Comparison of four models for end-stage liver disease in evaluating the prognosis of cirrhosis

AIM: To investigate the prognostic value of the model for end-stage liver disease (MELD) and three new MELD-based models combination with serum sodium in decompensated cirrhosis patients-the MELD with the incorporation of serum sodium (MELD-Na), the integrated MELD (iMELD), and the MELD to sodium (MESO) index. METHODS: A total of 166 patients with decompensated cirrhosis were enrolled into the study. MELD, MELD- Na, iMELD and MESO scores were calculated for each patient following the original formula on the first day of admission. All patients were followed up at least 1 year. The predictive prognosis related with the four models was determined by the area under the receiver operating characteristic curve (AUC) of the four parameters. Kaplan-Meier survival curves were made using the cut-offs identif ied by means of receiver operating characteristic (ROC). RESULTS: Out of 166 patients, 38 patients with signifi cantly higher MELD-Na (28.84 ± 2.43 vs 14.72 ± 0.60), iMELD (49.04 ± 1.72 vs 35.52 ± 0.67), MESO scores (1.59 ± 0.82 vs 0.99 ± 0.42) compared to the survivors died within 3 mo (P < 0.001). Of 166 patients, 75 with markedly higher MELD-Na (23.01 ± 1.51 vs 13.78 ± 0.69), iMELD (44.06 ± 1.19 vs 34.12 ± 0.69), MESO scores (1.37 ± 0.70 vs 0.93 ± 0.40) than the survivors died within 1 year (P < 0.001). At 3 mo of enrollment, the iMELD had the highest AUC (0.841), and was followed by the MELD-Na (0.766), MESO (0.723), all larger than MELD (0.773); At 1year, the iMELD still had the highest AUC (0.783), the difference between the iMELD and MELD was statistically significant (P < 0.05). Survival curves showed that the three new models were all clearly discriminated the patients who survived or died in short-term as well as intermediate-term (P < 0.001). CONCLUSION: Three new models, changed with serum sodium (MELD-Na, iMELD, MESO) can exactly predict the prognosis of patients with decompensated cirrhosis for short and intermediate period, and may enhance the prognostic accuracy of MELD. The iMELD is better prognostic model for outcome prediction in patients with decompensated cirrhosis.

Chinese guidelines on the management of liver cirrhosis(abbreviated version)

Based on reviews of the literature and experts’consensus,the Chinese Society of Hepatology developed guidelines for the diagnosis and treatment of liver cirrhosis,in order to improve clinical practice.In addition to what has been covered in previously published guidelines on the management of cirrhosis complications,these guidelines add new sections and provide updates.The guidelines emphasize the early diagnosis of the cause and assessment of complications.Comprehensive treatments including etiological treatment and complication management should be initiated immediately.In addition,regular monitoring,especially surveillance of hepatocellular carcinoma,is crucial for managing patients.

Alpha-1 antitrypsin deficiency and the risk of hepatocellular carcinoma in end-stage liver disease

AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study(N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension(ascites,variceal bleeding,thrombocytopenia,or hepatic encephalopathy). A1 ATD was diagnosed using phenotype characterization(MZ or ZZ),liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules,or both. Patients with other causes of liver diseases such as hepatitis C virus(HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities,biopsy findings,or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-tointerval analysis for interval censored data.RESULTS:This study included 675 patients. 7% of subjects had A1ATD(n = 47). Out of all subjects who did not have A1 ATD,46% had HCV,17% had alcoholic liver disease,19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1 ATD,15 had a primary diagnosis of A1ATD(PI*ZZ phenotype and PAS+ globules),8 had a PI*MZ phenotype alone,14 had PAS+ alone,and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4(25th,75 th percentiles:1,5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29%(n = 199). In the A1 ATD group,the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis(P = 0.001). Patients with ESLD due to A1 ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis,1.5% in patients with NASH and 0.9% in alcohol-induced liver disease(P < 0.001).CONCLUSION:Within this group of patients with ESLD,there was no significant association between A1 ATD and increased risk of HCC.

