Editing Hepatitis (section)

== Treatment ==
The treatment of hepatitis varies according to the type, whether it is acute or chronic, and the severity of the disease.
* Activity: Many people with hepatitis prefer bed rest, though it is not necessary to avoid all physical activity while recovering.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" />
* Diet: A high-calorie diet is recommended.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /> Many people develop nausea and cannot tolerate food later in the day, so the bulk of intake may be concentrated in the earlier part of the day.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /> In the acute phase of the disease, intravenous feeding may be needed if patients cannot tolerate food and have poor oral intake subsequent to nausea and vomiting.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" />
* Drugs: People with hepatitis should avoid taking drugs metabolized by the liver.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /> [[Glucocorticoid]]s are not recommended as a treatment option for acute viral hepatitis and may even cause harm, such as development of chronic hepatitis.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" />
* Precautions: [[Universal precautions]] should be observed. Isolation is usually not needed, except in cases of hepatitis A and E who have fecal incontinence, and  in cases of hepatitis B and C who have uncontrolled bleeding.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" />

=== Hepatitis A ===
{{main|Hepatitis A}}

Hepatitis A usually does not progress to a chronic state, and rarely requires hospitalization.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /><ref name="WHO Hep A Fact Sheet July 2015" /> Treatment is supportive and includes such measures as providing intravenous (IV) hydration and maintaining adequate nutrition.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /><ref name="WHO Hep A Fact Sheet July 2015" />

Rarely, people with the hepatitis A virus can rapidly develop liver failure, termed ''fulminant hepatic failure'', especially the elderly and those who had a pre-existing liver disease, especially hepatitis C.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /><ref name="WHO Hep A Fact Sheet July 2015" /> Mortality risk factors include greater age and chronic hepatitis C.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /> In these cases, more aggressive supportive therapy and liver transplant may be necessary.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" />

=== Hepatitis B ===
{{main|Hepatitis B}}

==== Acute ====
In healthy patients, 95–99% recover with no long-lasting effects, and antiviral treatment is not warranted.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" /> Age and comorbid conditions can result in a more prolonged and severe illness. Certain patients warrant hospitalization, especially those who present with clinical signs of ascites, peripheral edema, and hepatic encephalopathy, and laboratory signs of [[hypoglycemia]], prolonged [[prothrombin time]], low serum [[Albumin human|albumin]], and very high serum [[bilirubin]].<ref name="Harrison's Principles, chapter 360 (Acute Viral)" />

In these rare, more severe acute cases, patients have been successfully treated with antiviral therapy similar to that used in cases of chronic hepatitis B, with nucleoside analogues such as [[entecavir]] or [[Tenofovir disoproxil|tenofovir]]. As there is a dearth of clinical trial data and the drugs used to treat are prone to developing [[Drug resistance|resistance]], experts recommend reserving treatment for severe acute cases, not mild to moderate.<ref name="Harrison's Principles, chapter 360 (Acute Viral)" />

