UNASSIGNED: Ammonia levels predicted hospitalisation in a recent landmark study not accounting for portal hypertension and systemic inflammation severity. We investigated (i) the prognostic value of venous ammonia levels (outcome cohort) for liver-related outcomes while accounting for these factors and (ii) its correlation with key disease-driving mechanisms (biomarker cohort).
UNASSIGNED: (i) The outcome cohort included 549 clinically stable outpatients with evidence of advanced chronic liver disease. (ii) The partly overlapping biomarker cohort comprised 193 individuals, recruited from the prospective Vienna Cirrhosis Study (VICIS: NCT03267615).
UNASSIGNED: (i) In the outcome cohort, ammonia increased across clinical stages as well as hepatic venous pressure gradient and United Network for Organ Sharing model for end-stage liver disease (2016) strata and were independently linked with diabetes. Ammonia was associated with liver-related death, even after multivariable adjustment (adjusted hazard ratio [aHR]: 1.05 [95% CI: 1.00-1.10]; p = 0.044). The recently proposed cut-off (≥1.4 × upper limit of normal) was independently predictive of hepatic decompensation (aHR: 2.08 [95% CI: 1.35-3.22]; p <0.001), non-elective liver-related hospitalisation (aHR: 1.86 [95% CI: 1.17-2.95]; p = 0.008), and - in those with decompensated advanced chronic liver disease - acute-on-chronic liver failure (aHR: 1.71 [95% CI: 1.05-2.80]; p = 0.031). (ii) Besides hepatic venous pressure gradient, venous ammonia was correlated with markers of endothelial dysfunction and liver fibrogenesis/matrix remodelling in the biomarker cohort.
UNASSIGNED: Venous ammonia predicts hepatic decompensation, non-elective liver-related hospitalisation, acute-on-chronic liver failure, and liver-related death, independently of established prognostic indicators including C-reactive protein and hepatic venous pressure gradient. Although venous ammonia is linked with several key disease-driving mechanisms, its prognostic value is not explained by associated hepatic dysfunction, systemic inflammation, or portal hypertension severity, suggesting direct toxicity.
UNASSIGNED: A recent landmark study linked ammonia levels (a simple blood test) with hospitalisation/death in individuals with clinically stable cirrhosis. Our study extends the prognostic value of venous ammonia to other important liver-related complications. Although venous ammonia is linked with several key disease-driving mechanisms, they do not fully explain its prognostic value. This supports the concept of direct ammonia toxicity and ammonia-lowering drugs as disease-modifying treatment.

UNASSIGNED: This study was planned to evaluate triceps skinfold thickness (TSFT), mid-arm muscle circumference (MAMC) and bioelectrical impedance analysis (BIA) for assessing body composition using dual-energy X-ray absorptiometry (DEXA) (reference) and to predict fat mass (FM) and fat-free mass (FFM) in patients with cirrhosis.
UNASSIGNED: FM and FFM were assessed by using DEXA and BIA. Skin-fold calliper was used for measuring TSFT, and MAMC was calculated. Bland-Altman plot was used to determine agreement and linear regression analysis for obtaining equations to predict FM and FFM.
UNASSIGNED: Patients with cirrhosis (n = 302, 241 male, age 43.7 ± 12.0 years) were included. Bland-Altman plot showed very good agreement between BIA and DEXA for the estimation of FM and FFM. Majority of patients were within the limit of agreement: FM (98%) and FFM (96.4%). BIA shows a positive correlation with DEXA:FM (r = 0.73, P ≤ 0.001) and FFM (r = 0.86, P ≤ 0.001). DEXA (FM and FFM) shows a positive correlation with TSFT (r = 0.69, P ≤ 0.01) and MAMC (r = 0.61, P ≤ 0.01). The mean difference between the observed and predicted value of FM and FFM by BIA in the developmental set was 0.01 and 0.05, respectively; whereas in the validation set, it was -0.13 and 0.86, respectively. The mean difference between the observed and predicted value of TSFT and MAMC in the developmental set was 0.43 and 0.07; whereas, in the validation set, it was 0.16 and 0.48, respectively.
UNASSIGNED: Anthropometry (TSFT and MAMC) and BIA are simple and easy to use and can be a substitute of DEXA for FM and FFM assessment in routine clinical settings in patients with cirrhosis.