Tongue thickness in health vs cirrhosis of the liver:Prospective observational study

BACKGROUNDMalnutrition affects 40%-90% of patients with cirrhosis of the liver. L3 skeletalmuscle index (L3SMI) is presently accepted as the most objective and quantitativemeasure available for sarcopenia, a surrogate marker of malnutrition. L3SMIapplication is, however, limited by non-availability of computed tomographyscanning in remote areas, cost, need for extensive training, and the risk ofexposure to radiation. Therefore, an alternative dependable measure with wideravailability is needed. Malnutrition causes sarcopenia not only in skeletal musclesbut also in other muscular structures such as the psoas muscle, diaphragm andtongue. We therefore hypothesised that the tongue, being easily accessible forinspection and for measurement of thickness using ultrasonography, may be usedto document sarcopenia.AIMTo measure and compare tongue thickness in healthy individuals and in patientswith cirrhosis of the liver and to study its correlation with conventionalprognostic scores for patients with cirrhosis of the liver.METHODSTongue thickness was measured using ultrasonography. One hundred twentysubjects of either gender aged 18 to 65 years were studied, with 30 subjects in eachgroup. The tongue thickness was compared between groups based on “ChildTurcotte Pugh” (CTP) scores. The correlations between measured tonguethickness and “Model for end stage liver disease” (MELD) score and between age and measured tongue thickness were also assessed.RESULTSMean tongue thickness (mean ± SD) in patients with CTP class A, B and C was4.39 ± 0.39 cm, 4.19 ± 0.53 cm, and 3.87 ± 0.42, respectively, and was 4.33 ± 0.49 cmin normal healthy individuals. Significant differences were seen in tonguethickness between patients with CTP class C and those with CTP class A and B (P< 0.05). Patients with CTP class C also had a significantly reduced tonguethickness than normal individuals (P < 0.05). However, no significant differencewas seen in tongue thickness between patients with CTP class A and B andnormal individuals. A statistically significant, negative correlation was foundbetween MELD score and tongue thickness (r = -0.331) (P < 0.001). No correlationwas observed between L3SMI and MELD score (r = 0.074, P = 0.424). L3SMI(mean ± SD) in healthy subjects was 39.66 ± 6.8 and was 38.26 ± 8.88 in patientswith CTP class C, and the difference was not significant. No significant correlationwas found between age of the patients and tongue thickness. Intra-classcorrelation coefficient was used to determine the reliability of the tonguethickness measurements. The intra-class correlation coefficient was 0.984 (95%CI:0.979-0.989) and was indicative of good reliability.CONCLUSIONTongue thickness measured by ultrasonography, correlates significantly with theseverity of liver disease, as assessed by CTP and MELD scores. The patients with aCTP score ≥ 10 have significantly reduced tongue thickness as compared tonormal individuals and those with less severe liver disease and CTP scores of 5-9.No significant difference in tongue thickness was found between healthyindividuals and CTP class A and B patients.

Markers of bacterial translocation in end-stage liver disease

Bacterial translocation(BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence.BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT.

Sarcopenia in the prognosis of cirrhosis: Going beyond the MELD score

Estimating the prognosis of patients with cirrhosis remains challenging, because the natural history of cirrhosis varies according to the cause, presence of portal hypertension, liver synthetic function, and the reversibility of underlying disease. Conventional prognostic scoring systems, including the Child-Turcotte-Pugh score or model for endstage liver diseases are widely used; however, revised models have been introduced to improve prognostic performance. Although sarcopenia is one of the most common complications related to survival of patients with cirrhosis, the newly proposed prognostic models lack a nutritional status evaluation of patients. This is reflected by the lack of an optimal index for sarcopenia in terms of objectivity, reproducibility, practicality, and prognostic performance, and of a consensus definition for sarcopenia in patients with cirrhosis in whom ascites and edema may interfere with body composition analysis. Quantifying skeletal muscle mass using cross-sectional abdominal imaging is a promising tool for assessing sarcopenia. As radiological imaging provides direct visualization of body composition, it is useful to evaluate sarcopenia in patients with cirrhosis whose body mass index, anthropometric measurements, or biochemical markers are inaccurate on a nutritional assessment. Sarcopenia defined by cross-sectional imaging-based muscular assessment is prevalent and predicts mortality in patients with cirrhosis. Sarcopenia alone or in combination with conventional prognostic systems shows promise for a cirrhosis prognosis. Including an objective assessment of sarcopenia with conventional scores to optimize the outcome prediction for patients with cirrhosis needs further research.

