Clinical characteristics,predictors, and survival among patients with hepatopulmonary syndrome

Background. Hepatopulmonary syndrome (HPS) is a complication of advanced liver disease. The impact of HPS on survival is not clearly understood.Material and methods. A prospective study was carried out at Department of Medicine, King Edward Medical University Lahore from June 2011 to May 2012. Patients with cirrhosis of liver were evaluated for presence of HPS with arterial blood gas analysis and saline bubble echocardiography. All patients were followed for 6 months for complications and mortality. Cox regression analysis was done to evaluate role of HPS on patient survival.Results. 110 patients were included in the study. Twenty-nine patients (26%) had HPS. MELD score was significantly higher (p < 0.01) in patients with HPS (18.93 ± 3.51) as compared to that in patients without HPS (13.52 ± 3.3). Twenty two (75.9%) patients of Child class C, 5 (17.2%) patients of Child class B and 2 (6.9%) patients of Child class A had HPS (P 0.03). The clinical variables associated with presence of HPS were spider nevi, digital clubbing, dyspnea, and platypnea. HPS significantly increased mortality during six month follow up period (HR: 2.47, 95% CI: 1.10-5.55). Child-Pugh and MELD scores were also associated with increased mortality. HPS was no longer associated with mortality when adjustment was done for age, gender, Child-Pugh, and MELD scores (HR: 0.44, 95% CI: 0.14-1.41). Both the Child-Pugh and MELD scores remained significantly associated with mortality in the multivariate survival analysis.Conclusions. HPS indicates advanced liver disease. HPS does not affect mortality when adjusted for severity of cirrhosis.     

Serum cholesterol predicts transplant-free survival in cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt

BackgroundMalnutrition is frequent in patients with cirrhosis and has been associated with poor prognosis. The Model for End-stage Liver Disease (MELD) score was created to predict survival after Transjugular Intrahepatic Porto-systemic Shunt (TIPS) but lacks a nutritional parameter.AimsTo evaluate the prognostic value of serum cholesterol in patients with cirrhosis undergoing TIPS and to develop a prognostic score to predict survival.MethodsAn explorative cross-sectional study was conducted of cirrhotic patients undergoing TIPS from 2008 until 2019. Exclusion criteria were liver transplantation or hepatocellular carcinoma before TIPS. Risk analysis was used to compare survival according to clinical and analytical data. The diagnostic performance of serum cholesterol added to MELD was evaluated and confirmed in an external validation cohort.ResultsThe final cohort of 100 patients had a mean MELD score of 14±5 and cholesterol of 122±51 mg/dL. MELD (p < 0,05) and both cholesterol (p < 0,05) and low-density lipoprotein levels (LDL-C) (p < 0,05) were independent predictors of post-TIPS transplant-free survival with an optimal cut-off of 106 mg/dL for serum cholesterol. The combined MELD-cholesterol risk score improved diagnostic accuracy of each parameter separately, and this was confirmed in the external cohort.ConclusionSerum cholesterol and LDL-C are independent predictors of transplant-free survival in cirrhotic patients undergoing TIPS. The MELD-cholesterol score slightly improved prognostic accuracy.Lay SummaryAs an objective and easily measured indicator of both nutritional status and hepatic function, serum cholesterol could be useful to predict transplant-free survival in patients with cirrhosis undergoing TIPS. It can enable health care providers to identify high-risk patients and to optimize nutritional status before TIPS.     

Relative Adrenal Insufficiency is Associated with the Clinical Outcome in Patients with Stable Decompensated Cirrhosis

