Hepatitis

From Wikipedia, the free encyclopedia - View original article

Hepatitis
Classification and external resources

Alcoholic hepatitis evident by fatty change, cell necrosis, Mallory bodies
ICD-10K75.9
ICD-9573.3
DiseasesDB20061
MedlinePlus001154
MeSHD006505
 
Jump to: navigation, search
Hepatitis
Classification and external resources

Alcoholic hepatitis evident by fatty change, cell necrosis, Mallory bodies
ICD-10K75.9
ICD-9573.3
DiseasesDB20061
MedlinePlus001154
MeSHD006505

Hepatitis (plural hepatitides) is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar (ἧπαρ), the root being hepat- (ἡπατ-), meaning liver, and suffix -itis, meaning "inflammation" (c. 1727).[1] The condition can be self-limiting (healing on its own) or can progress to fibrosis (scarring) and cirrhosis.

Hepatitis may occur with limited or no symptoms, but often leads to jaundice, anorexia (poor appetite) and malaise. Hepatitis is acute when it lasts less than six months and chronic when it persists longer. A group of viruses known as the hepatitis viruses cause most cases of hepatitis worldwide, but it can also be due to toxins (notably alcohol, certain medications, some industrial organic solvents and plants), other infections and autoimmune diseases.

Contents

Signs and symptoms

Acute

Initial features are of nonspecific flu-like symptoms, common to almost all acute viral infections and may include malaise, muscle and joint aches, fever, nausea or vomiting, diarrhea, and headache. More specific symptoms, which can be present in acute hepatitis from any cause, are: profound loss of appetite, aversion to smoking among smokers, dark urine, yellowing of the eyes and skin (i.e., jaundice) and abdominal discomfort. Physical findings are usually minimal, apart from jaundice in a third and tender hepatomegaly (swelling of the liver) in about 10%. Some exhibit lymphadenopathy (enlarged lymph nodes, in 5%) or splenomegaly (enlargement of the spleen, in 5%).[2]

Acute viral hepatitis is more likely to be asymptomatic in younger people. Symptomatic individuals may present after convalescent stage of 7 to 10 days, with the total illness lasting 2 to 6 weeks.[3]

A small proportion of people with acute hepatitis progress to acute liver failure, in which the liver is unable to clear harmful substances from the circulation (leading to confusion and coma due to hepatic encephalopathy) and produce blood proteins (leading to peripheral edema and bleeding). This may become life-threatening and occasionally requires a liver transplant.

Chronic

Chronic hepatitis often leads to nonspecific symptoms such as malaise, tiredness and weakness, and often leads to no symptoms at all. It is commonly identified on blood tests performed either for screening or to evaluate nonspecific symptoms. The occurrence of jaundice indicates advanced liver damage. On physical examination there may be enlargement of the liver.[4]

Extensive damage and scarring of liver (i.e. cirrhosis) leads to weight loss, easy bruising and bleeding tendencies, peripheral edema (swelling of the legs) and accumulation of ascites (fluid in the abdominal cavity). Eventually, cirrhosis may lead to various complications: esophageal varices (enlarged veins in the wall of the esophagus that can cause life-threatening bleeding) hepatic encephalopathy (confusion and coma) and hepatorenal syndrome (kidney dysfunction).

Acne, abnormal menstruation, lung scarring, inflammation of the thyroid gland and kidneys may be present in women with autoimmune hepatitis.[4]

Diagnosis

Diagnosis can be made using various Hepatitis biochemical markers in conjunction with the history and physical.

The following are biochemical markers used in the diagnosis of hepatitis:

Hepatitis A

Data taken from Medline Plus[5] and Lab Tests Online.[6]

MarkerDetection TimeDescriptionSignificanceNote
HAV-specific IgM--Recent infection of virus-
Total HAV antibody (IgG & IgM)-Enzyme Immunoassay for antibodiesPositive test demonstrates previous exposure to HAV-

Hepatitis C

MarkerDetection TimeDescriptionSignificanceNote
HCV-RNA1–3 weeksPCRDemonstrates presence or absence of virusResults may be intermittent during course of infection. Negative result is not indicative of absence.
anti-HCV5–6 weeksEnzyme Immunoassay for antibodiesDemonstrates past or present infectionHigh false positive in those with autoimmune disorders and populations with low virus prevalence.
ALT5–6 weeks-Peak in ALT coincides with peak in anti-HCVFluctuating ALT levels is an indication of active liver disease.

Data taken from the WHO website on Hepatitis C.[7]

Pathology

The liver, like all organs, responds to injury in a limited number of ways and a number of patterns have been identified. Liver biopsies are rarely performed for acute hepatitis and because of this the histology of chronic hepatitis is better known than that of acute hepatitis.

Acute

In acute hepatitis the lesions (areas of abnormal tissue) predominantly contain diffuse sinusoidal and portal mononuclear infiltrates (lymphocytes, plasma cells, Kupffer cells) and swollen hepatocytes. Acidophilic cells (Councilman bodies) are common. Hepatocyte regeneration and cholestasis (canalicular bile plugs) typically are present. Bridging hepatic necrosis (areas of necrosis connecting two or more portal tracts) may also occur. There may be some lobular disarray. Although aggregates of lymphocytes in portal zones may occur these are usually neither common nor prominent. The normal architecture is preserved. There is no evidence of fibrosis or cirrhosis (fibrosis plus regenerative nodules). In severe cases prominent hepatocellular necrosis around the central vein (zone 3) may be seen.

In submassive necrosis – a rare presentation of acute hepatitis – there is widespread hepatocellular necrosis beginning in the centrizonal distribution and progressing towards portal tracts. The degree of parenchymal inflammation is variable and is proportional to duration of disease.[8][9] Two distinct patterns of necrosis have been recognised: (1) zonal coagulative necrosis or (2) panlobular (nonzonal) necrosis.[10] Numerous macrophages and lymphocytes are present. Necrosis and inflammation of the biliary tree occurs.[11] Hyperplasia of the surviving biliary tract cells may be present. Stromal haemorrhage is common.

