Alcoholic and Non-Alcoholic Liver Diseases: Promising Molecular Drug Targets and their Clinical Development

2020 ◽  
Vol 17 ◽  
Author(s):  
Komal Thapa ◽  
Ajmer Singh Grewal ◽  
Neha Kanojia ◽  
Lata Rani ◽  
Neelam Sharma ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Liver Diseases ◽  
Drug Targets ◽  
Clinical Investigation ◽  
Treatment Options ◽  
Clinical Status ◽  
Lipid Lowering ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Liver Diseases

Alcoholic and non-alcoholic fatty liver diseases have become a serious concern whole over the world. Both these liver diseases have an identical pathology, starting from simple steatosis to cirrhosis and ultimately to hepatocellular carcinoma. Treatment options for alcoholic liver disease (ALD) are still same as it was 50 years ago which includes corticosteroids, pentoxifylline, antioxidants, nutritional support and abstinence; and for non-alcoholic fatty liver disease (NAFLD) weight loss, insulin sensitizers, lipid lowering agents and anti-oxidants are the only treatment options. Despite of broad research in understanding the disease pathophysiology, limited treatments are available for clinical use. Some therapeutic strategies based on targeting a specific molecule have been developed to lessen the consequences of disease and are under clinical investigation. Therefore, focus on multiple molecular targets will help to develop an efficient therapeutic strategy. This review comprises of brief overview of pathogenesis of ALD and NAFLD; recent molecular drug targets explored for ALD and NAFLD that may prove to be effective for multiple therapeutic regimens and also clinical status of these promising drug targets for liver diseases.

scholarly journals Liquid Biopsy for the Diagnosis of Viral Hepatitis, Fatty Liver Steatosis, and Alcoholic Liver Diseases

2020 ◽  
Vol 21 (10) ◽  
pp. 3732
Author(s):  
Ciniso Sylvester Shabangu ◽  
Jee-Fu Huang ◽  
Hui-Hua Hsiao ◽  
Ming-Lung Yu ◽  
Wan-Long Chuang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Viral Hepatitis ◽  
Liquid Biopsy ◽  
Liver Diseases ◽  
Liver Steatosis ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Liver Diseases

During the progression from hepatitis to fibrosis, cirrhosis, and liver failure, the accumulation of stressed/damaged hepatocyte elements associated with liver inflammation is critical. The causes of hepatocyte injuries include viral hepatitis infections, alcoholic hepatitis, and non-alcoholic fatty liver disease. Hepatocyte-derived extracellular vesicles (Hep-EVs) released from stressed/damaged hepatocytes are partly responsible for liver disease progression and liver damage because they activate non-parenchymal cells and infiltrate inflammatory cells within the liver, which are in turn are an important source of EVs. This cell-to-cell signaling is prevalent during inflammation in many liver diseases. Accordingly, special emphasis should be placed on liquid biopsy methods for the long-term monitoring of chronic liver diseases. In the present review, we have highlighted various aspects of current liquid biopsy research into chronic liver diseases. We have also reviewed recent progress on liquid biopsies that focus on cell-free DNA (cfDNA), long non-coding RNA (lncRNA), and the proteins in EVs as potential diagnostic tools and novel therapeutic targets in patients with viral hepatitis, fatty liver steatosis, and alcoholic liver diseases.

scholarly journals Hypoxia-Inducible Factors as Key Players in the Pathogenesis of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Lorenz M. W. Holzner ◽  
Andrew J. Murray
Keyword(s):  
Transcription Factors ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Treatment Options ◽  
Redox Homeostasis ◽  
Health Concern ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) are a major public health concern with high and increasing global prevalence, and a significant disease burden owing to its progression to more severe forms of liver disease and the associated risk of cardiovascular disease. Treatment options, however, remain scarce, and a better understanding of the pathological and physiological processes involved could enable the development of new therapeutic strategies. One process implicated in the pathology of NAFLD and NASH is cellular oxygen sensing, coordinated largely by the hypoxia-inducible factor (HIF) family of transcription factors. Activation of HIFs has been demonstrated in patients and mouse models of NAFLD and NASH and studies of activation and inhibition of HIFs using pharmacological and genetic tools point toward important roles for these transcription factors in modulating central aspects of the disease. HIFs appear to act in several cell types in the liver to worsen steatosis, inflammation, and fibrosis, but may nevertheless improve insulin sensitivity. Moreover, in liver and other tissues, HIF activation alters mitochondrial respiratory function and metabolism, having an impact on energetic and redox homeostasis. This article aims to provide an overview of current understanding of the roles of HIFs in NAFLD, highlighting areas where further research is needed.

Liver disease

2019 ◽  
pp. 367-384
Author(s):  
Nina Vodošek Hojs ◽  
Aftab Ala ◽  
Debasish Banerjee
Keyword(s):  
Cardiovascular Disease ◽  
Liver Disease ◽  
Hepatitis C ◽  
Fatty Liver ◽  
Viral Hepatitis ◽  
Liver Dysfunction ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Cardiovascular disease in patients with liver disease, previously uncommon, is rising because of an increasing incidence of non-alcoholic fatty liver disease and better survival of patients with viral hepatitis, particularly hepatitis C. Liver dysfunction alters the pharmacokinetics and pharmacodynamics of many drugs, and hence careful use and dose adjustments are necessary. This chapter describes common cardiovascular conditions and the pharmacotherapy in patients with different liver diseases.

