Compensated Cirrhosis Patients Research Articles

Thrombotic Long-Term Consequences of SARS-CoV-2 Infection in Patients with Compensated Cirrhosis: A Propensity Score-Matched Analysis of a U.S. Database.

Cirrhosis causes an imbalance in the coagulation pathway and leads to a tendency for both bleeding and clotting. SARS-CoV-2 has been reported to be associated with a hypercoagulable state. This study examines SARS-CoV-2's impact on hemostasis in compensated patients with cirrhosis. We analyzed the US Collaborative Network, which comprises 63 HCOs in the U.S.A. Compensated cirrhosis patients were split into two groups: SARS-CoV-2-positive and -negative. Patients' baseline characteristics were used in a 1:1 propensity score-matched module to create comparable cohorts. We compared the risk of portal vein thrombosis (PVT), deep venous thrombosis (DVT), and pulmonary embolism (PE) at 6 months, and 1 and 3 years. Of 330,521 patients, 27% tested positive and 73% remained negative. After PSM, both cohorts included 74,738 patients. Patients with SARS-CoV-2 had a higher rate of PVT compared to those without at 6 months (0.63% vs 0.5%, p < 0.05), 1 year (0.8% vs 0.6%, p < 0.05), and 3 years (1% vs. 0.7%, p < 0.05), a higher rate of DVT at 6 months (0.8% vs. 0.4%, p < 0.05), 1 year (1% vs. 0.5%, p < 0.05), and 3 years (1.4% vs. 0.8%, p < 0.05), and a higher rate of PE at 6 months (0.6% vs. 0.3%, p < 0.05), 1 year (0.7% vs. 0.4%, p < 0.05), and 3 years (1% vs. 0.6%, p < 0.05). The presence of SARS-CoV-2 infection in patients with compensated cirrhosis was associated with a higher rate of PVT, DVT, and PE at 6 months, and 1 and 3 years.

Carvedilol to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by liver stiffness: study protocol for a randomied, double-blind, placebo-controlled, multicentre trial in China

IntroductionPatients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus....

Comparison of Lymphocyte/Monocyte ratio (LMR) with Child-Pugh Score and MELD Score in the Determination of Hepatic Dysfunction Severity and Outcome in Cirrhotic Patient

Background: Lymphocyte/monocyte ratio (LMR) is a simple and effective marker that has the potential to predict the severity of hepatic dysfunction in a cirrhotic patient, like the Model for End-Stage Liver Disease (MELD) score and the Child- Pugh (CP) score. However, the usefulness of this newer tool has not yet been tested. Objectives: Comparison of Lymphocyte/Monocyte ratio with Child-Pugh Score and MELD Score in the determination of hepatic dysfunction severity in patients with cirrhosis was the objective of the study. Materials and Methods: This cross-sectional analytical study was conducted on cases of cirrhotic patients in the Department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University, dated from September 2018 to August 2019. A total of 40 compensated cases and 82 decompensated cases were included in the process of obtaining informed written consent. Information about clinical profile, laboratory parameters (complete blood count including ESR, serum total bilirubin, serum albumin, ALT, AST, serum creatinine, prothrombin time, INR, etc.) were collected. LMR, MELD score, and CP score were calculated both in compensated and decompensated cirrhotic patients to assess the relationship with the severity of hepatic dysfunction. The correlation between LMR and the CP/MELD score was established by the Pearson correlation test. The receiver operating characteristic (ROC) curve and cut-off values of LMR were obtained, and areas under the ROC (AUROC) curve were calculated to identify the best LMR and/or the MELD score or CPS for predicting hepatic decompensation. The Bland-Altman plot and the Heliey- MacNeil test were used for comparison of measurement techniques. The data were analyzed with the help of SPSS version 20. Observation and Results: The mean age of the decompensated group was higher than that of the compensated group (p&lt;0.05). The mean values for LMR and MELD and CP scores were 7.93±3.08, 5.25±0.43 &amp; 7.10 ±1.19, respectively. Average LMR was significantly higher in compensated cirrhosis patients while CP and MELD Score was lower in that group (p&lt;0.001). MELD and CP were positively correlated with each other (p&lt;0.001). LMR was negatively correlated to both MELD and CP scores (p&lt;0.001). Of all patients, only 4 died (3.3%) and rest 118 (96.7%) survived. The cut off value of LMR, CP and MELD were LMR ≤ 2.18 (sensitivity: 75%, specificity: 87.3%), CPS ≥13.5 (sensitivity: 75%, specificity: 98.3%) &amp; MELD ≥30.5 (sensitivity: 75%, specificity: 94.9%) respectively. Pairwise comparison showed that the difference between the AUCs of MELD and LMR was not statistically significant (0.953 vs 0.887; p=0.081). Patients in the low LMR group showed decreased survival than those in the high LMR group (p=0.000). The no survived group had lower LMR and higher MELD and CP scores than those of the survived group (p&lt;0.001). Conclusion: In comparison with Child-Pugh Score and MELD Score in the determination of hepatic dysfunction severity in cirrhotic patients, Lymphocyte/ Monocyte ratio is a useful tool.

