Risk factors for mortality in patients with alcoholic hepatitis and assessment of prognostic models: A population-based study

BACKGROUND:

Severe alcoholic hepatitis (AH) is associated with a substantial risk for short-term mortality.

OBJECTIVES:

To identify prognostic factors and validate well-known prognostic models in a Canadian population of patients hospitalized for AH.

METHODS:

In the present retrospective study, patients hospitalized for AH in Calgary, Alberta, between January 2008 and August 2012 were included. Stepwise logistic regression models identified independent risk factors for 90-day mortality, and the discrimination of prognostic models (Model for End-stage Liver Disease [MELD] and Maddrey discriminant function [DF]) were examined using areas under the ROC curves.

RESULTS:

A total of 122 patients with AH were hospitalized during the study period; the median age was 49 years (interquartile range [IQR] 42 to 55 years) and 60% were men. Median MELD score and Maddrey DF on admission were 21 (IQR 18 to 24) and 45 (IQR 26 to 62), respectively. Seventy-three percent of patients received corticosteroids and/or pentoxifylline, and the 90-day mortality was 17%. Independent predictors of mortality included older age, female sex, international normalized ratio, MELD score and Maddrey DF (all P<0.05). For discrimination of 90-day mortality, the areas under the ROC curves of the prognostic models (MELD 0.64; Maddrey DF 0.68) were similar (P>0.05). At optimal cut-offs of ≥22 for MELD score and ≥37 for Maddrey DF, both models excluded death with high certainty (negative predictive values 90% and 96%, respectively).

CONCLUSIONS:

In patients hospitalized for AH, well-known prognostic models can be used to predict 90-day mortality, particularly to identify patients with a low risk for death.     

Prevalence and short‐term outcome of acute kidney injury in patients with acute‐on‐chronic liver failure: A meta‐analysis

Acute kidney injury (AKI) in patients with acute‐on‐chronic liver failure (ACLF) is a distinct syndrome to that in patients with cirrhosis, yet is less characterized. The aim of this meta‐analysis was to investigate the impact of AKI on outcome of ACLF. We searched PubMed, Web of Science and Cochrane Library for original articles that evaluated the impact of AKI on outcome of ACLF from 2011 to 2019. Odds ratio (OR) with 95% confidence interval (CI) for 1‐month and 3‐month mortality was calculated. The response rate of vasoconstrictor for hepatorenal syndrome (HRS)‐AKI was assessed. Eight relevant articles with 3610 patients were included. The prevalence of AKI in ACLF patients was 41% (95% CI 32%‐50%). The presence of AKI was significantly associated with 1‐month mortality of ACLF (OR 3.98, 95% CI 3.09‐5.12; P < .001) and 3‐month mortality (OR 4.98, 95% CI 3.59‐6.92; P < .001). Additionally, patients with AKI stage ≥2 showed a higher 3‐month mortality than stage 1 (OR 3.89, 95% CI 2.60‐5.82; P < .001), and those of stage 3 had a higher mortality than stage ≤2 (OR 3.77, 95% CI 2.10‐6.77; P < .001). The pooled response rate of vasoconstrictors was 32% (95% CI 26%‐37%). This meta‐analysis indicated that about 40% of ACLF patients complicated with AKI and the presence of AKI substantially increased the short‐term mortality, together with a poor response rate of vasoconstrictors for HRS‐AKI.     

