Signs and symptoms

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Hepatitis has a broad spectrum of presentations that range from a complete lack of symptoms to severe liver failure. The acute form of hepatitis, generally caused by viral infection, is characterized by constitutional symptoms that are typically self-limited. Chronic hepatitis presents similarly, but can manifest liver specific signs and symptoms with longstanding inflammation and damage to the organ.

Acute Hepatitis

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Acute viral hepatitis follows a pattern of infection that involves three distinct phases:

  1. The initial prodromal phase involves non-specific and flu-like symptoms common to many acute viral infections. This includes fatigue, nausea, vomiting, poor appetite, joint pain, and headaches. Fever, when present, is most common in cases of hepatitis A and E. Patients can experience liver-specific symptoms, including choluria (dark urine) and clay-colored stools, late in this phase.
  2. Clinical jaundice (yellowing of the skin) and icterus (yellowing of the eyes) follow the prodrome after about 1-2 weeks and can last for up to 4 weeks. The constitutional symptoms above typically resolve by this time, but patients will develop hepatomegaly (an enlarged liver) and right upper abdominal pain or discomfort. 10-20% of patients will also experience an enlarged spleen, while some patients will also experience a mild unintentional weight loss.
  3. The recovery phase is characterized by resolution of the clinical symptoms of hepatitis with persistent elevations in liver lab values and potentially a persistently enlarged liver. All cases of hepatitis A and E are expected to fully resolve after 1-2 months. A majority of hepatitis B cases are also self-limited and will resolve in 3-4 months, but few cases of hepatitis C will resolve completely.

Both drug-induced hepatitis and autoimmune hepatitis can present very similarly to acute viral hepatitis, with slight variations in symptoms depending on the cause. Cases of drug-induced hepatitis can involve signs of an allergic reactions including rash, fever, serositis (inflammation of a body membrane), elevated eosinophils (white blood cells), and suppression of bone marrow activity.

Fulminant Hepatitis

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Fulminant hepatitis, or massive hepatic necrosis (cell death), is a rare and life-threatening complication of acute hepatitis that can occur in cases of hepatitis B,D, and E in addition to drug-induced and autoimmune hepatitis. The complication more frequently occurs in instances of hepatitis B and D co-infection at a rate of 2-20% and in pregnant women with hepatitis E at rate of 15-20% of cases. In addition to the signs of acute hepatitis above, patients can also demonstrate signs of coagulopathy (abnormal coagulation studies with easy bruising and bleeding) and encephalopathy (confusion, disorientation, and somnolence). Mortality due to fulminant hepatitis is typically the result of various complications including cerebral edema, catastrophic gastrointestinal bleeding, sepsis, respiratory failure, or renal failure. Cases of fulminant hepatitis often require liver transplantation, as survival without transplantation can be as low as 25%.

Chronic Hepatitis

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Chronic hepatitis is often times asymptomatic early on in its course and is detected only by liver laboratory studies for screening purposes or to evaluate non-specific symptoms. As the inflammation progresses, patients can develop constitutional symptoms similar to acute hepatitis including fatigue, nausea, vomiting, poor appetite, and joint pain. Jaundice and icterus can both occur as well, but occur much later in the disease process and are typically a sign of advanced disease. Chronic hepatitis interferes with hormonal functions of the liver which can result in acne, hirsutism (abnormal hair growth), and amenorrhea (lack of menstrual period) in women. Extensive damage and scarring of the liver over time defines cirrhosis, a condition in which the liver's ability to function is permanently impeded. This results in jaundice, weight loss, coagulopathy, ascites (abdominal fluid collection), and peripheral edema (leg swelling). Cirrhosis can lead to other life-threatening complications such as hepatic encephalopathy, esophageal varices, and hepatorenal synrome.

Society and culture

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Economic Burden

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Overall, hepatitis accounts for a significant portion of healthcare expenditures in both developing and developed nations, and is expected to rise in a number of developing countries.[1][2] While hepatitis A infections are self-limted events, they are associated with significant costs in the United States.[3] It has been estimated that direct and indirect costs are approximately $1817 and $2459 respectively per case, and that an average of 27 work days is lost per infected adult.[3] A 1997 report demonstrated that a single hospitalization related to hepatitis A cost an average of $6,900 and resulted in around $500 million in total annual healthcare costs.[4] Cost effectiveness studies have found widespread vaccination of adults to not be feasible, but have stated that a combination hepatitis A and B vaccination of children and at risk groups (people from endemic areas, healthcare workers) may be.[5]

Hepatitis B accounts for a much larger percentage of health care spending in endemic regions like Asia.[6][7] In 1997 it accounted for 3.2% of South Korea's total health care expenditures and resulted in $696 million in direct costs.[7] A large majority of that sum was spent on treating disease symptoms and complications directly.[8] Chronic hepatitis B infections are not as endemic in the United States, but accounted for $357 million in hospitalization costs in the year 1990.[1] That number grew to $1.5 billion in 2003, but remained stable as of 2006, which may be attributable to the introduction effective drug therapies and vaccination campaigns.[1][2]

