Cirrhosis-related Complications Research Articles

Gut microbiome and metabolome signatures in liver cirrhosis-related complications.

Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to time-of-flight-mass spectrometry. Correlation analyses were performed targeting the gut- microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC > 0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

Long-term albumin improves the outcomes of patients with decompensated cirrhosis and diabetes mellitus: Post hoc analysis of the ANSWER trial.

Type-2 diabetes mellitus is a frequent comorbidity of cirrhosis independently associated with cirrhosis-related complications and mortality. This post hoc analysis of the ANSWER trial database assessed the effects of long-term human albumin (HA) administration on top of the standard medical treatment (SMT) on the clinical outcomes of a subgroup of 85 outpatients with liver cirrhosis, uncomplicated ascites and insulin-treated diabetes mellitus type 2 (ITDM). Compared to patients in the SMT arm, the SMT + HA group showed a better overall survival (86% vs. 57%, p = .016) and lower incidence rates of paracenteses, overt hepatic encephalopathy, bacterial infections, renal dysfunction and electrolyte disorders. Hospital admissions did not differ between the two arms, but the number of days spent in hospital was lower in the SMT + HA group. In conclusion, in a subgroup of ITDM outpatients with decompensated cirrhosis and ascites, long-term HA administration was associated with better survival and a lower incidence of cirrhosis-related complications.

Financial burden in a US cohort of patients with HCC.

High financial burden for patients has been reported for multiple types of cancer, but there are limited data in those with HCC. We aimed to describe the financial burden for patients diagnosed with HCC and identify correlates of high financial burden. We used the IQVIA PharMetrics Plus for Academics database to identify commercially insured patients diagnosed with HCC between 2006 and 2021. Patient financial liability was defined as the difference between allowed and paid amounts from adjudicated insurance claims. We reported total and HCC-related financial liabilities (i.e., cost for HCC-related claims), with high total financial liability defined as ≥$3000 annually and high HCC-related financial liability as ≥$1000 annually. We used multivariable logistic regression modeling to identify factors associated with high total and HCC-related financial liability. Among 11,609 patients with HCC, the median total financial liability during the year after HCC diagnosis was $2955 (Q1-Q3: $972-$6293). Nearly half (45%) of patients experienced high total financial liability, with the greatest liability incurred in the 3-month period immediately following HCC diagnosis. Older age, increased comorbidity, and cirrhosis-related complications were associated with higher total patient liability. Patient liability also varied by type of HCC treatment, with systemic therapy and liver transplantation having the highest financial liability in multivariable analysis. However, only 66.7% of the patients experienced HCC-related liability. Patients with HCC experience significant financial liability underscoring a need for price transparency as well as financial counseling in this population.

Strategic considerations in health economics for the complete treatment of patients with chronic HBV infection

The World Health Organization (WHO) released the Global Health Sector Strategy 2016, which explicitly proposes a 90% reduction in the new hepatitis B virus (HBV) infection rate and a 65% reduction in HBV-related mortality by 2030. However, at present, there are still 296 million chronic hepatitis B virus-infected patients worldwide, and nearly 900,000 patients die every year from cirrhosis and liver cancer caused by HBV infection. Antiviral treatment for chronic hepatitis B virus infection can effectively inhibit HBV replication, reduce liver inflammation and necrosis, effectively block and reverse liver fibrosis, and even early cirrhosis, thereby lowering cirrhosis-related complications, liver cancer, and liver disease-related mortality. Although the domestic and foreign guidelines have gradually eased antiviral treatment indications for chronic hepatitis B, there are still a considerable number of chronic hepatitis B patients with nonconformity who cannot receive antiviral treatment because they do not meet the existing standards, resulting in the progression of more severe diseases. This study analyzed the prevalence of hepatitis B, the therapeutic effect of antiviral drugs, domestic and international guideline treatment standards, the assessment of key indicators changes in the guidelines, comprehensively considered the coverage rate and treatment standards for antiviral treatment, and explored the changes in disease burden and cost-effectiveness following increasing the coverage rate and reducing treatment thresholds in order to achieve the global strategic goal of eliminating hepatitis B as soon as possible as a public health threat.

Complications associated with HCV-related liver cirrhosis and their relationship with diabetic control. A tertiary care center study in Peshawar, Pakistan.

