Primary biliary cirrhosis (PBC) is an autoimmune liver disease that predominantly affects women and characterized by chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and subsequent fibrosis. The serologic hallmark of PBC is the presence of antimitochondrial antibodies (AMA), which are found in 95% of patients with PBC. The AMA are directed against the 2-oxo-acid dehydrogenase complexes located on the inner membrane of mitochondria. Although the role of AMA in the pathogenesis of PBC is unknown, the presence of antibodies has allowed detailed immunological definition of the antigenic epitopes, the autoantibodies and the T-cell response. Theories have been proposed regarding the mechanism of immune-mediated bile duct damage in PBC, including the possible role of T-cell-mediated cytotoxicity and molecular mimicry. PBC is usually diagnosed based on the triad of elevated alkaline phosphatase, AMA, and characteristic histological changes on liver biopsy. Biochemical liver abnormalities tests are consistent with the presence of cholestasis and reveal an elevation of both serum alkaline phosphatase and γ-glutamyl transpeptidase, with or without elevation of aminotransferase levels. Ursodeoxycholic acid (UDCA), a dihydroxy bile acid, appears to be the only effective therapy in preventing or delaying the need for liver transplantation. However, a number of patients receiving UDCA still develop progressive disease and require transplantation; at present, liver transplantation is the only effective therapy for end-stage PBC.

1 Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan 2 Clinical Research Center, NHO Nagasaki Medical Center and Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 2-1001-1 Kubara, Omura 856-8562, Japan 3Department of Pharmacy, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan 4Department of Legal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan

Objective Interferon-free regimens of direct-acting antiviral agents have improved the treatment response for chronic hepatitis C virus (HCV) infection, and improvement in the serum albumin level during interferon-free therapy has been reported. The aim of this study was to identify the factors that influence the improvement in the serum albumin level in patients receiving interferon-free antiviral therapy. Methods This retrospective, multicenter study consisted of 471 Japanese patients with chronic hepatitis and compensated liver cirrhosis infected with HCV who completed 12-week interferon-free sofosbuvir (SOF)-based therapy [SOF plus ledipasvir for genotype 1 (n=276) and SOF with ribavirin for genotype 2 (n=195)]. We evaluated the changes in the serum albumin level from baseline to the end of treatment (ΔAlb). Results When compared with the normal-albumin group (baseline serum albumin >35 g/L, n=406), the low-albumin group (baseline serum albumin ≤35 g/L, n=65) showed a significant increase in the mean ΔAlb (5.5 g/L vs. 1.0 g/L, p<0.001). In the low-albumin group, a multivariate logistic regression analysis extracted diabetes mellitus as a negative predictive factor of median ΔAlb >5.0 g/L (odds ratio: 0.19, 95% confidence interval: 0.048-0.79, p=0.020). In the low-albumin group, the mean ΔAlb was significantly lower in the diabetic patients (n=14) than in the non-diabetic patients (n=51) (3.9 g/L and 5.7 g/L, p=0.049). Conclusion Interferon-free SOF-based therapy significantly improved the serum albumin in the low-albumin group patients with chronic HCV infection. However, the improvement in the serum albumin level was significantly lower in the diabetic patients than in the non-diabetic patients.

A previous genome- wide association study (GWAS) performed in 963 Japanese individuals (487 primary biliary cholangitis [PBC] cases and 476 healthy controls) identified TNFSF15 (rs4979462) and POU2AF1 (rs4938534) as strong susceptibility loci for PBC. In this study, we performed GWAS in additional 1,923 Japanese individuals (894 PBC cases and 1,029 healthy controls),and combined the results with the previous data. This GWAS, together with a subsequent replication study in an independent set of 7,024 Japanese individuals (512 PBC cases and 6,512 healthy controls), identified PRKCB (rs7404928) as a novel susceptibility locus for PBC ( odds ratio [OR] = 1.26, P = 4.13 x 10(-9)). Furthermore, a primary functional variant of PRKCB (rs35015313) was identified by genotype imputation using a phased panel of 1,070 Japanese individuals from a prospective, general population cohort study and subsequent in vitro functional analyses. These results may lead to improved understanding of the disease pathways involved in PBC, forming a basis for prevention of PBC and development of novel therapeutics.

