Therapeutic Pipeline in Alcohol-Associated Liver Disease

Thakral, Nimish; Deutsch‐Link, Sasha; Singal, Ashwani K.

doi:10.1055/s-0042-1759614

Cited by 5 publications

(6 citation statements)

References 126 publications

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“…Despite alcohol-related disorders' high prevalence and negative impact, treatment rates among individuals reported to have harmful alcohol consumption are estimated to be below 5%. 22 Increased awareness and education on all levels, including health care providers, social workers, and patients, and counselling services must be estab- with end-stage liver disease. 16 Similarly, several studies from Europe and Australia confirmed a remarkable reduction in in-hospital mortality among patients with cirrhosis before the COVID-19 pandemic.…”

Section: Discussionmentioning

confidence: 99%

“…Our study showed a steady increment in the burden, morbidity and mortality of ALD‐related cirrhosis during the COVID‐19 pandemic. Despite alcohol‐related disorders' high prevalence and negative impact, treatment rates among individuals reported to have harmful alcohol consumption are estimated to be below 5% 22 . Increased awareness and education on all levels, including health care providers, social workers, and patients, and counselling services must be established.…”

Section: Discussionmentioning

confidence: 99%

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Trends in aetiology‐based hospitalisation for cirrhosis before and during the COVID‐19 pandemic in the United States

Kim

Perumpail

Wijarnpreecha

et al. 2023

Aliment Pharmacol Ther

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Summary Background Patients with pre‐existing cirrhosis and COVID‐19 may have a poor prognosis. Aim To evaluate the temporal trends in aetiology‐based hospitalisations and potential predictors of in‐hospital mortality during hospitalisation with cirrhosis before and during the COVID‐19 pandemic. Methods Based on the US National Inpatient Sample 2019–2020, we determined quarterly trends in aetiology‐based hospitalisations with cirrhosis and decompensated cirrhosis, and identified predictors of in‐hospital mortality during hospitalisation with cirrhosis. Results We analysed 316,418 hospitalisations, representing 1,582,090 hospitalisations with cirrhosis. Hospitalisations for cirrhosis increased at a relatively higher rate during the COVID‐19 era. Hospitalisation rates for alcohol‐related liver disease (ALD)‐related cirrhosis increased significantly (quarterly percentage change [QPC]: 3.6%, 95% CI: 2.2%–5.1%), with a notably higher rate during the COVID‐19 era. In contrast, hospitalisation rates for hepatitis C virus (HCV)‐related cirrhosis decreased steadily with a trend of −1.4% of QPC (95% CI: −2.5% to −0.1%). Quarterly trends in the proportion of ALD‐ (QPC: 1.7%, 95% CI: 0.9%–2.6%) and nonalcoholic fatty liver disease‐related (QPC: 0.7%, 95% CI: 0.1%–1.2%) hospitalisations with cirrhosis increased significantly but declined steadily for viral hepatitis. The COVID‐19 era and COVID‐19 infection were independent predictors of in‐hospital mortality during hospitalisation with cirrhosis and decompensated cirrhosis. Compared with HCV‐related cirrhosis, ALD‐related cirrhosis was associated with a 40% higher risk of in‐hospital mortality. Conclusion In‐hospital mortality in cirrhosis was higher in the COVID‐19 era than in the pre‐COVID‐19 era. ALD is the leading aetiology‐specific cause of in‐hospital mortality in cirrhosis with an independent detrimental impact of COVID‐19 infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Trends in aetiology‐based hospitalisation for cirrhosis before and during the COVID‐19 pandemic in the United States

Kim

Perumpail

Wijarnpreecha

et al. 2023

Aliment Pharmacol Ther

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“…proteomic, transcriptomic, epigenomic, metabolomic, and single‐cell sequencing technologies) have yielded deeper insights into the pathogenesis of AH. This could be of great relevance for the development of new targeted treatment approaches and personalized management 7,10,11,25,58 …”

Section: Current Management Approaches Of Ahmentioning

confidence: 99%

“…The mortality rate for patients with moderate AH (MELD 11-20) ranges from 3 to 10% within 3 months from presentation and may increase up to 20% at one year. 7,58 The mortality of patients with severe AH who do not respond to medical treatment is estimated to be 30%-40% at 1-month and can increase up to a 6-month mortality of 70% without transplantation. 11 The long-term prognosis of AH is primarily determined by the occurrence of alcohol relapse.…”

