Novel MDMs identified in this study proved to accurately detect HCC via plasma testing. Further optimization and clinical testing of this promising approach are indicated. This article is protected by copyright. All rights reserved.

SummaryBackgroundData on liver transplantation (LT) in acute on chronic liver failure (ACLF) are scanty.AimTo perform meta‐analysis on outcomes after LT for ACLF compared with ACLF patients not receiving LT or with LT recipients for indications other than ACLF.MethodsWe pooled data from 12 studies on LT outcomes among ACLF patients.ResultsAmong nine studies, 22 238 LT recipients for ACLF vs 30 791 for non‐ACLF were younger by 1.1 years, less males (64% vs 66.4%), and higher model for end‐stage disease score by 14.5 (14.4‐14.6), P < 0.01 for all. Post‐transplant patient survival at 30 day, 90 day, 6 months, 1 year and 5 years was lower in ACLF: 96.2% vs 98.1%, 92.6% vs 96.2%, 89.9% vs 94.4%, 86.0% vs 91.9%, 66.9% vs 80.7% respectively, P < 0.01 for all. ACLF patients stayed longer in hospital and ICU by 5.7 and 10.5 days respectively, P < 0.001, with similar post‐transplant complications [74.4% vs 55.5%, P = 0.12]. Among three studies, 441 LT recipients for ACLF vs 301 ACLF patients not selected for LT had better 30 day and 1 year survival: 95.2% vs 60% and 85.3% vs 28.2% respectively, P < 0.001. Outcomes were worse in ACLF‐3 and better for ACLF‐1 and ACLF‐2 patients at the time of LT.ConclusionIn this pooled analysis with a large sample size across the globe, LT for select patients with ACLF provided survival benefit. However, larger prospective studies are needed to further refine selection criteria, especially for ACLF‐3 patients as basis for improving outcomes and optimal utilisation of scarce donor pool.

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TE appears reliable in distinguishing different stages of liver fibrosis in children. However, its values vary according to the disease type. For that, a disease-specific estimation of cut-off values for fibrosis staging is worthy.

Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are becoming the leading causes of chronic liver disease worldwide, significantly impacting public health and healthcare cost.The development of fibrosis is the main factor leading to early mortality and morbidity in NAFLD and ALD. Thus, it is important to timely and reliably evaluate these diseases at early stages, when fibrosis is not advanced or when steatosis predominates. Liver biopsy has been the standard of reference for fibrosis and steatosis, however, its invasiveness precludes its widespread use. There is growing research on non-invasive methods for diagnosing and stratifying fibrosis and steatosis in NAFLD and ALD. This review presents clinical evidence on the use of non-invasive assessment of liver disease (blood-based and imaging-based) in patients with NALFD and ALD, and proposes algorithms incorporating these tests into their management.

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In a recent study in signal transduction and targeted therapy, Zhou et al. provided novel experimental data on the role of DNAdependent protein kinase catalytic subunit (DNA-PKcs) in causing abnormalities in the structure and function of mitochondria of hepatocytes, leading to liver injury and alcohol-associated liver disease (ALD). 1 Mitochondria play a crucial role in cellular energy metabolism and in reactive species formation. 2 Several studies in both animal and human models have demonstrated that alcohol intake alters mitochondrial morphology and function by causing impairment of mitochondrial biogenesis, mitochondrial DNA damage, lipid accumulation, oxidative stress, and hepatocellular apoptosis. 2,3 Therefore, identification of the mechanisms through which alcohol induces mitochondrial dysfunction and liver injury is vital for understanding of the pathogenesis of ALD.Mitochondrial fission and mitophagy are important processes for maintaining mitochondrial homeostasis. 4 In a study conducted by the same group, impairment of mitochondrial fission and mitophagy through upregulation of nuclear receptor subfamily 4 group A member 1 (NR4A1) and subsequent activation of the DNA-PKcs/p53 pathway resulted in mitochondrial dysfunction, with reduction in mitochondrial potential, oxidative stress, calcium overload, mitochondrial respiratory collapse, and ATP deficiency. NR4A1 gene encodes the steroid-thyroid hormone-retinoid receptor superfamily, and the encoded protein acts as transcription factor. Genetic deletion of NR4A1 or DNA-PKcs reversed mitochondrial dysfunction and prevented diet-induced nonalcoholic fatty liver disease. 5 The role of NR4A1/DNA-PKcs/P53 pathway in the regulation of mitochondrial fission and mitophagy, however, has not been studied in ALD.In this issue of signal transduction and targeted therapy, Zhou et al. demonstrate the role of DNA-PKcs in the pathogenesis of ALD. In ethanol-fed mice, DNA-PKcs was significantly upregulated and activated in comparison with controls. The activation of DNA-PKcs was associated with the development of severe ALD in wildtype (WT) mice treated with alcohol, with hepatocyte vacuolation, fibrosis, steatosis, increased lipid droplets, and elevation in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and AST/ALT ratio. These findings were absent in liver-specific DNA-PKcs knockout (DNA-PKcsLKO) mice treated with alcohol. In addition, transcription of inflammation/fibrosis markers, such as monocyte chemotactic protein 1, macrophage inflammatory protein 1α, interleukin 8, and increased mitochondrial apoptosisrelated proteins were seen in WT mice treated with alcohol, but not in DNA-PKcs knockout mice treated with alcohol. Other markers for mitochondrial dysfunction, such as oxidative stress, impaired mitochondrial biogenesis, and distorted morphology were also detected in alcohol-treated WT mice but not in DNA-PKcs knockout mice.Alcohol-induced mitochondrial fission characterized by formation of small, round fragmented mitochondria was mediated...

Objectives: Management of alcohol use disorder (AUD) is rarely used in patients with liver disease. We performed a systematic review to examine the impact of AUD management among patients with liver disease. Methods: Twenty studies fulfilling the inclusion and exclusion criteria on 38,329 patients (7072 receiving AUD intervention) with liver disease (15 with liver disease and 6 liver transplant [LT] recipients) were analyzed. One study was common to both groups. Variable follow-up period across studies was weighted for sample size and converting to person-years. Primary outcome was alcohol use, and secondary outcomes were liver decompensation and patient mortality. Results: Abstinence and alcohol relapse rates/person-year with AUD intervention among liver disease patients were 0.41 (0.27-0.55) and 0.42 (0.30-0.755), similar for integrated (colocated liver and addiction clinics) versus concomitant (separate hepatology and addiction clinics) intervention. Compared with standard of care, odds for decompensation with AUD intervention (n = 1), 30-day readmission (n = 1), and patient mortality (n = 2) were lower by 44%, 59%, and 58% respectively. Similar figures were 1.24 (0.86-1.80) for abstinence and 0.52 (0.24-0.14) for relapse. Among LT recipients, odds for alcohol relapse and mortality with follow-up integrated with addiction team versus hepatology alone were 0.48 (0.25-0.72) and 0.29 (0.08-0.99), respectively. Conclusions: Follow-up of LT recipients in an integrated clinic with addiction team is associated with improved outcomes. Simultaneous management of AUD in patients with liver disease improves liver-related outcomes. Large prospective studies are needed to examine benefits of AUD intervention in patients with liver disease.