MELD accurately predicts mortality in patients with alcoholic hepatitis

Assessing severity of disease in patients with alcoholic hepatitis (AH) is useful for predicting mortality, guiding treatment decisions, and stratifying patients for therapeutic trials. The traditional disease-specific prognostic model used for this purpose is the Maddrey discriminant function (DF). The model for end-stage liver disease (MELD) is a more recently developed scoring system that has been validated as an independent predictor of patient survival in candidates for liver transplantation. The aim of the present study was to examine the ability of MELD to predict mortality in patients with AH. A retrospective cohort study of 73 patients diagnosed with AH between 1995 and 2001 was performed at the Mayo Clinic in Rochester, Minnesota. MELD was the only independent predictor of mortality in patients with AH. MELD was comparable to DF in predicting 30-day mortality (c-statistic and 95% CI: 0.83 [0.71-0.96] and 0.74 [0.62-0.87] for MELD and DF, respectively, not significant) and 90-day mortality (c-statistic and 95% CI: 0.86 [0.77-0.96] and 0.83 [0.74-0.92] for MELD and DF, respectively, not significant). A MELD score of 21 had a sensitivity of 75% and a specificity of 75% in predicting 90-day mortality in AH. In conclusion, MELD is useful for predicting 30-day and 90-day mortality in patients with AH and maintains some practical and statistical advantages over DF in predicting mortality rate in these patients. MELD is a useful clinical tool for gauging mortality and guiding treatment decisions in patients with AH, particularly those complicated by ascites and/or encephalopathy.     

Assessment of scoring systems for acute-on-chronic liver failure at predicting short-term mortality in patients with alcoholic hepatitis

AIMTo assess the performance of proposed scores specific for acute-on-chronic liver failure in predicting short-term mortality among patients with alcoholic hepatitis.METHODSWe retrospectively collected data from 264 patients with clinically diagnosed alcoholic hepatitis from January to December 2013 at 21 academic hospitals in Korea. The performance for predicting short-term mortality was calculated for Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), CLIF Consortium Organ Failure score (CLIF-C OFs), Maddrey’s discriminant function (DF), age, bilirubin, international normalized ratio and creatinine score (ABIC), Glasgow Alcoholic Hepatitis Score (GAHS), model for end-stage liver disease (MELD), and MELD-Na.RESULTSOf 264 patients, 32 (12%) patients died within 28 d. The area under receiver operating characteristic curve of CLIF-SOFA, CLIF-C OFs, DF, ABIC, GAHS, MELD, and MELD-Na was 0.86 (0.81-0.90), 0.89 (0.84-0.92), 0.79 (0.74-0.84), 0.78 (0.72-0.83), 0.81 (0.76-0.86), 0.83 (0.78-0.88), and 0.83 (0.78-0.88), respectively, for 28-d mortality. The performance of CLIF-SOFA had no statistically significant differences for 28-d mortality. The performance of CLIF-C OFs was superior to that of DF, ABIC, and GAHS, while comparable to that of MELD and MELD-Na in predicting 28-d mortality. A CLIF-SOFA score of 8 had 78.1% sensitivity and 79.7% specificity, and CLIF-C OFs of 10 had 68.8% sensitivity and 91.4% specificity for predicting 28-d mortality.CONCLUSIONCLIF-SOFA and CLIF-C OF scores performed well, with comparable predictive ability for short-term mortality compared to the commonly used scoring systems in patients with alcoholic hepatitis.     

Collagen proportionate area predicts long-term mortality in patients with alcoholic hepatitis

Background and aimsThere are several short-term prognostic scores for alcoholic hepatitis (AH) that combine demographical and biochemical parameters. The extent of liver fibrosis may also be relevant to the prognosis of AH with potential added value. We evaluated collagen proportionate area (CPA) as a predictor of short and long-term mortality in AH.MethodsWe retrospectively included patients with biopsy-verified AH. Clinical, laboratory and outcome data were collected. CPA and five AH scores were calculated: Maddrey's DF, MELD, GAHS, ABIC, and the Lille Model. Predictors of short and long-term all-cause mortality were assessed using Cox regression analysis.ResultsWe included 140 patients with AH. In total, 67 (48%) patients died after a median follow-up of 66 (IQR 102) months, with 17 (12%) dying within the first 90-days. CPA was not a predictor of 90-days mortality and had no additional value to the prognostic AH scores on short-term mortality. However, CPA predicted long-term mortality independently of prognostic AH scores. Importantly, CPA and abstinence from alcohol were independent predictors of long-term mortality in patients alive 90 days after the biopsy.ConclusionCPA predicts long-term mortality in patients with AH independently of abstinence from alcohol but has no prognostic value on short-term mortality.     

