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.

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.

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.

Background and aimsRecently, the number of follicular helper T (Tfh) cells expressing interleukin (IL)-21 was found to increase in peripheral blood of human and murine models of autoimmune hepatitis (AIH). IL-21, the most recently discovered member of the type-I cytokine family, exerts various effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. We aimed to assess the relationship of serum IL-21 levels in patients with type I AIH with clinical and laboratory parameters and histology.MethodsNinety-two Japanese patients with liver disease (22 AIH, 20 primary biliary cholangitis, 19 drug-induced liver injury, 8 acute hepatitis B, 8 chronic hepatitis C, 10 non-alcoholic steatohepatitis, 5 viral hepatitis) and 10 healthy volunteers were recruited. Serum IL-21 levels were detected by enzyme-linked immunosorbent assay. Real-time polymerase chain reaction measured mRNA levels of Bcl-6, IL-21, and CXCR5 (Tfh-related factors) in peripheral mononuclear cells.ResultsMean age at diagnosis of AIH was 58.6 years, male-to-female ratio was 4:18, 18.2 % of participants had cirrhosis, and 22.7 % had severe disease. IL-21 levels were significantly increased in the serum of patients with AIH compared to those with other liver diseases and controls (p < 0.0001). Particularly, serum IL-21 levels were significantly increased in severe AIH cases compared to non-severe cases (p < 0.05). Serum IL-21 levels correlated positively with total serum bilirubin levels (r = 0.46, p < 0.05), grading of necroinflammatory activity (r = 0.68, p < 0.005) and negatively with serum albumin levels in patients with AIH (r = −0.49, p < 0.05). In patients with biochemical remission of AIH, serum IL-21 levels remained elevated and correlated positively with serum IgG levels (r = 0.84, p < 0.01). Expression of Tfh-related factors, such as Bcl-6 and IL-21, in peripheral blood mononuclear cells of patients with AIH was significantly higher than that in healthy volunteers.ConclusionsIL-21 may play an important role in the pathogenesis and severity of AIH, and may present a promising target for AIH therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-2512-y) contains supplementary material, which is available to authorized users.

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.