Proton Pump Inhibitors Increases Longitudinal Risk of Mortality, Decompensation, and Infection in Cirrhosis: A Meta-Analysis.

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) are frequently prescribed to cirrhotic patients, but there is limited longitudinal evidence regarding their effects. This study aimed to assess the impact of PPIs on adverse events in cirrhotic patients. METHODS: A comprehensive search was conducted using the Medline and Embase databases to identify relevant articles. Pooled hazard ratios (HRs) using DerSimonian and Laird random-effects model were calculated to evaluate the risk of adverse events such as long-term mortality, hepatic decompensation, hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and overall infection in cirrhotic patients with PPI use. RESULTS: The analysis included 28 studies with 260,854 cirrhotic patients. The prevalence of PPI use among cirrhotic patients was 55.93%. The use of PPIs was not significantly associated with short-term mortality in cirrhotic patients. However, long-term mortality (HR 1.321, 95% CI 1.103-1.581, P = 0.002), decompensation (HR 1.646, 95% CI 1.477-1.835, P < 0.001), HE (HR 1.968, 95% CI 1.372-2.822, P < 0.001), SBP (HR 1.751, 95% CI 1.649-1.859, P < 0.001), and infection (HR 1.370, 95% CI 1.148-1.634, P < 0.001) were significantly associated with PPI use. Sensitivity analysis with prospective studies yielded similar results. CONCLUSION: PPIs should be reserved for appropriate indications at lowest effective dose for cirrhotic patients due to the potential harm.

Efficacy and Safety of Statin for Hepatocellular Carcinoma Prevention Among Chronic Liver Disease Patients: A Systematic Review and Meta-analysis.

INTRODUCTION AND AIM: Hepatocellular carcinoma (HCC) is a deadly complication among patients with chronic liver disease (CLD). Controversies on the efficacy and safety of statin to prevent HCC among patients with CLD remain despite the growing evidences. We aim to investigate the efficacy and safety of using statin for HCC prevention among adult with CLD. METHODS: We performed a systematic search of 4 electronic databases (PubMed/MEDLINE, EMBASE, Cochrane library, and ClinicalTrial.gov) up to April 15, 2020. We selected all types of studies evaluating the statin use and the risk of HCC among CLD patients, regardless of language, region, publication date, or status. The primary endpoint was the pooled risk of HCC. The secondary endpoint was the risk of statin-associated myopathy. RESULT: From 583 citations, we included a total of 13 studies (1,742,260 subjects, 7 types of statins), fulfilling the inclusion criteria, evaluating efficacy and safety of statin in CLD patients for HCC prevention. All studies were observational (2 nested case-control studies, 11 cohort studies), and no randomised trial was identified. We found that statin user has a lower pooled risk of HCC development (hazard ratio=0.57, 95% confidence interval: 0.52-0.62, I2=42%). HCC reduction was consistent among statin users in cirrhosis, hepatitis B virus, and hepatitis C virus infections. The risk of statin-associated myopathy was similar between statin user and nonuser (hazard ratio=1.07, 95% confidence interval=0.91-1.27). CONCLUSION: Statin use was safe and associated with a lower pooled risk of HCC development among adults with CLD. Given the bias with observation studies, prospective randomised trial is needed to confirm this finding.

Validation of the Expanded Baveno-VI Criteria for Screening Gastroscopy in Asian Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND: The expanded Baveno-VI criteria may further reduce the need for screening gastroscopy compared to Baveno-VI criteria. AIM: We sought to validate the performance of these criteria in a cohort of compensated advanced chronic liver disease (cACLD) patients with predominantly hepatitis B infection. METHODS: Consecutive cACLD patients from 2006 to 2012 with paired liver stiffness measurements and screening gastroscopy within 1 year were included. The expanded Baveno-VI criteria were applied to evaluate the sensitivity (SS), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) for the presence of high-risk varices (HRV). RESULTS: Among 165 cACLD patients included, 17 (10.3%) had HRV. The commonest etiology of cACLD was chronic hepatitis B (36.4%) followed by NAFLD (20.0%). Application of expanded Baveno-VI criteria avoided more screening gastroscopy (43.6%) as compared to the original Baveno-VI criteria (18.8%) without missing more HRV (1 with both criteria). The overall SS, SP, PPV and NPV of the expanded Baveno-VI criteria in predicting HRV were 94.1%, 48.0%, 17.2% and 98.6%, respectively. CONCLUSION: Application of the expanded Baveno-VI criteria can safely avoid screening gastroscopy in 43.6% of cACLD patients with an excellent ability to exclude HRV.