BackgroundThe clinical impact of relative adrenal insufficiency (AI) on patients with stable decompensated cirrhosis (DeCi) has not been yet elucidated.AimExplore the association between AI and outcome [death or liver transplantation (LT)] in patients with DeCi.Material and methodsPatients with DeCi presenting no active complication have been included. Clinical and laboratory data, including serum levels of corticosteroid-binding globulin (CBG), interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNFa) were recorded in each participant. Salivary cortisol (SC) and serum total cortisol (STC) were assessed at (T0) and 1 h (T60) after intravenous injection of 250 |ig corticotropin.Results113 consecutive patients were totally tested. Median SC was 3.9 ng/mL and 15.5 ng/mL and median STC was 10.7 ng/dL and 22.7 ng/dL at T0 and T60 respectively. The patients with AI [group 1, n = 34 (30%)] had significantly lower systolic blood pressure (106 ± 12 vs. 113 ± 13 mmHg, p = 0.05), serum sodium (133 ± 7 vs. 137 ± 12 mEq/ L, p = 0.04), HDL (29.9 ± 14 vs. 38.6 ± 18 mg/dL, p = 0.034) and albumin (2.7 ± 0.5 vs. 3.1 ± 0.5 g/dL, p = 0.002), but higher direct bilirubin (median: 1.6 vs. 0.8 mg/dL, p = 0.029) compared to those without AI [group 2, n = 79 (70%)]. Moreover, group 1 patients presented more frequently past history of spontaneous bacterial peritonitis (SBP) [10/34 (29.4%) vs. 6/79 (7.5%), p = 0.002]. AI was significantly associated with death [HR = 2.65, 95% C.I.: 1.55 - 4.52, p = 0.003 over a follow up period of 12 (6-48) months.]ConclusionsThe presence of AI in patients with stable DeCi predispose to obvious clinical implications since it is associated with circulatory dysfunction, previous history of SBP and worse survival.     

Relative adrenal insufficiency in cirrhotic patients with ascites (hepatoadrenal syndrome)

AimRelative adrenal insufficiency (RAI) has been reported in critically ill patients with cirrhosis. We evaluated the prevalence of RAI and its relationship to clinical course in non-septic cirrhosis patients with ascites.MethodsThe study included 66 consecutive non-septic cirrhosis patients with ascites. RAI was defined by a delta cortisol lower than 9 μg/dL and/or a peak cortisol lower than 18 μg/dL.ResultsSixty-six patients with cirrhosis and ascites were studied. The mean Child-Turcotte-Pugh (CTP) and model for end stage liver disease (MELD) scores were 10.6 ± 1.9 and 21.5 ± 7.3, respectively. The prevalence of RAI in patients with cirrhosis and ascites was 47% (31/66). The prevalence of RAI in patients with and without spontaneous bacterial peritonitis, renal failure and type 1 hepatorenal syndrome (HRS) was comparable. Baseline hyponatremia was common in RAI (42% versus 17%, p = 0.026). There was a significant correlation of prevalence of RAI with prothrombin time, international normalized ratio, MELD scores and CTP class. During follow-up, there was no association between RAI and the risk to develop new infections, severe sepsis, type 1 HRS and death.ConclusionsRAI is common in non-septic cirrhotic patients with ascites and its prevalence increases with severity of liver disease. However, it does not affect the short-term outcome in these patients.     

Long-term survival and clinical outcomes following direct-acting antiviral (DAA) treatment in HCV decompensated cirrhosis in Brazil: a real-world study

IntroductionThe outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario.Patients and methodsThis was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method.ResultsOne hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p < 0.001).ConclusionsDecompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.     

Circulating levels of pentraxin-3 (PTX3) in patients with liver cirrhosis

BackgroundDespite the circulating levels of PTX3 were related to the severity of various diseases, there are no studies investigating its role in patients with liver cirrhosis. We aimed to study PTX3 levels in patients with liver cirrhosis.Material and methodsA prospective cohort study included 130 patients hospitalized for acute decompensation of liver cirrhosis, 29 stable cirrhotic outpatients and 32 healthy controls evaluated in a tertiary hospital in Southern Brasil.ResultsThe median PTX3 level was significantly higher in stable cirrhotic patients compared to controls (2.6 vs. 1.1 ng/mL; p < 0.001), hospitalized cirrhotic patients compared to controls (3.8 vs. 1.1 ng/mL; p < 0.001), and hospitalized cirrhotic patients compared to stable cirrhotic patients (3.8 vs. 2.6 ng/ mL; p = 0.001). A positive correlation was found between PTX3 and serum creatinine (r = 0.220; p = 0.012), Chronic Liver Failure -Sequential Organ Failure Assessment score (CLIF-SOFA) (r = 0.220; p = 0.010), MELD (r = 0.279; p = 0.001) and Child-Pugh score (r = 0.224; p = 0.010). Significantly higher levels of PTX3 were observed in patients on admission with ACLF (8.9 vs. 3.1 ng/mL; p < 0.001) and MELD score ≥ 20 (6.6 vs. 3.4 ng/mL; p = 0.002). Death within 90 days occurred in 30.8% of patients and was associated with higher levels of PTX3 (5.3 vs. 3.4 ng/mL; p = 0.009). The probability of Kaplan-Meier survival was 77.0% in patients with PTX-3 < 5.3 ng mL (upper tercile) and 53.5% in those with PTX3 ≥ 5.3 ng/mL (p = 0.002).ConclusionThese results indicate the potential for use of PTX3 as an inflammatory biomarker for the prognosis of patients with hepatic cirrhosis.     

