151, 152 Megamitochondria in alcoholic hepatitis may be associated with a milder form of AH, a lower incidence of cirrhosis and fewer complications with a good long-term survival.153 AH is associated with perivenular and pericellular fibrosis which may be a harbinger of future cirrhosis, especially in patients who continue to abuse alcohol or those who are coinfected with hepatitis C virus.33, 154 Mallory bodies, Bcl-2 inhibitor giant mitochondria, neutrophilic

infiltration, and fibrosis may be seen in conditions other than ALD.155 Although a liver biopsy may not be practical in the management of all patients, it has been shown that physicians’ clinical impression may correlate only moderately well with the histologic findings on liver biopsy. Studies that have included a liver biopsy in all patients with presumed AH have shown histologic confirmation in only 70%-80% of patients.156 The incentive to make a definitive histologic diagnosis, however, is partly dependent on the possible risks of a biopsy, as well as the risks involved with particular treatments. If no treatment for ALD or AH is contemplated, based on noninvasive estimates of an individual patient’s prognosis, it usually is not necessary to make a histologic

diagnosis. Alternatively, if an investigational treatment or a therapy with associated risk is contemplated, the risk-benefit ratio involved in pursuing a liver biopsy may change. Recommendation: 1 Clinicians should discuss alcohol use with patients, and any suspicion of possible abuse Talazoparib research buy or excess should prompt use of a structured questionnaire and further evaluation (Class I, level C). Decisions regarding treatment are critically dependent on the ability to estimate a given patient’s prognosis. Many individual clinical and laboratory features, many along with specific histologic features have also been tested as measures of disease prognosis. In AH, the Maddrey discriminant function (MDF), a disease-specific

prognostic score, has been used to stratify a patient’s severity of illness.157 The initial formula was derived in the context of clinical trials of alcoholic hepatitis, and later modified to: MDF = 4.6 (Patient’s prothrombin time − control prothrombin time) + total bilirubin (mg/dL).158 Patients with a score of greater than or equal to 32 were at the highest risk of dying, with a one month mortality as high as 30%-50%.151 In particular, those with evidence of both hepatic encephalopathy and an elevated MDF were at highest risk. Although relatively easy to use, and based on standard laboratory tests, several drawbacks to the use of the MDF have been noted. Although it is a continuous measure, its interpretation (using a threshold of 32) has converted it into an essentially categorical method of classification. Once patients have exceeded that threshold, their risk for dying is higher, but not specified.