Clinical course and prognostic factors of hepatorenal syndrome: A retrospective single-center cohort study

AIM: To investigate clinical and biochemical features of hepatorenal syndrome (HRS), to assess short and long-term survival evaluating potential predictors of early mortality.METHODS: Sixty-two patients with liver cirrhosis and renal failure, defined as a serum creatinine value > 1.5 mg/dL on at least two measurements within 48 h, admitted to our tertiary referral Unit from 2001 to 201, were retrospectively reviewed. Among them, 33 patients (53.2%) fulfilled the revised criteria of the International Ascites Club for the diagnosis of HRS. Twenty-eight patients were treated with combinations of terlipressin and albumin, two with dopamine and albumin, and three with albumin alone. No patients were suitable for liver transplantation. Complete response was defined as normalization of creatinine levels to less than 1.5 mg/dL, partial response as a decrease of at least 50% but not to less than 1.5 mg/dL, no response as no reduction in creatinine or a decrease of less 50% compared to pre-treatment values. All of the patients were followed up for at least 1 year until January 2013.RESULTS: HRS type 1 was diagnosed in 15 patients (45.5%). Hepatitis C virus infection was the primary etiology (69.6%), followed by alcohol (15.2%), and cryptogenesis (15.2%). Complete response to therapy was obtained in only 3 cases (9.1%) and partial response in 7 patients (21.2%). Median survival was 30 d (range: 10-274) without significant differences between type 1 and type 2 HRS. By univariate analysis, Child-Pugh class C (P = 0.009), presence of hepatocellular carcinoma (P = 0.04), low serum sodium (P = 0.02), high bilirubin values (P = 0.009) and high Model for End-stage Liver Disease (MELD) score (P = 0.03) were predictive factors of 30-d mortality. By multivariate analysis, only serum sodium < 132 mEq/L (OR = 31.39; P = 0.02) and MELD score > 27 (OR = 18.72; P = 0.01) were independently associated with a survival of less than one month.CONCLUSION: HRS still has a poor prognosis, even when vasoactive drug therapies are extensively used.     

MELD score is a better prognostic model than Child-Turcotte-Pugh score or Discriminant Function score in patients with alcoholic hepatitis

BACKGROUND/AIMS: The aim of the present study was to compare MELD score, Child-Turcotte-Pugh (CTP) score, modified Maddrey's Discriminant Function (DF) score, and the related variables in predicting in-hospital mortality of patients with alcoholic hepatitis. METHODS: A retrospective chart review and statistical analyses were done on 202 patients consecutively admitted for alcoholic hepatitis from 1997 to 2002 at the Liver Unit at Rancho Los Amigos Medical Center. RESULTS: Twenty-nine patients died during the hospitalization. Admission MELD score (OR 1.1, P=0.005), first week MELD score (OR 1.2, P<0.0001), and first week increase in MELD score (OR 1.3, P<0.0001) were independently associated with in-hospital mortality. The area under the receiver operating curve (AUC) for the first week increase in MELD score was higher compared to CTP score (P=0.0004) and DF score (P=0.059). Moreover, the first week MELD score >/=20 had the best sensitivity (91%) and specificity (85%) compared with admission or first week change MELD score. CONCLUSIONS: The present study indicates that in patients with alcoholic hepatitis, admission, first week, and first week change in MELD score are significantly independent predictors for in-hospital mortality. MELD score is a more valuable model than CTP or DF score in patients admitted with alcoholic hepatitis.     

Access to Liver Transplantation in the MELD Era: Role of Ethnicity and Insurance

Factors contributing to inequitable access to liver transplantation include socioeconomic status, geographic location, and delayed referral. The aim of this study is to identify the factors associated with a high MELD at the time of listing. Using the UNOS database, we identified all adults listed from 2002 to 2006. Data collected included demographics, insurance payor (private and government, i.e., Medicaid and non-Medicaid), diagnosis, and MELD score categorized as low (<20) and high (≥20). The results obtained show that a high MELD was associated with age, ethnicity, and insurance (P < 0.001). By multivariate analysis, insurance (OR = 1.21, 95% CI = 1.13–1.30, P < 0.001) and ethnicity (OR = 1.55, 95% CI = 1.28–1.88, P < 0.001) were independently associated with high MELD. In conclusion, ethnic minorities and liver transplant candidates with Medicaid are more likely to have a high MELD score at initial listing. The above results suggest that the type of insurance and ethnicity are independently associated with a high MELD (i.e., sicker patients).     