Prognostic impact of age on outcomes of hepatic decompensation in patients with compensated cirrhosis (CHESS2102): an international, multicenter cohort study.

Baveno VII criteria (B7C) and Baveno VI criteria (B6C) have been widely used to estimate the risk of hepatic decompensation. However, the impact of age on these criteria warrants further investigation. The international, multicenter cohort study included 1138 patients with compensated cirrhosis (median follow-up of 40.6 months), aiming to evaluate the value of age in predicting hepatic decompensation. We identified age as an independent predictor of hepatic decompensation, with 60 years determined as the optimal cut-off value. The occurrence of decompensation was 18.7% and 6.7% in the older (age ≥60 years) and younger (age <60 years) groups, respectively (p < 0.001). We subsequently integrated age into the existing Baveno criteria. In patients not meeting Baveno criteria (defined as not meeting B6C or B7C), the older group exhibited a significantly elevated risk of decompensation compared to the younger group (p < 0.05). However, no significant difference was observed between the older and younger groups in patients meeting Baveno criteria (p > 0.05). In conclusion, our study demonstrated that integrating age into the Baveno criteria could enhance the assessment of hepatic decompensation. Age should be considered before discharging patients with compensated cirrhosis from the surveillance of hepatic decompensation.

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.

INTRODUCTION: Patients 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. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy. METHODS AND ANALYSIS: This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073864.

Incidence and type of adverse events in patients taking vonoprazan: A systematic review and meta-analysis.

Background: Vonoprazan, a novel acid-suppressive drug, is non-inferior to proton pump inhibitors (PPIs) for the management of gastric acid-related diseases. However, the safety of vonoprazan has not been systematically evaluated yet. Objectives: To elucidate the incidence and type of adverse events (AEs) in patients taking vonoprazan. Design: Systematic review and meta-analysis. Data sources and methods: PubMed, EMBASE, and Cochrane Library databases were searched for all studies reporting the safety of vonoprazan. The incidences of any AEs, drug-related AEs, serious AEs, AEs leading to drug discontinuation, and common AEs were pooled. Odds ratios (ORs) were calculated to compare the incidence of AEs between patients taking vonoprazan and PPIs. Results: Seventy-seven studies were included. The pooled incidences of any AEs, drug-related AEs, serious AEs, and AEs leading to drug discontinuation were 20, 7, 1, and 1%, respectively. The incidences of any AEs (OR = 0.96, p = 0.66), drug-related AEs (OR = 1.10, p = 0.44), serious AEs (OR = 1.14, p = 0.36), and AEs leading to drug discontinuation (OR = 1.09, p = 0.55) were not significantly different between patients taking vonoprazan and PPIs. In subgroup analyses, patients with peptic ulcer disease (PUD) had higher incidences of any AEs, serious AEs, and AEs leading to drug discontinuation than those with gastroesophageal reflux disease (GERD), Helicobacter pylori (H. pylori) infection, and artificial ulcer after gastric endoscopic submucosal dissection (ESD), but patients with H. pylori infection had a higher incidence of drug-related AEs than those with PUD, GERD, and artificial ulcer after gastric ESD. The incidence of AEs was higher in patients taking long-term use of vonoprazan than those taking short-term use of vonoprazan. Conclusion: Vonoprazan is well tolerated and shows similar safety compared to PPIs. The safety of vonoprazan may be primarily influenced by its indications and duration. Registration: PROSPERO CRD42022314982.

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease.

Background: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no appropriate guidance on CKD in individuals with MAFLD. Furthermore, there has been little attention paid to the link between MAFLD and CKD in the Nephrology community. Methods and Results: Using a Delphi-based approach, a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD. Conclusions: This Delphi-based consensus statement provided guidance on the epidemiology, mechanisms, management and treatment of MAFLD and CKD, as well as the relationship between the severity of MAFLD and risk of CKD, which establish a framework for the early prevention and management of these two common and interconnected diseases.

Acute liver failure and seizure: a case report of an unusual presentation of acute painless aortic dissection.

