Editing Hepatitis (section)

=== Steatohepatitis ===

[[Steatohepatitis]] is seen in both alcoholic and non-alcoholic liver disease and is the culmination of a cascade of events that began with injury.  In the case of [[Non-alcoholic fatty liver disease|non-alcoholic steatohepatitis]], this cascade is initiated by changes in metabolism associated with obesity, insulin resistance, and lipid dysregulation.<ref name="Hardy Oakley Anstee Day">{{Cite journal|last1=Hardy|first1=Timothy|last2=Oakley|first2=Fiona|last3=Anstee|first3=Quentin M.|last4=Day|first4=Christopher P.|date=2016-03-03|title=Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum|journal=Annual Review of Pathology|doi=10.1146/annurev-pathol-012615-044224|issn=1553-4014|pmid=26980160|volume=11|pages=451–96|url=https://zenodo.org/record/3452754}}{{Dead link|date=February 2022 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref name="Yoon & Cha Pathogenesis">{{Cite journal|last1=Yoon|first1=Hye-Jin|last2=Cha|first2=Bong Soo|date=2014-11-27|title=Pathogenesis and therapeutic approaches for non-alcoholic fatty liver disease|journal=World Journal of Hepatology|volume=6|issue=11|pages=800–811|doi=10.4254/wjh.v6.i11.800|issn=1948-5182|pmc=4243154|pmid=25429318 |doi-access=free }}</ref> In [[alcoholic hepatitis]], chronic excess alcohol use is the culprit.<ref name="Chayanupatkul & Liangpunsakul" />  Though the inciting event may differ, the progression of events is similar and begins with accumulation of free [[fatty acid]]s (FFA) and their breakdown products  in the liver cells in a process called [[steatosis]].<ref name="Hardy Oakley Anstee Day" /><ref name="Yoon & Cha Pathogenesis" /><ref name="Chayanupatkul & Liangpunsakul" /> This initially reversible process overwhelms the [[hepatocyte]]'s ability to maintain lipid homeostasis leading to a toxic effect  as fat molecules accumulate and are broken down in the setting of an [[Cellular stress response|oxidative stress response]].<ref name="Hardy Oakley Anstee Day" /><ref name="Yoon & Cha Pathogenesis" /><ref name="Chayanupatkul & Liangpunsakul" />  Over time, this abnormal lipid deposition triggers the [[immune system]] via [[Toll-like receptor|toll-like receptor 4]] (TLR4) resulting in the production of inflammatory [[cytokine]]s such as TNF that cause liver cell injury and death.<ref name="Hardy Oakley Anstee Day" /><ref name="Yoon & Cha Pathogenesis" /><ref name="Chayanupatkul & Liangpunsakul" />  These events mark the transition to [[steatohepatitis]] and in the setting of chronic injury, [[fibrosis]] eventually develops setting up events that lead to cirrhosis and hepatocellular carcinoma.<ref name="Hardy Oakley Anstee Day" /> Microscopically, changes that can be seen include steatosis with large and swollen hepatocytes ([[Ballooning degeneration|ballooning]]), evidence of cellular injury and cell death (apoptosis, necrosis), evidence of inflammation in particular in [[Liver|zone 3 of the liver]], variable degrees of fibrosis and [[Mallory body|Mallory bodies]].<ref name="Hardy Oakley Anstee Day" /><ref name="Definition, epidemiology, and magnitude">{{Cite journal|last1=Basra|first1=Sarpreet|last2=Anand|first2=Bhupinderjit S.|date=2011-05-27|title=Definition, epidemiology and magnitude of alcoholic hepatitis|journal=World Journal of Hepatology|volume=3|issue=5|pages=108–113|doi=10.4254/wjh.v3.i5.108|issn=1948-5182|pmc=3124876|pmid=21731902 |doi-access=free }}</ref><ref>{{Cite journal|last1=Haga|first1=Yuki|last2=Kanda|first2=Tatsuo|last3=Sasaki|first3=Reina|last4=Nakamura|first4=Masato|last5=Nakamoto|first5=Shingo|last6=Yokosuka|first6=Osamu|date=2015-12-14|title=Nonalcoholic fatty liver disease and hepatic cirrhosis: Comparison with viral hepatitis-associated steatosis|journal=World Journal of Gastroenterology|volume=21|issue=46|pages=12989–12995|doi=10.3748/wjg.v21.i46.12989|issn=2219-2840|pmc=4674717|pmid=26675364 |doi-access=free }}</ref>