Cirrhosis Mortality Research Articles

Low Absolute Eosinophil Count Predicts In-Hospital Mortality in Cirrhosis With Systemic Inflammatory Response Syndrome.

IntroductionChronic liver disease (CLD) or Cirrhosis is one of the most common causes of morbidity as well as mortality. Child-Turcotte-Pugh (CTP) score and the model for end-stage liver disease (MELD) are useful to assess the long-term prognosis of a patient with CLD. When a patient with CLD is admitted with an acute illness leading to systemic inflammatory response syndrome (SIRS), these scores may not be reliable to predict the short-term prognosis and survival. Absolute eosinophils count (AEC) allows the rapid identification of patients at increased risk for sepsis-related mortality in patients.MethodsThis was a cross-sectional study conducted among patients in a tertiary care hospital in South India during a period of one and a half years between October 2018 and April 2020. Cirrhotic patients with SIRS aged between 16 years and 80 years were included in the study. AEC was measured as a part of automated complete blood counts. Patient demographics, lab parameters, and outcomes in terms of mortality were studied. Continuous variables were expressed as mean ± SD/median and categorical variables were expressed in frequency. Receiver operating characteristic (ROC) curve analysis was used to find an ideal cutoff for AEC in predicting hospital mortality. Multi-variate Cox regression analysis was performed to find predictors of mortality.ResultsA total of 100 patients who fit the pre-determined criteria for cirrhosis with SIRS were enrolled in the study. Sixteen (16%) patients died at the end of the study while 84 (84%) were alive. Using a ROC curve, the area under the curve (AUC) was 0.716 with 95% CI of AUC (0.564-0.867), the p-value was found to 0.006, a cut-off of eosinophil count of 198.5 cells/uL was found to be the cut-off for the prediction of in-hospital mortality in this subset of patients with cirrhosis and sepsis with SIRS, with a sensitivity of 75% and specificity of 38.1%. In a multi-variate Cox regression analysis, only age (hazard ratio {HR}: 1.175, 95%CI, 1.084 to 1.275, p<0.001) , CRP (HR : 1.008, 95%CI, 1.00 to 1.015, p=0.042) values, total leukocyte counts (TLC) (HR: 1.226, 95%CI, 1.116 to 1.346, p<0.001) and AEC (HR: 0.993, 95%CI, 0.987 to 0.999, p=0.016) were found to be statistically significant independent predictors of mortality.ConclusionsThe presence of eosinopenia may be considered as an in-expensive warning biomarker for poorer clinical outcomes in the form of in-hospital mortality in hospitalized cirrhotic patients. Other biomarkers such as CRP and TLC could also play a role both independently and in conjunction with AEC to predict outcomes and mortality in cirrhotic patients with sepsis and SIRS.

CLIF-C AD Score Predicts Development of Acute Decompensations and Survival in Hospitalized Cirrhotic Patients.

Patients with decompensated cirrhosis are at increased risk of mortality, even in absence of ACLF. The CLIF-C AD score (CLIF-C ADs) was proposed as a prognostic score but lacks sufficient validation. Our aim was to describe clinical characteristics and hospital evolution according to score groups and evaluate prognostic capability of CLIF-C ADs alone or in combination with other scores. Two hundred and sixty-six patients (55 ± 14years, ascites in 63%, MELD 14 ± 5) were included, and classified as high, intermediate and low CLIF-C ADs in 13, 60 and 27% of cases. Development of new complications of cirrhosis during hospitalization and survival at 3months were evaluated. Patients with high CLIF-C ADs had more severe systemic inflammation parameters and higher frequency of organ dysfunction. CLIF-C ADs ≥ 60, when compared to intermediate and low groups, was associated with higher incidence of complications of cirrhosis (90% vs 70% and 49%, p < 0.001) and lower survival (93%, 80% and 50%, p < 0.0001). In multivariate analysis, CLIF-C ADs, ascites and MELD were predictors of survival [(AUROC 0.76 (95% CI 0.69-0.83)]. Absence of ascites or MELD < 14 identified patients with intermediate CLIF-C ADs and good survival (89 and 84%, respectively). CLIF-C ADs predicts survival in cirrhotic patients with AD. High CLIF-C ADs is associated with higher frequency of organ dysfunction, increased risk of new complications of cirrhosis and high short-term mortality. On the contrary, individuals with low CLIF-C ADs, as well as those with intermediate score without ascites or with low MELD have excellent prognoses.