SARS-CoV-2 Infection Is an Independent Risk Factor for Decompensation in Cirrhosis Patients.

SARS-CoV-2 causes varied gastrointestinal symptoms. Cirrhosis patients face higher mortality rates from it, especially those with decompensated cirrhosis. This study examines SARS-CoV-2's impact on decompensation in previously compensated cirrhotic patients. We analyzed the Global Collaborative Network, comprising 98 healthcare organizations across sixteen countries, using TriNetX's deidentified research database. Compensated cirrhosis patients were split into two groups: one with SARS-CoV-2-positive patients and another testing negative. Using a 1:1 propensity score matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then assessed decompensation, mortality, and GI bleed at 1 and 3 months. Out of 252,631 identified compensated cirrhosis patients, 27.3% (69,057) tested SARS-CoV-2-positive, while 72.6% (183,574) remained negative. Post PSM, 61,963 patients were in each group. SARS-CoV-2-positive patients showed significantly higher decompensation rates (4.4% vs. 1.9% at 1 month; 6% vs. 2.6% overall). Rates of complications, like ascites, SBP, HE, and HRS, increased notably. Mortality (2.5% vs. 1.7% at 1 month; 3.6% vs. 2.7% at 3 months) and GI bleed (1.3% vs. 0.9% at 1 month; 1.9% vs. 1.2% at 3 months) were also elevated in SARS-CoV-2 patients. SARS-CoV-2 increases decompensation over 2-fold in compensated cirrhosis patients and raises mortality and increases rates of complications at 1 and 3 months.

Prognostic value of virtual portal pressure gradient response in compensated cirrhotic patients treated with carvedilol.

This study aimed to assess the prognostic significance of virtual portal pressure gradient (vPPG) response to carvedilol in patients with compensated cirrhosis (CC). Compensated cirrhosis patients with high-risk varices were prospectively enrolled to receive carvedilol for prevention of first variceal hemorrhage (VH) and followed up for 1year. The vPPG response was defined as a reduction of vPPG >10% from baseline after 1-month therapy. Logistic and Cox regression analyses were performed to identify independent predictors for vPPG response and first decompensation, respectively. Competitive risk models were constructed to predict disease progression, and validated using the C-index, Kaplan-Meier analysis, competitive risk analysis, and calibration curves. A total of 129 patients completed this study, of whom 56 (43.4%) achieved vPPG response and were referred as vPPG responders. Baseline vPPG, red color sign, Model for End-stage Liver Disease score, serum monocyte chemoattractant protein-1 (MCP-1), and laminin levels significantly correlated with vPPG response, which itself was further documented as an independent predictor of VH, ascites, and overall decompensation events in CC. Moreover, the red color sign or Child-Turcotte-Pugh score effectively predicted VH, while ascites correlated well with portal flow velocity or MCP-1. The predictive models for VH and ascites showed a good discrimination with C-index values of 0.747 and 0.689 respectively, and the high consistency on calibration curves. The vPPG response could be used as a noninvasive tool for prediction of disease progression in patients with CC.

Alterations in the gut microbiota and the efficacy of adjuvant probiotic therapy in liver cirrhosis.

