Circulating myostatin levels as a prognostic biomarker in patients with acute liver failure and late-onset hepatic failure.

AIM: Myostatin is a myokine involved in muscle mass regulation. The associations between circulating myostatin levels and clinical characteristics in patients with acute liver failure (ALF) and late-onset hepatic failure (LOHF) are unclear. METHODS: In this retrospective study, 51 patients with ALF or LOHF were included. Serum myostatin was measured using an enzyme-linked immunosorbent assay. RESULTS: Myostatin levels were significantly lower in patients with ALF and LOHF than in controls (ALF/LOHF: 2522 pg/mL, controls: 3853 pg/mL, p = 0.003). The prevalence of low myostatin in deceased patients was significantly higher than that in spontaneous survivors and patients who underwent liver transplantation. Patients with low myostatin levels had a high incidence of complications. There was a positive correlation between the psoas muscle index and serum myostatin levels. Patients with low myostatin levels had shorter 1-year transplant-free survival and shorter 1-year overall survival than patients with high myostatin levels. Low serum myostatin levels were associated with poor prognosis independent of the Japanese scoring system for ALF ≥3, King's College criteria, or model for end-stage liver disease score >30.5. The combination of serum myostatin levels and prognostic models for ALF significantly stratified patients according to 1-year prognosis. CONCLUSIONS: Low serum myostatin levels were associated with a low psoas muscle index, complication rate, and poor prognosis in patients with ALF and LOHF. Assessment of circulating myostatin levels may improve the prediction of outcomes in patients with ALF and LOHF.

Association between sleep duration and a new onset of nonalcoholic fatty liver disease.

Objective A short sleep duration is associated with non-alcoholic fatty liver disease (NAFLD). However, the causal relationship between a short sleep duration and the onset of NAFLD remains unknown because of the lack of any longitudinal studies. Therefore, we evaluated the association between sleep duration and the onset of NAFLD. Methods We evaluated health checkup data for 1,862 NAFLD-free Japanese adults aged 33-86 years at baseline and followed those individuals for a median of 41 months. Hepatic steatosis was examined using ultrasonography (US). The Cox proportional hazards model was used to evaluate the association between sleep duration and NAFLD onset. Results Among the 1,862 participants, 483 (25.9%) developed NAFLD. The proportion of women who developed NAFLD was the highest in the group with a sleep duration of <6 hours and lowest in the group with a sleep duration of 7 to <8 hours. The multivariable-adjusted hazard ratio (95% confidence interval) for the onset of NAFLD in women with a sleep duration <6 hours compared with those with a sleep duration of 7 to <8 hours was 1.55 (1.09-2.20; p=0.02). Conclusions In women, a short sleep duration was independently associated with the onset of NAFLD, thus suggesting that an adequate sleep duration can be a promising preventive factor for the onset of NAFLD in women.

Characteristics of peripheral blood mononuclear cells and potential related molecular mechanisms in patients with autoimmune hepatitis: a single-cell RNA sequencing analysis.

Autoimmune hepatitis (AIH) is an immune disorder characterized by hypergammaglobulinemia, autoantibodies, and chronic active hepatitis on liver histology. However, immune cell population characteristics in AIH patients remain poorly understood. This study was designed to analyze peripheral blood mononuclear cell (PBMC) characteristics in AIH through single-cell RNA sequencing (scRNA-seq) and explore potential AIH-related molecular mechanisms. We generated 3690 and 3511 single-cell transcriptomes of PBMCs pooled from 4 healthy controls (HCs) and 4 AIH patients, respectively, by scRNA-seq. These pooled PBMC transcriptomes were used for cell cluster identification and differentially expressed gene (DEG) identification. GO functional enrichment analysis was performed on the DEGs to determine the most active AIH immune cell biological functions. Although the PCA-based uniform manifold approximation and projection (UMAP) algorithm was used to cluster cells with similar expression patterns in the two samples, 87 up- and 12 downregulated DEGs were retained in monocytes and 101 up- and 15 downregulated DEGs were retained in NK cells from AIH PBMCs. Moreover, enriched GO terms in the PBMC-derived monocyte and NK cell clusters were related mainly to antigen processing and presentation, IFN-γ-mediated signaling, and neutrophil degranulation and activation. These potential molecular mechanisms may be important targets for AIH treatment.

