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Cochrane Database of Systematic Reviews

Glucocorticosteroides para pacientes con hepatitis alcohólica

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Información

DOI:
https://doi.org/10.1002/14651858.CD001511.pub3Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 02 noviembre 2017see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:

  1. Grupo Cochrane de Hepatobiliar

Copyright:
  1. Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

  • Chavdar S Pavlov

    Correspondencia a: The Cochrane Hepato‐Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    [email protected]

    Clinic of Internal Diseases Propedeutics, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

  • Daria L Varganova

    Department of Gastroenterology, Ulyanovsk Regional Clinical Hospital, Ulyanovsk, Russian Federation

  • Giovanni Casazza

    The Cochrane Hepato‐Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università degli Studi di Milano, Milan, Italy

  • Emmanuel Tsochatzis

    Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK

  • Dimitrinka Nikolova

    The Cochrane Hepato‐Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

  • Christian Gluud

    The Cochrane Hepato‐Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

Contributions of authors

CP, DV, and GC: drafted the review.
DN, ET, and CG: revised the review.
CP and DV are the guarantors of the review.
All authors approved the review.

Sources of support

Internal sources

  • The Cochrane Hepato‐Biliary Group Editorial Team Office, Denmark.

External sources

  • No sources of support supplied

Declarations of interest

CP: no financial, academic, or personal conflicts of interest.
DV: no financial, academic, or personal conflicts of interest.
GC: no financial, academic, or personal conflicts of interest.
ET: no financial, academic, or personal conflicts of interest.
DN: no financial, academic, or personal conflicts of interest.
CG: no financial, academic, or personal conflicts of interest.

Acknowledgements

Cochrane Review Group funding acknowledgement: the Danish State is the largest single funder of Cochrane Hepato‐Biliary through its investment in the Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark. Disclaimer: The views and opinions expressed in this review are those of the authors and do not necessarily reflect those of the Danish State or the Copenhagen Trial Unit.

Peer reviewers: Kurinchi S Gurusamy, UK; Michael Ronan Lucey, USA.
Contact editor: Dario Conte, Italy.
Sign‐off editor: Mirella Fraquelli, Italy.

Version history

Published

Title

Stage

Authors

Version

2019 Apr 09

Glucocorticosteroids for people with alcoholic hepatitis

Review

Chavdar S Pavlov, Daria L Varganova, Giovanni Casazza, Emmanuel Tsochatzis, Dimitrinka Nikolova, Christian Gluud

https://doi.org/10.1002/14651858.CD001511.pub4

2017 Nov 02

Glucocorticosteroids for people with alcoholic hepatitis

Review

Chavdar S Pavlov, Daria L Varganova, Giovanni Casazza, Emmanuel Tsochatzis, Dimitrinka Nikolova, Christian Gluud

https://doi.org/10.1002/14651858.CD001511.pub3

2016 Jun 17

Glucocorticosteroids for people with alcoholic hepatitis

Protocol

Chavdar S Pavlov, Emmanuel Tsochatzis, Giovanni Casazza, Dimitrinka Nikolova, Edvard Volcek, Christian Gluud

https://doi.org/10.1002/14651858.CD001511.pub2

1999 Jan 25

Glucocorticosteroids for alcoholic hepatitis

Protocol

Humberto Saconato, Christian Gluud, Erik Christensen, Álvaro N Atallah

https://doi.org/10.1002/14651858.CD001511

Differences between protocol and review

  • Review author team changed.

  • We removed the word 'alcohol' from the outcome "Alcohol liver‐related mortality up to three months follow‐up after end of treatment" as it was superfluous.

  • Outcomes

    • All‐cause mortality is now better defined. Duration of treatment varied across the trials and also mortality data for up to three‐months' follow‐up. This is why we have modified all‐cause mortality to all‐cause mortality at the end of treatment, up to three months' follow‐up after randomisation, and one year following randomisation. Thus, our primary time point has become "all‐cause mortality up to three months' follow‐up after randomisation".

    • Trials also reported data on liver‐related mortality, any complication, and non‐serious adverse events up to three months' follow‐up after randomisation. Thus, three months' follow‐up after randomisation has also become our primary time point for the latter outcomes. However, serious adverse events were reported mostly during the treatment period.

    • Regarding exploratory outcomes, we created tables, as we did not have sufficient data for analysis.

