Day-4 Lille Score Is a Good Prognostic Factor and Early Predictor in Assessing Therapy Response in Patients with Liver Cirrhosis and Severe Alcoholic Hepatitis

Foncea, Camelia; Sporea, Ioan; Lupușoru, Raluca; Moga, Tudor; Bende, Felix; Şirli, Roxana; Popescu, Alina

doi:10.3390/jcm10112338

Cited by 18 publications

(18 citation statements)

References 27 publications

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“…To treat sAH, corticosteroids remain the first line of treatment; however, they might not be effective in all patients due to non-response to corticosteroids ( 123 ). Therefore, it is critically important to calculate the efficacy of steroids by Lille score after 4 or 7 days of treatment, which is based on age, total bilirubin levels, baseline creatinine, albumin levels, prothrombin time, and repeat total bilirubin levels ( 124 , 125 ). Based on the Lille scores, patients can be categorized into a full responder, partial responder, and non-responder having a Lille score of ≤0.16, 0.16–0.56, and >0.56, respectively.…”

Section: Strategies For the Management Of Aclfmentioning

confidence: 99%

“…Undoubtedly, the corticosteroid response is lower in patients with ACLF than those without ACLF, and further decreases with ACLF grades ( 126 ), which could be due to the fact that corticosteroids are more effective in patients at the preliver failure stage. Patients who have the Lille score <0.45 designate poor response to corticosteroids and poor survival rate at 6 months ( 125 ). On the other hand, corticosteroid responders get survival benefits, but due to the risk of bacterial infection, careful evaluation considering the risk to benefit ratio should be investigated prior to the introduction of corticosteroids in ACLF and sAH patients.…”

Section: Strategies For the Management Of Aclfmentioning

confidence: 99%

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Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

Khanam

Kottilil

2021

Front. Med.

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Acute-on-chronic liver failure (ACLF) is a multifaceted condition with poor treatment options and high short-term mortality. ACLF can develop in patients with or without liver cirrhosis, where patients with decompensated cirrhosis display a higher risk of short-term mortality. Pathophysiological mechanisms include systemic inflammation due to bacterial and fungal infections and acute hepatic insult with drug, alcohol, and viral hepatitis. Cryptogenic factors also contribute to the development of ACLF. The clinical outcome of patients with ACLF gets further complicated by the occurrence of variceal hemorrhage, hepatorenal syndrome, hepatic encephalopathy, and systemic immune dysfunction. Regardless of the better understanding of pathophysiological mechanisms, no specific and definitive treatment is available except for liver transplantation. The recent approach of regenerative medicine using mesenchymal stem cells (MSCs) could be advantageous for the treatment of ACLF as these cells can downregulate inflammatory response by inducing antiinflammatory events and prevent hepatic damage and fibrosis by inhibiting hepatic stellate cell activation and collagen synthesis. Moreover, MSCs are involved in tissue repair by the process of liver regeneration. Considering the broad therapeutic potential of MSCs, it can serve as an alternative treatment to liver transplant in the near future, if promising results are achieved.

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Section: Strategies For the Management Of Aclfmentioning

confidence: 99%

Section: Strategies For the Management Of Aclfmentioning

confidence: 99%

Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

Khanam

Kottilil

2021

Front. Med.

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“…As a result, we aimed to compare LM performance at day 1 (LM4) to LM performance at day 7 (LM7) as an earlier predictor of corticosteroid therapy response and survival in patients with SAH. The Lille Model (30), which includes a measurement of response to treatment on day 7 of corticosteroid therapy, can be used to assess improvement (3,30). According to the validated cutoff value >0.45, nearly 40% of patients with SAH are classified as non-responders to corticosteroids, which is associated with a 6-month survival rate as low as 25% and necessitates the discontinuation of prednisolone due to lack of therapeutic benefit.…”

Section: Discussionmentioning

confidence: 99%

“…Acute liver failure (ALF) is prevalent in cirrhosis patients, although the symptoms start with systemic inflammation and jaundice. (3,4). Recovery is achieved through natural and reparative methods, such as alcohol withdrawal and supportive and symptomatic care.…”

