Safety, feasibility, and acceptability of physiotherapy combined with strength training using active video games for older patients with musculoskeletal conditions.

Purpose: This study aimed to determine the safety, feasibility, and acceptability of physiotherapy (PT) combined with strength training using active video games (AVG) for older patients with musculoskeletal conditions.

Methods: Sixteen patients underwent AVG + PT on day 1 and only conventional physiotherapy (CPT) on day 2. The AVG was conducted in 6 upper- and lower-limb training performed in standing position using Ring Fit Adventure (RFA) on Nintendo Switch.

Machine learning in primary biliary cholangitis: A novel approach for risk stratification.

Background & Aims: Machine learning (ML) provides new approaches for prognostication through the identification of novel subgroups of patients. We explored whether ML could support disease sub-phenotyping and risk stratification in primary biliary cholangitis (PBC).

Methods: ML was applied to an international dataset of PBC patients.

Furosemide as a factor to deteriorate therapeutic efficacy of tolvaptan in patients with decompensated cirrhosis.

Aim: To optimize the therapeutic strategy for patients with decompensated cirrhosis manifesting hepatic ascites and/or edema, factors affecting the outcome of patients receiving tolvaptan were evaluated.

Methods: The subjects were 165 patients receiving tolvaptan including 116 patients (70%) also treated with furosemide. The therapeutic efficacy of tolvaptan was defined as "effective" when a body weight reduction of 1.

Furosemide as a factor to deteriorate therapeutic efficacy of rifaximin in patients with decompensated cirrhosis.

Aim: To optimize the therapeutic strategy for cirrhotic patients manifesting hepatic encephalopathy, factors affecting the outcome of patients receiving rifaximin were evaluated.

Methods: The subjects were 95 patients receiving rifaximin. Serum ammonia levels were measured serially during rifaximin treatment.

A validation study of the Ursodeoxycholic Acid Response Score in Japanese patients with primary biliary cholangitis.

Background/purpose: Although ursodeoxycholic acid (UDCA) is a first-line treatment for primary biliary cholangitis (PBC), 20%-30% of patients with PBC exhibit an incomplete response to UDCA. Recently, the UDCA Response Score was proposed for predicting response to UDCA using pretreatment parameters in patients with PBC. We aimed to validate the UDCA Response Score in Japanese patients with PBC.

Bezafibrate Improves GLOBE and UK-PBC Scores and Long-Term Outcomes in Patients With Primary Biliary Cholangitis.

In Japan, bezafibrate (BF) is a second-line agent for primary biliary cholangitis (PBC) that is refractory to ursodeoxycholic acid (UDCA) treatment. From a retrospective cohort (n = 873) from the Japan PBC Study Group, we enrolled 118 patients who had received UDCA monotherapy for at least 1 year followed by combination therapy with UDCA+BF for at least 1 year. GLOBE and UK-PBC scores after UDCA monotherapy (i.

Serum asunaprevir concentrations showing correlation with the extent of liver fibrosis as a factor inducing liver injuries in patients with genotype-1b hepatitis C virus receiving daclatasvir plus asunaprevir therapy.

Aims: Liver injury can occur during antiviral therapies with direct-acting antivirals (DAAs), potentially necessitating discontinuation of the therapies, with consequent worsening of the sustained viral response (SVR) rates, in patients with hepatitis C virus (HCV). To clarify the mechanisms involved in serum transaminase level elevation, we performed a retrospective evaluation of the serum concentrations of daclatasvir and asunaprevir, both classified as DAAs, in patients receiving treatment with a combination of the two drugs.

Methods: Subjects were 278 Japanese patients with genotype-1b HCV who received daclatasvir plus asunaprevir therapy for more than 4 weeks.

Significance of NS5B Substitutions in Genotype 1b Hepatitis C Virus Evaluated by Bioinformatics Analysis.

To evaluate the effects of HCV NS5B amino acid substitutions on treatment outcome in Ledipasvir (LDV)/Sofosbuvir (SOF) for Japanese patients with genotype 1b HCV infection, NS5B sequences were examined in i) seven patients experiencing virologic failure after LDV/SOF in real-world practice, ii) 109 SOF-naïve patients, iii) 165 patients enrolled in Phase-3 LDV/SOF trial. A218S and C316N were detected in all patients with viral relapse; the percentages of these substitutions in SOF-naïve patients were 64.2% and 55.

Retreatment with sofosbuvir/ledipasvir with or without lead-in interferon-β injections in patients infected with genotype 1b hepatitis C virus after unsuccessful daclatasvir/asunaprevir therapy.

Aim: To improve the therapeutic efficacy of sofosbuvir/ledipasvir (SOF/LDV) for the retreatment of patients after daclatasvir/asunaprevir (DCV/ASV), a customized therapy with or without lead-in interferon (IFN)-β injections was formulated according to the types of resistance-associated substitutions (RAS) in the non-structural protein (NS)5A region of genotype 1b hepatitis C virus (HCV).

