Pharmacokinetics and Safety of Ranirestat in Patients With Hepatic Impairment.

Ranirestat is an aldose reductase inhibitor hypothesized to improve diabetic neuropathy. An open-label, single-dose, parallel-group study was conducted to compare pharmacokinetic (PK) characteristics of an oral dose of ranirestat across subjects with normal hepatic function and patients with mild and moderate hepatic impairment because ranirestat is expected to be used by patients with diabetes mellitus, possibly including those with hepatic impairment. To evaluate the necessity for dose adjustment, PK profiles and tolerability were studied at the dose of 40 mg, the expected optimal clinical dose in patients with diabetic neuropathy and normal hepatic function.

Effects of Zinc Acetate on Serum Zinc Concentrations in Chronic Liver Diseases: a Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial and a Dose Adjustment Trial.

The essential trace element zinc maintains liver functions. Liver diseases can alter overall zinc concentrations, and hypozincemia is associated with various hepatic pathologies. Modulating systemic zinc through dietary supplementation is potentially useful for liver diseases.

Pharmacokinetics and Safety After a Single Dose of Imarikiren in Subjects with Renal or Hepatic Impairment.

Background And Objective: Imarikiren hydrochloride (TAK-272; SCO-272) is a novel direct renin inhibitor. The objective of this study was to determine the effects of renal impairment (RI) or hepatic impairment (HI) on the pharmacokinetics and safety of imarikiren.

Methods: This phase I, open-label, parallel-group comparative study evaluated the pharmacokinetics and safety of a single 40 mg oral dose of imarikiren in RI [mild, moderate, severe, or end-stage renal disease (ESRD), and on hemodialysis] or HI (mild or moderate) subjects compared with subjects with normal renal or hepatic function.

An association between dietary habits and traffic accidents in patients with chronic liver disease: A data-mining analysis.

The incidence of traffic accidents in patients with chronic liver disease (CLD) is high in the USA. However, the characteristics of patients, including dietary habits, differ between Japan and the USA. The present study investigated the incidence of traffic accidents in CLD patients and the clinical profiles associated with traffic accidents in Japan using a data-mining analysis.

Exendin‑4, a glucagon‑like peptide‑1 receptor agonist, modulates hepatic fatty acid composition and Δ‑5‑desaturase index in a murine model of non‑alcoholic steatohepatitis.

Glucagon‑like peptide‑1 (GLP‑1) is involved in the development of non‑alcoholic steatohepatitis (NASH), which is characterized by fatty acid imbalance. The aim of this study was to investigate the effects of the GLP‑1 receptor (GLP‑1R) agonist, exendin‑4 (Ex‑4), on hepatic fatty acid metabolism and its key enzyme, Δ‑5‑desaturase, in a murine model of NASH. NASH was induced in db/db mice fed a methionine‑choline deficient (MCD) diet.

Dipeptidyl peptidase-4: a key player in chronic liver disease.

Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A representative target peptide is glucagon-like peptide-1, and inactivation of glucagon-like peptide-1 results in the development of glucose intolerance/diabetes mellitus and hepatic steatosis.

Dipeptidyl Peptidase IV Inhibitor Improves Insulin Resistance and Steatosis in a Refractory Nonalcoholic Fatty Liver Disease Patient: A Case Report.

A 67-year-old Asian woman was referred to Kurume University Hospital due to abnormal liver function tests. She was diagnosed with nonalcoholic fatty liver disease (NAFLD). NAFLD was treated by diet therapy with medication of metformin and pioglitazone; however, NAFLD did not improve.

Lipid profile is associated with the incidence of cognitive dysfunction in viral cirrhotic patients: A data-mining analysis.

Aim:   Cognitive dysfunction (CD) is frequently observed in cirrhotic patients. However, the biochemical profiles associated with CD remain unclear. We investigated the biochemical profiles associated with the incidence of CD in cirrhotic patients by using multivariate analyses, including a decision-tree algorithm.

Nutritional assessments for ordinary medical care in patients with chronic liver disease.

Aim:   In patients with chronic liver disease who are at risk of malnutrition, simple and useful assessments for nutritional status should be established for ordinary medical care. The prognostic nutritional index (PNI) and controlling nutritional status (CONUT) are simple assessments constructed of only two or three laboratory data. We aimed to describe the potential of PNI and CONUT as a nutritional assessment tool in patients with chronic liver disease.