UNASSIGNED: Radiofrequency ablation (RFA) is a standard treatment for small inoperable hepatocellular carcinoma (HCC). Studies on mid- and long-term outcome of RFA as first-line therapy for HCC from India are limited.
UNASSIGNED: We evaluated consecutive HCC patients who underwent RFA as primary treatment modality at our institute between July 2009 and April 2016. The median follow-up period was 26 months, range 1-84 months. We evaluated post-RFA tumor response, disease-free survival (DFS), overall survival (OS), and local tumor progression (LTP). Prognostic factors were also analyzed.
UNASSIGNED: In 147 patients (male:female = 121:26; mean age, 59.2 years), 209 RFA sessions were done for 228 lesions (mean size of 21.5 ± 8.3 mm, range 10-50 mm). Primary success rate was 94.2%. The estimated cumulative proportion survival at 1, 3, and 5 years was 90.2%, 63.8%, and 60.2%, respectively. The cumulative incidence of LTP estimated at 1, 3, and 5 years was 13.1%, 19.7%, and 20.1%, respectively. The mean estimate of LTP-free survival was 53.6 months (95% confidence interval: 0.49-0.58) which is 58.2 months in <3 cm lesions and 20.4 months in >3 cm lesions (P < 0.01). There was no significant difference in LTP rates between lesions in perivascular versus nonperivascular location (P = 0.71) and surface versus parenchymal lesions (P = 0.66). The mean DFS was 30.3 months (95% CI: 25.6-35.0). For OS, age and Child-Turcotte-Pugh class B were significant factors while for LTP, tumor size >3 cm was significant. Higher baseline alpha-fetoprotein level and LTP were poor predictors for DFS. Complication rate per RFA session was 7/209 (3.3%).
UNASSIGNED: RFA is a safe and effective curative modality for first-line treatment of HCC < 3 cm.

BACKGROUND: To study the differences in outcome and predictors of mortality in acute-on-chronic liver failure (ACLF) precipitated by hepatic or extrahepatic insults.
METHODS: Consecutive patients of cirrhosis with acute decompensation were prospectively included and followed up for 90 days from admission. ACLF was defined based on chronic liver failure (CLIF) acute-on-chronic liver failure in cirrhosis (CANONIC study) criteria. Acute worsening due to acute viral hepatitis A and E, hepatitis B flare, alcoholic hepatitis, autoimmune hepatitis flare, or drug-induced liver injury were categorized as hepatic ACLF and that due to bacterial infection, upper gastrointestinal bleed or surgery as extrahepatic ACLF. Patients with both hepatic and extrahepatic insults were included in combined insult group.
RESULTS: Of 179 patients of acute decompensation, 122 had ACLF (hepatic insults 47 and extrahepatic insults 51). Alcohol (64.8%) was the most common etiology of cirrhosis while infection (36%) was the most common acute insult followed by alcoholic hepatitis (24.6%). Higher proportion of extrahepatic ACLF patients had history of prior decompensation than hepatic ACLF patients (62.7% vs. 27.7%, P < 0.001). There was no difference in mortality among hepatic and extrahepatic ACLF groups at 28 and 90 days (53.2% vs. 56.9%, P = 0.715 and 85% vs. 74.5%, P = 0.193, respectively). Area under receiver-operating curve (AUROC) for 28-day mortality in extrahepatic ACLF group was 0.788, 0.724, 0.718, 0.634, and 0.726 and in hepatic-ACLF group was 0.786, 0.625, 0.802, 0.761, and 0.648 for chronic liver failure-sequential organ failure assessment (CLIF-SOFA), model for end stage liver disease (MELD), integrated MELD score (iMELD), acute physiology and chronic health evaluation score (APACHE-II), and Child-Turcotte-Pugh score scores, respectively.
CONCLUSIONS: There is no difference in mortality among hepatic and extrahepatic ACLF groups at 28 and 90 days. iMELD and CLIF-SOFA have highest AUROC to predict 28-day mortality in hepatic and extrahepatic ACLF groups, respectively.