Prevalence, clinical characteristics and related mortality of cirrhosis in a tertiary hospital setting in Sub Saharan Africa

Background: Published data on the prevalence and mortality associated to cirrhosis is rare in Cameroon. The aim of this study was to determine the prevalence, clinical and para clinical characteristics and associated mortality of cirrhosis at the Yaounde University Teaching Hospital (YUTH), Cameroon. Methods: Files of patient’s followed up or admitted for cirrhosis at the YUTH between June 1st 2016 and June 30th 2018 were reviewed. The diagnosis of cirrhosis was made based on clinical, biological, ultrasonographic and/or endoscopic signs of portal hypertension and chronic liver failure. In other to establish the cause of cirrhosis, markers of documented chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) was sought in the file of the patients and if not present, hepatitis C antibody and hepatitis B surface antigen testing were requested. In patients negative for HBV and HCV markers, alcohol intake was considered as a cause of cirrhosis in someone who have been consuming more than 30 g/day (for males) or more than 20 g/day (for females) of alcohol. Data analyses were performed using Epi info V 3.5.4. Results: During the period of study, 1748 patients were admitted in the internal medicine unit among which 117 had cirrhosis giving a prevalence of 6.7%. There were 67 males (57.3%) and 50 females (42.7%). The mean age of patients was 51 +/- 19.862 years. Patients with HCV related cirrhosis were older (mean age: 68years) than those with HBV induced cirrhosis (mean age: 38years). The most frequent signs were ascites 104 patients (88.9%), asthenia 92(78.6%), hepatomegaly 68(58.1%), jaundice 61(52.1%), abdominal distension 54(46.2%) and gastrointestinal bleeding 29(24.8%). Anaemia was present in 58 patients (49.6%), thrombocytopenia in 56 patients (47.9%), low prothrombine time in 64 patients (54.7%). Mean serum albumine was 27.59 g/l (6-70), mean total bilirubine 49.41mg/l (3-275mg/l), mean AFP 75693 mg/ml (0.8-1578022). Spontaneous bacterial peritonitis was found in 21 patients (17.9%) Performed in 30 patients (25.6%), upper digestive endoscopy showed oesophageal varices in 27 patients (90%), hypertensive gastropathy in 17 patients (56.7%) and an ulcer in 3 patients (10%). Found in 47 patients (40.2%), HBV infection was the most frequent cause of cirrhosis followed by chronic HCV infection in 43 cases (36.8%) and alcohol intake in 26 patients (22.2%). The most frequent Child-Pugh class was C in 32 patients (48.5%) followed by Child-Pugh B and A in 26 patients (39.4%) and 8 patients (12.1%) respectively. Mortality rate was estimated at 20.5% (24 patients) and death was attributed to hepatic encephalopathy in 19 patients, gastrointestinal bleeding in 3 patients and spontaneous bacterial peritonitis in 2 patients. Conclusion: Liver cirrhosis is frequent in our setting, mostly diagnosed on advanced stages with complications. The most common causes are viral hepatitis B and C. The mortality rate is high.

COVID-19 and Chronic Viral Liver Diseases

Coronavirus causes an outbreak of viral pneumonia that spread throughout the world. Liver injury is becoming more widely recognized as a component of the clinical picture of COVID-19 infection. We aimed to review this relation in a concise way. This review article includes a large number of patients from both western and eastern countries with no clear difference of liver affection. The more severe and frequent liver injury, the more severe COVID-19 infection. Up to half of patients developed hepatitis with serum ALT elevation. Both hepatocellular and/or ductular injury were observed as evidenced by alkaline phosphatase elevation. Increase incidence of morbidity and mortality had been recorded in patients with CLD. Cirrhosis mortality extended in line with the Child-Turcotte-Pugh class. The incidence of ACLF in CLD patients with COVID 19 is not clear. There are no significant associations with the etiology of liver disease and death in cirrhosis. COVID-19 hinders HCV elimination by 2030. Patients should continue their medications if already receiving treatment. Patients with occult or resolved HBV and COVID-19 who are receiving immunosuppressive agents should use antiviral therapy to prevent viral flare-ups.

Non-selective beta-blockers increase overall and liver mortality in alcoholic cirrhosis with MELD≥12 over 5 years of follow-up.

