Severe Complication Of Cirrhosis Research Articles

Controversies in terlipressin and transplantation in the United States: How do we MELD the two?

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a severe complication of cirrhosis that carries a poor prognosis. The recent Food and Drug Administration approval of terlipressin has substantial implications for managing HRS-AKI and liver allocation in the United States. Terlipressin has been available in Europe for over a decade, and several countries have adapted policy changes such as Model for End-Stage Liver Disease (MELD) score "lock" for HRS-AKI. In this article, we outline the European experience with terlipressin use and explore the question of whether terlipressin treatment for HRS-AKI should qualify for the MELD score "lock" in the United States in those who respond to therapy. Arguments for the MELD lock include protecting waitlist priority for terlipressin responders or partial responders who may miss offers due to MELD reduction in the terlipressin treatment window. Arguments against MELD lock include the fact that terlipressin may produce a durable response and improve overall survival and that equitable access to terlipressin is not guaranteed due to cost and availability. We subsequently discuss the proposed next steps for studying terlipressin implementation in the United States. A successful approach will require the involvement of all major stakeholders and the mobilization of our transplant community to spearhead research in this area.

Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis.

Acute kidney injury (AKI) is common in hospitalized patients with cirrhosis. Hepatorenal syndrome (HRS) is a type of AKI known as HRS-AKI. It is a severe complication of cirrhosis with high morbidity and mortality. While certain vasoconstrictor medications have been shown to improve HRS-AKI, no clear transplant-free survival benefit has been reported with medical therapies. Patients with HRS-AKI should be considered for urgent liver transplantation evaluation. In this review, we discuss the most recent updates on the definition, diagnosis, and management of AKI in cirrhosis, with special a emphasis on HRS.

Population characteristics, healthcare pathways and outcomes of patients with cirrhosis hospitalized with overt hepatic encephalopathy in France: A study of the French Hospital‐Discharge Database

Hepatic encephalopathy (HE) is a severe complication of cirrhosis, independently associated with a poor survival. The objectives of this study were to describe the prevalence of overt hepatic encephalopathy (OHE) requiring hospitalization, and the healthcare pathways and outcomes of patients hospitalized for OHE in France. Data from the French Hospital‐Discharge Database (Programme de Medicalisation des Systemes d'information, PMSI) within the 5-year period from 2014 to 2018 were analysed. Since the disease lacks a PMSI code in the ICD-10, an identification algorithm was developed. The analysis identified 57,191 patients with OHE including 48,566 patients (85 %) who had been hospitalized twice or more during the study period. Each year, an average of over 20,000 patients were hospitalized in France for OHE as the primary or secondary reason for hospitalization. Among these patients, between 11,500 and 13,500 had been hospitalized at least twice in that year with an average of 3.4 hospitalisations per year. 25 % of admissions occurred following consultation at the emergency unit. Among hospitalisations, 15 % involved admission to the critical care resuscitation unit or intensive care. For all patients identified as suffering from OHE and hospitalized, the 5-year mortality was 46.5 % (26,621 patients). This pioneering study revealed that, in France, despite a probable underestimation of OHE episodes due to the lack of specific PMSI coding, the prevalence of OHE was very high, with frequent recurrences and readmissions, and high mortality.

THE TREATMENT OF HEPATORENAL SYNDROME WITH TERLIPRESSIN: CONTINUOUS INTRAVENOUS INFUSION VS INTRAVENOUS BOLUSES A RANDOMISED CONTROLLED STUDY ON SYNDROME

Objective: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis, with terlipressin and albumin being the most common treatment. The study aimed to compare the effectiveness and safety of continuous intravenous infusion vs. intravenous boluses of terlipressin in treating type 1 h.
 Methods: A randomized controlled trial was conducted on cirrhosis patients with type 1 h. Patients were allocated to receive terlipressin via continuous infusion (TERLI-INF group) or intravenous boluses (TERLI-BOL group). Demographic, clinical, and laboratory data were collected, and treatment details were recorded. The primary endpoint was the frequency of drug-related adverse events. Secondary endpoints included therapy responsiveness and 90-day transplant-free survival.
 Results: Both groups exhibited similar baseline characteristics. While treatment length and cumulative albumin doses were comparable, TERLI-INF patients received lower terlipressin doses. Severe treatment-related adverse events differed between groups. Univariate analysis identified several baseline parameters significantly associated with response to terlipressin. The study supports continuous terlipressin infusion's superiority in treating type 1 h, with lower adverse event rates and improved patient response.
 Conclusion: The study concludes that continuous intravenous terlipressin infusion is safer and more effective in treating type 1 h in decompensated cirrhosis patients compared to intravenous boluses. Lower terlipressin dosages were effective in continuous infusion, indicating improved safety. The MELD score was an independent predictor of response, and therapy responsiveness was associated with improved 90 d survival.