Lifestyle factors affecting new-onset nonalcoholic fatty liver disease.

Evidence for the influence of lifestyle factors on nonalcoholic fatty liver disease (NAFLD) onset is limited because the association between lifestyle factors and NAFLD has been reported mostly in cross-sectional studies. Our purpose was to elucidate which lifestyle factors are associated with NAFLD onset by performing a longitudinal study. This was a longitudinal study of 1,713 Japanese participants who underwent multiple health checkups from June 2013 to the end of March 2018 and were not diagnosed with NAFLD at the first health checkup at Watari Hospital in Fukushima, Japan. Baseline characteristics, including lifestyle factors, were compared among participants with and without NAFLD. Cox proportional hazards models were used to identify the association between lifestyle factors and NAFLD onset. Among the 1,713 participants, 420 (24.5 %) developed NAFLD during the observation period (median 47 months). There were significant differences in body mass index and hepatobiliary enzyme levels between participants with and without NAFLD. In Cox proportional hazards models, eating between meals (hazard ratio (HR): 2.08, 95 % confidence interval (CI): 1.25-3.45, p < 0.01) and eating fast (HR: 1.59, 95 % CI: 1.26-2.00, p < 0.01) were risk factors for NAFLD onset in men and women, respectively. Moreover, fast walking was a protective factor against NAFLD onset in women (HR: 0.76, 95 % CI: 0.60-0.96, p = 0.02). These findings could help to identify patients at risk and prevent future NAFLD onset.

Influence of serum Gas6 levels on prognosis in patients with hepatocellular carcinoma.

OBJECTIVE: The prediction of prognosis in hepatocellular carcinoma patients is important for switching treatment. The association between circulating growth arrest-specific 6 levels and prognosis in hepatocellular carcinoma patients is unknown. METHODS: We retrospectively analysed the association between serum growth arrest-specific 6 levels and clinical findings in 132 patients with hepatocellular carcinoma. Serum growth arrest-specific 6 levels were measured using enzyme-linked immunosorbent assay. RESULTS: Amongst 132 patients, the Barcelona Clinic Liver Cancer stage was classified as 0, A, B, C and D in 19, 48, 41, 18 and 6 patients, respectively. Serum growth arrest-specific 6 levels in hepatocellular carcinoma patients were higher than those in healthy controls (28.4 ng/mL vs. 19.6 ng/mL, P < 0.001), and growth arrest-specific 6 levels were positively correlated with soluble Axl levels. In the entire cohort, high growth arrest-specific 6 levels were associated with a shorter survival period (hazard ratio: 1.78 per 20 ng/mL, 95% confidence interval: 1.01-3.16, P = 0.045). In early and intermediate-stage hepatocellular carcinoma patients treated with transcatheter arterial chemoembolization (n = 59), we determined a cut-off value of 36.4 ng/mL based on the receiver operating characteristic curve to predict death within 3 years, and high growth arrest-specific 6 levels were associated with a high cumulative incidence of portal vein tumour thrombosis (Gray's test: P = 0.010) and shorter overall survival (log-rank: P = 0.005). CONCLUSIONS: Serum growth arrest-specific 6 levels were associated with prognosis in hepatocellular carcinoma patients. In early and intermediate-stage hepatocellular carcinoma patients who underwent transcatheter arterial chemoembolization, high growth arrest-specific 6 levels were associated with a high incidence of portal vein tumour thrombosis. Circulating growth arrest-specific 6 levels may be a useful prognostic marker in hepatocellular carcinoma patients.

Association between equol and non-alcoholic fatty liver disease in Japanese women in their 50s and 60s.

