Rumi Mifuji

Hepatic iron accumulation is associated with disease progression and resistance to interferon/ribavirin combination therapy in chronic hepatitis C

Background and Aims:  Liver iron accumulation in patients with chronic hepatitis C (CHC) has received increasing attention in recent years. The aim of this study was to determine the prevalence and severity of liver iron deposition in CHC, to assess its relationship with clinical, biochemical and histological characteristics, and to study its influence on the response to interferon (IFN) plus ribavirin combination therapy.

Genetic polymorphisms of bilirubin uridine diphosphate‐glucuronosyltransferase gene in Japanese patients with Crigler–Najjar syndrome or Gilbert's syndrome as well as in healthy Japanese subjects

Background and Aim:  Numerous mutations of bilirubin uridine diphosphate‐glucuronosyltransferase gene (UGT1A1) have been reported in patients with familial unconjugated hyperbilirubinemia. The UGT1A1 mutation appears to be considerably different among ethnic groups. To clarify the incidence of this gene mutation in the Japanese population, the presence of UGT1A1 mutation was investigated in a group of Japanese patients with Crigler–Najjar syndrome type 2 (CNS2) and Gilberts syndrome (GS), as well as in healthy anicteric subjects.

Increased hepatic and renal expressions of multidrug resistance‐associated protein 3 in Eisai hyperbilirubinuria rats

Background and Aim:  Eisai hyperbilirubinuria rats (EHBR) are animal models of Dubin–Johnson syndrome, which suffer from jaundice due to impaired biliary excretion of bilirubin glucuronides. In EHBR, deficiency of multidrug resistance‐associated protein 2 (mrp2) causes defective biliary excretion of numerous organic anions. However, little is known about the expression of other organic anion transporters in this mrp2‐deficient model. The aim of the present study was to investigate adaptive expressions of mrp1, mrp3, mrp6, organic anion transporting polypeptide 1 (oatp1) and oatp2 in liver and kidney of EHBR.

Restriction of dietary calories, fat and iron improves non‐alcoholic fatty liver disease

Background:  The pathogenesis of non‐alcoholic steatohepatitis (NASH) is unclear. Recent studies suggested that oxidative stress plays an important role in the mechanism of NASH. Excessive accumulation of iron in the liver causes oxidative stress. The aim of the present study was to evaluate the grade of hepatic iron accumulation and the therapeutic response to restriction of calories, fat and iron in patients with non‐alcoholic fatty liver disease (NAFLD).

Role of transferrin receptor 2 in hepatic accumulation of iron in patients with chronic hepatitis C

Background and Aim:  Iron deposition in the liver is a common finding in patients with chronic hepatitis C (CH‐C). The mechanism of this hepatic accumulation of iron is not completely understood. This study assessed if the protein expression of transferrin receptor 2 (TfR2) is upregulated in the liver of patients with CH‐C and if TfR2 protein mediates iron accumulation during hepatitis C virus (HCV) infection.

Dubin-Johnson-like black liver with normal bilirubin level

Black liver is a common finding in Dubin-Johnson syndrome (DJS), which is caused by the lack of multidrug resistance-associated protein 2 (MRP2). Impaired excretion of epinephrine metabolites is believed to be a cause of black liver in DJS. Recently, we experienced a patient with black liver whose serum bilirubin level was normal. Coarse brown granules were observed in the hepatocytes, and this finding closely resembled that observed in DJS. However, the granules were negative for Schmorl staining. The MRP2 gene did not show any mutation. Immunostaining study demonstrated MRP2 protein expression in the liver, and it was localized in the canalicular membranes of hepatocytes. This case illustrates for the first time that DJS is not the only cause of black liver.

Green juice-associated granulomatous hepatitis.

non. Mohan et al. (4) concluded that, until further studies are available, anti-TNF therapy should be avoided in patients with pre-existing MS and discontinued if new neurologic symptoms develop in a patient without history of neurologic disease. Anti-TNF treatment of two patients with rapidly progressive MS showed an increase in gadolinium-enhancing lesions in brain MRI after each treatment. Lymphocyte counts and IgG index in the cerebrospinal fluid also increased. Clinically significant neurologic change did not occur (5). Other studies dealing with anti-TNF in the treatment of MS have also noted negative effects associated with lenercept and infliximab (6). GI literature discussing the use of infliximab in patients with inflammatory bowel disease fails to mention pre-existing neurologic problems, in particular MS. The adverse effects of anti-TNF agents in MS are supported by the rheumatology and neurology reports. The use of infliximab for Crohn’s disease should be avoided in patients with MS. We think that this potential risk should be highlighted as a relative contraindication for gastroenterologists using infliximab.