Comparison between Society of Thoracic Surgeons Score and logistic EuroSCORE for predicting mortality in patients referred for transcatheter aortic valve implantation

Background

The primary inclusion criteria from both the Society of Thoracic Surgeons (STS) score and the logistic EuroSCORE are currently used to identify high-risk and inoperable patients eligible for transcatheter aortic valve implantation (TAVI). We aimed to examine the correlation between STS and logistic EuroSCOREs and their performance characteristics in patients referred for TAVI.

Methods

The study cohort consisted of 718 high-risk patients with severe aortic stenosis who were considered for participation in a TAVI clinical trial. The performance of the STS and logistic EuroSCOREs was evaluated in three groups: (a) medical management or balloon aortic valvuloplasty (BAV), 474 (66%); (b) 133 patients (18.5%) with surgical aortic valve replacement (AVR); (c) 111 (15.4%) with TAVI. The mean age was 81.8±8.1 years, and 394 (54.8%) were female.

Results

The mean STS score was 11.5±6.1, and the mean logistic EuroSCORE was 39.7±23.0. Pearson correlation coefficient showed moderate correlation between the STS and logistic EuroSCOREs (r=0.61, P<.001). At a median follow-up of 190 days (range, 67–476), 282 patients (39.2%) died. The STS and logistic EuroSCOREs were both higher in patients who died as compared to those in survivors (13.1±6.2 vs.10.0±5.8 and 43.4±23.1 vs. 37.5±22, respectively; P<.001). The observed and predicted 30-day mortality rates in the medical/BAV group were 10.1% observed, 12.3% by STS and 43.1% by logistic EuroSCORE. In the surgical AVR group, the rates were 12.8% observed, 8.4% by STS and 25.6% by logistic EuroSCORE. In the TAVI group, the rates were 11.7% observed, 11.8% by STS and 41.2% by logistic EuroSCORE. The odds ratio (OR) for 30-day mortality in the medical/BAV group was 1.05 (P=.01) with STS and 1.003 (P=.7) with logistic EuroSCORE. In the surgical AVR group, the OR was 1.09 (P=.07) with STS and 1.007 (P=.6) with logistic EuroSCORE. In the TAVI group, the OR was 1.14 (P=.03) with STS and 1.03 (P=.04) with logistic EuroSCORE.

Conclusion

In high-risk patients with severe aortic stenosis, STS score is superior to the logistic EuroSCORE in predicting mortality. Clinical judgment should play a major role in the selection of patients with severe aortic stenosis for the different therapeutic options.     

Model for end-stage liver disease (MELD) score,as a prognostic factor for post-operative morbidity and mortality in cirrhotic patients,undergoing hepatectomy for hepatocellular carcinoma

Background/aims:

To evaluate the ability of the model for end-stage liver disease (MELD) in predicting the post-hepatectomy outcome for hepatocellular carcinoma (HCC).

Methods:

Between 2001 and 2004, 69 cirrhotic patients with HCC underwent hepatectomy and the results were retrospectively analysed. MELD score was associated with post-operative mortality and morbidity, hospital stay and 3-year survival.

Results:

Seventeen major and 52 minor resections were performed. Thirty-day mortality rate was 7.2%. MELD ≤ 9 was associated with no peri-operative mortality vs. 19% when MELD > 9 (P < 0.02). Overall morbidity rate was 36.23%; 48% when MELD > 9 vs. 25% when MELD ≤ 9 (P < 0.02). Median hospital stay was 12 days [8.8 days, when MELD ≤ 9 and 15.6 days when MELD > 9 (P = 0.037)]. Three-year survival reached 49% (66% when MELD ≤ 9; 32% when MELD > 9 (P < 0.01). In multivariate analysis, MELD > 9 (P < 0.01), clinical tumour symptoms (P < 0.05) and American Society of Anesthesiologists (ASA) score (P < 0.05) were independent predictors of peri-operative mortality; MELD > 9 (P < 0.01), tumour size >5 cm (P < 0.01), high tumour grade (P = 0.01) and absence of tumour capsule (P < 0.01) were independent predictors of decreased long-term survival.

