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== Diagnosis == {| class="wikitable" style = "float: right; margin-left:15px; text-align:center" ! scope="col" |Most elevated aminotransferase ! scope="col" |Cause |- | rowspan="9" | ALT |Chronic hepatitis B, C, and D |- |Nonalcoholic liver disease |- |Acute viral hepatitis |- |Medications/toxins |- |Autoimmune hepatitis |- |Wilson's disease |- |Alpha-1-antitrypsin deficiency |- |Hemochromatosis |- |''Ischemic hepatitis (severe elevation up to thousands)'' |- | rowspan="2" | AST |Alcoholic liver disease |- |Cirrhosis |} [[File:Histopathology of acute hepatitis.jpg|thumb|Histopathology of acute hepatitis with lobular disarray and associated lymphocytic inflammation, acidophil body formation (arrow) and bilirubinostasis.]] Diagnosis of hepatitis is made on the basis of some or all of the following: a person's signs and symptoms, medical history including sexual and substance use history, blood tests, [[Medical imaging|imaging]], and [[liver biopsy]].<ref name="Friedman 55e" /> In general, for viral hepatitis and other acute causes of hepatitis, the person's blood tests and clinical picture are sufficient for diagnosis.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /><ref name="Friedman 55e" /> For other causes of hepatitis, especially chronic causes, blood tests may not be useful.<ref name="Friedman 55e" /> In this case, liver biopsy is the [[Gold standard (test)|gold standard]] for establishing the diagnosis: [[Histopathology|histopathologic]] analysis is able to reveal the precise extent and pattern of inflammation and [[fibrosis]].<ref name="Friedman 55e" /> Biopsy is typically not the initial diagnostic test because it is invasive and is associated with a small but significant risk of bleeding that is increased in people with liver injury and cirrhosis.<ref>{{cite journal|last=Grant|first=A|year=1999|title=Guidelines on the use of liver biopsy in clinical practice|journal=Gut|volume=45|issue=Suppl 4|pages=1β11|doi=10.1136/gut.45.2008.iv1|pmc=1766696|pmid=10485854|quote=The main cause of mortality after percutaneous liver biopsy is intraperitoneal haemorrhage as shown in a retrospective Italian study of 68 000 percutaneous liver biopsies in which all six patients who died did so from intraperitoneal haemorrhage. Three of these patients had had a laparotomy, and all had either cirrhosis or malignant disease, both of which are risk factors for bleeding.|author2=Neuberger J}}</ref> Blood testing includes [[Liver function tests|liver enzymes]], [[serology]] (i.e. for autoantibodies), [[nucleic acid test]]ing (i.e. for hepatitis virus DNA/RNA), [[Blood chemistry study|blood chemistry]], and [[complete blood count]].<ref name="Friedman 55e" /> Characteristic patterns of liver enzyme abnormalities can point to certain causes or stages of hepatitis.<ref>{{cite journal|last=Green|first=RM|date=October 2002|title=AGA technical review on the evaluation of liver chemistry tests|journal=Gastroenterology|volume=123|issue=4|pages=1367β84|doi=10.1053/gast.2002.36061|pmid=12360498|author2=Flamm, S|doi-access=free}}</ref><ref>{{cite journal|last=Pratt|first=DS|date=Apr 27, 2000|title=Evaluation of abnormal liver-enzyme results in asymptomatic patients|journal=The New England Journal of Medicine|volume=342|issue=17|pages=1266β71|doi=10.1056/NEJM200004273421707|pmid=10781624|author2=Kaplan, MM}}</ref> Generally, [[Aspartate transaminase|AST]] and [[Alanine transaminase|ALT]] are elevated in most cases of hepatitis regardless of whether the person shows any symptoms.<ref name="Friedman 55e" /> The degree of elevation (i.e. levels in the hundreds vs. in the thousands), the predominance for AST vs. ALT elevation, and the ratio between AST and ALT are informative of the diagnosis.<ref name="Friedman 55e" /> [[Medical ultrasound|Ultrasound]], [[CT scan|CT]], and [[Magnetic resonance imaging|MRI]] can all identify steatosis (fatty changes) of the liver tissue and nodularity of the liver surface suggestive of cirrhosis.<ref>{{Cite journal|last1=Ito|first1=Katsuyoshi|last2=Mitchell|first2=Donald G.