Prednisolone or Pentoxifylline for Alcoholic Hepatitis

Thursz, Mark; Richardson, Paul; Allison, Michael; Austin, Andrew; Bowers, Megan; Day, Christopher P.; Downs, Nichola; Gleeson, Dermot; Ala, Aftab; Grant, Allister; Hood, S.; Masson, Steven; McCune, Anne; Mellor, John M.; O’Grady, John; Patch, David; Ratcliffe, Ian; Roderick, Paul; Stanton, Louise; Vergis, Nikhil; Wright, Mark; Ryder, Stephen; Forrest, Ewan

doi:10.1056/nejmoa1412278

Cited by 649 publications

(713 citation statements)

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“…The only difference between the two cohorts was related to the period of enrollment; patients in the first cohort were enrolled during 2013, and those of the validation cohort were enrolled in 2014 and 2015. The response to steroid in our population of SAH was slightly higher with fewer NRs compared to Western countries (35%) 4, 29. The reasons for these differences between countries are unclear but may involve differences in genetic and environmental factors between Indian and Western patients that contribute to differences in the response to corticosteroids.…”

Section: Discussionmentioning

confidence: 64%

Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome

Maras

Das

Sharma

et al. 2018

Hepatology Communications

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Severe alcoholic hepatitis (SAH) has a high mortality rate, and corticosteroid therapy is effective in 60% patients. This study aimed to investigate a baseline metabolic phenotype that could help stratify patients not likely to respond to steroid therapy and to have an unfavorable outcome. Baseline urine metabolome was studied in patients with SAH using ultra‐high performance liquid chromatography and high‐resolution mass spectrometry. Patients were categorized as responders (Rs, n = 52) and nonresponders (NRs, n = 8) at day 7 according to the Lille score. Multivariate projection analysis identified metabolites in the discovery cohort (n = 60) and assessed these in a validation cohort of 80 patients (60 Rs, 20 NRs). A total of 212 features were annotated by using metabolomic/biochemical/spectral databases for metabolite identification. After a stringent selection procedure, a total of nine urinary metabolites linked to mitochondrial functions significantly discriminated nonresponders, most importantly by increased acetyl‐L‐carnitine (12‐fold), octanoylcarnitine (4‐fold), decanoylcarnitine (4‐fold), and alpha‐ketoglutaric acid (2‐fold) levels. Additionally, urinary acetyl‐L‐carnitine and 3‐hydroxysebasic acid discriminated nonsurvivors (P < 0.01). These urinary metabolites significantly correlated to severity indices and mortality (r > 0.3; P < 0.01) and were associated with nonresponse (odds ratio >3.0; P < 0.001). In the validation cohort, baseline urinary acetyl‐L‐carnitine documented an area under the receiver operating curve of 0.96 (0.85‐0.99) for nonresponse prediction and a hazard ratio of 3.5 (1.5‐8.3) for the prediction of mortality in patients with SAH. Acetyl‐L‐carnitine at a level of >2,500 ng/mL reliably segregated survivors from nonsurvivors (P < 0.01, log‐rank test) in our study cohort. Conclusion: Urinary metabolome signatures related to mitochondrial functions can predict pretherapy steroid response and disease outcome in patients with SAH. (Hepatology Communications 2018;2:628‐643)

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Section: Discussionmentioning

confidence: 64%

Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome

Maras

Das

Sharma

et al. 2018

Hepatology Communications

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“…The STOPAH investigators found that while prednisolone was associated with a non-significant reduction in mortality, neither steroid (14% treatment vs. 18% non-treatment, P = 0.06) nor pentoxifylline (16% treatment vs. 16% non-treatment, P = 0.69) were effective in reducing 28-day mortality. 13 Long-term survival was unaffected by treatment as no differences in mortality between treatment groups were noted at 90-day or 1-year follow-up. 13 While not without its limitations, such as lack of liver biopsy diagnosis confirmation and appreciably lower mortality rates than previous trials, STOPAH is the largest, most comprehensive piece of AH literature currently available.…”

Section: Discussionmentioning

confidence: 90%

Pharmacologic Treatment of Alcoholic Hepatitis: Examining Outcomes Based on Disease Severity Stratification