Conclusion:

MELD score seems to predict outcome of cirrhotic patients with HCC, after hepatectomy.     

Body Mass Index is Associated with Barrett Esophagus and Cardiac Mucosal Metaplasia

A positive association between body mass index (BMI) and risk of esophageal adenocarcinoma has been reported. Barrett esophagus (BE) is a precursor lesion for esophageal adenocarcinoma. Cardiac mucosa (CM) and BE are both reflux-induced metaplastic columnar epithelia in the esophagus. We investigated the association between BMI and BE/CM in a case-control study. A total of 174 BE patients, 333 CM patients, and 274 controls were included in this study. Multivariate logistic regression methods were used to estimate odds ratios (OR) for BE or CM associated with BMI. Linear regression analysis was employed to examine the relationship between length of columnar lined esophagus (CLE) and BMI. A dose-dependent relationship was found between BMI and BE (P=.0004). The multivariate-adjusted OR for BE was 3.3 (95% confidence interval [CI], 1.6–6.7) when obese individuals (BMI ≥30 kg/m²) were compared to lean individuals (BMI < 22 kg/m²). Similarly, a dose-dependent relationship was found between BMI and CM (P=.03). The multivariate-adjusted OR for CM comparing obese to lean persons was 1.8 (95% CI, 1.04–3.10). The length of CLE was positively related to BMI (P=.04). In conclusion, BMI is associated with BE and CM and appears to act early in the sequence of events leading from gastroesophageal reflux disease to metaplasia (CM and BE) to dysplasia and finally to adenocarcinoma.     

Clinical, laboratory and genetic markers associated with erosions and remission in patients with early inflammatory arthritis: a prospective cohort study

We investigated the relationship between clinical, laboratory and genetic markers and outcome measures in 159 patients with recent onset of inflammatory arthritis (IA). The majority of patients were managed in community-based rheumatology practice. Median duration of arthritis at baseline was 3 months with median follow-up of 4.0 years (range 0–10). Markers of disease activity and 1987 ACR criteria for rheumatoid arthritis (RA) were estimated every 6 months for the first 2 years and annually thereafter. Presence of shared epitopes (SE) was established by PCR-based method. Main outcome variables were attainment of remission and presence of erosions on X-rays of hands and feet at 3 years. Remission was seen in 34.3% of patients and was independently related to age 60 and older (odds ratio (OR) 3.2; 95% confidence interval (CI), 1.2–8.7) and inversely to the presence of rheumatoid factor (RF) (OR 8.3; 95% CI, 3.2–21.3 for persistent arthritis). Patients with two SE were likely to have persistent arthritis (P=0.006), but this was not significant when corrected for RF. Independent predictors for erosions at 3 years were RF (OR 7.5; 95% CI, 1.9–29.5) and area under the curve for number of swollen joints (OR 1.08; 95% CI, 1.02–1.16). SE status was not predictive of erosions at 3 years (OR 1.6; 95% CI, 0.7–3.7). In univariate analysis, patients possessing DERAA motif on DRB1 were less likely to have erosive disease than without this motif at 4 years (OR 0.21; 95% CI, 0.0–0.9, P=0.037) but this finding was partly explained by adjusting for RF (adjusted OR 0.24; 95% CI 0.04–1.37). In this study of recent onset IA, active disease and RF were associated with poor outcome. Whilst SE did not predict erosive disease, patients with DERAA motif may be protected against erosions whilst the presence of two SE alleles suggests persistence of arthritis.     

