Comprehensive analysis of genetic aberrations linked to tumorigenesis in regenerative nodules of liver cirrhosis.

Background: Hepatocellular carcinoma (HCC) recurrently develops in cirrhotic liver containing a number of regenerative nodules (RNs). However, the biological tumorigenic potential of RNs is still unclear. To uncover the molecular bases of tumorigenesis in liver cirrhosis, we investigated the genetic aberrations in RNs of cirrhotic tissues using next-generation sequencing.

Serum IFN-λ3 Levels Correlate with Serum Hepatitis C Virus RNA Levels in Symptomatic Patients with Acute Hepatitis C.

Background: Recent genome-wide association studies demonstrated that 2 single nucleotide polymorphisms (SNPs), upstream of the interferon-λ (IFNL) 3 gene, are associated with the spontaneous clearance of hepatitis C virus (HCV) in symptomatic patients with acute hepatitis C (AHC). Although these 2 SNPs, rs8099917 and rs12979860, have established their significant roles in the innate immunity response to spontaneously clear HCV in patients with AHC, the detailed mechanisms of their roles remain largely unknown.

Aim: This study is aimed at clarifying the factors affecting IFNL3 production and assessing the roles of IFNL3 in AHC.

Influence of hyperglycemia on liver inflammatory conditions in the early phase of non-alcoholic fatty liver disease in mice.

Objectives: A non-alcoholic fatty liver disease (NAFLD) has high prevalence and now important issue of public health. In general, there exists strong interaction between NAFLD and diabetes, but the detailed mechanism is unclear. In this study, we determined the effects of hyperglycemia on progression in the early phase of NAFLD in mice.

Activation of TNF-α-AID axis and co-inhibitory signals in coordination with Th1-type immunity in a mouse model recapitulating hepatitis B.

Hepatitis B virus (HBV) infection evokes host immune responses that primarily determine the outcome of HBV infection and the clinical features of HBV-associated liver disease. The precise mechanisms by which host factors restrict HBV replication, however, are poorly understood due to the lack of useful animal models that recapitulate immune responses to HBV. Here, we performed comprehensive immunologic gene expression profiling of the liver of a mouse model recapitulating anti-HBV immune response using a high sensitivity direct digital counting system.

[An Overview of NAFLD/NASH in Japan].

Clinical identity of nonalcoholic steatohepatitis (NASH) has established it as a chronic liver disease since the 1990s in the USA and in the 21st century in Japan, although its significance is not well recognized in Japanese society. It is characterized as a chronic liver disease, differentiated from viral liver disease and alcoholic liver disease. Nonalcoholic fatty liver disease (NAFLD) comprises nonalcoholic fatty liver (NAFL) and NASH.

Characteristics of Hypovascular versus Hypervascular Well-Differentiated Hepatocellular Carcinoma Smaller Than 2 cm - Focus on Tumor Size, Markers and Imaging Detectability.

Objectives: The characteristics of hypovascular and hypervascular well-differentiated hepatocellular carcinomas (HCCs) were compared in terms of tumor size, tumor markers and detectability by imaging modalities.

Methods: Well-differentiated HCC nodules that are smaller than 2 cm (n = 27) were evaluated in 27 patients using histopathology and divided into 2 groups: hypovascular (n = 10) and hypervascular (n = 17). The diagnostic sensitivity of imaging modalities was then evaluated for efficiency in disclosing tumor size and tumor markers in the 2 types.

Mutational diversity of NS5A and NS3 during triple therapy (telaprevir, pegylated-interferon-α 2b and ribavirin) for genotype 1b chronic hepatitis C: The Kobe Hepatitis Therapeutic Group.

Telaprevir, a non-structural (NS)3/4A protease inhibitor, is a direct-acting antiviral drug that inhibits viral replication. Triple therapy with telaprevir, pegylated interferon, and ribavirin is a standard therapeutic regimen for patients with genotype 1b chronic hepatitis C virus (HCV) infection and a high viral load. Several factors, including mutations in the NS5A gene, are important predictors of the efficacy of interferon therapy.

Outcome of double-filtration plasmapheresis plus interferon treatment in nonresponders to pegylated interferon plus ribavirin combination therapy.

Objectives: We assessed the outcome of double-filtration plasmapheresis (DFPP) combined with pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy in patients infected with hepatitis C virus (HCV)-1b whose HCV had not disappeared during PEG-IFN/RBV combination therapy, or who had relapsed after the end of the therapy. Additionally, we investigated factors predictive of sustained virological response (SVR), including host and viral genetic factors, to DFPP plus IFN/RBV therapy.

Methods: A total of 40 patients infected with HCV-1b whose HCV virus had not been eradicated by previous PEG-IFN/RBV therapy were enrolled for treatment by DFPP plus IFN/RBV.

Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotypes 2a and 2b and high viral load.

Objective: We investigated the impact of host genetics represented by the single nucleotide polymorphism (SNP) of the IL28B gene and viral genetic variations within the nonstructural protein 5A (NS5A) [including the interferon (IFN)/ribavirin (RBV) resistance-determining region (IRRDR) and the IFN sensitivity-determining region (ISDR)] on the outcome of pegylated IFN and RBV (PEG-IFN/RBV) treatment.

Methods: Sixty-six patients infected with hepatitis C virus (HCV)-2a or HCV-2b who received PEG-IFN/RBV for 24 weeks were examined.

Results: In HCV-2a, the major genotype of IL28B SNP showed a tendency toward association with sustained virological response (SVR) and rapid virological response (RVR), and four or more mutations in IRRDR (IRRDR[2a] ≥4) and one or more mutations in ISDR plus its carboxyl-flanking region (ISDR/+C[2a] ≥1) were significantly associated with SVR and RVR.

