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Background/Objectives: Coronavirus Disease 2019 (COVID-19) can cause liver injury and a deterioration of hepatic function. The Model for End-Stage Liver Disease (MELD) score is a good predictor for poor prognosis of hospitalized COVID-19 patients in the United States, Egypt and Turkey. Nevertheless, the best cut-off value for the MELD score to predict mortality in the Mexican population has yet to be established. Methods: A total of 234 patients with COVID-19 were studied in a tertiary-level hospital. Patients were stratified into survivors (n = 139) and non-survivors (n = 95). Receiver operating characteristic curves, Cox proportional hazard models, Kaplan-Meier method, and Bonferroni corrections were performed to identify the predictors of COVID-19 mortality. Results: MELD score had an area under the curve of 0.62 (95% CI: 0.56-0.68; p = 0.0009), sensitivity = 53.68%, and specificity = 73.38%. Univariate Cox proportional hazard regression analysis suggested that the leukocytes > 10.6, neutrophils > 8.42, neutrophil-to-lymphocyte ratio (NLR) > 8.69, systemic immune-inflammation index (SII) > 1809.21, MELD score > 9, and leukocyte glucose index (LGI) > 2.41 were predictors for mortality. However, the multivariate Cox proportional hazard model revealed that only the MELD score >9 (Hazard Ratio [HR] = 1.83; 95% confidence interval [CI]: 1.2-2.8; Pcorrected = 0.03) was an independent predictor for mortality of COVID-19. Conclusions: Although the MELD score is used for liver transplantation, we suggest that a MELD score >9 could be an accurate predictor for COVID-19 mortality at admission to ICU requiring mechanical ventilation.

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INTRODUCTION AND AIMS: Sodium can be measured with direct or indirect methods; abnormal plasma total protein concentration can impact on sodium measured by indirect ion-selective electrodes (ISE). Serum sodium is an important item to determine the Model for End Stage Liver Disease Sodium (MELD-Na) score, commonly used for liver graft allocation. Patients with cirrhosis usually have hypoproteinemia. The aim of this study was to determine if there was a significant difference between the MELD-Na scores calculated based on the results of two different serum sodium ISE: indirect and direct. METHODS: This was a retrospective study; we included 166 patients that underwent liver transplant assessment, and that had paired (i.e. same date and time) direct and indirect sodium determinations. We calculated the MELD-Na scores with both sodium determinations, and we compared them. RESULTS: There was a significant difference between MELD-Na scores; the mean difference was 0.4±1.3. If MELD-Na score had been determined by the sodium measured by the direct ISE, 69 patients (42%) would have stayed in the same place on the waiting list, 67 patients (40%) would have moved up, and 30 patients (18%) would have moved down. CONCLUSIONS: There was a statistically significant difference between the MELD-Na scores calculated based on the two different sodium concentrations, which would theoretically result in changes in the order of the waiting list. This finding should prompt studies to assess if MELD-Na calculated based on direct methods has a better performance to predict clinically relevant outcomes.

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Objectives: Orthotopic liver transplantation (OLT) remains the definitive treatment for patients afflicted with end-stage liver disease (ESLD). Transjugular intrahepatic portosystemic shunts (TIPS) have been adapted as a bridge to transplantation, allowing partial normalization of portal pressure and associated symptom improvement. Conflicting evidence exists on TIPS' impact on operative procedures. This study aimed to analyze available evidence on patients who underwent OLT with prior TIPS compared to OLT alone with the intent to determine TIPS' impact on surgical outcomes. Material and Methods: Following PRISMA guidelines, a systematic review was conducted, identifying studies comparing TIPS + OLT versus OLT alone in patients with ESLD. Data were analyzed using Review Manager 5.3. Results: Thirteen studies were included. Operative time, packed red blood cells transfusions, intensive care unit admission, length of stay, dialysis, serum creatinine levels, ascites, vascular complications, bleeding revisions, reintervention, and other complications rates were similar between both groups. Fresh frozen plasma transfusion -2.88 units (-5.42, -0.35; p= 0.03), was lower in the TIPS + OLT group. Conclusion: Our study found TIPS can be safely employed without having detrimental impacts on OLT outcomes, furthermore, these findings also suggest TIPS does not increase bleeding or complications.

