Seiji Nakanishi

Recent clinical features of Wilson’s disease with hepatic presentation

BackgroundWe carried out this study to evaluate recent clinical features of Wilson’s disease (WD) with hepatic presentation, especially in terms of age, degree of liver injury, and association with hepatocellular carcinoma (HCC).MethodsSixteen patients with hepatic manifestations were diagnosed with WD in the period 1976–2003. We divided this period into two periods, “past” and “recent”. The diagnosis was based on the presence of Kayser-Fleisher rings, low serum copper levels, low serum ceruloplasmin levels, increased urinary copper concentrations before or after D-penicillamine challenge, and increased hepatic copper concentrations. This retrospective study was done at Ehime University Hospital.ResultsFour patients, including a pair of siblings, had a family history of WD. Four patients had parental consanguinity. There were 6 patients aged over 40 years in the recent period, whereas no patients in the past period were over 40. Four patients had neurological manifestations. Ten patients had liver cirrhosis and 5 had chronic hepatitis. Two had fatty liver without obesity. All patients in the past period had liver cirrhosis. Three patients with liver cirrhosis were found to have HCC during the follow up. All patients were treated with either D-penicillamine or trientine chloride, or both. However, four patients had to discontinue these agents due to the side effects.ConclusionsRecently, the number of patients diagnosed with WD has been increasing, not only in terms of those with classical-type WD but also in terms of elderly patients or patients with non-cirrhotic liver injury such as fatty liver and chronic hepatitis. The various clinical features of WD should be recognized and particular attention should focus on HCC as a complication.

Therapeutic efficacy of decreased nitrite production by bezafibrate in patients with primary biliary cirrhosis.

BackgroundThe therapeutic efficacy of bezafibrate, a hypolipidemic drug, has been shown in patients with primary biliary cirrhosis (PBC) in some pilot studies; however, little is known regarding the mechanism of action of bezafibrate in PBC. This study was conducted to evaluate the therapeutic efficacy, as well as to gain insight about the possible mechanism of action, of bezafibrate in PBC.MethodsSixteen patients with PBC were administered with bezafibrate (400 mg/day) either with (n = 10) or without ursodeoxycholic acid (UDCA; n = 6). The peripheral blood of these patients was collected before and at different times after therapy commencement, and antigen-presenting dendritic cells (DCs) were then cultured. The DCs were enriched and cultured with Staphylococcus aureus Cowan strain-1 for 48 h to evaluate their capacity to produce nitrite.ResultsOne month after the start of bezafibrate therapy, the serum levels of alkaline phosphatase (P = 0.0005), γ-glutamyl transpeptidase (P = 0.0006), total cholesterol (P = 0.0072), and immunoglobulin M (P = 0.0281) were decreased significantly compared to those before patients started bezafibrate therapy. The levels of nitrite produced by DCs decreased in all patients with PBC within 1 month of commencement of bezafibrate therapy. Moreover, decreased nitrite production by DCs was also seen when nitrite production was evaluated 1 year after the start of bezafibrate therapy.ConclusionsThis study reconfirms the therapeutic efficacy of bezafibrate in patients with PBC, including those with UDCA-resistant PBC. Downregulation of nitrite production by DCs may have some relationship with the therapeutic efficacy of bezafibrate; however, further study will be needed to clarify whether or not the antiinflammatory activity of bezafibrate is mediated through nitrite production.

Change of acute hepatitis B transmission routes in Japan.

Background. Many years have passed since various prophylactic policies for preventing hepatitis B virus (HBV) transmission were begun. We studied the chronological alterations in HBV infectious routes in patients with acute hepatitis B in the past 27 years. Methods. Seventy-two patients with acute HBV infection who were admitted to our hospital during the period 1976 to 2002 were enrolled in this study. This study was divided into two periods (first period, 1976–1990; and second period, 1991–2002), and the HBV infectious routes were studied. Results. Infectious routes have been changing. Posttransfusion hepatitis was seen only in the first period. In the second period, sexual transmission was the major infectious route (68%), followed by infection at a medical facility or occupational exposure such as needlestick injury (8%). Conclusions. Transmission from sexual contact has become the main infectious route of HBV in Japan.

Drug-induced hepatitis with hepatic granuloma due to saridon

A 38-year-old Japanese woman with no past history of liver disease developed liver dysfunction associated with fever, anorexia, and general malaise following the prolonged administration of saridon. A liver biopsy demonstrated multiple noncaseating epithelioid granulomas within hepatic lobules, with an inflammatory cell infiltrate of the lobular parenchyma and portal tracts. Viral markers and autoantibodies were negative. Lymphocyte stimulation tests for saridon and for isopropylantipyrine, one of the constituents of saridon, were positive, and therefore a diagnosis of drug-induced hepatitis due to administration of saridon was made. Her symptoms resolved and liver function test results returned to normal following discontinuation of the drug. The possibility of drug-induced hepatitis must be considered when liver dysfunction or systemic symptomatology develops during saridon therapy.

Clinical usefulness of quantitative evaluation of visceral fat by ultrasonography.