Objective: To determine the frequencies of liver cirrhosis-associated complications in patients with HCV+ diabetic patients and its association with HbA1C. Study Design: Observational Cross-sectional study. Setting: Medical Wards of Khyber Teaching Hospital. Period: October 2019 to November 2020. Methods: After approval from the hospital ethical committee, all HCV positive diabetic patients were enrolled in the study. Informed consent was obtained and relevant examination was performed. Hematemesis was diagnosed clinically, while venous blood was sent for all routine and relevant specialized investigations. Twenty-four-hour urinary output was calculated. Abdominal ultrasounds and Triphasic CT abdomen were done where required. Data were collected on structurally designed proforma. All data were entered into SPSS version 22. Results: A total of 62 patients were enrolled. The mean age was 49. 23 years ± 11.72 SD. Twenty-three patients (37.1%) were males, while 39 patients (62.9%) were females. Forty-nine patients (79%) were PCR-positive for HCV. Most patients (58.1%) had less than five years duration of HCV. Frequency of SBP was 16.1%, hepatic encephalopathy was 22.6%, ascites was 40.3%, hematemesis was 11.3%, portal vein hypertension was 45.2%, and HCC 3.2%. On post-stratification, significant associations emerged with age, where SBP (p <0.01), hepatic encephalopathy (p<0.001), and ascites (p<0.0001), increased with advancing age, while hematemesis (p<0.04) and portal vein hypertension (p<0.04) were more pronounced in younger patients. Conclusion: In conclusion, individuals with both chronic HCV and diabetes mellitus exhibit an increased risk of cirrhosis-related complications. The most common complication was portal vein hypertension followed by ascites and hepatic encephalopathy. The complications like SBP, Hepatic encephalopathy and ascites associated with increasing age.

Acute and non-acute decompensation of liver cirrhosis (47/130).

In the traditional view, the occurrence of cirrhosis-related complications, such as hepatic encephalopathy, formation of ascites or variceal haemorrhage, marks the transition to the decompensated stage of cirrhosis. Although the dichotomous stratification into a compensated and decompensated state reflects a prognostic water-shed moment and remains to hold its prognostic validity, it represents an oversimplification of clinical realities. A broadening understanding of pathophysiological mechanisms underpinning decompensation have led to the identification of distinct prognostic subgroups, associated with different clinical courses following decompensation. Data provided by the PREDICT study uncovered three distinct sub-phenotypes of acute decompensation (AD). Moreover, acute-on-chronic liver failure (ACLF) has been established as a distinct clinical entity for many years, which is associated with a high short-term mortality. Recently, non-acute decompensation (NAD) has been proposed as a distinct pathway of decompensation, complementing current concepts of the spectrum of decompensation. In contrast to AD, NAD is characterized by a slow and progressive development of complications, which are often presented at first decompensation and/or in patients in an earlier stage of chronic liver disease. Successful treatment of AD or NAD may lead to a clinical stabilization or even the concept of recompensation. This review aims to provide an overview on current concepts of decompensation and to delineate recent advances in our clinical and pathophysiological understanding.

Helicobacter pylori Infection and Complications of Cirrhosis.

