No contribution of the ABCB11 p.444A polymorphism in Japanese patients with drug-induced cholestasis.

European studies have revealed that the ABCB11 c.1331T>C (V444A) polymorphism (rs2287622) C-allele frequency is higher among patients with drug-induced cholestasis. Given the low incidence of this disease, however, this association has not been sufficiently elucidated. We aimed to investigate the significance of this polymorphism in Japanese patients. We determined ABCB11 V444A polymorphism frequencies and HLA genotypes in two independent drug-induced cholestasis cohorts. Expression and taurocholate transport activity of proteins from 444A variants were analyzed using Madin-Darby canine kidney II cells. In cohort 1 (n = 40), the V444A polymorphism C-allele frequency (66%) was lower than that in controls (n = 190, 78%), but this difference was not significant (P = 0.09). In cohort 2 (n = 119), comprising patients with cholestatic (n = 19), hepatocellular (n = 74), and mixed (n = 26) liver injuries, the C-allele frequency was lower among patients with cholestatic liver injury (68%) than among those with hepatocellular (75%) or mixed liver injury (83%), although this difference was not significant. In cohort 1, HLA-A*0201 was observed more frequently in patients (22%) than in controls [11%; P = 0.003; odds ratio, 2.4 (95% confidence interval, 1.4-4.0)]. Taurocholate transport activity of 444A-encoded protein was significantly lower than that of 444V-encoded protein (81% of 444V, P < 0.05) because of the reduced protein stability. In conclusion, ABCB11 444A had slightly reduced transport activity, but it did not contribute to the occurrence of drug-induced cholestasis in Japanese patients. Therefore, genetic susceptibility to acquired cholestasis may differ considerably by ethnicity.

Weight-based high- and low-dose ribavirin in combination with peginterferon α-2b therapy for genotype 2 chronic hepatitis C: A randomized trial.

AIM: The optimal ribavirin dose in the treatment of patients infected with hepatitis C virus (HCV) genotype 2 remains to be elucidated. We aimed to seek the optimal ribavirin dose required for this genotype in a randomized trial. METHODS: We compared the efficacy and tolerability of the 24-week peginterferon α-2b (1.5 µg/kg/week) therapy in combination with a weight-based higher dose (600-1000 mg) and lower dose (400-800 mg) of ribavirin for genotype 2 patients. Noninferior margin was set at 10%. RESULTS: A total of 120 patients were randomized to a higher-dose or a lower-dose group. Sustained virological response (SVR) by intention-to-treat analysis was achieved in 47/58 (81.0%, 90% confidential interval [CI]: 72.6-89.5) patients in the higher-dose group and 41/60 (68.3%, 90% CI: 58.5-78.2) patients in the lower-dose group (difference, -12.7%; 90% CI, -25.7 to 0.3). Relapse rates were 10% and 21.6% in the higher-dose and the lower-dose groups, respectively. Multiple logistic regression analysis showed that ribavirin dose/kg body weight was the only significant predictor of SVR (≥9.5 mg/kg per day vs <9.5 mg/kg per day; odds ratio = 3.34; 95% CI, 1.41-7.92; P = 0.006). Twenty-one (36.2%) in the higher-dose group required ribavirin dose reduction because of anemia, whereas seven patients (11.7%) did in the lower-dose group (P < 0.01). Three of the higher-dose group and two of the lower-dose group required premature termination of therapy. CONCLUSIONS: Weight-based lower-dose ribavirin regimen was not equivalent to the higher-dose counterpart in the treatment of HCV genotype 2. We discourage treating these patients with low-dose ribavirin regimens. The peginterferon therapy in combination with ribavirin at a weight-based higher dose (600-1000 mg) remains the standard-of-care treatment for this genotype.

Differential impact of adherence to pegylated interferon and ribavirin in the treatment of genotype 1 high viral titer chronic hepatitis C.

To clarify the impact of adherence, we treated 122 genotype 1 high viral titer chronic hepatitis C patients with pegylated interferon (peg-IFN) and ribavirin for 48 weeks at nine referral hospitals, and evaluated the prognostic factors with a focus on the adherence to the treatment. This study included 68 (55.7%) treatment-naïve patients and 54 (44.3%) patients who did not respond to the previous treatment. Multivariate analysis revealed adherence to peg-IFN and ribavirin as the only significant predictor. Sustained virological response (SVR) rate was 72.2%, 19.0%, and 27.3% in patients given ≥80%, 60%-80%, and <60% dose peg-IFN, respectively, and was 68.6%, 41.2%, and 5.3% in those given ≥80%, 60%-80%, and <60% dose ribavirin, respectively. SVR rate sharply fell when exposure to peg-IFN was below 80% whereas it decreased in a stepwise manner as for ribavirin. Therefore, ≥80% of peg-IFN and as much as possible dose of ribavirin are desired to achieve SVR in the treatment of genotype 1 high viral titer chronic hepatitis C.

A case of primary jejunal cancer diagnosed by preoperative small intestinal endoscopy.

The patient was a 37-year-old female. She was brought to our hospital by ambulance with nausea and vomiting. Abdominal ultra sound and abdominal enhanced CT scan showed a tumor in left side of the abdominal aorta 6 cm in size, and it showed an expanded stomach and duodenum. Upper gastrointestinal series revealed an apple core sign in upper jejunum near the Treitz' ligament. Small intestinal endoscopy (XSIF-240 endoscope, Olympus Inc.) revealed stenosis related to an epithelially protruding lesion with an irregular surface in the jejunum on the anal side of the horizontal duodenal peduncle. Biopsy suggested a well-differentiated adenocarcinoma. Scintigraphy showed hot spot in left middle abdomen. Under a diagnosis of primary jejunum cancer, Partial resection of the jejunum and partial resection of the transverse colon was performed. Histopathologically, the tumor was well differentiated adenocarcinoma exposed serosal surface. Postoperatively, the stage was evaluated as III (T3, N1, M0). Preoperative diagnosis to use small intestinal endoscopy was effectiveness. We report a patient with primary jejunum cancer in whom a definitive diagnosis was made before surgery.

A case of colon lymphangioma treated with laparoscopy-assisted ileocecal resection.

We encountered a patient with colon lymphangioma and performed laparoscopy-assisted ileocecal resection. The patient was a 68-year-old male who visited our hospital for weight loss in May 1999. Since fecal occult blood was positive on close examination, colonoscopy was performed. A light-permeable, transparent, and pedunculated polyp was found in the ascending colon and diagnosed as submucosal tumor. The patient was admitted for close examination and treatment. Abdominal CT detected a tumor in the ascending colon accompanied by disturbed surrounding adipose tissue, suggesting extramural invasion of the tumor. Based on the diagnosis of extramural submucosal tumor of the ascending colon, ileocecal resection was performed with laparoscopic assistance. The laparoscopic findings were as follows: 1) Lymph vascular dilatation filled with lymph expanding on the serosal surface, 2) light-permeability/translucency, 3) laparoscopic cushion sign, and 4) lymph vascular dilatation in the surrounding adipose tissue. Laparoscopy-assisted surgery was useful for the diagnosis and treatment of colon lymphangioma, and characteristic laparoscopic findings were noted. Laparoscopic surgery is a useful for a diagnosis and the treatment of large lymphangioma of colon.