An analytic approach to addressing inductance problems in power semiconductor devices has been developed by researchers in Japan. These power devices are often used in half-bridges, a technology that has recently advanced with the introduction of wide band-gap semiconductor devices, such as SiC and GaN FETs. These developments - affording high-voltage, large-current and high-speed characteristics ...

False turn-on phenomenon is a critical problem in power converters. The key factor in the analysis of the phenomenon is the Cdv/dt. However, this factor is not so important any longer if parasitic inductances are taken into account. The mathematical analysis reported presents that the false turn-on problem with parasitic inductances is characterised by two frequencies and four types of balancing factors. The peak gate oscillation voltage can also be evaluated in two different cases. These peak values are evaluated by comparing the mathematical results with simulation results by PSIM and the errors are 5.60 and 2.99%.

Primary biliary cirrhosis(PBC)is a chronic cholestatic liver disease and the association of osteoporosis is high. In this paper, the practical guidelines for PBC of Japan as well as those of America(AASLD)and Europe(EASL)are mentioned. Description of each guideline is essentially the same;taking sufficient calcium(1,000~1,200 mg/day)with vitamin D and weight-bearing exercise, and thereafter medication such as alendronate is recommended.

We report an elderly case of adult-onset Still’s disease (AOSD) with atypical presentation. The patient, an 80-year-old female, visited our hospital due to itchy linear urtical rash with low grade fever which occurred after taking a significant amount of blowfish milt four days before. Oral prednisolone of 30mg/day was successful. However, remittent fever appeared after reducing the prednisolone dose accompanied by the similar skin lesion. Hyperferritinemia was evident on the admission and the diagnosis of AOSD was made. We should keep in mind the presence of AOSD with atypical presentation in elderly patients.

Aim: The aim of the present study is to evaluate the factors influencing biochemical response to treatment and the value of biochemical response for predicting long-term outcomes in Japanese patients with primary biliary cirrhosis (PBC).Methods: Biochemical response to ursodeoxycholic acid (UDCA) or UDCA plus bezafibrate was defined as good (upper limit of normal [ULN]), fair (1.5 x ULN) or poor (>1.5 x ULN) at 2 years after initiation of UDCA treatment. Associations between various factors (including age, sex, autoantibody status and histological variables at baseline), biochemical response to treatment and long-term outcomes were evaluated in 164 Japanese PBC patients.Results: Anti-gp210 positivity and a higher bile duct loss score were significant risk factors for worse alkaline phosphatase (ALP) response (odds ratios [OR], 2.78 and 1.85, respectively). Age, anti-gp210 positivity and anticentromere positivity were significant risk factors for worse alanine aminotransferase (ALT) response (OR, 1.05, 4.0 and 2.77, respectively). Anti-gp210 positivity and a higher hepatitis score were significant risk factors for worse immunoglobulin (Ig)M response (OR, 2.10 and 2.06, respectively). Worse ALP and IgM response were significant risk factors for progression to late-stage disease without jaundice (OR, 2.27 and 2.32, respectively). Worse ALT response was a significant risk factor for progression to late-stage disease with persistent jaundice (OR, 11.11).Conclusion: Biochemical response to treatment at 2 years, which is influenced by autoantibody status and histological variables at baseline, can predict long-term outcomes in Japanese patients with PBC.

BACKGROUND & AIMS:Through a genome-wide association study of a Japanese population, we recently identified TNFSF15, a gene encoding TNF-like ligand 1A (TL1A), as a susceptibility gene for primary biliary cirrhosis (PBC). We investigated the clinical significance of TL1A and one of its receptors, decoy receptor 3 (DcR3), in PBC.METHODS:We analysed the systemic and local expression of TL1A and DcR3 in 110 PBC patients and 46 healthy controls using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction and immunohistochemical staining.RESULTS:Serum TL1A levels were significantly increased in PBC patients at both early and late stages as compared with healthy controls, and its levels were significantly decreased in early-stage PBC patients after ursodeoxycholic acid (UDCA) treatment. TL1A was immunohistochemically localized to biliary epithelial cells, Kupffer cells, blood vessels and infiltrating mononuclear cells in the PBC liver. In addition, TL1A messenger RNA expression was increased in the PBC liver as compared with the non-diseased liver. Serum DcR3 levels were also significantly increased in PBC patients, and were significantly decreased after UDCA treatment in early-stage PBC patients.CONCLUSIONS:These results indicate that TL1A and DcR3 may play an important role in the pathogenesis of PBC.

