Autoantibody to GNAS in Early Detection of Hepatocellular Carcinoma: A Large-Scale Sample Study Combined with Verification in Serial Sera from HCC Patients

The aim of this study was to explore the value of autoantibody to GNAS in the early detection of hepatocellular carcinoma (HCC). In a large-scale sample set of 912 participants (228 cases in each of HCC, liver cirrhosis (LC), chronic hepatitis B (CHB), and normal controls (NCs) groups), autoantibody to GNAS was detected with a positive result in 47.8% of HCC patients, which was significantly higher than that in patients with LC (35.1%), CHB (19.7%), and NCs (19.7%). Further analysis showed that the frequency of autoantibody to GNAS started increasing in compensated cirrhosis patients (37.0%) with a jump in decompensated cirrhosis patients (53.2%) and reached a peak in early HCC patients (62.4%). The increasing autoantibody response to GNAS in patients at different stages was closely associated with the progression of chronic liver lesions. The result from 44 human serial sera demonstrated that 5 of 11 (45.5%) HCC patients had elevated autoantibody to GNAS before and/or at diagnosis of HCC. Moreover, 46.1% and 62.4% of high positive rates in alpha-fetoprotein (AFP) negative and early-stage HCC patients can supplement AFP in early detection of HCC. These findings suggest that autoantibody to GNAS could be used as a potential biomarker for the early detection of HCC.

Drug Therapy for Non-Alcoholic Steatohepatitis-Induced Liver Fibrosis

Aim. An overview of current pharmacotherapy for non-alcoholic steatohepatitis (NASH)-associated liver fibrosis.Key points. In current clinical recommendations, therapeutic measures in non-alcoholic fatty liver disease should include lifestyle change, body weight normalisation, NASH-associated liver fibrosis-specific drug therapy and treatment for metabolic syndrome-related diseases. Given a lack of approved antifibrotic therapies in NASH, several drugs have nevertheless demonstrated an adequate efficacy and safety in phase 3 clinical trials, also in compensated cirrhosis, which allows their practical validation in phase 4.Conclusion. The understanding of liver fibrosis as an adverse natural consequence of non-alcoholic fatty liver disease clearly attests for an early introduction and wide use of antifibrotic therapy to improve NASH outcomes and avoid associated complications.

Mortality following elective and emergency colectomy in patients with cirrhosis: a population-based cohort study from England

Background Patients with cirrhosis undergoing colectomy have a higher risk of postoperative mortality, but contemporary estimates are lacking and data on associated risk and longer term outcomes are limited. This study aimed to quantify the risk of mortality following colectomy by urgency of surgery and stage of cirrhosis. Data sources. Linked primary and secondary-care electronic healthcare data from England were used to identify all patients undergoing colectomy from January 2001 to December 2017. These patients were classified by the absence or presence of cirrhosis and severity. Case fatality rates at 90 days and 1 year were calculated, and cox regression was used to estimate the hazard ratio of postoperative mortality controlling for age, gender and co-morbidity. Results Of the total, 36,380 patients undergoing colectomy, 248 (0.7%) had liver cirrhosis, and 70% of those had compensated cirrhosis. Following elective colectomy, 90-day case fatality was 4% in those without cirrhosis, 7% in compensated cirrhosis and 10% in decompensated cirrhosis. Following emergency colectomy, 90-day case fatality was higher; it was 16% in those without cirrhosis, 35% in compensated cirrhosis and 41% in decompensated cirrhosis. This corresponded to an adjusted 2.57 fold (95% CI 1.75–3.76) and 3.43 fold (95% CI 2.02–5.83) increased mortality risk in those with compensated and decompensated cirrhosis, respectively. This higher case fatality in patients with cirrhosis persisted at 1 year. Conclusion Patients with cirrhosis undergoing emergency colectomy have a higher mortality risk than those undergoing elective colectomy both at 90 days and 1 year. The greatest mortality risk at 90 days was in those with decompensation undergoing emergency surgery.