BACKGROUND: Painless aortic dissection presenting with seizure and acute liver failure is uncommon. We described a case of early recognition leading to successful treatment of painless aortic dissection with atypical presentation. CASE SUMMARY: A young lady presented with generalized tonic-clonic seizures coupled with hepatitic pattern of deranged liver function test. Examination revealed blood pressure of 99/75 mmHg and hepatic flap. Electrocardiography showed sinus tachycardia. Urgent bedside echocardiography showed preserved cardiac function without significant valvular pathology, but noted a moderate pericardial effusion. Abdominal Ultrasound excluded liver cirrhosis or biliary obstructions. Viral hepatitis serologies and anti-liver panel were negative. She was progressively hypotensive with concurrent acute liver failure and oliguric acute kidney injury. Despite no chest pain, her rising serum troponin and widened mediastinum prompted an urgent computed-tomography aortogram, which showed a 4.3 cm dilatation of ascending thoracic aorta with acute haemopericardium and cardiac tamponade. She was diagnosed with malperfusion syndrome from Stanford type A aortic dissection. She underwent emergent ascending aorta and aortic arch repair and dialysis. She experienced complete recovery in her kidney, liver, and neurological function post-operatively. DISCUSSION: Painless aortic dissection masquerade as acute liver failure is uncommon. We describe a successful early recognition of malperfusion syndrome from painless aortic dissection, thus providing window for timely, life-saving intervention. Clinical challenges in this case include: (i) atypical presentation of aortic dissection, (ii) worsening acute liver failure which could lead to unnecessary liver transplantation, and (iii) risk of contrast-induced nephropathy in the setting of acute renal failure.

Control of Large-Area Orderliness of a 2D Supramolecular Chiral Microstructure by a 1D Interference Field.

Self-organized periodic micro/nanostructures caused by stimulus-responsive structural deformation often occur in anisotropic self-assembled supramolecular systems (e.g., liquid crystal systems). However, the long-range orderliness of these structures is often beyond control. In this article, we first demonstrate that a large-area disordered two-dimensional (2D) microgrid chiral structure appears in the cholesteric liquid crystal (CLC) reactive mixture because of the photopolymerization-induced Helfrich deformation effect under exposure to the single UV-laser beam. The result is attributed to the impact of an internal longitudinal strain, which is caused by the pitch contraction of the CLC-monomer region through the continuing compression of the thickening CLC polymer layer adhered on the illuminated substrate of the sample during photopolymerization. The experimental results further show that a one-dimensional (1D) UV-laser interference field can be used to effectively control the postformed 2D microgrid structure to arrange in an orderly manner throughout the large exposed area (an order of centimeter). The optimum ability for controlling the orderliness of the microgrid structure can be achieved if the spacing width of the interference field approximates the periodicity of the postformed 2D microgrids. Several factors, such as the pitch of the CLC mixture and the included angle and intensity of the two interfering laser beams, which influence the orderliness and properties of the 2D microgrid structure, are explored in this study. The result of this research opens a new page to improve the applicability of the Helfrich deformation phenomenon and further provides a reference platform for manipulating, modifying, and even tailoring periodic micro/nanostructures in self-organized supramolecular soft-matter systems for application in advanced optics/photonics.

Efficacy and Safety of IV albumin for non-spontaneous bacterial peritonitis infection among patients with cirrhosis: A systematic review and meta-analysis.

Efficacy and Safety of intravenous albumin for non-spontaneous bacterial peritonitis infection among patients with cirrhosis: A systematic review and meta-analysis of randomized controlled trials INTRODUCTION: Bacterial infection is a common cause of acute-on-chronic liver failure (ACLF) and death among cirrhosis. The benefit of intravenous (IV) albumin among cirrhosis with non-SBP infection remains unclear as individual studies are underpowered to detect the survival benefit of IV albumin. AIM: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of intravenous albumin for non-SBP infection among cirrhosis patients. METHODS: We performed a systematic search of electronic databases (Pubmed, MEDLINE and Clinicalkey) up to 1st December 2019. Studies evaluating IV albumin for non-SBP infection were selected. Using random effect model, the pooled odds ratio (OR), 95% confidence interval (95%CI) and heterogeneity were assessed. RESULTS: A total of 3 RCTs (406 subjects) fulfilling the inclusion criteria among 218 citations were identified. There was no significant heterogeneity across included studies. In this meta-analysis, we found that the pooled risk of renal impairment (RI) (OR=0.58, 95%CI: 0.28-1.23, I2=0%), mortality at 30 days (OR=1.61, 95%CI: 0.87-3.00, I2=0%) as well as mortality at 90 days (OR=1.30, 95%CI: 0.81-2.07, I2=0%) were similar between albumin and control group. Pooled event of pulmonary edema occurred more commonly in albumin group (OR 5.17, 95%CI 1.62-16.47, I2=0%). More subjects achieved resolution of ACLF in IV albumin group as compared to control group (OR=0.11, 95%CI: 0.02-0.69, p=0.02). CONCLUSION: Albumin did not reduce the risk of RI and mortality, yet increases the risk of pulmonary edema. Albumin may promote recovery of ACLF, however, more data is required to validate this benefit.