Fish to meat intake ratio and cooking oils are associated with hepatitis C virus carriers with persistently normal alanine aminotransferase levels.

Aim:   Dietary habits are involved in the development of chronic inflammation; however, the impact of dietary profiles of hepatitis C virus carriers with persistently normal alanine transaminase levels (HCV-PNALT) remains unclear. The decision-tree algorithm is a data-mining statistical technique, which uncovers meaningful profiles of factors from a data collection. We aimed to investigate dietary profiles associated with HCV-PNALT using a decision-tree algorithm.

Development of intrahepatic cholangiocarcinoma after a 14-year follow-up of a patient with primary sclerosing cholangitis and ulcerative colitis.

Intrahepatic cholangiocarcinoma (ICC) is one of the life-threatening complications of primary sclerosing cholangitis (PSC). However, the incidence of ICC in Japanese PSC patients is low, and the association between the development of ICC and morbidity duration of PSC is largely unknown. Here, we describe a case of ICC that developed after a long-term follow-up of a patient with PSC and ulcerative colitis (UC).

Supplementation before endoscopic therapy for esophageal varices reduces mental stress in patients with liver cirrhosis.

Background/aims: Esophageal varices are often seen in cirrhotic patients. Because endoscopic therapy for esophageal varices forces such patients to go on an extended fast until the endoscopic therapy occurs, physical and psychological stresses are induced. The aims of this study were to investigate the effects of a nutritional supplement before endoscopic therapy on such stresses, and on the safety of therapy.

Insulin resistance and chronic liver disease.

Increased insulin resistance is frequently associated with chronic liver disease and is a pathophysiological feature of hepatogenous diabetes. Distinctive factors including hepatic parenchymal cell damage, portal-systemic shunting and hepatitis C virus are responsible for the development of hepatogenous insulin resistance/diabetes. Although it remains unclear whether insulin secretion from pancreatic beta cells is impaired as it is in type 2 diabetes, retinopathic and cardiovascular risk is low and major causes of death in cirrhotic patients with diabetes are liver failure, hepatocellular carcinoma and gastrointestinal hemorrhage.

Serum level of free fatty acids is associated with nocturnal hypoglycemia in cirrhotic patients with HCV infection: a pilot study.

Background/aims: Nocturnal hypoglycemia is an aggravating factor for liver cirrhosis. However, in patients with compensated liver cirrhosis, a clinical parameter associated with nocturnal hypoglycemia remains unclear. The aim of this study is to investigate a clinical parameter associated with nocturnal hypoglycemia in patients with hepatitis C virus (HCV)-related compensated liver cirrhosis.

Redox state of albumin is not associated with colloid osmotic pressure.

Serum albumin exists in oxidized and reduced forms. Although the oxidation of albumin affects some of its functions, the relationship between oxidized albumin and colloid osmotic pressure (COP) remains unclear. The aim of this study was to determine whether there is an association between oxidized albumin and COP.

Hybrid training of voluntary and electrical muscle contractions reduces steatosis, insulin resistance, and IL-6 levels in patients with NAFLD: a pilot study.

Background: Physical inactivity is a risk factor for the development of non-alcoholic fatty liver disease (NAFLD). "Hybrid training", a training that involves both voluntary and electrical muscle contractions, causes beneficial alterations in muscles even after short durations of exercise. The aim of this study was to investigate the therapeutic efficacy of hybrid training in patients with NAFLD.

The pathogenesis, complications and therapeutic strategy for hepatitis C virus-associated insulin resistance in the era of anti-viral treatment.

Recent experimental and clinical studies have shown that chronic hepatitis C virus (HCV) infection causes insulin resistance. Since insulin resistance decreases response to antiviral treatments, promotes inflammatory and fibrogenic reactions and increases a risk of hepatocellular carcinoma (HCC), amelioration of insulin resistance may be a novel therapeutic target, which could improve the prognosis in patients with HCV-related chronic liver disease. Despite the increased awareness of health risk of insulin resistance, there is no common therapeutic strategy for HCV-associated insulin resistance.

Subjective global assessment is not sufficient to screen patients with defective hepatic metabolism.