The histology may show some correlation with the cause:

Where patients have recovered from this condition, biopsies commonly show multiacinar regenerative nodules (previously known as adenomatous hyperplasia).[12]

Massive hepatic necrosis is also known and is usually rapidly fatal. The pathology resembles that of submassive necrosis but is more markered in both degree and extent.

Chronic

Chronic hepatitis has been better studied and several conditions have been described.

Chronic active hepatitis was the term used to described cases of hepatitis for more than 6 months with portal based inflammation, fibrosis, disruption of the terminal plate and piecemeal necrosis. This term has now been replaced by the diagnosis of 'chronic hepatitis with piecemeal (periportal) necrosis (or interface hepatitis) with or without fibrosis.'[13]

Chronic persistent hepatitis was the term used to describe chronic hepatitis with no significant periportal necrosis or regeneration with a fairly dense mononuclear portal infiltrate. Councilman bodies are frequently seen within the lobule. This condition is now referred to as 'chronic hepatitis without piecemeal necrosis (or interface hepatitis).'[13]

Chronic lobular hepatitis was the term used to describe chronic hepatitis with persistent parenchymal focal hepatocyte necrosis (apoptosis) with mononuclear sinusoidal infiltrates. This is now referred to as 'chronic hepatitis without piecemeal necrosis (or interface hepatitis).'[13]

These terms have since been deprecated.[13] This was done because it was realised that these conditions could alter over time and what might have been regarded as a relatively benign lesion could still progress to cirrhosis. The simpler term 'chronic hepatitis' is now preferred in association with the causative agent (when known) and a grade based on the degree of inflammation, piecemeal or bridging necrosis (interface hepatitis) and the stage of fibrosis. Several grading systems have been proposed but none have been adopted universally.

Cirrhosis is a diffuse process characterized by regenerative nodules that are separated from one another by bands of fibrosis. It is the end stage for many chronic liver diseases. The pathophysiological process that results in cirrhosis is as follows: hepatocytes are lost through a gradual process of hepatocellular injury and inflammation. This injury stimulates a regenerative response in the remaining hepatocytes. The fibrotic scars limit the extent to which the normal architecture can be reestablished as the scars isolate groups of hepatocytes. This results in nodules formation. Angiogenisis (new vessel formation) accompanies scar production which results in the formation of abnormal channels between the central hepatic veins and the portal vessels. This in turn causes shunting of blood around the regenerating parenchyma. Normal vascular structures including the sinusoidal channels may be obliterated by fibrotic tissue leading to portal hypertension. The overall reduction in hepatocyte mass, in conjunction with the portal blood shunting, prevents the liver from accomplishing its usual functions – the filtering of blood from the gastrointestinal tract and serum protein production. These changes give rise to the clinical manifestations of cirrhosis.

Specific cases

Most of the causes of hepatitis cannot be distinguished on the basis of the pathology but some do have particular features that are suggestive of a particular diagnosis.

The presence of micronodular cirrhosis, Mallory bodies and fatty change within a single biopsy are highly suggestive of alcoholic injury.[14] Perivenular, pericellular fibrosis (known as 'chicken wire fibrosis' because of its appearance on trichrome or van Gieson stains) with partial or complete obliteration of the central vein is also very suggestive of alcohol abuse.

Cardiac, ischemic and venous outflow obstruction all cause similar patterns.[15] The sinusoids are often dilated and filled with erythrocytes. The liver cell plates may be compressed. Coagulative necrosis of the hepatocytes can occur around the central vein. Hemosiderin and lipochrome laden macrophages and inflammatory cells may be found. At the edge of the fibrotic zone cholestasis may be present. The portal tracts are rarely significantly involved until late in the course.

Biliary tract disease including primary biliary cirrhosis, sclerosing cholangitis, inflammatory changes associated with idiopathic inflammatory bowel disease and duct obstruction have similar histology in their early stages. Although these diseases tend to primarily involve the biliary tract they may also be associated with chronic inflammation within the liver and difficult to distinguish on histological grounds alone. The fibrotic changes associated with these disease principally involve the portal tracts with cholangiole proliferation, portal tract inflammation with neutrophils surrounding the cholangioles, disruption of the terminal plate by mononuclear inflammatory cells and occasional hepatocyte necrosis. The central veins are either not involved in the fibrotic process or become involved only late in the course of the disease. Consequently the central–portal relationships are minimally distorted. Where cirrhosis is present it tends to be in the form of a portal–portal bridging fibrosis.

Hepatitis E causes different histological patterns that depend on the host's background.[16] In immunocompetent patients the typical pattern is of severe intralobular necrosis and acute cholangitis in the portal tract with numerous neutrophils. This normally resolves without sequelae. Disease is more severe in those with preexisting liver disease such as cirrhosis. In the immunocompromised patients chronic infection may result with rapid progression to cirrhosis. The histology is similar to that found in hepatitis C virus with dense lymphocytic portal infiltrate, constant peacemeal necrosis and fibrosis.

Causes

Acute

Chronic

Discussion

Alcoholic hepatitis

Ethanol, mostly in alcoholic beverages, is a significant cause of hepatitis. Usually alcoholic hepatitis comes after a period of increased alcohol consumption. Alcoholic hepatitis is characterized by a variable constellation of symptoms, which may include feeling unwell, enlargement of the liver, development of fluid in the abdomen ascites, and modest elevation of liver blood tests. Alcoholic hepatitis can vary from mild with only liver test elevation to severe liver inflammation with development of jaundice, prolonged prothrombin time, and liver failure. Severe cases are characterized by either obtundation (dulled consciousness) or the combination of elevated bilirubin levels and prolonged prothrombin time; the mortality rate in both categories is 50% within 30 days of onset.

Alcoholic hepatitis is distinct from cirrhosis caused by long term alcohol consumption. Alcoholic hepatitis can occur in patients with chronic alcoholic liver disease and alcoholic cirrhosis. Alcoholic hepatitis by itself does not lead to cirrhosis, but cirrhosis is more common in patients with long term alcohol consumption. Patients who drink alcohol to excess are also more often than others found to have hepatitis C.[citation needed] The combination of hepatitis C and alcohol consumption accelerates the development of cirrhosis.

