Case 3 -

End-stage Alcoholic Liver Disease Schuyler Sanderson, Hospital Pathology Associates, Minneapolis, MN

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Clinical History 26 year old female presented to Emergency Department with leg pain and swelling. Physical examination revealed pitting edema, facial swelling, and a distended abdomen. Bright red blood was identified on rectal examination. The patient was in respiratory distress and continued to deteriorate requiring intubation. Abdominal imaging revealed fatty infiltration of the liver. Endoscopic examination (colonoscopy and EGD) revealed only small hemorrohoids without varices or other source of GI bleeding. The patient developed progressive hypotension and bradycardia within days of presenting to the Emergency Department. Resuscitation efforts failed and she was pronounced dead on hospital day 3. Pertinent Laboratory Data: Laboratory data on admission: AST: 89 (10-42) ALT: 23 (10-40) Alk P: 137 (34-104) Bili (T): 9.9 Ammonia: 135 (11-35) INR: 2.7 Ethanol: 0.225 (<0.010) Case 3 - Figure 1 This H&E stained section reveals a moderate degree of macrovesicular steatosis in the lobular parenchyma that shows general architectural disorder due to extensive pericellular fibrosis. There is only minimal mononuclear inflammatory cell inflammation but scattered apoptotic hepatocytes are identified. Occasional ballooned hepatocytes are present. Case 3 - Figure 2 This H&E stained section demonstrates a severely injury hepatic parenchyma. Ballooning degeneration, Mallory body formation, apoptotic hepatocytes, and scattered foci of canalicular bile plugging are apparent. Case 3 - Figure 3 This H&E stained section reveals a focus of sclerosing hyaline necrosis in this liver. The central vein (right lower corner) is mostly occluded and the surrounding parenchyma demonstrates necrosis with marked hepatocellular injury and fibrosis. Case 3 - Figure 4 This H&E stained section represents a region of lobular parenchyma with moderate hepatocellular injury. Ballooning degeneration and Mallory body formation are conspicuous. Case 3 - Figure 5 HE 5 Case 3 - Figure 6 The trichrome stained slide reveals marked pericellular fibrosis. Mallory bodies are readily identified as blue-gray amorphous structures in the injured hepatocytes Case 3 - Figure 7 The trichrome stained slide reveals marked pericellular fibrosis and Mallory bodies. Case 3 - Figure 8 The trichrome stained slide reveals sclerosing hyaline necrosis. Introduction: This is the case of a 26 year old female patient who presented to a local clinic with leg swelling, abdominal distension, and rectal bleeding while seeking a prescription refill and a general medical examination for a new job. During her very initial examination, the condition was considered serious enough to be directed to the local ED. She was promptly hospitalized and therapeutic interventions were offered. Her condition deteriorated rapidly and she died from complications of end-stage liver disease. The following is an explanation of findings in her autopsy case. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: The liver, at autopsy, demonstrated moderate macrovesicular steatosis associated with moderate necroinflammatory activity and cirrhosis. The necroinflammatory activity is manifest by prominent ballooning degeneration, abundant Mallory body formation, sparse lobular inflammation, and scattered degenerated or apoptotic hepatocytes. There is prominent and diffuse pericellular fibrosis and multifocal sclerosing hyaline necrosis identified. Differential Diagnoses: End-stage Alcoholic liver disease Wilson's disease Drug reaction Non-alcoholic fatty liver disease Final Diagnosis: End-stage Alcoholic Liver Disease Case Discussion: The clinical course for this patient was one of rapid deterioration following a rather chronic and severe suffering from alcoholic liver disease. The patient presented with manifestations of end-stage liver disease and had an elevated blood alcohol concentration. Despite efforts at counseling for substance abuse and administration of lactulose, prednisolone, and furosemide the complication of her liver damage were too severe. This patient reported significant alcohol consumption at age 18 and at times was consuming on average 1 liter of vodka per day. The morphologic findings in the liver clearly demonstrate an active steatohepatitis with cirrhosis. There is marked degeneration and Mallory bodies are easily recognized. The liver demonstrated sclerosing hyaline necrosis and cholestasis. The marked pericellular fibrosis and cirrhosis manifest clinically with portal hypertension through ascites and bleeding hemorrhoids. Her failing liver offered many clinical lab abnormalities typical for alcoholic cirrhosis. Her clinical history, which is critical in the diagnosis of alcoholic liver disease, unfortunately offers a sad a history of fatal alcohol abuse. Briefly, alcoholic liver disease is a complex disease process. The true prevalence of alcoholic liver disease is unknown but approximately 7.4% of US adults meet DSM-IV criteria for alcohol abuse/dependence [1]. Injury patterns in alcoholic liver disease may range from simple steatosis, alcoholic hepatitis, alcoholic foamy degeneration, and alcoholic cirrhosis. The morphologic features of alcoholic liver disease are previously well described [2]. Risk factors for alcoholic liver disease are diverse and prior studies have examined the dose of ingested alcohol. The variability in reporting and bias in these data has yielded significant differences in daily volumes associated with disease development. One study described the development of alcoholic liver disease in only 13.5% of studied people with very high daily intake (>120 g/day) [3]. Others describe an increased risk of developing cirrhosis with >60-80 g/day (men) and >20 g/day (women) over a ten year period [4]. The diagnosis of alcoholic liver disease is generally rendered clinically. Liver biopsy is recommended to confirm the diagnosis if there is clinical uncertainty or if medical treatment is contemplated [5]. The morphologic findings in alcoholic liver disease are not entirely specific and may be seen in other conditions [6]. Once the diagnosis is established, treatment decision need to be based upon prognosis for alcoholic liver disease. Several scoring systems have been developed, including the Maddrey discriminant function (MDF) [7], the combined clinical and laboratory index of the University of Toronto [8], the Beclere model [9], the MELD [10], and the Glasgo Alcoholic Hepatitis Score (GAHS) [11]. Therapy is directed against abstinence. Additional recommended therapies include nutritional support and steroids based upon disease severity as scored with one of the above described systems [5]. Conclusion(s): This is the case of a 26 year old female patient who died from alcoholic liver disease References: Alcohol use and alcohol use disorders in the United States: main findings from the 2001-2002 National Epidemiologic Survey on Alcohol Use and Related Conditions (NESARC). National Institutes of Health (U.S.); National Institute on Alcohol Abuse and Alcoholism (U.S.); CSR, Incorporated 2006 Bethesda, Md: National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. Lefkowitch JH. 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