Estimating liver function in a large cirrhotic cohort: Signal intensity of gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid-enhanced MRI

BackgroundTo assess whether gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid-enhanced MRI study is useful to estimate liver function in comparison to the presence or absence of cirrhosis, Child Pugh (CP), Model for End-stage Liver Disease (MELD), ALBI scores and biochemical test.MethodsWe retrospectively reviewed all consecutive Gd-EOB-DTPA-enhanced-MRI studies performed between 2010 and 2016 in patients with focal liver lesions undergoing clinical evaluation. Patients were divided in study and control group according to the presence of cirrhosis, and then classified by CP, MELD and ALBI. Signal intensity was calculated through the liver-to-muscle ratio in portal- (SI-POR) and hepatobiliary-phase(SI-HEP).ResultsThree-hundred-three Gd-EOB-DTPA liver-enhanced-MRI studies were included. One-hundred-ninety-one patients (63%) were cirrhotic. SI-HEP was significantly lower in cirrhotic group (0.55 ± 0.29 vs 0.66 ± 0.40, p = 0.004).The SI-HEP progressively decreased from CP-A to CP-C (0.59 ± 0.28 to 0.25 ± 0.19, p < 0.0001) and a significant difference was found between MELD ≤ 9 and MELD > 9 groups (0.61 ± 0.31 vs 0.49 ± 0.28, p = 0.007). No differences between ALBI grades were evident. Among biochemical parameters a moderate correlation was found among SI-HEP and total bilirubin, AST and albumin.ConclusionSI-HEP after Gd-EOB-DTPA-enhanced-MRI effectively stratified patients with different Child Pugh grades and MELD scores. This technique could hence be useful as a novel radiological marker to estimate the underlying liver function.     

Acute Variceal Bleeding: Does Octreotide Improve Outcomes in Patients with Different Functional Hepatic Reserve?

Background. Current guidelines do not differentiate in the utilization of vasoactive drugs in patients with cirrhosis and acute variceal bleeding (AVB) depending on liver disease severity.Material and methods. In this retrospective study, clinical outcomes in 100 patients receiving octreotide plus endoscopic therapy (ET) and 216 patients with ET alone were compared in terms of failure to control bleeding, in-hospital mortality, and transfusion requirements stratifying the results according to liver disease severity by Child-Pugh (CP) score and MELD.Results. In patients with CP-A or those with MELD < 10 octreotide was not associated with a better outcome compared to ET alone in terms of hospital mortality (CP-A: 0.0 vs. 0.0%; MELD < 10: 0.0 vs. 2.9%, p = 1.00), failure to control bleeding (CP-A: 8.7 vs. 3.7%, p = 0.58; MELD < 10: 5.3 vs. 4.3%, p = 1.00) and need for transfusion (CP-A: 39.1 vs. 61.1%, p = 0.09; MELD < 10: 63.2 vs. 62.9%, p = 1.00). Those with severe liver dysfunction in the octreotide group showed better outcomes compared to the non-octreotide group in terms of hospital mortality (CP-B/C: 3.9 vs. 13.0%, p = 0.04; MELD > 10: 3.9 vs. 13.3%, p = 0.03) and need for transfusion (CP-B/C: 58.4 vs. 71.6%, p = 0.05; MELD > 10: 50.6 vs. 72.7%, p < 0.01). In multivariate analysis, octreotide was independently associated with in-hospital mortality (p = 0.028) and need for transfusion (p = 0.008) only in patients with severe liver dysfunction (CP-B/C or MELD > 10).Conclusion. Patients with cirrhosis and AVB categorized as CP-A or MELD < 10 had similar clinical outcomes during hospitalization whether or not they received octreotide.     