Ascorbic Acid Deficiency Prevalence and Associated Cognitive Impairment in Alcohol Detoxification Inpatients: A Pilot Study

Malnutrition has been reported in alcohol use disorder patients as having a possible influence on cognitive function. The aim of this study was to analyse the prevalence of ascorbic acid (AA) deficiency in inpatients admitted for alcohol detoxification and the associated factors, including cognitive impairment in the early period of abstinence. A retrospective chart review was conducted. The AA level was categorised into three groups: deficiency (AAD) (<2 mg/L), insufficiency (AAI) (2–5 mg/L) and normal level. The cognitive impairment was screened using the Montreal Cognitive Assessment (MoCA). Ninety-six patients were included (74 men; mean age 49.1 years (±11.5)). Twenty-seven AAD (28.1%) and twenty-two AAI (22.9%) were observed. In multivariate analysis, risk factors for AAD versus normal AA level were men (OR 17.8, 95%CI (1.63–194)), compensated cirrhosis (OR 9.35, 95%CI (1.60–54.6)) and street homelessness (OR 5.76, 95%CI (1.24–26.8) versus personal housing). The MoCA score was available for 53 patients (mean MoCA score: 25.7 (±3.3)). In multivariate analysis, the natural logarithm of AA (β = 1.18, p = 0.037) and sedative use disorder (β = −2.77, p = 0.046) were associated with the MoCA score. AAD and AAI are frequent in inpatients admitted for alcohol detoxification. A low level of AA was associated with cognitive impairment in the early period of abstinence.

Efficacy of Glecaprevir/Pibrentasvir for Real-World HCV Infected Patients in the Northern Part of Tokyo, Japan

Hepatis virus C (HCV) infection causes liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. The objective of our study was to examine the effects of the HCV nonstructural protein (NS) 3/4A inhibitor glecaprevir/NS5A inhibitor pibrentasvir on real-world HCV patients in the northern part of Tokyo, Japan. Although 106 patients were consecutively included, a total of 102 HCV-infected patients with chronic hepatitis or compensated cirrhosis, who received 8- or 12-week combination treatment with glecaprevir/pibrentasvir and were followed up to week 12 after the end of treatment were analyzed retrospectively. Only three patients discontinued treatment due to adverse events; however, they achieved a sustained virologic response at 12 weeks (SVR12). Finally, SVR rates were 99.0% (101/102). Only one patient without liver cirrhosis was a treatment relapser who received hepatic resection for HCC approximately two years after commencement of the 8-week combination treatment with glecaprevir/pibrentasvir. After the exclusion of patients with HCV genotype 1b and P32 deletion in the HCV NS5A region, a 12-week combination of glecaprevir/pibrentasvir led to SVR12 in all nine direct-acting antiviral-experienced patients. Glecaprevir/pibrentasvir had a high efficacy and an acceptable safety profile for real-world HCV patients in a single hospital in Japan.

Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure

Background and aims Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. Methods A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis. Results Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36–0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43–0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred. Conclusions The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.

Efficacy of Sofosbuvir, Daclatasvir and Ribavirin combination therapy in treatment naive hepatitis C patients at tertiary care hospital of South Punjab

Introduction: Hepatitis C has gradually become endemic in Pakistan, with infectivity rates one of the highest in the world. The emergence of direct acting antivirals (DAAs) has become a ray of sunshine in eradicating this menace from this region. The combination of sofosbuvir, daclatasvir and ribavirin (SOF/DACLA/RIBA) has had phenomenal success all over the world in eradicating this virus. Our study aims to see the effectiveness of this regime in this part of the world. Methods: After approval from the institutional review board (IRB), retrospective analysis of data of treatment naive patients who have been treated with the above mentioned regimen was collected to assess the efficacy by calculating the sustained virological response (SVR) at 12 weeks after completion of therapy. Results: Data of 300 patients (172 females, 128 males) was collected. Mean age was 39.66 years. Majority (almost 90%) of patients were from District Multan Age range was from 18 years to 60 years. Eighty-three percent of the patients were non-cirrhotics, 15.7% had compensated cirrhosis, while only 1 % had decompensated cirrhosis. Out of the 300 patients, 291 patients had undetectable HCV RNA on polymerase chain reaction (PCR) at 12 weeks after completion of treatment, achieving SVR rates of 97%. There was no significant association of SVR rates with gender and age of patients. Conclusion: The combination of SOF/DACA/RIBA is highly efficacious for treatment of hepatitis C patients. Key Words: sofosbuvir, daclatasvir, efficacy, sustained virological response, hepatitis C