==== Chronic ====
Chronic hepatitis B management aims to control viral replication, which is correlated with progression of disease.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> Seven drugs are approved in the United States:<ref name="Harrison's Principles, chapter 362 (Chronic)" />
* [[Adefovir dipivoxil]], a nucleotide analogue, has been used to supplement lamivudine in patients who develop resistance, but is no longer recommended as first-line therapy.<ref name="Harrison's Principles, chapter 362 (Chronic)" />
* [[Entecavir]] is safe, well tolerated, less prone to developing resistance, and the most potent of the existing hepatitis B antivirals; it is thus a first-line treatment choice.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> It is not recommended for lamivudine-resistant patients or as monotherapy in patients who are HIV positive.<ref name="Harrison's Principles, chapter 362 (Chronic)" />
* Injectable [[interferon alpha]] was the first therapy approved for chronic hepatitis B.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> It has several side effects, most of which are reversible with removal of therapy, but it has been supplanted by newer treatments for this indication.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> These include long-acting interferon bound to [[polyethylene glycol]] (pegylated interferon) and the oral nucleoside analogues.<ref name="Harrison's Principles, chapter 362 (Chronic)" />
* [[Lamivudine]] was the first approved oral nucleoside analogue.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> While effective and potent, lamivudine has been replaced by newer, more potent treatments in the Western world and is no longer recommended as first-line treatment.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> It is still used in areas where newer agents either have not been approved or are too costly.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> Generally, the course of treatment is a minimum of one year with a minimum of six additional months of "consolidation therapy."<ref name="Harrison's Principles, chapter 362 (Chronic)" /> Based on viral response, longer therapy may be required, and certain patients require indefinite long-term therapy.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> Due to a less robust response in Asian patients, [[consolidation therapy]] is recommended to be extended to at least a year.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> All patients should be monitored for viral reactivation, which if identified, requires restarting treatment.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> Lamivudine is generally safe and well tolerated.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> Many patients develop resistance, which is correlated with longer treatment duration.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> If this occurs, an additional antiviral is added.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> Lamivudine as a single treatment is contraindicated in patients coinfected with HIV, as resistance develops rapidly, but it can be used as part of a multidrug regimen.<ref name="Harrison's Principles, chapter 362 (Chronic)" />
* [[Pegylated interferon]] (PEG IFN) is dosed just once a week as a subcutaneous injection and is both more convenient and effective than standard interferon.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> Although it does not develop resistance as do many of the oral antivirals, it is poorly tolerated and requires close monitoring.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> PEG IFN is estimated to cost about $18,000 per year in the United States, compared to $2,500–8,700 for the oral medications. Its treatment duration is 48 weeks, unlike oral antivirals which require indefinite treatment for most patients (minimum one year).<ref name="Harrison's Principles, chapter 362 (Chronic)" /> PEG IFN is not effective in patients with high levels of viral activity and cannot be used in immunosuppressed patients or those with cirrhosis.<ref name="Harrison's Principles, chapter 362 (Chronic)" />
* [[Telbivudine]] is effective but not recommended as first-line treatment; as compared to entecavir, it is both less potent and more resistance prone.<ref name="Harrison's Principles, chapter 362 (Chronic)" />
* [[Tenofovir disoproxil|Tenofovir]] is a nucleotide analogue and an antiretroviral drug that is also used to treat HIV infection.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> It is preferred to adefovir both in lamivudine-resistant patients and as initial treatment since it is both more potent and less likely to develop resistance.<ref name="Harrison's Principles, chapter 362 (Chronic)" />
First-line treatments currently used include PEG IFN, entecavir, and tenofovir, subject to patient and physician preference.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> Treatment initiation is guided by recommendations issued by The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) and is based on detectable viral levels, [[HBeAg]] positive or negative status, [[Alanine transaminase|ALT]] levels, and in certain cases, family history of HCC and liver biopsy.<ref name="Harrison's Principles, chapter 362 (Chronic)" /> In patients with compensated cirrhosis, treatment is recommended regardless of HBeAg status or ALT level, but recommendations differ regarding HBV DNA levels; AASLD recommends treating at DNA levels detectable above 2x10<sup>3</sup> IU/mL; EASL and WHO recommend treating when HBV DNA levels are detectable at any level.<ref name="Harrison's Principles, chapter 362 (Chronic)" /><ref name="WHO guidelines for chronic Hepatitis B" /> In patients with decompensated cirrhosis, treatment and evaluation for liver transplantation are recommended in all cases if HBV DNA is detectable.<ref name="Harrison's Principles, chapter 362 (Chronic)" /><ref name="WHO guidelines for chronic Hepatitis B" /> Currently, multidrug treatment is not recommended in treatment of chronic HBV as it is no more effective in the long term than individual treatment with entecavir or tenofovir.<ref name="Harrison's Principles, chapter 362 (Chronic)" />

=== Hepatitis C ===
{{main|Hepatitis C}}
The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) recommend antiviral treatment for all patients with chronic hepatitis C infection except for those with additional chronic medical conditions that limit their life expectancy.<ref name="AASLD-IDSA"/>