Hepatitis C virus infection in patients with primary biliary cirrhosis

Background and aim. The aim of this study is to evaluate the role of hepatitis C virus (HCV) infection in patients with primary biliary cirrhosis (PBC).Material and methods. On the basis of a retrospective review of medical records, all patients consecutively diagnosed with PBC or HCV infection between 1999 and 2011 and who had a regular follow-up of at least 3 years were included in the study. Clinical characteristics, especially the severity of cirrhosis, were analyzed in PBC patients with HCV infection (PBC-HCV), PBC patients without HCV infection (PBC-only), and patients with only HCV infection (HCV-only).Results. A total of 76 patients with PBC, including 9 patients with HCV infection, were analyzed. Of the PBC-HCV patients, 7 (7/9, 77.8%) were women with a mean age of 55.11 ± 14.29 years. Age- and sex-matched PBC-only patients (n = 36) and HCV-only patients (n = 36) were used as control groups. In comparison to the PBC-only controls, PBC-HCV patients had a greater severity of cirrhosis based on Child-Pugh (p = 0.019) and Model for End-Stage Liver Disease (MELD) (p = 0.01) scores. However, no significant difference in the severity of cirrhosis was found between the PBC-HCV and HCV-only control patients (p = 0.94 in Child-Pugh scores; p = 0.64 in MELD scores).Conclusions. In PBC patients with concomitant HCV infection, aggressive management may be warranted in view of the associated more severe liver cirrhosis.     

IGF-I and IGFBP-3 serum levels in patients hospitalized for complications of liver cirrhosis

Background. IGF-I and IGFBP-3 are part of IGF system and, due to their predominantly hepatic synthesis, they seem to correlate with hepatic dysfunction intensity. Aims. To investigate the significance of IGF-I and IGFBP-3 in patients with decompensated liver disease.Material and methods. Cross-sectional study that included cirrhotic patients admitted to hospital due to complications of the disease, in whom IGF-I and IGFBP-3 serum levels were measured by chemiluminescence. Results. Seventy-four subjects with a mean age of 53.1 ± 11.6 years were included in the study, 73% were males. IGF-I levels were positively correlated with IGFBP-3 and albumin, and negatively correlated with Child-Pugh, MELD, creatinine, INR and aPTT ratio. IGFBP-3 levels were positively correlated with IGF-I and albumin, and negatively correlated with Child-Pugh, MELD, creatinine, INR, total bilirubin and aPTT ratio. Significantly lower scores of IGF-I and IGFBP-3 were observed in patients with higher MELD values and higher Child-Pugh classes (P < 0.05).Conclusions. In cirrhotic patients admitted to hospital due to complications of the disease, IGF-I and IGFBP-3 serum levels were associated with variables related to liver dysfunction and to more advanced liver disease. The levels of these markers seem to undergo little influence from other clinical and laboratory variables, therefore mainly reflecting hepatic functional status.     

The performance of prognostic models as predictors of mortality in patients with acute decompensation of cirrhosis

