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Review
. 2017 Mar 31;3(3):CD011646.
doi: 10.1002/14651858.CD011646.pub2.

Pharmacological interventions for alcoholic liver disease (alcohol-related liver disease): an attempted network meta-analysis

Elena Buzzetti  1 , Maria Kalafateli  1 , Douglas Thorburn  1 , Brian R Davidson  2 , Maja Thiele  3 , Lise Lotte Gluud  4 , Cinzia Del Giovane  5 , Gro Askgaard  6 , Aleksander Krag  7 , Emmanuel Tsochatzis  1 , Kurinchi Selvan Gurusamy  2
Affiliations
Review

Pharmacological interventions for alcoholic liver disease (alcohol-related liver disease): an attempted network meta-analysis

Elena Buzzetti et al. Cochrane Database Syst Rev. .

Abstract

Background: Alcohol-related liver disease is due to excessive alcohol consumption. It includes a spectrum of liver diseases such as alcohol-related fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Mortality associated with alcoholic hepatitis is high. The optimal pharmacological treatment of alcoholic hepatitis and other alcohol-related liver disease remains controversial.

Objectives: To assess the comparative benefits and harms of different pharmacological interventions in the management of alcohol-related liver disease through a network meta-analysis and to generate rankings of the available pharmacological interventions according to their safety and efficacy in order to identify potential treatments. However, even in the subgroup of participants when the potential effect modifiers appeared reasonably similar across comparisons, there was evidence of inconsistency by one or more methods of assessment of inconsistency. Therefore, we did not report the results of the network meta-analysis and reported the comparative benefits and harms of different interventions using standard Cochrane methodology.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform and randomised controlled trials registers until February 2017 to identify randomised clinical trials on pharmacological treatments for alcohol-related liver diseases.

Selection criteria: Randomised clinical trials (irrespective of language, blinding, or publication status) including participants with alcohol-related liver disease. We excluded trials that included participants who had previously undergone liver transplantation and those with co-existing chronic viral diseases. We considered any of the various pharmacological interventions compared with each other or with placebo or no intervention.

Data collection and analysis: Two review authors independently identified trials and independently extracted data. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CIs) using both fixed-effect and random-effects models based on available-participant analysis with Review Manager. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE.

Main results: We identified a total of 81 randomised clinical trials. All the trials were at high risk of bias, and the overall quality of the evidence was low or very low for all outcomes. Alcoholic hepatitisFifty randomised clinical trials included 4484 participants with alcoholic hepatitis. The period of follow-up ranged from one to 12 months. Because of concerns about transitivity assumption, we did not perform the network meta-analysis. None of the active interventions showed any improvement in any of the clinical outcomes reported in the trials, which includes mortality (at various time points), cirrhosis, decompensated cirrhosis, liver transplantation. None of the trials reported health-related quality of life or incidence of hepatocellular carcinoma. Severe alcoholic hepatitisOf the trials on alcoholic hepatitis, 19 trials (2545 participants) included exclusively participants with severe alcoholic hepatitis (Maddrey Discriminat Function > 32). The period of follow-up ranged from one to 12 months. There was no alteration in the conclusions when only people with severe alcoholic hepatitis were included in the analysis.

Source of funding: Eleven trials were funded by parties with vested interest in the results. Sixteen trials were funded by parties without vested interest in the results. The source of funding was not reported in 23 trials. Other alcohol-related liver diseasesThirty-one randomised clinical trials included 3695 participants with other alcohol-related liver diseases (with a wide spectrum of alcohol-related liver diseases). The period of follow-up ranged from one to 48 months. The mortality at maximal follow-up was lower in the propylthiouracil group versus the no intervention group (OR 0.45, 95% CI 0.26 to 0.78; 423 participants; 2 trials; low-quality evidence). However, this result is based on two small trials at high risk of bias and further confirmation in larger trials of low risk of bias is necessary to recommend propylthiouracil routinely in people with other alcohol-related liver diseases. The mortality at maximal follow-up was higher in the ursodeoxycholic acid group versus the no intervention group (OR 2.09, 95% CI 1.12 to 3.90; 226 participants; 1 trial; low-quality evidence).

