Clinical use of molecular targeted agents for primary small bowel adenocarcinoma: A multicenter retrospective cohort study by the Osaka Gut Forum.

Primary small bowel adenocarcinoma (SBA) is a rare cancer for which effective treatment strategies have not yet been established. The results of previous retrospective studies suggest that chemotherapy contributes to a longer survival time in patients with SBA. However, there are few case reports about the efficacy of molecular targeted agent-containing chemotherapy for SBA.

Long-term follow up of peginterferon-α-2a treatment of hepatitis B e-antigen (HBeAg) positive and HBeAg negative chronic hepatitis B patients in phase II and III studies.

Aim: We analyzed the 5-year post-treatment response to peginterferon α-2a (PEG IFN-α-2a) in hepatitis B e-antigen (HBeAg) positive and negative chronic hepatitis B patients.

Methods: One hundred and thirty-seven chronic hepatitis B (CHB) patients receiving 90 μg or 180 μg of PEG IFN-α-2a for 24 or 48 weeks in phase II or III studies were enrolled in the study, including 100 HBeAg positive patients and 37 HBeAg negative patients; 121 patients (88.4%) had genotype C.

S100A8 Production in CXCR2-Expressing CD11b+Gr-1high Cells Aggravates Hepatitis in Mice Fed a High-Fat and High-Cholesterol Diet.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with a spectrum of presentations. S100A8 has been suggested to play a pivotal role as an endogenous immune-activator in inflammatory diseases. In this study, we investigated the involvement of S100A8 in the development of NAFLD.

The impact of an inosine triphosphate pyrophosphatase genotype on bilirubin increase in chronic hepatitis C patients treated with simeprevir, pegylated interferon plus ribavirin.

Background: Hyperbilirubinemia, mild or moderate, is a commonly observed laboratory abnormality in chronic hepatitis C patients treated with simeprevir with pegylated interferon (Peg-IFN) plus ribavirin. In this prospective, multicenter study, we aimed to investigate the clinical features and factors associated with bilirubin increases during the therapy.

Methods: A total of 192 patients with chronic hepatitis C who were treated with simeprevir with Peg-IFN plus ribavirin were analyzed.

Renal dysfunction is an independent risk factor for bleeding after gastric ESD.

Background And Study Aims: The number of patients with chronic kidney disease (CKD) is increasing worldwide and gastric cancer sometimes occurs with CKD. However, the safety and feasibility of endoscopic submucosal dissection (ESD) for patients with CKD are not clear. The aim of this study is to clarify the feasibility and safety of gastric ESD for patients with CKD.

Invariant natural killer T cell deficiency leads to the development of spontaneous liver inflammation dependent on γδT cells in mice.

Background: Immune tolerance is maintained in the liver, and perturbation of tolerance can lead to immune-mediated liver diseases such as autoimmune hepatitis (AIH). Invariant natural killer T (iNKT) cells and γδT cells have been shown to maintain immune homeostasis as regulatory cells and to play pathogenic roles in immune-mediated diseases as effector cells. We hypothesized that iNKT cells and γδT cells are involved in the maintenance of hepatic immune tolerance and immune-mediated liver disease.

Impact of alpha-fetoprotein on hepatocellular carcinoma development during entecavir treatment of chronic hepatitis B virus infection.

Background: Entecavir (ETV) is one of the first-line nucleoside analogs for treating patients with chronic hepatitis B virus (HBV) infection. However, the hepatocellular carcinoma (HCC) risk for ETV-treated patients remains unclear.

Methods: A total of 496 Japanese patients with chronic HBV infection undergoing ETV treatment were enrolled in this study.

The prospective randomized study on telaprevir at 1500 or 2250 mg with pegylated interferon plus ribavirin in Japanese patients with HCV genotype 1.

Background: Triple therapy with telaprevir (TVR), pegylated interferon and ribavirin has improved antiviral efficacy in patients with chronic hepatitis C (CH-C). However, the severe adverse effects caused by TVR are important to resolve. In this prospective, randomized, multicenter, open-label study, the antiviral efficacy and safety in the reduced administration of TVR were examined.

[Bypass surgery or stent placement for biliary obstruction in patients with unresectable pancreatic cancer].

The therapeutic strategy for biliary obstruction in patients with unresectable pancreatic cancer is controversial. We compared complications and prognosis between 2 groups: the B group, 8 patients who were diagnosed as having inoperable pancreatic cancer at laparotomy and underwent bypass surgery, and the S group, 7 patients who underwent endoscopic stent placement for biliary obstruction due to clinically unresectable pancreatic cancer. Although 1 patient developed cholangitis and surgical site infection in the B group, there was no difference in the duration of hospital stay between the 2 groups.

Post-treatment levels of α-fetoprotein predict incidence of hepatocellular carcinoma after interferon therapy.