PurposeThe aim of this work was to evaluate the usefulness of a proposed method for visceral fat volume assessment by ultrasonography (US) in identifying those at risk of metabolic syndrome, and also to establish the most suitable cutoff level of waist circumference for the diagnosis of visceral adiposity.MethodsOne hundred and fifty-two outpatients with metabolic diseases such as hypertension, diabetes, or dyslipidemia were studied. The total visceral fat volume (total-VFA) was measured by computed tomography (CT), the visceral fat area at the level of the umbilicus was measured by CT (CT-VFA), and the visceral fat area was also measured by US (US-VFA), as we recently proposed.ResultsSignificant correlation coefficients were found between total-VFA and CT-VFA, US-VFA, and waist circumference in men but not in women. The correlation co-efficient between US-VFA and waist circumference was significantly positive in men and weakly positive in women. According to receiver–operator characteristic curves, the cutoff value of waist circumference yielding the maximal sensitivity plus specificity for predicting more than 100 cm2 of US-VFA was 85 cm in men and 84 cm in women. The change in US-VFA was significantly larger than that in waist circumference after a 6-month interval.ConclusionThe US-measured visceral fat area is more useful than waist circumference in a clinical setting.

Laparoscopic findings of liver cirrhosis due to non-alcoholic steatohepatitis

A 42‐year‐old Japanese man was admitted to our hospital for investigation of abnormal liver function tests. He had no history of drug use, and drank little alcohol. Body mass index was 30. Serum was negative for viral markers and autoantibodies. Laparoscopy revealed diffuse small nodules on the liver surface. Liver biopsy revealed small nodules with pericellular fibrosis and macrovesicular fat deposition throughout the acini. Some inflammatory changes were observed. Liver cirrhosis due to non‐alcoholic steatohepatitis (NASH) was diagnosed. NASH displays similar histological and laparoscopic characteristics to alcoholic liver diseases.

Predictors of treatment efficacy and ALT non‐normalization with sofosbuvir/ribavirin therapy for patients with hepatitis C virus genotype 2

The tolerability and efficacy of sofosbuvir and ribavirin in patients infected with hepatitis C virus (HCV) genotype 2 were investigated under actual clinical conditions. A total of 208 patients with chronic HCV genotype 2 infection were treated with sofosbuvir 400 mg and ribavirin (weight‐based dosing) for 12 weeks. Treatment discontinuation and sustained virological response 12 (SVR12) were evaluated. Moreover, factors associated with SVR12, hemoglobin decreasing to less than 10 g/dL during treatment, and alanine aminotransferase (ALT) non‐normalization after treatment were evaluated. In all patients, SVR12 responses were 96.1% (200/208). About 6 of 8 patients (3.8%) who did not achieve SVR12 were re‐treatment patients, and eight patients who did not achieve SVR all had liver cirrhosis. Multivariate analysis also identified body mass index (OR = 0.79; P < 0.001), platelet count (OR = 0.88; P = 0.003), and estimated glomerular filtration rate (eGFR) (OR = 0.96; P = 0.007) as independent contributing factors associated with hemoglobin decreasing to less than 10 g/dL during treatment, and only Mac‐2 Binding Protein Glycosylation isomer (M2BpGi) (OR = 2.46; P = 0.017) as an independent contributing factor associated with ALT non‐normalization after treatment. Cirrhotic patients may have a relatively high rate of treatment failure. In patients whose M2BpGi levels are elevated, their ALT tended to not normalize after treatment completion. These patients who did not achieve normalization of ALT after sofosbuvir plus RBV treatment need more careful observation for emergence of hepatocellular carcinoma even after achievement of SVR.

Sustained virological response of patients with hepatitis C virus genotype 2 depends on pegylated interferon compliance

Aim:  Patients infected with hepatitis C virus (HCV) genotype 2 are more sensitive to interferon (IFN) therapy than those infected with genotype 1, but 10–20% of patients do not achieve a sustained viral response (SVR) to combination therapy with pegylated (PEG) IFN and ribavirin (RBV). This study examines the prognostic factors associated with SVR in patients infected with HCV genotype 2 treated with PEG IFN and RBV.

PELIOSIS HEPATIS: IMPROVEMENT OF ESOPHAGEAL VARICES AFTER THE SURGICAL TREATMENT OF PLACENTAL SITE TROPHOBLASTIC TUMOR OF THE UTERUS

We report a case of peliosis hepatis associated with placental site trophoblastic tumor (PSTT) of the uterus. A 46‐year‐old woman was admitted to our hospital with complaints of leg edema, pleural effusion and ascites, complicated with esophageal varices. Peritoneoscopy did not show any evidence of liver cirrhosis and liver biopsy revealed peliosis hepatis. Later, uterine tumor was detected and, after a hysterectomy, peliosis hepatis and esophageal varices were dramatically improved. We suggest that the uterine tumor caused peliosis hepatis with fibrosis and that portal hypertension developed as a consequence of these lesions. The present case is of interest because esophageal varices were improved without ordinary treatment.

Predictors of hepatocellular carcinoma occurrence after direct-acting antiviral therapy in patients with HCV infection: Predictors of HCC after DAA therapy

The predictors for the development of hepatocellular carcinoma (HCC) after direct‐acting antiviral (DAA) treatment were investigated.