Once it is acquired, persistence of the hepatitis C virus is the rule, resulting in chronic hepatitis C. The goal of treatment is prevention of hepatocellular carcinoma (HCC).<ref name="Messori Badiani Tripoli">{{Cite journal|last1=Messori|first1=Andrea|last2=Badiani|first2=Brigitta|last3=Trippoli|first3=Sabrina|date=2015-12-01|title=Achieving Sustained Virological Response in Hepatitis C Reduces the Long-Term Risk of Hepatocellular Carcinoma: An Updated Meta-Analysis Employing Relative and Absolute Outcome Measures|journal=Clinical Drug Investigation|volume=35|issue=12|pages=843–850|doi=10.1007/s40261-015-0338-y|issn=1179-1918|pmid=26446006|s2cid=41365729}}</ref> The best way to reduce the long-term risk of HCC is to achieve sustained virological response (SVR).<ref name="Messori Badiani Tripoli" /> SVR is defined as an undetectable viral load at 12 weeks after treatment completion and indicates a cure.<ref name="Revolution">{{Cite journal|last1=Thiagarajan|first1=Prarthana|last2=Ryder|first2=Stephen D.|date=2015-12-01|title=The hepatitis C revolution part 1: antiviral treatment options|journal=Current Opinion in Infectious Diseases|volume=28|issue=6|pages=563–571|doi=10.1097/QCO.0000000000000205|issn=1473-6527|pmid=26524328|s2cid=11926260}}</ref><ref name="Enhancing our understanding">{{Cite journal|last1=Gogela|first1=Neliswa A.|last2=Lin|first2=Ming V.|last3=Wisocky|first3=Jessica L.|last4=Chung|first4=Raymond T.|date=2015-03-01|title=Enhancing our understanding of current therapies for Hepatitis C virus (HCV)|journal=Current HIV/AIDS Reports|volume=12|issue=1|pages=68–78|doi=10.1007/s11904-014-0243-7|issn=1548-3568|pmc=4373591|pmid=25761432}}</ref> Currently available treatments include indirect and direct acting antiviral drugs.<ref name="Revolution"/><ref name="Enhancing our understanding"/> The indirect acting antivirals include [[pegylated interferon]] (PEG IFN) and [[ribavirin]] (RBV), which in combination have historically been the basis of therapy for HCV.<ref name="Revolution"/><ref name="Enhancing our understanding"/> Duration of and response to these treatments varies based on genotype.<ref name="Revolution"/><ref name="Enhancing our understanding"/> These agents are poorly tolerated but are still used in some resource-poor areas.<ref name="Revolution"/><ref name="Enhancing our understanding"/> In high-resource countries, they have been supplanted by direct acting antiviral agents, which first appeared in 2011; these agents target proteins responsible for viral replication and include the following three classes:<ref name="Revolution"/><ref name="Enhancing our understanding"/>
* [[NS3 (HCV)|NS3]] and [[NS4A (Hepacivirus)|NS4A]] [[Protease inhibitor (pharmacology)|protease inhibitor]]s, including [[telaprevir]], [[boceprevir]], [[simeprevir]], and others
* [[NS5A (hepacivirus)|NS5A]] inhibitors, including [[ledipasvir]], [[daclatasvir]], and others
* [[NS5B inhibitors]], including [[sofosbuvir]], [[dasabuvir]], and others
These drugs are used in various combinations, sometimes combined with ribavirin, based on the patient's [[genotype]], delineated as genotypes 1–6.<ref name="Enhancing our understanding"/> Genotype 1 (GT1), which is the most prevalent genotype in the United States and around the world, can now be cured with a direct acting antiviral regimen.<ref name="Enhancing our understanding"/> First-line therapy for GT1 is a combination of sofosbuvir and ledipasvir (SOF/LDV) for 12 weeks for most patients, including those with advanced fibrosis or cirrhosis.<ref name="Enhancing our understanding"/> Certain patients with early disease need only 8 weeks of treatment while those with advanced fibrosis or cirrhosis who have not responded to prior treatment require 24 weeks.<ref name="Enhancing our understanding"/> Cost remains a major factor limiting access to these drugs, particularly in low-resource nations; the cost of the 12-week GT1 regimen (SOF/LDV)  has been estimated at US$94,500.<ref name="Revolution"/>