To identify the genetic factors involved in the pathogenesis of primary biliary cirrhosis (PBC), we focused on the organic cation transporter 1 (OCT1/SLC22A1), which is closely associated with phosphatidylcholine synthesis in hepatocytes.

We evaluated the safety, efficacy, and morbidity associated with the treatment of displaced mandibular condylar neck fractures using a retromandibular transparotid approach to reduce and rigidly fix using two 2.0-mm locking miniplates. Our surgical inclusion criteria were: patient selection of open reduction and fixation, displaced unilateral condylar fractures with derangement of occlusion, and bilateral condylar fractures with an anterior open bite. The study group consisted of 19 patients who underwent surgery for 19 mandibular condylar neck fractures; patients were analyzed prospectively, with more than 6 months of follow-up, and were evaluated in terms of functional results, scar formation, postoperative complications, and stability of fixation. The results showed that functional occlusion identical to the preoperative condition and correct anatomical reduction of the condylar segments in centric occlusion, followed by immediate functional recovery, was achieved in all patients. No patient suffered from any major or permanent complication postoperatively, although there were two cases (11%) of temporary facial nerve palsy, which resolved completely within 3 months. Surgical scars were barely visible. The retromandibular transparotid approach with open reduction and rigid internal fixation for displaced condylar neck fractures of the mandible is a feasible and safe, minimally invasive surgical technique that provides reliable clinical results.

Recent genome-wide association studies suggest that genetic factors contribute to primary biliary cirrhosis (PBC) susceptibility. Although several reports have demonstrated that the interleukin (IL) 12 signaling pathway is involved in PBC pathogenesis, its precise genetic factors have not been fully clarified. Here, we performed an association analysis betweenIL12A,IL12RB, andsignal transducer and activator of transcription 4 (STAT4)genetic variations and susceptibility to PBC. Single nucleotide polymorphisms (SNPs) were genotyped in 395 PBC patients and 458 healthy subjects of Japanese ethnicity and evaluated for associations with PBC susceptibility, anti-nuclear antibody (ANA) status, and anti-mitochondrial antibody (AMA) status. We detected significant associations with PBC susceptibility for severalSTAT4SNPs (rs10168266;P=9.4×10-3, rs11889341;P=1.2×10-3, rs7574865;P=4.0×10-4, rs8179673;P=2.0×10-4, and rs10181656;P=4.2×10-5). Three risk alleles (rs7574865;P=0.040, rs8179673;P=0.032, and rs10181656;P=0.031) were associated with ANA status, but not with AMA positivity. Our findings confirm thatSTAT4is involved in PBC susceptibility and may play a role in ANA status in the Japanese population.

The objective of this study was to identify the mechanism by which mandibular condyle chondrocytes regulate the extracellular matrix. Primary rabbit condylar chondrocytes were isolated, cultured, and treated with transforming growth factor beta 1 (TGF-β1). Cells were then assayed for the following: urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1), collagen types I and II, β1 integrin expression, and proliferative activity. TGF-β1 induced synthesis of collagen type II, αVβ1 integrin, and PAI-1. TGF-β1 induced the growth of chondrocytes and suppressed the synthesis of uPA. Chondrocyte regulation of the extracellular matrix is mediated by TGF-β1. Synthesis of collagen type II, αVβ1 integrin, and PAI-1 is induced, while uPA is suppressed. Also, TGF-β1 induces cellular growth.

九州内肝臓専門医療機関の多施設研究により，1型，高ウイルスC型慢性肝炎（CHC）に対するペグインターフェロン（PEG-IFN）α-2a+リバビリン（RBV）療法の有効性，安全性について検討を行なった．総数は320例，抗ウイルス効果判定症例は288例，安全性評価症例は310例．持続ウイルス陰性化（SVR）率はIntention-to-treatで53.1％，Per Protocol Set（44週間以上投与）で59.6％であった．13～36週目のRNA陰性化例では，延長投与が有効であった．SVRに寄与する因子は，治療前では年齢，BMI，総コレステロール，ウイルス量であったが，治療開始後では12週目までのウイルス陰性化のみであった．有害事象による治療中止例は14例（4.5％）であり，難治性CHCに対するPEG-IFNα-2a+RBV療法は安全性が高く，50％以上のSVR率が期待できる．