The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.
Regardless of the presence of cirrhosis, patients with CHB, TB ≥12 mg/dL and INR ≥1.5 should be diagnosed with ACLF. The new criteria diagnosed nearly 20% more patients with an HBV aetiology with ACLF, thus increasing their opportunity to receive timely intensive management.
In infants born to hepatitis B surface antigen (HBsAg)-positive mothers, failure after passive-active immunization still occurs. The role of maternal hepatitis B DNA level and other risk factors in this setting remains unclear. This study retrospectively evaluated virologic and other risk factors associated with immunoprophylaxis failure in infants born to HBsAg-positive mothers. Between January 2007 and March 2010, we reviewed the clinical and virologic tests in 869 mother-infant pairs. All infants received the identical passive-active immunization schedule after birth. The failure infants (HBsAg positive at 7-12 months of age) were compared to infants who were HBsAg negative when tested during this time period. Among 869 infants, 27 (3.1%) infants were immunoprophylaxis failures and the other 842 (96.9%) infants remained HBsAg negative. When mothers' pre-delivery HBV DNA levels were stratified to <6, 6-6.99, 7-7.99 and ≥ 8 log(10) copies/mL, the corresponding rates of immunoprophylaxis failure were 0%, 3.2% (3/95), 6.7% (19/282) and 7.6% (5/66), respectively (P < 0.001 for the trend). All failure infants were born to hepatitis B e antigen (HBeAg)-positive mothers. Multivariate logistic regression analysis identified maternal HBV DNA levels [odds ratio (OR) = 1.88, 95% confidence interval (CI): 1.07-3.30] and detectable HBV DNA in the cord blood (OR = 39.67, 95% CI: 14.22-110.64) as independent risk factors for immunoprophylaxis failure. All failure infants were born to HBeAg-positive mothers with HBV DNA levels ≥ 6 log(10) copies/mL. The presence of HBV DNA in cord blood predicted failure to passive-active immunization.
Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.
The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.
Metabolic syndrome (MetS), characterized as obesity, insulin resistance, and non-alcoholic fatty liver diseases (NAFLD), is associated with vitamin D insufficiency/deficiency in epidemiological studies, while the underlying mechanism is poorly addressed. On the other hand, disorder of gut microbiota, namely dysbiosis, is known to cause MetS and NAFLD. It is also known that systemic inflammation blocks insulin signaling pathways, leading to insulin resistance and glucose intolerance, which are the driving force for hepatic steatosis. Vitamin D receptor (VDR) is highly expressed in the ileum of the small intestine, which prompted us to test a hypothesis that vitamin D signaling may determine the enterotype of gut microbiota through regulating the intestinal interface. Here, we demonstrate that high-fat-diet feeding (HFD) is necessary but not sufficient, while additional vitamin D deficiency (VDD) as a second hit is needed, to induce robust insulin resistance and fatty liver. Under the two hits (HFD+VDD), the Paneth cell-specific alpha-defensins including α-defensin 5 (DEFA5), MMP7 which activates the pro-defensins, as well as tight junction genes, and MUC2 are all suppressed in the ileum, resulting in mucosal collapse, increased gut permeability, dysbiosis, endotoxemia, systemic inflammation which underlie insulin resistance and hepatic steatosis. Moreover, under the vitamin D deficient high fat feeding (HFD+VDD), Helicobacter hepaticus, a known murine hepatic-pathogen, is substantially amplified in the ileum, while Akkermansia muciniphila, a beneficial symbiotic, is diminished. Likewise, the VD receptor (VDR) knockout mice exhibit similar phenotypes, showing down regulation of alpha-defensins and MMP7 in the ileum, increased Helicobacter hepaticus and suppressed Akkermansia muciniphila. Remarkably, oral administration of DEFA5 restored eubiosys, showing suppression of Helicobacter hepaticus and increase of Akkermansia muciniphila in association with resolving metabolic disorders and fatty liver in the HFD+VDD mice. An in vitro analysis showed that DEFA5 peptide could directly suppress Helicobacter hepaticus. Thus, the results of this study reveal critical roles of a vitamin D/VDR axis in optimal expression of defensins and tight junction genes in support of intestinal integrity and eubiosis to suppress NAFLD and metabolic disorders.
Aims:Corona virus disease 2019 has rapidly become the most severe public health issue all over the world. Despite respiratory symptoms, hepatic injury has also been observed in clinical settings. This study aimed to investigate the risk factors involved with hepatic injury in the patients with COVID-19.Methods: A total of 85 hospitalized patients who were diagnosed with COVID-19 in Beijing You'an Hospital were retrospectively analyzed. According to liver function, they were divided into ALT normal group (n=52) and ALT elevation group (n=33).Clinical features and laboratory data were compared between the two groups. The independent risk factors for liver injury were analyzed.Results: There were 33 patients with hepatic injury in our study, accounting for 38.8%(33/85). The patients in ALT elevation group were older than those in ALT normal group. The levels of lactic acid, CRP, myoglobin, and neutrophils were significantly higher in ALT elevation group. The lymphocytes and albumin were significantly lower in ALT elevation group. The proportion of severe and critical patients in ALT elevation group was significantly higher. Multivariate logistic regression analysis showed CRP ≥ 20 mg/L and lymphocyte count< 1.1×10^9/L were independently related to hepatic injury. Conclusions:Lymphopenia and CRP may serve as the risk factors related to hepatic injury in patients with COVID-19, which might be related to inflammatory cytokine storm in liver injury. Early detection and timely treatment of hepatic injury in patients with COVID-19 are necessary.
Objective The artificial liver support system (ALSS) is used frequently as a first‐line treatment for hepatitis B virus‐associated acute‐on‐chronic liver failure (HBV‐ACLF). This study aims to compare the therapeutic efficacy of double plasma molecular adsorption system (DPMAS) with sequential half‐dose plasma exchange (PE) (DPMAS+PE) and full‐dose PE in patients with HBV‐ACLF. Methods A total of 131 hospitalized patients who were diagnosed with HBV‐ACLF and underwent DPMAS+PE or PE were retrospectively analyzed. According to the treatment methods used, they were divided into PE group (n = 77) and DPMAS+PE group (n = 54). The main evaluation indexes included the change of liver function and the 28‐days liver transplant‐free survival rates after the different treatments. Results There were no significant differences on severity of illness between PE group and DPMAS+PE group (P > 0.05). The total bilirubin (TBIL) levels immediately after treatment, and at 24 and 72 hours after treatment were markedly decreased in DPMAS+PE group than that in PE group (52.3 ± 9.4% vs 42.3 ± 7.2%, P < 0.05; 24.2 ± 10.0% vs 13.5 ± 13.0%, P < 0.05; 24.8 ± 13.1% vs 14.9 ± 14.9%, P < 0.05; respectively). The 28‐days survival rates was 62.3% and 72.2% in PE and DPMAS+PE groups (P = 0.146). Furthermore, the 28‐days survival rates were significantly higher in DPMAS+PE group than that in PE group (57.4% vs 41.7%, P = 0.043) in the intermediate‐advanced stage patients. Conclusion Compared with PE alone, DPMAS+PE might more effectively improve temporary TBIL in ACLF patients, and improve the 28‐days survival rates in HBV‐ACLF patients with intermediate‐advanced stage. Therefore, DPMAS+PE may be an available ALSS treatment for HBV‐ACLF patients.
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