Differential hepatic features presenting in Wilson disease-associated cirrhosis and hepatitis B-associated cirrhosis

BACKGROUND Cirrhosis is a chronic late stage liver disease associated with hepatitis viruses,alcoholism, and metabolic disorders, such as Wilson disease(WD). There are no clear markers or clinical features that define cirrhosis originating from these disparate origins. We hypothesized that cirrhosis is not one disease and cirrhosis of different etiology may have differential clinical hepatic features.AIM To delineate the liver features between WD-associated cirrhosis and hepatitis Bassociated cirrhosis in the Chinese population.METHODS In this observational study, we reviewed the medical data of consecutive inpatients who had WD-associated cirrhosis or hepatitis B-associated cirrhosis from January 2010 to August 2018, and excluded patients who had carcinoma,severe heart or pulmonary diseases, or other liver diseases. According to the etiology of cirrhosis, patients were divided into two groups: WD-associated cirrhosis group(60 patients) and hepatitis B-associated cirrhosis group(56 patients). The liver fibrosis degree, liver function indices, and portal hypertension features of these patients were compared between the two groups.RESULTS No inter-group differences were observed in the diagnostic liver fibrosis markers,however, clinical features clearly defined the origin of cirrhosis. WD-associated cirrhosis patients(16-29 years) had lower levels of alanine transaminase,aspartate transaminase, and bilirubin, lower prothrombin time, lower incidence of hepatic encephalopathy, and lower portal vein diameter(P < 0.05), compared to cirrhosis resulting from hepatitis B in older patients(45-62 years). Importantly,they had decreased risks of progression from Child-Pugh grade A to B(odds ratio = 0.046, 95% confidence interval: 0.006-0.387, P = 0.005) and of ascites(odds ratio = 0.08, 95% confidence interval: 0.01-0.48, P = 0.005). Conversely, WDassociated cirrhosis patients had a higher risk of splenomegaly(odds ratio = 4.15,95% confidence interval: 1.38-12.45, P = 0.011).CONCLUSION WD-associated cirrhosis presents a higher risk of splenomegaly associated with leukopenia and thrombocytopenia, although revealing milder liver dysfunction and portal hypertension symptoms, which recommends WD patients to be monitored for associated complications.

Impact of COVID-19 on the clinical status of patients with Wilson disease

The coronavirus disease 2019(COVID-19)pandemic has greatly impacted health systems.Many guidelines on chronic liver diseases have been released to optimize the use of medical resources and patient management.However,most of these guidelines have been established through expert consensus because the existing data do not provide strong evidence for developing effective recommendations.As Wilson disease(WD)is a rare chronic liver disease,the impact of COVID-19 on the clinical status of patients with WD is unclear.The present study showed a marked shortage of medical resources for clinically managing patients with WD during the pandemic.Although patients with WD who consistently took anticopper therapy showed no significant differences in hepatic and extrahepatic markers before and after the pandemic,their complication incidences,especially the infection incidence,were significantly increased during the study period.Therefore,patients with WD should be encouraged to adhere to anticopper therapy and be closely monitored to prevent infections and other complications.The present study provides a clinical basis for further managing WD during the pandemic.

Supplementation with high-GABA-producing Lactobacillus plantarum L5 ameliorates essential tremor triggered by decreased gut bacteria-derived GABA

Background Theγ-aminobutyric acid(GABA)hypothesis posits a role of GABA deficiency in the central nervous system in the pathogenesis and progression of essential tremor(ET).However,the specific causative factor for GABA deficiency is not clear.The gut microbiota in mammals has recently been considered as a significant source of GABA.Furthermore,the GABA-based signals originating from the intestine can be transmitted to the brain through the“enteric nervous system-vagus nerve-brain”axis.However,the plausible contribution of gut microbiota to ET seems inspiring but remains obscure.Methods Fecal samples from patients with ET and healthy controls were examined by metagenomic sequencing to compare the composition of gut microbiota and the expression of genes involved in GABA biosynthesis.The impact of gut microbiota on ET was explored through transplantation of fecal microbiota from patients with ET into the murine ET model.Lactic acid bacteria producing high amounts of GABA were identified through whole-genome sequencing and ultra-performance liquid chromatography-tandem mass spectrometry.Subsequently,mice were treated with the high-GABA-producing strain Lactobacillus plantarum L5.Tremor severity,behavioral tests,pro-inflammatory cytokines,GABA concentration,and gut microbiota composition were examined in these mice.Results The gut microbiota of patients with ET demonstrated an impaired GABA-producing capacity and a reduced fecal GABA concentration.Transplantation of the gut microbiota from patients with ET induced an extension of tremor duration and impaired mobility in the murine model of ET.L5 exhibited an augmented GABA-producing capacity,with the De Man-Rogosa-Sharpe culture broth containing 262 mg/l of GABA.In addition,administration of L5 significantly decreased the tremor severity and enhanced the movement capability and grasping ability of ET mice.In vivo mechanistic experiments indicated that L5 reshaped the gut microbial composition,supplemented the mucosa-associated microbiota with GABA-producing capacity,increased the GABA concentrations in the cerebellum,and diminished inflammation in the central nervous system.Conclusions These findings highlight that deficiency of GABA-producing gut microbes plays an essential role in the pathogenesis of ET and that L5 is a promising candidate for treating ET.