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We report a case of fatal fulminant liver failure complicating Wilson's disease that is unique in several respects. The illness supervened after several years of medical noncompliance in a patient who had been previously diagnosed and successfully treated with penicillamine. Re-institution of penicillamine therapy 2 weeks prior to the fulminant decompensation failed to prevent it. Renal failure in this patient was apparently secondary to rhabdomyolysis. Addition of penicillamine to a peritoneal dialysis solution allowed chelation and removal of over 14 mg per day of copper but without apparent benefit. Exchange transfusion and high dose dexamethasone therapy (24 mg/day) were equally ineffective in reversing the liver failure. Other reported cases have also been fatal. The best treatment for fulminant Wilson's disease is prevention by diagnosis in a pre-symptomatic stage and institution of carefully supervised life-long therapy with penicillamine.

Aim/Background: The spectrum of histopathological features in non-alcoholic fatty liver disease (NAFLD) has been well described. At least two scoring systems have been established. We propose here a system in which numerical scores are obtained using the different features. Methods: Twenty-five cases of well-defined NAFLD were idengified. Two pathologists blinded to idengifiers and clinical data independently scored the liver biopsies twice for portal fibrosis (PF: 0–6), lobular inflammation and necrosis (LIN: 0–3), Mallory bodies (MB: 0–3), hepatocyte ballooning (HB: 0–3), perisinusoidal fibrosis (PSF: 0–3) and fatty change (FC: 1–4). The κ statistic tested observer concordance. Non-parametric measures of correlation and hierarchical cluster analysis were used to elaborate a grading system. Results: A broad spectrum of NAFLD was observed. Intra- and interobserver concordance was satisfactory. An activity score was created (AS: 0–12) as the sum of LIN, MB, HB and PSF, but not FC. A system for severity of NAFLD was developed: Grade 1 (PF: 0–2 and AS: 0–4), Grade 2 (PF: 3 or AS: 5–7) and Grade 3 (PF: 4–6 or AS: 8–12). Diabetes, elevated alkaline phosphatase and decreased platelets were associated with advanced grade. Conclusions: This simple, reproducible NAFLD score produces a three-tier severity grade. This numerical system may prove useful in assessing disease severity and interval changes.

Gastrointestinal stromal tumors (GIST), although the most common mesenchymal neoplasms of the gastrointestinal (GI) tract, account for

Background: Abnormal methionine metabolism occurs in animals fed ethanol and in end-stage cirrhotic patients. Expected consequences of these abnormalities include reduced hepatic S-adenosylmethionine and glutathione (GSH) levels, impaired transmethylation, and reduced homocysteine catabolism, resulting in the often-observed hyperhomocystinemia in cirrhotic patients. These parameters have not been examined simultaneously in patients with less advanced alcoholic liver disease. Methods: Six patients hospitalized for alcoholic hepatitis were studied. Plasma was analyzed for homocysteine, methionine, and GSH levels. Liver biopsies diagnosed acute alcoholic hepatitis and underlying fibrosis. Liver specimens were processed for messenger RNA (mRNA) levels and various metabolites and were compared with those of six normal controls. Results: Three patients had cirrhosis, and three had only portal fibrosis. Plasma levels of homocysteine and methionine were increased in two of the three patients with cirrhosis but not in the patients with fibrosis. All patients had markedly lower plasma GSH levels (mean ± SD: 0.27 ± 0.19 μM, which is at least 10-fold lower than the normal range). Hepatic S-adenosylmethionine levels were reduced by 50%, whereas methionine, GSH, and cysteine levels were reduced by 70–80%. The mRNA levels of most enzymes involved in methionine metabolism and GSH synthesis were decreased, whereas albumin expression was unchanged. Despite the well known induction of cytochrome P450 2E1 in chronic alcoholics, its mRNA levels were nearly 70% lower in these patients. Conclusions: In alcoholic hepatitis, abnormal hepatic gene expression in methionine and GSH metabolism occurs and often contributes to decreased hepatic methionine, S-adenosylmethionine, cysteine, and GSH levels. It may be important to replenish these thiols in patients hospitalized with alcoholic hepatitis.

We report a case of "naturally-occurring" (nonred blood cell stimulated) anti-K1. The patient had never received a blood transfusion. Red blood cell antibody screening panels showed agglutination with K:1 red blood cells at room temperature and not in the anti-globulin test. Testing with 2-mercaptoethanol showed the antibody to be IgM. The antibody is "naturally-occurring" and may be associated with pulmonary tuberculosis.