Helicobacter pylori is a significant contributor to conditions such as peptic ulcer disease, gastric cancer, gastric mucosa-associated lymphoid tissue lymphoma, and colorectal cancer. Recent studies have suggested a potential link between H. pylori and cirrhosis. However, the impact of H. pylori on cirrhosis-related mortality, inpatient outcomes, and decompensating events remains unclear. Considering the widespread availability of H. pylori testing and effective treatment options, there is a potential rationale for eradicating H. pylori in cirrhotic patients to mitigate the morbidity and mortality associated with cirrhosis. This study aims to investigate the association between H. pylori and inpatient outcomes and complications related to cirrhosis. The National Inpatient Sample (NIS) database, a part of the Healthcare Cost & Utilization Project, was utilized for this study. Inpatient data from the years 2016 through 2019 were extracted for patients with a primary discharge diagnosis of cirrhosis and a concurrent diagnosis of H. pylori infection. The primary outcomes included inpatient mortality, length of stay, and cost of care. Secondary outcomes involved cirrhosis-related complications during hospitalization, such as gastrointestinal bleeding, hepatic encephalopathy, and hepatorenal syndrome. Over the years 2016 to 2019, 416,410 patients received a primary discharge diagnosis of cirrhosis. Among them, 990 patients (0.2%) had a secondary diagnosis of H. pylori infection. Those with both cirrhosis and H. pylori tended to be younger on average (mean age 54.25 vs. 57.18 years, p=0.01) and more frequently fell within the age range of 18-49 (33.84% vs. 24.71%, P=0.01). H. pylori-infected patients were also more likely to be male (70.71% vs. 63.11%, P<0.028), of Hispanic race (36.4% vs. 18.6%, p< 0.1), and of Black race (20.2% vs. 8.1%, p< 0.1). While H. pylori-exposed patients had lower in-hospital mortality (0.51% vs. 4.44%, p=0.007), their mean length of stay was higher (6.97 days vs. 5.75, p=0.002). The overall cost of care was comparable between the H. pylori-exposed and non-exposed groups (mean USD18,106.18 vs. $16,543.49, P=0.160). H. pylori-exposed patients had a higher overall rate of cirrhosis-related complications (84.85% vs. 67.59%, p< 0.001), gastrointestinal bleeding (48.48% vs. 27.34%, p< 0.001), and hepatorenal syndrome (70.71% vs. 46.99%, p< 0.001), and these differences persisted in multivariable analysis. Initially, rates of hepatic encephalopathy were higher in H. pylori non-exposed patients (21.57% vs. 15.66%, p=0.04), but this discrepancy was corrected after adjusting for potential confounders. While patients in this study were diagnosed with both H. pylori and cirrhosis by discharge, it cannot be definitively concluded that H. pylori was the direct cause of cirrhosis complications. Recognizing this uncertainty, further studies are needed better to understand the associations between cirrhosis and H. pylori complications. Distinguishing the causes of cirrhosis and its relationship with H. pylori may offer deeper insights into whether H. pylori is a causative factor or merely correlated in its effects on patients with cirrhosis.

Hypercholesterolemia Is Associated With Dysregulation of Lipid Metabolism and Poor Prognosis in Primary Biliary Cholangitis

Hypercholesterolemia is frequently diagnosed in patients with primary biliary cholangitis (PBC). However, its association with the prognosis and lipid metabolism is unknown. In this study, we aimed to investigate the prognostic value of baseline total cholesterol (TC) levels in PBC and characterized the associated lipid metabolism. Five hundred and thirty-one patients with PBC without prior cirrhosis-related complications were randomly divided into the derivation and validation cohorts at a ratio of 7:3. Complete clinical data were obtained and analyzed. The endpoints were defined as liver-related death, liver transplantation, and cirrhosis-related complications. Lipidomics was performed in 89 patients and 28 healthy controls. Baseline TC was independently associated with poor liver-related outcomes, and adjusted C-statistics were 0.80 (95% confidence interval [CI]: 0.74-0.85) and 0.88 (95% CI: 0.78-0.91) in the derivation and validation cohorts, respectively. The predictive ability of TC for disease outcomes was stable over time and comparable with the Globe score. The 200mg/dL cut-off optimally divided patients into low- and high-TC groups. A combination of TC and Globe score provided a more accurate stratification of patients into risk subgroups. Lipidomics indicated an up-regulation of lipid families in high-TC patients. Pathway analysis of 66 up-regulated lipids revealed the dysregulation of glycerophospholipid and sphingolipid metabolism in high-TC patients, which were associated with poor liver-related outcomes. Our results indicate that patients with PBC having baseline TC levels above 200 mg/dL have unique lipidome characteristics and are at a higher risk of poor liver-related outcomes.

Screening and assessment of malnutrition in patients with liver cirrhosis.

