definition:
inflammation of the liver producing temporary or permanent hepatocyte damage caused by infectious, toxic or autoimmune processes
etiology:
VIRAL:
There are 4 major kinds of viral hepatitis: type A, type B, type C, type D, mand E. Although these types can be distinguished by laboratory testing, all four may present a clinically similar picture. Long term outcomes vary widely with each type. Other less common viral causes of hepatitis include infectious mononucleosis, yellow fever, and cytomegalovirus.
Hepatitis A: The associated microorganism is an enterovirus and the disease is spread by the fecal-oral route. It is contagious during the incubation period of 2-6 weeks but only for a few days once symptoms appear. Epidemics are frequent, as the virus is spread very easily through food and water. Often, the disease may be so mild it is unrecognized and only blood work would discern the virus's presence. It does not create a carrier state and does not lead to chronic liver disease. Rarely, fatalities occur from fulminant hepatitis. Unlike the other hepatitis types which are seen in all ages equally, hepatitis A in seen mostly in children and young adults. Immunity is life-long following infection.
Hepatitis B: The associated organism is a hepadnavirus and the disease is spread primarily parenterally and through sexual contact. Perinatal transmission occurs. It is endemic in Southeast Asia and sub-Saharanan Africa, where a significant protion of the population acquires the disease, often early in life. This type has a more complex course, including subclinical carrier state, acute hepatitis, chronic hepatitis, post-hepatic necrosis, and hepatocellular cancer. Medical personnel, especially surgeons, dentists, dialysis staff and others in contact with blood are at particular risk for accidental transmission. The incubation time ranges from 4-25 weeks (average is 30 days).
Hepatitis C: The associated virus is of the Flaviviridae family. Ten genotypes have been identified, numbered I through X using Roman numerals. This disease was known as non-A non-B hepatitis until the identification of the specific agent and test development in 1989. It is also spread parenterally, most commonly through transfusion and IV drug use with sharing of needles. Sexual transmission does occur, though at a rate of 0-3% per year among monogamous couples. A high percentage of cases run a subclinical course and are found only on followup of routine lab tests showing unexpected elevations of liver transanimases. The incubation period is six to seven weeks. About 25% of those with acute infection become symptomatic. Only one third develop jaundice. If apparent, illness lasts from 2 to 12 weeks. While the course is rarely fulminant, greater than 85% will experience chronic infection. Chronic hepatitis C-induced cirrhosis is a risk factor for hepatocellular carcinoma.
Hepatitis D: (Delta agent) The agent is a "defective" RNA virus that requires the hepatitis B virus for replication.This can coinfect with HBV or superinfect a person who is in a chronic carrier of hepatitis B. It is endemic in HBV carriers of the Mediterranean area and parts of South America. It is spread percutaneously and occasionally sexually.
Hepatitis E: a newly identified virus, thought to be a calcivirus, similar to the A virus in many respects. Primarily, perhaps exclusively, oral fecal transmission. It causes a self-limited infection and has no chronic or carrier state. It is unique in that it has a 20% mortality rate in pregnant women who become infected during the third trimester. It is endemic in third-world countries, is waterborne and infection rates rise after flooding.
TOXIC
Hepatitis may also follow exposure to substances like carbon tetrachloride, benzene, tetracyclines, amanita mushrooms, arsenic, acetaminophen, chaparral, phosphorus and alcohol. Either of two mechanisms may be involved: direct hepatotoxicity or idiosyncratic reaction.
AUTOIMMUNE
Autoimmune processes such as systemic lupus erythematosis occasionally produce hepatitis.
OBESITY
Excessive adipose deposition in the liver causes steatohepatitis. While patients are generally asymptomatic, liver enzyme abnormalities may be found.
