nucleoside analogues. lamivudine was the first approved oral nucleoside analogue. while effective and potent, lamivudine has been replaced by newer, more potent treatments in the western world and is no longer recommended as first-line treatment. it is still used in areas where newer agents either have not been approved or are too costly. generally, the course of treatment is a minimum of one year with a minimum of six additional months of "consolidation therapy." based on viral response, longer therapy may be required, and certain patients require indefinite long-term therapy. due to a less robust response in asian patients, consolidation therapy is recommended to be extended to at least a year. all patients should be monitored for viral reactivation, which if identified, requires restarting treatment. lamivudine is generally safe and well tolerated. many patients develop resistance, which is correlated with longer treatment duration. if this occurs, an additional antiviral is added. 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. pegylated interferon (peg ifn) is dosed just once a week as a subcutaneous injection and is both more convenient and effective than standard interferon. although it does not develop resistance as do many of the oral antivirals, it is poorly tolerated and requires close monitoring. 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). peg ifn is not effective in patients with high levels of viral activity and cannot be used in immunosuppressed patients or those with cirrhosis. telbivudine is effective but not recommended as first-line treatment; as compared to entecavir, it is both less potent and more resistance prone. tenofovir is a nucleotide analogue and an antiretroviral drug that is also used to treat hiv infection. 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. first-line treatments currently used include peg ifn, entecavir, and tenofovir, subject to patient and physician preference. 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, alt levels, and in certain cases, family history of hcc and liver biopsy. 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 2x103 iu/ml; easl and who recommend treating when hbv dna levels are detectable at any level. in patients with decompensated cirrhosis, treatment and evaluation for liver transplantation are recommended in all cases if hbv dna is detectable. 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. hepatitis c main article: 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. 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). the best way to reduce the long-term risk of hcc is to achieve sustained virological response (svr). svr is defined as an undetectable viral load at 12 weeks after treatment completion and indicates a cure. currently available treatments include indirect and direct acting antiviral drugs. the indirect acting antivirals include pegylated interferon (peg ifn) and ribavirin (rbv), which in combination have historically been the basis of therapy for hcv. duration of and response to these treatments varies based on genotype. these agents are poorly tolerated but are still used in some resource-poor areas. 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: ns3/4a protease inhibitors, including telaprevir, boceprevir, simeprevir, and others ns5a inhibitors, including ledipasvir, daclatasvir, and others ns5b polymerase 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. 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. 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. 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. 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. hepatitis d main article: 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. hepatitis e main article: hepatitis e hepatitis e virus similar to hepatitis a, treatment of hepatitis e is supportive and includes rest and ensuring adequate nutrition and hydration. hospitalization may be required for particularly severe cases or for pregnant women. alcoholic hepatitis first-line treatment of alcoholic hepatitis is treatment of alcoholism. for those who abstain completely from alcohol, 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. in addition to referral to psychotherapy and other treatment programs, treatment should include nutritional and psychosocial evaluation and treatment. patients should also be treated appropriately for related signs and symptoms, such as ascites, hepatic encephalopathy, and infection. severe alcoholic hepatitis has a poor prognosis and is notoriously difficult to treat. 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). available treatment options include pentoxifylline (ptx), which is a nonspecific tnf inhibitor, corticosteroids, such as prednisone or prednisolone (cs), corticosteroids with n-acetylcysteine (cs with nac), and corticosteroids with pentoxifylline (cs with ptx). data suggest that cs alone or cs with nac are most effective at reducing short-term mortality. unfortunately, corticosteroids are contraindicated in some patients, such as those who have active gastrointestinal bleeding, infection, kidney failure, or pancreatitis. 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. unfortunately, there are currently no drug treatments that decrease these patients' risk of dying in the longer term, at 3–12 months and beyond. weak evidence suggests milk thistle extracts may improve survival in alcoholic liver disease and improve certain liver tests (serum bilirubin and ggt) without causing side effects, but a firm recommendation cannot be made for or against milk thistle without further study. 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. 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, although the result of treatment efficacy is comparative. 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. prognosis acute hepatitis nearly all patients with hepatitis a infections recover completely without complications if they were healthy prior to the infection. similarly, acute hepatitis b infections have a favorable course towards complete recovery in 95–99% of patients. certain factors may portend a poorer outcome, such as co-morbid medical conditions or initial presenting symptoms of ascites, edema, or encephalopathy. overall, the mortality rate for acute hepatitis is low: ~0.1% in total for cases of hepatitis a and b, but rates can be higher in certain populations (super infection with both hepatitis b and d, pregnant women, etc.). in contrast to hepatitis a & b, hepatitis c carries a much higher risk of progressing to chronic hepatitis, approaching 85–90%. cirrhosis has been reported to develop in 20–50% of patients with chronic hepatitis c. other rare complications of acute hepatitis include pancreatitis, aplastic anemia, peripheral neuropathy, and myocarditis. fulminant hepatitis despite the relatively benign course of most viral cases of hepatitis, fulminant hepatitis represents a rare but feared complication. fulminant hepatitis most commonly occurs in hepatitis b, d, and e. about 1–2% of cases of hepatitis e can lead to fulminant hepatitis, but pregnant women are particularly susceptible, occurring in up to 20% of cases. mortality rates in cases of fulminant hepatitis rise over 80%, but those patients that do survive often make a complete recovery. liver transplantation can be life-saving in patients with fulminant liver failure. hepatitis d infections can transform benign cases of hepatitis b into severe, progressive hepatitis, a phenomenon known as superinfection. chronic hepatitis acute hepatitis b infections become less likely to progress to chronic forms as the age of the patient increases, with rates of progression approaching 90% in vertically transmitted cases of infants compared to 1% risk in young adults. overall, the five-year survival rate for chronic hepatitis b ranges from 97% in mild cases to 55% in severe cases with cirrhosis. most patients who acquire hepatitis d at the same time as hepatitis b (co-infection) recover without developing a chronic infection. in people with hepatitis b who later acquire hepatitis d (superinfection), chronic infection is much more common at 80–90%, and liver disease progression is accelerated. chronic hepatitis c progresses towards cirrhosis, with estimates of cirrhosis prevalence of 16% at 20 years after infection. while the major causes of mortality in hepatitis c is end stage liver disease, hepatocellular carcinoma is an important additional long term complication and cause of death in chronic hepatitis. rates of mortality increase with progression of the underlying liver disease. series of patients with compensated cirrhosis due to hcv have shown 3,5, and 10-year survival rates of 96, 91, and 79% respectively. the 5-year survival rate drops to 50% upon if the cirrhosis becomes decompensated. epidemiology hepatitis a hepatitis a is found throughout the world and manifests as large outbreaks and epidemics associated with fecal contamination of water and food sources. hepatitis a viral infection is predominant in children ages 5–14 with rare infection of infants. infected children have little to no apparent clinical illness, in contrast to adults in whom greater than 80% are symptomatic if infected. infection rates are highest in low resource countries with inadequate public sanitation and large concentrated populations. in such regions, as much as 90% of children younger than 10 years old have been infected and are immune, corresponding both to lower rates of clinically symptomatic disease and outbreaks. the availability of a childhood vaccine has significantly reduced infections in the united states, with incidence declining by more than 95% as of 2013. paradoxically, the highest rates of new infection now occur in young adults and adults who present with worse clinical illness. specific populations at greatest risk include: travelers to endemic regions, men who have sex with men, those with occupational exposure to non-human primates,