Bone marrow derived stem cells for the treatment of end-stage liver disease

End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver transplantation, but due to the several limitations of this procedure, the interest in alternative therapeutic strategies is increasing. In particular, the potential of bone marrow stem cell(BMSC) therapy in cirrhosis has been explored in different trials. In this article, we evaluate the results of 18 prospective clinical trials, and we provide a descriptive overview of recent advances in the research on hepatic regenerative medicine. The main message from the currently available data in the literature is that BMSC therapy is extremely promising in the context of liver cirrhosis. However, its application should be further explored in randomized, controlled trials with large cohorts and long follow-ups.

Corrected QT interval in cirrhosis:A systematic review and metaanalysis

BACKGROUND Corrected QT(QTc)interval is prolonged in patients with liver cirrhosis and has been proposed to correlate with the severity of the disease.However,the effects of sex,age,severity,and etiology of cirrhosis on QTc have not been elucidated.At the same time,the role of treatment,acute illness,and liver transplantation(Tx)remains largely unknown.AIM To determine the mean QTc in patients with cirrhosis,assess whether QTc is prolonged in patients with cirrhosis,and investigate whether QTc is affected by factors such as sex,age,severity,etiology,treatment,acute illness,and liver Tx.METHODS In the present systematic review and meta-analysis,the searching protocol“{[QTc]OR[QT interval]OR[QT-interval]OR[Q-T syndrome]}AND{[cirrhosis]OR[Child-Pugh]OR[MELD]}”was applied in PubMed,EMBASE,and Google Scholar databases to identify studies that reported QTc in patients with cirrhosis and published after 1998.Seventy-three studies were considered eligible.Data concerning first author,year of publication,type of study,method used,sample size,mean age,female ratio,alcoholic etiology of cirrhosis ratio,Child-Pugh A/B/C ratio,mean model for end-stage liver disease(MELD)score,treatment withβ-blockers,episode of acute gastrointestinal bleeding,formula for QT correction,mean pulse rate,QTc in patients with cirrhosis and controls,and QTc according to etiology of cirrhosis,sex,Child-Pugh stage,MELD score,and liver Tx status(pre-Tx/post-Tx)were retrieved.The Newcastle-Ottawa quality assessment scale appraised the quality of the eligible studies.Effect estimates,expressed as proportions or standardized mean differences,were combined using the randomeffects,generic inverse variance method of DerSimonian and Laird.Subgroup,sensitivity analysis,and meta-regressions were applied to assess heterogeneity.RESULTS QTc combined mean in patients with cirrhosis was 444.8 ms[95%confidence interval(CI):440.4-449.2;P<0.001 when compared with the upper normal limit of 440 ms],presenting high heterogeneity(I2=97.5%;95%CI:97.2%-97.8%);both Egger’s and Begg’s tests showed non-significance.QTc was elongated in patients with cirrhosis compared with controls(P<0.001).QTc was longer in patients with Child-Pugh C cirrhosis when compared with Child-Pugh B and A(P<0.001);Child-Pugh B patients presented longer QTc when compared with Child-Pugh A patients(P=0.003).The MELD score was higher in patients with cirrhosis with QTc>440 ms when compared with QTc≤440 ms(P<0.001).No correlation of QTc with age(P=0.693),sex(P=0.753),or etiology(P=0.418)was detected.β-blockers shortened QTc(P<0.001).QTc was prolonged during acute gastrointestinal bleeding(P=0.020).Tx tended to improve QTc(P<0.001).No other sources of QTc heterogeneity were revealed.CONCLUSION QTc is prolonged in cirrhosis independently of sex,age,and etiology but is correlated with severity and affected byβ-blockers and acute gastrointestinal bleeding.QTc is improved after liver Tx.