Non-cardioselective beta-blocker (NSBB) effects on mortality in cirrhosis are controversial. We evaluated the impact of NSBBs on mortality according to liver severity and mortality cause. Two hundred and fifty-eight patients with alcoholic cirrhosis were included in a retroprospective cohort: 129 NSBB-treated and 129 controls. The NSBB group had the following significant baseline differences: higher MELD, more frequent previous gastrointestinal bleeding, large oesophageal varices (OV) and lower heart rate. Propranolol dose was 160mg/d in 81% of NSBB patients. (i) Liver function: during 5.3 ± 2.6 years of follow-up, MELD progression was higher in NSBB patients: 1 (-1-4) than in controls: 0 (-1-1) (P = .017). (ii) Overall survival: no significant differences were observed between NSBBs and controls (Kaplan-Meier curves: P=.291). In multivariate Cox analysis, baseline MELD interacted with NSBB (P=.011). Thus, the NSBB hazard ratio (HR) was 0.99 (0.50-1.98) in MELD<12 vs 3.17 (1.19-8.42) in MELD≥12. (iii) Liver survival: NSBB decreased liver survival (Kaplan-Meier: P=.031). In multivariate Cox analysis, baseline MELD interacted with NSBB (P<.001). The NSBB HR was 0.81 (0.30-2.19) in MELD<12 vs 6.23 (1.94-20.0) in MELD≥12. In competing risk multivariate analysis for liver mortality, the MELD-NSBB interaction was significant (P<.001): the NSBB HR was 1.02 (0.36-2.91) in MELD<12 vs 9.24 (3.18-26.9) in MELD≥12. 4) Non-liver survival: contrastingly, non-liver survival was increased by NSBBs, especially in MELD≥12 (competing Kaplan-Meier: P=.044). These results were confirmed in propensity risk score (PRS)-matched patients. In alcoholic cirrhosis with rather high propranolol doses, overall and liver survival are significantly aggravated when MELD is ≥12.

Active Vitamin D3 Treatment Attenuated Bacterial Translocation via Improving Intestinal Barriers in Cirrhotic Rats.

Pathological bacterial translocation from the disrupted intestinal barrier leads to substantial complications and mortality in liver cirrhosis. Vitamin D is reported as beneficial to gut barriers in some animal models. However, its effect on cirrhotic bacterial translocation is unknown. The authors aim to investigate the effects of calcitriol on bacterial translocation in cirrhotic rats. Cirrhotic rats are administrated with a 2-week course of active vitamin D3 (calcitriol, 0.1μgkg-1 per day) or vehicleby oral gavage after thioacetamide (TAA) injection for 16 weeks. Bacterial translocation, gut permeability, gut microbiota, and associated mechanisms are investigated. Calcitriol treatment significantly attenuates bacterial translocation and reduces intestinal permeability in TAA-induced cirrhotic rats. It upregulates the expressions of occludin in the small intestine and claudin-1 in the colon of cirrhotic rats directly independent of intrahepatic status. Even when a short period of calcitriol treatment do not reduce intestinal bacterial overgrowth, it induces a remarkable change of bacterial diversities and enrichment of Muribaculaceae, Bacteroidales, Allobaculum, Anaerovorax, and Ruminococcaceae. Calcitriol treatment attenuates intestinal permeability, reduces bacterial translocation, and enriches potentially beneficial gut microbiota in cirrhotic rats that may enable it as a potential therapeutic agent to prevent cirrhotic complications.

Low incidence of HCC in chronic hepatitis C patients with pretreatment liver stiffness measurements below 17.5 kilopascal who achieve SVR following DAAs

To evaluate the ability of pretreatment liver stiffness measurements (pLSM) to predict hepatocellular carcinoma (HCC), incident decompensation and all-cause mortality in chronic hepatitis C (CHC) patients who achieved sustained virological response (SVR) after treatment with direct-acting antivirals (DAAs). 773 CHC patients with SVR after DAA treatment and no prior liver complications were identified retrospectively. Optimized cut-off of 17.5 kPa for incident HCC was selected by maximum Youden's index. Patients were grouped by pLSM: <10 kPa [reference], 10-17.4 kPa and ≥17.5 kPa. Primary outcomes were incident hepatocellular carcinoma and secondary outcomes were incident decompensated cirrhosis and all-cause mortality, analyzed using cox-regression. Median follow-up was 36 months and 43.5% (336) had cirrhosis (LSM>12.5 kPa). The median pLSM was 11.6 kPa (IQR 6.7-17.8, range 2.5-75) and pLSM of <10 kPa, 10-17.4 kPa and 17.5-75 kPa was seen in 41.5%, 32.2% and 26.3%. During a median follow-up time of 36 months, 11 (1.4%) developed HCC, 14 (1.5%) developed decompensated cirrhosis, and 38 (4.9%) patients died. A pLSM of 17.5 kPa identified patients with a high risk of HCC with a negative predictive value of 98.9% and incidence rate of HCC in the 17.5-75 kPa group of 1.40/100 person years compared to 0.14/100 person years and 0.12/100 person years in the 10-17.4 kPa and <10 kPa groups, p<0.001. Pretreatment LSM predicts risk of HCC, decompensation and all-cause mortality in patients with SVR after DAA treatment. Patients with a pLSM <17.5 kPa and no other risk factors for chronic liver disease appear not to benefit from HCC surveillance for the first 3 years after treatment. Longer follow-up is needed to clarify if they can be safely excluded from post treatment HCC screening hereafter.

