Complication Of Cirrhosis Research Articles

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.

Understanding the pathogenesis of portal vein thrombosis in liver cirrhosis: We are still on the way.

Portal vein thrombosis (PVT) is a common complication of liver cirrhosis. In this issue of the Journal of Clinical Ultrasound: Sonography and other Imaging Techniques, a systematic review and meta‐analysis by Giri et al assessed the role of portal system hemodynamics for predicting the presence and development of PVT in liver cirrhosis.

Effects of endoscopic variceal ligation on survival in cirrhotic patients

Acute esophageal variceal bleeding (AEVB) is a serious complication of liver cirrhosis and is leading cause in hepatic failure and death. Endoscopic variceal ligation (EVL) is the mainstream treatment mode for management of esophageal varices. The aim of the study was to investigate survival rate in urgent - elective (secondary AEVB prophylaxis) and elective (primary AEVB prophylaxis) groups. This article intends to investigate regimens and long-term outcomes of primary or secondary prophylaxis of AEVB in 161 cirrhotic patients. A new risk factor for cirrhosis decompensation stratification is proposed. It is based on a number of necessary EVL bands to achieve sustained (at least 12 months) varix elimination. This study showed that survival rate was strongly inversely dependent on this newly proposed varix elimination index.

Management of cirrhotic ascites: Seven-step treatment protocol based on the Japanese evidence-based clinical practice guidelines for liver cirrhosis 2020.

Liver cirrhosis is a severe illness, associated with multiple complications, which can lead to liver failure. One of the major complications of cirrhosis is ascites. This review describes a stepped treatment approach for the management of ascites in Japanese patients with cirrhosis. It is broadly based on the 2020 update of the Japanese clinical practice guidelines for liver cirrhosis, which is briefly compared with guidelines from Europe and the United States. Step 1 is sodium restriction at a level suitable for Japanese individuals (5-7 g/day), Step 2 is albumin treatment to counteract underlying hypoalbuminemia, Step 3 is initiation of diuretic treatment with spironolactone, followed by add-on loop diuretic treatment at Step 4. Patients refractory to sodium restriction and sodium diuretics can be treated with tolvaptan (Step 5) - a vasopressin V2 receptor antagonit that is available in Japan. Patients at Steps 6 and 7 have refractory ascites and are treated with large volume paracentesis (LVP) in combination with an albumin infusion. High-dose albumin infusion (6-8 g/L) at the time of LVP has recently become possible in Japan. Cell-free and concentrated ascites reinfusion therapy (CART) is also an option at Step 6. Two of the treatment options at Step 7 are limited in Japan (transjugular intrahepatic portosystemic shunts are not approved, and access to liver donors is very limited), but patients can undergo a peritoneovenous shunt if no other options are available. While challenges remain in the treatment of ascites, adopting this stepwise treatment approach may improve patient outcomes. This article is protected by copyright. All rights reserved.

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.

5-MTHF enhances the portal pressure reduction achieved with propranolol in patients with cirrhosis: A randomized placebo-controlled trial