Source of funding: Twelve trials were funded by parties with vested interest in the results. Three trials were funded by parties without vested interest in the results. The source of funding was not reported in 16 trials.

Authors' conclusions: Because of very low-quality evidence, there is uncertainty in the effectiveness of any pharmacological intervention versus no intervention in people with alcoholic hepatitis or severe alcoholic hepatitis. Based on low-quality evidence, propylthiouracil may decrease mortality in people with other alcohol-related liver diseases. However, these results must be confirmed by adequately powered trials with low risk of bias before propylthiouracil can be considered effective.Future randomised clinical trials should be conducted with approximately 200 participants in each group and follow-up of one to two years in order to compare the benefits and harms of different treatments in people with alcoholic hepatitis. Randomised clinical trials should include health-related quality of life and report serious adverse events separately from adverse events. Future randomised clinical trials should have a low risk of bias and low risk of random errors.

PubMed Disclaimer

Conflict of interest statement

This report is independent research funded by the National Institute for Health Research (NIHR Cochrane Programme Grants, 13/89/03 ‐ Evidence‐based diagnosis and management of upper digestive, hepato‐biliary, and pancreatic disorders). The views expressed in this publication are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR, or the Department of Health.

Kurinchi Gurusamy, Emmanuel Tsochatzis, and Brian Davidson have no financial disclosures.