Author response: Meta-analysis of magnetic resonance spectroscopy in the diagnosis of hepatic encephalopathy.

The authors thank Dr. Gupta for the comment on our article.1 Hepatic encephalopathy (HE) is associated with significant morbidity and mortality in cirrhosis; its pathophysiology is incompletely understood. Our meta-analysis was a review of magnetic resonance spectroscopy (MRS) data in HE, which confirmed a specific metabolic pattern, consisting of increased glutamine/glutamate—with reduced choline—and myo-inositol, particularly in the parietal lobes.1 The changes increased with the severity of HE. We agree that this would have limited diagnostic utility in overt HE, which is clinically obvious. We strongly disagree, however, about covert or minimal HE (MHE), which are defined as the presence of neuropsychologic or neurophysiologic abnormalities in patients with no obvious—i.e., at least disorientation for time or asterixis—clinical signs of overt HE. Here, there is a potential role for MRS in diagnosis, monitoring, and investigation. In a recent French cohort of cirrhotic individuals with and without MHE, HE pattern MRS changes in the pallidum were present in 95% of MHE vs 0% of unimpaired patients ( p < 0.001), suggesting MRS could outperform other modalities of MHE diagnosis.2 MRS may also have a significant role in future pathophysiologic and pharmacologic HE studies.

Nontumoral Portal Vein Thrombosis: A Challenging Consequence of Liver Cirrhosis

Nontumoral portal vein thrombosis (PVT) is an increasingly recognized complication in patients with cirrhosis. Substantial evidence shows that portal flow stasis, complex thrombophilic disorders, and exogenous factors leading to endothelial dysfunction have emerged as key factors in the pathogenesis of PVT. The contribution of PVT to hepatic decompensation and mortality in cirrhosis is debatable; however, the presence of an advanced PVT increases operative complexity and decreases survival after transplantation. The therapeutic decision for PVT is often determined by the duration and extent of thrombosis, the presence of symptoms, and liver transplant eligibility. Evidence from several cohorts has demonstrated that anticoagulation treatment with vitamin K antagonist or low molecular weight heparin can achieve recanalization of the portal vein, which is associated with a reduction in portal hypertension-related events and improved survival in cirrhotic patients with PVT. Consequently, interest in direct oral anticoagulants for PVT is increasing, but clinical data in cirrhosis are limited. Although the most feared consequence of anticoagulation is bleeding, most studies indicate that anticoagulation therapy for PVT in cirrhosis appears relatively safe. Interestingly, the data showed that transjugular intrahepatic portosystemic shunt represents an effective adjunctive therapy for PVT in cirrhotic patients with symptomatic portal hypertension if anticoagulation is ineffective. Insufficient evidence regarding the optimal timing, modality, and duration of therapy makes nontumoral PVT a challenging consequence of cirrhosis. In this review, we summarize the current literature and provide a potential algorithm for the management of PVT in patients with cirrhosis.

Development, Validation, and Evaluation of a Simple Machine Learning Model to Predict Cirrhosis Mortality

Machine-learning algorithms offer better predictive accuracy than traditional prognostic models but are too complex and opaque for clinical use. To compare different machine learning methods in predicting overall mortality in cirrhosis and to use machine learning to select easily scored clinical variables for a novel cirrhosis prognostic model. This prognostic study used a retrospective cohort of adult patients with cirrhosis or its complications seen in 130 hospitals and affiliated ambulatory clinics in the integrated, national Veterans Affairs health care system from October 1, 2011, to September 30, 2015. Patients were followed up through December 31, 2018. Data were analyzed from October 1, 2017, to May 31, 2020. Potential predictors included demographic characteristics; liver disease etiology, severity, and complications; use of health care resources; comorbid conditions; and comprehensive laboratory and medication data. Patients were randomly selected for model development (66.7%) and validation (33.3%). Three different statistical and machine learning methods were evaluated: gradient descent boosting, logistic regression with least absolute shrinkage and selection operator (LASSO) regularization, and logistic regression with LASSO constrained to select no more than 10 predictors (partial pathway model). Predictor inclusion and model performance were evaluated in a 5-fold cross-validation. Last, the predictors identified in the most parsimonious (the partial path) model were refit using maximum-likelihood estimation (Cirrhosis Mortality Model [CiMM]), and its predictive performance was compared with that of the widely used Model for End Stage Liver Disease with sodium (MELD-Na) score. All-cause mortality. Of the 107 939 patients with cirrhosis (mean [SD] age, 62.7 [9.6] years; 96.6% male; 66.3% white, 18.4% African American), the annual mortality rate ranged from 8.8% to 15.3%. In total, 32.7% of patients died within 3 years, and 46.2% died within 5 years after the index date. Models predicting 1-year mortality had good discrimination for the gradient descent boosting (area under the receiver operating characteristics curve [AUC], 0.81; 95% CI, 0.80-0.82), logistic regression with LASSO regularization (AUC, 0.78; 95% CI, 0.77-0.79), and the partial path logistic model (AUC, 0.78; 95% CI, 0.76-0.78). All models showed good calibration. The final CiMM model with machine learning-derived clinical variables offered significantly better discrimination than the MELD-Na score, with AUCs of 0.78 (95% CI, 0.77-0.79) vs 0.67 (95% CI, 0.66-0.68) for 1-year mortality, respectively (DeLong z = 17.00; P < .001). In this study, simple machine learning techniques performed as well as the more advanced ensemble gradient boosting. Using the clinical variables identified from simple machine learning in a cirrhosis mortality model produced a new score more transparent than machine learning and more predictive than the MELD-Na score.