Background. Although several prognostic models have been proposed for cirrhotic patients listed for transplantation, the performance of these scores as predictors of mortality in patients admitted for acute decompensation of cirrhosis has not been satisfactorily investigated.Aims. To study MELD, MELD-Na, MESO, iMELD, Refit-MELD and Refit MELD-Na models as prognostic predictors in cirrhotic patients admitted for acute decompensation, and to compare their performance between admission and 48 hours of hospitalization to predict in-hospital mortality.Material and methods. This cohort study included cirrhotic patients admitted to hospital due to complications of the disease. Individuals were evaluated on admission and after 48 h of hospitalization, and mortality was evaluated during the present admission.Results. One hundred and twenty-three subjects with a mean age of 54.26 ± 10.79 years were included; 76.4% were male. Mean MELD score was 16.43 ± 7.08 and 52.0% of patients were Child-Pugh C. Twenty-seven patients (22.0%) died during hospitalization. Similar areas under the curve (AUROCs) for prognosis of mortality were observed when different models were compared on admission (P > 0.05) and after 48 h of hospitalization (P > 0.05). When models executed after 48 h of hospitalization were compared to their corresponding model calculated on admission, significantly higher AUROCs were obtained for all models (P < 0.05), except for MELD-Na (P = 0.075) and iMELD (P = 0.119).Conclusion. The studied models showed similar accuracy as predictors of in-hospital mortality in cirrhotic patients admitted for acute decompensation. However, the performance of these models was significantly better when applied 48 h after admission when compared to their calculation on admission.     

Value of the model for end-stage liver disease for predicting survival in hepatocellular carcinoma patients treated with transarterial chemoembolization

Objective. The aim of this study was to evaluate the prognostic value of the model for end-stage liver disease (MELD) and its modified forms, and to compare these scoring systems with other staging systems for hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE). Material and methods. A total of 325 patients who underwent TACE for the initial treatment of HCC between January 2000 and May 2007 were enrolled in the study. Before TACE was carried out, MELD, MELD-Na, Child-Pugh score, Okuda stage, CLIP score, JIS score, BCLC stage, and UICC stage were checked. After one month, ?MELD and ?MELD-Na were calculated. Results. Mean MELD/MELD-Na/?MELD/?MELD-Na scores were 7.5±3.7, 8.0±4.7, ?0.2±3.5 and 0.04±4.5, respectively. MELD (p=0.009) and MELD-Na (p=0.017) significantly correlated with survival, but ?MELD and ?MELD-Na did not (p >0.05). The Child-Pugh score and other staging systems correlated significantly with survival (p <0.05). The AUROC values for 3, 12, and 36 months’ survival were 0.633, 0.545, and 0.615 for MELD; 0.655, 0.555, and 0.612 for MELD-Na; 0.639, 0.616, and 0.691 for Child-Pugh score; 0.714, 0.662, and 0.717 for the Okuda score; 0.837, 0.86, and 0.792 for the CLIP score; 0.859, 0.814, and 0.808 for the JIS score; 0.846, 0.833, and 0.749 for BCLC stage; and 0.878, 0.812, and 0.735 for UICC stage, respectively. Conclusions. MELD and MELD-Na showed good correlations with survival, especially for patients with early-stage disease. However, these were not superior to those of other staging systems or Child-Pugh score. These parameters should only be used as supportive data.     

The impact of diabetes mellitus in mortality of patients with compensated liver cirrhosis-a prospective study

Background. It has been suggested that DM may reduce survival of patients with liver cirrhosis (LC). Nevertheless only few prospective studies assessing the impact of DM on mortality of cirrhotic patients have been published, none in compensated LC.Aims. (i) to study the impact of DM on mortality and (ii) to identify predictors of death.Methods. Patients with compensated LC with and without DM were studied. Survival was analyzed by the Kaplan-Meier Method. Univariate and multivariate analysis was performed to determine independent predictors of mortality.Results. 110 patients were included: 60 without DM and 50 with DM. Diabetic patients had significantly higher frequency of cryptogenic cirrhosis, anemia, hypoalbuminemia, and hypercreatininemia. They also had significantly higher BMI and Child-Pugh score. The 2.5-years cumulative survival was significantly lower in patients with DM (48 vs. 69%, p < 0.05). By univariate analysis: DM, female gender, serum creatinine > 1.5 mg/dL, Child-Pugh score class C and cryptogenic cirrhosis were significant. However, only serum creatinine > 1.5 mg/dL and Child-Pugh score class C were independent predictors of death.Conclusion: DM was associated with a significant increase in mortality in patients with compensated liver cirrhosis. Serum creatinine > 1.5 mg/dL and Child-Pugh score class C were independent predictors of death.     

