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Diagnostic challenges continue to impede development of effective therapies for successful management of alcohol-associated hepatitis (AH), creating an unmet need to identify noninvasive biomarkers for AH. In murine models, complement contributes to ethanol-induced liver injury. Therefore, we hypothesized that complement proteins could be rational diagnostic/prognostic biomarkers in AH. Here, we performed a comparative analysis of data derived from human hepatic and serum proteome to identify and characterize complement protein signatures in severe AH (sAH). The quantity of multiple complement proteins was perturbed in liver and serum proteome of patients with sAH. Multiple complement proteins differentiated patients with sAH from those with alcohol cirrhosis (AC) or alcohol use disorder (AUD) and healthy controls (HCs). Serum collectin 11 and C1q binding protein were strongly associated with sAH and exhibited good discriminatory performance among patients with sAH, AC, or AUD and HCs. Furthermore, complement component receptor 1-like protein was negatively associated with pro-inflammatory cytokines. Additionally, lower serum MBL associated serine protease 1 and coagulation factor II independently predicted 90-day mortality. In summary, meta-analysis of proteomic profiles from liver and circulation revealed complement protein signatures of sAH, highlighting a complex perturbation of complement and identifying potential diagnostic and prognostic biomarkers for patients with sAH.

It is still sometimes difficult to differentiate alcohol-associated hepatitis (AH) from other liver problems. In this edition of AJG, Atkinson et al. showed that keratin-18 (intermediate filament protein) is a promising biomarker for predicting histological severity of AH, defining the type of hepatocyte death (necrosis vs apoptosis), predicting 90-day mortality, and predicting the response to corticosteroid therapy in severe AH. The authors conclude that K18 is diagnostic, prognostic, and may be a theragnostic marker for prednisolone therapy and note that “serum K18 estimation should be adopted into routine clinical practice.” We agree.

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions. Alcohol-associated liver disease is the main cause of liver-related morbidity and mortality globally. This Consensus Statement makes recommendations for the design, best practice and conduct of clinical trials to evaluate the effects of alcohol use in alcohol-associated liver disease and alcohol use disorder.

Abstract Alcohol-associated liver disease (ALD) is a significant global health challenge, encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis, and contributed to 25% of global cirrhosis deaths in 2019. The identification of both modifiable (e.g. heavy drinking, metabolic syndromes) and non-modifiable risk factors (e.g. genetic predispositions) is crucial for effective disease management. Alcohol use assessment and treatment, by using both behavioral therapy and pharmacotherapeutic modalities, nutrition support, and optimization of liver disease modifiers, form the cornerstone of management. Advances in medical therapies, such as fecal microbiota transplantation and novel agents such as IL-22, are being explored for their therapeutic potential. A unifying theme in ALD care is the need for a personalized approach to management, accounting for the spectrum of the disease and individual patient characteristics, to tailor interventions effectively. Finally, it is essential to address the challenges to effective ALD treatment, including socioeconomic, logistical, and stigma-related barriers, to improve patient outcomes. This review discusses the current knowledge on ALD, including epidemiology, pathophysiology, risk factors, and management strategies, highlighting the critical role of integrated care models.

This chapter contains sections titled: Tests for detection of injury to hepatocytes (serum enzyme tests) Tests of the liver's biosynthetic capacity Tests of the liver's capacity to transport organic anions and to metabolize organic compounds Tests used to detect fibrosis in the liver Tests used to detect chronic inflammation or fibrosis in the liver or altered immunoregulation Use of liver function tests Further reading References