The number of patients with nonalcoholic fatty liver diseases (NAFLD) including nonalcoholic steatohepatitis (NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma (HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice.

Poly(dibutylstannane) and poly(dioctylstannane) were obtained by electrochemical polymerization of dibutyldichlorostannane and dioctyldichlorostannane, respectively, in a one-compartment cell equipped with a platinum cathode and a silver anode, using tetrabutylammonium perchlorate and DME as the supporting electrolyte and the solvent, respectively.

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The incident rates of hepatocellular carcinoma in all the malignancies were approximately 6% in the NAFLD group and two-thirds in the HCV group.

A 38-year-old woman was referred to our institution due to epigastralgia. She presented with obstructive jaundice and eosinophilia. Endoscopic retrograde cholangiopancreatography showed diffuse narrowing from the distal common bile duct to the bifurcation of the hepatic ducts. An endoscopic plastic biliary stent was inserted; the specimen obtained from the common bile duct wall revealed dense infiltration by eosinophils. Treatment was started with prednisolone 60 mg daily. The patient's biliary stenosis and eosinophilia gradually improved. Eosinophilic infiltration in the lungs or stomach is relatively common, but it is rare in the common bile duct. Most of the reported cases of eosinophilic cholangitis presented with eosinophilia; our patient's eosinophil count was over 1000/mm 3 . Since our patient had allergies to pollen and house dust, a relationship between the allergies and the eosinophilic cholangitis was suspected, but no cause was identified.

Objective Chronic kidney disease (CKD) is present in patients with nonalcoholic fatty liver disease (NAFLD). The aim of this retrospective study was to assess the cumulative development incidence and predictive factors for new onset of CKD in Japanese patients with NAFLD. Methods A total of 5,561 NAFLD patients without CKD were enrolled. CKD was defined as either an estimated glomerular filtration rate of <60 mL/min/1.73 m 2 or dipstick proteinuria (! 1). A blood sample and a urine sample were taken for routine analyses during follow-up. The mean observation period was 5.5 years. The primary goal is the new development of CKD. Independent factors associated with new development of CKD were analyzed by using the Kaplan-Meyer method and the Cox proportional hazards model. Results Of 5.561 NAFLD patients, 263 patients developed CKD. The cumulative development rate of CKD was 3.1% at the 5th year and 12.2% at the 10th year. Multivariate Cox proportional hazards analysis showed that CKD development in patients with NAFLD occurred when patient had low level of GFR of 60-75 mL/ min/1.73 m 2 [hazard ratio:2.75; 95% confidence interval (CI) =1.93-3.94; p<0.001], age of !50 years (hazard ratio: 2.67; 95% CI=2.06-3.46; p<0.001), diabetes (hazard ratio: 1.92; 95% CI=1.45-2.54; p<0.001), hypertension (hazard ratio: 1.69; 95% CI=1.25-2.29; p<0.001), and elevated serum gamma-glutamyltransferase of !109 IU/L(hazard ratio: 1.35; 95% CI=1.02-1.78; p=0.038). Conclusion Our retrospective study indicates that the annual incidence of CKD in Japanese patients with NAFLD is about 1.2%. Five factors of low eGFR level, aging, type 2 diabetes, hypertension, and elevated gamma-glutamyltransferase, increases the risk of the development of CKD.

Recently, we demonstrated that plant DNA virus replication was inhibited in planta by using an artificial zinc finger protein (AZP) and created AZP-based transgenic plants resistant to DNA virus infection. Here we apply the AZP technology to the inhibition of replication of a mammalian DNA virus, human papillomavirus type 18 (HPV-18). Two AZPs, designated AZP HPV -1 and AZP HPV -2, were designed by using our nondegenerate recognition code table and were constructed to block binding of the HPV-18 E2 replication protein to the replication origin. Both of the newly designed AZPs had much higher affinities towards the replication origin than did the E2 protein, and they efficiently blocked E2 binding in vitro. In transient replication assays, both AZPs inhibited viral DNA replication, especially AZP HPV -2, which reduced the replication level to approximately 10%. We also demonstrated in transient replication assays, using plasmids with mutant replication origins, that AZP HPV -2 could precisely recognize the replication origin in mammalian cells. Thus, it was demonstrated that the AZP technology could be applied not only to plant DNA viruses but also to mammalian DNA viruses.The papillomaviruses are double-stranded DNA viruses that induce benign proliferative squamous epithelial and fibroepithelial lesions (warts and papillomas) in their natural hosts. They have been isolated from a variety of animal species, and Ͼ100 human papillomavirus (HPV) types have been identified and fully sequenced so far (reviewed in reference 13). A subgroup of HPVs classified as "high-risk" viruses, including HPV types 16,18,31, 35, 39, 45, 51, 52, 58, and 59, has been found to be associated with the development of cervical cancer (1, 28). Each year, about 500,000 such infections at the uterine cervix undergo malignant conversion, making cervical cancer the second most common malignancy in women worldwide (17). About 90% of such tumors contain high-risk HPVs, with HPV-16 and -18 being the most prevalent. The incidence shows no evidence of declining, and current treatment options are limited (http://www.boehringer-ingelheim.ca/research/res _area_humpap.asp). Therefore, effective antiviral therapies/ treatments for this widespread and troublesome disease are clearly needed.The papillomavirus proteins required for viral DNA replication are the viral E1 and E2 proteins (reviewed in reference 9). The E1 protein is a 70-to 80-kDa nuclear phosphoprotein possessing DNA helicase activity (reviewed in reference 29). Sequence-specific binding of E1 to the viral origin of replication is most likely mediated by the papillomavirus E2 protein (2, 6, 26, 30, 31); E2 bound to the origin recruits E1 to the origin, which results in initiation of the replication process. The 43-to 50-kDa E2 protein comprises two well-conserved functional domains linked by a hinge domain (reviewed in reference 14). The amino-terminal domain of E2 is necessary for direct association with the E1 protein. The carboxyl-terminal portion of E2 binds a 12-base-pair palindromic DNA...

Aim:The goal of the study was to evaluate the efficacy and safety of balloon-occluded transarterial chemoembolization (B-TACE) of hepatocellular carcinoma (HCC) using miriplatin (a lipophilic anticancer drug) and gelatin particles.Methods: B-TACE was performed for 62 HCC nodules in 33 patients who could not be treated by surgical resection or radiofrequency ablation. All 33 patients had a history of transarterial chemoembolization (TACE) treatment prior to B-TACE. As a historical comparison, we investigated 40 nodules in 28 patients treated by TACE using a conventional microcatheter (C-TACE), miriplatin and gelatin particles. The therapeutic effect per tumor was compared between the groups based on the Response Evaluation Criteria in Cancer Study Group of Japan (RECICL) and side-effects were compared based on the Common Terminology Criteria for Adverse Events (ver. 4.0). Results:The therapeutic efficacy after 4-12 weeks was evaluated in 59 nodules in the B-TACE group and in 37 nodules in the C-TACE group. Of these nodules, TE4 occurred in 29 (49.2%) in the B-TACE group and in 10 (27%) in the C-TACE group. Local efficacy was significantly higher in nodules treated by B-TACE than by C-TACE. The side-effects on hepatic function were similar in the two groups. Conclusion:Our results suggest that B-TACE with miriplatin is a useful treatment for hepatocellular carcinoma.