Original Article/Liver
Progress in hepatitis B virus-related acute-on-chronic liver failure treatment in China: A large, multicenter, retrospective cohort study using a propensity score matching analysis

https://doi.org/10.1016/j.hbpd.2021.05.010Get rights and content

Abstract

Background

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) has a high short-term mortality. However, the treatment progression for HBV-ACLF in China in the past decade has not been well characterized. The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.

Methods

This study retrospectively compared short-term (28/56 days) survival rates of two different nationwide cohorts (cohort I: 2008-2011 and cohort II: 2012-2015). Eligible HBV-ACLF patients were enrolled retrospectively. Patients in the cohorts I and II were assigned either to the standard medical therapy (SMT) group (cohort I-SMT, cohort II-SMT) or artificial liver support system (ALSS) group (cohort I-ALSS, cohort II-ALSS). Propensity score matching analysis was conducted to eliminate baseline differences, and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.

Results

Short-term (28/56 days) survival rates were significantly higher in the ALSS group than those in the SMT group (P < 0.05) and were higher in the cohort II than those in the cohort I (P < 0.001). After propensity score matching, short-term (28/56 days) survival rates were higher in the cohort II than those in the cohort I for both SMT (60.7% vs. 53.0%, 50.0% vs. 39.8%, P < 0.05) and ALSS (66.1% vs. 56.5%, 53.0% vs. 44.4%, P < 0.05) treatments. The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments (P = 0.046). Multivariate logistic regression analysis revealed that ALSS (OR = 0.962, 95% CI: 0.951-0.973, P = 0.038), nucleos(t)ide analogs (OR = 0.927, 95% CI: 0.871-0.983, P = 0.046), old age (OR = 1.028, 95% CI: 1.015-1.041, P < 0.001), total bilirubin (OR = 1.002, 95% CI: 1.001-1.003, P = 0.004), INR (OR = 1.569, 95% CI: 1.044-2.358, P < 0.001), COSSH-ACLF grade (OR = 2.683, 95% CI: 1.792-4.017, P < 0.001), and albumin (OR = 0.952, 95% CI: 0.924-0.982, P = 0.002) were independent factors for 28-day mortality.

Conclusions

The treatment for patients with HBV-ACLF has improved in the past decade.

Introduction

Hepatitis B virus (HBV) infection is a global public health threat that causes considerable liver-related morbidity and mortality [1]. In China, 78 million people are currently estimated to be infected with the HBV; of these, 28 million have active hepatitis and account for nearly one-third of all chronic infections worldwide [2,3]. HBV-related acute hepatitis and the reactivation of HBV are the leading causes of liver failure in Asia [4]. HBV-related acute-on-chronic liver failure (HBV-ACLF) is a common syndrome with high mortality in the Asia-Pacific and African regions [5]. HBV-ACLF is most commonly caused by acute and severe exacerbation of chronic hepatitis B (CHB) [6], which is in contrast to Western countries where drugs, alcohol, and hepatitis C are the major causes of liver failure [7].

The mortality is extremely high (30% to 70%) in patients with ACLF unless patients promptly receive liver transplantation (LT). However, LT is often not available due to the shortage of donors [8]. The treatment of ACLF has been improving with an aim of increasing the survival or maintaining the condition of the patient until a donor is available. Over the past few decades, a variety of artificial liver support systems (ALSSs), including the molecular adsorbent recirculating system (MARS), Prometheus, and other methods, have been employed to treat liver failure [9], [10], [11], [12]. MARS [13,14] and Prometheus [9] are the most widely used in countries outside of China. The plasma exchange (PE)-based ALSS is widely used in China, which innovatively uses plasma separators with an aperture of approximately 1/10 (membrane pore size = 0.03 micron) of that of a normal plasma separator for direct PE. This can remove toxic substances effectively in patients with liver failure, retain important plasma components, and reduce plasma dosage [15].

The attitudes towards nucleos(t)ide analogs are controversial. Some studies have reported that nucleos(t)ide analogs were not able to generate an obvious biochemical effect or slow down the progression of liver failure in patients with HBV-ACLF [16,17]. However, several studies have noted that nucleos(t)ide analogs effectively improved the status of patients with severe decompensated chronic liver disease and HBV-related liver failure [18], [19], [20], [21]. More evidence-based data are still needed to come to a consensus.

Treatment progression for HBV-ACLF in China in the past decade has not been well characterized. In this study, we assessed two different nationwide cohorts (from 2012 to 2015 and 2008 to 2011) to examine whether the treatment for HBV-ACLF has significantly improved during the past decade.

Section snippets

Study design

The present investigation was a multicenter, nationwide, retrospective cohort study. Between September 2008 and February 2011, we screened 1592 adults with HBV-ACLF at 10 Liver Disease Research Centers in China and enrolled patients in the cohort I. The patients in the cohort II were enrolled between December 2012 and March 2015 from 11 Liver Disease Research Centers. The patients in the cohorts I and II were assigned to the standard medical therapy (SMT) group (cohort I-SMT and cohort II-SMT)

Description of cohorts I and II

In the cohort I, 1226 patients with HBV-ACLF were enrolled; 533 (43.5%) and 693 (56.5%) of them received SMT and ALSS treatments, respectively. In the cohort II, 747 patients were enrolled; 410 (54.9%) and 337 (45.1%) of them received SMT and ALSS treatments, respectively (Fig. 1). The MELD score and COSSH-ACLF grade were not significantly different between the two cohorts (P = 0.801, P = 0.766, respectively; Table S1). The study revealed that the short-term (28/56 days) survival rates were

Discussion

HBV-ACLF is a complex syndrome that develops in patients with CHB. Patients with HBV-ACLF have specific clinical characteristics, including high short-term (28/90 days) mortality, high prevalence of liver and coagulation failure, and low prevalence of renal failure [23], [24], [25], which differ markedly from those of patients with non-HBV-related liver failure in the European Association for the Study of the Liver (EASL) and AASLD studies [23,24]. In this study, we explored the short-term

Acknowledgments

The authors thank Shao-Jie Xin, Zhi-Liang Gao, Zhong-Ping Duan, Tao Han, Yu-Ming Wang, Jian-He Gan, Chen Pan, Yong-Ping Chen, Qing Xie, Shu-Mei Lin for data collection.

CRediT authorship contribution statement

Lan-Lan Xiao: Formal analysis, Methodology, Writing - original draft. Xiao-Xin Wu: Formal analysis, Writing - original draft. Jia-Jia Chen: Data curation, Investigation, Project administration. Dong Yan: Data curation, Investigation, Project administration. Dong-Yan Shi: Data curation, Investigation, Project administration.

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