Drug-induced

A large number of drugs can cause hepatitis:[83]

The clinical course of drug-induced hepatitis is quite variable, depending on the drug and the patient's tendency to react to the drug. For example, halothane hepatitis can range from mild to fatal as can INH-induced hepatitis. Hormonal contraception can cause structural changes in the liver. Amiodarone hepatitis can be untreatable since the long half life of the drug (up to 60 days) means that there is no effective way to stop exposure to the drug. Statins can cause elevations of liver function blood tests normally without indicating an underlying hepatitis. Lastly, human variability is such that any drug can be a cause of hepatitis.

Other toxins

Other Toxins can cause hepatitis:

Metabolic disorders

Some metabolic disorders cause different forms of hepatitis. Hemochromatosis (due to iron accumulation) and Wilson's disease (copper accumulation) can cause liver inflammation and necrosis.

Non-alcoholic steatohepatitis (NASH) is effectively a consequence of metabolic syndrome.

Obstructive

"Obstructive jaundice" is the term used to describe jaundice due to obstruction of the bile duct (by gallstones or external obstruction by cancer). If longstanding, it leads to destruction and inflammation of liver tissue.

Autoimmune

Anomalous presentation of human leukocyte antigen (HLA) class II on the surface of hepatocytes, possibly due to genetic predisposition or acute liver infection; causes a cell-mediated immune response against the body's own liver, resulting in autoimmune hepatitis.

Alpha 1-antitrypsin deficiency

In severe cases of alpha 1-antitrypsin deficiency (A1AD), the accumulated protein in the endoplasmic reticulum causes liver cell damage and inflammation.

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the occurrence of fatty liver in people who have no history of alcohol use. It is most commonly associated with obesity (80% of all obese people have fatty liver). It is more common in women. Severe NAFLD leads to inflammation, a state referred to as non-alcoholic steatohepatitis (NASH), which on biopsy of the liver resembles alcoholic hepatitis (with fat droplets and inflammatory cells, but usually no Mallory bodies).

The diagnosis depends on medical history, physical exam, blood tests, radiological imaging and sometimes a liver biopsy. The initial evaluation to identify the presence of fatty infiltration of the liver is medical imaging, including such ultrasound, computed tomography (CT), or magnetic resonance (MRI). However, imaging cannot readily identify inflammation in the liver. Therefore, the differentiation between steatosis and NASH often requires a liver biopsy. It can also be difficult to distinguish NASH from alcoholic hepatitis when the patient has a history of alcohol consumption. Sometimes in such cases a trial of abstinence from alcohol along with follow-up blood tests and a repeated liver biopsy are required.

NASH is becoming recognized as the most important cause of liver disease second only to hepatitis C in numbers of patients going on to cirrhosis.[citation needed]

Ischemic hepatitis

Ischemic hepatitis is caused by decreased circulation to the liver cells. Usually this is due to decreased blood pressure (or shock), leading to the equivalent term "shock liver". Patients with ischemic hepatitis are usually very ill due to the underlying cause of shock. Rarely, ischemic hepatitis can be caused by local problems with the blood vessels that supply oxygen to the liver (such as thrombosis, or clotting of the hepatic artery[disambiguation needed] which partially supplies blood to liver cells). Blood testing of a person with ischemic hepatitis will show very high levels of transaminase enzymes (AST and ALT), which may exceed 1000 U/L. The elevation in these blood tests is usually transient (lasting 7 to 10 days). It is rare that liver function will be affected by ischemic hepatitis.

Giant cell hepatitis

Giant cell hepatitis is a rare form of hepatitis (~100 cases reported) that predominantly occurs in children. Diagnosis is made on the basis of the presence of hepatocellular multinucleate giant cells.[10][87][88] Cases presenting in adults are rare and tend to be rapidly progressive.[89][90][91][92][93] The cause is currently unknown but an infectious cause is suspected.[94][95] The condition tends to improve with the use of ribivirin suggesting a viral origin.[96][97] Hepatitis E,[98] hepatitis C,[99] paramyxovirus,[100][101][102][103] papillomavirus[104][105] and Human herpes virus 6[106][107] have been suggested as causes. A similar condition has been reported in cats but it is not known if there is any connection between these conditions.[108]

