Clinical features of Wilson disease: Analysis of 10 cases.

AIM: The diagnosis of Wilson disease is based on the results of several clinical and biochemical tests. This study aimed to clarify the clinical features and spectrum of Wilson disease, including severe Wilson disease. METHODS: Between 1985 and 2009, 10 patients with clinical, biochemical or histological evidence of Wilson disease were either diagnosed or had a previously established diagnosis confirmed at Fukuoka University Hospital. Severe Wilson disease was defined by a serum prothrombin time ratio of more than 1.5 or serum prothrombin activity of less than 50%. The 10 Wilson disease patients were divided into two groups, one containing three non-severe patients and the other containing seven severe patients, and the biochemical features of the patients in these two groups were compared. RESULTS: The mean age at diagnosis was 21.5 ± 11.7 years (range, 7-39). Decreased serum ceruloplasmin, enhanced 24-h urinary copper excretion, presence of Kayser-Fleischer rings and histological signs of chronic liver damage were confirmed in 100%, 100%, 66.7% and 100% of patients, respectively. Severe Wilson disease patients had higher levels of serum ceruloplasmin and serum copper (P < 0.05, P < 0.05, respectively) than non-severe patients. CONCLUSION: In severe Wilson disease patients, the serum ceruloplasmin and serum copper levels were higher than those in non-severe Wilson disease patients.

Alternative transporter pathways in patients with untreated early-stage and late-stage primary biliary cirrhosis.

BACKGROUND/AIMS: The hepatic expression of bile acid transporters is altered in experimental cholestasis and it is unclear whether regulation exists in human cholestatic diseases. We investigated the expression of genes involved in bile acid detoxification, basolateral export and nuclear factor regulation in untreated primary biliary cirrhosis (PBC). METHODS: Liver tissues were obtained from patients with early-stage and late-stage PBC. The hepatic expression levels of messenger RNAs were determined by the real-time reverse transcription polymerase chain reaction. RESULTS: The hepatic expression of multidrug-resistance protein 4 messenger RNA was significantly upregulated in early-stage and late-stage PBC patients compared with controls. The hepatic expression of multidrug-resistance protein 2 and multidrug-resistance protein 3 messenger RNAs was significantly elevated only in early-stage PBC patients. The hepatic expression levels of farnesoid X receptor, fetoprotein transcription factor and constitutive androstane receptor mRNAs were correlated with those of multidrug-resistance protein 2, multidrug-resistance protein 3 and multidrug-resistance protein 4 respectively. CONCLUSIONS: The hepatic expression of multidrug-resistance protein 4 was enhanced in patients with untreated PBC at all stages. However, the hepatic expression of multidrug-resistance protein 2 and multidrug-resistance protein 3 was enhanced only in early-stage patients. The lack of upregulation of these proteins might contribute to the progression of PBC.

Budd-Chiari syndrome: two cases with different courses.

We report two cases of Budd-Chiari syndrome. Case 1: A 57-year-old man presented with leg edema and esophageal varices. Cavography showed obstruction of the inferior vena cava with antiphospholipid syndrome. Further, the patient showed positive serology for hepatitis C virus and consumed large quantities of alcohol. Percutaneous transluminal angioplasty was performed on this patient and anticoagulants administered; leg edema and esophageal varices were ameliorated although liver biopsy showed cirrhosis without evident congestion. More than 9 months since the diagnosis, restenosis of the inferior vena cava has not occurred. Case 2: A 73-year-old woman presented abdominal pain but no edema or varices. Cavography showed membranous obstruction of the inferior vena cava which required no therapy. Manifestation of portal hypertension was not present and liver function was maintained although liver biopsy showed obvious congestion. These cases showed untypical features against histopathology, and careful observation will be required for emergence of hepatocellular carcinoma.

Combination therapy of lamivudine and adefovir in Japanese patients with chronic hepatitis B.

PURPOSE: This study aimed to clarify the long-term efficacy of the lamivudine treatment in Japanese patients with chronic hepatitis B either with or without lamivudine resistance or with or without adefovir add-on treatment. METHODS: We followed 110 patients who received lamivudine for more than 12 months, including 67 hepatitis B e antigen (HBeAg)-positive and 43 HBeAg-negative patients. RESULTS: The median follow-up after the onset of lamivudine was 48 (range = 12-86) months. In all the patients with or without lamivudine resistance, the level of alanine aminotransferase (ALT) normalization decreased from 70.0% at 1 year to 36.4% at 5 years and the loss of serum HBV DNA level decreased from 72.7% at 1 year to 31.8% at 5 years. Sixty patients (54.6%) developed a lamivudine-resistant mutation, and this occurrence was more frequently observed in those who were HBeAg-positive (P < 0.01), those with a low level of ALT (P < 0.05), and those with a high level of serum HBV DNA (P < 0.01). Thirty-six of 60 patients received adefovir in addition to lamivudine to treat breakthrough hepatitis. A Cox proportional hazards model analysis revealed the level of baseline HBV DNA to be the best predictive factor for the virus recrudescence (risk ratio = 0.466, 95% confidence interval [CI]: 0.246-0.842, P = 0.011) and the breakthrough hepatitis (risk ratio = 0.444, 95% CI: 0.218-0.879, P = 0.019). We carefully monitored the efficacy of this treatment both in patients who received adefovir and in those who did not since the beginning of the lamivudine treatment. The normalization level of ALT was 61.4% at 5 years and the loss of serum HBV DNA was 61.4% at 5 years since lamivudine was started. A histologic improvement was observed in patients with ALT levels less than two times the upper limit of normal at the time of a second liver biopsy. CONCLUSIONS: Although the efficacy of lamivudine is limited because of breakthrough hepatitis, adefovir was used as a salvage treatment of patients with lamivudine-resistant chronic hepatitis B. In addition, lamivudine was used for the treatment of Japanese patients with chronic hepatitis B with or without lamivudine resistance, and was found to be useful regarding the long-term virologic and biochemical responses.

Nonalcoholic steatohepatitis associated with psoriasis vulgaris.

A 24-year-old man was admitted to our hospital because of liver dysfunction. He had been diagnosed as having psoriasis vulgaris at 18 years of age. Physical examination demonstrated obesity, general erythema, and hepatomegaly. Laboratory data revealed elevated serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and glucose. A histological examination of the liver revealed macrovesicular fatty change and infiltration of inflammatory cells, including lymphocytes and polymorphonuclear cells, within the liver lobules. Pericentral fibrosis and pericellular fibrosis were also recognized. He was diagnosed as having nonalcoholic steatohepatitis (NASH), based on the fact that he had no habit of drinking alcohol, as well as psoriasis vulgaris and diabetes mellitus. We herein report a very rare case of NASH associated with psoriasis vulgaris.