Woman With Jaundice,Anorexia, and Abdominal Pain

A 52-year-old woman is hospitalized because she has had jaundice, anorexia, and occasional nausea and vomiting for about 2 weeks. She has also had moderate pain in the epigastrium and right upper quadrant, but it has not been severe enough to require analgesics. She denies hematemesis and hematochezia.HISTORY
Until now, the patient has been healthy; she takes no medications. However, she drinks about half a bottle of whiskey per day and likely consumes more on weekends. She does not smoke and has never abused drugs. During the month before admission, she has been depressed; she has engaged in binge drinking, has eaten very little, and has missed work for the past 2 weeks.PHYSICAL EXAMINATION
Temperature is 38.2^oC (100.8^oF); heart rate, 108 beats per minute; and blood pressure, 130/75 mm Hg. Oxygen saturation on room air is normal. No lymphadenopathy or oral lesions are noted, but mucous membranes are dry. Two spider angiomata are present on the left shoulder. Heart and lungs arenormal. Abdomen is soft, with good bowel sounds and no appreciable ascites. There is tender hepatomegaly; the liver edge is palpable 4 finger-widths below the ribs and crossing into the midline. Below the knees, 2+ edema is present. Mentation is slow but oriented. Stool is heme-negative on 2 examinations. The morning after admission, asterixis is noted.LABORATORY AND IMAGING RESULTS
Hemoglobin level is 10.5 g/dL. White blood cell count is 19,000/μL with90% neutrophils and a slight left shift. Mean corpuscular volume is 105 fL.Serum sodium level is 112 mEq/L; chloride level, 91 mEq/L; and potassiumlevel, 3.4 mEq/L. Creatinine level is 1.7 mg/dL and blood urea nitrogen level,29 mg/dL. Bilirubin level is 22 mg/dL; alkaline phosphatase level, 673 U/L;aspartate transaminase (AST) level, 211 U/L; and alanine transaminase (ALT)level, 55 U/L. Prothrombin time (PT) is 27 seconds, and INR is 2.3 (with acontrol PT of 12 seconds). Abdominal ultrasonography reveals significant hepatomegalyand moderate splenomegaly, no gallstones or dilated bile ducts, apatent portal vein, and no ascites.Which of the following is the most appropriate next step?A.Urgent surgical consultation for cholecystectomy and bile duct exploration.B.Detailed blood testing for hepatitis C genotype and viral load titer.C.Prompt, aggressive diuresis with loop diuretics.D.Administration of corticosteroids and pentoxifylline (after infection is excluded by appropriate cultures and studies).CORRECT ANSWER: D
This patient's history strongly suggests alcoholic liver disease. The quantity andduration of alcohol ingestion correlate with the development of alcoholic liverdisease (alcoholic steatosis, hepatitis, and cirrhosis), although it is impossibleto predict with certainty which patients will have hepatic complications. It haslong been thought that the consumption of 80 g of alcohol (approximately 7 ozof hard liquor or seven 12-oz beers) daily for 10 to 12 years was necessary toproduce significant hepatic injury. However, recent data suggest that theamount of alcohol required may be significantly less, especially in women (4 ozof hard liquor daily for men, 1 to 2 oz for women).¹Characteristic features of alcoholic hepatitis.Affected patients typicallypresent with fever, change in mental status, increased abdominal girth, abdominalpain, nausea, vomiting, jaundice, edema, and rash. Physical findings may includeasterixis, hepatosplenomegaly, ascites, caput medusae, telangiectasia, andguaiac-positive stool. Pertinent laboratory findings include hyperbilirubinemia,elevated AST/ALT levels in a ratiogreater than 2:1, leukocytosis (particularlyneutrophilia), anemia, thrombocytopenia,coagulopathy (manifestedby an increased PT), rising serumcreatinine level, hypoglycemia, and elevatedammonia level.Useful tests.In this patient, anabdominal ultrasonogram showedno gallstones or dilated bile ducts.Thus, her jaundice is nonobstructive,and a surgical consultation for cholecystectomyand bile duct exploration(choice A) is inappropriate.When alcoholic hepatitis is suspected,obtain viral hepatitis serologies--particularly for hepatitis C; infectionappears to be strongly linkedwith rapid progression of alcoholicliver disease.