[Show abstract][Hide abstract] ABSTRACT: Liver fibrosis remains an important risk factor for hepatocarcinogenesis in patients with chronic hepatitis C even after the eradication of hepatitis C virus (HCV). However, it is difficult to estimate liver fibrosis based on liver biopsy after the eradication of HCV. We investigated the ability of laboratory indices to predict liver fibrosis in patients with sustained virologic response (SVR) to antiviral therapy. Three laboratory liver fibrosis indices (aspar-tate aminotransferase-platelet ratio index (APRI), FIB-4 index, and Forns index) were calculated based on data at the time of initial pretreatment liver biopsy and at second liver biopsy performed approximately 5 years after SVR in 115 patients who underwent serial liver biopsies. The indices at the time of initial biopsy were compared to histological degree of liver fibrosis in initial biopsy, and laboratory indices at the time of second liver biopsy were compared to the degree of fibrosis in second biopsy. In both comparisons, there were significant increases in all 3 indices with the increase of liver fibrosis grade as assessed in liver biopsy specimens. All 3 indices at the time of second biopsy were able to predict moderate to advanced (METAVIR score F2-4) and advanced (F3-4) fibrosis on liver biopsy, with the area under the receiver-operating characteristics curve >0.8 and the accuracy >70%. All 3 laboratory indices of fibrosis accurately reflected liver fibrosis in patients with SVR for 5 years despite the normalization of serum liver transaminase activity and the lack of liver inflammation.
PLoS ONE 07/2015; DOI:10.1371/journal.pone.0133515 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the value of preoperative screening colonoscopies in patients with biliary tract cancer.
A total of 544 patients with biliary tract cancer who underwent preoperative screening colonoscopies between January 2005 and December 2012 were retrospectively analyzed.
Synchronous colorectal neoplasia was detected in 199 patients (36.7 %), with adenocarcinomas detected in 21 (3.9 %) patients, carcinoids in two (0.4 %) patients, and adenomas in 176 (32.4 %) patients. Of those with adenomas, 32 patients were diagnosed with advanced adenomas, defined as adenomas with a maximum diameter of >1 cm, villous histology, or high-grade dysplasia because these characteristics implied the risk of malignant transformation. Fifty-five (10.1 %) of the patients with colorectal neoplasia required resection (11 surgical and 44 endoscopic resections). There were no major adverse events related to the resection. Univariate and multivariate analyses revealed that smoking status [ex-smoker + current smoker vs. non-smoker: odds ratio (OR) 2.32; 95 % confidence interval (CI) 1.30-4.21] and advanced age (≥70 vs. ≤69 years: OR 2.22; 95 % CI 1.24-3.91) were independent risk factors of having a colorectal neoplasia that required resection.
In patients with biliary tract cancer, preoperative screening colonoscopy was feasible and provided valuable clinical information. Synchronous colorectal neoplasia was detected in a substantial number of patients. Preoperative screening colonoscopies should be considered especially in high-risk patients such as smokers and elderly patients.
Journal of Gastroenterology 05/2015; DOI:10.1007/s00535-015-1092-x · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We showed previously that UBXD8 plays a key role in proteasomal degradation of lipidated ApoB in hepatocarcinoma cell lines. In the present study, we aimed to investigate the functions of UBXD8 in liver in vivo. For this purpose, hepatocyte-specific UBXD8 knockout (UBXD8-LKO) mice were generated. They were fed with a normal or high-fat diet, and the phenotypes were compared with those of littermate control mice. Hepatocytes obtained from UBXD8-LKO and control mice were analyzed in culture. After 26 wk of a high-fat diet, UBXD8-LKO mice exhibited macrovesicular steatosis in the periportal area and microvesicular steatosis in the perivenular area, whereas control mice exhibited steatosis only in the perivenular area. Furthermore, UBXD8-LKO mice on a high-fat diet had significantly lower concentrations of serum triglyceride and VLDL than control mice. A Triton WR-1339 injection study revealed that VLDL secretion from hepatocytes was reduced in UBXD8-LKO mice. The decrease of ApoB secretion upon UBXD8 depletion was recapitulated in cultured primary hepatocytes. Accumulation of lipidated ApoB in lipid droplets was observed only in UBXD8-null hepatocytes. The results showed that depletion of UBXD8 in hepatocytes suppresses VLDL secretion, and could lead to periportal steatosis when mice are fed a high-fat diet. This is the first demonstration that an abnormality in the intracellular ApoB degradation mechanism can cause steatosis, and provides a useful model for periportal steatosis, which occurs in several human diseases.
PLoS ONE 05/2015; 10(5):e0127114. DOI:10.1371/journal.pone.0127114 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prevalence of nonalcoholic fatty liver disease (NAFLD) is higher in men than in women, but according to some epidemiological studies, this gender difference disappears after menopause. Estrogen therapy protects against NAFLD and nonalcoholic steatohepatitis (NASH) after menopause. We investigated the therapeutic effect of raloxifene, a second-generation selective estrogen-receptor modulator, on NASH induced by a choline-deficient high-fat (CDHF) diet in female ovariectomized (OVX) mice.
Seven-week-old female C57BL/6J mice were divided into three experimental groups as follows: (1) sham operation (SHAM group), (2) ovariectomy (OVX group), and (3) ovariectomy + raloxifene (intraperitoneal injection, 3 mg/kg body weight/day; OVX + RLX group). These three groups of mice were fed a CDHF diet for 8 weeks; choline-sufficient high-fat (CSHF) diet was used as control diet. Serum biochemical indicators of hepatic function and liver histological changes were evaluated.
Compared with CSHF diet, ovariectomy enhances liver injury and fibrosis in CDHF diet-fed mice. Serum alanine aminotransferase (ALT) levels were significantly lower in the OVX + RLX group than in the OVX group. The OVX group developed extensive steatosis with inflammation and fibrosis. Lobular inflammatory scores and fibrosis staging in the OVX + RLX group were significantly lower than in the OVX group. Furthermore, the OVX + RLX group exhibited significantly higher expression of hepatic estrogen receptor-α, which was significantly lower in the OVX group than in the SHAM group.
Raloxifene may ameliorate progression of liver fibrosis of NASH induced by CDHF diet in ovariectomized female mice, and up-regulation of estrogen receptor-α may play an important role in the beneficial effects of raloxifene on NASH.
Digestive Diseases and Sciences 04/2015; DOI:10.1007/s10620-015-3660-6 · 2.55 Impact Factor