BACKGROUND AND AIM: Equol is a metabolite of soy isoflavone and has estrogenic activity. The incidence of non-alcoholic fatty liver disease (NAFLD) increases after menopause in women, which is thought to result in a decrease in estrogen. This study aimed to evaluate the association between equol and NAFLD. METHODS: We evaluated 1185 women aged 50-69 years who underwent health check-ups at four health centers in Fukushima, Japan. Equol producers were defined by a urinary equol concentration of 1.0 µM or more. In addition to comparison between equol producers and non-producers, the association between equol and NAFLD was estimated using logistic regression analysis adjusting for fast walking and eating habits. RESULTS: Of the 1185 participants, 345 (29.1%) women were equol producers. The proportions of women who had NAFLD (34.8% vs 45.2%) were significantly lower in the equol-producing group than in the non-producing group. Multivariable logistic regression analysis showed that equol production was significantly associated with NAFLD (odds ratio = 0.66, 95% confidence interval: 0.51-0.86). CONCLUSIONS: Equol production was significantly associated with NAFLD in women in their 50s and 60s.

Transarterial embolization for ruptured pancreaticoduodenal artery aneurysm due to segmental arterial mediolysis combined with median arcuate ligament syndrome: a case report.

A 75-year-old female with a history of Parkinson's disease treatment and hypertension presented at the emergency section with sudden onset of right abdominal pain. Contrast-enhanced computed tomography revealed beaded irregular stenosis and dilation of the superior mesenteric artery (SMA) and an aneurysm in the branch of the pancreaticoduodenal artery (PDA) that communicates with the common hepatic artery and SMA. Additionally, a hematoma had formed in the retroperitoneal space, and extravasation of contrast medium from the pancreaticoduodenal artery aneurysm (PDAA) into the hematoma was observed. The celiac artery (CA) was compressed by the median arcuate ligament; stenosis of the CA at its origin and dilation on the distal side were observed. Based on the imaging findings, it was diagnosed that PDAA was ruptured, SMA developed segmental arterial mediolysis (SAM), and CA developed median arcuate ligament syndrome (MALS). The ruptured PDAA was thought to be caused by SAM combined with MALS. Transcatheter arterial embolization (TAE) was performed for the ruptured PDAA. To the best of our knowledge, there have been no reports of TAE for a ruptured PDAA caused by SAM and MALS. After TAE, the PDAA did not re-rupture.

Esophagobronchial fistula complicated by esophageal achalasia treated by per-oral endoscopic myotomy.

A 48-year-old man who underwent balloon dilation for esophageal achalasia more than 20 years prior developed severe dysphagia and cough during mealtimes. Endoscopic findings showed a markedly dilated esophagus with residue, narrowing of the esophagogastric junction (EGJ), and a fistula in the middle thoracic esophagus. Esophagography showed narrowing of the EGJ and outflow of contrast from the esophagus to the bronchus. In addition, computed tomography showed marked esophageal dilatation and diffuse granular shading in both lungs. Based on these imaging findings, the patient was diagnosed with deterioration of esophageal achalasia and an esophagobronchial fistula (EBF) secondary to achalasia. The increased intra-esophageal pressure caused by the achalasia was suspected to have inhibited the closure of the EBF. Therefore, we believed that per-oral endoscopic myotomy (POEM) would help treat the achalasia and simultaneously contribute to closing of the EBF. Immediately after POEM, the dysphagia and cough improved. Furthermore, the EBF was closed. 14 months after POEM, the patient did not exhibit deterioration of esophageal achalasia and EBF. To the best of our knowledge, there have been no reports of POEM implemented in cases of esophageal achalasia complicated by EBF. Therefore, this case is worth reporting.

Sigmoid Colon Varices due to Massive Thrombosis of a Noncirrhotic Extrahepatic Portosystemic Shunt.

A 33-year-old man presented with hepatic encephalopathy and was diagnosed to have a noncirrhotic extrahepatic portosystemic shunt (NCPSS). He presented with abdominal pain 16 months after the NCPSS diagnosis. Computed tomography revealed thrombosis between the intrahepatic portal vein and the left internal iliac vein, including the NCPSS, and varices of the sigmoid colon. Thrombosis was treated with danaparoid sodium and antithrombin III followed by edoxaban. After treatment, the thrombosis disappeared from the intrahepatic portal vein, but it remained in the NCPSS. The sigmoid colon varices were followed up without any treatment. Follow-up is needed in NCPSS patients in order to make an early detection of complications.