signs and symptoms
signs and symptoms:
(may represent the entire course of several of the hepatidities for many patients)
anicteric phase:
malaise
fever
aversion to cigarettes
altered liver function tests
preicteric phase:
anorexia, nausea and vomiting
malaise
fever
weakness
headache
myalgia
enlarged, tender liver
dark urine
occasionally a patient will experience arthalgias and hives
jaundice phase: follows 3-10 days later
dark urine and jaundice including the sclera; jaundice worsens for 1-2 weeks and then gradually disappears during the 2-4 week recovery period; when the jaundice appears, most the patients begin to feel better, as the systemic symptoms decline
liver enlarged and tender; the edge is smooth
mild splenomegaly is present in 15-20% of patients
lab findings: general
note: see below for specific disease indicators
AST/SGOT: elevated minimally to extraordinarily (does not correlate with disease severity)
ALT/SGPT: elevated as above (does not correlate with disease severity)
GGT: elevated as above
(+) urinary bilirubin
differential: atypical lymphocytes, , relative lymphocytosis, depending on type
WBCs: low, normal and rarely high
(+) serum bilirubin
prolonged PT in severe disease with hepatic synthetic failure
hepatitis A
lab findings:
viral antigen HAAg: during acute infection (not generally used clinically)
IgM: appears early in the disease but disappears after a few weeks
IgG (anti-HA): appears after a few weeks, and probably persists for life
hepatitis B
lab findings:
active infection is recognized by the presence of hepatitis B surface antigen (HBsAg), which can appear 1-6 weeks before clinical disease is evident; it usually disappears during convalescence
related antibody (HBsAb) appears weeks to months later and usually persists for life
in 10% of patients, HBsAg persists and HBsAb does not develop; these patients are likely to develop chronic hepatitis or become subclinical carriers of the virus
the IgM antibody (HBcAb) to the core antigen of the virus (HBcAg) typically appears at the beginning of the disease, signifying viral replication, and gradually decreases from then on.
the antigen (HBeAg) is only found in HBsAg-(+) serum; the meaning of its presence is debatable, although it is generally thought to presage more serious sequelae, unless its antibody (HBeAb) is also present.
hepatitis C:
This area of specialty practice is evolving rapidly.
lab findings:
suspect this if elevated ALT continuously or intermittently, especially if any blood exposure.
(+) anti-HCV by EIA (may not be positive for several weeks in acute infection)
Recombinant Immunoblot Assay (RIBA) useful for confirmation
Viral load and Genotype may help with treatment decisions. Useful only if the patient is willing to undergo antiviral therapies.
Liver biopsy helps with staging and treatment decisions.
hepatitis D:
lab findings:
in acute infection, anti-D antibody of IgM is detectable in the serum.
serum shows large anti-D titers of both IgG and IgM if the disease becomes chronic
hepatitis D:
lab findings:
Available in research settings.
course and prognosis
hepatitis A: The prognosis is very favorable; the disease is usually mild and benign and no carrier state exists. It typically lasts for 4-8 weeks. Conventional treatment and prophylaxis comprises injection of hepatitis A vaccine. One is protective and a second confers long-term immunity.
hepatitis B: The prognosis is guarded, and is worse with age and debility. The disease can be severe and 5-10% of patients will develop the chronic state. Prophylactic treatment comprises injection of hepatitis B vaccine, series of three, now routinely required for children in several states of the U.S. Interferon may be used in selected cases for treatment.
type C: The prognosis is guarded. The disease is moderate in expression, but a carrier state can follow in 10-50% of patients. Conventional treatment is expensive, inconvenient and uncomfortable. Treatment more difficult with most of the genotypes. Interferon and ribavirin in combination are used. Hepatitis may develop into submassive hepatic necrosis (fatal in about 20%), or fulminant hepatitis (70-95% mortality).
type D: worsens prognosis for type B.
type E: generally benign and self-limited except in pregnant patients who acquire the infection in the third trimester. In this setting mortality approaches 20%.
Occasionally, any hepatitis may develop into massive hepatic necrosis (fatal in about 20%), or fulminant hepatitis (70-95% mortality).
differential diagnosis
hepatitis variants
other abdominal infections
bile duct obstruction
infectious mononucleosis
footnotes
Cleaver, E. T. Hepatitis C Guidelines Personal communication, February, 1999
Greenberger, Norton J. Hepatitis C: More common than suspected, Clinical Focus
Greenberger P. Hidden risk of hepatitis C. J Womens Health 1998 Sep;7(7):797-798.
Hubbard, Patricia. Hepatitis C, Journal Article 1997.
Schiff, Eugene R., Viral Hepatitis Today, Emergency Medicine. November 15, 1992
Sharara AI, Hunt CM, Hamilton JD. Hepatitis C. Ann Intern Med 1996 Oct 15;125(8):658-668. (Review)
Wilson, Jean D., et al, editors. Harrisons Principals of Internal Medicine Companion Handbook 12th Ed Pub McGraw-Hill, Inc 1991.