BACKGROUND: Traditionally, Maddrey discriminant function (DF) score has been used for stratifying the prognosis of alcoholic hepatitis. Recently, the Model for end-stage liver disease (MELD) score has been applied to alcoholic hepatitis and some investigators consider MELD score as a better prognostic indicator. Another new prognostic approach, Lille model has been also suggested to accurately identify patients at high risk of death. Therefore, this prospective study was aimed to compare MELD, DF, Child-Turcotte-Pugh (CTP) scores and Lille model for predicting the short-term mortality in Indian patients with alcoholic hepatitis.
METHODS: We calculated the DF, CTP, MELD and Lille scores in patients hospitalized with alcoholic hepatitis & evaluated if the scores predicted in-hospital mortality.
RESULTS: A total of 104 patients were enrolled and thirty-two (30.7%) patients died during the hospitalization (2-30 days). Admission DF score (OR 1.1, P < 0.04), CTP (OR 2, P < 0.05) MELD score (OR 2.2, P < 0.005) and first week MELD score (OR 1.1, P < 0.05) were independently associated with in-hospital mortality. The area under the receiver-operating curve (AUROC) for the admission and day 7 MELD score was significantly higher than CTP score and was comparable to DF score and Lille model (AUC & 95% CI: 0.97 [0.95-1.0], 0.99 [0.99-1.0], 0.91 [0.83-0.91] and 0.92 [0.86-0.98] for MELD at admission & day 7, admission DF and Lille model, respectively). The MELD score >14 at admission and >12 at day 7 had high sensitivity and specificity in predicting short-term mortality (96%, 89% and 95%, 98% respectively). The cutoff of 0.45 for the Lille model was able to identify 79% of the observed deaths, whereas DF score ≥32 for DF were able to identify 85%.
CONCLUSIONS: MELD score, as a predictive model for assessment of short-term mortality in alcoholic hepatitis is better than CTP and comparable to DF and Lille model.

OBJECTIVE: The role of model for end-stage liver disease (MELD) among Indian patients with cirrhosis is uncertain. We studied and compared MELD with Child-Turcotte-Pugh (CTP) and creatinine-modified-CTP (CrCTP) scores for predicting 1-, 3-, and 6-months mortality.
METHODS: One-hundred and two patients with cirrhosis were studied. The CrCTP was calculated by adding creatinine score of 0, 2 and 4 with creatinine levels of ≤1.2mg/dL, 1.3-1.8 mg/dL and ≥1.9mg/dL, respectively to CTP score. Survival curves were plotted and receiver operating characteristics (ROC) curves were used to compare the scores. Predictors of mortality were analyzed using Cox proportional hazards model.
RESULTS: Scores of CTP, CrCTP, and MELD have excellent diagnostic accuracy for predicting mortality (c-statistics >0.85). The MELD was superior to CTP for predicting 3-months [c-statistic and 95% confidence interval, 0.967 (0.911-0.992) vs 0.884 (0.806-0.939)] and 6-months [0.977 (0.925-0.996) vs 0.908 (0.835-0.956)] mortality (P=0.05), while CrCTP [0.958 (0.899-0.988)] was better than CTP for predicting 3-months mortality (P=0.02). Serum creatinine (hazard ratio 4.43, P<0.0001) is a strong independent predictor of mortality.
CONCLUSIONS: The MELD accurately predicts mortality in cirrhosis and is better than CTP for predicting the short-term and intermediate-term mortality. Adding serum creatinine to CTP though significantly improves its diagnostic accuracy for short-term mortality; however, it remains lower than MELD alone.