Liver cirrhosis is the end stage of various chronic liver diseases (CLDs). The gut microbiota can impact the liver environment and trigger chronic liver inflammation through the gut-liver axis. Alteration of the gut microbiota has become an effective strategy in the biological treatment of cirrhosis. Twenty-eight patients with liver cirrhosis and 16 healthy individuals were included, and fresh stool samples were collected. We analyzed changes in the gut microbiota between groups by 16S rRNA sequencing and evaluated the association between microbiota alterations and hepatic function. Additionally, 102 cirrhotic patients were retrospectively enrolled and divided into a probiotic group (n=44) and a nonprobiotic group (n=58) in addition to standard treatment for cirrhosis. Patients were monitored for hematological parameters and hepatic function during the six-month follow-up. The gut microbiota profile of patients with cirrhosis was greatly different from that of healthy individuals, presenting with significantly reduced α diversity and decreased abundance of representative SCFA-producing bacteria including Firmicutes, Coprococcus and Clostridium IV. The pathogenic bacteria Gammaproteobacteria, Veillonella, and Bacilli were greatly enriched in cirrhotic patients. Additionally, patients with decompensated cirrhosis (DCPC) had a significantly reduced abundance of Oscillibacter compared to compensated cirrhosis (CPC), which is also a SCFA-producing bacteria, and the lower Firmicutes to Bacteroidetes ratio and enhanced MDR values were also shown in DCPC patients compared to CPC patients. In addition, the abundance of Firmicutes was negatively related to hepatic function in cirrhotic patients, including the levels of ALT, AST, and DBIL. From the retrospective study, we found that biochemical improvements in alanine transaminase (ALT) and total bilirubin (TBIL) were obtained in DCPC patients who received oral probiotic therapy compared with the nonprobiotic group. Severe microbial dysbiosis existed in patients with liver cirrhosis, especially patients who reached the decompensatory stage. SCFA-producing bacteria were significantly reduced in cirrhosis. Altered gut microbiota cause changes in functional modules, which may contribute to cirrhosis progression and are associated with clinical prognosis. Adjuvant probiotic supplementation to enhance SCFA-producing bacteria can be a prospective therapy for patients with cirrhosis.

Effectiveness and safety of 8-week glecaprevir/pibrentasvir in HCV treatment-naïve patients with compensated cirrhosis: real-world experience from Taiwan nationwide HCV registry.

Large-scale real-world data of the 8-week glecaprevir/pibrentasvir (GLE/PIB) therapy for treatment-naïve patients of chronic hepatitis C virus (HCV) infection with compensated cirrhosis is scarce. The TASL HCV Registry (TACR) is an ongoing nationwide registry program that aims to set up a database and biobank of patients with chronic HCV infection in Taiwan. In this study, data were analyzed as of 31 October 2021 for treatment-naïve HCV patients with compensated cirrhosis receiving 8-week GLE/PIB therapy. Effectiveness reported as sustained virologic response at off-therapy week 12 (SVR12) and safety profiles were assessed. Patient characteristics potentially related to SVR12 were also evaluated. Of the 301 patients enrolled, 275 had available SVR12 data. The SVR12 rate was 98.2% (270/275) in the modified intention-to-treat (mITT) population and 89.7% (270/301) in the ITT population. For those mITT patients with genotype 3, FibroScan > 20kPa, platelet < 150,000/µl, and FibroScan > 20kPa and platelet < 150,000/µl, the SVR12 rates were 100% (6/6), 100% (12/12), 98.0% (144/147), 100% (7/7), respectively. Overall, 24.9% (75/301) patients experienced adverse events (AEs). The most frequent AEs (> 5%) included fatigue (9.0%) and pruritus (7.0%). Seven (2.3%) patients experienced serious AEs and two (0.7%) resulted in permanent drug discontinuation. None of them were considered as GLE/PIB-related. In this large-scale real-world Taiwanese cohort, 8-week GLE/PIB therapy was efficacious and well tolerated for treatment-naïve compensated cirrhosis patients. SVR12 rates were similarly high as in the clinical trials, including those with characteristics of advanced liver disease.

