Rapidly Progressive Liver Failure in a 65-Year-Old Woman

A 65-year-old white woman was referred to New England Medical Center Hospital (NEMCH) for liver transplantation because of cirrhosis and worsening jaundice. She had initially presented to her private physician 13 months earlier complaining of epigastric discomfort. Upper gastrointestinal endoscopy revealed gastritis, for which she was given Sucralfate. She was next seen 2 months before referral because of jaundice. There was no fever, abdominal pain, nausea, vomiting, myalgias, or arthralgias. There was no history of blood transfusions, exposure to hepatitis, or alcohol abuse. Her only medications were Sucralfate and estrogen. Her history included an abdominal hysterectomy and appendectomy, both performed many years earlier. Results of a physical examination 2 months before referral were within normal limits except for scleral icterus and a liver edge that was palpated 5 cm below the right costal margin. Results of selected blood tests at that time were hematocrit, 38%; mean red blood cell volume, 90; white blood cell count, 8100; platelet count, 193,000; alanine aminotransferase (ALT), 400 III/L; aspartate aminotransferase (AST), 300 III/L; serum bilirubin, 6.9 mg/dL (118 Fmol/L); alkaline phosphatase, 166 III/L; albumin, 4 g/dL (40 g/L); and globulin, 4 g/dL (40 g/L). The prothrombin time, partial thromboplastin time, sodium, potassium, chloride, bicarbonate, blood urea nitrogen, and creatinine were all within normal limits. The results of the following tests were also negative or normal: hepatitis B surface antigen (HBsAg), anti-HBs, antibody to hepatitis B core antigen (anti-HBc), hepatitis A antibody, antimitochondrial antibody, antinuclear antibody, anti-smooth muscle antibody, serum iron, and serum transferrin. Abdominal ultrasonography showed a normal gallbladder, no gallstones, and normal-caliber intrahepatic and extrahepatic bile ducts. Abdominal computed tomography showed an enlarged spleen, normal pancreas, normal liver, and normal-sized bile ducts. A technetium sulfer-colloid scan showed splenomegaly and increased bone marrow uptake. The patient was then admitted to her local hospital. An endoscopic retrograde cholangiopancreatogram showed normal bile ducts and pancreatic duct. Colonoscopy was also performed, and results were unremarkable. A percutaneous liver biopsy demonstrated cirrhosis, widespread ballooning degeneration and necrosis of hepatocytes, many multinucleated hepatocytes, regenerating nodules, and an intense, mononuclear cell inflammation in the portal and periportal areas, The diagnosis was “cirrhosis with superimposed acute hepatic injury.” The cause of the liver disease was unclear, and the liver biopsy slides were sent to a university hospital pathologist for a second opinion. This resulted in a more detailed description of the histopathologic changes and a lengthy differential diagnosis but no specific diagnosis. Because of the uncertainty raised by the liver biopsy findings, no specific treatment was given. Rather, the patient was followed up at weekly intervals during which time the serum bilirubin concentration gradually increased to 33.1 mg/dL (966 kmol/L) and the prothrombin time to 16.2 seconds. The AST level fluctuated between 288 and 434 III/L and the ALT level between 184 and 246 III/L, both without any trend. The serum hematocrit decreased to 29% and the serum albumin level to 2.7 g/dL (27 g/L). The patient was now totally disabled. She had severe fatigue and anorexia and had lost 15 lb. The patient was advised that liver transplantation was her only hope. She was referred to NEMCH and seen the next day. When initially seen in the gastroenterology clinic of NEMCH, the patient was normotensive and looked chronically ill and wasted. Her skin and sclerae were intensely jaundiced. There were many large spider nevi over the thorax, neck, and face. Lymph nodes were not enlarged. The