People infected with chronic hepatitis C tend to be frequent users of the health care system globally.[9] It has been estimated that a person infected with hepatitis C in the United States will result in a monthly cost of $691.[9] That number nearly doubles to $1,227 for people with compensated cirrhosis, while the monthly cost of people with decompensated cirrhosis is almost five times as large at $3,682.[9] The wide ranging effects hepatitis make it difficult to estimate indirect costs, but studies have purported a total cost of $6.5 billion annually in the United States. In Canada, 56% of HCV related costs are attributable to cirrhosis and total expenditures related to the virus are expected to peak at CAD$396 million in the year 2032.[10]

Notable Cases

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The largest outbreak of hepatitis A virus in United States history occurred among people who ate at a now defunct Mexican food restaurant located in Monaca, Pennsylvania in late 2003. Over 550 people who visited a restaurant between September and October 2003 were infected with the virus, three of whom died as a direct result. The outbreak was brought to the attention of health officials when local emergency medicine physicians noticed a significant increase in the number of cases of hepatitis A in the county. After conducting its investigation, the CDC attributed the source of the outbreak to the use of contaminated raw green onion. The restaurant was purchasing its green onion stock from farms in Mexico at the time. It is believed that the green onions may have been contaminated through the use of contaminated water for crop irrigation, rinsing, or icing or by handling of the vegetables by infected individuals. Green onion had caused similar outbreaks of hepatitis A in the southern United States prior to this, but not to the same magnitude. The CDC believes that the restaurant's use of a large communal bucket for chopped raw green onion allowed non-contaminated plants to be mixed with contaminated ones, increasing the number of vectors of infection and amplifying the outbreak. The restaurant was closed once it was discovered to be the source, and over 9,000 people were given hepatitis A immune globulin because they had either eaten at the restaurant or had been in close contact with someone who had.

  1. ^ a b c Udompap, Prowpanga; Kim, Donghee; Kim, W. Ray. "Current and Future Burden of Chronic Nonmalignant Liver Disease". Clinical Gastroenterology and Hepatology. 13 (12): 2031–2041. doi:10.1016/j.cgh.2015.08.015. PMC 4618163. PMID 26291665. {{cite journal}}: no-break space character in |title= at position 56 (help)
  2. ^ a b Lemoine, Maud; Eholié, Serge; Lacombe, Karine. "Reducing the neglected burden of viral hepatitis in Africa: Strategies for a global approach". Journal of Hepatology. 62 (2): 469–476. doi:10.1016/j.jhep.2014.10.008.
  3. ^ a b Koslap-Petraco, Mary Beth; Shub, Mitchell; Judelsohn, Richard. "Hepatitis A: Disease Burden and Current Childhood Vaccination Strategies in the United States". Journal of Pediatric Health Care. 22 (1): 3–11. doi:10.1016/j.pedhc.2006.12.011.
  4. ^ Previsani, Nicoletta; Lavanchy, Daniel (2000). "WHO| Hepatitis A" (PDF). World Health Organization Global Alert and Response. World Health Organization. Retrieved March 5, 2016.
  5. ^ Anonychuk, Andrea M.; Tricco, Andrea C.; Bauch, Chris T.; Pham, Ba'; Gilca, Vladimir; Duval, Bernard; John-Baptiste, Ava; Woo, Gloria; Krahn, Murray (2008-01-01). "Cost-effectiveness analyses of hepatitis A vaccine: a systematic review to explore the effect of methodological quality on the economic attractiveness of vaccination strategies". PharmacoEconomics. 26 (1): 17–32. ISSN 1170-7690. PMID 18088156.
  6. ^ Chan, Henry Lik-Yuen; Jia, Jidong (2011-01-01). "Chronic hepatitis B in Asia—new insights from the past decade". Journal of Gastroenterology and Hepatology. 26: 131–137. doi:10.1111/j.1440-1746.2010.06544.x. ISSN 1440-1746.
  7. ^ a b Dan, Yock Young; Aung, Myat Oo; Lim, Seng Gee (2008-05-01). "The economics of treating chronic hepatitis B in Asia". Hepatology International. 2 (3): 284–295. doi:10.1007/s12072-008-9049-2. ISSN 1936-0533. PMC 2716880. PMID 19669256.
  8. ^ Lavanchy, D. (2004-03-01). "Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures". Journal of Viral Hepatitis. 11 (2): 97–107. ISSN 1352-0504. PMID 14996343.
  9. ^ a b c Younossi, Z. M.; Kanwal, F.; Saab, S.; Brown, K. A.; El-Serag, H. B.; Kim, W. R.; Ahmed, A.; Kugelmas, M.; Gordon, S. C. (2014-03-01). "The impact of hepatitis C burden: an evidence-based approach". Alimentary Pharmacology & Therapeutics. 39 (5): 518–531. doi:10.1111/apt.12625. ISSN 1365-2036.
  10. ^ Myers, Robert P.; Krajden, Mel; Bilodeau, Marc; Kaita, Kelly; Marotta, Paul; Peltekian, Kevork; Ramji, Alnoor; Estes, Chris; Razavi, Homie (2014-05-01). "Burden of disease and cost of chronic hepatitis C infection in Canada". Canadian Journal of Gastroenterology & Hepatology. 28 (5): 243–250. ISSN 2291-2797. PMC 4049256. PMID 24839620.