See also

References

  1. ^ "Online Etymology Dictionary". Etymonline.com. http://www.etymonline.com/index.php?search=hepatitis&searchmode=none. Retrieved 2012-08-26. 
  2. ^ Ryder S, Beckingham I (2001). "Acute hepatitis". BMJ 322 (7279): 151–153. doi:10.1136/bmj.322.7279.151. PMC 1119417. PMID 11159575. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1119417/. 
  3. ^ a b Bain VG, Ma M. "Ch. 14: Acute Viral Hepatitis". First principle of gastroenterology. http://www.gastroresource.com/GITextbook/en/Chapter14/14-4.htm.  (an online text book)
  4. ^ a b Chronic hepatitis at Merck Manual of Diagnosis and Therapy Home Edition
  5. ^ "Hepatitis virus panel: MedlinePlus Medical Encyclopedia". Nlm.nih.gov. 2012-07-27. http://www.nlm.nih.gov/medlineplus/ency/article/003558.htm. Retrieved 2012-08-26. 
  6. ^ "Hepatitis A: The Test". Labtestsonline.org. http://labtestsonline.org/understanding/analytes/hepatitis-a/tab/test. Retrieved 2012-08-26. 
  7. ^ "WHO | Hepatitis C". Who.int. 2010-12-08. http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index3.html#diagnostic. Retrieved 2012-08-26. 
  8. ^ Boyer JL, Klatskin G (1970). "Pattern of necrosis in acute viral hepatitis. Prognostic value of bridging (subacute hepatic necrosis)". N. Engl. J. Med. 283 (20): 1063–71. doi:10.1056/NEJM197011122832001. PMID 4319402. 
  9. ^ Gimson AE (July 1996). "Fulminant and late onset hepatic failure". Br J Anaesth 77 (1): 90–8. doi:10.1093/bja/77.1.90. PMID 8703634. http://bja.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=8703634. 
  10. ^ a b Kirsch R, Yap J, Roberts EA, Cutz E (April 2009). "Clinicopathologic spectrum of massive and submassive hepatic necrosis in infants and children". Hum. Pathol. 40 (4): 516–26. doi:10.1016/j.humpath.2008.07.018. PMID 19121848. http://linkinghub.elsevier.com/retrieve/pii/S0046-8177(08)00447-4. 
  11. ^ Nakanuma Y, Sasaki M, Terada T, Harada K (1994). "Intrahepatic peribiliary glands of humans. II. Pathological spectrum". J. Gastroenterol. Hepatol. 9 (1): 80–6. doi:10.1111/j.1440-1746.1994.tb01221.x. PMID 8155873. 
  12. ^ Wanless IR (September 1995). "Terminology of nodular hepatocellular lesions". Hepatology 22 (3): 983–993. doi:10.1002/hep.1840220341. PMID 7657307. http://onlinelibrary.wiley.com/doi/10.1002/hep.1840220341/abstract. 
  13. ^ a b c d Gastroenterology IWPotWCo (August 1994). "Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994". Am. J. Gastroenterol. 89 (8 Suppl): S177–81. PMID 8048409. 
  14. ^ "Alcoholic liver disease: morphological manifestations. Review by an international group". Lancet 1 (8222): 707–11. March 1981. PMID 6110925. 
  15. ^ Arcidi JM, Moore GW, Hutchins GM (August 1981). "Hepatic morphology in cardiac dysfunction: a clinicopathologic study of 1000 subjects at autopsy". Am. J. Pathol. 104 (2): 159–66. PMC 1903755. PMID 6455066. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1903755/. 
  16. ^ Selves J, Kamar N, Mansuy JM, Péron JM (December 2010). "[Hepatitis E virus: A new entity"] (in French). Ann Pathol 30 (6): 432–8. doi:10.1016/j.annpat.2010.10.003. PMID 21167429. http://www.masson.fr/masson/S0242-6498(10)00317-2. 
  17. ^ a b c d e Miguet JP, Coaquette A, Bresson-Hadni S, Lab M (June 1990). "[The other types of viral hepatitis]" (in French). Rev Prat 40 (18): 1656–9. PMID 2164704. 
  18. ^ Briese T, Paweska JT, McMullan LK, et al. (May 2009). Buchmeier, Michael J. ed. "Genetic detection and characterization of Lujo virus, a new hemorrhagic fever-associated arenavirus from southern Africa". PLoS Pathog. 5 (5): e1000455. doi:10.1371/journal.ppat.1000455. PMC 2680969. PMID 19478873. http://dx.plos.org/10.1371/journal.ppat.1000455. 
  19. ^ Appannanavar SB, Mishra B (July 2011). "An update on crimean congo hemorrhagic Fever". J Glob Infect Dis 3 (3): 285–92. doi:10.4103/0974-777X.83537. PMC 3162818. PMID 21887063. http://www.jgid.org/article.asp?issn=0974-777X;year=2011;volume=3;issue=3;spage=285;epage=292;aulast=Appannanavar. 
  20. ^ Peters W (June 2002). "Novel and challenging infections of man. A brief overview". Parassitologia 44 (1–2): 33–42. PMID 12404808. 
  21. ^ Glass GE, Watson AJ, LeDuc JW, Childs JE (1994). "Domestic cases of hemorrhagic fever with renal syndrome in the United States". Nephron 68 (1): 48–51. doi:10.1159/000188086. PMID 7991040. 
  22. ^ Olsson GE, Leirs H, Henttonen H (August 2010). "Hantaviruses and their hosts in Europe: reservoirs here and there, but not everywhere?". Vector Borne Zoonotic Dis. 10 (6): 549–61. doi:10.1089/vbz.2009.0138. PMID 20795916. 
  23. ^ Ikegami T, Makino S (May 2011). "The pathogenesis of Rift Valley fever". Viruses 3 (5): 493–519. doi:10.3390/v3050493. PMC 3111045. PMID 21666766. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3111045/. 
  24. ^ Burke RL, Kronmann KC, Daniels CC, et al. (November 2011). "A Review of Zoonotic Disease Surveillance Supported by the Armed Forces Health Surveillance Center". Zoonoses Public Health 59 (3): 164–75. doi:10.1111/j.1863-2378.2011.01440.x. PMID 22128834. 
