Acute variceal bleeding portends poor outcomes in patients with acute-on-chronic liver failure: a propensity score matched study from the APASL ACLF Research Consortium (AARC).

Limited data exist regarding outcomes of acute variceal bleeding (AVB) in patients with acute-on-chronic liver failure (ACLF), especially in those with hepatic failure. We evaluated the outcomes of AVB in patients with ACLF in a multinational cohort of APASL ACLF Research Consortium (AARC). Prospectively maintained data from AARC database on patients with ACLF who developed AVB (ACLF-AVB) was analysed. This data included demographic profile, severity of liver disease, and rebleeding and mortality in 6 weeks. These outcomes were compared with a propensity score matched (PSM) cohort of ACLF matched for severity of liver disease (MELD, AARC score) without AVB (ACLF without AVB). Of the 4434 ACLF patients, the outcomes in ACLF-AVB (n = 72) [mean age-46 ± 10.4 years, 93% males, 66% with alcoholic liver disease, 65% with alcoholic hepatitis, AARC score: 10.1 ± 2.2, MELD score: 34 (IQR: 27-40)] were compared with a PSM cohort selected in a ratio of 1:2 (n = 143) [mean age-44.9 ± 12.5 years, 82.5% males, 48% alcoholic liver disease, 55.7% alcoholic hepatitis, AARC score: 9.4 ± 1.5, MELD score: 32 (IQR: 24-40)] of ACLF-without AVB. Despite PSM, ACLF patients with AVB had a higher baseline HVPG than without AVB (25.00 [IQR: 23.00-28.00] vs. 17.00 [15.00-21.75] mmHg; p = 0.045). The 6-week mortality in ACLF patients with or without AVB was 70.8% and 53.8%, respectively (p = 0.025). The 6-week rebleeding rate was 23% in ACLF-AVB. Presence of ascites [hazard ratio (HR) 2.2 (95% CI 1.03-9.8), p = 0.026], AVB [HR 1.9 (95% CI 1.2-2.5, p = 0.03)], and MELD score [HR 1.7 (95% CI 1.1-2.1), p = 0.001] independently predicted mortality in the overall ACLF cohort. Development of AVB confers poor outcomes in patients with ACLF with a high 6-week mortality. Elevated HVPG at baseline represents a potential risk factor for future AVB in ACLF.

Sharma S ，Agarwal S ，Saraya A ，Choudhury A ，Mahtab MA ，Alam MS ，Saigal S ，Kim DJ ，Eapen CE ，Goel A ，Ning Q ，Devarbhavi H ，Singh V ，Shukla A ，Hamid S ，Hu J ，Tan SS ，Arora A ，Sahu MK ，Rela M ，Jothimani D ，Rao PN ，Kulkarni A ，Ghaznian H ，Lee GH ，Zhongping D ，Sood A ，Goyal O ，Lesmana LA ，Lesmana RC ，Treeprasertsuk S ，Yuemin N ，Shah S ，Tao H ，Dayal VM ，Shaojie X ，Karim F ，Abbas Z ，Sollano JD ，Kalista KF ，Shreshtha A ，Payawal D ，Omata M ，Sarin SK ，APASL ACLF Research Consortium (AARC) for APASL ACLF Working Party ... -  《-》

Risk stratification based on acute-on-chronic liver failure in cirrhotic patients hospitalized for acute variceal bleeding.

