Alcoholic Hepatitis: Lost in Translation

Woolbright, Benjamin L.; Jaeschke, Hartmut

doi:10.14218/jcth.2017.00054

Cited by 10 publications

(12 citation statements)

References 99 publications

(142 reference statements)

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“…An overwhelming number of patients with excessive alcohol consumption and alcoholic hepatitis present with marked fibrosis 18 . In alcoholic liver disease, the fibrogenic response in the liver after the uptake of alcohol is driven by acetaldehyde.…”

Section: Pathogenesis Of Hepatic Fibrosismentioning

confidence: 99%

Recent advances in understanding liver fibrosis: bridging basic science and individualized treatment concepts

Weiskirchen

Tacke

2018

F1000Res

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Hepatic fibrosis is characterized by the formation and deposition of excess fibrous connective tissue, leading to progressive architectural tissue remodeling. Irrespective of the underlying noxious trigger, tissue damage induces an inflammatory response involving the local vascular system and the immune system and a systemic mobilization of endocrine and neurological mediators, ultimately leading to the activation of matrix-producing cell populations. Genetic disorders, chronic viral infection, alcohol abuse, autoimmune attacks, metabolic disorders, cholestasis, alterations in bile acid composition or concentration, venous obstruction, and parasite infections are well-established factors that predispose one to hepatic fibrosis. In addition, excess fat and other lipotoxic mediators provoking endoplasmic reticulum stress, alteration of mitochondrial function, oxidative stress, and modifications in the microbiota are associated with non-alcoholic fatty liver disease and, subsequently, the initiation and progression of hepatic fibrosis. Multidisciplinary panels of experts have developed practice guidelines, including recommendations of preferred therapeutic approaches to a specific cause of hepatic disease, stage of fibrosis, or occurring co-morbidities associated with ongoing loss of hepatic function. Here, we summarize the factors leading to liver fibrosis and the current concepts in anti-fibrotic therapies.

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Section: Pathogenesis Of Hepatic Fibrosismentioning

confidence: 99%

Recent advances in understanding liver fibrosis: bridging basic science and individualized treatment concepts

Weiskirchen

Tacke

2018

F1000Res

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“…In patients with underlying alcoholic cirrhosis, it can present as acute-on-chronic liver failure (ACLF), with very poor prognosis and high mortality in the absence of best medical standard of care or liver transplantation. 1,2 Recommended treatment options for AH, even though beneficial in select patients in the short term, are not without risksuch as sepsis and multiorgan failure with corticosteroid use, rapidly progressive extrahepatic organ failures and high risk of alcohol relapse that foretell poor outcomes with liver transplantation. 3,4 In regions entrenched in complementary and alternative medicine (CAM) medical practices, such as India, the use of alternative systems of medicines, such as Ayurveda, Siddha, Homeopathy, Unani and proprietary herbal drugs for management of acute as well as chronic liver diseases, is on the rise.…”

Section: Introductionmentioning

confidence: 99%

Outcomes and Toxicology of Herbal Drugs in Alcoholic Hepatitis – A Single Center Experience from India

Philips¹,

Rajesh²,

George³

et al. 2019

Journal of Clinical and Translational Hepatology

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Background and Aims: We aimed to study clinical outcomes and liver biopsy features of alcoholic hepatitis (AH) patients on complementary and alternative medicines (CAMs) and to analyze the retrieved drugs for chemical and toxic components linked to drug-induced liver injury. Methods: We retrospectively assessed clinical, biochemical and liver biopsy features of AH patients on CAM with drug-induced liver injury (AH-CAM, n = 27) and compared them to a control group (classical AH, n = 29) on standard of care. Patients without liver biopsy evaluation and other causes for liver disease were excluded. Samples of the CAMs (n = 42) from patients were retrieved and assessed for chemical and toxins. Results: All were males, and significantly worse clinical presentation, biochemical severity, and liver disease scores were notable in patients with AH-CAM. Traditional Ayurvedic-polyherbal formulations were the most commonly used CAM. On liver histology, varying grades of severe-necrosis, severe hepatocellular, canalicular, cholangiolar cholestasis with predominant lymphocytic-portal-inflammation and varying grades of interface-hepatitis were noted in AH-CAM. Analysis of CAMs revealed presence of heavy metals up to 100,000 times above detectable range and adulterants, such as antibiotics, chemotherapy agents, nonsteroidal anti-inflammatory drugs, alcohols, antidepressants, anxiolytics, and recreational drugs. On follow up, a significantly higher number of patients with AH on CAM died at end of 1, 3-and-6-months compared to controls (37% vs. 83%, 29% vs. 62%, 18% vs. 52% respectively; p < 0.001). Conclusions: Patients with AH and CAM-related druginduced liver injury have extremely poor short-term survival in the absence of liver transplantation compared to those patients with AH on evidence-based management. Early transplant referral and educating on and curbing of CAM use in severe liver disease through strict monitoring of unregulated traditional health practices can help ease the burden of liver-related death.

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“…These observations largely mirror previous data found in alcoholic hepatitis patients by our own group (5). Further studies are necessary in this area in large, multi-institutional cohorts to validate the potential for cK18-to-K18 ratio or the individual values alone to predict mortality (7). Multiple studies have now confirmed increases in K18 and cK18 in AH patients (5,6).…”

mentioning

confidence: 99%

“…Previous work from our laboratory has noted that K18 levels can increase to as much as 30,000 U/L in the absence of increases in ALT in alcoholic hepatitis (5). As such, while K18 is likely a very good biomarker of liver injury in multiple models, K18 elevations in ACLF patients, especially those with alcoholic hepatitis, may be related to factors other than just cell death (5,7). This hypothesis is further supported by the terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay (3,5).…”

mentioning

confidence: 99%

“…Given this information, it is difficult to discern the exact modality of cell death, or whether there are other mechanisms at play. It remains a possibility that a portion of cK18 and K18 is derived from other tissues, or potentially, is released from the liver through mechanisms other than traditional cell death (7). There is a need for studies that can delineate where cK18 and K18 arise from in some diseases with systemic inflammation and multi-organ dysfunction.…”

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confidence: 99%

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