Correlation between serum liver fibrosis markers and early gastroesophageal varices among patients with compensated liver cirrhosis: a cross-sectional analysis

Background and aimPortal hypertension is a common complication of chronic liver diseases responsible for most liver cirrhosis consequences. In patients with portal hypertension, oesophagogastric variceal bleeding is a leading cause of death. Most research has focused on high-risk gastroesophageal varices and bleeding, with only a few studies on early varices. However, early intervention of gastroesophageal varices was found to better improve the prognosis and reduce mortality, but there is still no relevant research. Ultrasonic endoscopy is a combination of endoscopy and ultrasonic imaging. It can gastroscopically detect varices around the oesophagus and stomach and detect oesophageal collateral veins and perforating veins earlier, which is helpful for the early diagnosis of varices. Therefore, this study aimed to explore the correlation between serum fibrosis markers and early gastroesophageal varices in compensated cirrhosis patients.MethodsThis study included 791 patients with compensated cirrhosis. The selected patients were categorized into three groups. The early gastroesophageal varices group included patients with gastroesophageal varices found by endoscopic ultrasonography but not by gastroscopy. The no gastroesophageal varices group underwent endoscopic ultrasonography and gastroscopy without varices. In addition, gastroesophageal varices can be detected with both techniques. Multiple logistic regression analysis explored the association of serum fibrosis markers with early gastroesophageal varices.ResultsAmong the 791 compensated liver cirrhosis patients, 198 patients were without gastroesophageal varices, 279 patients had early gastroesophageal varices, 314 patients had gastroesophageal varices, and both techniques could detect varices. There was a positive correlation between serum fibrosis markers and early gastroesophageal varices. In univariate logistic regression analysis, the patients with early gastroesophageal varices had lower platelet counts (P = 0.034) and higher aspartate aminotransferase (P = 0.046), total bilirubin (P = 0.041), hyaluronic acid (P < 0.001), laminin (P < 0.001), type III procollagen (P = 0.005), type IV collagen (P = 0.002), liver stiffness measurement (P = 0.001), APRI (P = 0.019) and FIB-4 (P = 0.002). Multivariate analysis showed that laminin (OR 1.011; 95% CI 1.004-1.017, P = 0.001) was an independent risk factor for predicting early gastroesophageal varices in compensated cirrhosis patients.ConclusionHigher laminin was independently associated with early gastroesophageal varices in compensated cirrhosis patients.

Use of serum Golgi protein 73 for screening chronic hepatitis B virus infection patients needing antiviral therapy in the community.

Use of serum Golgi protein 73 for screening chronic hepatitis B virus infection patients needing antiviral therapy in the community.

Variability of noninvasive MRI and biological markers in compensated cirrhosis: insights for assessing disease progression

BackgroundWe annually monitored stable compensated cirrhosis (CC) patients to evaluate serial variation in blood serum, liver stiffness, and multiparametric magnetic resonance imaging (mpMRI) measures to provide reference change values (RCV) and sample size measures for future studies.MethodsPatients were recruited from a prospectively followed CC cohort, with assessments at baseline and annually over three years. We report on blood markers, transient elastography liver stiffness measures (LSM) and noninvasive mpMRI (volume, T1 mapping, blood flow, perfusion) of the liver, spleen, kidneys, and heart in a stable CC group and a healthy volunteer (HV) group. Coefficient of variation over time (CoVT) and RCV are reported, along with hazard ratio to assess disease progression. Sample size estimates to power future trials of cirrhosis regression on mpMRI are presented.ResultsOf 60 CC patients enrolled, 28 with stable CC were followed longitudinally and compared to 10 HVs. CoVT in mpMRI measures was comparable between CC and HV groups. CoVT of Enhanced Liver Fibrosis score was low (< 5%) compared to Fibrosis-4 index (17.9%) and Aspartate Aminotransferase-to-Platelet-Ratio Index (19.4%). A large CoVT (20.7%) and RCV (48.3%) were observed for LSM. CoVT and RCV were low for liver, spleen, and renal T1 values (CoVT < 5%, RCV < 8%) and volume (CoVT < 10%, RCV < 16%); haemodynamic measures were high (CoVT 12–25%, RCV 16–47%).ConclusionsEvidence of low CoVT and RCV in multiorgan T1 values. RCV and sample size estimates are provided for future longitudinal multiorgan monitoring in CC patients.Trial registrationClinicalTrials.gov identifier: NCT02037867, Registered: 05/01/2013.