  25. ^ Fever with thrombocytopenia associated with a novel Bunyavirus in China. N Engl J Med. 2011 Mar 16. Full text
  26. ^ Weiss SR, Leibowitz JL (2011). "Coronavirus pathogenesis". Adv. Virus Res.. Advances in Virus Research 81: 85–164. doi:10.1016/B978-0-12-385885-6.00009-2. ISBN 9780123858856. PMID 22094080. http://linkinghub.elsevier.com/retrieve/pii/B978-0-12-385885-6.00009-2. 
  27. ^ a b Naides SJ (May 1998). "Rheumatic manifestations of parvovirus B19 infection". Rheum. Dis. Clin. North Am. 24 (2): 375–401. doi:10.1016/S0889-857X(05)70014-4. PMID 9606764. 
  28. ^ Charrel RN, de Lamballerie X (2003). "[The Alkhurma virus (family Flaviviridae, genus Flavivirus): an emerging pathogen responsible for hemorrhage fever in the Middle East]" (in French). Med Trop (Mars) 63 (3): 296–9. PMID 14579470. 
  29. ^ Ramos-De La Medina A, Remes-Troche JM, González-Medina MF, et al. (April 2011). "[Abdominal and gastrointestinal symptoms of Dengue fever. Analysis of a cohort of 8559 patients"] (in Spanish; Castilian). Gastroenterol Hepatol 34 (4): 243–7. doi:10.1016/j.gastrohep.2011.01.012. PMID 21474206. http://www.elsevier.es/en/linksolver/ft/pii/S0210-5705(11)00125-7. 
  30. ^ a b Gritsun TS, Nuttall PA, Gould EA (2003). "Tick-borne flaviviruses". Adv. Virus Res.. Advances in Virus Research 61: 317–71. doi:10.1016/S0065-3527(03)61008-0. ISBN 0120398613. PMID 14714436. 
  31. ^ Tandon BN, Acharya SK (April 1987). "Viral diseases involving the liver". Baillieres Clin. Gastroenterol. 1 (2): 211–30. doi:10.1016/0950-3528(87)90002-9. PMID 2822180. 
  32. ^ Xiong W (November 2010). "[Clinical efficacy of treating infant cytomegalovirus hepatitis with ganciclovir and impact on cytokines]" (in Chinese). Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 26 (11): 1130–2. PMID 21322282. 
  33. ^ Okano M, Gross TG (November 2011). "Acute or Chronic Life-Threatening Diseases Associated With Epstein-Barr Virus Infection". Am. J. Med. Sci. 343 (6): 483–9. doi:10.1097/MAJ.0b013e318236e02d. PMID 22104426. 
  34. ^ Gallegos-Orozco JF, Rakela-Brödner J (October 2010). "Hepatitis viruses: not always what it seems to be". Rev Med Chil 138 (10): 1302–11. doi:10.4067/S0034-98872010001100016. PMID 21279280. http://www.scielo.cl/cgi-bin/fbpe/fbtext?pid=S0034-98872010001100016&lng=en&nrm=iso&tlng=en. 
  35. ^ Papic N, Pangercic A, Vargovic M, Barsic B, Vince A, Kuzman I (September 2011). "Liver involvement during influenza infection: perspective on the 2009 influenza pandemic". Influenza Other Respi Viruses 6 (3): e2–5. doi:10.1111/j.1750-2659.2011.00287.x. PMID 21951624. 
  36. ^ Bondarenko VI, Zadorozhnaia VI (March 1992). "[The role of enteroviruses in the etiology of diseases of the pancreas, kidneys and liver]" (in Russian). Lik. Sprava (3): 58–62. PMID 1329355. 
  37. ^ Zaidi SA, Singer C (May 2002). "Gastrointestinal and hepatic manifestations of tickborne diseases in the United States". Clin. Infect. Dis. 34 (9): 1206–12. doi:10.1086/339871. PMID 11941547. http://www.cid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11941547. 
  38. ^ Organ EL, Rubin DH (1998). "Pathogenesis of reovirus gastrointestinal and hepatobiliary disease". Curr. Top. Microbiol. Immunol.. Current Topics in Microbiology and Immunology 233 (Pt 2): 67–83. doi:10.1007/978-3-642-72095-6_4. ISBN 978-3-642-72097-0. PMID 9599932. 
  39. ^ Heyman P, Cochez C, Hofhuis A, et al. (January 2010). "A clear and present danger: tick-borne diseases in Europe". Expert Rev Anti Infect Ther 8 (1): 33–50. doi:10.1586/eri.09.118. PMID 20014900. http://www.future-drugs.com/doi/abs/10.1586/eri.09.118?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed. 
  40. ^ Siński E, Welc-Faleciak R, Pogłód R (2011). "Babesia spp. infections transmitted through blood transfusion". Wiad Parazytol 57 (2): 77–81. PMID 21682090. 
  41. ^ Massei F, Gori L, Macchia P, Maggiore G (September 2005). "The expanded spectrum of bartonellosis in children". Infect. Dis. Clin. North Am. 19 (3): 691–711. doi:10.1016/j.idc.2005.06.001. PMID 16102656. http://linkinghub.elsevier.com/retrieve/pii/S0891-5520(05)00064-4. 
  42. ^ Yang HW, Jung SH, Han HY, et al. (June 2008). "[Clinical feature of Fitz-Hugh-Curtis syndrome: analysis of 25 cases"] (in Korean). Korean J Hepatol 14 (2): 178–84. doi:10.3350/kjhep.2008.14.2.178. PMID 18617765. http://www.koreanjhepatol.org/journal/view.php?year=2008&vol=14&no=2&spage=178. 
  43. ^ Parveen, M.D. Kumar, Michael, M.D. Clark, ed. (2005). "Figure 7.12 (Some causes of acute parenchymal damage)". Clinical Medicine. Philadelphia, PA: W.B. Saunders. ISBN 0-7020-2763-4. 
  44. ^ Blanco JR, Oteo JA (December 2002). "Human granulocytic ehrlichiosis in Europe". Clin. Microbiol. Infect. 8 (12): 763–72. doi:10.1046/j.1469-0691.2002.00557.x. PMID 12519349. http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1198-743X&date=2002&volume=8&issue=12&spage=763. 
  45. ^ Scholing M, Schneeberger PM, van den Dries P, Drenth JP (June 2007). "Clinical features of liver involvement in adult patients with listeriosis. Review of the literature". Infection 35 (4): 212–8. doi:10.1007/s15010-007-6006-2. PMID 17646920. 