The development and advancement of malnutrition is associated not only with the progression of hepatic dysfunction, but also with cirrhosis-related complications. However, the prevalence of malnutrition reported in different studies varies widely due to differences in diagnostic methods and patient investigation settings. Therefore, we need to identify malnourished patients promptly and accurately. The purpose of this review was to compare the validity and reliability of nutritional screening tools and to select the most appropriate nutritional risk screening for patients with cirrhosis. We compared nutritional risk screening tools such as the Nutritional Risk Screening 2002 (NRS-2002), Malnutrition Universal Screening Tool (MUST), Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) and Liver Disease Undernutrition Screening Tool (LDUST). Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) is more feasible to screen cirrhotic patients for nutritional risk, and is highly reproducible, considering the impact of sodium and water retention; so it is practical to screen cirrhotic patients via RFH-NPT for nutritional risk, subsequently, to evaluate the nutritional status of patients with nutritional risk via the Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria. L3-SMI (third lumbar-skeletal muscle index) can accurately define sarcopenia in cirrhotic patients and also be used for clinical nutritional status assessment.

Comparative effectiveness of tenofovir versus entecavir in patients with hepatitis B virus-related cirrhosis in Taiwan: a retrospective cohort study.

Background: Tenofovir and entecavir demonstrated substantial effectiveness in the reversion of fibrosis and reversed cirrhosis in patients with hepatitis B virus (HBV)-related cirrhosis. However, there has not been a definitive conclusion regarding the association between entecavir and tenofovir on the risk of cirrhosis-related complications. Therefore, this study aimed to investigate the comparative effectiveness between tenofovir and entecavir in HBV-related cirrhosis patients. Methods: This was a retrospective study using Taiwan's Health Insurance Research Database. We enrolled newly diagnosed HBV-related cirrhosis patients who initiated entecavir and tenofovir between 2011 and 2019. Treatment groups were determined by the initial HBV antiviral medication prescribed. The primary composite outcome was the development of hepatocellular carcinoma (HCC), death from any causes, and liver transplantation. The secondary outcomes included all the individual components of the primary outcome. The incidence rate was calculated for each outcome for both treatment groups using the Fine-Gray subdistribution hazard models. Propensity score adjustment was used to balance treatment groups. Results: A total of 7,316 propensity score-matched treatment-naïve patients and 3,524 propensity score-matched treatment-experienced patients were included. Within treatment-naïve patients, those receiving tenofovir showed significantly lower hazards of developing the composite outcome (HR, 0.79; p < 0.0001), hepatocellular carcinoma (HR, 0.86; p = 0.027), mortality (HR, 0.75; p < 0.0001), and liver transplantation (HR, 0.70; p = 0.0189) than those receiving entecavir. As for treatment-experienced patients, tenofovir was associated with a significantly lower risk of the composite outcome (HR, 0.82; p = 0.0033) and hepatocellular carcinoma (HR, 0.60; p < 0.0001), but it did not show a significantly different risk of all-cause mortality (HR, 0.93; p = 0.3374) or liver transplantation (HR, 1.17; p = 0.5112) compared to entecavir. Conclusion: Tenofovir presented a significantly lower incidence of cirrhosis-related complications than entecavir in patients with hepatitis B virus-related cirrhosis. However, no statistically significant difference in death and liver transplantation was seen in treatment-experienced patients.

Allopurinol Prevents Cirrhosis-Related Complications: A Quadruple Blind Placebo-Controlled Trial

BackgroundComplications associated with liver cirrhosis are various and potentially fatal. The treatment options to counteract hepatic decompensation are limited. Therefore, the study aimed to explore the use of allopurinol in preventing the recurrence of liver cirrhosis-related complications. MethodsOne hundred patients with hepatic decompensation were randomized into 1:1 ratio to receive either allopurinol 300 mg or placebo tablets once daily for 6 months. The primary endpoint was the incidence of cirrhosis-related complications (overt ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatorenal syndrome, and hepatic encephalopathy). ResultsSix months following treatment, allopurinol reduced the relative risk (RR) of any first complication experienced after enrollment by 56% (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.27-0.62); P ˂ .001). Allopurinol decreased the RR of overt ascites by 67% (HR 0.33; 95% CI, 0.0098-0.94); P = .039] and reduced the RR of spontaneous bacterial peritonitis by about 75% (HR 0.25; 95% CI, 0.05-0.76; P = .01). Likewise, allopurinol was linked to an 80% reduction in the RR of developing hepatorenal syndrome (HR 0.2; 95% CI, 0.04-0.87; P = .033). ConclusionAllopurinol significantly decreased the recurrence of overall liver cirrhosis-related complications. Therefore, allopurinol may constitute a promising agent for patients with hepatic decompensation. These positive outcomes could be a result of its ability to reduce bacterial translocation and inflammation. ClinicalTrials.gov identifierNCT005545670.