Association between Low Testosterone Levels and Sarcopenia in Cirrhosis: A Cross-sectional Study

Introduction and aim. Sarcopenia is an independent predictor of mortality in cirrhosis. Hypogonadism is common in cirrhosis and has been associated with sarcopenia in non-cirrhotic chronic liver disease populations. The aim of this study is to investigate if sarcopenia is associated with low testosterone levels in patients with cirrhosis.Material and methods. This is a retrospective analysis of prospectively collected data of 211 cirrhotic patients undergoing evaluation for liver transplantation. Sarcopenia was defined by computed tomography (CT) scan using specific cutoffs of the 3rd lumbar vertebra skeletal muscle index (L3 SMI). Morning testosterone levels were obtained in all patients.Results. Of the 211 patients, sarcopenia was noted in 94 (45%). Testosterone levels were lower in sarcopenic patients (10.7 ± 1.1 vs. 13.7 ± 1.4 nmol/L, p = 0.03) and hypotestosteronemia was more frequent in them too (34 vs. 16%, p = 0.004). In males, those with sarcopenia had lower testosterone levels (14.6 ± 1.4 vs. 21.9 ± 1.8, p = 0.002), and the corresponding frequency of hypotestosteronemia (42 vs. 19%, p = 0.006) was also higher. There were no significant differences in female patients. There was a weak correlation between L3 SMI and testosterone levels (r 0.37, p < 0.001). On multivariable regression analysis including sex, body mass index (BMI), hypotestosteronemia, MELD and etiology of cirrhosis, only hypotestosteronemia (RR 2.76, p = 0.005) and BMI (RR 0.88, p < 0.001) were independently associated with sarcopenia.Conclusion. Low testosterone levels are associated with sarcopenia in male cirrhotic patients. The potential therapeutic effect of testosterone to reverse sarcopenia in these patients warrants evaluation in future trials.     

Serum cholesterol is a significant and independent mortality predictor in liver cirrhosis patients

Background and Aim. Accurate assessment of cirrhotic patient’s prognosis is essential for decisions regarding the course of treatment. Therefore we aimed to confirm and quantify the predictive value of serum cholesterol and serum triglycerides in liver cirrhosis patients.Material and methods. We performed a retrospective observational cohort study on consecutive patients with liver cirrhosis (n = 191). Relevant clinical and laboratory variables were obtained from patients‘ charts and patients were followed for two months. Mortality was the main outcome.Results. Thirty-eight patients died in the follow-up period. Significant difference was observed in the level of total serum cholesterol between surviving and deceased patients (2.27 ± 1.02 mmol/L vs. 2.97 ± 1.00 mmol/L, P < 0.0001 respectively). Cholesterol was confirmed as a significant predictor of mortality in univariate logistic regression analysis, and independent predictor beside bilirubin, creatinine and MELD score in multivariate logistic regression analysis. Addition of serum cholesterol level to a prognostic model based on total bilirubin, creatinine and INR increased its accuracy by 4%. Adding cholesterol to the MELD score improved prediction accuracy by 3%. There was no significant difference in serum levels of triglycerides between surviving and deceased patients.Conclusion. Serum cholesterol is a routinely measured parameter, which has independent prognostic value in patients with liver cirrhosis.     

Galectin-3 is associated with glomerular filtration rate and outcome in patients with stable decompensated cirrhosis