Do total parenteral nutrition and bowel rest reduce the risk for perforation in patients with gastrointestinal tract lymphoma receiving chemotherapy?

OBJECTIVES: Gastrointestinal tract (GIT) lymphoma is associated with a risk for perforation while the patient is receiving chemotherapy. The role of total parenteral nutrition (TPN) and bowel rest in preventing perforation is unknown. The aim of this study was to examine the clinical outcomes of TPN and bowel rest in patients with GIT lymphoma who were receiving chemotherapy. METHODS: We reviewed all patients with GIT biopsy-proven lymphoma in our institution between 2013 and 2017. Patients were stratified into two groups, with and without TPN and bowel rest during chemotherapy. We identified 158 patients with GIT lymphoma. Of these, 47 (29.7%) received TPN and bowel rest before chemotherapy. Patients who received TPN were younger, more likely to have aggressive lymphoma in the small or large bowel. The primary outcome was to compare the perforation rate between the two groups. Secondary outcome analysis included infection rate and survival. RESULTS: Patients with perforation had significantly poorer survival. Perforation rate was similar between the TPN and the non-TPN groups (8.5% versus 2.7%, P = 0.197). Overall survival was similar between the two groups (P = 0.659). The TPN group had a higher infection rate (odds ratio, 5.32; 95% confidence interval, 1.36-20.8) after adjustment for covariates (age, types of lymphoma, and location of lymphoma). CONCLUSION: The present study demonstrated that TPN and bowel rest did not reduce the risk for perforation among patients with GIT lymphoma who were receiving chemotherapy. As the practice of prophylactic TPN and bowel rest was associated with higher infection risk and longer hospitalization, we do not recommend such practice for all patients with GIT lymphoma receiving chemotherapy.

Economic evaluation of direct-acting antivirals for the treatment of genotype 3 hepatitis C infection in Singapore.

BACKGROUND AND AIM: The prohibitively high cost of direct-acting antivirals (DAA) for hepatitis C virus (HCV) infection remains a barrier to treatment access in Singapore. We aimed to evaluate whether DAA as first-line therapy would be cost-effective for genotype 3 (GT3) HCV patients compared with pegylated interferon and ribavirin (PR). METHODS: A decision tree analysis was used to compare the costs and outcomes of DAA and PR as first-line therapy. Treatment effectiveness, defined as sustained virological response, was assessed using a retrospective cohort of treated GT3 HCV patients. Direct medical costs were estimated from the payer's perspective using billing information. We obtained health utilities from published literature. We performed extensive one-way sensitivity analyses and probabilistic sensitivity analyses to account for uncertainties regarding the model parameters. RESULTS: In base case analysis, first-line therapy with DAA and PR yielded quality-adjusted life years (QALYs) of 0.69 and 0.62 at a cost of USD 54 634 and USD 23 857, respectively. The resultant incremental cost-effectiveness ratio (ICER) (USD 449 232/QALY) exceeded the willingness-to-pay threshold (USD 53 302/QALY). The ICER was robust for uncertainties regarding the model parameters. The cost of DAA is the key factor influencing the cost-effectiveness of HCV treatment. At current price, DAA as first-line therapy is not cost-effective compared with PR, with or without consideration of retreatment. Threshold analysis suggested that DAA can be cost-effective if it costs less than USD 17 002 for a 12-week treatment course. CONCLUSION: At current price, DAA as first-line therapy is not cost-effective compared with PR in GT3 HCV patients in Singapore.