Taiga Otsuka

Sarcopenia is a risk factor for the recurrence of hepatocellular carcinoma after curative treatment

Sarcopenia, initially proposed as decreased of muscle mass and strength, is associated with aging and malignant diseases. The aim of the present study was to determine whether there is a correlation between sarcopenia and the recurrence of hepatocellular carcinoma (HCC) after curative treatment.

Effects of home-based exercise and branched-chain amino acid supplementation on aerobic capacity and glycemic control in patients with cirrhosis.

The aim of the current study is to examine whether home‐based step exercise at anaerobic threshold (AT) and branched‐chain amino acid (BCAA) supplementation improve aerobic capacity, ectopic fat in liver and muscle, and glycemic control in patients with liver cirrhosis.

Factors Associated with Post-Progression Survival in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

Sorafenib exerts modest antitumor activity in patients with advanced hepatocellular carcinoma (HCC), and radiological progressive disease (rPD) does not always correspond to so-called clinical progressive disease (cPD). We evaluated 101 patients who initiated sorafenib treatment for HCC and assessed post-progression survival (PPS) using the Cox proportional hazards model. PPS was calculated from the date of the first rPD until the date of death or the last follow-up. Using Cox model analysis of the 76 patients who experienced first rPD, we identified the Child-Pugh class, Eastern Cooperative Oncology Group performance status, the best antitumor response during treatment (using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1) and α-fetoprotein levels as independent factors affecting PPS. When these factors were used to define scores ranging from zero to five with a cutoff value of two, PPS of patients who received best supportive care (BSC) after rPD was not statistically significantly different from that of patients who received post-rPD therapy with scores ≥2 (p = 0.220). In contrast, the PPS for the post-rPD therapy group was significantly longer compared with the BSC patients with scores <2 (p < 0.001). Patients who scored ≥2 at their first rPD were judged cPD and as candidates for BSC.

Gemcitabine in patients with intraductal papillary mucinous neoplasm with an associated invasive carcinoma of the pancreas.

Objectives The standard chemotherapy for invasive ductal carcinoma of the pancreas (IDC) is gemcitabine; however, the efficacy of gemcitabine in invasive intraductal papillary mucinous neoplasm with an associated invasive carcinoma of the pancreas (IPMN-IC) is still unknown. Methods Because it is difficult to distinguish between IPMN-IC and IDC based only on radiological findings in advanced unresectable cases, recurrent cases after surgical resection were analyzed to identify the efficacy of gemcitabine monotherapy for IPMN-IC. Results Between 1992 and 2010, 128 patients with IPMN-IC and 548 patients with IDC underwent pancreatic resection at the National Cancer Center Hospital. Twelve patients with IPMN-IC and 73 patients with IDC had recurred after surgery and subsequently underwent gemcitabine at the standard dosage. The disease-control rates were comparable between the IPMN-IC and IDC patients (58.3% vs 59.4%). The median progression-free survival was 2.8 and 4.1 months in the IPMN-IC and IDC patients, respectively (P = 0.46). Also, no statistically significant difference in the median survival times was observed between the 2 groups (9.3 vs 8.8 months, respectively; P = 0.09). Conclusions Among patients who had IPMN-IC and IDC with recurrent disease after resection, there was no significant difference in treatment outcomes after gemcitabine.

Phase I study of nintedanib in Japanese patients with advanced hepatocellular carcinoma and liver impairment.