Methods: Thirty-three patients failing prior DCV/ASV received SOF/LDV for 12 weeks. Patients with HCV carrying unfavorable NS5A-RAS and/or those previously treated with simeprevir were given lead-in IFN-β injections twice a day for 2 weeks; sequential changes in the NS5A-RAS during the injection period were evaluated using deep sequencing.

Chronic hepatitis caused by hepatitis C virus showing a discrepancy between serogroup and genotype because of intergenotypic 2b/1b recombination: A pitfall in antiviral therapy with direct-acting antivirals.

A 40-year-old male patient with virologic relapse after daclatasvir plus asunaprevir therapy for a serogroup 1 hepatitis C virus (HCV) infection visited our hospital for retreatment. Virologic examinations revealed that a genotype 2b HCV strain carrying both NS3-S122N / D168A and NA5A-R30Q / L31M / Q54H / Y93H mutations had relapsed. The patient received sofosbuvir plus ribavirin therapy, but virologic relapse occurred once again.

"Reversi-type virologic failure" involved in the development of non-structural protein 5A resistance-associated variants (RAVs) in patients with genotype 1b hepatitis C carrying no signature RAVs at baseline.

Aims: The therapeutic efficacy of daclatasvir/asunaprevir was inferior in patients with non-structural protein 5A (NS5A)-R30Q mutant hepatitis C virus strains at baseline, compared with those with wild-type strains, even though the half maximal effective concentration of NS5A inhibitors was lower in mutant strains than in wild-type strains. In these patients, R30Q and Y93H mutant strains, which are highly resistant to NS5A inhibitors, emerged at virologic failure. The mechanisms involved in such virologic failure were examined.

Sequential therapy consisting of glucocorticoid infusions followed by granulocyte-monocyte absorptive apheresis in patients with severe alcoholic hepatitis.

Background: Activated leukocytes infiltrating the liver contribute to the provocation of alcoholic hepatitis. Glucocorticoid induces the demargination of leukocytes from the hepatic sinusoids, whereas granulocyte-monocyte absorptive apheresis (GMA) removes leukocytes from the circulation. Thus, the usefulness of a sequential therapy consisting of glucocorticoid infusions followed by GMA was evaluated in patients with severe alcoholic hepatitis.

Development of rare resistance-associated variants that are extremely tolerant against NS5A inhibitors during daclatasvir/asunaprevir therapy by a two-hit mechanism.

Aim: The virologic characteristics of resistance-associated variants (RAVs) developing in patients receiving dual oral therapy with daclatasvir/asunaprevir, including those with previous triple therapy with simeprevir, were evaluated.

Methods: A total of 206 patients with genotype-1b HCV infection, including 5 patients with previous simeprevir therapy, were treated with daclatasvir/asunaprevir for 24 weeks. Resistance-associated variants in the NS5A regions at baseline and during/after therapy were evaluated using cycling-probe real-time polymerase chain reaction combined with direct sequencing.

Effects of Alcohol Consumption on Hepatocarcinogenesis in Japanese Patients With Fatty Liver Disease.

Background & Aims: The effect of ethanol consumption on hepatocarcinogenesis in patients with fatty liver disease (FLD) is not clear. We aimed to investigate the influence of alcohol consumption on hepatocarcinogenesis and determine the risk factors for hepatocellular carcinoma (HCC) in a large number of Japanese patients with FLD without viral hepatitis.

Methods: This multicenter, retrospective cohort study was conducted at a specialized center for hepatology in Japan and included 9959 patients with FLD without viral hepatitis, diagnosed by ultrasonography from January 1997 through December 2011.

Significance of variants associated with resistance to NS5A inhibitors in Japanese patients with genotype 1b hepatitis C virus infection as evaluated using cycling-probe real-time PCR combined with direct sequencing.

Background: Dual oral therapy with daclatasvir plus asunaprevir yielded an SVR rate of 85% among patients with genotype 1b HCV. Treatment failure mainly occurred in patients with pre-existing HCV with NS5A-Y93H mutation. The significance of the mutation was evaluated.

Randomized study comparing vitamin D3 and 1α-Hydroxyvitamin D3 in combination with pegylated interferon/ribavirin therapy for chronic hepatitis C.

Background And Aim: An intention-to-treat prospective randomized study was carried out to compare the potentiation of antiviral efficacies between cholecalciferol, non-activated vitamin D3 supplement, and alfacalcidol, activated 1α-Hydroxyvitamin D3 [1α (OH)-vitamin D3].

Methods: Chronic hepatitis patients with genotype 1b hepatitis C virus (HCV) infection showing serum HCV-RNA levels greater than 5 Log IU/mL received oral administration of cholecalciferol (2000 IU/day) or alfacalcidol (0.5 μg/day) for 4 weeks, and then they were given pegylated interferon (Peg-IFN)-α2a plus ribavirin therapy in combination with either vitamin D3 for 48 or 72 weeks according to the response-guided manner.