Incidence and outcomes of acute kidney injury including hepatorenal syndrome in hospitalized patients with cirrhosis in the US

Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis. We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other). A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p= 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all). AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed. Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US.

Dietary Management in Patients with Liver Cirrhosis and Renal Failure

Cirrhosis patients are prone to develop kidney dysfunction. Hepatorenal failure (HRS) is one of the most severe complications of cirrhosis. Majority of cirrhosis patients have higher nutritional requirements owing to hyper catabolic state. The macronutrient intake is tailored to suit liver failure in cirrhosis patients with renal failure while regarding fluid and minerals like sodium; potassium etc weightage is given for the renal failure. Energy intake of 30 kcal/kg/day and protein intake of 1.2 g/kg/day for maintenance of nutritional status and 35 kcal/kg/day and 1.5 g/kg/day protein for improvement of nutritional status is recommended. Dietary protein of at least 1.0-1.2g/kg/day may be sufficient to prevent negative nitrogen balance. Multiple meals and snacks containing food rich in carbohydrates should be given to reduce the risk of hypoglycemia, Late evening snacks and a breakfast containing some proteins to shorten the period of fasting is recommended. Medium chain triglycerides should be used in case of fat malabsorbtion. In cirrhotic patients with ascites the recommended intake of sodium is nearly 80 mmol day or 2 g of sodium. Hyperkalemia may occur in HRS (or AKI) and patients using potassium sparing diuretics Hypokalemia has to be avoided as it can precipitate HE Micronutrients and vitamins need to administer for treating confirmed or clinically suspected deficiency Appropriate, adequate and timely nutritional management with individualized and intensive dietary counselling is the key component to prevent malnutrition.

S1375 Role of Rifaximin in the Prevention of Acute Variceal Bleeding in Cirrhosis: A Systematic Review and Meta-Analysis

Introduction: Acute variceal bleeding is one of the most severe complications of cirrhosis and is associated with high mortality. Rifaximin has been shown to be efficacious in the treatment of hepatic encephalopathy (HE). Some studies have also shown rifaximin to be beneficial in decreasing the risk of initial episode of variceal bleeding and to decrease the risk of re-bleeding in those with prior variceal hemorrhage. We performed a systematic review and meta-analysis to evaluate the efficacy of rifaximin in prevention of acute variceal bleeding. Methods: A systematic literature search was performed at PubMed, Embase, Web of Science and Cochrane library database until March 2022. All studies that evaluated the role of rifaximin in prevention of initial episode of variceal bleeding or risk of re-bleeding in cirrhotic patients were included in the meta-analysis. The analysis was performed using Revman 5.4 software. Results: Seven studies including 1999 patients were included in the final meta-analysis. Of these, 3 studies were randomized controlled trials (RCTs) and 4 studies were observational studies. Out of 1999 included patients, 769 patients received rifaximin along with standard care management and 1230 patients received standard of care management only. Patients in the rifaximin group had significantly lower odds of acute variceal bleeding with OR= 0.43 (95% CI: 0.31, 0.58), I2=0. We also performed a subgroup analysis including only RCTs, which although showed trend toward lower risk of variceal bleeding in rifaximin group but did not reach statistically significance OR=0.58 (0.27, 1.28). In a second subgroup analysis, patients who received rifaximin also had significantly lower odds of spontaneous bacterial peritonitis (SBP) OR= 0.15 (0.10, 0.22), risk of acute kidney injury/hepatorenal syndrome (AKI/HRS) OR=0.39 (0.22, 0.68) and HE OR=0.37 (0.21, 0.68). Publication bias was deferred as number of studies were less than 10. (Figure) Conclusion: Rifaximin is associated with lower odds of variceal bleeding, SBP, AKI/HRS and HE in patients with cirrhosis. Although the overall analysis demonstrates rifxamin can decrease the risk of variceal bleeding this loses statistical significance when only RCTs were included in the analysis. Therefore, additional RCTs are needed to further evaluate if there is any benefit of rifaximin in reducing the risk of variceal bleeding and to justify its use aside from the treatment HE.Figure 1.: Forest plot for variceal bleeding.