Albumin infusion reduces ascite occurrence in Child-Pugh B patients treated by Atezolizumab-Bevacizumab for advanced HCC.

Long-term albumin infusions have been associated with improved outcomes in decompensated cirrhotic patients. This study aimed to evaluate the impact of albumin infusion on the prognosis of Child-Pugh B patients undergoing treatment with AtezoBev for advanced hepatocellular carcinoma (HCC). We conducted a retrospective multicentric study that included all Child-Pugh B cirrhotic patients treated with AtezoBev since 2020. We examined the effects of albumin infusion (40g every 3 weeks) on overall survival (OS) and the occurrence of cirrhosis-related complications. Time-to-event data were analyzed using Kaplan-Meier with the log-rank test and Cox models. Forty-seven HCC patients with a Child-Pugh B score who received AtezoBev were included, of whom 26% also received albumin infusions every 3 weeks. The two groups were similar in terms of liver function and HCC parameters. The median OS was 4.4 and 5.8 months (p=0.42) for patients who did or did not receive albumin, respectively. The occurrence of hepatic encephalopathy and variceal bleeding was similar between the two groups. However, albumin infusions were associated with a significantly lower rate of ascites expansion/development (13% versus 57%, p=0.005). Cox analysis revealed that a history of ascites (HR=3.82 [95% CI: 1.73-8.48]) was independently associated with a higher risk of ascites expansion/development, whereas albumin infusions were protective (HR=0.07 [95% CI: 0.01-0.54]). Albumin infusion did not improve overall survival in Child-Pugh B HCC patients treated with AtezoBev, but it significantly reduced the expansion/development of ascites.

Implementing Better Standard Instruments for Detecting Cirrhosis in Hepatitis C Patients.

An increasing number of hepatitis C diagnoses in the younger population could partly be due to the rising opioid epidemic and intravenous drug use. Using hepatic venous portal gradient (HVPG) and liver stiffness tests, this study investigates better early diagnostic markers in identifying cirrhosis-related complications compared to percutaneous liver biopsy in hepatitis C patients. Scholarly journal articles were surveyed using PubMed and MeSH terms. Articles published more than 15 years ago were excluded. Various databases from the New England Journal of Medicine and the Centers for Disease Control and Prevention were also referenced to support the hypothesis. There is substantial affirmation from cohort and clinical studies that transient elastography and HVPG can indicate advancing chronic inflammatory and fibrotic stages of cirrhosis in comparison to liver biopsy. Additionally, they are helpful in predicting overall mortality from complications such as esophageal varices. The use of liver stiffness measurements and HVPG appears to be equivalent and/or superior to liver biopsy in assessing advancing cirrhosis. As hepatitis C cases continue to rise, it is crucial to search for alternative methods to better suit the needs of the patients and to improve their overall prognosis and potential treatments. Liver biopsy as the gold standard for cirrhosis assessment is questionable when less invasive instrumental tools are available in practice that have been shown to predict progressing fibrosis.

Spleen stiffness: a new tool to predict high-risk varices in cirrhotic patients.

Cirrhosis is one of the major causes of morbidity and mortality worldwide. Portal hypertension is the major contributor of cirrhosis-related complications and is defined as a hepatic venous pressure gradient (HVPG)>5mmHg. Measurement of HVPG is an invasive, difficult, and costly procedure. Therefore, it is only performed in specialized centers. Liver stiffness measured with transient elastography is one of the most studied noninvasive markers of portal hypertension, and spleen elastography has recently emerged as an important adjuvant tool. The development of a new probe (100Hz) that more reliably reflect the grade of portal hypertension evaluated by spleen stiffness measurement has improved the accuracy of this technique. The aim of this work was to evaluate the accuracy of spleen stiffness with the new dedicated probe to predict the presence of high-risk varices, as well as to determine the ideal cutoff to predict it. Prospective study of cirrhotic patients admitted to upper endoscopy that were also submitted to liver and spleen elastography with the 100-Hz probe by the same blinded operator in a tertiary center. We included 209 cirrhotic patients, with mean age of 61.9years (±9.9), 77.0% male. The most common etiology was alcoholic liver disease (72.7%). The median value of liver elastography was 25.3 [4.5-75] kPa, and the median value of spleen elastography was 42.4 [7.6-100] kPa. At the cutoff of 53.25kPa, we obtained sensitivity of 100% and specificity of 72.6% to predict high-risk varices, and, according to this cutoff, 133/175 of esophagogastroduodenoscopy could have been spared (76.0%), while according to Baveno guidelines, only 51/175 would have been spared (29.1%). In the era of noninvasive exams, spleen elastography with the 100-Hz probe emerges as an excellent tool for prediction of presence of high-risk varices. At the cutoff of 53.25kPa, spleen elastography avoids upper endoscopy for screening for high-risk varices, promising to be become part of the hepatologists' daily routine.