This phase I, dose‐escalation study evaluated the safety, preliminary efficacy and pharmacokinetics of nintedanib, a triple angiokinase inhibitor, in Japanese patients with advanced hepatocellular carcinoma and mild/moderate liver impairment. Thirty patients with unresectable hepatocellular carcinoma were enrolled to groups, depending on whether liver impairment was mild (group I, aspartate aminotransferase and alanine aminotransferase ≤2× upper limit of normal and Child–Pugh score 5 [n = 14] or 6 [n = 2]) or moderate (group II, Child–Pugh score 5–6 and aspartate aminotransferase or alanine aminotransferase >2× to ≤5× upper limit of normal [n = 7] or Child–Pugh score 7 [n = 7]); 22 patients had prior sorafenib treatment. Nintedanib was given twice daily in 28‐day cycles until disease progression or unacceptable adverse events, starting at 150 mg (group I) or 100 mg (group II) and escalating to 200 mg. The primary objective was to define the maximum tolerated dose based on occurrence of dose‐limiting toxicities during cycle 1 (grade ≥3 non‐hematological and grade 4 hematological adverse events). No dose‐limiting toxicities were reported during cycle 1 and the maximum tolerated dose for both groups was 200 mg twice daily. The most frequent adverse events were gastrointestinal (diarrhea, nausea, vomiting, and decreased appetite). No patients discontinued nintedanib due to adverse events; 31% of group I and 21% of group II had dose reductions. Median time to progression was 2.8 months (95% confidence interval, 1.05–5.52) for group I and 3.2 months (95% confidence interval, 0.95–6.70) for group II. Nintedanib showed a manageable safety profile and efficacy signals, including in patients previously treated with sorafenib. Clinical trial registration NCT01594125; 1199.120 (ClinicalTrials.gov).

Chronic Hepatitis C Treatment with Daclatasvir Plus Asunaprevir Does Not Lead to a Decreased Quality of Life

Objective The aim of this study was to determine if direct-acting antiviral (DAA) treatment with daclatasvir (DCV) plus asunaprevir (ASV) for 24 weeks influenced the health-related quality of life (HRQOL) at 12 and 24 weeks after treatment initiation [end of treatment (EOT)]. Methods This was a prospective, longitudinal study comparing the HRQOL of patients receiving DAA treatment at 12 weeks after treatment initiation and EOT with the HRQOL at baseline. We used a Japanese-validated version of the 8-item Short Form Health Survey (SF-8) to assess the HRQOL of patients. This score can be compared to the Japanese normative sample scores of SF-8. Wilcoxon signed-rank tests were used to compare the HRQOL before treatment, 12 weeks after treatment initiation, and at EOT. Patients We enrolled patients who received 24-week combination therapy using DCV and ASV for HCV at Saga University Hospital between November 2014 and July 2015. Those who discontinued treatment due to relapse or adverse reactions during the treatment period were excluded from the study. Results There were no significant changes in any of the SF-8 subscales, Physical component scores (PCS) or mental component scores (MCS) during the treatment period for both males and females. Conclusion Our study makes a significant contribution to the literature because 24-week DAA treatment with DCV plus ASV did not decrease the HRQOL at 12 or 24 weeks after treatment initiation.

Multicenter retrospective analysis of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma.

We conducted a multicenter retrospective analysis to evaluate the efficacy of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. We enrolled 36 patients with pathologically proven, unresectable combined hepatocellular and cholangiocarcinoma treated with systemic chemotherapy. The log‐rank test determined the significance of each prognostic factor. Elevated alpha‐fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19‐9 levels were observed in 58.3%, 16.7% and 38.9% of patients, respectively. First‐line chemotherapy included platinum‐containing regimens consisting of gemcitabine/cisplatin (n = 12) and fluorouracil/cisplatin (n = 11), sorafenib (n = 5) and others (n = 8). The median overall and progression‐free survival times were 8.9 and 2.8 months, respectively, with an overall response rate of 5.6%. Prognostic factors associated with negative outcomes included poor performance status, no prior primary tumor resection, a Child‐Pugh class of B, and elevated carcinoembryonic antigen levels with a hazard ratio of 2.25, 2.48, 3.25 and 2.84 by univariate analysis, respectively. The median overall survival times of the gemcitabine/cisplatin, fluorouracil/cisplatin, sorafenib and other groups were 11.9, 10.2, 3.5 and 8.1 months, respectively. Multivariate analysis revealed that the overall survival of patients within the sorafenib monotherapy group was poor compared with platinum‐containing regimens (HR: 15.83 [95% CI: 2.25‐111.43], P = .006). All 7 patients in the sorafenib group had progressive disease, including 2 patients with second‐line therapy. In conclusion, the platinum‐containing regimens such as gemcitabine/cisplatin were associated with more favorable outcomes than sorafenib monotherapy for unresectable combined hepatocellular and cholangiocarcinoma.