Nonsurgical Secondary Prophylaxis of Esophageal Variceal Bleeding in Cirrhotic Patients: A Systematic Review and Network Meta-analysis.

The aim of this study was to evaluate the effectiveness of nonsurgical secondary prophylaxis interventions for esophageal varices (EV) rebleeding in cirrhotic patients using network meta-analysis. Secondary prophylaxis of EV rebleeding in cirrhosis is searched on PubMed, Embase, and the Cochrane Library databases. The quality of literatures was extracted by 2 independent investigators according to the requirements of Cochrane Handbook for Systematic Reviews of Interventions, Version 5.0.0. Meta-analysis was performed on Review Manager 5.3 software for the incidence of cirrhosis EV rebleeding, rebleeding-related mortality, and overall mortality; and STATA 15.1 software was used for network meta-analysis. In all, 57 randomized controlled trials were reviewed. Endoscopic band ligation (EBL)+argon plasma coagulation has not been recommended by guidelines, and it is rarely used; the number of existing studies and the sample size are small. Considering poor stability of the combined results, these studies were excluded; 55 literatures were included. In terms of reducing the incidence of rebleeding, transjugular intrahepatic portosystemic shunt (TIPS) surface under the cumulative ranking curve (SUCRA) (94.3%) was superior to EBL+endoscopic injection sclerotherapy (EIS) (84.4%), EIS+β-blockers (77.9%), EBL (59.8%), EBL+β-blockers+isosorbide-5-mononitrate (52.7%), EBL+β-blockers (51.4%), EIS (34.2%), β-blockers+isosorbide-5-mononitrate (23.7%), β-blockers (20.8%), and placebo (0.8%). In reducing rebleeding-related mortality, TIPS SUCRA (87.2%) was more efficacious than EBL+EIS (83.5%), EIS (47.9%), EBL+β-blockers (47.4%), β-blockers (41.8%), EBL (34.5%), and placebo (7.6%). In reducing overall mortality, TIPS SUCRA (81.1%) was superior to EBL+EIS (68.9%), EIS+β-blockers (59.2%), EBL+β-blockers (55.4%), EIS (48.8%), EBL (48.7%), β-blockers (34.2%), placebo (3.6%). TIPS was more effective in reducing the incidence of cirrhosis EV rebleeding, rebleeding-related mortality, and overall mortality in cirrhosis. Combined with the above results, TIPS is more likely to be recommended as a secondary prophylaxis intervention for EV in cirrhosis.

Assessment of Liver Fibrosis In Non-Alcoholic Fatty Liver Disease Using Real-Time Elastography

Background: Non-alcoholic fatty liver disease (NAFLD) become a challenge as it`s prevalence, difficulty to diagnose and complex pathogenesis representing about 20% of common liver disorders Patients with NAFLD are at higher risk for adverse outcomes such as cirrhosis, HCC and liver-related mortality. Aim and objectives : We aim to assess the applicability and performance of real-time elastography for the diagnosis of liver fibrosis.Methods: One hundred and thirty subjects attended damanhour medical national institute hepatology and gastroenterology outpatient clinic were divided into two groups; Group (I): Hundred cases having NAFLD by ultrasound, Group (II): thirty healthy subjects as control.Results: Fibrosis stages in NAFLD patients significantly higher than in the control group diagnosed by real time elastrography (P = 0.001). There was an agreement between Realtime Elastrography and FIB-4 index and NAFLD fibrosis score 93% and 86% respectively and diagnostic performance of real time elastrography in advanced liver fibrosis ≥F3 was assessed in comparing with FIB-4 index show sensitivity 90%, specifity 93.3%, PPV 60%, NPV 98.8%, accuracy 93%, AUC0.917, 95%CI 0.81-1.0 and (p = 0.001). Conclusion : Real time elastography may be useful in diagnosis of fibrosis in non-alcoholic fatty liver disease.

Nonalcoholic Fatty Liver Disease: A Drug Revolution Is Coming.