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INTRODUCTION AND OBJECTIVES: There is a shortage of ideal donor organs with consequential increasing waitlist times, drop-off, and mortality. Teams have thus extended the donor criteria. Little is known about patients' actual choices and what factors may influence their decisions regarding different extended criteria liver grafts. PATIENTS AND METHODS: The documented acceptance or refusal of seven extended criteria liver graft types of patients consented for transplant in a single institution over a 2-year period was reviewed. Patient factors including sex, age, indication, aetiology, and model for end-stage liver disease (MELD) score were analysed using logistic regression. RESULTS: Most patients were willing to accept most graft types. MELD score did not impact the acceptance or refusal of any graft type. Older patients and those with hepatocellular carcinoma (HCC) or ascites had significantly higher rates of acceptance. Hepatitis B or C disease aetiology was predictive of willingness to accept a similarly infected graft, respectively. HCC was predictive of acceptance of grafts from donors with a cancer history. CONCLUSIONS: In general, patients embrace the available extended criteria donors. Our analysis suggests that consent should be revisited as patients deteriorate or ameliorate on the waitlist, especially if in the form of ascites or HCC but not necessarily MELD score.

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Critically ill cirrhotic patients have high in-hospital mortality and utilize significant health care resources as a consequence of the need for multiorgan support. Despite this fact, their mortality has decreased in recent decades due to improved care of critically ill patients. Acute-on-chronic liver failure (ACLF), sepsis and elevated hepatic scores are associated with increased mortality in this population, especially among those not eligible for liver transplantation. No score is superior to another in the prognostic assessment of these patients, and both liver-specific and intensive care unit-specific scores have satisfactory predictive accuracy. The sequential assessment of the scores, especially the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure Consortium (CLIF)-SOFA scores, may be useful as an auxiliary tool in the decision-making process regarding the benefits of maintaining supportive therapies in this population. A CLIF-ACLF > 70 at admission or at day 3 was associated with a poor prognosis, as well as SOFA score > 19 at baseline or increasing SOFA score > 72. Additional studies addressing the prognostic assessment of these patients are necessary.

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OBJECTIVE: This study aimed to evaluate outcomes in cirrhotic patients diagnosed with spontaneous bacterial empyema (SBE) compared with those without this complication. METHODS: We performed a retrospective cohort study of cirrhotic patients from a tertiary care center. The primary outcome was time to death or liver transplantation (LT) within one year after diagnosis of infection. We integrated three groups: patients with SBE (group A), patients with spontaneous bacterial peritonitis (SBP; group B), and cirrhotic patients without SBP or SBE (group C), matched by age, model for end-stage liver disease-sodium (MELD-Na) score and year of infection. Outcomes were analyzed using a Cox regression model adjusted for cardiovascular risk factors and MELD-Na score. RESULTS: Between January 1999 and February 2019, 4829 cirrhotic patients were identified. Among them, 73 (1.5%) had hepatic hydrotorax, of whom 22 (30.1%) were diagnosed with SBE. Median age in group A was 58 years, 50% were men, and median MELD-Na was 21.5. Compared with group C, the hazard ratio of death or LT during the first year after infection was 2.98 (95% confidence interval [CI] 1.43-6.22, P = 0.004) for group A and 1.23 (95% CI 0.65-2.32, P = 0.522) for group B. CONCLUSIONS: Our results suggest that patients with SBE have a worse outcome during the first year after infection is diagnosed. Patients who develop SBE should be promptly referred for transplant evaluation. SBE may emerge as new indication that could benefit from MELD exception points.

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Coronavirus disease 2019 (COVID-19), an infection caused by severe acute respiratory syndrome coronavirus-type 2 (SARS-CoV-2), has emerged as a serious threat to public health. Liver transplant (LT) recipients may be at increased risk of acquisition of SARS-CoV-2 infection and higher morbidity and mortality due to constant contact with health-care services, the use of immunosuppressants and frequent comorbidities. In the first part of this review we discuss (1) the epidemiology and risk factors for SARS-CoV-2 infection in LT recipients; (2) the clinical and laboratory features of COVID-19 in this specific population, highlighting differences in presenting signs and symptoms with respect to general populations and (3) the natural history and prognostic factors in LT recipients hospitalized with COVID-19, with particular focus on the possible role of immunosuppression. Thereafter, we review the potential therapeutic options for COVID-19 treatment and prevention. Specifically, we give an overview of current practice in immunosuppressant regimen changes, showing the potential benefits of this strategy, and explore safety and efficacy issues of currently approved drugs in LT recipients. The last topic is dedicated to the potential benefits and pitfalls of vaccination.

