Potential relevance of cytoplasmic viral sensors and related regulators involving innate immunity in antiviral response.

Background & Aims: Clinical significance of molecules involving innate immunity in treatment response remains unclear. The aim is to elucidate the mechanisms underlying resistance to antiviral therapy and predictive usefulness of gene quantification in chronic hepatitis C (CH-C).

Methods: We conducted a human study in 74 CH-C patients treated with pegylated interferon alpha-2b and ribavirin and 5 nonviral control patients.

The presence of steatosis and elevation of alanine aminotransferase levels are associated with fibrosis progression in chronic hepatitis C with non-response to interferon therapy.

Background/aims: Interferon (IFN) therapy leads to regression of hepatic fibrosis in chronic hepatitis C patients who achieve a sustained virologic response (SVR), while the beneficial effect is limited in those who fail to do so. The aim of the present study was to define factors associated with progression of fibrosis in patients who do not achieve a SVR.

Methods: Fibrosis staging scores were compared between paired liver biopsies before and after IFN in 97 chronic hepatitis C patients who failed therapy.

Serum KL-6 as a novel tumor marker for hepatocellular carcinoma in hepatitis C virus infected patients.

The up-regulation of MUC1 protein is associated with malignant phenotype of cancer. We investigated the significance of KL-6, one of the MUC1 antigens, as a tumor marker in hepatitis C virus positive hepatocellular carcinoma (HCC). Serum KL-6 was determined in 203 patients with chronic hepatitis (CH), 47 patients with liver cirrhosis (LC) and 78 patients with HCC.

Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C.

Background/aims: To elucidate whether ribavirin acts as a mutagen in the clinical setting and to clarify the relationship between ribavirin-induced mutations and virological response to combined therapy.

Methods: Thirty-four patients with hepatitis C virus (HCV) genotype 1b received ribavirin monotherapy for 4 weeks, followed by a 24-week course of IFN/ribavirin therapy. HCV mutations during a non-treatment observation period and during subsequent ribavirin monotherapy were determined, and the relationship between mutations and response to subsequent IFN/ribavirin therapy was evaluated.

Polymerase domain B mutation is associated with hepatitis relapse during long-term lamivudine therapy for chronic hepatitis B.

Breakthrough hepatitis remains the major issue in long-term lamivudine therapy for chronic hepatitis B. However, the emergence of drug-resistant hepatitis B virus (HBV) is not always accompanied by a relapse of hepatitis. To elucidate factors predictive of breakthrough hepatitis, 53 patients with genotype C of HBV on long-term lamivudine therapy were analyzed.

Development of hepatocellular carcinoma after interferon therapy in chronic hepatitis C. Is it possible to reduce the incidence by ribanirin and IFN combination therapy?

Objectives: Although the incidence of hepatocellular carcinoma (HCC) has been shown to be reduced after interferon (IFN) monotherapy in chronic hepatitis C, the risk factors for the development of HCC have not been fully understood. The aim of this study is to investigate the risk factors for the development of HCC after IFN in chronic hepatitis C as well as whether the incidence of HCC will be reduced by ribavirin and IFN combination therapy or not.

Methods: 495 patients with chronic hepatitis C and which received IFN monotherapy were followed and the incidence and risk factors for the development of HCC were examined.

Prospective randomized crossover trial of combination therapy with bezafibrate and UDCA for primary biliary cirrhosis.

The aim of this study was to evaluate the effects of the combination therapy with bezafibrate and ursodeoxycholic acid (UDCA) for primary biliary cirrhosis (PBC), compared to UDCA monotherapy. Sixteen patients with compensated PBC were divided randomly into two groups. Group A received treatment with bezafibrate and UDCA for 6 months, while group B received UDCA alone, treatment protocols were then exchanged for another 6 months.

A comparison of the exponential decay slope between PEG-IFN alfa-2b/ribavirin and IFN alfa-2b/ribavirin combination therapy in patients with chronic hepatitis C genotype 1b infection and a high viral load.

Objectives: A high virological response rate can often be shown to be obtained with PEG-IFN alpha-2b and ribavirin combination therapy in chronic hepatitis C patients. Viral dynamics have been utilized for the evaluation of antiviral effects, especially the exponential second decay slope, which represents the elimination of infected cells.

Methods: Forty-nine patients were randomly assigned to the IFN alpha-2b group (n = 26) or the PEG-IFN alpha-2b group (n = 23).

Core promoter/pre-core mutations are associated with lamivudine-induced HBeAg loss in chronic hepatitis B with genotype C.

Background/aims: To clarify the factors associated with the efficacy of lamivudine.

Methods: Variables including basic core promoter (BCP) and pre-core (PreC) mutations were evaluated in 60 chronic hepatitis B e antigen (HBeAg)-positive patients with genotype C. Thirty patients were treated with lamivudine and the remaining 30 patients were age- and sex-matched controls.

Assessment of Kupffer cells by ferumoxides-enhanced MR imaging is beneficial for diagnosis of hepatocellular carcinoma: comparison of pathological diagnosis and perfusion patterns assessed by CT hepatic arteriography and CT arterioportography.

To investigate the clinical significance of the radiographic assessment of Kupffer cells and hemodynamics in the diagnosis of hepatocellular nodules, both magnetic resonance (MR) imaging enhanced by ferumoxides and CT hepatic arteriography (CTHA)/CT arterioportography (CTAP) were undertaken for 118 patients with 158 primary nodular hepatocellular lesions. The radiographic findings were analyzed in the context of the pathological diagnosis. Among nodules presumed to be pre- or early HCC by CTHA/CTAP, all 13 hyperintense nodules identified by MR imaging (MRI) were found pathologically to be hepatocellular carcinoma (HCC).

Interferon-stimulated gene expression and hepatitis C viral dynamics during different interferon regimens.

Background/aims: To address the molecular mechanism for enhanced antiviral efficacy associated with a frequent dosing of interferon (IFN)-beta.

Methods: Serum hepatitis C viral (HCV) dynamics, double-stranded RNA-activated protein kinase (PKR) mRNA and MxA mRNA levels in peripheral blood mononuclear cells (PBMC) were analyzed serially in 140 patients who were randomly assigned to a twice daily (3 MU bid) or once daily (6 MU qd) administration group.

Results: In twice daily group, the rate of HCV decline during the second phase was 2-fold greater than in the once daily group (P=0.

A case of primary leiomyoma of the liver in a patient without evidence of immunosuppression.

A 31-year-old Japanese male was admitted to our hospital for investigation of an asymptomatic nodular lesion of the liver detected by abdominal ultrasonography (US) during a routine medical examination. Computed tomography (CT) revealed a single, hypovascular mass 35 mm in diameter, within the left lobe of the liver. The tumor demonstrated hypointensity on T1-weighted, and hyperintensity on T2-weighted magnetic resonance (MR) imaging.