Efficacy and safety of Fuzheng Huayu tablet on persistent advanced liver fibrosis following 2 years entecavir treatment: A single arm clinical objective performance criteria trial

Ethnopharmacological relevanceAntiviral therapy can alleviate liver fibrosis in chronic hepatitis B, but it has a limited effect on advanced liver fibrosis/cirrhosis. Traditional Chinese medicine (TCM), particularly FuZheng HuaYu (FZHY) tablet, appears to have an antifibrotic effect, but its improving resolution of hepatitis b virus (HBV) -associated advanced fibrosis and experienced anti-viral treatment has not been investigated. Aim of the studyTo observe the safety and efficacy of adjunctive FZHY on the HBV-associated cirrhosis patients who received 2 years of entecavir but still with advanced fibrosis. MethodsAn open-label, multicentre, single arm trial. 251 patients were included and treated with TCM consisted of FZHY tablets 1.6 g and granules, three times a day in addition to entecavir 0.5 mg daily for an additional 48 weeks. Primary outcome was regression of fibrosis (the proportion of patients with a 1-point decrease in the Ishak liver fibrosis score from baseline to week 48). ResultsFibrosis regression occurred in 94 of 184 patients with paired liver biopsy (51.09%, 95% CI: 43.9～58.0). In 132 compensated cirrhosis patients (Ishak score ≥5), 56.06% (74/132, 95% CI: 47.5～64.2) showed fibrosis regression and reached the goal of 54% (15% more than entecavir mono-therapy). 10 patients occurred adverse reaction, most of them were mild, and all recovered or achieved remission. ConclusionsThe combination therapy of FZHY, TCM granules and ETV could regress the liver fibrosis in the patients with HBV cirrhosis, who experienced 2 years of ETV treatment, and it is safe and well tolerated.

ADAMTS-13/von Willebrand factor ratio: A prognostic biomarker for portal vein thrombosis in compensated cirrhosis. A prospective observational study

Background and aimsIn cirrhosis, decreased portal flow velocity, thrombophilia factors, and portal hypertension are considered risk factors for portal vein thrombosis (PVT). In cirrhosis, the transformation of the stellate cells causes a progressive decrease of ADAMTS-13, while VWF multimers secretion by endothelial cells is strongly enhanced. This imbalance leads to an accumulation of ultra-large VWF multimers that in sinusoidal circulation could favor PVT both in intra- and extra-hepatic branches, mostly in decompensated cirrhosis. This prospective study was aimed at identifying possible clinical, biochemical, and hemostatic factors predictive for non-tumoral PVT in a cohort of patients with compensated cirrhosis. MethodsSeventynine compensated cirrhosis patients were prospectively followed for 48 months, receiving a periodic Doppler-ultrasound liver examination associated with an extensive evaluation of clinical, biochemical, and hemostatic profile. ResultsFive patients developed PVT (cumulative prevalence = 6.3%), occurring 4–36 months after enrollment. In logistic regression analysis, the ADAMTS-13/VWF:GpIbR ratio < 0.4 was the only independent variable significantly associated with PVT (OR 14.6, 95% C.I.:1.36–157.2, p = 0.027). A Cox-regression-analysis confirmed this finding (HR = 7.7, p = 0.027). ConclusionsThe ADAMTS-13/VWF ratio < 0.4 measured in compensated cirrhosis could be a reliable predictive biomarker for PVT development, paving the way to novel therapeutic strategies to prevent and treat PVT in this clinical setting.

Efficacy and safety of sofosbuvir/velpatasvir with or without ribavirin in hepatitis C genotype 3 compensated cirrhosis: A meta-analysis