HIF-1α associated logistic regression model serves for predicting decompensation of hepatitis B cirrhosis

Background HIF-1α is relevant to inflammation and fibrosis in hepatitis B virus (HBV)-related liver diseases. Thus, we designed a predictive model for decompensated cirrhosis. Methods Peripheral plasma HIF-1α levels were measured in 52 subjects, including 20 patients with HBV-related-compensated-cirrhosis (HBV-CC), 20 patients with HBV-related-decompensated-cirrhosis (HBV-DC) that underwent transjugular intrahepatic portosystemic shunt (TIPS), and 12 healthy controls (HC). Portal plasma HIF-1α levels were detected in HBV-DC patients. The correlation between clinical data and HIF-1α levels was assessed, logistic regression and nomogram were used to develop prediction model. Results Plasma HIF-1α levels were significantly higher in HBV-DC patients than that in HBV-CC patients and healthy controls (DC: 656.34±417.96, CC: 294.23±138.03, HC: 194.63±54.14, pg/ml; P = 0.0004). Plasma HIF-1α levels were positively correlated with total bile acid, total bilirubin, APRI, FIB-4, and MELD scores, and negatively correlated with albumin and platelets. Multivariate logistic regression manifested that total bilirubin (OR = 19.439; 95% CI: 1.486–254.320, P = 0.024), spleen thickness (OR = 75.144; 95% CI: 4.157–1358.440, P = 0.003) and HIF-1α concentrations above 341.78 pg/ml (OR = 23.580; 95% CI: 1.842–301.781, P = 0.015) were markedly associated with HBV-DC and thus included in the nomogram. The terrific cut-off value for the probability of HBV-DC was > 45%, and area under the curve was 0.954 (P < 0.001), with 95% sensitivity and specificity. Conclusions HIF-1α is related to biochemical liver parameters, cirrhosis grade, and progression to HBV-DC. Our model has preferable predictive value for HBV-DC.

Gene profiling of Toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure

Objectives Toll-like receptors (TLRs) on neutrophils play a crucial role in detecting pathogens and organ/tissue injury in acute-on-chronic liver failure (ACLF). However, little is known about the exact mechanisms and potential signalling pathways. The aim of this study was to investigate alterations in TLR signalling pathways in neutrophils of ACLF patients. Methods Twenty-seven patients with compensated cirrhosis (n = 9), decompensated cirrhosis (n = 9) and ACLF (n = 9) were enrolled in the study. Neutrophils were isolated, and alterations in TLR signalling pathways were evaluated using an RT2 Profiler™ PCR Array. The fold change for each gene (2(−∆∆CT)) was compared among the groups. Genes with a fold change ratio of ≥ 2 or ≤ 0.5 along with a p value of < 0.05 were considered to be differentially expressed. Results A total of 17 genes were upregulated in neutrophils from patients with compensated cirrhosis and were mainly distributed in adaptors, TLR-interacting proteins and downstream pathways. Six genes were detected in patients with decompensated cirrhosis. A trend of downregulation of genes in the TLR signalling pathway was observed in neutrophils of patients with cirrhosis and ACLF. TLR3, IFNG, IL1B, TBK1, CCL2 and LTA were downregulated in neutrophils. Moreover, CD14 and IL10 were upregulated in neutrophils of ACLF patients. Conclusions TLR signalling pathway genes were differentially regulated in neutrophils between cirrhosis and ACLF. In ACLF patients, defective expression of TLR3 and IFN, along with enhanced CD14 and IL10 expression, was characterized by transcriptional alterations of neutrophils.