Anticoagulation Against Portal Vein Thrombosis Reduces Mortality and Liver Cirrhosis-related Complications: A Propensity Score-matched Study.

Portal vein thrombosis (PVT) is one of the common complications of liver cirrhosis (LC). Although anticoagulation contributes to thrombus resolution and is considered the first-choice treatment, its impact on patients' prognosis is still controversial. This study aims to clarify the benefit of anticoagulation on mortality, liver function, and the incidence of LC-related complications in cirrhotic PVT patients. We conducted a multicenter retrospective review in which we included 78 eligible patients with PVT out of 439. After propensity score matching, 21 cirrhotic PVT patients were included in each one of the untreated control and anticoagulation groups. Overall survival was significantly improved in the anticoagulation group compared to the control group (p = 0.041), along with PVT size reduction (53.3% vs 108.2%, p = 0.009). At the time of CT follow-up, the anticoagulation group demonstrated a lower ALBI score (p = 0.037) and its prevalence of massive ascites was significantly lower (p = 0.043) compared to the control group. The incidence of overt encephalopathy was also lower in the anticoagulation group (p = 0.041). The cumulative incidence of bleeding events did not differ significantly between the two groups. Anticoagulation improves the survival of patients with cirrhotic PVT. Preserved liver function and reduced risks of cirrhosis-related complications under the treatment may have contributed to a better prognosis. Given its efficacy and safety, anticoagulation is worth initiating in patients with PVT. This article is protected by copyright. All rights reserved.

Use of albumin infusion for cirrhosis-related complications: An international position statement

Background & AimsNumerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy. MethodsThirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications. ResultsTwelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion. ConclusionsBased on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated. Impact and implicationsThirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion.

The rationale and study design of two phase II trials examining the effects of BI 685509, a soluble guanylyl cyclase activator, on clinically significant portal hypertension in patients with compensated cirrhosis

BackgroundClinically significant portal hypertension (CSPH) drives cirrhosis-related complications (i.e. hepatic decompensation). Impaired nitric oxide (NO) bioavailability promotes sinusoidal vasoconstriction, which is the initial pathomechanism of CSPH development. Activation of soluble guanylyl cyclase (sGC), a key downstream effector of NO, facilitates sinusoidal vasodilation, which in turn may improve CSPH. Two phase II studies are being conducted to assess the efficacy of the NO-independent sGC activator BI 685509 in patients with CSPH due to various cirrhosis aetiologies.MethodsThe 1366.0021 trial (NCT05161481) is a randomised, placebo-controlled, exploratory study that will assess BI 685509 (moderate or high dose) for 24 weeks in patients with CSPH due to alcohol-related liver disease. The 1366.0029 trial (NCT05282121) is a randomised, open-label, parallel-group, exploratory study that will assess BI 685509 (high dose) alone in patients with hepatitis B or C virus infection or non-alcoholic steatohepatitis (NASH) and in combination with 10 mg empagliflozin in patients with NASH and type 2 diabetes mellitus for 8 weeks. The 1366.0021 trial will enrol 105 patients, and the 1366.0029 trial will enrol 80 patients. In both studies, the primary endpoint is the change from baseline in hepatic venous pressure gradient (HVPG) until the end of treatment (24 or 8 weeks, respectively). Secondary endpoints include the proportion of patients with an HVPG reduction of >10% from baseline, the development of decompensation events and the change from baseline in HVPG after 8 weeks in the 1366.0021 trial. In addition, the trials will assess changes in liver and spleen stiffness by transient elastography, changes in hepatic and renal function and the tolerability of BI 685509.DiscussionThese trials will enable assessment of the short-term (8 weeks) and longer-term (24 weeks) safety of BI 685509, and the effect of sGC activation by BI 685509 on CSPH due to various cirrhosis aetiologies. The trials will use central readings of the diagnostic gold standard HVPG for the primary endpoint, and changes in established non-invasive biomarkers, such as liver and spleen stiffness. Ultimately, these trials will provide key information for developing future phase III trials.Trial registration1366.0021: EudraCT no. 2021–001285-38; ClinicalTrials.gov NCT05161481. Registered on 17 December 2021, https://www.clinicaltrials.gov/ct2/show/NCT05161481.1366.0029: EudraCT no. 2021–005171-40; ClinicalTrials.gov NCT05282121. Registered on 16 March 2022, https://www.clinicaltrials.gov/ct2/show/NCT05282121.

