. Adequate B12 status helps with clearance of hepatitis C from the circulation of infected patients. However, overly high serum B12 levels may also foster viral replication and are associated with concentrations of hepatitis C RNA levels.[28]

Orders

See Basic Diet Orders Chapter

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.

References

  1. Lednar WM et al: Frequency of illness associated with epidemic hepatitis A virus infections in adults. Am J Epidemiol 122:226, 1985  [PMID:3860002]
  2. Kemmer NM, Miskovsky EP: Hepatitis A. Infect Dis Clin North Am 14:605, 2000  [PMID:10987112]
  3. Kim WR, Ishitani MB, Dickson ER. Rising burden of hepatitis B in the United States: Should the ‘other’ virus be forgotten? Hepatology . 2002;36:222A.
  4. Iqbal K et al: Epidemiology of Acute Hepatitis B in the United States From Population-Based Surveillance, 2006-2011. Clin Infect Dis 61:584, 2015  [PMID:25904365]
  5. Alter MJ et al: The changing epidemiology of hepatitis B in the United States. Need for alternative vaccination strategies. JAMA 263:1218, 1990  [PMID:2304237]
  6. Alter MJ: Epidemiology of hepatitis C. Hepatology 26:62S, 1997  [PMID:9305666]
  7. Smedile A et al: Infection with the delta agent in chronic HBsAg carriers. Gastroenterology 81:992, 1981  [PMID:7286594]
  8. Khuroo MS et al: Incidence and severity of viral hepatitis in pregnancy. Am J Med 70:252, 1981  [PMID:6781338]
  9. Kane MA et al: Epidemic non-A, non-B hepatitis in Nepal. Recovery of a possible etiologic agent and transmission studies in marmosets. JAMA 252:3140, 1984  [PMID:6438353]
  10. Centers for Disease Control and Prevention (CDC): Hepatitis E among U.S. travelers, 1989-1992. MMWR Morb Mortal Wkly Rep 42:1, 1993  [PMID:8418395]
  11. Kamar N et al: Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med 358:811, 2008  [PMID:18287603]
  12. Daniels D, Grytdal S, Wasley A, Centers for Disease Control and Prevention (CDC). Surveillance for acute viral hepatitis - United States, 2007. MMWR Surveill Summ . 2009;58:1-27.
  13. Gerberding JL: The infected health care provider. N Engl J Med 334:594, 1996  [PMID:8569829]
  14. Nelson PK et al: Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet 378:571, 2011  [PMID:21802134]
  15. Smedile A et al: Influence of delta infection on severity of hepatitis B. Lancet 2:945, 1982  [PMID:6127458]
  16. Koff RS: Clinical manifestations and diagnosis of hepatitis A virus infection. Vaccine 10 Suppl 1:S15, 1992  [PMID:1335649]
  17. Kamar N et al: Pegylated interferon-alpha for treating chronic hepatitis E virus infection after liver transplantation. Clin Infect Dis 50:e30, 2010  [PMID:20113176]
  18. Kamar N et al: Ribavirin for chronic hepatitis E virus infection in transplant recipients. N Engl J Med 370:1111, 2014  [PMID:24645943]
  19. Stapleton JT: Passive immunization against hepatitis A. Vaccine 10 Suppl 1:S45, 1992  [PMID:1335658]
  20. Zhu FC et al: Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet 376:895, 2010  [PMID:20728932]
  21. Wu D, Guo CY: Epidemiology and prevention of hepatitis A in travelers. J Travel Med 20:394, 2013 Nov-Dec  [PMID:24165384]
  22. Yugo DM, Meng XJ: Hepatitis E virus: foodborne, waterborne and zoonotic transmission. Int J Environ Res Public Health 10:4507, 2013  [PMID:24071919]
  23. Yasutake K et al: Nutrition therapy for liver diseases based on the status of nutritional intake. Gastroenterol Res Pract 2012:, 2012  [PMID:23197979]
  24. Oliveira LP, de Jesus RP, Boulhosa RS, et al. Effect of soy protein supplementation in patients with chronic hepatitis C: a randomized clinical trial. World J Gastroenterol . 18;18:2203-2211.
  25. Maggio R et al: Normocaloric low cholesterol diet modulates Th17/Treg balance in patients with chronic hepatitis C virus infection. PLoS ONE 9:, 2014  [PMID:25532016]
  26. Villar LM et al: Association between vitamin D and hepatitis C virus infection: a meta-analysis. World J Gastroenterol 19:5917, 2013  [PMID:24124339]
  27. Refaat B et al: Vitamin D and chronic hepatitis C: effects on success rate and prevention of side effects associated with pegylated interferon-α and ribavirin. Int J Clin Exp Med 8:10284, 2015  [PMID:26379820]
  28. Mechie NC et al: Association of serum vitamin B12 levels with stage of liver fibrosis and treatment outcome in patients with chronic hepatitis C virus genotype 1 infection: a retrospective study. BMC Res Notes 8:, 2015  [PMID:26109044]

Last updated: November 28, 2017

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TY - ELEC T1 - Viral Hepatitis ID - 1342052 Y1 - 2017/11/28/ PB - Nutrition Guide for Clinicians UR - https://nutritionguide.pcrm.org/nutritionguide/view/Nutrition_Guide_for_Clinicians/1342052/all/Viral_Hepatitis ER -