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Journal of Clinical and Experimental... 2023Alcoholic hepatitis is a clinical syndrome with or without pre-existing chronic liver disease (CLD), and the majority of patients present with acute-on-chronic liver...
Alcoholic hepatitis is a clinical syndrome with or without pre-existing chronic liver disease (CLD), and the majority of patients present with acute-on-chronic liver failure (ACLF) having a high 28-day mortality. The treatment of alcoholic hepatitis is suboptimal with corticosteroid having one 1month survival benefit but not translated to a survival benefit beyond six months. Survival benefit has been observed in only about 50-60% of treated patients. Long-term survival depends on underlying liver function and abstinence from alcohol. Relapse is reported in nearly half of the patients who recover from alcoholic hepatitis and even up to 17% after liver transplant. The data on repeated episodes of severe alcoholic hepatitis due to relapse and response to therapy are largely unknown. Here, we report a case of alcoholic hepatitis on three occasions in a period of 2 years follow-up and each time treated with steroids and had complete clinical recovery.
PubMed: 37440953
DOI: 10.1016/j.jceh.2022.12.017 -
Liver International : Official Journal... Mar 2020
Topics: Ethanol; Hepatitis, Alcoholic; Humans; Prognosis; Recurrence
PubMed: 32124541
DOI: 10.1111/liv.14343 -
Annals of Hepatology 2024Alcohol is the leading cause of preventable liver morbidity and mortality worldwide, as it is also the most frequent cause of advanced liver disease. Alcohol-associated... (Review)
Review
Alcohol is the leading cause of preventable liver morbidity and mortality worldwide, as it is also the most frequent cause of advanced liver disease. Alcohol-associated liver disease (ALD) covers different phenotypes ranging from steatosis to the development of inflammation (steatohepatitis), fibrosis and ultimately, in a proportion of patients, the development of liver cirrhosis and its associated complications. ALD has a complex pathogenesis that includes the interplay of both genetic and environmental factors, yet the precise mechanisms are largely unknown. Alcohol-associated hepatitis (AH) is a severe clinical presentation of ALD, which is characterized by abrupt jaundice and clinical decompensations of liver disease. AH occurs in a percentage of patients with underlying ALD and active alcohol consumption. Currently, there are no approved targeted therapies able to interfere in the pathogenesis of ALD and halt the progression of the disease, therefore alcohol abstinence is the most effective measure to improve prognosis in this patient population. In this regard, alcohol cessation remains the first-line treatment in all stages of alcohol disease. In patients with advanced ALD nonresponding to medical therapy, liver transplantation is the only approach that improves prognosis, and it should be considered in patients with decompensated cirrhosis. In the last years, AH has emerged as a new indication of early liver transplantation in non-responders to medical therapy, with promising results in highly selected patients. In this review, we provide an update on the epidemiology, risk factors, natural history, diagnosis, pathogenesis, and current treatments for ALD, taking into account the importance of assessing and managing alcohol consumption as the etiological factor and the main driver of prognosis in patients with ALD.
Topics: Humans; Liver Diseases, Alcoholic; Hepatitis, Alcoholic; Risk Factors; Liver; Alcohol Drinking; Fatty Liver; Ethanol
PubMed: 37832648
DOI: 10.1016/j.aohep.2023.101162 -
World Journal of Hepatology Jul 2020Alcohol consumption is one of the leading causes of the global burden of disease and results in high healthcare and economic costs. Heavy alcohol misuse leads to... (Review)
Review
Alcohol consumption is one of the leading causes of the global burden of disease and results in high healthcare and economic costs. Heavy alcohol misuse leads to alcohol-related liver disease, which is responsible for a significant proportion of alcohol-attributable deaths globally. Other than reducing alcohol consumption, there are currently no effective treatments for alcohol-related liver disease. Oxidative stress refers to an imbalance in the production and elimination of reactive oxygen species and antioxidants. It plays important roles in several aspects of alcohol-related liver disease pathogenesis. Here, we review how chronic alcohol use results in oxidative stress through increased metabolism the cytochrome P450 2E1 system producing reactive oxygen species, acetaldehyde and protein and DNA adducts. These trigger inflammatory signaling pathways within the liver leading to expression of pro-inflammatory mediators causing hepatocyte apoptosis and necrosis. Reactive oxygen species exposure also results in mitochondrial stress within hepatocytes causing structural and functional dysregulation of mitochondria and upregulating apoptotic signaling. There is also evidence that oxidative stress as well as the direct effect of alcohol influences epigenetic regulation. Increased global histone methylation and acetylation and specific histone acetylation inhibits antioxidant responses and promotes expression of key pro-inflammatory genes. This review highlights aspects of the role of oxidative stress in disease pathogenesis that warrant further study including mitochondrial stress and epigenetic regulation. Improved understanding of these processes may identify novel targets for therapy.
