What's the Take Home?

A 52-Year-Old Man with Jaundice

Ronald N. Rubin, MD
Volume 65 - Issue 10 - October 2025

  • Correct answer: D. Regardless of acute scoring schemes or therapies provided, the main factor for long-term survival is prolonged abstinence.

    Discussion. The presented patient clearly has some form of significant liver disease with an acute-to-subacute presentation. He is jaundiced—a red flag finding for significant liver disease—and his associated findings are tender hepatomegaly, ascites, spider telangiectasias, and obtundation with asterixis consistent with mild hepatic encephalopathy.

    This biochemistry demonstrates typical findings of liver failure with hyponatremia, hypoalbuminemia, elevated INR consistent with synthetic hepatic failure. Finally, and importantly, there is a strong background of past and ongoing prodigious, excessive alcohol abuse and the classic definite, yet not extreme, transaminase elevations with AST/ALT ratio greater than 2 to 1. In summary, he is very typical for the diagnosis of chronic alcoholic liver disease punctuated by onset of acute alcoholic hepatitis.

    Acute alcoholic hepatitis is a serious entity characterized by the acute onset of worsening liver disease superimposed upon pre-existing alcoholic liver disease with rapid worsening of liver failure, multi-organ failure, and an alarming 90-day mortality of 20% to 50% in severe cases.1,2

    Unfortunately, keywords of "unknown" and "poorly understood" characterize the demographics and pathophysiology of acute alcoholic hepatitis. Why this acute complication occurs in some, but not all, patients is unknown, but it is overrepresented in women and Hispanics.1 The pathophysiology is poorly understood with myriad suspected alcohol-induced abnormalities including excessive alcohol metabolites of acetaldehyde accumulation with resultant lipid peroxidation (e.g., the fatty liver of alcoholism) and abnormal multiple hyperactivation of inflammatory cytokines and other pathways.1 These complexities are not so neatly documented or explained, in contrast to, for example, diabetic ketoacidosis. Even recent scholarly reviews1,2 offer only postulates.

    The diagnosis of acute alcoholic hepatitis is generally straightforward and utilizes clinical findings of history, physical examination, and basic laboratory findings. The patient will usually present with a core history of alcohol abuse, often with friends or family noting increased usage and decreased functioning by the patient in recent weeks. Authoritative reference groups use the following criteria:

    1. Onset of jaundice within the previous 8 weeks.
    2. Ongoing use of alcohol with more than three drinks/day for women and more than four drinks/day for men, with less than a 60-day abstinence period before the onset of jaundice.
    3. Bilirubin above 3.0 mg/dl.
    4. AST level above 50 IU/L, AST/ALT ratio greater than 1.5, and both AST and ALT less than 400 IU/L.
    5. Exclusion of other causation (eg, viral hepatitis, obstructive jaundice, autoimmune hepatitis).1,2
       

    Confirmation with liver biopsy (Answer A) is infrequently required except for complex cases involving transaminases that are above 400 IU/L, hepatotoxins such as acetaminophen in the history, or when an alcohol history is obtained from either the patient or family is uncertain.

    In biopsy cases, the transjugular approach is preferred and reveals the classic PMN infiltration, ballooned hepatocytes, and Mallory hyaline bodies. But such biopsy will only be needed in a very small percentage of cases, so Answer A is not optimal here.

    Therapy and management. There are two abiding overall strategies needing attention in cases of alcoholic hepatitis:

    1. How to keep the patient alive for the 30+ days required for adequate alcohol abstention and the intrinsic healing process of the liver to occur.
    2. How to attain long-term survival.

    The current literature describes a 20% to 50% acute (90-day) mortality in severe cases of alcoholic hepatitis and an unfortunate replay in many patients who do initially survive.

    Generally, the therapeutics involve extreme intensive care unit (ICU) care for all acute episodes, followed by behavioral therapy focused more on alcohol cessation than the liver itself. The emergence of early liver transplantation in acute alcoholic hepatitis has now materialized as a methodology that melds the acute and chronic long-term strategies, helping to keep the patient alive acutely and offering bona fide long-term mortality benefit out to 5 years and counting.3,4

    Specific therapy continues to involve corticosteroids, which have stood the test of time. It is acknowledged and supported by multiple studies that corticosteroids, specifically prednisolone 40 mg IV daily for 4 weeks, have a statistical benefit for survival in severe alcoholic hepatitis at 30 days. Unfortunately, there is no longer-term benefit in the steroid group versus controls at 60–90 days.5,6

    Over time, the development of the MELD scoring system at initial diagnosis has defined which patients benefit from prednisolone therapy—namely those with MELD scores between 20–39.1,7. Such patients should be started on steroids, then re-evaluated at day 7 using another scoring system, LILLE, to confirm response or lack thereof. A LILLE score below 0.45 indicates response and continuation of steroids for the full 4 weeks.

    Over the years, other therapies—specifically pentoxifylline and N-acetylcysteine in attempts to dampen intrahepatic injury and inflammation—have been evaluated but do not add to steroid efficacy.1 Meanwhile, in this acute treatment phase, careful monitoring and supportive therapeutics in the ICU setting are required to keep the patient alive and free from (or addressing) the difficult ancillary complications and needs of these very sick patients. Three of the main required tactics are nutrition, infection monitoring and control, and renal and/or electrolyte management required to avoid acute renal injury. Both infection and acute renal injury are documented to increase mortality very significantly in the critical initial 30-day period.1,2

    What about patients not responsive to steroids and those who survive longer term? This is where early liver transplantation as a strategy has come into play. Traditionally, patients with alcoholism were not considered candidates for transplantation until they could prove abstinence for more than 6 months, because the transplant community did not want to use these precious organs in relapsing alcoholics. However, severe cases have up to a 50% mortality at 90 days in the acute event—so many never even get a chance to achieve the 6-month abstinence goal.