Spontaneous bacterial empyema: a tertiary care center experience and a systematic review

ABSTRACT Background Spontaneous bacterial empyema (SBE) is an infection of a preexisting hepatic hydrothorax (HH). We aim to describe the experience in managing SBE in a liver transplant (LT) referral center and assessing the incidence and mortality rates of SBE after conducting a systematic review. Methods 992 patients with cirrhosis were retrospectively reviewed from 2015 to 2020. SBE was diagnosed by (i) positive microbiological culture and polymorphonuclear leukocyte count >250 cells/µL or (ii) negative microbiological culture, compatible clinical course, and polymorphonuclear count >500 cells/µL in pleural fluid. Furthermore, we conducted a comprehensive literature search of MEDLINE, EMBASE, and Google Scholar for studies evaluating SBE. Results Twelve patients (10.4%) had spontaneous bacterial empyema out of 115 patients with HH. Five patients underwent LT, 6 had died, and 1 did not get transplanted and was alive throughout the duration of follow-up. Ten studies were included in the systematic review. Pooled incidence in patients with HH was 19.03%. Only 20.69% of the patients received a LT. Pooled mortality rate was 46.45%, with only 3.45% of the patients dying post-transplant. Conclusion SBE is a severe complication of cirrhosis and HH. LT may provide a survival benefit. Thus, patients should be considered for early transplant.

Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy.

Mild micro-hepatic encephalopathy (MHE) is a severe complication of cirrhosis. At present, there are differences in the consistency of detection strategies and treatment directions for MHE. The characteristic changes in intestinal microbiota and serum metabolites in MHE patients and the possible relevant interaction mechanisms would inevitably affect the developmental direction of MHE. Therefore, the changes in the characteristics of intestinal microbiota and serum metabolites of MHE patients were determined, and the possible interactions between them were analyzed. Stool and serum tests were performed on both the MHE patients and healthy individuals. The 16S rRNA gene high-throughput sequencing and bioinformatics analyses were used to analyze the differences in intestinal microbiota in MHE patients. The serum metabolites were detected using liquid LC-MS/MS (liquid chromatography-mass spectrometry) technology, and the differences in the metabolic networks of blood metabolites in MHE patients were analyzed. A comprehensive bioinformatics analysis approach was adopted to identify the composition and characteristics of microbiota and serum metabolites and the possible correlation between them. The main characteristics of the structural imbalance in the intestinal microbiota of MHE patients included a decrease in the number of beneficial bacteria at the levels of phylum, class, order, family, and genus and an increase in the pathogenic bacteria, resulting in substantial changes in the relative abundances of bacteria in the intestinal microbiota. The main predicted functions that showed significant differences included chromosome, amino acid-related enzymes, methane metabolism, and arginine and proline metabolism. The detection of serum metabolites resulted in 10 different metabolites, including taurocholic acid, citrulline, d-phenyl-lactic acid, l-tyrosine, benzoate, phenylalanine, linoleic acid, eicosapedienic acid, alpha-dimorphecolic acid, and dehydroepiandrosterone. The subsequent metabolite pathways analysis showed differences in the metabolism of linoleic acid, phenyl-propane, caffeine, arginine, proline, glycine, serine, threonine, tyrosine, and pyrimidine compared to the control group. In summary, it seems that the changes in the microbiome that we have identified have resulted in corresponding changes to the serum metabolome. In turn, this may represent changes in the absorption of metabolites from the gut or reflect the changed metabolic capacity of the MHE liver or both. There were characteristic changes in the intestinal microbiota and serum metabolites in the MHE patients. There might be a related interaction mechanism between the two, which would provide evidence and direction for the detection and treatment strategies of MHE.

Acute Kidney Injury in Patients with Liver Cirrhosis: Prevalence, Predictors, and In-Hospital Mortality at a District Hospital in Ghana.