Owens

Snyder

Twilla

2016

Journal of Clinical and Experimental Hepatology

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Objectives: Maddrey discriminant function (MDF) score is a measure of disease prognosis in alcoholic hepatitis (AH) used to identify patients at highest risk of mortality and determine the need for initiation of pharmacologic treatment. The purpose of this study was to evaluate the effects of pharmacologic therapy for hospitalized AH patients as stratified by MDF score. Methods: A retrospective review of patients with an AH diagnosis admitted to a Methodist LeBonheur Healthcare adult hospital between 06/2009 and 06/2014 was conducted. Patients !18 years of age with an ICD-9 code for AH were evaluated. Results: Of the 493 patients screened, 234 met the inclusion criteria, comprised of 62 patients with an MDF ! 32 (treatment, n = 42 vs. no treatment, n = 20) and 172 patients with an MDF < 32 (treatment, n = 15 vs. no treatment, n = 157). For the patients with an MDF ! 32, there was no statistically significant difference between the treatment group vs. non-treatment group regarding 28-day mortality (31% vs. 11%, respectively; P = 0.18) and 6-month mortality (45% treatment vs. 38% non-treatment; P = 0.75). For the patients with an MDF <32, there was no statistically significant difference between the treatment group vs. non-treatment group regarding 28-day mortality (0% vs. 7%, respectively; P > 0.99) and 6-month mortality (11% treatment vs. 13% non-treatment; P > 0.99). There was no difference in incidence of acute kidney injury, hepatorenal syndrome, development of infection or hepatic encephalopathy between the treatment vs. non-treatment groups. Conclusions: Pharmacologic treatment showed no survival benefit, regardless of disease severity. Given the mortality risk seen in mild-moderate AH patients not receiving treatment and concern for a possible treatment ceiling effect in severe AH patients, more data are needed to adequately assess the utility of MDF in selecting appropriate candidates for AH treatment. ( J CLIN EXP HEPATOL 2016;6:275-281)

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“…In its severe form, AH can result in 20-50 % mortality at 3 months. The only available therapies that improve survival are corticosteroids and liver transplantation [5,6]. The efficacy of pentoxifylline is debatable, based on recent large clinical trials [6].…”

mentioning

confidence: 99%

“…The only available therapies that improve survival are corticosteroids and liver transplantation [5,6]. The efficacy of pentoxifylline is debatable, based on recent large clinical trials [6]. The efficacy of prednisolone has been shown in meta-analyses of individual data and was partially confirmed in the recent STOPAH trial [6,7].…”

mentioning

confidence: 99%

“…The efficacy of pentoxifylline is debatable, based on recent large clinical trials [6]. The efficacy of prednisolone has been shown in meta-analyses of individual data and was partially confirmed in the recent STOPAH trial [6,7]. Unfortunately, many patients do not respond to prednisolone and performing salvage liver transplantation is not feasible in most centers.…”

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confidence: 99%

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Alcoholic hepatitis: should we combine old drugs for better results?

Cabezas

Bataller

2016

Hepatol Int

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Alcoholic liver disease (ALD) is the main cause of cirrhosis worldwide [1]. Despite its high prevalence, ALD has received little attention in the liver community and there is a clear lack of programs for early detection and novel targeted therapies for advanced forms. ALD encloses a wide spectrum of features, ranging from simple steatosis, steatohepatitis, and cirrhosis to hepatocellular carcinoma [2]. Patients with underlying ALD and heavy alcohol intake can develop an episode of alcoholic hepatitis (AH), the most severe form of ALD [3]. AH is characterized by an abrupt onset of jaundice and/or liver decompensation. Patients with AH often show signs of systemic inflammation at admission, and are prone to infections and kidney injury, which can lead to multi-organ dysfunction within a few days [4]. In its severe form, AH can result in 20-50 % mortality at 3 months. The only available therapies that improve survival are corticosteroids and liver transplantation [5,6]. The efficacy of pentoxifylline is debatable, based on recent large clinical trials [6]. The efficacy of prednisolone has been shown in meta-analyses of individual data and was partially confirmed in the recent STOPAH trial [6,7]. Unfortunately, many patients do not respond to prednisolone and performing salvage liver transplantation is not feasible in most centers. Therefore, there is an urgent need to provide these patients with novel targeted therapies. In the last two decades, there have been several attempts to test old and novel drugs in patients with severe AH, ranging from classic drugs [8] to monoclonal antibodies [9] or stimulating factors [10]

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Prednisolone or Pentoxifylline for Alcoholic Hepatitis

Cited by 649 publications

References 22 publications

Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome

Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome

Pharmacologic Treatment of Alcoholic Hepatitis: Examining Outcomes Based on Disease Severity Stratification

Alcoholic hepatitis: should we combine old drugs for better results?

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