  46. ^ Drebber U, Kasper HU, Ratering J, et al. (July 2008). "Hepatic granulomas: histological and molecular pathological approach to differential diagnosis--a study of 442 cases". Liver Int. 28 (6): 828–34. doi:10.1111/j.1478-3231.2008.01695.x. PMID 18312287. 
  47. ^ Raby N, Forbes G, Williams R (March 1990). "Nocardia infection in patients with liver transplants or chronic liver disease: radiologic findings". Radiology 174 (3 Pt 1): 713–6. PMID 2406779. http://radiology.rsnajnls.org/cgi/pmidlookup?view=long&pmid=2406779. 
  48. ^ Mohammed JP, Mattner J (July 2009). "Autoimmune disease triggered by infection with alphaproteobacteria". Expert Rev Clin Immunol 5 (4): 369–379. doi:10.1586/ECI.09.23. PMC 2742979. PMID 20161124. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2742979/. 
  49. ^ Kaplan MM (November 2004). "Novosphingobium aromaticivorans: a potential initiator of primary biliary cirrhosis". Am. J. Gastroenterol. 99 (11): 2147–9. doi:10.1111/j.1572-0241.2004.41121.x. PMID 15554995. 
  50. ^ Selmi C, Gershwin ME (July 2004). "Bacteria and human autoimmunity: the case of primary biliary cirrhosis". Curr Opin Rheumatol 16 (4): 406–10. doi:10.1097/01.bor.0000130538.76808.c2. PMID 15201604. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1040-8711&volume=16&issue=4&spage=406. 
  51. ^ Selmi C, Balkwill DL, Invernizzi P, et al. (November 2003). "Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic-metabolizing bacterium". Hepatology 38 (5): 1250–7. doi:10.1053/jhep.2003.50446. PMID 14578864. 
  52. ^ Yen TH, Chang CT, Lin JL, Jiang JR, Lee KF (May 2003). "Scrub typhus: a frequently overlooked cause of acute renal failure". Ren Fail 25 (3): 397–410. doi:10.1081/JDI-120021152. PMID 12803503. 
  53. ^ Park JI, Han SH, Cho SC, et al. (September 2003). "[Outbreak of hepatitis by Orientia tsutsugamushi in the early years of the new millenium"] (in Korean). Taehan Kan Hakhoe Chi 9 (3): 198–204. PMID 14515037. http://www.koreanjhepatol.org/journal/view.php?year=2003&vol=9&no=3&spage=198. 
  54. ^ a b Bernabeu-Wittel M, Segura-Porta F (March 2005). "[Rickettsioses"] (in Spanish; Castilian). Enferm. Infecc. Microbiol. Clin. 23 (3): 163–72. doi:10.1157/13072167. PMID 15757589. http://www.elsevier.es/en/linksolver/ft/ivp/0213-005X/23/163. 
  55. ^ Brown JM, McNeil MM (2003). "Nocardia, Rhodococcus, Gordonia, Actinomadura, Streptomyces, and other aerobic actinomycetes". In Murray PR, Baron EJ, Jorgensen JH, Pfaller MA, Yolken RH. Manual of clinical microbiology (8th ed.). Washington DC: American Society for Microbiology. pp. 502–531. 
  56. ^ Connor BA, Schwartz E (October 2005). "Typhoid and paratyphoid fever in travellers". Lancet Infect Dis 5 (10): 623–8. doi:10.1016/S1473-3099(05)70239-5. PMID 16183516. http://linkinghub.elsevier.com/retrieve/pii/S1473-3099(05)70239-5. 
  57. ^ Elishkewitz K, Shapiro R, Amir J, Nussinovitch M. Hepatitis in scarlet fever. Isr Med Assoc J 6(9):569-570
  58. ^ Cook GC (December 1997). "Liver involvement in systemic infection". Eur J Gastroenterol Hepatol 9 (12): 1239–47. PMID 9471032. 
  59. ^ Bottone EJ (April 1997). "Yersinia enterocolitica: the charisma continues". Clin. Microbiol. Rev. 10 (2): 257–76. PMC 172919. PMID 9105754. http://cmr.asm.org/cgi/pmidlookup?view=long&pmid=9105754. 
  60. ^ a b c d e f g Seitz HM (1995). "[Parasitic diseases of the liver]" (in German). Verh Dtsch Ges Pathol 79: 241–8. PMID 8600687. 
  61. ^ Chen XM, LaRusso NF (August 2002). "Cryptosporidiosis and the pathogenesis of AIDS-cholangiopathy". Semin. Liver Dis. 22 (3): 277–89. doi:10.1055/s-2002-34505. PMID 12360421. http://www.thieme-connect.com/DOI/DOI?10.1055/s-2002-34505. 
  62. ^ Michiels JF, Hofman P, Bernard E, et al. (November 1994). "Intestinal and extraintestinal Isospora belli infection in an AIDS patient. A second case report". Pathol. Res. Pract. 190 (11): 1089–93; discussion 1094. doi:10.1016/S0344-0338(11)80908-8. PMID 7746744. 
  63. ^ Walther Z, Topazian MD (September 2009). "Isospora cholangiopathy: case study with histologic characterization and molecular confirmation". Hum. Pathol. 40 (9): 1342–6. doi:10.1016/j.humpath.2009.01.020. PMID 19447468. http://linkinghub.elsevier.com/retrieve/pii/S0046-8177(09)00076-8. 
  64. ^ Anand AC, Puri P (September 2005). "Jaundice in malaria". J. Gastroenterol. Hepatol. 20 (9): 1322–32. doi:10.1111/j.1440-1746.2005.03884.x. PMID 16105116. http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0815-9319&date=2005&volume=20&issue=9&spage=1322. 
  65. ^ a b Miller TA (1979). "Hookworm infection in man". Adv. Parasitol.. Advances in Parasitology 17: 315–84. doi:10.1016/S0065-308X(08)60552-7. ISBN 9780120317172. PMID 395835. 
  66. ^ Gavin PJ, Kazacos KR, Shulman ST (October 2005). "Baylisascariasis". Clin. Microbiol. Rev. 18 (4): 703–18. doi:10.1128/CMR.18.4.703-718.2005. PMC 1265913. PMID 16223954. http://cmr.asm.org/cgi/pmidlookup?view=long&pmid=16223954. 