Long‐term outcomes of direct acting antivirals in post‐transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis

Long‐term functional outcomes of sofosbuvir‐based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post‐transplant hepatitis C virus (HCV) recurrence. Seventy‐three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24‐week sofosbuvir with ribavirin±pegylated interferon or interferon‐free sofosbuvir‐based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82‐112) weeks. Twelve of 73 (16.4%) died (10 non‐FCH, 2 FCH) and two underwent re‐LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non‐FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow‐up, MELD and Child‐Turcotte‐Pugh scores improved both in non‐FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short‐treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long‐term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child‐Turcotte‐Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals‐based treatments for severe post‐transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long‐term survival. The setting of severe HCV recurrence may require the identification of “too‐sick‐to‐treat patients” to avoid futile treatments.     

Mortalité hospitalière des patients cirrhotiques admis en milieu de soins intensifs: facteurs pronostiques et apport des scores de gravité

Aims

To identify the frequency and the predictive factors of mortality in cirrhotic patients admitted to intensive care unit and to precise the performances of three gravity scores for predicting the mortality in these patients.

Material and methods

We performed a retrospective study based on consecutive cirrhotic patients admitted to our intensive care unit.

Results

We studied 286 patients. Mortality occurred in 113 patients (39.5%). Predictive factors of mortality were presence of comorbidities (adjusted OR: 2.6; P = 0.008), hyperbilirubinemia > 50 μmol/l (adjusted OR: 3.6; P = 0.04), INR > 2.125 (adjusted OR: 15.1; P < 0.0001), serum leucocyte count > 10,000/mm³ (adjusted OR: 6.2; P = 0.004), dyskaliemia (adjusted OR: 4.1; P = 0.008), creatininemia > 125 μmol/l (adjusted OR: 8.4; P = 0.001), and treatment with vasopressive agents (adjusted OR: 34.4; P < 0.0001). SPAS II and MELD score were more discriminating than Child-Pugh scores with AUC of 0.96, 0.94 and 0.80. SPAS II and MELD scores were more calibrated than Child-Pugh score, particularly in cirrhotic patients with high risk of mortality.

Conclusion

Mortality in cirrhotic patients in intensive care unit is associated with several factors, particularly renal involvement and hemodynamic failure. SPAS II and MELD scores are more accurate for predicting the mortality in these patients than Child-Pugh score.     

Soluble TNF-R1, but not tumor necrosis factor alpha, predicts the 3-month mortality in patients with alcoholic hepatitis

BACKGROUND/AIMS: In alcoholic hepatitis (AH), soluble TNF alpha receptor-1 (sTNF-R1) is increased. Elevated TNF alpha predicts mortality, but infection influences TNF alpha values. In patients with AH, we determined the prognostic value of TNF alpha, sTNF-R1, and lipopolysaccharide binding protein (LBP) and CD14, both involved in endotoxemia-associated inflammation. METHODS: One hundred and eight cirrhotic patients (Pugh score 10 [6-13]) and biopsy-proven AH (Maddrey's DF <32: n=46; > or =32: n=62) without associated infection were included within 8 days of admission and followed-up for 3 months. Cytokines were measured using specific immunoassays. Patients with severe AH received steroids. RESULTS: Twenty four patients died at a median time of 35 days (range: 3-89). The overall survival was 78%. Multivariate Cox regression analysis showed that sTNF-R1 was an independent predictor of mortality, (OR 4.33: 95% CI [1.12-16.75]). Pugh's score (P=0.618), Maddrey's DF (P=0.182), creatinine (P=0.197), TNF alpha (P=0.319), LBP (P=0.362), and CD14 (P=0.347) were not related to survival. CONCLUSIONS: In patients with AH, sTNF-R1 measured at admission is an independent predictor of survival at 3 months. Provided that TNF-R1 mediates the cytotoxic actions of TNFalpha, these results support the concept of dysregulated TNF alpha metabolism in AH.     