Astellas funded Douglas Thorburn for his attendance at the International Liver Transplantation Society meeting in 2014. Douglas Thorburn has also received GBP 25,000 from Boston Scientific to fund a clinical research fellow in 2013. There are no other financial disclosures to report.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included trials.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
4
4
Trial Sequential Analysis of mortality at maximal follow‐up (alcoholic hepatitis): glucocorticosteroids versus no intervention and pentoxifylline versus no intervention. Based on an alpha error of 2.5%, power of 90% (beta error of 10%), a relative risk reduction (RRR) of 20%, a control group proportion observed in the trials (Pc = 34.8%), and diversity observed in the analyses (78% and 56%), the accrued sample size (1147 participants for glucocorticosteroids versus no intervention and 881 participants for pentoxifylline versus no intervention) was lower than the diversity‐adjusted required information size (DARIS) (10,187 participants for glucocorticosteroids versus no intervention and 5232 participants for pentoxifylline versus no intervention). The Z‐curve (blue line) crosses the conventional boundaries (dotted green lines) favouring glucocorticosteroids and pentoxifylline for the two comparisons, but does not cross the conventional boundaries after the large trial (Thursz 2015). The Z‐curve does not cross any of trial sequential monitoring boundaries (dotted red lines). This indicates that there is a high risk of random errors in both these comparisons.
5
5
Trial Sequential Analysis of mortality at maximal follow‐up (alcoholic hepatitis): colchicine versus no intervention and insulin plus glucagon versus no intervention. Based on an alpha error of 2.5%, power of 90% (beta error of 10%), a relative risk reduction (RRR) of 20%, a control group proportion observed in the trials (Pc = 34.8%), and diversity observed in the analyses (0% and 52%), the accrued sample size (139 participants for colchicine versus no intervention and 265 participants for insulin plus glucagon versus no intervention) was lower than the diversity‐adjusted required information size (DARIS) (2205 participants for colchicine versus no intervention and 4579 participants for insulin plus glucagon versus no intervention). The Z‐curve (blue line) does not cross the conventional boundaries (dotted green lines) or the trial sequential monitoring boundaries (dotted red lines). This indicates that there is a high risk of random errors in both these comparisons.
6
6
Trial Sequential Analysis of mortality at maximal follow‐up (alcoholic hepatitis): propylthiouracil versus no intervention. Based on an alpha error of 2.5%, power of 90% (beta error of 10%), a relative risk reduction (RRR) of 20%, a control group proportion observed in the trials (Pc = 34.8%), and diversity observed in the analyses (0%), the accrued sample size (108 participants) was only a small proportion of the diversity‐adjusted required information size (DARIS) (2205 participants); therefore, the trial sequential monitoring boundaries were not drawn.The Z‐curve (blue line) does not cross the conventional boundaries (dotted green lines). This indicates that there is a high risk of random errors in this comparison.
7
7
Trial Sequential Analysis of mortality at maximal follow‐up (severe alcoholic hepatitis): glucocorticosteroids versus no intervention and pentoxifylline versus no intervention. Based on an alpha error of 2.5%, power of 90% (beta error of 10%), a relative risk reduction (RRR) of 20%, a control group proportion observed in the trials (Pc = 40.9%), and diversity observed in the analyses (98% and 76%), the accrued sample size (607 participants for glucocorticosteroids versus no intervention and 726 participants for pentoxifylline versus no intervention) was lower than the diversity‐adjusted required information size (DARIS) (72,755 participants for glucocorticosteroids versus no intervention and 7148 participants for pentoxifylline versus no intervention). For glucocorticosteroids versus no intervention, the accrued sample size was so small that the trial sequential monitoring boundaries were not drawn. The Z‐curve (blue line) crosses the conventional boundaries (dotted green lines) favouring glucocorticosteroids and pentoxifylline for the two comparisons, but does not cross the conventional boundaries after the large trial (Thursz 2015). The Z‐curve does not cross any of trial sequential monitoring boundaries (dotted red lines) for pentoxifylline versus no intervention. This indicates that there is a high risk of random errors in both these comparisons.
8
8
Trial Sequential Analysis of mortality at maximal follow‐up (alcohol‐related disorders (others)): anabolic steroids versus no intervention and antioxidants versus no intervention. Based on an alpha error of 2.5%, power of 90% (beta error of 10%), a relative risk reduction (RRR) of 20%, a control group proportion observed in the trials (Pc = 25.2%), and diversity observed in the analyses (0% in the both the comparisons), the accrued sample size (248 participants for anabolic steroids versus no intervention and 255 participants for antioxidants versus no intervention) was lower than the diversity‐adjusted required information size (DARIS) (3428 participants for both comparisons). The Z‐curve (blue line) does not cross the conventional boundaries (dotted green lines) or the trial sequential monitoring boundaries (dotted red lines). This indicates that there is a high risk of random errors in both these comparisons.
9
9
Trial Sequential Analysis of mortality at maximal follow‐up (alcohol‐related disorders (others)): colchicine versus no intervention and propylthiouracil versus no intervention. Based on an alpha error of 2.5%, power of 90% (beta error of 10%), a relative risk reduction (RRR) of 20%, a control group proportion observed in the trials (Pc = 25.2%), and diversity observed in the analyses (44% and 0%), the accrued sample size (604 participants for colchicine versus no intervention and 423 participants for propylthiouracil versus no intervention) was lower than the diversity‐adjusted required information size (DARIS) (6071 participants for colchicine versus no intervention and 3428 participants for propylthiouracil versus no intervention). For the comparison of colchicine versus no intervention, the Z‐curve (blue line) does not cross the conventional boundaries (dotted green lines) or the trial sequential monitoring boundaries (dotted red lines). For the comparison, propylthiouracil versus no intervention, the Z‐curve crosses the conventional boundaries while it does not cross the trial sequential monitoring boundaries. This indicates that there is a high risk of random errors in both these comparisons.
10
10
The network plots showing the comparisons in there were at least two trials. The size of the node (circle) provides a measure of the number of trials in which the particular intervention was included as one of the arms. The thickness of the line provides a measure of the number of direct comparisons between two nodes (interventions). Five outcomes (mortality at maximal follow‐up, 30‐days mortality, 90‐days mortality, decompensated cirrhosis, and adverse events (number) have intervention comparisons in which direct and indirect estimates were available ('closed loops').
 Legend: _ = plus; AntiTNF = anti‐TNF (tumour necrosis factor); Control = No active intervention; GSF = granulocyte stimulating factor; NAC = N‐acetyl cysteine; SAMe = S‐adenosyl methionine.
11
11
IF (Inconsistency Factor) plots of mortality at maximal follow‐up in which direct and indirect estimates were available. There appears to be inconsistency as the confidence intervals do not overlap 1 for the following loops: no intervention ‐ glucocorticosteroids ‐ pentoxifylline plus glucocorticosteroids (confidence intervals: 0.00 to 0.14) and glucocorticosteroids ‐ pentoxifylline plus glucocorticosteroids ‐ pentoxifylline (0.00 to 0.78).
12
12
Forest plot of mortality at maximal follow‐up (network meta‐analysis estimates and direct comparisons when available): Both fixed‐effect model and random‐effects model for other interventions compared to no intervention are provided. The direct estimates and network meta‐analysis estimates are similar. Based on the network meta‐analysis, it appears that GSF plus pentoxifylline, glucocorticosteroids plus metadoxine, and pentoxifylline plus metadoxine decrease mortality at maximal follow‐up compared with no intervention. Abbreviations: GSF = granulocyte stimulating factor; TNF = tumour necrosis factor; SAMe = S‐adenosyl methionine.
13
13
The top figure shows the surface area under the curve constructed on the basis of the ranking probabilities. The bottom figure shows the probability of each intervention being best, second best, third best, and so on. None of the interventions seems to be clearly better than others, although GSF plus pentoxifylline appears to be one of the top‐ranking interventions.
 