Non-alcoholic fatty liver disease is associated with greater risk of 30-day hospital readmission in the United States (U.S.)

Introduction and ObjectivesData about 30-day readmission for patients with chronic liver disease (CLD) and their contribution to CLD healthcare burden are sparse. Patterns, diagnoses, timing and predictors of 30-day readmissions for CLD from 2010-2017 were assessed. Materials and MethodsNationwide Readmission Database (NRD) is an all-payer, all-ages, longitudinal administrative database, representing 35 million discharges in the US population yearly. We identified unique patients discharged with CLD including hepatitis B (HBV) and C (HCV), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) from 2010 through 2017. Survey-weight adjusted multivariable analyses were used. ResultsFrom 2010 to 2017, the 30-day readmission rate for CLD decreased from 18.4% to 17.8% (p=.008), while increasing for NAFLD from 17.0% to 19. 9% (p<.001). Of 125,019 patients discharged with CLD (mean age 57.4 years, male 59.0%) in 2017, the most common liver disease was HCV (29.2%), followed by ALD (23.5%), NAFLD (17.5%), and HBV (4.3%). Readmission rates were 20.5% for ALD, 19.9% for NAFLD, 16.8% for HCV and 16.7% for HBV. Compared to other liver diseases, patients with NAFLD had significantly higher risk of 30-day readmission in clinical comorbidities adjusted model (Hazard ratio [HR]=1.08 [95% confidence interval 1.03-1.13]). In addition to ascites, hepatic encephalopathy, higher number of coexisting comorbidities, comorbidities associated with higher risk of 30-day readmission included cirrhosis for NALFD and HCV; acute kidney injury for NAFLD, HCV and ALD; HCC for HCV, and peritonitis for ALD. Cirrhosis and cirrhosis-related complications were the most common reasons for 30-day readmission, followed by sepsis. However, a large proportion of patients (43.7% for NAFLD; 28.4% for HCV, 39.0% for HBV, and 29.1% for ALD) were readmitted for extrahepatic reasons. Approximately 20% of those discharged with CLD were readmitted within 30 days but the majority of readmissions occurred within 15 days of discharge (62.8% for NAFLD, 63.7% for HCV, 74.3% for HBV, and 72.9% for ALD). Among readmitted patients, patients with NAFLD or HCV readmitted ≤30-day had significantly higher costs and risk of in-hospital mortality (NAFLD +5.69% change [95% confidence interval, 2.54%-8.93%] and odds ratio (OR)=1.58 [1.28-1.95]; HCV +9.85% change [95%CI:6.96%-12.82%] and OR=1.31, 1.08-1.59). ConclusionsEarly readmissions for CLD are prevalent causing economic and clinical burden to the US healthcare system, especially NAFLD readmissions. Closer surveillance and attention to both liver and extrahepatic medical conditions immediately after CLD discharge is encouraged.