    In carefully selected cases when liver transplantation is used early, within the initial 90-day period of acute alcoholic hepatitis prednisolone failures, it works—with decreased early mortality and overall mortality benefit extending out 5 years.3,4

    When properly selected, the alcohol relapse rate in the transplant group is manageable and reasonable: 10% at 1 year and 20% at 3 years, with overall benefits in liver morbidity and mortality at 2 years similar to post-transplantation results in patients who had completed the 6-month abstinence rule.3

    Patient follow-up. The patient was transferred to the ICU for management. There was agreement that the clinical findings sufficed to diagnose acute alcoholic hepatitis without need for transjugular liver biopsy, which makes Answer A incorrect.

    Enteral feedings with appropriate caloric and protein administration were initiated. Echo-guided fine-needle sampling of the ascites was negative for elevated WBC or organisms, excluding spontaneous peritonitis.

    Careful fluid management with monitoring of intake, output, blood pressure, and renal function was undertaken. Urine output remained good. MELD score was calculated to be 28, so prednisolone 40 mg IV/day was started.

    Since it was realized that liver transplantation issues would be difficult to navigate in a patient with alcohol-related hepatitis, inquiries along those lines were initiated early on. Although hepatic studies did not improve, his clinical status remained essentially stable, and a calculation of his LILLE model at day 7 was 0.38. Thus, prednisolone was continued, and in the ensuing 2 weeks, marked clinical and biochemical improvement was seen. He completed a 4-week course and was discharged to home care.

    He does have a supportive family and good health insurance such that behavioral and pharmacotherapy for alcoholism will be put into place. He was well and without alcohol relapse at his 3-month evaluation.

    What’s the Take Home? Acute alcoholic hepatitis is a severe and life-threatening complication of alcoholic liver disease. It can be defined and diagnosed using clinical parameters—e.g., jaundice onset within the previous 6 weeks; ongoing heavy alcohol consumption of more than 6 months; serum bilirubin greater than 3.0 mg/dl; AST/ALT transaminases with ratio above 1.5 but with both levels under 400 IU—and appropriate exclusion of other diagnoses such as viral hepatitis and biliary obstruction.

    In complex cases with questionable alcohol histories, the diagnosis can be made by transjugular liver biopsy featuring ballooned hepatocytes, PMN infiltration, and classical Mallory bodies. The illness is dangerous with a 20% to 50% 90-day mortality rate in hospital-requiring cases and a 20% one-year mortality even in more moderate cases.1

    In severe cases, there exist validated schemes to estimate prognosis as well as guide therapy. The classical MELD score is an excellent static evaluation for prognosis and management decisions, whereas the LILLE score at day 7 is a good dynamic evaluator of disease pace and response to therapy. Thus, Answer B is not correct.

    There is essentially one specific therapeutic for severe alcoholic hepatitis—glucocorticoids. Appropriate ancillary maneuvers include adequate enteral nutrition, monitoring for and treating coincident infection, and professional renal/electrolyte care to avoid acute kidney injury.

    An ongoing and evolving issue in therapy is the use and role of hepatic transplantation in the early, acute setting. Traditionally, the transplant community required 6 months of documented alcohol abstinence, which is too late for many patients.

    If we can and do liver transplantations for steatohepatitis (now the leading liver transplant indication in the United States) related to obesity—a behavior causation situation—and if we now routinely CT screen for lung cancer in heavy smokers—another behavior causation situation—then how can we ignore the science of what is good therapeutics in alcoholic liver disease because we "disapprove" of the behavior that caused it?

    AUTHOR
    Ronald N. Rubin MD1,2

    AFFILIATIONS
    1Lewis Katz School of Medicine at Temple University, Philadelphia, PA
    2Department of Medicine, Temple University Hospital, Philadelphia, PA

    CITATION
    Rubin RN. A 73-year-old man with febrile illness. Consultant. 2025;65(9):DOI:10.25270/con.2025.09.000002

    DISCLOSURES
    The author reports no relevant financial relationships.

    CORRESPONDENCE:
    Ronald N. Rubin, MD, Temple University Hospital, 3401 N. Broad Street, Philadelphia, PA 19140 (blooddocrnr@yahoo.com)

    References

    1. Dattaler R, Arab JB, Shah VH. Alcohol-associated hepatitis. N Engl J Med. 2022;387(26):2436-2448. doi:10.1056/NEJMra2207599
    2. Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease: a review. JAMA. 2021;326(2):165-176. doi:10.1001/jama.2021.7683
    3. Lee BP, Chen PH, Haugen C, et al. Three-year results of a pilot program in early liver transplantation for severe alcoholic hepatitis. Ann Surg. 2017;265(1):20-29. doi:10.1097/SLA.0000000000001831
    4. Lee BP, Mehta N, Platt L, et al. Outcomes of early liver transplantation for patients with severe alcoholic hepatitis. Gastroenterology. 2018;155(2):422-430. doi:10.1016/j.gastro.2018.04.021
    5. Porter HP, Simon FR, Cope CE II, Volwiler W, Forster LF. Corticosteroid therapy in severe alcoholic hepatitis: a double-blind trial. N Engl J Med. 1971;284(24):1350-1355.
    6. Maddrey WC, Boitnott JK, Bedine MS, Weber FC Jr, Mezey E, White RJ Jr. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology. 1978;75(2):173-179.
    7. Morales-Arráez D, Ventura-Cots M, Altamirano J, et al. The MELD score is superior to the Maddrey discriminant function score to predict short-term mortality in alcohol-associated hepatitis: a global study. Am J Gastroenterol. 2022;117(2):301-310. doi:10.14309/ajg.0000000000001596