Background Acute kidney injury (AKI) is one of the most severe complications of cirrhosis and portends an ominous prognosis with an estimated mortality of about 50% in a month and 65% within a year. Infection and hypovolemia have been found to be the main precipitating factors of AKI in liver cirrhosis. Early detection and treatment of AKI may improve outcomes. AKI in patients with liver cirrhosis in Ghana and their impact on inpatient mortality are largely unknown. This study was aimed at determining the prevalence, precipitating factors, predictors, and in-hospital mortality of AKI in patients with liver cirrhosis admitted to a district hospital in Ghana. Methods Consecutive hospitalized patients with liver cirrhosis from 1 January 2018 to 30 April 2020 were recruited. Patient's demographic data and clinical features were collected using a standardized questionnaire. Biochemical and haematological tests as well as abdominal ultrasound scans were done for all patients. All patients were then followed up until discharge or death. Results There were 117 (65.4%) males out of the 179 patients with a mean age of 49.94 and 45.84 years for those with and without AKI, respectively. The prevalence of AKI was 27.9% (50/179). Out of 50 participants with AKI, 64.0% (32/50) died, contributing 41.0% of all in-patient mortality amongst participants. There was a significant association between AKI and death (p ≤ 0.001). The major precipitating factors of AKI were infections (60.0%), hypovolemia (20.0%) due to gastrointestinal bleeding and gastroenteritis, and refractory ascites (16.0%). Alkaline phosphatase, INR, model for end-stage liver disease sodium, sodium, and blood urea nitrogen were independent predictors of AKI. Conclusion AKI was common among patients with liver cirrhosis with high in-patient mortality. Identification of these precipitants and independent predictors of AKI may lead to prompt and targeted treatment with reduction in patient mortality.

Epidemiology and Outcomes of Hospitalizations Due to Hepatocellular Carcinoma

BackgroundHepatocellular Carcinoma (HCC) is a severe complication of cirrhosis and the incidence of HCC has been increasing in the United States (US). We aim to describe the trends, characteristics, and outcomes of hospitalizations due to HCC across the last decade.MethodsWe derived a study cohort from the Nationwide Inpatient Sample (NIS) for the years 2008-2017. Adult hospitalizations due to HCC were identified using the International Classification of Diseases (9th/10th Editions) Clinical Modification diagnosis codes (ICD-9-CM/ICD-10-CM). Comorbidities were also identified by ICD-9/10-CM codes and Elixhauser Comorbidity Software (Agency for Healthcare Research and Quality, Rockville, Maryland, US). Our primary outcomes were in-hospital mortality and discharge to the facility. We then utilized the Cochran-Armitage trend test and multivariable survey logistic regression models to analyze the trends, outcomes, and predictors.ResultsA total of 155,436 adult hospitalizations occurred due to HCC from 2008-2017. The number of hospitalizations with HCC decreased from 16,754 in 2008 to 14,715 in 2017. Additionally, trends of in-hospital mortality declined over the study period but discharge to facilities remained stable. Furthermore, in multivariable regression analysis, predictors of increased mortality in HCC patients were advanced age (OR 1.1; 95%CI 1.0-1.2; p< 0.0001), African American (OR 1.3; 95%CI 1.1-1.4;p< 0.001), Rural/ non-teaching hospitals (OR 2.7; 95%CI 2.4-3.3; p< 0.001), uninsured (OR 1.9; CI 1.6-2.2; p< 0.0001) and complications like septicemia and pneumonia as well as comorbidities such as hypertension, diabetes mellitus, and renal failure. We observed similar trends in discharge to facilities.ConclusionsIn this nationally representative study, we observed a decrease in hospitalizations of patients with HCC along with in-hospital mortality; however, discharge to facilities remained stable over the last decade. We also identified multiple predictors significantly associated with increased mortality, some of which are potentially modifiable and can be points of interest for future studies.

Liver transplantation for acute-on-chronic liver failure predicts post-transplant mortality and impaired long-term quality of life.

