Hiromichi Imaizumi

The Association between Sleep Duration and Non-Alcoholic Fatty Liver Disease among Japanese Men and Women

Objective: To examine the relationship between sleep duration and non-alcoholic fatty liver disease (NAFLD). Methods: We evaluated 3,968 subjects who underwent health check-ups from June 2012 to May 2013 at the Watari Hospital Health Center in Fukushima Prefecture in Japan. Fatty liver was detected by ultrasonography. Sleep duration and lifestyle factors were estimated using a questionnaire. Sleep duration was categorized into the following groups: ≤6, 6 to ≤7, >7 to ≤8, and >8 h. The four sleep duration groups were compared using the χ2 test and Kruskal-Wallis test. Results: In total, 2,172 subjects were enrolled. The overall prevalence of NAFLD was 29.6% (men, 38.0%; women, 25.3%). The proportion of NAFLD tended to decrease as sleep duration increased in men. The proportion with NAFLD was lowest in the group with a sleep duration of 6 to ≤7 h and highest in the groups with sleep durations of ≤6 and >8 h in women. The distribution showed a U-shaped curve. The age-adjusted odds ratio (OR) (95% confidence interval (CI)) for subjects with NAFLD with a sleep duration ≤6 h compared to the reference (6 to ≤7 h) was 1.44 (1.06-1.96) in women. Conclusion: Sleep shortage tends to be associated with NAFLD in women and may be mediated by body adiposity.

Simple Resistance Exercise helps Patients with Non-alcoholic Fatty Liver Disease

To date, only limited evidence has supported the notion that resistance exercise positively impacts non-alcoholic fatty liver disease. We evaluated the effects of resistance exercise on the metabolic parameters of non-alcoholic fatty liver disease (NAFLD) in 53 patients who were assigned to either a group that performed push-ups and squats 3 times weekly for 12 weeks (exercise group; n=31) or a group that did not (control; n=22). Patients in the control group proceeded with regular physical activities under a restricted diet throughout the study. The effects of the exercise were compared between the 2 groups after 12 weeks. Fat-free mass and muscle mass significantly increased, whereas hepatic steatosis grade, mean insulin and ferritin levels, and the homeostasis model assessment-estimated insulin resistance index were significantly decreased in the exercise group. Compliance with the resistance exercise program did not significantly correlate with patient background characteristics such as age, sex, BMI and metabolic complications. These findings show that resistance exercise comprising squats and push-ups helps to improve the characteristics of metabolic syndrome in patients with non-alcoholic fatty liver disease.

Reduced brain activity in female patients with non-alcoholic fatty liver disease as measured by near-infrared spectroscopy

Patients with non-alcoholic fatty liver disease (NAFLD) have impaired health-related quality of life including physical and mental state. Near-infrared spectroscopy (NIRS) is a useful tool for evaluation of brain activity and depressive state. This study aimed to determine the brain activity of female NAFLD patients using NIRS. Cerebral oxygenated hemoglobin (oxy-Hb) concentration during a verbal fluency task (VFT) was measured using NIRS in 24 female NAFLD patients and 15 female healthy controls. The Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire was administered to both groups before NIRS. There was no significant difference in CES-D score between groups. However, the oxy-Hb concentration and number of words during the VFT were less in NAFLD compared to healthy controls. The mean value of oxy-Hb concentration during 0–60 s VFT in the frontal lobe was also smaller in NAFLD patients compared to healthy controls (0.082 ± 0.126 vs. 0.183 ± 0.145, P < 0.001). Cerebral oxygen concentration is poorly reactive in response to VFT in female NAFLD patients. This may indicate an association between decreased brain activity and NAFLD regardless of depression.

Drug-induced Liver Injury with HHV-6 Reactivation.

Liver dysfunction was identified in a 16-year-old boy hospitalized with high fever and abdominal pain and fullness. He had received pharmacotherapy for a headache 2 months previously and other drugs for a high fever 4 days prior to being admitted to our hospital. The patients liver dysfunction was consistent with and fulfilled the criteria for drug induced liver injury, but the laboratory findings showed elevated procalcitonin levels, hyponatremia and leukocytosis. Moreover, we confirmed the presence of human herpesvirus 6 (HHV-6) DNA. The patient exhibited symptoms of high fever and abdominal pain and fullness but no exanthema. The clinical and laboratory findings did not satisfy the criteria for drug-induced hypersensitivity syndrome, and we speculate that the diversity of clinical and laboratory findings may have resulted from HHV-6 reactivation. To the best of our knowledge, this is the first case report on drug-induced liver injury with various findings due to HHV-6 reactivation. HHV-6 reactivation should be considered in patients with drug induced liver injury even in the absence of exanthema.

Reduced frontal activation during verbal fluency task in chronic hepatitis C patients with interferon-based therapy as measured by near-infrared spectroscopy

Psychiatric side‐effects are the main reason for discontinuation of interferon (IFN)‐based therapy. Recent developments in near‐infrared spectroscopy (NIRS) have enabled non‐invasive clarification of brain functions in psychiatric disorders. We prospectively evaluated brain activation in 20 chronic hepatitis C patients with or without IFN‐based therapy by using NIRS during a verbal fluency task (VFT).