Background & Aims: In patients with chronic hepatitis C virus (HCV) infection, lack of sustained virologic response (SVR) 24 weeks after the end of interferon therapy is a significant risk factor for hepatocellular carcinoma (HCC). Although many pretreatment factors are known to affect HCC incidence, less is known about post-treatment factors-many change during the course of interferon therapy.

Methods: We performed a prospective study, collecting data from 2659 patients with chronic hepatitis C without a history of HCC who had been treated with pegylated interferon (Peg-IFN) plus ribavirin from 2002 through 2008 at hospitals in Japan.

Using early viral kinetics to predict antiviral outcome in response-guided pegylated interferon plus ribavirin therapy among patients with hepatitis C virus genotype 1.

Background: HCV kinetics during treatment demonstrated strong association with the antiviral outcome of patients treated with pegylated interferon (Peg-IFN) plus ribavirin. However, the relationship between HCV kinetics and pre-treatment factors remains unclear.

Methods: Of 547 patients with HCV genotype 1 treated with Peg-IFN alfa-2b plus ribavirin, 401 completed the response-guided therapy and were assessed for per protocol analysis.

Incidence of hepatocellular carcinoma in HCV-infected patients with normal alanine aminotransferase levels categorized by Japanese treatment guidelines.

Background: This study was conducted to evaluate Japanese treatment guidelines for patients with chronic hepatitis C virus (HCV) infection and normal alanine aminotransferase (N-ALT) levels from the viewpoint of the incidence of hepatocellular carcinoma (HCC).

Methods: Four groups of patients with chronic HCV infection treated with pegylated interferon (Peg-IFN) plus ribavirin, and classified according to the N-ALT guidelines, were examined for HCC incidence: group A (n = 353), ALT ≤30 IU/L and platelet (PLT) ≥15 × 10(4)/mm(3); group B (n = 123), ALT ≤30 IU/L and PLT <15 × 10(4)/mm(3); group C (n = 233), 30 < ALT ≤ 40 IU/L and PLT ≥15 × 10(4)/mm(3); and group D (n = 100), 30 < ALT ≤ 40 IU/L and PLT <15 × 10(4)/mm(3). The mean observation period was 36.

Long-term effect of lamivudine treatment on the incidence of hepatocellular carcinoma in patients with hepatitis B virus infection.

Background: Nucleotide analogues have recently been approved for the treatment of patients with hepatitis B virus (HBV) infection. However, it is still controversial whether the decrease of HBV-DNA amount induced by treatment with nucleotide analogues can reduce the risk of hepatocellular carcinoma (HCC) development in HBV patients.

Methods: A total of 293 HBV patients without HCC who were treated with lamivudine (LAM) were enrolled in a multicenter trial.

Reducing Peg-IFN doses causes later virologic response or no response in HCV genotype 1 patients treated with Peg-IFN alfa-2b plus ribavirin.

Background: The timing to the first undetectable hepatitis C virus (HCV) RNA level is strongly associated with sustained virologic response in pegylated interferon (Peg-IFN) plus ribavirin combination therapy for patients with chronic hepatitis C (CH-C) with genotype 1. This study was conducted to clarify the impact of drug exposure to Peg-IFN on the timing of HCV RNA negativity in Peg-IFN plus ribavirin combination therapy for CH-C patients with genotype 1.

Methods: A total of 1409 patients treated with Peg-IFN alfa-2b plus ribavirin were enrolled and classified into four categories according to the Peg-IFN dosage.

Efficacy of pegylated interferon plus ribavirin combination therapy for hepatitis C patients with normal ALT levels: a matched case-control study.

Background: The antiviral effect of pegylated interferon (Peg-IFN) plus ribavirin combination therapy in chronic hepatitis C (CHC) patients with normal alanine aminotransferase (ALT) levels (N-ALT) has been reported to be equivalent to that for patients with elevated ALT levels (E-ALT). However, the actual antiviral effect in N-ALT patients remains obscure because efficacy can be overestimated in patients with an advantageous background.

Methods: In this study, 386 patients were extracted, for a matched case-control study, from 1320 CHC patients treated with Peg-IFN alpha-2b plus ribavirin combination therapy; 193 N-ALT patients [116 with hepatitis C virus genotype 1 (HCV-1), 77 with HCV genotype 2 (HCV-2)] were matched with 193 E-ALT patients by a propensity score method using the variables of age, sex, IFN treatment history, body mass index, and platelet counts.

A patient with rheumatoid arthritis treated with tocilizumab together with lamivudine prophylaxis after remission of infliximab-reactivated hepatitis B.

A 59-year-old woman with rheumatoid arthritis was treated quite successfully with infliximab, but her serum aminotransferase levels were markedly elevated; this was diagnosed as acute exacerbation of hepatitis B and she was treated with lamivudine, and infliximab was discontinued. The rheumatoid arthritis disease activity was uncontrollable after the discontinuation of infliximab, and we therefore initiated tocilizumab treatment (after obtaining the patient's informed consent) together with lamivudine prophylaxis. After tocilizumab administration her rheumatoid arthritis disease activity was significantly attenuated, and the activity has remained low, without re-exacerbation of the hepatitis, for more than 2 years since the initiation of the tocilizumab.