BACKGROUNDHepatitis C virus (HCV) is a leading cause of liver cirrhosis and hepatocellular carcinoma globally. Sofosbuvir/velpatasvir (SOF/VEL) is an effective pan-genotypic direct-acting antiviral combination for treatment of chronic HCV infection. While the addition of ribavirin (RBV) to SOF/VEL improved sustained virological response (SVR12) in genotype 3 (GT3) decompensated cirrhosis patients, the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear. AIMTo evaluate the efficacy and safety of SOF/VEL, with or without RBV in GT3 compensated cirrhosis patients. METHODSWe searched four electronic databases (PubMed/Medline, Embase, Cochrane Library and Web of Science) from inception up to June 2021 using both free text and MeSH terms. There was no restriction on language, geography, publication dates and publication status (full text or abstracts). All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL, with or without RBV, were included, regardless of age, gender or prior treatment experience. The primary outcome was sustained virological response 12-wk post-treatment (SVR12). The secondary outcome was treatment-related adverse events, as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL. The pooled relative risk (RR), 95%CI and heterogeneity (I2) were estimated using Review Manager version 5.3.RESULTSFrom 1752 citations, a total of seven studies (2 randomized controlled trials, 5 cohort studies) with 1088 subjects were identified. The SVR12 was similar in GT3 compensated cirrhosis patients, regardless of the use of RBV, for both the intention-to-treat RR 1.03, 95%CI: 0.99-1.07; I2 = 0%) and the per-protocol analysis (RR: 1.03, 95%CI: 0.99-1.07; I2 = 48%). The overall pooled rate of treatment-related adverse events was 7.2%. Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL (RR: 4.20, 95%CI: 1.29-13.68; I2 = 0%). Subgroup analysis showed that RBV was associated with a higher SVR12 in GT3 compensated cirrhosis patients with baseline resistance-associated substitutions. However, addition of RBV did not significantly increase the SVR12 among treatment-experienced GT3 compensated cirrhosis patients. CONCLUSIONRibavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL. Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients.

Geographic Distribution of HCV Genotypes and Efficacy of Direct-Acting Antivirals in Chronic HCV-Infected Patients in North and Northeast China: A Real-World Multicenter Study.

Objective To assess the geographic distribution of HCV genotypes, effectiveness, and safety of DAA treatment for HCV-infected patients in North and Northeast China. Methods The geographic distribution of HCV genotypes was analyzed in 2162 patients recruited from April 2018 to February 2021. Sustained virologic response rates at 12 (SVR12) or 24 (SVR24) weeks posttreatment and safety were analyzed in 405 patients who completed DAA treatment according to patient baseline characteristics and treatment. Results Four genotypes and six subtypes were identified as follows: 1b (1187, 54.90%), 2a (790, 36.54%), 3a/b (134, 6.20%), 6a/n (44, 2.04%), mixed genotypes (2a-6a or 2a-3a) (7, 0.32%). Overall, 99.01% patients achieved SVR12, while 98.43% achieved SVR24. All patients treated with elbasvir/grazoprevir (EBR/GZR), sofosbuvir/velpatasvir ± ribavirin (SOF/VEL ± RBV), and SOF/ledipasvir (LDV) achieved SVR12 or SVR24; 92.86% SVR12 and 95.83% SVR24 were observed in patients using SOF + RBV. SVR12 was higher in noncirrhosis versus compensated cirrhosis patients (100% vs. 97.09%, p=0.022). No severe drug-related adverse event was observed. Conclusions Genotypes 1b and 2a were dominant subtypes in North and Northeast China. The approved drug regimens EBR/GZR and SOF/LDV for subtype 1b and SOF/VEL for nongenotype 1b are the optimal effective and safety profile.

Evolución de los pacientes con infección crónica por hepatitis C con fibrosis avanzada o cirrosis curados con antivirales de acción directa. Seguimiento a largo plazo