  • As we did not have trials with low risk of bias, we calculated the diversity‐adjusted required information size (DARIS) for our Trial Sequential Analysis using data from all included trials.

  • We calculated and reported the Trial Sequential Analysis‐adjusted CI as a supplement to the naive 95% CI.

  • We changed the risk of type I error from 2.5% (as originally planned based on the three primary outcomes) into type I error of 1%, as we performed Trial Sequential Analysis on all primary and secondary outcomes.

Notes

Cochrane Reviews can be expected to have a high percentage of overlap in the methods section because of standardised methods. In addition, overlap may be observed across two of our protocols as they share at least four common authors.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Adult; Aged; Female; Humans; Male; Middle Aged;

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Study flow diagram
Figuras y tablas -
Figure 1

Study flow diagram

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Risk of bias graph: review authors' judgements about each risk of bias domain presented as percentages across all included studies
Figuras y tablas -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias domain presented as percentages across all included studies

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Risk of bias summary: review authors' judgements about each risk of bias domain for each included study
Figuras y tablas -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias domain for each included study

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All‐cause mortality up to three months after randomisation. Fifteen trials provided data. The diversity‐adjusted required information size (DARIS) was calculated based on all‐cause mortality of 30% in the control group; risk ratio reduction in the glucocorticosteroid group of 20%; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 62%. The required information size was 6734 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines) and did not enter the trial sequential monitoring area for futility (inner‐wedge with red outward sloping lines). The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.
Figuras y tablas -
Figure 4

All‐cause mortality up to three months after randomisation. Fifteen trials provided data. The diversity‐adjusted required information size (DARIS) was calculated based on all‐cause mortality of 30% in the control group; risk ratio reduction in the glucocorticosteroid group of 20%; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 62%. The required information size was 6734 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines) and did not enter the trial sequential monitoring area for futility (inner‐wedge with red outward sloping lines). The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.

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Funnel plot of comparison 1. Glucocorticosteroids versus no intervention/placebo, outcome 1.1 all‐cause mortality
Figuras y tablas -
Figure 5

Funnel plot of comparison 1. Glucocorticosteroids versus no intervention/placebo, outcome 1.1 all‐cause mortality

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All‐cause mortality at the end of treatment (median 28 days (range 3 days to 12 weeks) (post hoc analysis). Fourteen trials provided data. The diversity‐adjusted required information size (DARIS) was calculated based on all‐cause mortality of 22% in the control group; risk ratio reduction in the glucocorticosteroid group of 20%; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 59%. The required information size was 9242 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines) and did not enter the trial sequential monitoring area for futility (inner‐wedge with red outward sloping lines). The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.
Figuras y tablas -
Figure 6

All‐cause mortality at the end of treatment (median 28 days (range 3 days to 12 weeks) (post hoc analysis). Fourteen trials provided data. The diversity‐adjusted required information size (DARIS) was calculated based on all‐cause mortality of 22% in the control group; risk ratio reduction in the glucocorticosteroid group of 20%; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 59%. The required information size was 9242 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines) and did not enter the trial sequential monitoring area for futility (inner‐wedge with red outward sloping lines). The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.

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All‐cause mortality up to 1 year (post hoc analysis). Three trials provided data. The diversity‐adjusted required information size (DARIS) was calculated based on mortality in the control group of 40%; risk ratio reduction of 20% in the glucocorticosteroid group; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 0%. The required information size was 1695 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines). The cumulative Z‐curve crossed the inner‐wedge futility line (red outward sloping lines). The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.
Figuras y tablas -
Figure 7

All‐cause mortality up to 1 year (post hoc analysis). Three trials provided data. The diversity‐adjusted required information size (DARIS) was calculated based on mortality in the control group of 40%; risk ratio reduction of 20% in the glucocorticosteroid group; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 0%. The required information size was 1695 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines). The cumulative Z‐curve crossed the inner‐wedge futility line (red outward sloping lines). The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.

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Serious adverse events during treatment. There are 15 trials providing data. The diversity‐adjusted required information size (DARIS) was calculated based on an incidence rate of serious adverse events in the control group of 36%; risk ratio reduction of 20% in the glucocorticosteroid group; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 70%. The required information size was 6566 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines), but it entered the trial sequential monitoring area for futility (inner‐wedge futility line red outward sloping lines) indicating that sufficient information was provided. The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.
Figuras y tablas -
Figure 8

Serious adverse events during treatment. There are 15 trials providing data. The diversity‐adjusted required information size (DARIS) was calculated based on an incidence rate of serious adverse events in the control group of 36%; risk ratio reduction of 20% in the glucocorticosteroid group; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 70%. The required information size was 6566 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines), but it entered the trial sequential monitoring area for futility (inner‐wedge futility line red outward sloping lines) indicating that sufficient information was provided. The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.