BackgroundNewly introduced galectin-3 (gal-3) has been associated to impaired renal function. Gal-3 may become prognostic biomarker in hepatic diseases.AimTo investigate the association of gal-3 with prognosis and renal function in patients with stable decompensated cirrhosis.MethodWe studied prospectively 100 stable decompensated patients in our Department between 2010 and 2017. We measured gal-3 in serum samples. Patients’ renal function was assessed using ⁵¹Chromium-EDTA (“true GFR”).ResultsSeventy patients (70%) survived and 30 died (n = 16) or underwent LT (n = 14). Twenty nine patients (29%) had normal gal-3, 71 (71%) had ≥11.7 ng/mL; they differed significantly regarding mean “true”-GFR: 90 ± 20 mL/min vs. 76 ± 26 mL/min, p = 0.03 and mean creatinine: 0.83 ± 0.14 mg/dL vs. 0.97 ± 0.4 mg/dL, p = 0.05. Median gal-3 levels were 17.5 ng/mL (range 4.9–76.5 ng/mL); 49 patients with gal-3 ≥17.5 ng/mL had significantly higher MELD score, (15 ± 5 vs. 13 ± 4, p = 0.02) and worse “true” GFR (74 vs. 85 mL/min, p = 0.04). Gal-3 had good performance in predicting “true”-GFR < 60 mL/min; AUC: 0.71, 95%CI [0.58–0.85], best cut off value 17.5 ng/mL. Kaplan–Meier analysis, using median gal-3 (17.5 ng/mL) revealed different survival time for our patients (log-rank p = 0.04).ConclusionGal-3 proved trustworthy marker of established chronic kidney disease, with predictive ability in stable decompensated cirrhosis. Gal-3 came also a significant factor for our patients’ outcome.     

Comparison of the model for end-stage liver disease (MELD), MELD-Na and MELDNa for outcome prediction in patients with acute decompensated hepatitis

Background and aimThe model for end-stage liver disease (MELD) is used to predict the outcome of patients with cirrhosis. Incorporation of serum sodium (Na) into MELD may further increase its prognostic ability. Two Na-containing MELD models, MELD-Na and MELDNa, were proposed to enhance the prognostic ability. This study compared the predictive accuracy of these models for acute decompensated hepatitis.MethodsWe investigated the outcome of 182 patients with acute decompensated hepatitis.ResultsTwenty (11%) patients died at 3 months. The MELD-Na and MELDNa both had significantly higher area under the receiver operating characteristic curve (AUC) in comparison to MELD (MELD-Na: 0.908, MELDNa: 0.895, MELD: 0.823, p = 0.004 and 0.001, respectively). Among 96 patients without specific antiviral treatment, the MELD-Na and MELDNa consistently had significantly higher AUC than the MELD (MELD-Na: 0.901, MELDNa: 0.882, MELD: 0.810, p = 0.008 and 0.004, respectively). Three independent indicators, pre-existing cirrhosis (odds ratio [OR]: 5.67, 95% confidence interval [CI]: 1.72–18.7), serum albumin <3.7 g/dL (OR: 5.68, 95% CI: 1.18–27.03) and serum sodium (Na) < 138 mequiv./L (OR: 10.0, 95% CI: 2.08–47.62), were associated with 3-month mortality.ConclusionMELD-Na and MELDNa provide better prognostic accuracy than the MELD for patients with acute decompensated hepatitis. The adequacy of liver reserve determines the outcome of these patients.     

Treatment of Type-1 Hepatorenal Syndrome with Pentoxifylline: A Randomized Placebo Controlled Clinical Trial

Introduction. Type-1 hepatorenal syndrome (HRS-1) portends a poor prognosis in patients with cirrhosis. Currently available medical therapies are largely ineffective, save for liver transplantation. We aimed to determine if pentoxifylline (PTX) therapy in addition to the standard of care of volume expansion with albumin and vasoconstriction with midodrine and octreotide (AMO) is safe and efficacious compared to AMO in HRS-1 treatment.Material and methods. Hospitalized subjects with decompensated cirrhosis and HRS-1 were enrolled. PTX or placebo was administered with AMO therapy for up to 14 days. The primary endpoint was HRS-1 resolution (serum creatinine ≤ 1.5 g/dL for > 24 h). Secondary endpoints were change in creatinine and MELD score, partial treatment response, 30-and 180-day overall and transplant free survival.Results. Twelve subjects with mean age 58.9 ± 6.2 years were enrolled and randomized. Mean MELD score was 26.5 ± 7.4 and 58.3% were male. Overall cohort 30- and 180-day survival was 58.3% and 33.3% respectively. Two subjects underwent liver transplantation. HRS-1 resolution (16.7% vs. 16.7%, p = 1.000), partial treatment response (33.3% vs. 16.7%, p = 0.505), change in creatinine (+0.48 g/dL, 95% CI -0.49-1.46 vs. +0.03 g/dL, 95% CI -0.640.70, p = 0.427), 30-day survival (66.6% vs. 50.0%, p = 0.558) and 180-day survival (50.0% vs. 16.7%, p = 0.221) were similar between the two groups. Serious adverse events necessitating treatment discontinuation were rare (n = 1, PTX).Discussion. The addition of PTX to AMO in the treatment of HRS-1 is safe when compared to the current standard of care. Future large-scale prospective study to validate the efficacy of this treatment seems warranted.     