Section: Introductionmentioning

confidence: 99%

Influence of Pharmacokinetics in Responders and Non-Responders of Prednisolone Based Therapy in Alcoholic Hepatitis Patients

2022

pnr

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Background: Corticosteroids used to reduce short-term mortality in patients affected with severe alcoholic hepatitis. However, there are no independent studies associated with responders and non-responders in terms of the Lille score and pharmacokinetics.Objectives: The study's objective is to compare the Lille score and pharmacokinetics of alcoholic hepatitis patients after the intake of prednisolone drug.Methods: The total number of 24 patients were included out of that 8 patients were excluded due to intestinal bleeding, peptic ulcer and sepsis. Remaining 16 patients were analyzed for biochemical parameters to check alcoholic hepatitis condition.Results: The increase in liver enzyme marker such as AST, ALT, and, ALP and Maddrey discriminant function (MDF) score more than 32 was observed in patients which indicates the severity of alcoholic hepatitis. Later 4 patients were withdrawn from the studies, so that total of 12 patients were investigated for Lille score and pharmacokinetics. We used 7 days of periodic intake of prednisolone drug to identify the treatment effectiveness in alcoholic patients. After the end of 7 days of prednisolone treatment, changes in Lille score was observed among the patients. Based on this Lille score, responders and non-responders are categorized. Further, the pharmacokinetics study for prednisolone responders and non-responders was investigated to determine the differences in Tmax, Cmax, area under the curve (0-24 and (0-∞), and half-life values. The difference in Tmax, Cmax, area under the curve, and half-life values between responders and non-responders was not significant.Conclusion: Our result suggests that prednisolone has an effect on Lille score, despite no changes in pharmacokinetics. Early switching to another drug has no benefit for non-responders to corticosteroids. As a result, the problem of non-responder management remains unsolved in pharmacokinetics studies, and it requires further research in more patients at the molecular level.

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“…Patients without an improvement in the Lille score (>0.45 on day 7) are considered non-responders to GCs, and the GC therapy will be stopped [ 6 ]. A recent study indicates that the Lille score at day 4 can be used to predict the response to GC therapy in patients with sAH [ 14 ]. Although there have been various recent clinical studies regarding GC therapy of sAH, no review dedicated to GC therapy of sAH has been published in the last 5 years.…”

Section: Introductionmentioning

confidence: 99%

Narrative Review: Glucocorticoids in Alcoholic Hepatitis—Benefits, Side Effects, and Mechanisms

Lü

2022

JoX

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Alcoholic hepatitis is a major health and economic burden worldwide. Glucocorticoids (GCs) are the only first-line drugs recommended to treat severe alcoholic hepatitis (sAH), with limited short-term efficacy and significant side effects. In this review, I summarize the major benefits and side effects of GC therapy in sAH and the potential underlying mechanisms. The review of the literature and data mining clearly indicate that the hepatic signaling of glucocorticoid receptor (GR) is markedly impaired in sAH patients. The impaired GR signaling causes hepatic down-regulation of genes essential for gluconeogenesis, lipid catabolism, cytoprotection, and anti-inflammation in sAH patients. The efficacy of GCs in sAH may be compromised by GC resistance and/or GC’s extrahepatic side effects, particularly the side effects of intestinal epithelial GR on gut permeability and inflammation in AH. Prednisolone, a major GC used for sAH, activates both the GR and mineralocorticoid receptor (MR). When GC non-responsiveness occurs in sAH patients, the activation of MR by prednisolone might increase the risk of alcohol abuse, liver fibrosis, and acute kidney injury. To improve the GC therapy of sAH, the effort should be focused on developing the biomarker(s) for GC responsiveness, liver-targeting GR agonists, and strategies to overcome GC non-responsiveness and prevent alcohol relapse in sAH patients.

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Day-4 Lille Score Is a Good Prognostic Factor and Early Predictor in Assessing Therapy Response in Patients with Liver Cirrhosis and Severe Alcoholic Hepatitis

Cited by 18 publications

References 27 publications

Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

Influence of Pharmacokinetics in Responders and Non-Responders of Prednisolone Based Therapy in Alcoholic Hepatitis Patients

Narrative Review: Glucocorticoids in Alcoholic Hepatitis—Benefits, Side Effects, and Mechanisms

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