β-blockers reduce hepatic venous pressure gradient (HVPG) by decreasing portal inflow, with no reduction in intrahepatic vascular resistance. 5-Methyltetrahydrofolate (5-MTHF) can prevent oxidative loss of tetrahydrobiopterin (BH4), a cofactor for endothelial nitric oxide synthase coupling. It also converts homocysteine (tHcy) into methionine and enables the degradation of asymmetric dimethylarginine (ADMA), an inhibitor of endothelial nitric oxide synthase. The aim of this study was to evaluate the effects of 5-MTHF in combination with propranolol on HVPG and nitric oxide bioavailability markers in patients with cirrhosis and portal hypertension. Sixty patients with cirrhosis and HVPG ≥12mmHg were randomized 1:1 to receive treatment with 5-MTHF+propranolol or placebo+propranolol for 90 days under double-blind conditions. HVPG and markers of nitric oxide bioavailability (BH4, ADMA and tHcy) were measured again at the end of treatment. Groups were similar in terms of baseline clinical and hemodynamic data and nitric oxide bioavailability markers. HVPG decreased in both groups, but the magnitude of the change was significantly greater in the group treated with 5-MTHF+propranolol compared to placebo+propranolol (percentage decrease, 20 [29-9] vs. 12.5 [22-0], p=0.028), without differences in hepatic blood flow. At the end of treatment, 5-MTHF+propranolol (vs. placebo+propranolol) was associated with higher BH4 (1,101.4 ± 1,413.3 vs. 517.1 ± 242.8pg/ml, p<0.001), lower ADMA (109.3 ± 52.7 vs. 139.9 ± 46.7μmol/L, p=0.027) and lower tHcy (μmol/L, 11.0 ± 4.6 vs. 15.4 ± 7.2μmol/L, p=0.010) plasma levels. In patients with cirrhosis and portal hypertension, 5-MTHF administration significantly enhanced the HVPG reduction achieved with propranolol. This effect appears to be mediated by improved nitric oxide bioavailability in the hepatic microcirculation. 2014-002018-21. Currently, the pharmacological prevention of cirrhosis complications due to portal hypertension, such as esophageal varices rupture, is based on the use of β-blockers, but some patients still present with acute variceal bleeding, mainly due to an insufficient reduction of portal pressure. In this study, we sought to demonstrate that the addition of folic acid to β-blockers is more effective in reducing portal pressure than β-blockers alone. This finding could represent the basis for validation studies in larger cohorts, which could impact the future prophylactic management of variceal bleeding in cirrhosis. Enhancing the benefit of β-blockers with a safe, accessible, cost-effective drug could improve clinical outcomes in cirrhosis, which in turn could translate into a reduction in the rates and costs of hospitalization, and ultimately into improved survival.

Hematological Indices Are Useful in Predicting Complications of Liver Cirrhosis.

Liver cirrhosis is the final stage of chronic liver disease. We aimed to evaluate non-invasive scores as predictors of complications and outcome in cirrhotic patients. A total of 150 cirrhotic patients were included. Models for end-stage liver disease (MELD), albumin-bilirubin (ALBI) score, neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MoLR), and neutrophil-lymphocyte-albumin ratio (NLA) scores were tested in relation to the development of complications and mortality using receiver operating characteristic (ROC) curves. The ROC curve analysis showed (area under the curve) AUC values of NLR, NLA, ALBI, and MELD of 0.711, 0.730, 0.627, and 0.684, respectively, for short-term mortality. MELD, ALBI, and NLA scores showed a statistically significant correlation with hepatic encephalopathy (p = 0.000 vs. 0.014 vs. 0.040, respectively), and the MELD cut-off value of 16 had a sensitivity of 70% and a specificity of 52% (AUC: 0.671, 95% CI (0.577-0.765)). For the assessment of the presence of ascites, the AUC values for NLA and MoLR were 0.583 and 0.658, respectively, with cut-offs of 11.38 and 0.44. MELD, ALBI, and NLA are reliable predictors of hepatic encephalopathy. NLA and MoLR showed a significant correlation with the presence of ascites, and MELD, ALBI, NLR, and NLA have prognostic value to predict 30-day mortality in cirrhotic patients.

Liver transplantation for refractory hepatic hydrothorax is associated with a greater survival benefit compared to other complications of cirrhosis.

Hepatic hydrothorax (HH) is a significant complication of cirrhosis associated with increased mortality. Liver transplantation (LT) remains the best treatment modality. We aim to assess predictors of mortality and the survival benefit of LT in patients with HH. A prospectively maintained cohort of adult patients with cirrhosis, being evaluated for LT at our institution, was retrospectively reviewed from 2015 to 2020. The primary outcome was death or LT. Cox proportional hazard regression identified associations between covariates and death. We calculated the years saved due to LT by comparing patients who were on the waiting list with patients who received an LT. This was done by calculating the area under the Kaplan-Meier curve. Censoring occurred at the time of the last follow-up or death. Patients with refractory HH had the lowest median survival of only 0.26 years. Within the HH group, having a refractory HH group was significantly associated with an increased risk of mortality (HR 1.73; 95% CI 1.06-2.81; p -value 0.03). Refractory HH was also significantly associated with mortality when evaluated in the entire cohort and after adjusting for other covariates (HR 1.48, 95% CI 1.03-2.11; p -value 0.03). Patients with refractory HH had the highest 1-year survival benefit with LT (0.48y), followed by patients with non-refractory HH (0.28y), then patients with other complications of cirrhosis (0.19y). In this large study evaluating the prognostic impact of HH on patients with cirrhosis, refractory HH was an independent predictor of mortality. LT provides an additional survival benefit to patients with HH compared with those without HH.