The worldwide prevalence of non-alcoholic fatty liver disease is around 25%, and that of nonalcoholic steatohepatitis (NASH) ranges from 1.5% to 6.45%. Patients with NASH, especially those with fibrosis, are at higher risk for adverse outcomes such as cirrhosis and liver-related mortality. Although vitamin E, pioglitazone, and liraglutide improved liver histology in randomized trials, there are currently no Food and Drug Administration-approved drugs for NASH. Five pharmacologic agents—obeticholic acid, elafibranor, cenicriviroc, resmetirom, and aramchol—are being evaluated in large, histology-based phase 3 trials. Within 2 to 4 years, new and effective drugs for the treatment of NASH are expected. Additionally, many phase 2 trials are ongoing for various agents. Based on the results of phase 2 and 3 trials, combination treatments are also being investigated. Future treatment strategies will comprise drug combinations and precision medicine based on the different phenotypes of NASH and treatment response of the individual patient.

Future Alcohol-Attributable Mortality in France Using a Novel Generalizable Age-Period-Cohort Projection Methodology.

AimTo forecast age- and sex-specific alcohol-attributable mortality in France for the period 2015–2050 using a novel generalizable methodology that includes different scenarios regarding period and cohort change.MethodsFor the French national population aged 25–90 years (1979–2014), we estimated alcohol-attributable mortality by mortality from the main causes of death wholly attributable to alcohol, plus liver cirrhosis mortality. We modelled sex-specific alcohol-attributable mortality by adjusting for age, period and birth cohort. We forecasted the model parameters to obtain future age- and sex-specific alcohol-attributable mortality up until 2050 using a conventional baseline, scenario I (favourable period change) and scenario II (unfavourable cohort change).ResultsAlcohol-attributable mortality is clearly declining in France, with the decline decelerating from 1992 onwards. In 2014, the age-standardized alcohol-attributable mortality rates, in deaths per 100,000, were 34.7 among men and 9.9 among women. In 2050, the estimated rates are between 10.5 (prediction interval: 7.6–14.4; scenario I) and 17.6 (13.1–23.7; scenario II) among men, and between 1.1 (0.7–1.7; scenario I) and 1.8 (1.2–2.9; scenario II) among women; which implies declines of 58% for men and 84% for women (baseline).ConclusionAlcohol-attributable mortality in France is expected to further decline in the coming decades, accompanied by age pattern changes. However, France’s levels are not expected to reach the current lower levels in Italy and Spain for 15 years or more. Our results point to the value of implementing preventive policy measures that discourage alcohol consumption among people of all ages, but especially among adolescents.

The Eye as a Non-Invasive Window to the Microcirculation in Liver Cirrhosis: A Prospective Pilot Study.

Microcirculatory dysfunction is associated with organ failure, poor response to vasoactive drugs and increased mortality in cirrhosis, but monitoring techniques are not established. We hypothesized that the chorioretinal structures of the eye could be visualized as a non-invasive proxy of the systemic microvasculature in cirrhosis and would correlate with renal dysfunction. Optical Coherence Tomography (OCT) was performed to image the retina in n = 55 cirrhosis patients being assessed for liver transplantation. OCT parameters were compared with established cohorts of age- and sex-matched healthy volunteers (HV) and patients with chronic kidney disease (CKD). Retinal thickness, macular volume and choroidal thickness were significantly reduced relative to HV and comparable to CKD patients (macular volume: HV vs. cirrhosis mean difference 0.44 mm3 (95% CI 0.26–0.61), p ≤ 0.0001). Reduced retinal thickness and macular volume correlated with renal dysfunction in cirrhosis (macular volume vs. MDRD-6 eGFR r = 0.40, p = 0.006). Retinal changes had resolved substantially 6 weeks following transplantation. There was an inverse association between choroidal thickness and circulating markers of endothelial dysfunction (endothelin-1 r = −0.49, p ≤ 0.001; von Willebrand factor r = −0.32, p ≤ 0.05). Retinal OCT may represent a non-invasive window to the microcirculation in cirrhosis and a dynamic measure of renal and endothelial dysfunction. Validation in different cirrhosis populations is now required.