Clinical Outcomes of Acute Pancreatitis in Patients with Cirrhosis

Background and Aim: Acute Pancreatitis (AP) is a common disease requiring hospitalization. Though the mortality rate caused by pancreatitis decreased over the past few decades but patient’s organ failure causing mortality during acute pancreatitis is on the rise. The present study intended to assess the outcomes of acute pancreatitis in cirrhosis patients. Patients and Methods: This retrospective study was carried out on 180 acute pancreatitis patients admitted in the General Medicine and Gastroenterology Department of Central Hospital, Stadium Road Sargodha, Hayatabad Medical Complex Peshawar and Shaikh Khalifa bin Zayed Hospital, Muzaffarabad AJK for the duration from November 2021 to September 2022. Cirrhotic and non-cirrhotic patients were matched based on Propensity score matching (1:2). Inpatient mortality, systemic inflammatory response syndrome, length of hospital stay (LOS), and organ failure were the main outcomes. Model of End-stage Liver Disease (MELD) and Child-Pugh scores was used for cirrhotic patient’s subgroup analysis. Results: Of the total 180 AP patients, there were 60 cirrhotic (male 31 and females 29) and 120 (male 62 and females 58) non-cirrhotic patients. Based on Child-Pugh scores, the incidence of Child–Pugh scores A, B, and C was 17 (28.3%), 27 (45%), and 16 (26.7%) respectively. Based on cirrhosis etiology, the incidence of NAFLD (non-alcoholic fatty liver disease) , chronic hepatitis C, and autoimmune causes were 12 (20%), 42 (70%), and 6 (10%) respectively. Regarding diagnosis criteria, abdominal imaging diagnosed 56 (93.3%) patients whereas 4 (6.7%) were diagnosed based on liver biopsy. The mean BMI value in cirrhotic and non-cirrhotic groups was 28.4 and 26.8 kg/m2, p=0.51). Based on acute pancreatitis etiology, the incidence of gallstone-induced, idiopathic, and other in cirrhotic versus non-cirrhotic was 32 (53.3%) vs. 68 (56.7%), 12 (20%) vs. 30 (25%), and 16 (26.7%) and 22 (18.3%) respectively. Cirrhotic and non-cirrhotic patients’ outcomes such as inpatient mortality (6.8% vs. 1.7%), systemic inflammatory response syndrome (SIRS) (23.3% vs. 34.2%), and organ failure (13.3% vs 4.2%). Conclusion: The present study concluded the overall mortality and morbidity rates for cirrhotic and non-cirrhotic hospitalized with AP were similar. However, cirrhosis-related complications, portal hypertension and immunosuppression state such as sepsis, infections, and variceal bleed are likely to contribute to poorer outcomes and higher mortality compared to non-cirrhotic. Keywords: Acute pancreatitis, outcomes, acute liver injury

Outcomes of gout in patients with cirrhosis: A national inpatient sample-based study.

Hyperuricemia is a prerequisite for the development of gout. Elevated serum uric acid (UA) levels result from either overproduction or decreased excretion. A positive correlation between serum UA levels, cirrhosis-related complications and the incidence of nonalcoholic fatty liver disease has been established, but it is unknown whether hyperuricemia results in worsening cirrhosis outcomes. We hypothesize that patients with cirrhosis will have poorer gout outcomes. To explore the link between cirrhosis and the incidence of gout-related complications. This was a cross-sectional study. The national inpatient sample was used to identify patients hospitalized with gout, stratified based on a history of cirrhosis, from 2001 to 2013 via the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Primary outcomes were mortality, gout complications and joint interventions. The χ 2 test and independent t-test were performed to assess categorical and continuous data, respectively. Multiple logistic regression was used to control for confounding variables. Patients without cirrhosis were older (70.37 ± 13.53 years vs 66.21 ± 12.325 years; P < 0.05). Most patients were male (74.63% in the cirrhosis group vs 66.83%; adjusted P < 0.05). Patients with cirrhosis had greater rates of mortality (5.49% vs 2.03%; adjusted P < 0.05), gout flare (2.89% vs 2.77%; adjusted P < 0.05) and tophi (0.97% vs 0.75%; adjusted P = 0.677). Patients without cirrhosis had higher rates of arthrocentesis (2.45% vs 2.21%; adjusted P < 0.05) and joint injections (0.72% vs 0.52%; adjusted P < 0.05). Gout complications were more common in cirrhosis. Those without cirrhosis had higher rates of interventions, possibly due to hesitancy with performing these interventions given the higher complication risk in cirrhosis.