Seropositivity and Titers of Anti-Smooth Muscle Actin Antibody Are Associated with Relapse of Type 1 Autoimmune Hepatitis

Background It is important to avoid relapse in autoimmune hepatitis (AIH) because repeated multiple relapses have been associated with a worse prognosis. However, risk factors for relapse before initiation of treatment are not fully understood. The aim of this study was to find predictive markers for relapse of type 1 AIH. Material/Methods We reviewed the records of 53 patients diagnosed with type 1 AIH based on the revised scoring system proposed by the International Autoimmune Hepatitis Group (IAIHG) between 2009 and 2014 at 4 hospitals belonging to the Saga Study Group of Liver Diseases (SASLD). We analyzed the differences in background characteristics between patients with or without relapse. Results All patients achieved remission after treatment, and 9 (17%) subsequently relapsed. The relapsed patients were significantly younger and had a higher positive rate of anti-smooth muscle antibody (ASMA) than the non-relapsed patients (100% vs. 25%, P=0.0012). Moreover, relapse rate increased with titer of ASMA, while titer of antinuclear antibody was not associated with relapse rate. Conclusions ASMA is a useful predictive marker for relapse of type 1 AIH during or after withdrawal of medical therapy. More careful attention should be paid to immunosuppressive therapy in patients with high titers of ASMA.

Asunaprevir and daclatasvir in hemodialysis patients with chronic hepatitis C virus genotype 1b infection: Asunaprevir and daclatasvir in hemodialysis patients

Patients requiring hemodialysis show high morbidity with hepatitis C virus (HCV) infection, but there are difficulties associated with interferon‐based therapies. Asunaprevir and daclatasvir could help patients with HCV genotype 1b because the drugs have a nonrenal metabolism and show good viral eradication. We evaluated the efficacy and safety of combined asunaprevir and daclatasvir therapy.

Impact of Body Weight Reduction via Diet and Exercise on the Anti-Viral Effects of Pegylated Interferon Plus Ribavirin in Chronic Hepatitis C Patients with Insulin Resistance: A Randomized Controlled Pilot Trial

OBJECTIVE Insulin resistance (IR) modifies the anti-viral effects of interferon (IFN) therapy in patients with chronic hepatitis C (CHC). This prospective study evaluated whether lifestyle interventions improve the anti-viral response to treatment with pegylated (PEG)-IFN plus ribavirin (RBV) in patients with CHC. METHODS The study cohort consisted of 60 patients chronically infected with a high viral load of hepatitis C virus genotype 1b and a homeostasis model assessment of IR (HOMA-IR) value above 2. The patients were divided into two groups, an intervention group (n=26) and a control group (n=34). The patients in the intervention group were prescribed diet and exercise treatment for 3-6 months to reduce their body weight by ≥5% before starting treatment with PEG-IFN plus RBV. RESULTS Diet and exercise significantly reduced the HOMA-IR values in the intervention group, from 3.4 to 2.5 (p=0.0009), especially among the 15 patients who achieved a body weight reduction of ≥5%. The viral disappearance rate at 12 weeks was significantly higher in the intervention group among the patients with a ≥5% weight reduction than in the control group (53.3% vs. 23.5%, p=0.01). However, the sustained viral response (SVR) rates were similar. CONCLUSION Improvements in IR achieved through weight reduction via lifestyle interventions may enhance the early viral response to PEG-IFN plus RBV in patients with CHC. However, this intervention program has no effect on the SVR rate.