¹However, additional testing to determine hepatitis C viral loadand genotype (choice B) is not necessary at this point, especially in an acutelyill patient.Consider biopsy to confirm the diagnosis of alcoholic hepatitis and to definetreatment options. However, biopsy may not always be practical (eg,when coagulopathy is present) or necessary (eg, when alcoholic hepatitis isstrongly suspected based on laboratory values, imaging results, and physicalfindings).Treatment.Initial therapy for alcoholic hepatitis is largely supportive; itincludes nutritional supplementation and abstinence from alcohol, with appropriateprophylaxis for delirium tremens. Whether adjunctive drug therapy iswarranted depends on disease severity. Patients with a serum bilirubin level ofless than 5 mg/dL have a 1-month survival of 100% and a 3-year survival of78%; these patients generally require no pharmacologic treatment.Among patients with severe disease, inpatient mortality may be as highas 65%. Research suggests that severely ill patients may be fairly reliably identifiedby a discriminant function (DF) greater than 32.^2,3 DF is defined as: [4.6 *(PT - control time)] + serum bilirubin level [in mg/dL].In patients with alcoholic hepatitis who have a DF greater than 32, the 2-month mortality is 50%.¹Clinical trials demonstrated that corticosteroids significantlyreduced 1-month mortality in patients with alcoholic hepatitis who hada DF greater than 32, spontaneous hepatic encephalopathy, or both (thosewith acute infection or GI bleeding were excluded).^2,3 Another study of prednisolonesuggests that a circulating neutrophil count of greater than 5500/μLmay be used in place of encephalopathy as a marker for severe disease becausethis value correlates with neutrophilic inflammation on liver biopsy.⁴Despitegood short-term survival benefits, long-term data (follow-up longer than1 year) on the efficacy of corticosteroids in this setting are not yet available.Pentoxifylline, which may enhance red blood cell deformability and hepaticblood flow, also reduces mortality in patients with severe alcoholic hepatitis.⁵Thus, for patients with a DF greater than 32 plus either encephalopathyor a circulating neutrophil count greater than 5500/μL, corticosteroids may increaseshort-term survival. These agents are contraindicated in patients withacute infection--except viral hepatitis and HIV infection or AIDS--or activeor threatened GI bleeding. Pentoxifylline may also be beneficial, especially inthose who are unable to tolerate corticosteroids. Because this patient meetsthe criteria for adjunctive drug therapy (her DF is 91--accompanied by asterixisand a neutrophil count of 17,100/μL), choice D is the most appropriatenext step.This patient has severe hyponatremia. However, overly aggressive diuresis(choice C) in this setting--in which the creatinine level is elevated--caninitiate hepatorenal syndrome and worsen the situation.Outcome of this case.Prednisolone and pentoxifylline were started onday 2 of the patient's hospitalization. Fluid management corrected her serumsodium level to 124 mEq/L. PT and liver function parameters were unchanged.Overall, her sensorium remained intact, and she reported feeling "better." Onday 4, coffee-ground emesis and hypotension developed, and intubation andpressor therapy were initiated. Broad-spectrum antibiotics were also given empirically.On day 6, the patient became asystolic and died.

References:

REFERENCES:

1.

Menon DV, Gores GJ, Shah VH. Pathogenesis, diagnosis, and treatment of alcoholic liver diseases.

MayoClin Proc.

2001;76:1021-1029.

2.

Obeirne J, Patch D, Holt S, et al. Alcoholic hepatitis-the case for intensive management.

Postgrad Med J.

2000;76:504-507.

3.

McCullough AJ, O’Connor JFB. Alcoholic liver disease: proposed recommendations for the American Collegeof Gastroenterology.

Amer J Gastroenterol.

1998;93:2022-2036.

4.

Ramond MJ, Poynard T, Rueff B, et al. A randomized trial of prednisolone in patients with severe alcoholichepatitis.

N Engl J Med.

1992;326:507-512.

5.

Akriviadis E, Botla R, Briggs W, et al. Pentoxifylline improves short-term survival in severe acute alcoholichepatitis: a double blind, placebo-controlled trial.

Gastroenterology.

2000;119:1637-1648.