Editing Hepatitis (section)

=== Viral hepatitis ===

[[File:Stages of Liver disease NIDDK NIH.gif|thumb|upright=1.3|Stages of liver disease]]
The pathway by which hepatic viruses cause [[viral hepatitis]] is best understood in the case of hepatitis B and C.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /> The viruses do not directly activate [[apoptosis]] (cell death).<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /><ref name="Nakamoto & Kaneko">{{Cite journal|last1=Nakamoto|first1=Yasunari|last2=Kaneko|first2=Shuichi|date=2003-09-01|title=Mechanisms of viral hepatitis induced liver injury|journal=Current Molecular Medicine|volume=3|issue=6|pages=537–544|issn=1566-5240|pmid=14527085|doi=10.2174/1566524033479591}}</ref> Rather, infection of liver cells activates the [[Innate immune system|innate]] and [[Adaptive immune system|adaptive]] arms of the [[immune system]] leading to an inflammatory response which causes cellular damage and death, including viral-induced apoptosis via the induction of the death receptor-mediated signaling pathway.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /><ref name="Nakamoto & Kaneko" /><ref>{{Cite journal|last1=Lin|first1=Shaoli|last2=Zhang|first2=Yan-Jin|date=August 2017|title=Interference of Apoptosis by Hepatitis B Virus|journal=Viruses|language=en|volume=9|issue=8|page=230|doi=10.3390/v9080230|pmid=28820498|pmc=5580487|doi-access=free}}</ref><ref>{{Cite journal|last1=Cao|first1=Lei|last2=Quan|first2=Xi-Bing|last3=Zeng|first3=Wen-Jiao|last4=Yang|first4=Xiao-Ou|last5=Wang|first5=Ming-Jie|date=2016|title=Mechanism of Hepatocyte Apoptosis|journal=Journal of Cell Death|language=en|volume=9|pages=19–29|doi=10.4137/JCD.S39824|pmid=28058033|pmc=5201115}}</ref>  Depending on the strength of the immune response, the types of immune cells involved and the ability of the virus to evade the body's defense, infection can either lead to clearance (acute disease) or persistence (chronic disease) of the virus.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" />  The chronic presence of the virus within liver cells results in multiple waves of [[inflammation]], injury and [[wound healing]] that over time lead to scarring or [[fibrosis]] and culminate in [[hepatocellular carcinoma]].<ref name="Nakamoto & Kaneko" /><ref>{{Cite journal|last=Wong|first=Grace Lai-Hung|date=2014-09-01|title=Prediction of fibrosis progression in chronic viral hepatitis|journal=Clinical and Molecular Hepatology|volume=20|issue=3|pages=228–236|doi=10.3350/cmh.2014.20.3.228|issn=2287-285X|pmc=4197170|pmid=25320725}}</ref> People with impaired immune response are at greater risk of developing chronic infection.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /> [[Natural killer cell]]s are the primary drivers of the initial innate response and create a [[cytokine]] environment that results in the recruitment of [[T helper cell|CD4 T-helper]] and [[Cytotoxic T cell|CD8 cytotoxic T-cells]].<ref name="Rehermann Killer Cells">{{Cite journal|last=Rehermann|first=Barbara|date=2015-11-01|title=Natural Killer Cells in Viral Hepatitis|journal=Cellular and Molecular Gastroenterology and Hepatology|volume=1|issue=6|pages=578–588|doi=10.1016/j.jcmgh.2015.09.004|issn=2352-345X|pmc=4678927|pmid=26682281}}</ref><ref name="Heim & Thimme">{{Cite journal|last1=Heim|first1=Markus H.|last2=Thimme|first2=Robert|date=2014-11-01|title=Innate and adaptive immune responses in HCV infections|journal=Journal of Hepatology|volume=61|issue=1 Suppl|pages=S14–25|doi=10.1016/j.jhep.2014.06.035|issn=1600-0641|pmid=25443342|doi-access=free}}</ref>  [[Interferon type I|Type I interferons]] are the cytokines that drive the antiviral response.<ref name="Heim & Thimme" /> In chronic Hepatitis B and C, natural killer cell function is impaired.<ref name="Rehermann Killer Cells" />