Autologous mobilized peripheral blood CD34^+ cell infusion in non-viral decompensated liver cirrhosis

AIM: To study the effect of mobilized peripheral blood autologous CD34 positive(CD34+) cell infusion in patients with non-viral decompensated cirrhosis.METHODS: Cirrhotic patients of non-viral etiology were divided into 2 groups based on their willingness to be listed for deceased donor liver transplant(DDLT)(control, n = 23) or to receive autologous CD34+ cell infusion through the hepatic artery(study group, n= 22). Patients in the study group were admitted to hospital and received granulocyte colony stimulating factor injections 520 μg/d for 3 consecutive days to mobilize CD34+ cells from the bone marrow. On day 4,leukapheresis was done and CD34+ cells were isolated using CliniMAC magnetic cell sorter. The isolated CD34+ cells were infused into the hepatic artery under radiological guidance. The patients were discharged within 48 h. The control group received standard of care treatment for liver cirrhosis and were worked up for DDLT as per protocol of the institute. Both groups were followed up every week for 4 wk and then every month for 3 mo.RESULTS: In the control and the study group, the cause of cirrhosis was cryptogenic in 18(78.2%) and16(72.72%) and alcohol related in 5(21.7%) and6(27.27%), respectively. The mean day 3 cell count(cells/μL) was 27.00 ± 20.43 with a viability of 81.84± 11.99%. and purity of 80%-90%. Primary end point analysis revealed that at 4 wk, the mean serum albumin in the study group increased significantly(2.83± 0.36 vs 2.43 ± 0.42, P = 0.001) when compared with controls. This improvement in albumin was,however, not sustained at 3 mo. However, at the end of3 mo there was a statistically significant improvement in serum creatinine in the study group(0.96 ± 0.33 vs 1.42 ± 0.70, P = 0.01) which translated into a significant improvement in the Model for End-Stage Liver Disease score(15.75 ± 5.13 vs 19.94 ± 6.68,P = 0.04). On statistical analysis of secondary end points, the transplant free survival at the end of 1 mo and 3 mo did not show any significant difference(P =0.60) when compared to the control group. There was no improvement in aspartate transaminase, alanine transaminase, and bilirubin at any point in the study population. There was no mortality benefit in the study group. The procedure was safe with no procedural or treatment related complications.CONCLUSION: Autologous CD 34+ cell infusion is safe and effectively improves liver function in the short term and may serve as a bridge to liver transplantation.

Combined MELD and blood lipid level in evaluating the prognosis of decompensated cirrhosis

AIM: To evaluate the prognostic value of the combined model for end-stage liver disease (MELD) and blood lipid level in patients with decompensated cirrhosis. METHODS: A total of 198 patients with decompensated cirrhosis were enrolled into the study. The values of triglyceride (TG), cholesterol (TC), high density lipoproteins (HDL) and low density lipoprotein (LDL) of each patient on the fi rst day of admission were retrieved from the medical records, and MELD was calculated. All the patients were followed up for 1 year. The relationship between the change of blood lipid level and the value of MELD score was studied by analysis of variance. The prognostic factors were screened by multivariate Cox proportional hazard model. Draw Kaplan-Meier survival curves were drawn. RESULTS: Forty-f ive patients died within 3 mo and 83 patients died within 1 year. The levels of TG, TC, HDL and LDL of the death group were all lower than those of the survivors. The serum TG, TC, HDL and LDL levels were lowered with the increase of the MELD score. Multivariate Cox proportional hazard model showed that MELD ≥18 and TC ≤2.8 mmol/L were independent risk factors for prognosis of decompensated cirrhosis. Survival analysis showed that MELD ≥18 combined with TC ≤ 2.8 mmol/L can clearly discriminate between the patients who would survive and die in 1 year. CONCLUSION: MELD ≥18 and TC ≤2.8 mmol/L are two important indexes to predict the prognosis of patients with decompensated cirrhosis. Their combination can effectively predict the long-term prognosis of patients with decompensated cirrhosis.

Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma

AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.

Relationship between model for end-stage liver disease score and left ventricular function in patients with end-stage liver disease

BACKGROUND:Decreased cardiac contractility has been observed in cirrhosis,suggesting a latent cardiomyopathy in these patients.This study was designed to evaluate left ventricular structure and function in patients with end-stage liver disease by the model for end-stage liver disease(MELD) scoring system. METHODS:We recruited 82 patients(72 male,10 female; mean age 50.3±8.9 years)with end-stage liver disease who underwent orthotopic liver transplantation between January 2002 and May 2008.Seventy-eight patients had cirrhosis and 4 had primary liver cancer.Patients were categorized into three groups on the basis of MELD score:≤9(27 patients, 33%);10-19(40,49%);and≥20(15,18%).The relationship between MELD score and cardiac structure and function was determined.Preoperative assessments of blood biochemistry, blood coagulation,serum virology,echocardiography and electrocardiography were performed. RESULTS:MELD score was positively correlated with enlarged left atrial diameter,increased interventricular septum thickness(IVST),increased aortic flow,corrected QT interval (QTc)extension and cardiac output(P=0.033,0.002,0.000, 0.000 and 0.009,respectively).International normalized ratio also had a correlation with the above parameters and enlarged left ventricular end-diastolic diameter(P=0.043,0.010,0.000, 0.001,0.016 and 0.008,respectively).Serum creatinine was positively correlated with IVST(r=0.257,P=0.020),but negatively correlated with early maximal ventricular filling velocity/late diastolic or atrial velocity ratio(r=-0.300, P=0.006).A difference of QTc>440 ms among the three groups was statistically significant(χ2=9.791,P=0.007).CONCLUSIONS:Abnormalities in cardiac structure and function are common in patients with end-stage liver disease. MELD score is a practically useful approach for the assessment of cardiac function in such patients.

Application of a biochemical and clinical model to predict individual survival in patients with end-stage liver disease

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≤8 and high risk>8).RESULTS:In the validation cohort,all measures of fi t,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.

Liver cirrhosis-effect on QT interval and cardiac autonomic nervous system activity

AIM To examine the impact of liver cirrhosis on QT interval and cardiac autonomic neuropathy(CAN). METHODS A total of 51 patients with cirrhosis and 51 controls were examined. Standard 12-lead electrocardiogram recordings were obtained and QT as well as corrected QT interval(QTc) and their dispersions(dQT, dQTc) were measured and calculated using a computer-based program. The diagnosis of CAN was based upon the battery of the tests proposed by Ewing and Clarke and the consensus statements of the American Diabetes Association. CAN was diagnosed when two out of the four classical Ewing tests were abnormal. RESULTS QT, QTc and their dispersions were significantly longer(P < 0.01) in patients with cirrhosis than in controls. No significant differences in QT interval were found among the subgroups according to the etiology of cirrhosis. Multivariate regression analysis after controlling for age, gender and duration of cirrhosis demonstrated significant association between QT and presence of diabetes mellitus [standardized regression coefficient(beta) = 0.45, P = 0.02] and treatment with diuretics(beta = 0.55, P = 0.03), but not with the Child-Pugh score(P = 0.54). Prevalence of CAN was common(54.9%) among patients with cirrhosis and its severity was associated with the Child-Pugh score(r = 0.33, P = 0.02). Moreover, patients with decompensated cirrhosis had more severe CAN that those with compensated cirrhosis(P = 0.03). No significant association was found between severity of CAN and QT interval duration.CONCLUSION Patients with cirrhosis have QT prolongation. Treatment with diuretics is associated with longer QT. CAN is common in patients with cirrhosis and its severity is associated with severity of the disease.

Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage

AIM:To describe the prevalence,diagnosis,treatment,and outcomes of end stage liver disease(ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage(UGIH).METHODS:This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011.RESULTS:A total of 1249 patients were registered for severe UGIH in the data basis,461(36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen(75%) subjects required posterior nasal packing and 2(10%) embolization in addition to correction of coagulopathy. Five(25%) patients died in the hospital,12(60%) received orthotopic liver transplantation(OLT),and 3(15%) were discharged without OLT. The mortality rate was 63% in patients without OLT.CONCLUSION:Severe epistaxis in patients with ESLD is(1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH;and(2) associated with a high mortality rate in patients not receiving OLT.

“Weighing the risk”: Obesity and outcomes following liver transplantation

Obesity is on the rise worldwide. As a result, unprecedented rates of patients are presenting with end stage liver disease in the setting of non-alcoholic fatty liver disease(NAFLD) and are requiring liver transplantation. There are significant concerns that the risk factors associated with obesity and the metabolic syndrome might have a detrimental effect on the long term outcomes following liver transplantation. In general, short term patient and graft outcomes for both obese and morbidly obese patients are comparable with that of non-obese patients, however, several studies report an increase in peri-operative morbidity and increased length of stay. Continued studies documenting the long-term outcomes from liver transplantation are needed to further examine the risk of recurrent disease(NAFLD) and also further define the role risk factors such cardiovascular disease might play long term. Effective weight reduction in the post liver transplant setting may mitigate the risks associated with the metabolic syndrome long-term.

A retrospective study on use of palliative care for patients with alcohol related end stage liver disease in United States

BACKGROUND Palliative care(PC)has been shown to be beneficial in end stage liver disease(ESLD),yet the hospitalization data for PC utilization is unknown.AIM To identify the trend of PC utilization for the special population of alcoholassociated ESLD patients,factors affecting its use and ascertain its impact on healthcare utilization.METHODS We analyzed around 78 million discharges from the 2007-2014 national inpatient sample and 2010-2014 national readmission database including adult patients admitted for decompensated alcohol-associated cirrhosis.We identified patients with PC consultation as a secondary diagnosis.Odds ratios(OR)and means were adjusted for confounders using multivariate regression analysis models.RESULTS Out of the total 1421849 hospitalizations for decompensated liver cirrhosis,62782(4.4%)hospitalizations had a PC consult,which increased from 0.8%(1258)of all alcohol-associated ESLD hospitalizations in 2007 to 6.6%in 2014(P<0.01).Patient and hospital characteristics associated with increased odds of PC utilization were advanced age,lower income,Medicaid coverage,teaching institution,urban location,length of stay>3 d,prolonged ventilation,and administration of total parenteral nutrition(all P<0.01).Palliative encounters in alcohol-associated ESLD and acute-onchronic liver failure(ACLF)score were associated with increased odds of discharge to a rehabilitation facility,but significantly lower odds of 30-d readmissions(aOR:0.35,95%CI:0.31-0.41),lower total hospitalization charges and lower mean hospitalization days(all P<0.01).CONCLUSION Inpatient PC is sparingly used for patients with decompensated alcohol related liver disease,however it has increased over the past decade.PC consultation is associated with lower 30-d readmission rates on multivariate analysis,and lower hospitalization cost and length of stay in patients with ACLF score≥2.