Multicenter prospective study to optimize the efficacy of triple therapy with telaprevir in patients with genotype 1b hepatitis C virus infection according to an algorithm based on the drug Adherence, IL-28B Gene Allele and Viral Response Trial (AG & RGT).

Aim: To optimize the therapeutic efficacy of NS3/4A protease inhibitors, a multicenter prospective study was performed according to an algorithm based on the Adherence, IL-28B Gene Allele and Viral Response Trial (AG & RGT).

Methods: A total of 340 patients with genotype 1b hepatitis C virus (HCV) showing serum RNA levels of >5 log were enrolled. The duration of ribavirin/pegylated interferon (PEG IFN)-α-2b therapy was prolonged to 48 weeks in patients with unfavorable IL28B alleles showing adherence rates of less than 80% for either drug during the first 12 weeks even if RVR had been achieved, and in those in whom cEVR, but not RVR, was achieved; furthermore, to 72 weeks in those showing partial early viral response.

Telaprevir-induced, but not pegylated interferon-associated, retinopathy as a noteworthy adverse effect during triple antiviral therapy in patients with chronic hepatitis C.

Background: The significance of retinopathy during triple therapy with telaprevir is uncertain.

Methods: Ophthalmologic examination was done prospectively before and every month during the therapy in 95 CHC patients.

Results: Retinopathy was found in 46 (48.

Therapeutic strategy for patients with bleeding rectal varices complicating liver cirrhosis.

Aim: Although rupture of rectal varices is rarely encountered, it may provoke massive and fatal hemorrhage in patients with liver cirrhosis. We examined the clinical features of patients showing bleeding from rectal varices to establish a suitable therapeutic strategy for the lesions.

Methods: Twelve cirrhotic patients with bleeding rectal varices were enrolled.

Novel hepatitis B virus strain developing due to recombination between genotypes H and B strains isolated from a Japanese patient.

Aim: In Japan, genotypes B and C are the predominant genotypes isolated from patients with chronic hepatitis B, while genotype A predominates in patients with acute hepatitis B. Globalization, however, appears to have changed the distribution of the hepatitis B virus (HBV) genotypes. Thus, the viral characteristics of HBV genotypes other than genotypes A, B and C were examined.

Transcatheter arterial chemoembolization for hepatocellular carcinoma: Comparison of the therapeutic efficacies between miriplatin and epirubicin.

Aim: The therapeutic efficacy of transcatheter arterial chemoembolization (TACE) using miriplatin was evaluated in comparison with that using epirubicin in patients with hepatocellular carcinoma (HCC).

Methods: Two hundred and eight-nine HCC patients receiving TACE were retrospectively enrolled; none of the patients gave a previous TACE history. The short-term therapeutic efficacy was evaluated by computed tomography (CT) performed 1 month later.

SNPs in the promoter region of the osteopontin gene as a possible host factor for sex difference in hepatocellular carcinoma development in patients with HCV.

Aims: Four single nucleotide polymorphisms (SNPs) exist in the promoter region of the osteopontin (OPN) gene, namely, the SNPs at nucleotide (nt) -155, -616, and -1748 showing linkage disequilibrium to each other, and an independent SNP at nt -443. The significance of these SNPs in the risk of hepatocellular carcinoma (HCC) development was examined in patients with hepatitis C virus (HCV).

Methods: The SNPs at nt -155 and nt -443 were analyzed in 120 patients with HCC.

Retreatment with peginterferon α-2a + ribavirin in patients who failed previous peginterferon α-2b + ribavirin combination therapy.

Background/aims: Peginterferon (PEG-IFN) + ribavirin (RBV) combination therapy is the current standard of care for chronic hepatitis C. However, more than half of the patients cannot achieve sustained viral response (SVR). In Japan, the clinical benefit of retreatment with PEG-IFN + RBV combination retreatment is still unknown.

Inhibition of hepatocellular carcinoma by PegIFNα-2a in patients with chronic hepatitis C: a nationwide multicenter cooperative study.

Background: We investigated whether the administration of maintenance doses of interferon prevented hepatocellular carcinoma (HCC) in patients with chronic hepatitis C.

Methods: Study 1: A multicenter, retrospective, cooperative study was carried out to determine whether long-term administration of low-dose peginterferon alpha-2a (PegIFNα-2a) prevented HCC development in patients with chronic hepatitis C. In total, 594 chronic hepatitis C patients without a history of HCC were enrolled and treated with 90 μg PegIFNα-2a administered weekly or bi-weekly for at least 1 year.

Algorithm to determine the outcome of patients with acute liver failure: a data-mining analysis using decision trees.

Background: We established algorithms to predict the prognosis of acute liver failure (ALF) patients through a data-mining analysis, in order to improve the indication criteria for liver transplantation.

Methods: The subjects were 1,022 ALF patients seen between 1998 and 2007 and enrolled in a nationwide survey. Patients older than 65 years, and those who had undergone liver transplantation and received blood products before the onset of hepatic encephalopathy were excluded.