S0987 Treatment and Outcomes of Small Intestine Variceal Bleeding in Cirrhosis

INTRODUCTION: Hemorrhage from esophageal varices is a well characterized complication of portal hypertension; conversely, bleeding from ectopic varices is less well described. We aimed to compare a case series of patients with bleeding small intestine varices (SIV) to the existing literature of case reports to determine clinical outcomes. METHODS: We performed a retrospective study from January 2008-November 2019 at our institution. Natural language processing was used to identify adult patients with cirrhosis and SIV. Chart review was performed to verify SIV based on endoscopy, video capsule, or imaging, and to identify cases of bleeding. Patients with non-cirrhotic portal hypertension and stomal varices were excluded. Separately, we conducted a systematic literature review with a librarian to identify case reports of bleeding SIV in cirrhosis. We used the two-sample t-test for continuous variables and the Fischer’s exact test for categorical variables. The Kaplan-Meier limit curve was used to calculate survival. RESULTS: A total of 18 cases of bleeding SIV were identified at our institution (male n = 8; female n = 10). Mean age was 55.2 years (SD +/- 8.8). The group was predominantly Caucasian (n = 12). Mean MELD-Na was 18.8 (SD +/- 9.8) and alcohol was the predominant etiology for liver disease (n = 8). Varices were duodenal (n = 14), jejunal (n = 3), and ileal (n = 1). Endoscopy was the most frequent modality for detection (n = 11). Treatment and outcomes are shown – Figure 1. Two patients died from gastrointestinal hemorrhage. Median follow-up was 103 days with an overall mortality rate of 38.9%. Our literature search yielded 395 cases with 77 included for final analysis (male n = 45; female n = 32). Mean age was 52.3 years (SD +/- 12) and alcohol induced liver disease in most (n = 36). Race and disease severity data were poorly reported, otherwise our cases series and the published cases were matched for age, gender, etiology of liver disease, and SIV location. Length of stay 11.1 vs 9.7 days (P = 0.48) and transfusion requirements 11.1 vs 11.5 units RBCs (P = 1.00) were not different. Treatment and outcomes were compared with our case series – Table 1. There was a trend for lower mortality (18.2%) over a median follow-up period of 120 days – Figure 2. CONCLUSION: Bleeding SIV carry high morbidity and mortality in cirrhosis which may be under-reported due to publication bias. A high rate of failure to control initial bleeding across treatment modalities is concerning.Figure 1.: Outcomes of Small Intestine Varices Bleeding in the Case Series.Figure 2.: Kaplan-Meier Curve (P = 0.06).Table 1.: Outcomes of Small Intestine Varices Bleeding in Our Series Compared to Existing Literature

Prevalence of cirrhotic cardiomyopathy and its relationshipwith serum pro-brain natriuretic peptide, hepatorenal syndrome, spontaneous bacterial peritonitis, and mortality.

This study aims at estimating the prevalence of cirrhotic cardiomyopathy in a cohort of cirrhosis patients in northern India using the World Congress of Gastroenterology 2005 criteria and its relationshipwith grades of cirrhosis, itscomplications, and all-cause mortality. This was a prospective study in which 53 cirrhosis patients underwent the 2D color Doppler, and tissue Doppler echocardiography. Echocardiography findings were compared with thirty age- and sex-matched healthy controls. Additionally, serum pro-brain natriuretic peptide (pro-BNP) and troponin-T levels were measured. Patients were followed up for 6months to look for complications and mortality. 2D echocardiography findings revealed that diastolic cardiomyopathy with no gross systolic dysfunction was significantly prevalent in cirrhosis patients. Using the Montreal criteria, we found the incidence of diastolic cardiomyopathy to be 56.6%. Tissue Doppler echocardiography findings were also correlated. Diastolic dysfunction correlated with the severity of cirrhosis, and patients with higher Child score had more diastolic dysfunction. Serum pro-BNP levels and QTc interval were also higher in patients with diastolic dysfunction. On survival analysis, patients with cirrhotic cardiomyopathy had shortersurvival and greater frequency ofencephalopathy and hepatorenal syndrome (HRS) episodes as compared with cirrhotic patients without cardiomyopathy, though the differences were not statistically significant. The study showed that diastolic dysfunction washighly prevalent (56.6% of the study population) in cirrhosis patients. QTc interval and pro-BNP were also significantly raised. Also, complications of cirrhosis like HRS, spontaneous bacterial peritonitis, and hepatic encephalopathy were more common in the cirrhoticcardiomyopathy group.

S2185 “Red Nipple Sign”: A Precursor to “White Nipple Sign”