 Legend: 1: No active intervention; 2: Glucocorticosteroids; 3: Glucocorticosteroids plus anti‐TNF; 4: Glucocorticosteroids plus metadoxine; 5: Glucocorticosteroids plus N‐acetyl cysteine; 6: Glucocorticosteroids plus pentoxifylline; 7: Glucocorticosteroids plus SAMe; 8: GSF plus pentoxifylline; 9: N‐acetyl cysteine; 10: Pentoxifylline; 11: Pentoxifylline plus metadoxine. Abbreviations: GSF = granulocyte stimulating factor; TNF = tumour necrosis factor; SAMe = S‐adenosyl methionine.
14
14
IF (Inconsistency Factor) plots of 30‐days mortality in which direct and indirect estimates were available. There appears to be inconsistency for the loop 'no intervention ‐ glucocorticosteroids ‐ pentoxifylline plus glucocorticosteroids' as the confidence intervals do not overlap 1 (confidence intervals: 0.00 to 0.37).
15
15
Forest plot of 30‐days mortality (network meta‐analysis estimates and direct comparisons when available): Both fixed‐effect model and random‐effects model for other interventions compared to no intervention are provided. The direct estimates and network meta‐analysis estimates are similar. Based on the network meta‐analysis, it appears that glucocorticosteroids plus N‐acetyl cysteine and glucocorticosteroids plus metadoxine decrease 30‐days compared with no intervention. Abbreviations: TNF = tumour necrosis factor; SAMe = S‐adenosyl methionine.
16
16
The top figure shows the surface area under the curve constructed on the basis of the ranking probabilities. The bottom figure shows the probability of each intervention being best, second best, third best, and so on. None of the interventions seems to be clearly better than others, although glucocorticosteroids plus SAMe, glucocorticosteroids plus metadoxine, and glucocorticosteroids plus N‐acetyl cysteine appear to be the top‐ranking interventions.
 