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INTRODUCTION AND AIM: Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality, and predicting the prognosis is challenging. This study aimed to compare the performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC) in predicting the 90-day mortality in patients with hepatitis B virus (HBV)-associated ACLF (HBV-ACLF). MATERIALS AND METHODS: This prospective, observational study enrolled 54 patients with HBV-ACLF. The serum NGAL and CysC levels were determined. A multivariate logistic regression analysis was used to analyze the independent risk factors of mortality. RESULTS: Serum NGAL, but not CysC, was found to significantly correlate with the total bilirubin, international normalized ratio, and model for end-stage liver disease (MELD). Serum NGAL [odds ratio (OR), 1.008; 95% confidence interval (CI), 1.004-1.012; P < 0.01], but not CysC, was an independent risk factor for developing hepatorenal syndrome. Moreover, NGAL (OR, 1.005; 95% CI, 1.001-1.010; P < 0.01) along with the MELD score was independently associated with the overall survival in patients with HBV-ACLF. Patients with HBV-ACLF were stratified into two groups according to the serum NGAL level at baseline (low risk: <217.11 ng/mL and high risk: ≥ 217.11 ng/mL). The 90-day mortality rate was 22.73% (5/22) in the low-risk group and 71.88% (23/32) in the high-risk group. Moreover, NGAL, but not CysC, significantly improved the MELD score in predicting the prognosis of HBV-ACLF. CONCLUSION: The serum NGAL might be superior to CysC in predicting the prognosis of HBV-ACLF with the normal creatinine level.

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INTRODUCTION AND AIM: Considered as a healthcare quality indicator, hospital readmissions in decompensated cirrhosis predispose the patients and the society to physical, social and economic distresses. Few studies involving North American cohorts have identified different predictors. The aim of this study was to determine and validate the predictors of 1-month and 3-months readmission in an Asian cohort. MATERIAL AND METHODS: We prospectively studied 281 hospitalised patients with decompensated cirrhosis at a large tertiary care public hospital in India between August 2014 and August 2016 and followed them for 3 months. Data regarding demographic, laboratory and disease related risk factors were compiled. We used multivariate logistic regression to determine predictors of readmission at 1-month and 3-months and receiver operating curves (ROC) for significant predictors to obtain the best cut-offs. RESULTS: 1-month and 3-months readmission rates in our study were 27.8% and 42.3%, respectively. Model for End stage Liver Disease (MELD) score at discharge (OR:1.24, p < 0.001) and serum sodium (OR:0.94, p-0.039) independently predicted 1-month and MELD score (OR:1.11, p-0.003), serum sodium (OR:0.94, p-0.027) and male gender (OR:2.19, p-0.008) independently predicted 3-months readmissions. Neither aetiology nor complications of cirrhosis emerged as risk factors. MELD score >14 at discharge and serum sodium < 133 mEq/L best predicted readmissions; MELD score being a better predictor than serum sodium (p - 0.0001). CONCLUSIONS: High rates of early and late readmissions were found in our study. Further, this study validated readmission predictors in Asian patients. Structured interventions targeting this risk factors may diminish readmissions in decompensated cirrhosis.

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INTRODUCTION AND AIM: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis, but the clinical and prognostic significance of the progression of mental status in hospitalised cirrhotics is unknown. We aimed to investigate the prognostic significance of serial evaluation of HE in patients hospitalised for acute decompensation (AD) of cirrhosis. MATERIALS AND METHODS: Patients (n=293) were evaluated for HE (West-Haven criteria) at admission and at day-3 and classified in two groups: (1) Absent or improved HE: HE absent at admission and at day-3, or any improvement at day-3; (2) Unfavourable progression: Development of HE or HE present at admission and stable/worse at day-3. RESULTS: Unfavourable progression of HE was observed in 31% of patients and it was independently associated with previous HE, Child-Pugh C and acute-on-chronic liver failure (ACLF). MELD score and unfavourable progression of HE were independently associated with 90-day mortality. The 90-day Kaplan-Meier survival probability was 91% in patients with MELD<18 and absent or improved HE and only 31% in subjects with both MELD≥18 and unfavourable progression of HE. Unfavourable progression of HE was also related to lower survival in patients with or without ACLF. Worsening of GCS at day-3 was observed in 11% of the sample and was related with significantly high mortality (69% vs. 27%, P<0.001). CONCLUSION: Among cirrhotics hospitalised for AD, unfavourable progression of HE was associated with high short-term mortality and therefore can be used for prognostication and to individualise clinical care.

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BACKGROUND/OBJECTIVES: to compare the prognostic accuracy for 28 and 90-day transplant-free mortality of a modified CLIF-SOFA score (including a dynamic definition of acute kidney injury) with that of the classic CLIF-SOFA score and KDIGO score for acute kidney injury in patients with acute decompensation of cirrhosis. METHODS: A retrospective analysis of all admissions of acutely decompensated patients with cirrhosis was carried out from January 2012 to December 2014. Classic and modified CLIF-SOFA scores were analyzed, as well as acute kidney injury diagnosis using the KDIGO score regarding their accuracy for 28- and 90-day transplant free mortality prediction. RESULTS: 108 admissions were analyzed. Acute kidney injury diagnosis was met in 37 (34%) patients. Acute-on-chronic liver failure was diagnosed in 59 (55%) patients using the classic CLIF-SOFA score; and in 64 (59%) patients using the modified CLIF-SOFA score. Both CLIF-SOFA scores were highly effective in predicting 28-day transplant-free mortality (AUCROC 0.93 and 0.92, p = 0.34) as well as 90-day transplant-free mortality (AUCROC 0.79 and 0.78, p = 0.78). Acute kidney injury diagnosis had significantly lower accuracy in mortality assessment (28 and 90-day transplant free mortality AUCROC 0.67 [p = 0.002] and 0.63 [p = 0.02]). CONCLUSIONS: To our knowledge, this is the first evidence of the limited impact of modifying the fixed kidney injury definition currently used for acute-on-chronic liver failure.

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ABSTRACT Introduction and aims. Drug-induced liver injury (DILI) is rare; however, it is one of the important causes of acute liver failure which results in significant morbidity or mortality. Material and methods. Patients with suspected DILI were enrolled based on predefined criteria and followed up for at least 6 months or until normalization of liver tests. Causality assessment was done by applying the Roussel Uclaf Causality Assessment Method model. Results. We collected data from 82 individuals diagnosed with DILI at our hospital from 2014 through 2015 (41 men; median age, 38 years). The most commonly implicated drugs were antitubercular therapy (ATT) (49%), antiepileptic drugs (12%), complementary and alternative medicine (CAM) in 10%, antiretroviral drugs (9%) and non-steroidal anti-inflammatory drugs (6%). 8 out of 13 deaths were liver related. Also, liver related mortality was significantly higher for ATT DILI (17.5%) vs. those without (2.4%) (P = 0.02). There was no significant difference in overall as well as liver related mortality in hepatocellular, cholestatic or mixed pattern of injury. Laboratory parameters at one week after discontinuation of drug predicted mortality better than those at the time of DILI recognition. On multivariate logistic regression analysis, jaundice, encephalopathy, MELD (Model for end stage liver disease) score and alkaline phosphatase at one week, independently predicted mortality. Conclusion. DILI results in significant overall mortality (15.85%). ATT, anti-epileptic drugs, CAM and antiretroviral drugs are leading causes of DILI in India. Presence of jaundice, encephalopathy, MELD score and alkaline phosphatase at one week are independent predictors of mortality.(AU)

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The Model for End-Stage Liver Disease (MELD) score has gained wide acceptance for predicting survival in patients undergoing liver transplantation. The strength of this score remains in the mathematical formula derived from a multivariate Cox regression analysis; it is a continuous scale and lacks a ceiling or a floor effect with a wide range of discrimination. It is based on objective, reproducible, and readily available laboratory data and the wide range of samples which have been validated. Liver cirrhosis complications such as ascites, encephalopathy, spontaneous bacterial peritonitis and variceal bleeding were not considered in the MELD score underestimating their direct association with the severity of liver disease. In this regard, several recent studies have shown that clinical manifestations secondary to portal hypertension are good prognostic markers in cirrhotic patients and may add additional useful prognostic information to the current MELD. We review the feasibility of MELD score as a prognostic predictor in patients with liver cirrhosis-related complications.