|title=Imaging Diagnosis of Cirrhosis and Chronic Hepatitis|journal=Intervirology|volume=47|issue=3β5|pages=134β143|doi=10.1159/000078465|pmid=15383722|year=2004|s2cid=36112368}}</ref><ref>{{Cite journal|last1=Allan|first1=Richard|last2=Thoirs|first2=Kerry|last3=Phillips|first3=Maureen|date=2010-07-28|title=Accuracy of ultrasound to identify chronic liver disease|journal=World Journal of Gastroenterology|volume=16|issue=28|pages=3510β3520|doi=10.3748/wjg.v16.i28.3510|issn=1007-9327|pmc=2909550|pmid=20653059 |doi-access=free }}</ref> CT and especially MRI are able to provide a higher level of detail, allowing visualization and characterize such structures as vessels and tumors within the liver.<ref>{{Cite journal|last1=Sahani|first1=Dushyant V.|last2=Kalva|first2=Sanjeeva P.|date=2004-07-01|title=Imaging the Liver|journal=The Oncologist|language=en|volume=9|issue=4|pages=385β397|doi=10.1634/theoncologist.9-4-385|issn=1083-7159|pmid=15266092|doi-access=free}}</ref> Unlike steatosis and cirrhosis, no imaging test is able to detect liver inflammation (i.e. hepatitis) or fibrosis.<ref name="Friedman 55e" /> Liver biopsy is the only definitive diagnostic test that is able to assess inflammation and fibrosis of the liver.<ref name="Friedman 55e" /> === Viral hepatitis === {{Main|Viral hepatitis}} Viral hepatitis is primarily diagnosed through blood tests for levels of viral [[antigen]]s (such as the [[HBsAg|hepatitis B surface]] or [[HBcAg|core]] antigen), anti-viral antibodies (such as the anti-hepatitis B surface antibody or anti-hepatitis A antibody), or viral DNA/RNA.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /><ref name="Friedman 55e" /> In early infection (i.e. within 1 week), [[Immunoglobulin M|IgM]] antibodies are found in the blood.<ref name="Friedman 55e" /> In late infection and after recovery, [[Immunoglobulin G|IgG]] antibodies are present and remain in the body for up to years.<ref name="Friedman 55e" /> Therefore, when a patient is positive for IgG antibody but negative for IgM antibody, he is considered [[Immunity (medical)|immune]] from the virus via either prior infection and recovery or prior vaccination.<ref name="Friedman 55e" /> In the case of hepatitis B, blood tests exist for multiple virus antigens (which are different components of the [[:File:HBV.png|virion particle]]) and antibodies.<ref name="pmid26568915">{{cite journal |year=2015 |title=Update on hepatitis B and C virus diagnosis |journal=World Journal of Virology |volume=4 |issue=4 |pages=323β42 |doi=10.5501/wjv.v4.i4.323 |pmc=4641225 |pmid=26568915 |vauthors=Villar LM, Cruz HM, Barbosa JR, Bezerra CS, Portilho MM, Scalioni Lde P |doi-access=free }}</ref> The combination of antigen and antibody positivity can provide information about the stage of infection (acute or chronic), the degree of viral replication, and the infectivity of the virus.<ref name="pmid26568915" /> === Alcoholic versus non-alcoholic === The most apparent distinguishing factor between [[Alcoholic hepatitis|alcoholic steatohepatitis]] (ASH) and [[Nonalcoholic Steatohepatitis|nonalcoholic steatohepatitis]] (NASH) is a history of excessive alcohol use.<ref name="Neuman, French, et al">{{Cite journal|last1=Neuman|first1=Manuela G.|last2=French|first2=Samuel W.|last3=French|first3=Barbara A.|last4=Seitz|first4=Helmut K.|last5=Cohen|first5=Lawrence B.|last6=Mueller|first6=Sebastian|last7=Osna|first7=Natalia A.|last8=Kharbanda|first8=Kusum K.|last9=Seth|first9=Devanshi|date=2014-12-01|title=Alcoholic and non-alcoholic steatohepatitis|journal=Experimental and Molecular Pathology|volume=97|issue=3|pages=492β510|doi=10.1016/j.yexmp.2014.09.005|pmc=4696068|pmid=25217800}}</ref> Thus, in patients who have no or negligible alcohol use, the diagnosis is unlikely to be alcoholic hepatitis. In those who drink alcohol, the diagnosis may just as likely be alcoholic or nonalcoholic hepatitis especially if there is concurrent obesity, diabetes, and metabolic syndrome. In this case, alcoholic and nonalcoholic hepatitis can be distinguished by the pattern of liver enzyme abnormalities; specifically, in alcoholic steatohepatitis AST>ALT with ratio of AST:ALT>2:1 while in nonalcoholic steatohepatitis ALT>AST with ratio of ALT:AST>1.5:1.<ref name="Neuman, French, et al" /> Liver biopsies show identical findings in patients with ASH and NASH, specifically, the presence of [[Granulocyte|polymorphonuclear]] infiltration, hepatocyte [[necrosis]] and [[apoptosis]] in the form of [[ballooning degeneration]], [[Mallory body|Mallory bodies]], and fibrosis around veins and sinuses.<ref name="Friedman 55e" />
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