Among patients with cirrhosis, candidate selection and timing of liver transplantation (LT) remain problematic. Acute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis with excessive short-term mortality rates under conservative therapeutic measures. The role of LT in the management of ACLF is uncertain. To assess the impact of ACLF on post-LT survival and long-term graft function, morbidity and quality of life (QoL). We retrospectively analysed all cirrhosis patients undergoing LT at our institution between 01/2009 and 12/2014. Median follow-up was 8.7years. Long-term LT survivors were interviewed with established QoL questionnaires. Of 250 LT recipients, 98 fulfilled the EASL diagnostic ACLF criteria before LT ('ACLF-LT'). ACLF associated with reduced post-LT survival (HR for 6-month survival compared to non-ACLF-LT: 0.18; HR for 10-year-survival: 0.47; both P<.001) depending on ACLF severity before LT, and mainly inferred by infections both in the early and late phases after LT. In ACLF patients, CLIFc-OFs was superior to MELD score in predicting post-LT mortality. Long-term follow-up revealed comparable graft functions and comorbidity burden in ACLF-LT and non-ACLF-LT survivors. ACLF-LT patients reported significantly impaired health and QoL, particularly with regards to anxiety/depression and physical and psychological health (all P<.05). LabMELD score, presence of ACLF at LT and duration of post-LTintensive care associated with poor long-term QoL. ACLFpredicts impaired post-LT survival. While long-term graft function and extrahepatic comorbidities are comparable in ACLF and non-ACLF LT survivors, the strikingly low QoL in many ACLF-LT recipients warrants consideration during follow-up patient care.

Predicting mortality for hepatorenal syndrome with liver‐specific scores

Background Hepatorenal syndrome (HRS) is a severe complication of cirrhosis which has a high mortality rate. The treatment for HRS is costly. Therefore, it is paramount to choose wisely the patients who could benefit from it. The purpose of this study is to analyse and compare the role of liver-specific scores when predicting mortality for HRS patients. Design and Setting Historical cohort study conducted in a public tertiary care teaching hospital. Methods Data from medical records from 2010 to 2016 were obtained by searching the hospital electronic database for every patient who received terlipressin. Every chart was reviewed in order to determine the diagnosis of cirrhosis and HRS. The data in these medical records were reviewed and multiple variables were collected. and included in 46 patients. Liver-specific scores were calculated and ROC-curves pairwise comparisons were performed using DeLong test. Results Child-Turcotte-Pugh (CTP) was able to predict mortality in 30-, 90- and 365 days, with AUROC of 0.76, 0.75 and 0.72 respectively. Values of CTP above 12 were able to predict higher mortality for all patients, with sensitivity of 38%, 36% and 30% and specificity of 100%, 100% and 100% for 30-, 90- and 365-day mortality, respectively (P < 0.05). CLIF-SOFA, CLIF-C ACLF, MELD and MELD-Na were inferior to CTP. Conclusion CTP score was superior to other liver-specific scores for predicting mortality in a cohort of cirrhotic patients complicated with HRS in a tertiary teaching hospital.

Short-term mortality in patients with cirrhosis of the liver and acute kidney injury: A prospective observational study.

Renal failure is a common and severe complication of cirrhosis and confers poor prognosis. Serum creatinine is the most practical biomarker of renal function. Serum creatinine estimation in cirrhosis of the liver is affected by decreased formation, increased tubular secretion, increased volume of distribution, and interference by elevated bilirubin. Studies on the prognosis of cirrhotic patients using creatinine kinetics as a definition of acute kidney injury (AKI) proposed by the International Ascites Club are limited. In this single-center prospective observational study, decompensated cirrhotics with AKI defined by the International Ascites Club as the rise of serum creatinine ≥ 0.3mg/dL within 48h of admission or increase of serum creatinine ≥ 50% from stable baseline creatinine over the previous 3months were followed and assessed for the development of complications during hospital course and in-hospital and 30-day mortality. AKI developed in 142 out of 499 (28.45%) patients with cirrhosis. Twenty patients were excluded. The most common etiology of cirrhosis was alcohol (n = 64, 52%), and ascites was present in 115 (94%) patients. Eighty-two (67.21%) patients presented with AKI at the time of admission. Thirty-day mortality was 46.72% (57/122 patients). Hepatorenal syndrome had the highest mortality followed by AKI related to infection. Presence of jaundice and hepatic encephalopathy (HE) was associated with poor survival with adjusted hazard ratio of 3.54 and 2.17, respectively. On bivariate logistic regression analysis, jaundice, HE, type of AKI, AKI stage at maximum creatinine, bilirubin, serum glutamic oxaloacetic transaminase (SGOT), international normalized ratio (INR), and Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores were predictors of mortality (p < 0.05). Sensitivity, specificity, and accuracy of MELD > 29 and CTP score > 11 were 75.44%, 82%, and 78.70% and 66.67%, 81.54%, and 74.60%, respectively for predicting 30-day mortality. Development of AKI as defined by the International Ascites Club in cirrhosis confers high short-term mortality. Jaundice, HE, AKI stage, creatinine at enrollment, bilirubin, CTP, and MELD score were the predictors of mortality. Bullet points of the study highlights What is already known? • Renal failure is a common and severe complication of cirrhosis. • Serum creatinine is the most practical biomarker of renal function but it has many limitations in cirrhotic patients. • Creatinine kinetics-based definition of acute kidney injury (AKI) was proposed by the International Ascites Club. What is new in this study? • Short-term mortality (30days) in decompensated cirrhotic patients with AKI as defined by the International Ascites Club using creatinine kinetics was high. • AKI due to hepatorenal syndrome (HRS) has the highest short-term (30days) mortality followed by AKI due to infection in decompensated cirrhosis. • Detection of AKI using creatinine kinetics-based definition mayprompt anearly appropriate intervention. What are the future clinical and research implications of study findings? • Creatinine kinetics-based definition of AKI diagnose renal injury at anearlier stage; anappropriate intervention should be initiated at the earliestin these patients to improve patient survival.