  67. ^ a b Li CD, Yang HL, Wang Y (February 2010). "Capillaria hepatica in China". World J. Gastroenterol. 16 (6): 698–702. doi:10.3748/wjg.v16.i6.698. PMC 2817057. PMID 20135717. http://www.wjgnet.com/1007-9327/full/v16/i6/698.htm. 
  68. ^ Pokora Z (2001). "[Role of gastropods in epidemiology of human parasitic diseases]" (in Polish). Wiad Parazytol 47 (1): 3–24. PMID 16888946. 
  69. ^ Garcia HH, Moro PL, Schantz PM (October 2007). "Zoonotic helminth infections of humans: echinococcosis, cysticercosis and fascioliasis". Curr. Opin. Infect. Dis. 20 (5): 489–94. doi:10.1097/QCO.0b013e3282a95e39. PMID 17762782. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0951-7375&volume=20&issue=5&spage=489. 
  70. ^ Mordvinov VA, Yurlova NI, Ogorodova LM, Katokhin AV (March 2012). "Opisthorchis felineus and Metorchis bilis are the main agents of liver fluke infection of humans in Russia". Parasitol. Int. 61 (1): 25–31. doi:10.1016/j.parint.2011.07.021. PMID 21840415. http://linkinghub.elsevier.com/retrieve/pii/S1383-5769(11)00119-X. 
  71. ^ Singcharoen T, Rawd-Aree P, Baddeley H (January 1988). "Computed tomography findings in disseminated paragonimiasis". Br J Radiol 61 (721): 83–6. doi:10.1259/0007-1285-61-721-83. PMID 3349245. 
  72. ^ Soroczan W (1996). "[Strongyloidosis. II. Clinical manifestations]" (in Polish). Wiad Parazytol 42 (3): 291–312. PMID 9012132. 
  73. ^ Fried B, Reddy A, Mayer D (June 2011). "Helminths in human carcinogenesis". Cancer Lett. 305 (2): 239–49. doi:10.1016/j.canlet.2010.07.008. PMID 20667649. http://linkinghub.elsevier.com/retrieve/pii/S0304-3835(10)00345-9. 
  74. ^ Ishibashi H, Tsuchiya Y (1995). "[Hepatic toxocariasis]" (in Japanese). Ryoikibetsu Shokogun Shirizu (7): 48–50. PMID 8749411. 
  75. ^ Nikeghbalian S, Salahi R, Salahi H, et al. (December 2009). "Hepatic abscesses after liver transplant: 1997-2008". Exp Clin Transplant 7 (4): 256–60. PMID 20353378. http://www.ectrx.org/forms/ectrxcontentshow.php?year=2009&volume=7&issue=4&supplement=0&makale_no=0&spage_number=256&content_type=FULL%20TEXT. 
  76. ^ Romero FA, Razonable RR (April 2011). "Infections in liver transplant recipients". World J Hepatol 3 (4): 83–92. doi:10.4254/wjh.v3.i4.83. PMC 3098392. PMID 21603030. http://www.wjgnet.com/1948-5182/full/v3/i4/83.htm. 
  77. ^ Aidé MA (November 2009). "Chapter 4—histoplasmosis". J Bras Pneumol 35 (11): 1145–51. doi:10.1590/S1806-37132009001100013. PMID 20011851. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1806-37132009001100013&lng=en&nrm=iso&tlng=en. 
  78. ^ Chukwuma C (January 1996). "Microsporidium in AIDS patients: a perspective". East Afr Med J 73 (1): 72–5. PMID 8625869. 
  79. ^ Arcay L (May 2001). "[Human microsporidiosis]" (in Spanish; Castilian). Invest Clin 42 (Suppl 1): 3–42. PMID 11416983. 
  80. ^ Atías A (June 1995). "[Update on microsporidiosis in humans]" (in Spanish; Castilian). Rev Med Chil 123 (6): 762–72. PMID 8525232. 
  81. ^ Chan JC, Jeffers LJ, Gould EW, et al. (1990). "Visceral protothecosis mimicking sclerosing cholangitis in an immunocompetent host: successful antifungal therapy". Rev. Infect. Dis. 12 (5): 802–7. doi:10.1093/clinids/12.5.802. PMID 2237120. 
  82. ^ Narita M, Muder RR, Cacciarelli TV, Singh N (August 2008). "Protothecosis after liver transplantation". Liver Transpl. 14 (8): 1211–5. doi:10.1002/lt.21565. PMID 18668655. 
  83. ^ "Hepatitis as a result of chemicals and drugs". HealthAtoZ. Archived from the original on 2006-06-23. http://web.archive.org/web/20060623141402/http://www.healthatoz.com/healthatoz/Atoz/dc/caz/infc/hepa/hepres.jsp. Retrieved 2006-07-01. 
  84. ^ Lim JR, Faught PR, Chalasani NP, Molleston JP (2006). "Severe liver injury after initiating therapy with atomoxetine in two children". J. Pediatr. 148 (6): 831–4. doi:10.1016/j.jpeds.2006.01.035. PMID 16769398. 
  85. ^ Bastida G, Nos P, Aguas M, Beltrán B, Rubín A, Dasí F, Ponce J (2005). "Incidence, risk factors and clinical course of thiopurine-induced liver injury in patients with inflammatory bowel disease". Aliment Pharmacol Ther 22 (9): 775–82. doi:10.1111/j.1365-2036.2005.02636.x. PMID 16225485. 
  86. ^ Nadir A, Reddy D, Van Thiel DH (2000). "Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity". Am. J. Gastroenterol. 95 (12): 3634–7. doi:10.1111/j.1572-0241.2000.03386.x. PMID 11151906. 
  87. ^ Torbenson M, Hart J, Westerhoff M, et al. (October 2010). "Neonatal giant cell hepatitis: histological and etiological findings". Am. J. Surg. Pathol. 34 (10): 1498–503. doi:10.1097/PAS.0b013e3181f069ab. PMID 20871223. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0147-5185&volume=34&issue=10&spage=1498. 
  88. ^ Krokhina NB, Ushakova RA, Kobeleva IaM (2010). "[Significance of hepatic biopsy specimens in the diagnosis of liver disease in babies of the first year of life]" (in Russian). Arkh. Patol. 72 (1): 19–23. PMID 20369579. 
  89. ^ Hayashi H, Narita R, Hiura M, et al. (2011). "A case of adult autoimmune hepatitis with histological features of giant cell hepatitis". Intern. Med. 50 (4): 315–9. doi:10.2169/internalmedicine.50.4063. PMID 21325763. http://joi.jlc.jst.go.jp/JST.JSTAGE/internalmedicine/50.4063?from=PubMed. 