Background And Aims: Subjective global assessment (SGA) is useful for screening malnourished patients with several diseases, although it has been indicated to underestimate nutritional status for patients with liver disease. Accordingly, the aim of this study was to examine the usefulness of SGA as a nutritional screening tool for patients with liver disease, compared to patients with gastroenterological disease, without bias of personal ability and experience.

Methods: SGA was performed on 129 of hospitalized patients (86 with liver disease and 43 with gastroenterological disease).

Thrombocytopenia, an important interfering factor of antiviral therapy and hepatocellular carcinoma treatment for chronic liver diseases.

In patients with chronic liver diseases, thrombocytopenia is a common manifestation which interferes with antiviral therapy for hepatitis C virus (HCV), and with hepatocellular carcinoma (HCC) treatment. While thrombopoietin-receptor agonist is expected to improve thrombocytopenia for patients with chronic liver diseases in 2-3 weeks, there is still a lack of fundamental data about short-term variations in the natural course of platelet count in cirrhotic patients, and the impact of thrombocytopenia on antiviral therapy for HCV-infected patients and patients being treated for HCC. The aims of this study are to investigate sequential changes in platelet count and the impact of thrombocytopenia on antiviral therapy and HCC treatment in patients with chronic liver diseases.

Pigment epithelium-derived factor inhibits lysosomal degradation of Bcl-xL and apoptosis in HepG2 cells.

Pigment epithelium-derived factor (PEDF) has several biological actions on tumor cells, but its effects are cell-type dependent. The aim of this study was to examine the pathophysiological role of PEDF in hepatocellular carcinoma (HCC). PEDF expression was examined in various hepatoma cell lines and human HCC tissues, and was seen in various hepatoma cell lines including HepG2 cells.

Heating improves poor compliance with branched chain amino acid-rich supplementation in patients with liver cirrhosis: A before-after pilot study.

Although branched chain amino acid (BCAA) supplementation improves malnutrition in cirrhotic patients, patient compliance with the administration of BCAA-rich supplements is poor due to their bitter taste. Since temperature is an important factor affecting taste, we examined the effect of heating on the stability of BCAAs and on the compliance of patients with liver cirrhosis with BCAA-rich supplement administration. A thermal denaturation test was first conducted, in which the BCAA-rich supplement Aminoleban® EN was heated to 37, 60, or 80°C for 30 or 60 min.

Branched-chain amino acid supplements reduced ascites and increased the quality of life in a patient with liver cirrhosis: A case report.

Liver cirrhosis is frequently accompanied by malnutrition and hypoalbuminemia, which in turn commonly induces ascites in patients with liver cirrhosis. Ascites leads to abdominal distention and appetite loss, resulting in a deteriorated quality of life (QOL). Administration of branched-chain amino acid (BCAA)-rich supplements reduces hepatic encephalopathy and malnutrition.

Phase I clinical study of a peptide vaccination for hepatitis C virus-infected patients with different human leukocyte antigen-class I-A alleles.

Hepatitis C virus (HCV) infection has a high risk of liver cirrhosis and hepatocellular carcinoma at later stages. We recently identified a peptide derived from the HCV core protein capable of inducing both cellular and humoral responses to nearly all HCV-positive patients in Japan with different human leukocyte antigen (HLA)-class I-A alleles. To assess the safety and immune responses to this novel peptide, we conducted a phase I dose-escalation study of the vaccination for 26 HCV-positive patients who were either non-responders to the interferon-based therapy (n = 23) or refused it (n = 3).

A peptide derived from hepatitis C virus (HCV) core protein inducing cellular responses in patients with HCV with various HLA class IA alleles.

C35-44 peptide is a well known HLA-A2-restricted CTL epitope originating from hepatitis C virus (HCV) core protein. It was reported that the majority of HCV positive patients had significant levels of serum IgG specific to this peptide. This study addressed whether C35-44 peptide could induce CTL activity restricted to various HLA class IA alleles or could not.

Leukocytapheresis Therapy Improved Cholestasis in a Patient Suffering from Primary Sclerosing Cholangitis with Ulcerative Colitis.

Primary sclerosing cholangitis (PSC) is an autoimmune disease of the hepatobiliary system for which effective therapy has not been established. Leukocytapheresis (LCAP) therapy is known to effective in patients with ulcerative colitis (UC). In addition, effects of LCAP therapy were reported on some autoimmune diseases such as Crohn's disease, rheumatoid arthritis and rapidly progressive glomerulonephritis.