Beta-blockers and physical frailty in patients with endstage liver disease

AIM To investigate beta-blocker(BB) use in patients with cirrhosis and determine their effects on physical frailty and overall survival.METHODS Adult outpatients with cirrhosis listed for liver transplantation underwent testing of physical frailty using the performance-based Liver Frailty Index, comprised of chair stands, grip strength, and balance testing, as well as self-reported assessments of exhaustion and physical activity. BB use was assessed from medical chart review. Univariable and multivariable logistic regression were performed to determine BB use and their association with measures of physical frailty. Competing risk analyses were performed to determine the effect of BB use on wait-list mortality, as defined by death or delisting for being too sick for transplant.RESULTS Of 344 patients, 35% were female, median age was 60, median model for end stage liver disease was 15, and 53% were prescribed a BB. Compared to those not on BB, patients on BB were similar except for percentage female(25% vs 46%; P < 0.001) and BMI(29 vs 28; P = 0.008). With respect to tests of physical frailty, BB use was not associated with increased odds of frailty(by the Liver Frailty Index), exhaustion, or low physical activity. BB use was, however, significantly associated with a decreased adjusted risk of mortality(SHR 0.55; P = 0.005).CONCLUSION In patients with cirrhosis awaiting liver transplantation, BB use is not associated with physical frailty. We confirmed the known survival benefits with BB use, and concerns about adverse effects should not deter their utilization when indicated.

Clinical implications,diagnosis,and management of diabetes in patients with chronic liver diseases

Diabetes mellitus(DM)negatively affects the development and progression of chronic liver diseases(CLD)of various etiologies.Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality,the occurrence of hepatic decompensation,and the development of hepatocellular carcinoma(HCC).Unfortunately,early diagnosis and optimal treatment of DM can be challenging,due to the lack of established clinical guidelines as well as the medical complexity of this patient population.We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population.We reviewed the epidemiological and pathophysiological associations between DM and CLD,the impact of insulin resistance on the progression and manifestations of CLD,the pathogenesis of hepatogenic diabetes,as well as the practical challenges in diagnosis and monitoring of DM in this patient population.We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes.Finally,we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.

The prognostic significance of clinical and pathological features in hepatocellular carcinoma

The prognosis of patients with HCC still remains dismal. The life expectancy of HCC patients is hard to predict because of the high possibility of postoperative recurrence. Many factors, such as patient's general conditions, macroscopic tumor morphology, as well as tumor hictopathology features, have been proven of prognostic significance. Female HCC patient often has a better prognosis than male patient, which might be due to the receptor of sex hormones. Younger patients often have tumors with higher invasiveness and metastatic potentials, and their survival and prognosis are worse than the older ones. Co-existing hepatitis status and hepatic functional reserve have been confirmed as risk factors for recurrence. Serum alpha-fetoprotein (AFP) is useful not only for diagnosis, but also as a prognostic indicator for HCC patients. AFP mRNA has been proposed as a predictive marker of HCC cells disseminated into the circulation and for metastatic recurrence. Many pathologic features,such as tumor size, number, capsule state, cell differentiation, venous invasion, intrahepatic spreading, and advanced pTNM stage, are the best-established risk factors for recurrence and important aspects affecting the prognosis of patients with HCC. Marked inflammatory cell infiltration in the tumor could predict a better prognosis. Clinical stage is still the most important factor influencing on the prognosis. Extratumor spreading and lymph nodal metastasis are independent predictors for poor outcome. Soma new predictive systems have recently been proposed. Different strategies of treatment might have significant different effects on the patients'prognosis. To date, surgical resection is still the only potentially curative treatment for HCC,including localized postoperative recurrences.Extent of resection, blood transfusion, occlusion of porta hepatis, and blood loss affect the survival and prognosis of HCC patients. Regional therapies provide alternative ways to improve the prognosis of HCC patients who have no opportunity to receive surgical treatment or postoperative recurrence. The combination of these treatment modalities is hopeful to further improve the prognosis. The efficacies of neoadjuvant ( preoperative ) or adjuvant ( postoperative )chemotherapy or chemoembolization in preventing recurrence and on the HCC prognosis still remain great controversy, and deserve further evaluation.Biotherapy, including IFN-alpha therapy, will play more important role in preventing recurrence and metastasis of HCC after operation.