Alcoholic hepatitis: Prognosis and treatment

Alcoholic hepatitis (AH) is a type of acute-on-chronic liver failure and is the most severe form of alcoholic liver disease. AH occurs in patients with heavy alcohol abuse and underlying liver disease. In its severe form, AH carries a poor short-term prognosis. Although the existence of AH can be strongly suspected based on clinical and biochemical criteria, a definitive diagnosis requires a liver biopsy. There is a clear need to develop non-invasive markers for these patients. The prognosis of patients with AH can be established by different score systems (Maddrey's DF, ABIC, MELD and Glasgow). Recently, a histological scoring system able to estimate prognosis has been developed (Alcoholic Hepatitis Histological Score – AHHS). The management of patients with AH has changed little in the last few decades. In patients with severe form of AH, prednisolone and pentoxifylline are the first line therapy. Unfortunately, many patients do not respond and novel targeted therapies are urgently needed. Current research is aimed at identifying the main disease drivers and to develop animal models of true AH. For non-responders to medical therapy, the only curative option is to perform a salvage liver transplantation. This particular indication of liver transplantation is currently under debate and prospective studies should evaluate the specific patient evaluation and selection criteria.     

Poor outcomes after fibrinolytic therapy for ST-segment elevation myocardial infarction: Impact of age (A Meta-Analysis of a Decade of Trials)

Background: Fibrinolysis for ST-segment elevation myocardial infarction (STEMI) reduces mortality, but its relative efficacy and risks are age-dependent. We aimed to quantify the outcomes of fibrinolysis and adjunctive antithrombin therapy for STEMI stratified by age. Methods: We performed a meta-analysis of 11 published (1992–2001) randomized clinical trials of fibrinolysis in STEMI (sample size ≥3000, no age limit, no placebo-controlled arms) identified by MEDLINE through June 2005. Event rates and odds ratios (OR) in elderly vs. younger patients were calculated for mortality, intracranial hemorrhage (ICH) and total stroke (CVA). Elderly patients were defined as ≥75 years (GUSTO I, TIMI 9B, GUSTO III, COBALT, ASSENT-2, InTIME-II TIMI-17, ASSENT-3, GUSTO V, and HERO-2), except when defined as >65 or ≥70 years by the study (INJECT and ISIS-3). Results: Elderly (n = 24 531) vs. younger (n = 123 568) patients had increased rates of mortality (19.7% vs. 5.5%), ICH (1.4% vs. 0.5%) and CVA (3.5 vs. 1.2%) by 30–35 days; the excess risk for these events was substantial (OR mortality 4.37, 95% CI 4.16–4.58; ICH 2.83, 2.47–3.24; CVA 2.92, 2.62–3.25; p < 0.001 for all). Conclusions: Despite established mortality reductions with fibrinolysis for STEMI, elderly compared with younger patients, still have a three to four fold increased risk of mortality and adverse events when treated with fibrinolysis and antithrombin therapy in the modern era. These robust estimates of the anticipated rates for mortality, ICH, and CVA can be used as benchmarks to monitor the efficacy and safety of therapies in ongoing and newly completed clinical trials. Abbreviated abstract We aimed to quantify the outcomes of death, intracranial hemorrhage (ICH), and total cerebrovascular accidents (CVA) in elderly compared with younger patients treated with fibrinolysis for STEMI based on a meta-analysis of 11 randomized clinical trials (1992–2001) of more than 3000 patients. Elderly (n = 24 531) vs. younger (n = 123 568) patients had increased rates of mortality, ICH and CVA by 30–35 days; the excess risk was substantial (OR 4.37, 2.83, and 2.92 respectively, p < 0.001 for all). These robust estimates can be used as benchmarks to monitor the efficacy and safety of therapies in ongoing and newly completed clinical trials.     

Anti-cyclic citrullinated peptide antibody is associated with radiographic erosion in rheumatoid arthritis independently of shared epitope status

Shared epitope (SE) and anti-cyclic citrullinated peptide (CCP) antibody are known to be associated with rheumatoid arthritis (RA). The authors investigated their adjusted effects on RA from Korean population. Clinical features were evaluated in 226 RA patients; 164 healthy controls were enrolled. HLA-DRB1 typing for SE was done by polymerase chain reaction. Anti-CCP antibody levels were determined by enzyme linked immunosorbent assay. Logistic regression analysis method was used for adjusted effects. SE and anti-CCP antibody were associated with RA susceptibility. Anti-CCP antibody was associated with RA susceptibility independent of SE [odds ratio, OR 179.9 (95% confidence interval, CI 40.8–792.2), P < 0.001]. Anti-CCP antibody was associated with radiographic erosive changes independent of SE or rheumatoid factor [OR 3.9 (95% CI 1.1–13.3), P = 0.032]. Anti-CCP antibody was strongly associated with RA susceptibility and radiographic erosion of RA patients, independent of SE in Korean.     