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AIM: To investigate the capability of a biochemical and clinical model, BioCliM, in predicting the survival of cirrhotic patients. METHODS: We prospectively evaluated the survival of 172 cirrhotic patients. The model was constructed using clinical (ascites, encephalopathy and variceal bleeding) and biochemical (serum creatinine and serum total bilirubin) variables that were selected from a Cox proportional hazards model. It was applied to estimate 12-, 52- and 104-wk survival. The model¡¯s calibration using the Hosmer-Lemeshow statistic was computed at 104 wk in a validation dataset. Finally, the model¡¯s validity was tested among an independent set of 85 patients who were stratified into 2 risk groups (low risk ¡Ü 8 and high risk > 8). RESULTS: In the validation cohort, all measures of fit, discrimination and calibration were improved when the biochemical and clinical model was used. The proposed model had better predictive values (c-statistic: 0.90, 0.91, 0.91) than the Model for End-stage Liver Disease (MELD) and Child-Pugh (CP) scores for 12-, 52- and 104-wk mortality, respectively. In addition, the Hosmer-Lemeshow (H-L) statistic revealed that the biochemical and clinical model (H-L, 4.69) is better calibrated than MELD (H-L, 17.06) and CP (H-L, 14.23). There were no significant differences between the observed and expected survival curves in the stratified risk groups (low risk, P = 0.61; high risk, P = 0.77). CONCLUSION: Our data suggest that the proposed model is able to accurately predict survival in cirrhotic patients(AU)

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El trasplante hepático (TH) está indicado en pacientes con enfermedades hepáticas agudas o crónicas severas e irreversibles para las cuales no exista un tratamiento alternativo y en ausencia de contraindicaciones. Las indicaciones de TH pueden ser agrupadas en cuatro categorías: cirrosis hepática, hepatitis fulminante, tumores hepáticos y defectos genéticos de origen hepático que producen daño en otros órganos. Deben ser derivados para TH los pacientes con cirrosis que desarrollen cualquier complicación mayor o coagulopatía. La derivación precoz es "la clave del éxito" en la hepatitis fulminante por el alto riesgo de muerte y por tener una evolución mayormente impredecible. La oportunidad del TH es el momento en la historia natural de la hepatopatía cuando la sobrevida esperada es mayor con TH que en lista de espera. Estudios recientes han sugerido que el máximo beneficio del TH se obtiene en pacientes con MELD >15. Sin embargo, en algunos casos sin riesgo de muerte inminente, el objetivo del TH es mejorar la calidad de vida o prevenir contraindicaciones como la progresión del hepatocarcinoma cuando el tiempo de espera excede los 8 meses. Actualmente existe una marcada desproporción entre el número de donantes disponibles y el número creciente de potenciales receptores, lo que ha determinado un incremento progresivo del tiempo y mortalidad en lista. La racionalidad de distribuir los órganos en base al score de MELD es otorgar prioridad en la lista a los candidatos más enfermos y a aquellos que no pueden esperar como los pacientes con hepatocarcinoma.

Liver transplantation (OLT) is indicated in patients with severe and irreversible acute or chronic liver disease without alternative therapy and in the absence of contraindications. Indications for OLT can be grouped in four categories, namely cirrhosis, fulminant hepatitis, malignant hepatic tumors and liver-based genetic defects that trigger damage of other organs. Patients with cirrhosis should be referred for OLT after the onset of any of the major complications or coagulopathy. Early referral is crucial in fulminant hepatitis due to the high mortality with medical therapy and the unpredictable nature of this condition. Ideal timing for OLT is the moment in the natural history of the disease when the expected survival of patients on the waiting list is higher with than without OLT. Recent data suggest that maximal benefit of OLT is obtained in patients with a MELD score >15. However, in some cases with no imminent risk of death, OLT is indicated to improve quality of life or to prevent contraindications such as progression of hepatocellular carcinoma. At present, there is a marked disproportion between the number of donors available and the growing number of patients listed worldwide, which in turn has resulted in prolongation of the time-interval to OLT and waitlist mortality. The rationale of allocation systems utilizing the MELD score is to prioritize on the waiting list patients with severe liver dysfunction ("the sickest first") and those with hepatocellular carcinoma who may loose the benefits of OLT when waitlist time exceeds eight months.

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