=== Hepatitis D ===
{{main|Hepatitis D}}
Hepatitis D is difficult to treat, and effective treatments are lacking. Interferon alpha has proven effective at inhibiting viral activity but only on a temporary basis.<ref name="Interferon alpha">{{cite journal|title=Interferon alpha for chronic hepatitis D|journal = Cochrane Database of Systematic Reviews|issue = 12|pages = CD006002|last2=Khan|first2=Muhammad Arsalan|last3=Salih|first3=Mohammad|last4=Jafri|first4=Wasim|date=2011-12-07|language=en|doi=10.1002/14651858.cd006002.pub2|pmid = 22161394|pmc = 6823236|last1=Abbas|first1=Zaigham| volume=2011 }}</ref>

=== Hepatitis E ===
{{main|Hepatitis E}}
[[File:Hepatitis E virus.jpg|thumb|Hepatitis E virus]]
Similar to hepatitis A, treatment of hepatitis E is supportive and includes rest and ensuring adequate nutrition and hydration.<ref name="CDC - HEV FAQ">{{Cite web|url=https://www.cdc.gov/hepatitis/hev/hevfaq.htm|title=HEV FAQs for Health Professionals {{!}} Division of Viral Hepatitis {{!}} CDC|website=www.cdc.gov|access-date=2016-03-17|url-status=live|archive-url=https://web.archive.org/web/20160308031004/http://www.cdc.gov/hepatitis/hev/hevfaq.htm|archive-date=2016-03-08}}</ref> Hospitalization may be required for particularly severe cases or for pregnant women.<ref name="CDC - HEV FAQ" />

=== Alcoholic hepatitis ===
First-line treatment of alcoholic hepatitis is treatment of alcoholism.<ref name="Harrison's Principles chapter 363 (Alcohol)" /> For those who abstain completely from alcohol ([[teetotal]]), reversal of liver disease and a longer life are possible; patients at every disease stage have been shown to benefit by prevention of additional liver injury.<ref name="Harrison's Principles chapter 363 (Alcohol)" /><ref name="Chayanupatkul & Liangpunsakul" /> In addition to referral to psychotherapy and other treatment programs, treatment should include nutritional and psychosocial evaluation and treatment.<ref name="Harrison's Principles chapter 363 (Alcohol)" /><ref name="Chayanupatkul & Liangpunsakul" /><ref name="Comparative effectiveness - meta-analysis">{{Cite journal|last1=Singh|first1=Siddharth|last2=Murad|first2=Mohammad Hassan|last3=Chandar|first3=Apoorva K.|last4=Bongiorno|first4=Connie M.|last5=Singal|first5=Ashwani K.|last6=Atkinson|first6=Stephen R.|last7=Thursz|first7=Mark R.|last8=Loomba|first8=Rohit|last9=Shah|first9=Vijay H.|date=2015-10-01|title=Comparative Effectiveness of Pharmacological Interventions for Severe Alcoholic Hepatitis: A Systematic Review and Network Meta-analysis|journal=Gastroenterology|volume=149|issue=4|pages=958–970.e12|doi=10.1053/j.gastro.2015.06.006|issn=1528-0012|pmid=26091937}}</ref> Patients should also be treated appropriately for related signs and symptoms, such as ascites, hepatic encephalopathy, and infection.<ref name="Chayanupatkul & Liangpunsakul" />

