Prednisolone plus S-adenosil-l-methionine in severe alcoholic hepatitis

Tkachenko, Petr; Maevskaya, M. V.; Pavlov, Alexander; Komkova, Inna; Pavlov, Chavdar S; Vt, Ivashkin

doi:10.1007/s12072-016-9751-4

Cited by 26 publications

(22 citation statements)

References 16 publications

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“…In this regard, administration of an antioxidant cocktail, including vitamin E and NAC, along with nutritional supplements, to patients with AH failed to improve survival in this cohort, whereas Stewart et al, using a similar approach, reported increased short‐term outcome . Interestingly, however, the replenishment of hepatic GSH levels with either NAC or S‐adenosyl‐methionine (SAM) has been shown to increase the efficacy of prednisolone in patients with advanced ALD . Although SAM acts as a GSH precursor, it is a methyl donor and therefore regulates multiple targets in hepatocytes .…”

Section: Antioxidants Therapy: Critical Mitochondrial Antioxidants Bamentioning

confidence: 80%

Mitochondrial Oxidative Stress and Antioxidants Balance in Fatty Liver Disease

2018

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Fatty liver disease is one of the most prevalent forms of chronic liver disease that encompasses both alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) are intermediate stages of ALD and NAFLD, which can progress to more advanced forms, including cirrhosis and hepatocellular carcinoma. Oxidative stress and particularly alterations in mitochondrial function are thought to play a significant role in both ASH and NASH and recognized to contribute to the generation of reactive oxygen species (ROS), as documented in experimental models. Despite the evidence of ROS generation, the therapeutic efficacy of treatment with antioxidants in patients with fatty liver disease has yielded poor results. Although oxidative stress is considered to be the disequilibrium between ROS and antioxidants, there is evidence that a subtle balance among antioxidants, particularly in mitochondria, is necessary to avoid the generation of ROS and hence oxidative stress. Conclusion: As mitochondria are a major source of ROS, the present review summarizes the role of mitochondrial oxidative stress in ASH and NASH and presents emerging data indicating the need to preserve mitochondrial antioxidant balance as a potential approach for the treatment of human fatty liver disease, which may pave the way for the design of future trials to test the therapeutic role of antioxidants in fatty liver disease.

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Section: Antioxidants Therapy: Critical Mitochondrial Antioxidants Bamentioning

confidence: 80%

Mitochondrial Oxidative Stress and Antioxidants Balance in Fatty Liver Disease

2018

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“…Furthermore, the formation of PC is reduced in various chronic liver diseases including intrahepatic cholestasis, cholestasis of pregnancy, and alcoholic liver disease (149)(150)(151). There have been few randomized controlled trials to assess the efficacy of SAMe in chronic liver diseases (152,153), but in studies conducted thus far, SAMe treatment improved pruritus.…”

Section: Perspectivesmentioning

confidence: 99%

Liver inflammation and fibrosis

Koyama¹,

Brenner²

2017

Journal of Clinical Investigation

944

778

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Chronic liver inflammation leads to fibrosis and cirrhosis, which is the 12th leading cause of death in the United States. Hepatocyte steatosis is a component of metabolic syndrome and insulin resistance. Hepatic steatosis may be benign or progress to hepatocyte injury and the initiation of inflammation, which activates immune cells. While Kupffer cells are the resident macrophage in the liver, inflammatory cells such as infiltrating macrophages, T lymphocytes, neutrophils, and DCs all contribute to liver inflammation. The inflammatory cells activate hepatic stellate cells, which are the major source of myofibroblasts in the liver. Here we review the initiation of inflammation in the liver, the liver inflammatory cells, and their crosstalk with myofibroblasts.

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“…Although not statistically significant, the six-month survival rate is 90% in the prednisolone plus SAMe group vs 75% in the prednisolone group. Larger trials are needed to validate the study results[187]. …”

Section: New Therapeutic Optionsmentioning

confidence: 99%

Emerging concepts in alcoholic hepatitis

Fung¹,

Pyrsopoulos²

2017

WJH

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Severe alcoholic hepatitis is implicated as a costly, worldwide public health issue with high morbidity and mortality. The one-month survival for severe alcoholic hepatitis is low with mortality rates high as 30%-50%. Abstinence from alcohol is the recommended first-line treatment. Although corticosteroids remain as the current evidence based option for selected patients with discriminant function > 32, improvement of short-term survival rate may be the only benefit. Identification of individuals with risk factors for the development of severe alcoholic hepatitis may provide insight to the diverse clinical spectrum and prognosis of the disease. The understanding of the complex pathophysiologic processes of alcoholic hepatitis is the key to elucidating new therapeutic treatments. Newer research describes the use of gut microbiota modification, immune modulation, stimulation of liver regeneration, caspase inhibitors, farnesoid X receptors, and the extracorporeal liver assist device to aid in hepatocellular recovery. Liver transplantation can be considered as the last medical option for patients failing conventional medical interventions. Although the preliminary data is promising in patients with low risk of recividism, controversy remains due to organ scarcity. This review article comprehensively summarizes the epidemiology, pathophysiology, risk factors, and prognostic indicators of severe alcoholic hepatitis with a focus on the current and emerging therapeutics.

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Prednisolone plus S-adenosil-l-methionine in severe alcoholic hepatitis

Cited by 26 publications

References 16 publications

Mitochondrial Oxidative Stress and Antioxidants Balance in Fatty Liver Disease

Mitochondrial Oxidative Stress and Antioxidants Balance in Fatty Liver Disease

Liver inflammation and fibrosis

Emerging concepts in alcoholic hepatitis

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