Editing Hepatitis (section)

=== 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)" />