scholarly journals Diagnostic Accuracy of Serological Markers in Viral Hepatitis and Non Alcoholic Fatty Liver Disease. A Comparative Study in Tertiary Care Hospital of Western Nepal

1970 ◽  
Vol 1 (2) ◽  
pp. 60-63
Author(s):  
Ankush Mittal ◽  
Brijesh Sathian ◽  
Nishida Chandrasekharan ◽  
Akshay Lekhi ◽  
Shamim Mohammad Farooqui ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Viral Hepatitis ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Serological Markers ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Non Invasive ◽  
Alcoholic Fatty Liver Disease

Background: Liver diseases is apparently increasing and emerging as a major public health problem. Worldwide,  chronic hepatitis B has  become  the tenth leading cause of death  and  persons infected with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV), are about 350 million and  125 million respectively. The aim of current retrospective comparative study was concerned primarily to evaluate the significance of non invasive serological markers for diagnosing liver diseases and their predictive implications in Pokhara valley. Materials and Methods: It was a hospital based retrospective study carried out using the data maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st June 2009 and 31st   October 2010.  The variables collected were total protein, albumin, AST, ALT, total bilirubin, direct bilirubin.  Descriptive statistics and testing of hypothesis were used for the analysis. Data was analyzed using EPI INFO and SPSS 16 software. Results: Of 515 subjects, 120 were suffering from viral hepatitis and 88 had non alcoholic fatty liver disease. In cases of viral hepatitis, mean values of AST (CI 730.65 to 902.68) and ALT (CI 648.14 to 847.59) were markedly increased as compared to controls. Mild to moderate elevations in serum levels of aspartate aminotransferase (CI 43.42 to 49.49), alanine aminotransferase (CI 43.90 to 53.92) were the most common laboratory abnormalities found in patients with nonalcoholic fatty liver disease. Conclusion: Non invasive tests have demonstrated a reasonable ability to identify significant fibrosis, cirrhosis in particular, nor is it surprising that liver disease specialists and patients favour a non invasive approach.Key words: Viral hepatitis; Nonalcoholic fatty liver disease; Nepal.DOI: http://dx.doi.org/10.3126/nje.v1i2.5137 Nepal Journal of Epidemiology 2011;1 (2):60-63

scholarly journals Current and Future Treatments in the Fight against Non-Alcoholic Fatty Liver Disease

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1714 ◽  
Author(s):  
Benoit Smeuninx ◽  
Ebru Boslem ◽  
Mark A. Febbraio
Keyword(s):  
Risk Factor ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Treatment Options ◽  
Critical Factor ◽  
Developed Countries ◽  
Lifestyle Modifications ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Obesity is recognised as a risk factor for many types of cancers, in particular hepatocellular carcinoma (HCC). A critical factor in the development of HCC from non-alcoholic fatty liver disease (NAFLD) is the presence of non-alcoholic steatohepatitis (NASH). Therapies aimed at NASH to reduce the risk of HCC are sparse and largely unsuccessful. Lifestyle modifications such as diet and regular exercise have poor adherence. Moreover, current pharmacological treatments such as pioglitazone and vitamin E have limited effects on fibrosis, a key risk factor in HCC progression. As NAFLD is becoming more prevalent in developed countries due to rising rates of obesity, a need for directed treatment is imperative. Numerous novel therapies including PPAR agonists, anti-fibrotic therapies and agents targeting inflammation, oxidative stress and the gut-liver axis are currently in development, with the aim of targeting key processes in the progression of NASH and HCC. Here, we critically evaluate literature on the aetiology of NAFLD-related HCC, and explore the potential treatment options for NASH and HCC.

scholarly journals Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy

2019 ◽  
Vol 9 (1) ◽  
pp. 15 ◽  
Author(s):  
Giovanni Tarantino ◽  
Vincenzo Citro ◽  
Domenico Capone
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Clinical Investigation ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Complex Interactions ◽  
Diet And Exercise ◽  
Near Future ◽  
Alcoholic Fatty Liver Disease

Focusing on previously published mechanisms of non-alcoholic fatty liver disease (NAFLD), their uncertainty does not always permit a clear elucidation of the grassroot alterations that are at the basis of the wide-spread illness, and thus curing it is still a challenge. There is somehow exceptional progress, but many controversies persist in NAFLD research and clinical investigation. It is likely that hidden mechanisms will be brought to light in the near future. Hereby, the authors present, with some criticism, classical mechanisms that stand at the basis of NAFLD, and consider contextually different emerging processes. Without ascertaining these complex interactions, investigators have a long way left ahead before finding an effective therapy for NAFLD beyond diet and exercise.

scholarly journals Helicobacter pylori infection and fatty liver

2020 ◽  
pp. 146-153
Author(s):  
A. S. Sarsenbaevа ◽  
K. A. Ufimtsev ◽  
E. V. Domracheva
Keyword(s):  
Helicobacter Pylori ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Helicobacter Pylori Infection ◽  
Alcoholic Fatty Liver ◽  
Cancer Of The Stomach ◽  
The Subject ◽  
Alcoholic Fatty Liver Disease

Helicobacter pylori infection is widespread worldwide. It plays a signifi cant role in the pathogenesis of many diseases of the gastrointestinal tract, such as peptic ulcer, atrophic gastritis, and cancer of the stomach. Recently, a large number of works have appeared that indicate the association of Helicobacter pylori infection with extragastric diseases. Liver diseases, and especially fatty liver disease, are also widespread and actively studied. The association between Helicobacter pylori infection and non-alcoholic fatty liver disease has been the subject of many studies, but there is still insufficient evidence to make it clear.

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