AimsTo analyze laboratory parameters, clinical and fibrosis evolution in F3-F4 patients cured with direct-acting antivirals (DAA). Patients and methodsUnicenteric, observational and prospective study. All F3–F4 hepatitis C patients cured with DAA from 01/11/2014 to 31/08/2019 were included. A basal visit (BV) was performed and at 12 weeks (12w), 1, 2, 3 and 4 years after treatment.Demographic and laboratory variables, fibrosis measured by non-invasive tests, indirect markers of portal hypertension, the presence of esophageal varices, cirrhosis decompensation and hepatoceullar carcinoma were collected. Results169 patients were treated: 123 (72.8%) men, age 57.5±12 years; 117 (69.2%) with cirrhosis, 99 (84.6%) ChildA. 96,4% achieved SVR.The study was conducted for a median follow-up of 46.14 (2.89-62.55) months. It was observed a significant increase in platelets [155×103/μL (BV); 163×103/μL (12w)], cholesterol [158mg/dL (BV); 179mg/dL (12w)] and albumin [4.16g/dL (BV); 4.34g/dL (12w)] and a significant decrease in ALT [82UI/L (BV); 23UI/L (12w], AST [69UI/L (BV); 26UI/L (12w)], GGT [118UI/L (BV); 48UI/L (12w)] and bilirrubin [0.9mg/dL (BV); 0.7mg/dL (12w)]. Fibrosis also improved early in follow-up, both by serological methods and Fibroscan [19.9kPa (BV); 14.8kPa (12w; P<.05].8.1% of compensated cirrhosis patients had some decompensation. 4.5% developed esophageal varices.Nine patients (5.52%) had de novo hepatocellular carcinoma; 6 (3.68%) had hepatoceullar carcinoma in BV and 40% had a recurrence.During follow-up mortality was 9.2%. ConclusionsThere is an improvement in laboratory parameters and fibrosis measured by non-invasive methods in F3-F4 patients cured with DAA. However, the risk of decompensation and the incidence/recurrence of hepatocellular carcinoma still remain, so there is a need to follow these patients.

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.

Health-Related Quality of Life Among Liver Disorder Patients in Northern India.

Objective:The present study aims to determine the health-related quality of life (HRQoL) among liver disorder patients being treated in tertiary care hospital in north India and exploration of factors affecting HRQoL.Methodology:The HRQoL was assessed among 230 patients visiting either the outpatient department (OPD) or those admitted in high dependency unit (HDU) or liver intensive care unit (ICU) using direct measuring tools such as Euro QoL five-dimension questionnaire (EQ-5D) and EQ visual analog scale. Multivariate regression was used to explore the factors influencing HRQoL.Results:Mean EQ-5D scores among chronic hepatitis and compensated cirrhosis patients were 0.639 ± 0.062 and 0.562 ± 0.048, respectively. Among those who were admitted in the ICU or HDU, mean EQ-5D score was 0.295 ± 0.031. At discharge, this score improved significantly to 0.445 ± 0.055 (P < 0.001). The multivariate results implied that HRQoL was significantly better among patients with lower literacy level (P = 0.018) and those treated in OPD settings (P < 0.001).Conclusion:HRQoL is impaired among patients suffering from liver disorders specifically those admitted in ICU. Further, there is a need to generate more evidence to explore the impact of determinants and treatment-associated costs on the HRQoL.

Global real-world evidence of sofosbuvir/velpatasvir (SOF/VEL) as a highly effective treatment in underserved patient populations because of mental health disorders, incarceration or homelessness

The treatment of vulnerable populations must be prioritized to accomplish the WHO HCV elimination goals by 2030, including patients with mental health disorders, incarcerated patients or homeless patients. Simplifying the treatment cascade and rapid treatment start is key to achieving this goal, even more so in the COVID-19 era. Sofosbuvir/velpatasvir (SOF/VEL) is a protease inhibitor-free, pangenotypic, panfibrotic, single duration, single tablet regimen, to be taken without regards to food and with limited drug-drug interactions, allowing treatment simplification. Purpose: This real world data (RWD) analysis evaluates the effectiveness and safety of SOF/VEL for 12 weeks in a heterogeneous HCV population who suffer a mental health disorder, are incarcerated, or homeless. 33 clinical cohorts across Australia, Canada, Europe & USA included 1,888 patients, 280 of them (from 6 clinical cohorts) were treated in Canada and overall managed following local standards of care. Adults were included if SOF/VEL for 12 weeks was started before November 2019 and completed while suffering a mental health disorder, being incarcerated or homeless, irrespective of genotype (GT), presence of compensated cirrhosis (CC) or treatment experience. Exclusion criteria were history of decompensation, prior NS5A-inhibitor exposure, treatment duration >12 weeks or addition of ribavirin. Sustained virological response (SVR; ≥12 weeks after end-of-treatment) and time to treatment initiation were assessed. Overall analysis includes 1,888 (71.3% male) patients (1,422 with a mental health disorder, 526 incarcerated, 153 homeless) aged 50 years, 24.4% were taking antipsychotic drugs and 52.2% of patients had former or current intravenous drug use. 43.2% patients had HCV GT1, 11.6% GT2, 36.3% GT3, 5.9% GT4-6, and 3.0% mixed/unknown GT. 19.0% patients had CC and 12.4% were treatment-experienced. In 257 patients (13.6%), SVR was not evaluated due to non-virological or unknown reasons; 79.9% of those were lost to follow-up (LTFU). When SVR was measured, 98.0% (n=1598/1631) achieved SVR, with 97.6%, 98.9% and 100% in patients with a mental health disorder, incarcerated or homeless patients, respectively. SVR was 98.5% in non-cirrhotic and 95.4% in CC patients. SVR remained >95% under antipsychotic use or coexistence of two negative factors of non-response such as GT3 plus active drug use or psychiatric disorder. SVR was similar, irrespective of time from diagnosis to treatment. Detailed analysis of the Canadian cohort data will be presented at the conference. A test-and-treat strategy, easily implemented with SOF/VEL, and supported by the AASLD/ALEH/APASL/EASL joint call to action, could further enhance the population-level efficacy of HCV therapy by reducing the rate of non-virologic failure due to LTFU and related factors.