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Liver‐related mortality up to three months after randomisation. Fifteen trials provided data. The diversity‐adjusted required information size (DARIS) was calculated based on liver‐ related mortality of 30% in the control group; risk ratio reduction in the glucocorticosteroid group of 20%; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 68%. The required information size was 8059 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines) and did not enter the trial sequential monitoring area for futility (inner‐wedge with red outward sloping lines). The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.
Figuras y tablas -
Figure 9

Liver‐related mortality up to three months after randomisation. Fifteen trials provided data. The diversity‐adjusted required information size (DARIS) was calculated based on liver‐ related mortality of 30% in the control group; risk ratio reduction in the glucocorticosteroid group of 20%; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 68%. The required information size was 8059 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines) and did not enter the trial sequential monitoring area for futility (inner‐wedge with red outward sloping lines). The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.

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Any complications up to three months after randomisation. Fifteen trials provided data. The diversity‐adjusted required information size (DARIS) was calculated based on any complications of 44% in the control group; risk ratio reduction in the glucocorticosteroid group of 20%; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 75%. The required information size was 5887 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines). The cumulative Z‐curve crossed the inner‐wedge futility line (red outward sloping lines). The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.
Figuras y tablas -
Figure 10

Any complications up to three months after randomisation. Fifteen trials provided data. The diversity‐adjusted required information size (DARIS) was calculated based on any complications of 44% in the control group; risk ratio reduction in the glucocorticosteroid group of 20%; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 75%. The required information size was 5887 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines). The cumulative Z‐curve crossed the inner‐wedge futility line (red outward sloping lines). The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.

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Non‐serious adverse events up to three months after randomisation. Four trials provided data. The diversity‐adjusted required information size (DARIS) was calculated based on non‐serious adverse events of 5% in the control group; risk ratio reduction in the glucocorticosteroid group of 50%; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 0%. The required information size was 2698 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines) and did not enter the trial sequential monitoring area for futility (inner‐wedge with red outward sloping lines). The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.
Figuras y tablas -
Figure 11

Non‐serious adverse events up to three months after randomisation. Four trials provided data. The diversity‐adjusted required information size (DARIS) was calculated based on non‐serious adverse events of 5% in the control group; risk ratio reduction in the glucocorticosteroid group of 50%; type I error of 1%; and type II error of 20% (80% power). Trial diversity was 0%. The required information size was 2698 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines) and did not enter the trial sequential monitoring area for futility (inner‐wedge with red outward sloping lines). The green dotted lines show the conventional boundaries of the naive alpha of 5% equal to Z‐scores of +1.96 and ‐1.96.

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Comparison 1 Glucocorticosteroids versus no intervention/placebo, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 1.1

Comparison 1 Glucocorticosteroids versus no intervention/placebo, Outcome 1 All‐cause mortality.

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Comparison 1 Glucocorticosteroids versus no intervention/placebo, Outcome 2 Health‐related quality of life.
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Analysis 1.2

Comparison 1 Glucocorticosteroids versus no intervention/placebo, Outcome 2 Health‐related quality of life.

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Comparison 1 Glucocorticosteroids versus no intervention/placebo, Outcome 3 Number of participants with serious adverse events during treatment.
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Analysis 1.3

Comparison 1 Glucocorticosteroids versus no intervention/placebo, Outcome 3 Number of participants with serious adverse events during treatment.

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Comparison 1 Glucocorticosteroids versus no intervention/placebo, Outcome 4 Liver‐related mortality.
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Analysis 1.4

Comparison 1 Glucocorticosteroids versus no intervention/placebo, Outcome 4 Liver‐related mortality.

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Comparison 1 Glucocorticosteroids versus no intervention/placebo, Outcome 5 Any complication.
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Analysis 1.5

Comparison 1 Glucocorticosteroids versus no intervention/placebo, Outcome 5 Any complication.

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Comparison 1 Glucocorticosteroids versus no intervention/placebo, Outcome 6 Number of participants with non‐serious adverse events up to 3 months' follow‐up after randomisation.
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Analysis 1.6

Comparison 1 Glucocorticosteroids versus no intervention/placebo, Outcome 6 Number of participants with non‐serious adverse events up to 3 months' follow‐up after randomisation.

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Comparison 2 Subgroup analysis: all‐cause mortality up to 3 months after randomisation, Outcome 1 Severity of alcoholic hepatitis.
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Analysis 2.1

Comparison 2 Subgroup analysis: all‐cause mortality up to 3 months after randomisation, Outcome 1 Severity of alcoholic hepatitis.

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Comparison 2 Subgroup analysis: all‐cause mortality up to 3 months after randomisation, Outcome 2 Glucocorticosteroid (prednisolone) dose.
Figuras y tablas -
Analysis 2.2

Comparison 2 Subgroup analysis: all‐cause mortality up to 3 months after randomisation, Outcome 2 Glucocorticosteroid (prednisolone) dose.

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Comparison 2 Subgroup analysis: all‐cause mortality up to 3 months after randomisation, Outcome 3 Alcoholic hepatitis without cirrhosis and with cirrhosis.
Figuras y tablas -
Analysis 2.3

Comparison 2 Subgroup analysis: all‐cause mortality up to 3 months after randomisation, Outcome 3 Alcoholic hepatitis without cirrhosis and with cirrhosis.

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Comparison 2 Subgroup analysis: all‐cause mortality up to 3 months after randomisation, Outcome 4 Hepatorenal syndrome.
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Analysis 2.4

Comparison 2 Subgroup analysis: all‐cause mortality up to 3 months after randomisation, Outcome 4 Hepatorenal syndrome.

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Comparison 2 Subgroup analysis: all‐cause mortality up to 3 months after randomisation, Outcome 5 Ascites.
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Analysis 2.5

Comparison 2 Subgroup analysis: all‐cause mortality up to 3 months after randomisation, Outcome 5 Ascites.

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Comparison 3 Sensitivity analysis: all‐cause mortality, Outcome 1 Best‐worst scenario all‐cause mortality to 3 months follow‐up.
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Analysis 3.1

Comparison 3 Sensitivity analysis: all‐cause mortality, Outcome 1 Best‐worst scenario all‐cause mortality to 3 months follow‐up.

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Comparison 3 Sensitivity analysis: all‐cause mortality, Outcome 2 Worst‐best scenario all‐cause mortality to 3 months follow‐up.
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Analysis 3.2

Comparison 3 Sensitivity analysis: all‐cause mortality, Outcome 2 Worst‐best scenario all‐cause mortality to 3 months follow‐up.

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Comparison 4 Sensitivity analysis: serious adverse events, Outcome 1 Best‐worse scenario of serious adverse events during treatment.
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Analysis 4.1

Comparison 4 Sensitivity analysis: serious adverse events, Outcome 1 Best‐worse scenario of serious adverse events during treatment.

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Comparison 4 Sensitivity analysis: serious adverse events, Outcome 2 Worst‐best scenario of serious adverse events during treatment.
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Analysis 4.2

Comparison 4 Sensitivity analysis: serious adverse events, Outcome 2 Worst‐best scenario of serious adverse events during treatment.

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Summary of findings for the main comparison. Glucocorticosteroids for people with alcoholic hepatitis

Glucocorticosteroids for people with alcoholic hepatitis

Patient or population: participants with alcoholic hepatitis at high risk of mortality and morbidity

Settings: hospitals and clinics

Intervention: glucocorticosteroids

Comparison: placebo or no intervention

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo or no intervention

Glucocorticosteroids

All‐cause mortality: 3 months following randomisation

298 per 1000

278 per 1000

RR 0.90

(0.70 to 1.15)

1861

(15 RCTs)

⊕⊝⊝⊝1
very low

The Trial Sequential Analysis‐adjusted CI was 0.36 to 2.32

Health‐related quality of life: up to 3 months

(measured withEuropean Quality of Life ‐ 5 Dimensions‐3 Levels (EQ‐ 5D‐3L) scale)

The mean value is 0.592

The mean value is 0.553

MD ‐0.04; (‐0.11 to 0.03)

377

(1 RCT)

⊕⊕⊝⊝2

low

We did not perform Trial Sequential Analysis

Serious adverse events during treatment

361 per 1000

389 per 1000

RR 1.05

(0.85 to

1.29)

1861

(15 RCTs)

⊕⊕⊝⊝3
low

The Trial Sequential Analysis‐adjusted CI was 0.60 to 1.82

Liver‐related mortality: up to 3 months following randomisation

298 per 1000

277 per 1000

RR 0.89

(0.69 to 1.14)

1861

(15 RCTs)

⊕⊕⊝⊝4
low

The Trial Sequential Analysis‐adjusted CI was 0.32 to 2.45

Any complication: up to 3 months following randomisation

443 per 1000

474 per 1000

RR 1.04

(0.86 to 1.27)

1861

(15 RCTs)

⊕⊕⊝⊝5
low

The Trial Sequential Analysis‐adjusted CI was 0.67 to 1.63

Number of participants with non‐serious adverse events: up to 3 months' follow‐up after end of treatment

51 per 1000

120 per 1000

RR 1.99

(0.72 to 5.48)

160

(4 RCTs)

⊕⊝⊝⊝6
very low

The Trial Sequential Analysis‐adjusted CI was 0.01 to 249.60

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High quality: this research provides a very good indication of the likely effect; the likelihood that the effect will be substantially different is low.
Moderate quality: this research provides a good indication of the likely effect; the likelihood that the effect will be substantially different is moderate.
Low quality: this research provides some indication of the likely effect; however, the likelihood that it will be substantially different is high.
Very low quality: this research does not provide a reliable indication of the likely effect; the likelihood that the effect will be substantially different is very high.

1Downgraded 3 levels: 1 level due to within‐study risk of bias (high overall risk of bias in all the trials); 1 level due to inconsistency of the data (there is wide variation in the effect estimates across studies; there is little overlap of confidence intervals associated with the effect estimates; presence of moderate heterogeneity: I² = 45%; heterogeneity could be explained with selection bias); 1 level due to imprecision of effect estimates (the trial sequential analysis showed that additional evidence is needed and that we have not yet reached the required information size).
2Downgraded 2 levels: 1 level due to within‐study risk of bias (high overall risk of bias in the trial); 1 level due to imprecision of effect estimates.
3Downgraded 2 levels: 1 level due to within‐study risk of bias (high overall risk of bias in all the trials); 1 level due to inconsistency of the data (there is wide variation in the effect estimates across studies; there is little overlap of confidence intervals associated with the effect estimates; presence of moderate heterogeneity: I² = 36%; heterogeneity could be explained with selection bias).
4Downgraded 2 levels: 1 level due to within‐study risk of bias (high overall risk of bias in all the trials); 1 level due to inconsistency of the data (there is wide variation in the effect estimates across studies; there is little overlap of confidence intervals associated with the effect estimates; presence of moderate heterogeneity: I² = 46%; heterogeneity could be explained with selection bias).
5Downgraded 2 levels: 1 level due to within‐study risk of bias (high overall risk of bias in all the trials); 1 level due to inconsistency of the data (there is wide variation in the effect estimates across studies; there is little overlap of confidence intervals associated with the effect estimates; presence of moderate heterogeneity: I² = 41%; heterogeneity could be explained with selection bias).
6Downgraded 4 levels: 1 level due to within‐study risk of bias (high overall risk of bias in all the trials); 1 level due to inconsistency of the data (there is little overlap of confidence intervals associated with the effect estimates);1 level due to imprecision of effect estimates (the Trial Sequential Analysis showed that additional evidence is needed and that we have not yet reached the required information size); 1 level due to publication bias (only 4 trials with a small number of participants reported on non‐serious adverse events).

Figuras y tablas -
Summary of findings for the main comparison. Glucocorticosteroids for people with alcoholic hepatitis
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Table 1. Number of participants with most often occurring serious adverse events during treatment

Trial

Gastrointestinal haemorrhage

Hepatorenal syndrome (with or without hepatic failure)

Septicaemia

Hepatocellular carcinoma

Prednisolone

Placebo

Prednisolone

Placebo

Prednisolone

Placebo

Prednisolone

Placebo

Helman 1971

3

Porter 1971

4

2

Campra 1973

3

5

4

Blitzer 1977

3

2

2

2 fungal

1

Mendenhall 1977

Not reported

Maddrey 1978

1

1

3

6

Shumaker 1978

3

3

2

Depew 1980

2

1

2

1

Theodossi 1982

11

6

7

6

Bories 1987

3

3

2

Carithers 1989

2

4

1

Mendenhall 1984

2

Ramond 1992

1

2

1

1

De 2014

2

3

3

3

1
Figuras y tablas -
Table 1. Number of participants with most often occurring serious adverse events during treatment
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Table 2. Most often occurring serious adverse events in Thursz trial. Number of events.

Type of adverse event

Prednisolone group

Placebo group

Gastrointestinal haemorrhage plus

variceal bleeding

40

28

Infections

74

43

‐ lung

38

17

‐ sepsis

14

14
Figuras y tablas -
Table 2. Most often occurring serious adverse events in Thursz trial. Number of events.
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Comparison 1. Glucocorticosteroids versus no intervention/placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

15

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Up to 3 months after randomisation

15

1861

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.70, 1.15]

1.2 At the end of treatment

14

1824

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.66, 1.15]

1.3 At 1 year after randomisation

3

1343

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.91, 1.17]

2 Health‐related quality of life Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

2.1 Up to three months

1

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Up to one year

1

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

3 Number of participants with serious adverse events during treatment Show forest plot

15

1861

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.85, 1.29]

4 Liver‐related mortality Show forest plot

15

1861

Risk Ratio (M‐H, Random, 95% CI)

0.89 [0.69, 1.14]

4.1 Up to 3 months' follow‐up after randomisation

15

1861

Risk Ratio (M‐H, Random, 95% CI)

0.89 [0.69, 1.14]

5 Any complication Show forest plot

15

1861

Risk Ratio (M‐H, Random, 95% CI)

1.04 [0.86, 1.27]

5.1 Number of participants with complications up to 3 months' follow‐up after randomisation

15

1861

Risk Ratio (M‐H, Random, 95% CI)

1.04 [0.86, 1.27]

6 Number of participants with non‐serious adverse events up to 3 months' follow‐up after randomisation Show forest plot

4

160

Risk Ratio (M‐H, Fixed, 95% CI)

1.99 [0.72, 5.48]
Figuras y tablas -
Comparison 1. Glucocorticosteroids versus no intervention/placebo
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Comparison 2. Subgroup analysis: all‐cause mortality up to 3 months after randomisation

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Severity of alcoholic hepatitis Show forest plot

15

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Mild alcoholic hepatitis

4

182

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.58, 1.80]

1.2 Severe alcoholic hepatitis

14

1679

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.73, 1.16]

2 Glucocorticosteroid (prednisolone) dose Show forest plot

15

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 Less than or equal to 40 mg

10

1547

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.50, 1.14]

2.2 More than 40 mg

5

314

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.79, 1.30]

3 Alcoholic hepatitis without cirrhosis and with cirrhosis Show forest plot

15

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

3.1 Alcoholic hepatitis

3

123

Risk Ratio (M‐H, Random, 95% CI)

0.79 [0.18, 3.48]

3.2 Alcoholic hepatitis with cirrhosis

12

1738

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.74, 1.16]

4 Hepatorenal syndrome Show forest plot

10

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4.1 With hepatorenal syndrome

8

1382

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.85, 1.17]

4.2 Without hepatorenal syndrome

2

129

Risk Ratio (M‐H, Random, 95% CI)

0.56 [0.05, 6.49]

5 Ascites Show forest plot

13

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 With ascites

13

729

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.60, 1.12]
Figuras y tablas -
Comparison 2. Subgroup analysis: all‐cause mortality up to 3 months after randomisation
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Comparison 3. Sensitivity analysis: all‐cause mortality

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Best‐worst scenario all‐cause mortality to 3 months follow‐up Show forest plot

15

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Up to 3 months

15

1861

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.64, 1.05]

2 Worst‐best scenario all‐cause mortality to 3 months follow‐up Show forest plot

15

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Up to 3 months

15

1861

Risk Ratio (M‐H, Fixed, 95% CI)

1.21 [1.06, 1.37]
Figuras y tablas -
Comparison 3. Sensitivity analysis: all‐cause mortality
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Comparison 4. Sensitivity analysis: serious adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Best‐worse scenario of serious adverse events during treatment Show forest plot

15

1861

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.83, 1.21]

2 Worst‐best scenario of serious adverse events during treatment Show forest plot

15

1861

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [1.05, 1.31]
Figuras y tablas -
Comparison 4. Sensitivity analysis: serious adverse events
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