Association between Dietary Habits and Sarcopenia in Patients with Liver Cirrhosis.

Sarcopenia and sarcopenic obesity are frequent complications of cirrhosis, and the dietary patterns of patients with these diseases significantly impact the development of both conditions. This study aims to evaluate the adequacy of the dietary intake of patients with liver cirrhosis. A total of 201 patients with liver cirrhosis were included in this analysis. We evaluated the nutritional status of the patients as stated by EWGSOP2 criteria. Subjects were divided into three groups: non-sarcopenic, sarcopenic, and with sarcopenic obesity. We conducted a dietary assessment three times over nonconsecutive 24 h periods within a month. According to EWGSOP2 criteria, combining low handgrip strength with low skeletal muscle index, the prevalence of sarcopenia was 57.2%. Sarcopenic obesity was found in 25.3% of patients. In the sarcopenic group of patients, the energy intake was lower than the current recommendations. Regarding protein intake, the consumption was relatively low in both sarcopenia and sarcopenic obesity samples of patients (0.85 g/kg body weight and 0.77 g/kg BW, p < 0.0001). Patients had a median of 2-3 eating episodes daily, and they often missed late-evening snacks. In conclusion, diet quality in cirrhotic patients was relatively poor, and energy and protein intakes were lower than suggested.

Electrocardiographic characteristics of cirrhotic patients and their association with Child-Pugh score.

Cardiac dysfunction is a serious complication of cirrhosis which is usually asymptomatic. We investigated the clinical and electrocardiographic (ECG)-related factors among patients with cirrhosis and our aim was to find any associations between ECG changes and the etiology of cirrhosis, as well as Child-Pugh score. We hypothesized that some ECG-related factors, particularly prolonged QT interval, are more common in patients with cirrhosis. Also, these factors are associated with the severity of cirrhosis, measured by the Child-Pugh score. From April 2019 to December 2022, we reviewed admitted patients to Namazi and Abu-Ali Sina hospitals, Shiraz, Iran. Patients with confirmed diagnosis of cirrhosis and without concurrent disorders affecting the cardiovascular system were selected. Clinical and ECG-related data were then extracted for participants, and Child-Pugh score was calculated. A total of 425 patients were included; the median age was 36 years, and 245 patients (57.6%) were men. Cryptogenic and primary sclerosing cholangitis were the most common etiologies. Prolonged QT followed by early transitional zone were the most common ECG changes (24.7% and 19.8%, respectively), which were significantly associated with the etiology of cirrhosis and Child-Pugh class. Prolonged QT interval and presence of early transitional zone in patients with cirrhosis may indicate cardiac dysfunction, necessitating further evaluations.

Impact of Gastroenterology Consultation on the Clinical Outcomes of Patients Admitted With Hepatic Encephalopathy.

Introduction Hepatic encephalopathy (HE) is a common complication of cirrhosis and a common reason for hospital admission.We aimed to determine whether expert consultation from gastroenterology (GI) leads to better clinical outcomes for inpatients with HE. Methods A retrospective review was performed of all adult patients (age ≥ 18) admitted with HE to a tertiary care hospital between January 2013 and April 2018.Patients who received a GI consult were compared to patients who did not receive a GI consult (No consult group). The primary outcome was hospital length of stay (LOS); secondary outcomes were rates of 30-day hospital readmission and 90-day mortality.Multivariate analysis was conducted to adjust for known confounders. Results Four hundred and twenty-five patients (814 encounters) were included in the study; of these, 236 patients had received a GI consultation for HE.Patients in the GI consult group were younger (mean age 55 vs 58 years, p= 0.02) and had higher Model For End-Stage Liver Disease-sodium (MELD-Na) score (mean MELD-Na 23.5 vs 17.5, p<0.01) compared to patients who did not receive GI consultation.The precipitants of HE were significantly different between the groups: there was more spontaneous bacterial peritonitis (SBP) and GI bleeding (GIB) in the GI consult group and more lactulose non-adherence in the no consult group.There was no difference in the etiology of liver disease between the two groups.Median LOS for the GI consult group was six days vs three days in the no consult group (p<0.01); the incidence rate ratio was 1.79 (95%CI 1.59-2.02, p<0.01) on multivariate analysis. There was no difference in 30-day readmission or 90-day mortality between the two groups. Conclusion GI consultation for patients with HE admitted to a hospital medicine service may be associated with longer LOS.In selected patients admitted with HE, GI consultation may not be necessary to achieve good clinical outcomes.

Role of Galectin in Cardiovascular Conditions including Cirrhotic Cardiomyopathy.

Abnormal cardiac function in the setting of cirrhosis and in the absence of a primary cardiac disease is known as cirrhotic cardiomyopathy. The pathogenesis of cirrhotic cardiomyopathy is multifactorial but broadly is comprised of two pathways. The first is due to cirrhosis and synthetic liver failure with abnormal structure and function of many substances, including proteins, lipids, hormones, and carbohydrates such as lectins. The second is due to portal hypertension which invariably accompanies cirrhosis. Portal hypertension leads to a leaky, congested gut with resultant endotoxemia and systemic inflammation. This inflammatory phenotype comprises oxidative stress, cellular apoptosis, and inflammatory cell infiltration. Galectins exert all these pro-inflammatory mechanisms across many different tissues and organs, including the heart. Effective therapies for improving cardiac function in patients with cirrhosis are not available. Conventional strategies for other noncirrhotic heart diseases, including vasodilators, are not feasible because of the significant baseline vasodilation in cirrhotic patients. Therefore, exploring new treatment modalities for cirrhotic cardiomyopathy is of great importance. Galectin-3 inhibitors such as modified citrus pectin, N-acetyllactosamine, TD139 and GB0139 exert anti-apoptotic, anti-oxidative and anti-inflammatory effects and thus have potential therapeutic interest. This review briefly summarizes the physiological and pathophysiological role of galectin and specifically examines its role in cardiac disease processes. We present a more detailed discussion of galectin in cardiovascular complications of cirrhosis, particularly cirrhotic cardiomyopathy. Finally, therapeutic studies of galectin-3 inhibitors in cirrhotic cardiomyopathy are reviewed.

Proton pump inhibitor treatment is associated with acute-on-chronic liver failure in patients with advanced cirrhosis.

Acute-on-chronic liver failure (ACLF) is a fatal complication of cirrhosis. Hence, identification of risk factors for ACLF is crucial. Previous studies have linked proton pump inhibitor (PPI) treatment to complications of cirrhosis, however, a possible effect of PPI treatment on the risk of ACLF has not been investigated yet. Therefore, the present study aimed to characterize the impact of PPI treatment on ACLF development. A total of 642 patients hospitalized due to complications of cirrhosis were retrospectively identified, and PPI treatment during an observation period of 3 years following the hospitalization was reviewed. Subsequently, 74 patients with newly initiated PPI treatment at the time of hospitalization (PPI group) were 1:1 propensity score matched to 74 patients who received no PPI treatment (no-PPI group). Primary end point was the development of ACLF during the observation period, and secondary endpoints were mortality and upper gastrointestinal bleeding. PPI and no-PPI groups had comparably severe chronic liver disease at baseline. Nevertheless, the cumulative incidence of ACLF in the presence of death as competing risk was markedly higher in the PPI group compared with the no-PPI group. ACLF-related deaths contributed significantly to a higher 3-year mortality in the PPI group. Uni and multivariable competing risk regression models confirmed that PPI treatment was an independent predictor of ACLF in the study collective (subdistribution HR: 1.892, 95% CI: 1.092-3.281, p = 0.023). The impact of PPI treatment on ACLF development was particularly strong in patients with a model for end-stage liver disease score >12. Upper gastrointestinal bleeding was slightly less frequent in the PPI group. The present results indicate that PPI treatment could be a risk factor for ACLF in patients with advanced cirrhosis.

The role of CXCL8 and CCNB1 in predicting hepatocellular carcinoma in the context of cirrhosis: implications for early detection and immune-based therapies.

Cirrhosis is a serious condition characterized by the replacement of healthy liver tissue with scar tissue, which can progress to liver failure if left untreated. Hepatocellular carcinoma (HCC) is a concerning complication of cirrhosis. It can be challenge to identify individuals with cirrhosis who are at high risk of developing HCC, particularly in the absence of known risk factors. In this study, statistical and bioinformatics methods were utilized to construct a protein-protein interaction network and identify disease-related hub genes. We analyzed two hub genes, CXCL8 and CCNB1, and developed a mathematical model to predict the likelihood of developing HCC in individuals with cirrhosis. We also investigated immune cell infiltration, functional analysis under ontology terms, pathway analysis, distinct clusters of cells, and protein-drug interactions. The results indicated that CXCL8 and CCNB1 were associated with the development of cirrhosis-induced HCC. A prognostic model based on these two genes was able to predict the occurrence and survival time of HCC. In addition, the candidate drugs were also discovered based on our model. The findings offer the potential for earlier detection of cirrhosis-induced HCC and provide a new instrument for clinical diagnosis, prognostication, and the development of immunological medications. This study also identified distinct clusters of cells in HCC patients using UMAP plot analysis and analyzed the expression of CXCL8 and CCNB1 within these cells, indicating potential therapeutic opportunities for targeted drug therapies to benefit HCC patients.

Palliative care and end of life care in decompensated cirrhosis.

Palliative care and end of life care in decompensated cirrhosis.

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.

Neutrophil-to-lymphocyte ratio predicts 30-, 90-, and 180-day readmissions of patients with hepatic encephalopathy.

Hepatic encephalopathy (HE) is a significant complication of cirrhosis, known to be associated with hospital readmission. However, few new serological indicators associated with readmission in HE patients have been identified and reported. The objective of our study was to identify simple and effective predictors reated to readmission in HE patients. We conducted a retrospective study at a single center on adult patients admitted with HE from January 2018 to December 2022. The primary endpoint was the first liver-related readmission within 30, 90, and 180 days, and we collected electronic medical records from our hospital for sociodemographic, clinical, and hospitalization characteristics. We utilized logistic regression analysis and multiple linear regression analysis to determine the predictors that were associated with the readmission rate and the length of the first hospitalization. A total of 424 patients were included in the study, among whom 24 (5.7%), 63 (14.8%), and 92 (21.7%) were readmitted within 30, 90, and 180 days, respectively. Logistic regression analysis showed that insurance status, alcoholic liver disease (ALD), ascites, the model for end-stage liver disease (MELD) score, and neutrophil-to-lymphocyte ratio (NLR) were significantly associated with 30-, 90-, and 180-day readmissions. Age and hepatocellular carcinoma (HCC) were predictors of 90- and 180-day readmissions. ALD was identified as a unique predictor of readmission in men, while hypertension was a predictor of 180-day readmission in women. Variceal bleeding, chronic kidney disease, and MELD score were associated with the length of the first hospitalization. NLR at discharge was identified as a significant predictor of 30-, 90- and 180-day readmissions in patients with HE. Our findings suggest that incorporating NLR into routine clinical assessments could improve the evaluation of the prognosis of liver cirrhosis.

Efficacy of Co-Medications in Patients with Alcoholic Liver Disease

Background: Alcoholic liver disease (ALD) is still increasing and leads to acute liver injury but also liver cirrhosis and subsequent complications such as liver failure or hepatocellular carcinoma (HCC). As most patients fail to achieve alcohol abstinence, it is essential to identify alternative treatment options in order to improve the outcome of ALD patients. Methods: Evaluating two large cohorts of patients with ALD from the USA and Korea with a total of 12,006 patients, we investigated the effect on survival of aspirin, metformin, metoprolol, dopamine, and dobutamine drugs in patients with ALD between 2000 and 2020. Patient data were obtained through the “The Observational Health Data Sciences and Informatics consortium,” an open-source, multi-stakeholder, and interdisciplinary collaborative effort. Results: The use of aspirin (p = 0.000, p = 0.000), metoprolol (p = 0.002, p = 0.000), and metformin (p = 0.000, p = 0.000) confers a survival benefit for both AUSOM- and NY-treated cohorts. Need of catecholamines dobutamine (p = 0.000, p = 0.000) and dopamine (p = 0.000, p = 0.000) was strongly indicative of poor survival. β-Blocker treatment with metoprolol (p = 0.128, p = 0.196) or carvedilol (p = 0.520, p = 0.679) was not shown to be protective in any of the female subgroups. Conclusion: Overall, our data fill a large gap in long-term, real-world data on patients with ALD, confirming an impact of metformin, acetylsalicylic acid, and β-blockers on ALD patient’s survival. However, gender and ethnic background lead to diverse efficacy in those patients.

Serum myostatin and irisin as predictive biomarkers of sarcopenia, malnutrition and mortality in patients with decompensated liver cirrhosis

Malnutrition and sarcopenia are nowadays considered the main complications of liver cirrhosis (LC). Myokines are signal peptides synthesized in muscles that regulate muscle strength and mass and mediate crosstalk between skeletal muscles and other organs. It is unknown whether circulating myokines can be used as biomarkers of malnutrition and sarcopenia and have independent prognostic value in LC. The purpose of the study was to assess the relationship of serum levels of myokines myostatin and irisin with nutritional status, skeletal muscle status, and survival in decompensated LC patients. 74 patients (55.30±11.40 years) were involved in the prospective study. Nutritional status was assessed using the Patient-Generated Subjective Global Assessment, and skeletal muscle mass was assessed using the Skeletal Muscle Index. The concentration of serum myostatin and irisin was determined by enzyme immunoassay. Statistical data processing was performed in SPSS22 (© SPSS Inc.). It was established that the concentration of serum myostatin and irisin is not related to the LC severity according to the Child-Turcotte-Pugh, Model For End-Stage Liver Disease, and the grade of ascites. Patients with overt encephalopathy have higher myostatin levels. Patients with severe hypoalbuminemia have higher serum myostatin and lower serum irisin levels. The development of malnutrition and sarcopenia in decompensated LC patients is associated with increased serum myostatin concentration and decreased serum irisin concentration. Serum myostatin level can predict sarcopenia (AUC 0.834 in males and 0.827 in females, p&lt;0.01). Serum irisin level can predict severe malnutrition (AUC 0.830, p&lt;0.001). The mortality of patients with high myostatin levels (above 5.25 ng/ml in males and 3.55 ng/ml in females) and low irisin levels (less than 1.72 ng/ml) is significantly higher. In conclusion, the circulating myokines levels may be useful in the assessment of nutritional and skeletal muscle status, and prediction of mortality in LC patients.

Platelet-albumin-bilirubin score - a risk stratification scoring system to predict outcome of acute variceal bleeding in patients with cirrhosis.

Acute variceal bleed is a common complication of cirrhosis of liver. Up to 25% of patients with newly diagnosed varices will experience bleeding within 2 years. Of patients who have stopped bleeding, approximately one-third will rebleed within the next 6 weeks. Though scores like Child-Turcotte-Pugh (CTP) and Model of End-stage Liver Disease (MELD) predict the survival of upper gastrointestinal bleed, they have certain limitations in this regard. So, there is a need for reliable scoring system to assess the outcome of patients who had acute variceal bleed. To evaluate the platelet-albumin-bilirubin (PALBI) score in predicting outcome of acute variceal bleeding in patients with cirrhosis. A total of 130 patients who presented to our institute with acute variceal bleed over a period of 1 year were analyzed. CTP, MELD Na and PALBI scores were calculated for these patients on admission and the outcome was compared in the form of 90-day rebleeding rates. The areas under the receiver operating characteristic curves (AUROC) were calculated for this purpose. Mean age was 56 years; 80 were male (61.5%), 50 were female (38.5%), 62 CTP-A (47.7%), 53 CTP-B (40.8%), 15 CTP-C (11.5%); 63 PALBI 1 (48.5%), 23 PALBI 2 (17.8%), and 44 PALBI 3 (33.8%). 1 patient died in the due course of the study. The AUROC for predicting rebleeding was 0.732, 0.71 and 0.803 for CTP, MELD Na and PALBI scores, respectively. PALBI score on admission is a good predictor of outcomes in cirrhotics with acute variceal bleed.