  90. ^ Hartl J, Buettner R, Rockmann F, et al. (November 2010). "Giant cell hepatitis: an unusual cause of fulminant liver failure". Z Gastroenterol 48 (11): 1293–6. doi:10.1055/s-0029-1245476. PMID 21043007. http://www.thieme-connect.com/DOI/DOI?10.1055/s-0029-1245476. 
  91. ^ Gábor L, Pál K, Zsuzsa S (September 1997). "Giant cell hepatitis in adults". Pathol. Oncol. Res. 3 (3): 215–8. doi:10.1007/BF02899924. PMID 18470733. http://por.hu/1997/3/3/0215/0215a.pdf. 
  92. ^ Alexopoulou A, Deutsch M, Ageletopoulou J, et al. (May 2003). "A fatal case of postinfantile giant cell hepatitis in a patient with chronic lymphocytic leukaemia". Eur J Gastroenterol Hepatol 15 (5): 551–5. doi:10.1097/01.meg.0000050026.34359.7c. PMID 12702915. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0954-691X&volume=15&issue=5&spage=551. 
  93. ^ Bianchi L, Terracciano LM (November 1994). "[Giant cell hepatitis in adults]" (in German). Praxis (Bern 1994) 83 (44): 1237–41. PMID 7973279. 
  94. ^ Duhaut P, Bosshard S, Ducroix JP (November 2004). "Is giant cell arteritis an infectious disease? Biological and epidemiological evidence". Presse Médicale (Paris, France : 1983) 33 (19 Pt 2): 1403–8. doi:10.1016/S0755-4982(04)98939-7. PMID 15615251. 
  95. ^ Shet TM, Kandalkar BM, Vora IM (January 1998). "Neonatal hepatitis--an autopsy study of 14 cases". Indian J Pathol Microbiol 41 (1): 77–84. PMID 9581081. 
  96. ^ Hassoun Z, N'Guyen B, Cote J, et al. (September 2000). "A case of giant cell hepatitis recurring after liver transplantation and treated with ribavirin". Can. J. Gastroenterol. 14 (8): 729–31. PMID 11185540. http://www.pulsus.com/journals/abstract.jsp?sCurrPg=journal&jnlKy=2&atlKy=5390&isuKy=200&isArt=t. 
  97. ^ Durand F, Degott C, Sauvanet A, et al. (March 1997). "Subfulminant syncytial giant cell hepatitis: recurrence after liver transplantation treated with ribavirin". J. Hepatol. 26 (3): 722–6. doi:10.1016/S0168-8278(97)80440-0. PMID 9075682. 
  98. ^ Harmanci O, Onal IK, Ersoy O, Gürel B, Sökmensüer C, Bayraktar Y (December 2007). "Postinfantile giant cell hepatitis due to hepatitis E virus along with the presence of autoantibodies". Digestive Diseases and Sciences 52 (12): 3521–3. doi:10.1007/s10620-006-9698-8. PMID 17410455. 
  99. ^ Moreno A, Moreno A, Pérez-Elías MJ, Quereda C, Fernández-Muñoz R, Antela A, Moreno L, Bárcena R, López-San Román A, Celma ML, García-Martos M, Moreno S (October 2006). "Syncytial giant cell hepatitis in human immunodeficiency virus-infected patients with chronic hepatitis C: 2 cases and review of the literature". Human Pathology 37 (10): 1344–9. doi:10.1016/j.humpath.2006.05.003. PMID 16949926. 
  100. ^ Fimmel CJ, Guo L, Compans RW, et al. (October 1998). "A case of syncytial giant cell hepatitis with features of a paramyxoviral infection". Am. J. Gastroenterol. 93 (10): 1931–7. doi:10.1111/j.1572-0241.1998.00548.x. PMID 9772058. 
  101. ^ Krech RH, Geenen V, Maschek H, Högemann B (May 1998). "[Adult giant cell hepatitis with fatal outcome. Clinicopathologic case report and reflections on pathogenesis"] (in German). Pathologe 19 (3): 221–5. doi:10.1007/s002920050277. PMID 9648148. http://link.springer.de/link/service/journals/00292/bibs/8019003/80190221.htm. 
  102. ^ Koff RS (September 1991). "Acute and chronic giant cell hepatitis: a paramyxovirus infection?". Gastroenterology 101 (3): 863–4. PMID 1860651. 
  103. ^ Phillips MJ, Blendis LM, Poucell S, et al. (February 1991). "Syncytial giant-cell hepatitis. Sporadic hepatitis with distinctive pathological features, a severe clinical course, and paramyxoviral features". N. Engl. J. Med. 324 (7): 455–60. doi:10.1056/NEJM199102143240705. PMID 1988831. 
  104. ^ Drut R, Gómez MA, Drut RM, Cueto RE, Lojo M (1998). "[Human papillomavirus, neonatal giant cell hepatitis and biliary duct atresia]" (in Spanish; Castilian). Acta Gastroenterol. Latinoam. 28 (1): 27–31. PMID 9607071. 
  105. ^ Drut R, Gómez MA, Drut RM, Lojo MM (1996). "Human papillomavirus (HPV)-associated neonatal giant cell hepatitis (NGCH)". Pediatr Pathol Lab Med 16 (3): 403–12. PMID 9025842. 
  106. ^ Potenza L, Luppi M, Barozzi P, et al. (August 2008). "HHV-6A in syncytial giant-cell hepatitis". N. Engl. J. Med. 359 (6): 593–602. doi:10.1056/NEJMoa074479. PMID 18687640. 
  107. ^ Kuntzen T, Friedrichs N, Fischer HP, Eis-Hübinger AM, Sauerbruch T, Spengler U (October 2005). "Postinfantile giant cell hepatitis with autoimmune features following a human herpesvirus 6-induced adverse drug reaction". Eur J Gastroenterol Hepatol 17 (10): 1131–4. doi:10.1097/00042737-200510000-00020. PMID 16148562. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0954-691X&volume=17&issue=10&spage=1131. 
  108. ^ Suzuki K, Nakayama H, Doi K (February 2001). "Giant cell hepatitis in two young cats". J. Vet. Med. Sci. 63 (2): 199–201. doi:10.1292/jvms.63.199. PMID 11258461. http://joi.jlc.jst.go.jp/JST.JSTAGE/jvms/63.199?lang=en&from=PubMed. 

External links