INTRODUCTION: Cirrhosis affects approximately 3.6 out of every 1000 adults in North America and leads to about 32,000 deaths annually. Variceal hemorrhage occurs in 25–40% of patients with cirrhosis and is a major cause of cirrhosis related morbidity and mortality, associated with up to 20 percent mortality. Additionally, those patients who survive a variceal hemorrhage have a 70 percent chance of recurrent variceal hemorrhage within one year. CASE DESCRIPTION/METHODS: We present a case of a 70-year-old male with past medical history of alcoholic cirrhosis, hypertension and rheumatoid arthritis (taking nonsteroidal anti-inflammatory drugs [NSAIDs]) admitted with hematochezia and hematemesis. The patient was started on a proton pump inhibitor (PPI), octreotide and ceftriaxone, and underwent an emergent esophagogastroduodenoscopy (EGD). Two columns of large esophageal varices were identified extending from Z-line to mid-esophagus (Figure 1). One of the varices was noted to contain two adjacent red spots which appeared similar to stigmata labeled as “white nipple sign” but red in color (Figure 2). A decision was made to perform band ligation and one band was deployed to each variceal column base resulting in excellent decompressive effect. One additional band was then deployed over both “red spots,” which during suctioning into the bander cap began to actively spurt heme, however, bleeding resolved after band deployment. The sites of previous “red spots” were then noted to have classic “white nipple sign” appearance (Figure 3). The patient tolerated the procedure well, was monitored as inpatient and subsequently discharged home with follow-up in a hepatology clinic. DISCUSSION: Variceal hemorrhage is a gastrointestinal emergency with prognosis reliant on achieving hemostasis and preventing future hemorrhage. Therefore, it is extremely important to recognize endoscopic features of high-risk stigmata for future hemorrhage. The most commonly reported features are often described as “red signs,” and include red wales marks, cherry red spots and hematocystic spots. One stigma of recent hemorrhage is known as “white nipple sign,” which owes its appearance to the platelet-fibrin plug overlying a varix. On literature review, we found this to be the first case of showing endoscopic transition of a red spot (“red nipple sign”) into a “white nipple sign,” demonstrating likely pathogenesis from a finding significant for high risk of hemorrhage to the finding consistent with post hemorrhage state.Figure 1.: Two columns of large varices extending from z-line to mid-esophagus.Figure 2.: Close up endoscopic image of red spot overlying varix.Figure 3.: Site of previous red spot, subsequently noted to have "white nipple sign" after band ligation of varix.

Albumin administration in patients with decompensated liver cirrhosis: a meta-analytic update

End-stage liver disease and its related complications exert a huge disease burden and reduce the survival rates of many patients. Albumin administration for patients with decompensated liver cirrhosis has been a controversial topic of discussion. The aim of this study is to investigate whether albumin reduces the mortality and complications of liver cirrhosis compared to standard medical therapy (SMT) alone. Clinical trials in which albumin administration was compared to SMT in patients with liver cirrhosis were included in this meta-analysis. The primary outcome of this study was to evaluate the effect on reducing all-cause mortality. Ascites control, renal failure and hepatic encephalopathy were evaluated as secondary outcomes. Nine clinical trials with 1231 patients were recruited and analyzed using the quality effect model. Mortality rate was significantly reduced in the albumin group [relative risk (RR) 0.73, 95% confidence interval (CI) 0.56-0.96]. Heterogeneity was mild across all studies (I2 23.3%). Studies reporting long-term albumin (LTA) administration were found to have a significant decrease in mortality (RR 0.57, 95% CI 0.44-0.73). However, studies reporting short-term albumin administration were found to have no effect on mortality (RR 0.90, 95% CI 0.56-1.45). Furthermore, there was a significant decrease in the incidence of all secondary outcomes. This meta-analysis provides evidence that LTA administration is significantly effective in reducing the mortality of liver cirrhosis compared to SMT. Albumin administration was also shown to reduce the occurrence of ascites, renal failure and hepatic encephalopathy as complications of liver cirrhosis.

Long-term albumin administration in patients with cirrhosis and ascites: A meta-analysis of randomized controlled trials.

Ascites is a common complication of cirrhosis, and it is associated with increased mortality. The aim of this study was to evaluate the efficacy of long-term albumin administration in decreasing mortality and other complications of patients with cirrhosis and ascites. A systematic review was performed using MEDLINE and Embase databases. Randomized controlled trials evaluating long-term albumin administration in patients with cirrhosis and ascites were considered eligible, as long as at least one of the following outcomes was evaluated: mortality, recurrence of ascites/need for paracentesis, refractory ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, gastrointestinal bleeding, or adverse events. Meta-analysis was performed using the random-effects model, through the Mantel-Haenszel method. The study protocol was registered at PROSPERO platform (CRD42019130078). The literature search yielded 1517 references. Five randomized controlled trials fulfilled the selection criteria and were included in this meta-analysis, involving 716 individuals. Patients receiving long-term albumin had significantly lower risk of recurrence of ascites/need for paracentesis when compared with controls (risk ratio=0.56, 95% confidence interval=0.48-0.67, P<0.00001). There was no evidence of significant difference between the long-term albumin and control groups regarding mortality, refractory ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, gastrointestinal bleeding, or adverse events. Long-term albumin administration in patients with cirrhosis and ascites decreases recurrence of ascites/need for paracentesis. At this point, there is no evidence of significant benefits of long-term albumin administration regarding mortality or other complications of cirrhosis.