Drug-induced liver injury with autoimmune features complicated with hemophagocytic syndrome.

A 60-year-old woman was admitted to our hospital with non-coma acute liver failure. Based on a 1-month history of supplement use, negative viral hepatitis markers, positive antinuclear antibody test, high IgG level, positive HLA-DR4, liver biopsy findings of centrizonal necrosis, and inflammatory cell infiltration in the portal area, she was diagnosed with drug-induced liver injury (DILI) with autoimmune features or the acute hepatitis phase of autoimmune hepatitis (AIH). Although her liver disorder was ameliorated by administration of prednisolone and plasma exchange, anemia and thrombocytopenia were observed during the course of treatment. A bone marrow examination showed hemophagocytosis. Therefore, with no other evidence suggesting infection or malignancy, we determined that the patient had DILI complicated by hemophagocytic syndrome (HPS). Although HPS is very rarely seen in patients with DILI with autoimmune features or the acute hepatitis phase of AIH, this condition should be considered if cytopenia is observed in a patient with DILI.

Paralytic Ileus due to Superior Mesenteric Venous Thrombosis after Transarterial Injection for Hepatocellular Carcinoma

A 69-year-old man was admitted to hospital with abdominal pain. In the four years prior to his presentation, he had undergone repeated transarterial chemoembolizations and injections for hepatocellular carcinoma. He underwent his 8th transcatheter arterial therapy one month prior to admission. Abdominal X-rays and contrast-enhanced computed tomography showed large amounts of small intestinal gas and venous thrombosis from the portal vein to the superior mesenteric vein, respectively. The thrombosis was reduced after anticoagulation therapy (heparin, antithrombin III, danaparoid sodium and warfarin). This is the first case report of paralytic ileus due to superior mesenteric venous thrombosis after transcatheter arterial therapy for hepatocellular carcinoma with an arterioportal shunt.

Dysbiosis of oral microbiota and its association with salivary immunological biomarkers in autoimmune liver disease

The gut microbiota has recently been recognized to play a role in the pathogenesis of autoimmune liver disease (AILD), mainly primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). This study aimed to analyze and compare the composition of the oral microbiota of 56 patients with AILD and 15 healthy controls (HCs) and to evaluate its association with salivary immunological biomarkers and gut microbiota. The subjects included 39 patients with PBC and 17 patients with AIH diagnosed at our hospital. The control population comprised 15 matched HCs. Salivary and fecal samples were collected for analysis of the microbiome by terminal restriction fragment length polymorphism of 16S rDNA. Correlations between immunological biomarkers measured by Bio-Plex assay (Bio-Rad) and the oral microbiomes of patients with PBC and AIH were assessed. Patients with AIH showed a significant increase in Veillonella with a concurrent decrease in Streptococcus in the oral microbiota compared with the HCs. Patients with PBC showed significant increases in Eubacterium and Veillonella and a significant decrease in Fusobacterium in the oral microbiota compared with the HCs. Immunological biomarker analysis showed elevated levels of inflammatory cytokines (IL-1β, IFN-γ, TNF-α, IL-8) and immunoglobulin A in the saliva of patients with AILD. The relative abundance of Veillonella was positively correlated with the levels of IL-1β, IL-8 and immunoglobulin A in saliva and the relative abundance of Lactobacillales in feces. Dysbiosis of the oral microbiota is associated with inflammatory responses and reflects changes in the gut microbiota of patients with AILD. Dysbiosis may play an important role in the pathogenesis of AILD.

Utility of magnetic resonance elastography for predicting ascites in patients with chronic liver disease

This study aimed to evaluate the utility of magnetic resonance elastography (MRE) as a non‐invasive method for predicting ascites in patients with chronic liver disease (CLD).

Simple Resistance Exercise for 24 Weeks Decreases Alanine Aminotransferase Levels in Patients with Non-Alcoholic Fatty Liver Disease

Background Exercise therapy is effective and recommended for non-alcoholic fatty liver disease (NAFLD) based on the efficacy of hepatic fat reduction. However, the efficacies of exercise therapy are based on short-term intervention. Moreover, no reports have examined whether significant reductions in serum levels of alanine aminotransferase (ALT) are achieved with exercise therapy in patients with NAFLD. The aim of this study is to assess the effects of simple resistance exercise for 24 weeks in NAFLD. Methods 59 patients with NAFLD were assigned to a resistance exercise group ( n =28) or a control group ( n =31). The resistance exercise group performed 2 exercises (push-ups and squats) 3 times a week on nonconsecutive days for a trial periods of 24 weeks. Patients in the control group proceeded with regular physical activities under a restricted diet throughout the study. The effects of exercise were compared between groups after 24 weeks. Results Mean ALT level, homeostasis model assessment-estimated insulin resistance index and hepatic steatosis grade were all decreased in the resistance exercise group. Changes in ALT levels correlated negatively with changes in muscle:body weight ratio in the exercise group. Conclusion These data demonstrate that 24 weeks of simple resistance exercise comprising squats and push-ups represents an effective treatment for NAFLD.