Severe alcoholic hepatitis has a poor prognosis and is notoriously difficult to treat.<ref name="Harrison's Principles chapter 363 (Alcohol)" /><ref name="Chayanupatkul & Liangpunsakul" /><ref name="Comparative effectiveness - meta-analysis" /> Without any treatment, 20–50% of patients may die within a month, but evidence shows treatment may extend life beyond one month (i.e., reduce short-term mortality).<ref name="Harrison's Principles chapter 363 (Alcohol)" /><ref name="Comparative effectiveness - meta-analysis" /><ref name="STOPAH">{{Cite journal|last1=Thursz|first1=Mark|last2=Forrest|first2=Ewan|last3=Roderick|first3=Paul|last4=Day|first4=Christopher|last5=Austin|first5=Andrew|last6=O'Grady|first6=John|last7=Ryder|first7=Stephen|last8=Allison|first8=Michael|last9=Gleeson|first9=Dermot|date=2015-12-01|title=The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 × 2 factorial randomised controlled trial|journal=Health Technology Assessment|volume=19|issue=102|pages=1–104|doi=10.3310/hta191020|issn=2046-4924|pmid=26691209|pmc=4781103}}</ref> Available treatment options include [[pentoxifylline]] (PTX), which is a nonspecific [[TNF inhibitor]], [[corticosteroid]]s, such as [[prednisone]] or [[prednisolone]] (CS), corticosteroids with ''[[N-Acetylcysteine|N]]''[[N-Acetylcysteine|-acetylcysteine]] (CS with NAC), and corticosteroids with pentoxifylline (CS with PTX).<ref name="Comparative effectiveness - meta-analysis" /> Data suggest that CS alone or CS with NAC are most effective at reducing short-term mortality.<ref name="Comparative effectiveness - meta-analysis" /> Unfortunately, corticosteroids are contraindicated in some patients, such as those who have active gastrointestinal bleeding, infection, kidney failure, or pancreatitis.<ref name="Harrison's Principles chapter 363 (Alcohol)" /><ref name="Chayanupatkul & Liangpunsakul" /> In these cases PTX may be considered on a case-by-case basis in lieu of CS; some evidence shows PTX is better than no treatment at all and may be comparable to CS while other data show no evidence of benefit over placebo.<ref name="Comparative effectiveness - meta-analysis" /><ref name="STOPAH" /> Unfortunately, there are currently no drug treatments that decrease these patients' risk of dying in the longer term, at 3–12 months and beyond.<ref name="Comparative effectiveness - meta-analysis" />

Weak evidence suggests [[Milk Thistle|milk thistle]] extracts may improve survival in alcoholic liver disease and improve certain liver tests (serum bilirubin and [[Gamma-glutamyl transpeptidase|GGT]]) without causing side effects, but a firm recommendation cannot be made for or against milk thistle without further study.<ref>{{Cite journal|title=Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases|last1=Rambaldi|first1=Andrea|last2=Jacobs|first2=Bradly P|last3=Gluud|first3=Christian|date=2007-10-17|issn=1465-1858|language=en|doi=10.1002/14651858.cd003620.pub3|journal=Protocols|volume=2009 |pmid=17943794|pages=CD003620|issue=4|pmc=8724782 }}</ref>&nbsp;

The [[modified Maddrey's discriminant function]] may be used to evaluate the severity and prognosis in alcoholic hepatitis and evaluates the efficacy of using alcoholic hepatitis corticosteroid treatment.

===Metabolic hepatitis===
{{main|Non-alcoholic_fatty_liver_disease#Management}}
The main treatment of NASH  is gradual weight loss and increased physical activity. In the United States, no medications have been approved to treat this disease.<ref>{{cite web |title=Treatment for NAFLD & NASH - NIDDK |url=https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/treatment |website=National Institute of Diabetes and Digestive and Kidney Diseases |access-date=4 September 2023}}</ref>
=== Autoimmune hepatitis ===

Autoimmune hepatitis is commonly treated by immunosuppressants such as the corticosteroids prednisone or prednisolone, the active version of prednisolone that does not require liver synthesis, either alone or in combination with azathioprine, and some have suggested the combination therapy is preferred to allow for lower doses of corticosteroids to reduce associated side effects,<ref name=":0" /> although the result of treatment efficacy is comparative.<ref>{{Cite journal|last1=Summerskill|first1=W. H.|last2=Korman|first2=M. G.|last3=Ammon|first3=H. V.|last4=Baggenstoss|first4=A. H.|date=1975-11-01|title=Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared|journal=Gut|volume=16|issue=11|pages=876–883|doi=10.1136/gut.16.11.876|issn=0017-5749|pmc=1413126|pmid=1104411}}</ref>

Treatment of autoimmune hepatitis consists of two phases; an initial and maintenance phase. The initial phase consists of higher doses of corticosteroids which are tapered down over a number of weeks to a lower dose. If used in combination, azathioprine is given during the initial phase as well. Once the initial phase has been completed, a maintenance phase that consists of lower dose corticosteroids, and in combination therapy, azathioprine until liver blood markers are normalized. Treatment results in 66–91% of patients achieving normal liver test values in two years, with the average being 22 months.<ref name=":0" />