PubMed: 32821333
DOI: 10.4254/wjh.v12.i7.332 -
Clinical and Molecular Hepatology Oct 2020Alcohol-associated liver disease (ALD), which ranges from mild disease to alcohol-associated hepatitis and cirrhosis, is the most prevalent type of chronic liver disease... (Review)
Review
Alcohol-associated liver disease (ALD), which ranges from mild disease to alcohol-associated hepatitis and cirrhosis, is the most prevalent type of chronic liver disease and a leading cause of morbidity and mortality worldwide. Accumulating evidence reveals that programmed cell death (PCD) plays a crucial role in progression of ALD involving crosstalk between hepatocytes and immune cells. Multiple pathways of PCD, including apoptosis, necroptosis, autophagy, pyroptosis and ferroptosis, are reported in ALD. Interestingly, PCD pathways are intimately linked and interdependent, making it difficult to therapeutically target a single pathway. This review clarifies the multiple types of PCD occurring in liver and focuses on crosstalk between hepatocytes and innate immune cells in ALD.
Topics: Apoptosis; Autophagy; Hepatitis, Alcoholic; Humans; Liver Diseases, Alcoholic; Pyroptosis
PubMed: 32951412
DOI: 10.3350/cmh.2020.0142 -
Frontiers in Immunology 2022Hepatocellular carcinoma(HCC) is the sixth most common cancer in the world and is usually caused by viral hepatitis (HBV and HCV), alcoholic, and non-alcoholic fatty... (Review)
Review
Hepatocellular carcinoma(HCC) is the sixth most common cancer in the world and is usually caused by viral hepatitis (HBV and HCV), alcoholic, and non-alcoholic fatty liver disease(NAFLD). Viral hepatitis accounts for 80% of HCC cases worldwide. In addition, With the increasing incidence of metabolic diseases, NAFLD is now the most common liver disease and a major risk factor for HCC in most developed countries. This review mainly described the specificity and similarity between the pathogenesis of viral hepatitis(HBV and HCV)-induced HCC and NAFLD-induced HCC. In general, viral hepatitis promotes HCC development mainly through specific encoded viral proteins. HBV can also exert its tumor-promoting mechanism by integrating into the host chromosome, while HCV cannot. Viral hepatitis-related HCC and NASH-related HCC differ in terms of genetic factors, and epigenetic modifications (DNA methylation, histone modifications, and microRNA effects). In addition, both of them can lead to HCC progression through abnormal lipid metabolism, persistent inflammatory response, immune and intestinal microbiome dysregulation.
Topics: Carcinoma, Hepatocellular; Hepatitis C; Hepatitis, Viral, Human; Humans; Liver Neoplasms; MicroRNAs; Non-alcoholic Fatty Liver Disease; Viral Proteins
PubMed: 36189208
DOI: 10.3389/fimmu.2022.984728 -
Medicina (Kaunas, Lithuania) Feb 2024Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional... (Review)
Review
Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients' management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Transplantation; Cholangiocarcinoma; Bile Ducts, Intrahepatic; Bile Duct Neoplasms
PubMed: 38541138
DOI: 10.3390/medicina60030412 -
Seminars in Liver Disease Feb 2020Severe alcoholic hepatitis (SAH) is a condition characterized by jaundice and liver failure that develops after heavy and prolonged alcohol consumption. Infection... (Review)
Review
Severe alcoholic hepatitis (SAH) is a condition characterized by jaundice and liver failure that develops after heavy and prolonged alcohol consumption. Infection frequently complicates the natural history of the disease and is independently associated with mortality. Objective recognition and recording of infection are therefore essential in the evaluation of therapeutic interventions and for antibiotic stewardship. This review will evaluate infections that complicate SAH at admission and beyond. Factors that associate with the development of infection will be identified and clinical and laboratory techniques available to identify infection will be discussed. Common pathogens and frequently used antibiotics will be reviewed and recommendations will be made for the management of infection for SAH patients. New techniques to assess infection earlier and more precisely may improve diagnosis and treatment of this important driver of mortality in SAH.