ALBI and PALBI Grades Are Associated with the Outcome of Patients with Stable Decompensated Cirrhosis

Introduction and aim. Studies carried out mainly in patients with hepatocellular carcinoma (HCC), have shown the prognostic significance of albumin-bilirubin (ALBI) grade. Recently, another predictive score incorporating platelet count into ALBI, PALBI grade, was introduced in patients with HCC.Aim. We evaluated the ability of ALBI and PALBI grades in predicting the outcome (mortality / liver transplantation) of patients with stable decompensated cirrhosis with various etiology of liver diseases.Material and methods. We prospectively studied 325 patients with stable decompensated cirrhosis awaiting liver transplantation. Their clinical and laboratory characteristics were recorded including albumin, bilirubin levels, platelets. We estimated ALBI and PALBI grades for every patient. Conventional prognostic scores were also evaluated; Child-Pugh (CTP), Model for End stage Liver Disease (MELD). We followed them up and recorded their outcome.Results. Beyond MELD and CTP, ALBI and PALBI grades proved significant factors associated with the outcome (HR: 2.13, 95%CI [1.59, 2.85], p < 0.001 and HR: 2.06, 95%CI [1.47, 2.9], p < 0.001, respectively), and their predictive capability was established (ROC analysis; AUC: 0.695, 95% CI [0.634, 0.755] and AUC: 0.683, 95% CI [0.621,0.744], respectively). ALBI and PALBI performed better than CTP score (p = 0.0044 and p = 0.014, respectively). Categorization of our patients into three ALBI groups detected statistically different survival times. Accordingly, PALBI grade 3 compared to those with PALBI grade 1 and 2 patients, had worse outcome and significantly higher frequency of cirrhosis-related complicationsConclusions. ALBI and PALBI grades were validated and can be used to predict the outcome in patients with stable decompensated cirrhosis     

Alcoholic liver disease presents at advanced stage and progresses faster compared to non-alcoholic fatty liver disease

Background and objective. Steatohepatitis is a common cause of liver disease due to alcohol (ALD) or non-alcoholic fatty liver disease (NAFLD). We performed this study to compare natural history of ALD and NAFLD.Material and methods. Retrospective analysis of ALD or NAFLD patients managed at our center (2007-2011). ALD diagnosed by excluding other liver diseases (except HCV) and alcohol abuse of > 40 g/d in women and > 60 g/d in men for > 5 years. NAFLD diagnosed by excluding other liver diseases and a history of alcohol use of < 10 g/d. Cirrhosis was diagnosed using biopsy for uncertain clinical diagnosis.Results. Compared to patients with NAFLD (n = 365; mean age 50 yrs; 43% males; 53% diabetic), ALD patients (n = 206; mean age 51 yrs; 68% males; 24% diabetic) presented more often with cirrhosis or complications(46 vs. 12%; P< 0.0001) with a higher MELD score (13 ± 7 vs. 8 ± 8; P<0.0001). On logistic regression, ALD diagnosis was associated with presence of cirrhosis by over 4-fold (4.1 [1.8-9.1]) even after excluding 23 patients with concomitant HCV. Over median follow up of about 3 and 4 yrs among ALD and NAFLD patients respectively, ALD patients more frequently developed cirrhosis or its complications including HCC with worse transplant free survival (90 vs. 95%; P = 0.038).Conclusions. Compared to NAFLD, ALD patients present at an advanced stage of liver disease with a faster progression on follow-up. Prospective multicenter studies are needed to identify potential barriers to early referral of ALD patients as basis for development of strategies to improve outcome of patients with ALD.