IMPACT OF ACUTE KIDNEY INJURY STAGING ON PROGNOSIS OF PATIENTS WITH CIRRHOSIS.

Acute kidney injury (AKI) is a common and severe complication of cirrhosis. To evaluate the impact of AKI staging on 30-day mortality of patients with cirrhosis. We performed a retrospective cohort study of hospitalized patients with cirrhosis. Acute kidney injury (AKI) was diagnosed according to the International Club of Ascites recommendations and staged according to the European Association for the Study of the Liver guidelines. Comparisons between groups were made by one-way analysis of variance and Tukey test. Chi-square was calculated for dichotomous variables. Comparisons of renal impairment status among patients were performed using Kaplan-Meier statistics and differences between groups were analyzed using the log-rank test. A P-value <0.05 was considered to be statistically significant. Two hundred and thirty-two patients were included in the study. The diagnosis of AKI was performed in 98 (42.2%) of them. The overall 30-day mortality was 19.8% (46/232). Mortality increased as the degree of AKI progressed. Among patients who did not have AKI, mortality was 5.2% (7/134). When compared to patients without AKI, patients diagnosed with AKI stage 1a had mortality of 12.1% (4/33, P=0.152); patients with AKI stage 1b had mortality of 45% (18/40, P<0.001); and patients with AKI stages 2 or 3 had mortality of 68% (17/25, P<0.001). Moreover, it is noteworthy that full response to treatment was associated to a decreased mortality when compared to patients who did not show complete recovery of renal function (14.3% vs 57.9%, P<0.001). AKI stages 1b or greater, but not AKI stage 1a, are associated to higher 30-day mortality of patients with cirrhosis.

An unusual cause of portal hypertension in a cirrhotic patient

Gastrointerstinal bleeding is a frequent and severe complication of cirrhosis. The rupture of esophageal varices is the main cause of upper gastrointestinal bleeding in cirrhosis. It occurs in about 30 to 40% of patients with liver cirrhosis and esophageal varices. Multidisciplinary approach is need as it is a life threatening condition. Trans-jugular intra-hepatic portosystemic shunt (TIPS) is the elected procedure in the management of refractory bleeding to drug and endoscopic treatment. We report the case of the casual discovery of splenic arteriovenous fistula while performing TIPS in the context of alcoholic liver cirrhosis associating oesophageal varices and portal hypertension.

Validation of CLIF-C ACLF score to define a threshold for futility of intensive care support for patients with acute-on-chronic liver failure