Topics: Anti-Infective Agents; Antimicrobial Stewardship; Drug Resistance, Multiple; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Hepatitis, Alcoholic; Humans; Mycoses
PubMed: 31370067
DOI: 10.1055/s-0039-1693402 -
Experimental and Therapeutic Medicine May 2022Inflammatory liver diseases are, nowadays, multifactorial and wide-spread, thus having an important socio-economic impact. Although the therapeutic algorithms are... (Review)
Review
Inflammatory liver diseases are, nowadays, multifactorial and wide-spread, thus having an important socio-economic impact. Although the therapeutic algorithms are well-known in hepatitis, regardless of etiology, strategies to identify inflammatory hepatic lesions in early stages and to develop new epigenetic therapies should be prioritized. The main entities of inflammatory liver disease are: alcoholic and non-alcoholic fatty liver disease, autoimmune hepatitis, viral hepatitis and Wilson disease. The main epigenetic processes include: DNA methylation/demethylation, which imply changes in DNA tertiary structure; post-translational histone covalent changes (methylation/demethylation, acetylation/deacetylation, ubiquitination), that cause DNA-histone instability; synthesis of small, non-coding RNA molecules, called microRNAs, that modulate translational potential of transcripts (mRNAs) and post-translational modification of polypeptide chains. Consequently, the epigenetic interactions aforementioned, play an important modulatory role in disease progression and response to conventional therapies The present review focused on the main epigenetic changes in inflammatory liver conditions, considering a new perspective: Epigenetic therapy. This approach is more than welcomed, taking into consideration that conventional therapeutic strategies are almost exhausted.
PubMed: 35481220
DOI: 10.3892/etm.2022.11293 -
World Journal of Gastroenterology Sep 2021The global social, economic and political crises related to coronavirus disease 2019 (COVID-19) presumably had more indirect than direct negative impacts on health... (Review)
Review
The global social, economic and political crises related to coronavirus disease 2019 (COVID-19) presumably had more indirect than direct negative impacts on health systems. Drastic lifestyle changes, social isolation and distancing, and individual and global financial crises resulted in robust populations forfeiting healthy habits and seeking comfort in alcoholic beverages, drugs and unhealthy diets. The inevitable consequences are increases in the incidence of nonalcoholic fatty liver disease, viral hepatitis, acute alcoholic hepatitis, liver cirrhosis decompensation and ultimately liver-related mortality. The inaccessibility of regular clinical and sonographic monitoring systems has caused difficulties in the treatment of patients with chronic liver disease (CLD) and has prevented prompt hepatocellular carcinoma detection and treatment. A dramatic reduction in the number of liver donors and the transformation of numerous transplantation centers into COVID-19 units drastically decreased the rate of orthotopic liver transplantation. The indirect, unavoidable effects of the COVID-19 pandemic in the following years have yet to be determined. Substantial efforts in the management of patients with liver disease in order to overcome the inevitable COVID-19-related morbidity and mortality that will follow have yet to be initiated. Several questions regarding the impact of the COVID-19 pandemic on liver disease remain. The most important question for general CLD patients is: How will the modification of clinical practice during this pandemic affect the outcomes of CLD patients? This article reviews the influence of COVID-19 on patients with liver disease during the pandemic, with particular emphasis on the disease course associated with pandemic resolution.
Topics: COVID-19; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Pandemics; SARS-CoV-2
PubMed: 34629818
DOI: 10.3748/wjg.v27.i36.6039