Serum amyloid A and C-reactive protein positive nodule in alcoholic liver cirrhosis, hard to make definite diagnosis.

We describe a case of serum amyloid A (SAA) and C-reactive protein (CRP) positive nodule detected by immunohistochemical analysis in a 37-year-old woman with alcohol-related cirrhosis. Imaging studies at first admission pointed to hepatocellular carcinoma (HCC), a dysplastic nodule, an inflammatory pseudotumor or focal nodular hyperplasia (FNH). Ultrasonography-guided biopsy in Segment 2 showed minimal atypical changes, except for a slight increase in cell density and micronodular cirrhosis in the non-nodular portion.

Well-differentiated hepatocellular carcinoma detected as hypovascularity by only CT during hepatic arteriography.

We describe a well-differentiated hepatocellular carcinoma (HCC) with alcohol-related liver cirrhosis in a 69-year-old man. Ultrasonography (US) disclosed a 10 mm hypoechoic nodule in segment 4; Sonazoid contrast-enhanced US and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) revealed no defect in either the Kupffer phase or the hepatobiliary phase. Computed tomography during hepatic arteriography (CTHA), however, revealed a hypovascular nodule, but CT during arterial portography showed no perfusion defect.

Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load.

Background: This study explores pretreatment predictive factors for ultimate virological responses to pegylated interferon-α (1.5 μg/kg/week) and ribavirin (600-1000 mg/day) (PEG-IFN/RBV) combination therapy for patients infected with hepatitis C virus (HCV)-1b and a high viral load.

Methods: A total of 75 patients underwent PEG-IFN/RBV combination therapy for 48 weeks.

Double-Filtration Plasmapheresis plus Interferon-β for HCV-1b Patients with Non-Sustained Virological Response to Previous Combination Therapy.

Background And Aims: Double-filtration plasmapheresis (DFPP) together with interferon (IFN) administration produces a substantial reduction in the viral load during the early stages of treatment.

Methods: Based on their responses to previous pegylated IFN and ribavirin (PEG-IFN/RBV) therapy, 20 patients were divided into null virological response (NVR; n = 12) and relapse (n = 8) groups. DFPP was used in combination with IFN-β/RBV with subsequent administration of PEG-IFN-α2a/RBV therapy (DFPP + IFN-β/RBV then PEG-IFN/RBV).

Recent advances in the management of chronic hepatitis B.

There are seven approved treatments for adults with chronic hepatitis B virus infection in the United States and European countries: interferon-α, pegylated interferon-α, lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate. At present, two new analogues, entecavir and tenofovir are recommended as the first line therapy by the guidelines of European Association for the Study of the Liver and American Association Study for the Liver Diseases. On the other hand, regarding interferon therapy, use of pegylated interferon-α is recommended as the first line therapy instead of standard interferon-α by both guidelines.

A case of takotsubo cardiomyopathy with ventricular fibrillation after gastroenterological endoscopy.

We describe a case of takotsubo cardiomyopathy with ventricular fibrillation after gastroenterological endoscopy in a 66-year-old woman. Ten minutes after the upper and lower gastrointestinal endoscopic examinations, the patient lost consciousness, went into respiratory arrest, and became cyanotic; an electrocardiogram (ECG) showed ventricular fibrillation. Electrical defibrillation was applied three times resulting in the patient's recovery.

Diagnostic sensitivity of imaging modalities for hepatocellular carcinoma smaller than 2 cm.

Aim: To compare the imaging results with histology and to evaluate the diagnostic sensitivity of imaging modalities for hepatocellular carcinoma (HCC) smaller than 2 cm.

Methods: Nodules smaller than 2 cm (n = 34) revealed by ultrasonography (US) in 29 patients with liver cirrhosis were analyzed. Histological diagnosis of HCC was performed by ultrasonographic guidance: moderately-differentiated HCC (n = 24); well-differentiated HCC (n = 10).

Autoimmune thrombocytopenic purpura during pegylated interferon α treatment for chronic hepatitis C.

We describe a 72-year-old woman with chronic hepatitis C and autoimmune thrombocytopenic purpura (AITP) during pegylated interferon (PEG-IFN) alpha. Immunoglobulin G and antinuclear antibody were 2,113 mg/dL and 1,280 at the start, respectively. A liver biopsy negated autoimmune hepatitis.

Two cases of non-alcoholic steato-hepatitis developing from simple fatty liver.

We describe two cases of non-alcoholic steatohepatitis (NASH) developing from simple fatty liver and detected by histological examination in two women. In both cases hypertension and diabetes mellitus showed no exacerbation during follow-up; hepatitis C antibody and hepatitis B surface antigen were negative; ultrasound (US) and computed tomography (CT) revealed fatty liver (moderate in one patient and severe in the other). Body mass index (BMI) was 48 and 44 in 2004 and 2007, respectively, in one and 24 in both 2006 and 2007, respectively, in the other.

Outcome and early viral dynamics with viral mutation in PEG-IFN/RBV therapy for chronic hepatitis in patients with high viral loads of serum HCV RNA genotype 1b.

We investigated whether sustained virological response (SVR) and non-SVR by chronic hepatitis C patients to pegylated interferon plus ribavirin (PEG-IFN/RBV) combination therapy are distinguishable by viral factors such as the IFN/RBV resistance-determining region (IRRDR) and by on-treatment factors through new indices such as the rebound index (RI). The first RI (RI-1st; the viral load at week 1 divided by the viral load at 24 h) and the second RI (RI-2nd; the viral load at week 2 divided by the viral load at 24 h) were calculated. The subject patients were divided into 3 groups based on RI-1st and RI-2nd: an RI-A group (RI-1st < or = 1.