Section: Prognosismentioning

confidence: 99%

Management of alcoholic hepatitis: A clinical perspective

Kasper,

Lang,

Steffen

et al. 2023

Liver International

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Alcohol‐associated liver disease is the primary cause of liver‐related mortality worldwide and one of the most common indications for liver transplantation. Alcoholic hepatitis represents the most acute and severe manifestation of alcohol‐associated liver disease and is characterized by a rapid onset of jaundice with progressive inflammatory liver injury, worsening of portal hypertension, and an increased risk for multiorgan failure in patients with excessive alcohol consumption. Severe alcoholic hepatitis is associated with a poor prognosis and high short‐term mortality. During the COVID‐19 pandemic, rates of alcohol‐associated hepatitis have increased significantly, underscoring that it is a serious and growing health problem. However, adequate management of alcohol‐associated hepatitis and its complications in everyday clinical practice remains a major challenge. Currently, pharmacotherapy is limited to corticosteroids, although these have only a moderate effect on reducing short‐term mortality. In recent years, translational studies deciphering key mechanisms of disease development and progression have led to important advances in the understanding of the pathogenesis of alcoholic hepatitis. Emerging pathophysiology‐based therapeutic approaches include anti‐inflammatory agents, modifications of the gut‐liver axis and intestinal dysbiosis, epigenetic modulation, antioxidants, and drugs targeting liver regeneration. Concurrently, evidence is increasing that early liver transplantation is a safe treatment option with important survival benefits in selected patients with severe alcoholic hepatitis not responding to medical treatment. This narrative review describes current pathophysiology and management concepts of alcoholic hepatitis, provides an update on emerging treatment options, and focuses on the need for holistic and patient‐centred treatment approaches to improve prognosis.

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“…Еще более сложным вопросом является определение показаний к применению гепатопротекторов, выбор конкретного препарата, схемы и продолжительности лечения [4,5]. На фармацевтическом рынке представлено большое количество гепатопротекторов с разными составом, тропностью к печени и механизмами действия.…”

Section: Introductionunclassified

Comparative Evaluation of the Effect of Hepatoprotectors on Oxidative Homeostasis in the Blood of Patients with Alcoholic Hepatitis: A Randomized Experimental Study

Bykov

Ermakova

Popov

et al. 2023

Kuban. nauсh. med. vestnik

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Background. An analysis of published results on the chemical structure, pharmacodynamics and pharmacokinetics of hepatoprotective agents, as well as their practical application, shows that a holistic view on the pharmacology of hepatoprotective agents is yet to be developed. Thus, the relationship between antioxidant activity and the effectiveness of reducing hepatocyte cytolysis remains unclear. Another difficult question concerns indications for the application of hepatoprotectors, selection of a particular drug and treatment duration.Objectives. To investigate the effects of hepatoprotective agents with different mechanisms of action on the indicators of oxidative metabolism in the blood of patients with alcoholic hepatitis.Methods. Four groups of patients were involved in the study. The 1st group consisted of relatively healthy male patients (n = 15). The remaining groups (10 individuals in each) were represented by patients with moderate alcoholic hepatitis. Patients of the 2nd group received remaxol; patients of the 3rd group received ademetionine; patients of the 4th group received ursodeoxycholic acid. Prior to and following treatment, the indicators of cytolysis and oxidative stress in blood were determined. Statistical data processing was carried out using the StatPlus v 7 (AnalystSoft Inc.) software package.Results. According to the observed changes in the cytolytic syndrome marker enzymes, all three hepatoprotectors under study expressed comparable efficacy. After treatment according to any of the applied schemes, the ALT and AST activity in the blood plasma decreased by 56–68% and 75–81%, respectively, compared to their initial values. In comparison with the control group, the total antioxidant activity of the blood plasma decreased by 20–27%; the content of TBA-reactive products in the erythrocyte suspension increased by 61–87%. The remaxol, ademethionine or ursodeoxycholic acid therapy led to a partial normalization of the abovementioned parameters without significant differences between the experimental groups. The concentration of reduced glutathione in the erythrocyte suspension and the content of thiol groups in the blood plasma of patients were reduced in comparison with the control group by 16% and 26%, respectively. After therapy, these indicators also increased by 12–15%, although no predominant effect of either of the studied hepatoprotectors was revealed.Conclusion. The conducted comparative study indicated the absence of a specific antioxidant effect among the pharmacological mechanisms of action of remaxol, ademethionine and ursodeoxycholic acid. In this regard, further research should be carried out to investigate the effect of hepatoprotective drugs on pathobiochemical changes and to analyse a relationship between the antioxidant effect and the efficacy of reducing the level of hepatocyte cytolysis.

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Therapeutic Pipeline in Alcohol-Associated Liver Disease

Cited by 5 publications

References 126 publications

Trends in aetiology‐based hospitalisation for cirrhosis before and during the COVID‐19 pandemic in the United States

Trends in aetiology‐based hospitalisation for cirrhosis before and during the COVID‐19 pandemic in the United States

Management of alcoholic hepatitis: A clinical perspective

Comparative Evaluation of the Effect of Hepatoprotectors on Oxidative Homeostasis in the Blood of Patients with Alcoholic Hepatitis: A Randomized Experimental Study

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