BackgroundAcute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis and is defined by organ failure and high rates of short-term mortality. Patients with ACLF are managed with multiorgan support in the intensive care unit (ICU). Currently, it is unclear when this supportive care becomes futile, particularly in patients who are not candidates for liver transplant. The aim of this study was to determine whether the currently available prognostic scores can identify patients with ACLF in whom prolonged ICU care is likely to be futile despite maximal treatment efforts.MethodsData of 202 consecutive patients with ACLF admitted to the ICU at the Royal Free Hospital London between 2005 and 2012 were retrospectively analyzed. Prognostic scores for chronic liver diseases, such as Child-Pugh, Model for End-Stage Liver Disease (MELD), European Foundation for the study of chronic liver failure (CLIF-C) organ failure (OF), and CLIF-C ACLF, were calculated 48 hours after ICU admission and correlated with patient outcome after 28 days.ResultsThe CLIF-C ACLF score, compared with all other scores, most accurately predicted 28-day mortality, with an area under the receiver operator characteristic of 0.8 (CLIF-C OF, 0.75; MELD, 0.68; Child-Pugh, 0.66). A CLIF-C ACLF score cutoff ≥ 70 identified patients with a 100% mortality within 28 days. These patients had elevated inflammatory parameters representing a systemic inflammatory response, most often renal failure, compared with patients below this cutoff.ConclusionsPatients with ACLF and high CLIF-C ACLF score (≥ 70) after 48 hours of intensive care may reach a threshold of futility for further ongoing intensive support. The best treatment options in this scenario remain to be determined but may include palliative care.

Role of Right Liver Lobe Diameter/Serum Albumin Ratio in Esophageal Varices Assessment in Cirrhotic Patients

Background: Liver cirrhosis is a pathologic condition characterized by fibrosis of the liver parenchyma and evidence of regenerative activity, resulting in portal hypertension. Portal hypertension plays a crucial role in the transition from the pre-clinical to the clinical phase of the disease. Bleeding from ruptured esophagogastric varices is the most severe complication of cirrhosis and is the cause of death in about one third of cirrhotic patients. Cirrhotic patients frequently undergo screening endoscopy for the presence of varices. These recommendations imply a considerable burden of endoscopies and related costs. Objective: the aim of the study was to determine the predictive value of noninvasive parameters (Rt. lobe diameter/ serum albumin ratio) in the prediction of esophageal varices. Subjects and Methods: This study was done on 120 patients divided into four groups: Group A: includes 30 cirrhotic patients with esophageal varices (OVs) grade I to II. Group B: includes 30 cirrhotic patients with OVs grade III to IV. Group C: includes 30 cirrhotic patients without OVs. Group D: includes 30 none cirrhotic patients presented for esophagogastroduodenoscopy (EGD) screening because of other etiologic factors that are not associated with liver cirrhosis. All participants were subjected to clinical examination; laboratory investigations (CBC, Liver function tests including serum albumin concentration, prothrombin time and concentration, modified Child-Pugh score and abdominal ultrasonography (studying the right lobe and left lobe diameter, the presence of periportal thickening, the splenic longest axis and the presence of ascites and Portal vein diameter, Right liver lobe diameter/albumin ratio were calculated for all patients). Upper endoscopy was done for detection and grading of esophageal varices. Results: This study revealed that The predictors that showed statistically significantly associated with the presence of varices were increased right lobe diameter/Albumin ratio, shrunken Rt. hepatic lobe, splenomegaly, thrombocytopenia, and the more advanced liver disease (according to child class scoring of the patients), the more likely the presence of varices. Conclusion: Right lobe diameter/Albumin ratio is good predictor for the presence and grading of esophageal varices.

Placental growth factor inhibition targets pulmonary angiogenesis and represents a therapy for hepatopulmonary syndrome in mice.

CBDL in mice induces HPS, which is mediated by PlGF production; αPlGF treatment improves experimental HPS by counteracting pulmonary angiogenesis and might be an attractive therapeutic strategy for human HPS. (Hepatology 2017).

A Novel FibroScan Examination Dedicated to Spleen Stiffness Measurement

Esophageal varices (EVs) are among the most severe complications of cirrhosis, with a prevalence of 50% to 60% among cirrhotic patients. International guidelines therefore recommend that cirrhotic patients should be screened for the presence of EVs. The main objective of this study was to introduce a new spleen-dedicated FibroScan (Echosens, Paris, France) examination and to assess its performance in detecting large EVs (grade 2 and 3). This novel examination has been validated in simulation and phantom studies and has been used in a population of patients with chronic liver disease. The study described here suggests that the novel spleen-dedicated FibroScan examination performs better than the standard FibroScan for the detection of large EVs (area under the curve = 0.70 for the standard examination and 0.79 [p < 0.01] for the spleen examination), but further clinical studies are needed to investigate the role of spleen stiffness in the management of cirrhotic patients.