Liberal Policy in Living Donor Liver Transplantation for Hepatocellular Carcinoma: Lessons Learned

Background Living donor liver transplantation (LDLT) in cases of hepatocellular carcinoma (HCC) that do not fulfil accepted tumor criteria continues to be a matter of controversy. The aim of this study was to evaluate survival and prognostic factors associated with a liberal exclusionary policy. Material and Methods This is an analysis of data collected prospectively on 57 HCC patients who underwent LDLT at our institution between April 1998 and January 2007. Results Overall 3-year survival was 62%; this increased to 71% when 45-day mortality was excluded from the analysis. Age proved to be a predictor of survival irrespective of the 45-day mortality. In contrast, the Model for End stage Liver Disease (MELD) score predicted survival only when 45-day mortality was included in the analysis, while alpha fetoprotein (AFP) level predicted survival only when it was excluded. Significant cut-off values were patient age of over 60 years, MELD score above 22, and AFP level greater than 400 ng/ml. A scoring system was developed. Survival rate at 3 years—including 45-day mortality—was 72% for score =2 and 41% for score >2 (P = 0.0146). When 45-day mortality was excluded, the survival rate at 3 years was 90% for score =2 and 32% for score >2 (P = 0.00002). Conclusions Our results could further enhance current guidelines on age, MELD score, and AFP level for patients with HCC being evaluated to undergo LDLT.     

Development and validation of a prognostic model for patients with hepatorenal syndrome: A retrospective cohort study

BACKGROUNDHepatorenal syndrome (HRS) is a severe complication of cirrhosis with high mortality, which necessitates accurate clinical decision. However, studies on prognostic factors and scoring systems to predict overall survival of HRS are not enough. Meanwhile, a multicenter cohort study with a long span of time could be more convincing.AIMTo develop a novel and effective prognostic model for patients with HRS and clarify new prognostic factors. METHODSWe retrospectively enrolled 1667 patients from four hospitals, and 371 eligible patients were finally analyzed to develop and validate a novel prognostic model for patients with HRS. Characteristics were compared between survivors and non-survivors, and potential prognostic factors were selected according to the impact on 28-d mortality. Accuracy in predicting 28-d mortality was compared between the novel and other scoring systems, including Model for End-Stage Liver Disease (MELD), Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), and Chinese Group on the Study of Severe Hepatitis B-Acute-on-Chronic Liver Failure (COSSH-ACLF). RESULTSFive prognostic factors, comprised of gender, international normalized ratio, mean corpuscular hemoglobin concentration, neutrophil percentage, and stage, were integrated into a new score, GIMNS; stage is a binary variable defined by the number of failed organs. GIMNS was positively correlated with MELD, CLIF-SOFA, and COSSH-ACLF. Additionally, it had better accuracy [area under the receiver operating characteristic curve (AUROC): 0.830] than MELD (AUROC: 0.759), CLIF-SOFA (AUROC: 0.767), and COSSH-ACLF (AUROC: 0.759) in the derivation cohort (P < 0.05). It performed better than MELD and CLIF-SOFA in the validation cohort (P < 0.050) and had a higher AUROC than COSSH-ACLF (P = 0.122).CONCLUSIONWe have developed a new scoring system, GIMNS, to predict 28-d mortality of HRS patients. Mean corpuscular hemoglobin concentration and stage were first proposed and found to be related to the mortality of HRS. Additionally, the GIMNS score showed better accuracy than MELD and CLIF-SOFA, and the AUROC was higher than that of COSSH-ACLF.