Acute variceal bleeding (AVB) is a life-threatening complication of cirrhosis. Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of cirrhosis, multiple organ failures and high short-term mortality. This study aimed to evaluate the role of ACLF in the risk stratification of cirrhotic patients with AVB. Prospective data of 335 cirrhotic patients hospitalized for AVB were retrospectively extracted from Medical Information Mart for Intensive Care (MIMIC)-IV database. ACLF was defined by European Association for the Study of Liver-Chronic Liver Failure Consortium and diagnosed/graded with chronic liver failure-organ failure (CLIF-OF) score. Cox-proportional hazards regression analysis was performed to identify the risk factors for 6-week morality in AVB patients. Discrimination and calibration of prognostic scores were evaluated by plotting the receiver operating characteristics (ROC) curve and calibration curve, respectively. Overall performance was assessed by calculating the Brier score and R2 value. A total of 181 (54.0%) patients were diagnosed with ACLF (grade 1: 18.2%, grade 2: 33.7%, grade 3: 48.1%) at admission. The 6-week mortality in patients with ACLF was significantly higher than that in patients without ACLF (43.6% vs. 8.4%, P < 0.001) and increased in line with the severity of ACLF (22.5%, 34.2% and 63.8% for ACLF grade 1, 2 and 3, P < 0.001). In multivariate analysis, presence of ACLF remained as an independent risk factor for 6-week mortality after adjusting for confounding factors (HR = 2.12, P = 0.03). The discrimination, calibration and overall performance of CLIF-C ACLF and CLIF-C AD were superior to the traditional prognostic scores (CTP, MELD and MELD-Na) in the prediction of 6-week mortality of patients with and without ACLF, respectively. The prognosis of cirrhotic patients with AVB is poor when accompanied by ACLF. ACLF at admission is an independent predictor for the 6-week mortality in cirrhotic patients with AVB. CLIF-C ACLF and CLIF-C AD are the best prognostic scores in AVB patients with and without ACLF, respectively, and can be used for the risk stratification of these two distinct entities.

Zhu Z ，Jiang H 《-》

AARC score determines outcomes in patients with alcohol-associated hepatitis: a multinational study.

Acute-on-chronic liver failure (ACLF) is a severe form of alcoholic hepatitis (SAH). We aimed to study the natural course, response to corticosteroids (CS), and the role of the Asian Pacific Association for the Study of Liver (APASL) research consortium (AARC) score in determining clinical outcomes in AH patients. Prospectively collected data from the AARC database were analyzed. Of the 1249 AH patients, (aged 43.8 ± 10.6 years, 96.9% male, AARC score 9.2 ± 1.9), 38.8% died on a 90 day follow-up. Of these, 150 (12.0%) had mild-moderate AH (MAH), 65 (5.2%) had SAH and 1034 (82.8%) had ACLF. Two hundred and eleven (16.9%) patients received CS, of which 101 (47.87%) were steroid responders by day 7 of Lille's model, which was associated with improved survival [Hazard ratio (HR) 0.15, 95% CI 0.12-0.19]. AARC-ACLF grade 3 [OR 0.28, 0.14-0.55] was an independent predictor of steroid non-response and mortality [HR 3.29, 2.63-4.11]. Complications increased with degree of liver failure [AARC grade III vs. II vs I], bacterial infections [48.6% vs. 37% vs. 34.7%; p < 0.001); extrahepatic organ failure [66.9% vs. 41.8% vs. 35.4%; p < 0.001] respectively. The AARC score better discriminated 90-day mortality. Harrell's C-index was 0.72 compared to other scores. Nearly 4 of 5 patients with AH present with ACLF. Such patients have a higher risk of infections, organ failures, lower response to CS, and higher mortality. Patients with AH and ACLF with AARC grade 3 should be considered for an early liver transplant.

Maiwall R ，Pasupuleti SSR ，Choudhury A ，Kim DJ ，Sood A ，Goyal O ，Midha V ，Devarbhavi H ，Arora A ，Kumar A ，Sahu MK ，Maharshi S ，Duseja AK ，Singh V ，Taneja S ，Rao PN ，Kulkarni A ，Ghazinian H ，Hamid S ，Eapen CE ，Goel A ，Shreshtha A ，Shah S ，Hu J ，Prasad VGM ，Yuemin N ，Shaojie X ，Dhiman RK ，Chen T ，Ning Q ，Panackel C ，Niriella MA ，Lama TK ，Tan SS ，Dokmeci AK ，Shukla A ，Sharma MK ，Sarin SK ... -  《-》

Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS.

The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date. A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality. At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not. This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB. Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.

Trebicka J ，Gu W ，Ibáñez-Samaniego L ，Hernández-Gea V ，Pitarch C ，Garcia E ，Procopet B ，Giráldez Á ，Amitrano L ，Villanueva C ，Thabut D ，Silva-Junior G ，Martinez J ，Genescà J ，Bureau C ，Llop E ，Laleman W ，Palazon JM ，Castellote J ，Rodrigues S ，Gluud L ，Ferreira CN ，Barcelo R ，Cañete N ，Rodríguez M ，Ferlitsch A ，Mundi JL ，Gronbaek H ，Hernández-Guerra M ，Sassatelli R ，Dell'Era A ，Senzolo M ，Abraldes JG ，Romero-Gómez M ，Zipprich A ，Casas M ，Masnou H ，Primignani M ，Weiss E ，Catalina MV ，Erasmus HP ，Uschner FE ，Schulz M ，Brol MJ ，Praktiknjo M ，Chang J ，Krag A ，Nevens F ，Calleja JL ，Robic MA ，Conejo I ，Albillos A ，Rudler M ，Alvarado E ，Guardascione MA ，Tantau M ，Bosch J ，Torres F ，Pavesi M ，Garcia-Pagán JC ，Jansen C ，Bañares R ，International Variceal Bleeding Observational Study Group and Baveno Cooperation ... -  《-》

Identifying the early predictors of non-response to steroids in patients with flare of autoimmune hepatitis causing acute-on-chronic liver failure.

Early identification of non-response to steroids is critical in patients with autoimmune hepatitis (AIH) causing acute-on-chronic liver failure (ACLF). We assessed if this non-response can be accurately identified within first few days of treatment. Patients with AIH-ACLF without baseline infection/hepatic encephalopathy were identified from APASL ACLF research consortium (AARC) database. Diagnosis of AIH-ACLF was based mainly on histology. Those treated with steroids were assessed for non-response (defined as death or liver transplant at 90 days for present study). Laboratory parameters, AARC, and model for end-stage liver disease (MELD) scores were assessed at baseline and day 3 to identify early non-response. Utility of dynamic SURFASA score [- 6.80 + 1.92*(D0-INR) + 1.94*(∆%3-INR) + 1.64*(∆%3-bilirubin)] was also evaluated. The performance of early predictors was compared with changes in MELD score at 2 weeks. Fifty-five out of one hundred and sixty-five patients (age-38.2 ± 15.0 years, 67.2% females) with AIH-ACLF [median MELD 24 (IQR: 22-27); median AARC score 7 (6-9)] given oral prednisolone 40 (20-40) mg per day were analyzed. The 90 day transplant-free survival in this cohort was 45.7% with worse outcomes in those with incident infections (56% vs 28.0%, p = 0.03). The AUROC of pre-therapy AARC score [0.842 (95% CI 0.754-0.93)], MELD [0.837 (95% CI 0.733-0.94)] score and SURFASA score [0.795 (95% CI 0.678-0.911)] were as accurate as ∆MELD at 2 weeks [0.770 (95% CI 0.687-0.845), p = 0.526] and better than ∆MELD at 3 days [0.541 (95% CI 0.395, 0.687), p < 0.001] to predict non-response. Combination of AARC score > 6, MELD score > 24 with SURFASA score ≥ - 1.2, could identify non-responders at day 3 (concomitant- 75% vs either - 42%, p < 0.001). Baseline AARC score, MELD score, and the dynamic SURFASA score on day 3 can accurately identify early non-response to steroids in AIH-ACLF.

Sharma S ，Agarwal S ，Saraya A ，Choudhury AK ，Saigal S ，Soin AS ，Shukla A ，Sahu MK ，Lesmana LA ，Lesmana RC ，Shah SN ，Hu J ，Tan SS ，Jothimani D ，Rela M ，Ghazinyan HL ，Amrapurkar DN ，Eapen CE ，Goel A ，Payawal DA ，Hamid S ，Butt AS ，Zhongping D ，Singh V ，Duseja A ，Sood A ，Midha V ，Al Mahtab M ，Kim DJ ，Ning Q ，Kulkarni AV ，Rao PN ，Lee GH ，Treeprasertsuk S ，Shaojie X ，Karim MF ，Sollano JD ，Kalista KF ，Gani RA ，Prasad VGM ，Sarin SK ，APASL ACLF Research Consortium (AARC) for APASL ACLF working party ... -  《-》