Improved Mortality But Increased Economic Burden of Disease in Compensated and Decompensated Cirrhosis: A US National Perspective.

Cirrhosis remains a major burden on the health care system despite substantial advances in therapy and care. Studies simultaneously examining mortality, readmission, and cost of care are not available. Here, we hypothesized that improved patient care in the last decade might have led to improved outcomes and reduced costs in patients with cirrhosis. We identified compensated cirrhosis (CC) and decompensated cirrhosis (DC) patients using carefully chosen ICD-9/ICD-10 codes from the Nationwide Readmission Database (NRD) (years 2010 to 2016). We evaluated trends of 30-day all-cause mortality, 30-day readmission, and inflation-adjusted index hospitalization and readmission costs. Factors associated with mortality and readmission were identified using regression analyses. A total of 3,374,038 patients with cirrhosis were identified, of whom nearly 50% had a decompensating event on initial admission. The 30-day inpatient mortality rate for both CC and DC patients decreased from 2010 to 2016. The 30-day readmission rate remained stable for DC and declined for CC. Over the study period, 30-day readmission costs increased for DC and remained unchanged for CC. The median cost for index hospitalization remained nearly unchanged, but the cost of readmission increased for both CC and DC groups. Gastrointestinal diseases and infections were the leading cause of readmission in CC and DC patient groups. Inpatient mortality has decreased for CC and DC patients. Readmission has declined for CC patients and remained stable for DC patients. However, the economic burden of cirrhosis is rising.

Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development

There is a major unmet need to assess the prognostic impact of antifibrotics in clinical trials because of the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. A fibrosis progression signature (FPS) was defined to predict fibrosis progression within 5 years in patients with hepatitis C virus and nonalcoholic fatty liver disease (NAFLD) with no to minimal fibrosis at baseline (n= 421) and was validated in an independent NAFLD cohort (n= 78). The FPS was used to assess response to 13 candidate antifibrotics in organotypic exvivo cultures of clinical fibrotic liver tissues (n= 78) and cenicriviroc in patients with nonalcoholic steatohepatitis enrolled in a clinical trial (n= 19, NCT02217475). A serum protein-based surrogate FPS was developed and tested in a cohort of compensated cirrhosis patients (n= 122). A 20-gene FPS was defined and validated in an independent NAFLD cohort (adjusted odds ratio, 10.93; area under the receiver operating characteristic curve, 0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacologic target using clinical liver tissues. Systematic exvivo evaluation of 13 candidate antifibrotics identified rational combination therapies based on epigallocatechin gallate, which were validated for enhanced antifibrotic effect in exvivo culture of clinical liver tissues. In patients with nonalcoholic steatohepatitis treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of the PPARα pathway was absent in patients without fibrosis improvement, suggesting a benefit of combining PPARα agonism to improve the antifibrotic efficacy of cenicriviroc. A 7-protein serum protein-based surrogate FPS was associated with the development of decompensation in cirrhosis patients. The FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform antifibrotic drug development.