The efficacy of extended treatment with pegylated interferon plus ribavirin in patients with HCV genotype 1 and slow virologic response in Japan.

Background: Which patients with hepatitis C virus (HCV) genotype 1 can benefit from extended treatment with pegylated interferon (Peg-IFN) plus ribavirin is unknown, although the overall sustained virologic response (SVR) rate has been shown to improve in patients with a late virologic response (LVR), defined as detectable serum HCV RNA at week 12 and undetectable at week 24.

Methods: Among 1163 chronic hepatitis C patients with genotype 1 treated with Peg-IFN plus ribavirin combination therapy, 213 patients with an LVR were examined in this study. In addition, we selected 81 patients of matched sex and age from each of the 48- and 72-week treatment groups, using the propensity score, to compare the efficacy of the two treatment durations.

Efficacy of re-treatment with pegylated interferon plus ribavirin combination therapy for patients with chronic hepatitis C in Japan.

Background: It is still not known which patients with chronic hepatitis C who failed to respond to previous pegylated interferon (Peg-IFN) plus ribavirin therapy can benefit from re-treatment.

Methods: Seventy-four patients (HCV genotype 1, n = 56, genotype 2, n = 18) were re-treated with Peg-IFN plus ribavirin.

Results: On re-treatment, the sustained virologic response (SVR) rate was 41% for genotype 1 and 56% for genotype 2.

Indications and limitations for aged patients with chronic hepatitis C in pegylated interferon alfa-2b plus ribavirin combination therapy.

Background & Aims: This study investigated the efficacy and adverse effects of pegylated interferon (Peg-IFN) plus ribavirin therapy in aged patients with chronic hepatitis C (CH-C).

Methods: A total of 1040 naïve patients with CH-C (genotype 1, n=759; genotype 2, n=281), of whom 240 (23%) over 65 years old (y.o.

Two cases of treatment with infliximab which replaced long-term home parenteral nutrition and maintained remission in patients with Crohn disease.

[Case 1] A 41-year-old man had undergone multiple bowel resections and consequently short bowel syndrome with high-output jejunostomy developed. In July 2008, he started infliximab (IFX) treatment and achieved remission and recovery from cholestatic liver damage following the cessation of home parenteral nutrition (HPN). [Case 2] A 29-year-old woman chose HPN over enteral nutrition because of high-output fecal fluids through a rectovaginal fistula.

Successful treatment of HCV-related cryoglobulinemic glomerulonephritis with double-filtration plasmapheresis and interferon combination therapy.

A 67-year-old, hepatitis C virus (HCV)-positive woman was admitted to our hospital because of proteinuria and leg edema. Laboratory examination showed decreased serum albumin and complement activity and positive cryoglobulin. The HCV RNA genotype was 1b with high viral load.

[Investigation of simplified international diagnostic criteria for autoimmune hepatitis].

The simplified international diagnostic criteria for autoimmune hepatitis (AIH), re-revised by the International AIH Group in 2008, were investigated in 114 patients with AIH from 15 centers in Japan. While applying of the criteria, we had to pay attention to anti-nuclear antibody measurement methods, and liver histology scoring. Definite and probable AIH were diagnosed in 83 and 22 patients, respectively.

A multicenter, open-label, dose-ranging study to exploratively evaluate the efficacy, safety, and dose-response of tolvaptan in patients with decompensated liver cirrhosis.

Objectives: We examined the efficacy of tolvaptan, an orally effective nonpeptide vasopressin V(2) receptor antagonist, in a Japanese clinical study in patients with intractable ascites and/or lower limb edema associated with decompensated liver cirrhosis.

Methods: Tolvaptan was orally administrated at titrated doses of 15, 30, and 60 mg once daily after breakfast for 3 days at each dose to 18 liver cirrhosis patients with persistent ascites and/or lower limb edema despite receiving oral furosemide at 40 mg/day or higher.

Results: Decreased body weight and abdominal circumference and improvement of ascites and edema were observed following tolvaptan administration beginning from 15 mg.

Lamivudine-to-entecavir switching treatment in type B chronic hepatitis patients without evidence of lamivudine resistance.

Purpose: A considerable number of chronic hepatitis B (CH-B) patients remain under continuous lamivudine treatment, although switching treatment to entecavir could be beneficial. We investigated the antiviral efficacy of switching treatment to entecavir in CH-B patients without apparent evidence of lamivudine resistance during the preceding lamivudine treatment.

Methods: Forty-four CH-B patients, who underwent lamivudine treatment for more than 6 months and showed no evidence of lamivudine resistance, switched to entecavir.