 Legend: 1: No active intervention; 2: Glucocorticosteroids; 3: Glucocorticosteroids plus anti‐TNF; 4: Glucocorticosteroids plus metadoxine; 5: Glucocorticosteroids plus N‐acetyl cysteine; 6: Glucocorticosteroids plus pentoxifylline; 7: Glucocorticosteroids plus SAMe; 8: N‐acetyl cysteine; 9: Pentoxifylline; 10: Pentoxifylline plus metadoxine. Abbreviations: TNF = tumour necrosis factor; SAMe = S‐adenosyl methionine.
17
17
IF (Inconsistency Factor) plots of 90‐days mortality in which direct and indirect estimates were available. There appears to be no evidence of inconsistency in any of the loops as the confidence intervals of all the loops overlap 1.
18
18
Forest plot of 90‐days mortality (network meta‐analysis estimates and direct comparisons when available): Both fixed‐effect model and random‐effects model for other interventions compared to no intervention are provided. The direct estimates and network meta‐analysis estimates appear different. Based on the random‐effects network meta‐analysis and direct comparison, there is no evidence of differences between any of the comparisons. Abbreviations: GSF = granulocyte stimulating factor; TNF = tumour necrosis factor.
19
19
The top figure shows the surface area under the curve constructed on the basis of the ranking probabilities. The bottom figure shows the probability of each intervention being best, second best, third best, and so on. GSF plus pentoxifylline appears to be the top‐ranking intervention. Legend: 1: No active intervention; 2: Glucocorticosteroids; 3: Glucocorticosteroids plus anti‐TNF; 4: Glucocorticosteroids plus metadoxine; 5: Glucocorticosteroids plus N‐acetyl cysteine; 6: Glucocorticosteroids plus pentoxifylline; 7: GSF plus pentoxifylline; 8: Pentoxifylline; 9: Pentoxifylline plus metadoxine. Abbreviations: GSF = granulocyte stimulating factor; TNF = tumour necrosis factor.
20
20
Forest plot of liver transplantation (network meta‐analysis estimates and direct comparisons when available): Both fixed‐effect model and random‐effects model for other interventions compared to glucocorticosteroids are provided. Since there was only one trial for each comparison, random‐effects model is not applicable for direct comparisons. The direct estimates and network meta‐analysis estimates appear similar. There is no evidence of differences between any of the comparisons. Abbreviations: TNF = tumour necrosis factor.
21
21
The top figure shows the surface area under the curve constructed on the basis of the ranking probabilities. The bottom figure shows the probability of each intervention being best, second best, third best, and so on. Glucocorticosteroids plus pentoxifylline appears to be the top‐ranking intervention. Legend: 1: Glucocorticosteroids; 2: Glucocorticosteroids plus N‐acetyl cysteine; 3: Glucocorticosteroids plus pentoxifylline
22
22
IF (Inconsistency Factor) plots of decompensated cirrhosis in which direct and indirect estimates were available. There appears to be inconsistency in several loops as the confidence intervals do not overlap 1. The loops in which the confidence intervals do not overlap 1 are: no intervention ‐ glucocorticosteroids ‐ pentoxifylline plus glucocorticosteroids (confidence intervals: 0.32 to 0.88), glucocorticosteroids ‐ pentoxifylline ‐ metadoxine plus pentoxifylline (0.00 to 0.16), and glucocorticosteroids ‐ metadoxine plus glucocorticosteroids ‐ pentoxifylline (0.00 to 0.17).
23
23
Forest plot of decompensated cirrhosis (network meta‐analysis estimates and direct comparisons when available): Both fixed‐effect model and random‐effects model for other interventions compared to no intervention are provided. The direct estimates and network meta‐analysis estimates appear similar. Glucocorticosteroids plus metadoxine appears to have a lower decompensated cirrhosis rate than no intervention. There was no evidence of any differences in any other interventions versus no intervention in the random‐effects model. Abbreviations: TNF = tumour necrosis factor.
24
24
The top figure shows the surface area under the curve constructed on the basis of the ranking probabilities. The bottom figure shows the probability of each intervention being best, second best, third best, and so on. Glucocorticosteroids plus metadoxine appears to be the top‐ranking intervention. