Complications constitute a major risk factor for mortality in hepatitis B virus-related acute-on-chronic liver failure patients: a multi-national study from the Asia-Pacific region.
Huazhong University of Science and Technology1, Bangabandhu Sheikh Mujib Medical University2, Zhejiang University3, Capital Medical University4, Chinese PLA General Hospital5, Aga Khan University Hospital6, National University of Singapore7, Hebei Medical University8, Post Graduate Institute of Medical Education and Research9, Queen Mary University of London10, Ziauddin University11, Ankara University12
TL;DR: The Tongji prognostic predictor model score (TPPMs), which set the number of complications as one of the determinants, showed comparable or superior ability to the Chinese Group on the Study of Severe Hepatitis B–ACLF score (COSSH-ACLFs) and MELD–sodium score (MELD–Nas) in HBV– ACLF patients, especially in cirrhotic HBV-–AClF patients.
Abstract: Cirrhosis is a controversial determinant of mortality in HBV-related acute-on-chronic liver failure (HBV–ACLF). The present study aimed to explore the effects of cirrhosis and the associated risk factors, especially its complications, on the outcome of HBV–ACLF. A prospective–retrospective cohort of 985 patients was identified from the APASL–ACLF Research Consortium (AARC) database and the Chinese Study Group. Complications of ACLF (ascites, infection, hepatorenal syndrome, hepatic encephalopathy, upper gastrointestinal bleeding) as well as cirrhosis and the current main prognostic models were measured for their predictive ability for 28- or 90-day mortality. A total of 709 patients with HBV–ACLF as defined by the AARC criteria were enrolled. Among these HBV–ACLF patients, the cirrhotic group showed significantly higher mortality and complications than the non-cirrhotic group. A total of 36.1% and 40.1% of patients met the European Association for the Study of Liver (EASL)–Chronic Liver Failure consortium (CLIF-C) criteria in the non-cirrhotic and cirrhotic groups, respectively; these patients had significantly higher rates of mortality and complications than those who did not satisfy the CLIF-C criteria. Furthermore, among patients who did not meet the CLIF-C criteria, the cirrhotic group exhibited higher mortality and complication rates than the non-cirrhotic group, without significant differences in organ failure. The Tongji prognostic predictor model score (TPPMs), which set the number of complications as one of the determinants, showed comparable or superior ability to the Chinese Group on the Study of Severe Hepatitis B–ACLF score (COSSH–ACLFs), APASL–ACLF Research Consortium score (AARC–ACLFs), CLIF-C organ failure score (CLIF–C OFs), CLIF-C–ACLF score (CLIF-C–ACLFs), Model for End-Stage Liver Disease score (MELDs) and MELD–sodium score (MELD–Nas) in HBV–ACLF patients, especially in cirrhotic HBV-–ACLF patients. Patients with two (OR 4.70, 1.88) or three (OR 8.27, 2.65) complications had a significantly higher risk of 28- or 90-day mortality, respectively. The presence of complications is a major risk factor for mortality in HBV–ACLF patients. TPPM possesses high predictive ability in HBV–ACLF patients, especially in cirrhotic HBV–ACLF patients.
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01 Feb 2021
TL;DR: Current evidence shows that the pathophysiology of ACLF is closely associated with an intense systemic inflammation sustained by circulating pathogen-associated molecular patterns and damage- associated molecular patterns.
Abstract: The term acute-on-chronic liver failure (ACLF) defines an abrupt and life-threatening worsening of clinical conditions in patients with cirrhosis or chronic liver disease. In recent years, different definitions and diagnostic criteria for the syndrome have been proposed by the major international scientific societies. The main controversies relate to the type of acute insult (specifically hepatic or also extrahepatic), the stage of underlying liver disease (cirrhosis or chronic hepatitis) and the concomitant extrahepatic organ failure(s) that should be considered in the definition of ACLF. Therefore, different severity criteria and prognostic scores have been proposed and validated. Current evidence shows that the pathophysiology of ACLF is closely associated with an intense systemic inflammation sustained by circulating pathogen-associated molecular patterns and damage-associated molecular patterns. The development of organ failures may be a result of a combination of tissue hypoperfusion, direct immune-mediated damage and mitochondrial dysfunction. Management of ACLF is currently based on the supportive treatment of organ failures, mainly in an intensive care setting. For selected patients, liver transplantation is an effective treatment that offers a good long-term prognosis. Future studies on potential mechanistic treatments that improve patient survival are eagerly awaited.
73 citations
Cites methods from "Complications constitute a major ri..."
...JHEP Reports 2021 by AARC criteria.(21) Almost 80% of patients had complications, including bacterial or fungal infection in 32% of patients, hepatorenal syndrome in 15%, and gastrointestinal haemorrhage in 9%....
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TL;DR: In this article, the authors proposed a very intensive follow-up strategy and identification of low-risk patients for virological/clinical relapse by different biomarkers are the keys to stop the nucleoside analogs (NAs) treatment safely.
Abstract: Chronic hepatitis B virus (HBV) infection is currently incurable. Long-term treatment with potent and safe nucleos(t)ide analogs (NAs) can reduce hepatocellular carcinoma (HCC) and cirrhosis-related complications through profound viral suppression. However, indefinite therapy raises several crucial issues with pros and cons. Because seroclearance of hepatitis B surface (HBsAg) as functional cure is not easily achievable, a finite therapy including sequential 48-week pegylated interferon therapy may provide an opportunity to facilitate HBsAg seroclearance by the rejuvenation of exhausted immune cells. However, the cost of stopping NA is the high incidence of virological relapse and surge of alanine aminotransferase (ALT) levels, which may increase the risk of adverse outcomes (e.g., decompensation, fibrosis progression, HCC, or liver-related mortality). So far, the APASL criteria to stop NA treatment is undetectable HBV DNA levels with normalization of ALT; however, this criterion for cessation of treatment is associated with various incidence rates of virological/clinical relapse and more than 40% of NA-stoppers eventually receive retreatment. A very intensive follow-up strategy and identification of low-risk patients for virological/clinical relapse by different biomarkers are the keys to stop the NA treatment safely. Recent studies suggested that decreasing HBsAg level at the end-of-treatment to < 100–200 IU/mL seems to be a useful marker for deciding when to discontinue NAs therapy. In addition, several viral and host factors have been reviewed for their potential roles in predicting clinical relapse. Finally, the APASL guidance has proposed rules to stop NA and the subsequent follow-up strategy to achieve a better prognosis after stopping NA. In general, for both HBeAg-positive and HBeAg-negative patients who have stopped treatment, these measurements should be done every 1–3 months at the minimum until 12 months.
31 citations
TL;DR: An overview of the diagnostic criteria proposed by different scientific societies and the clinical characteristics of acute-on-chronic liver failure is provided in this article, where established and experimental treatments are also described.
Abstract: Acute-on-chronic liver failure (ACLF) is a syndrome that develops in patients with acutely decompensated chronic liver disease. It is characterised by high 28-day mortality, the presence of one or more organ failures (OFs) and a variable but severe grade of systemic inflammation. Despite the peculiarity of each one, every definition proposed for ACLF recognizes it as a proper clinical entity. In this paper, we provide an overview of the diagnostic criteria proposed by the different scientific societies and the clinical characteristics of the syndrome. Established and experimental treatments are also described. Among the former, the most relevant are directed to support organ failures, treat precipitating factors and carry out early assessment for liver transplantation (LT). Further studies are needed to better clarify pathophysiology of the syndrome and discover new therapies.
8 citations
TL;DR: Based on the COSSH-ACLF criteria, ALSS could better improve the short-term survival of HBV- ACLF patients than SMT alone, especially in those with HBv-AClF grade 1 orHBV-ACF with infection.
Abstract: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is difficult to treat and carries a high risk of short-term mortality. This study aimed to explore the effect of artificial liver support system (ALSS) on the survival of HBV-ACLF patients and to investigate which HBV-ACLF patients may benefit from ALSS treatment. We enrolled 132 patients hospitalized for HBV-ACLF according to the criteria of the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) from 425 ACLF patients who were determined to at least meet the Asian Pacific Association for the Study of the Liver criteria and followed up for 90 days. Overall 132 eligible patients were divided into two groups: standard medical treatment (SMT) group, which included 54 patients who underwent SMT alone, and ALSS group, which included 78 patients who underwent ALSS treatment plus SMT. The proportion of HBV-ACLF grade 1, 2, and 3 was 57.69%, 37.18%, and 5.13% in the ALSS group and 51.85%, 35.19%, and 12.96% in the SMT group, respectively. Bacterial infection was present in 43.6% of patients in the ALSS group and in 55.6% of patients in the SMT group. The mortality rates in the ALSS group at 28 and 90 days were significantly lower than those in the SMT group (23.08% vs. 48.15% and 33.33% vs. 57.41%, P < 0.05). ALSS was an independent factor related to both the 28- and 90-day survival of HBV-ACLF patients. Particularly, a higher cumulative survival rate in either patients with HBV-ACLF grade 1 or those with HBV-ACLF with bacterial infection was observed in the ALSS group. Moreover, ALSS had an independent influence on mortality. Based on the COSSH-ACLF criteria, ALSS could better improve the short-term survival of HBV-ACLF patients than SMT alone, especially in those with HBV-ACLF grade 1 or HBV-ACLF with infection.
8 citations
TL;DR: Evaluating the effectiveness of plasma perfusion combined with plasma exchange in patients with hepatitis B virus-related ACLF found PP’+ PE treatment significantly reversed organ failures and ameliorated the development of new organ failure and complications, thus reducing mortality risk of patients with HBV-ACLF.
Abstract: Artificial liver support systems (ALSS) have been shown to significantly reduce mortality in patients with acute-on-chronic liver failure (ACLF). However, the characteristics of patients who would benefit most from ALSS treatment are poorly understood. This study aimed to delineate the indicators for ALSS and evaluate the effectiveness of plasma perfusion combined with plasma exchange (PP + PE) in patients with hepatitis B virus-related ACLF (HBV-ACLF). A total of 898 patients with HBV-ACLF in a single center were enrolled retrospectively. Propensity score matching (PSM) was used in case-paired analysis. Hepatic or extra-hepatic organ failures were defined by Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) criteria. Complications included ascites, infection, hepatopulmonary syndrome, hepatorenal syndrome, hepatic encephalopathy and upper gastrointestinal bleeding. Numbers of organ failures or complications were used for risk stratification. Among all patients, 418 patients received standard medical therapy (SMT) and 480 received PP + PE plus SMT. After one-to-one paired PSM within the two groups without risk stratification, 293 pairs were enrolled. The PP + PE group displayed significantly lower mortality risk in both 28- and 90-day observation durations. When stratified, patients with two or more organ failures or complications from the PP + PE group showed greater decrease in mortality risk. Moreover, PP + PE treatment significantly increased the resolution of organ failures and complications and ameliorated the development of new organ failures and complications. PP + PE treatment significantly reversed organ failures and ameliorated the development of new organ failures and complications, thus reducing mortality risk of patients with HBV-ACLF.
6 citations
References
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Paris Diderot University1, University of Barcelona2, University of Padua3, Autonomous University of Barcelona4, Université libre de Bruxelles5, University of Paris6, University of Bologna7, University of Cambridge8, University of Turin9, Katholieke Universiteit Leuven10, Goethe University Frankfurt11, University of Bonn12
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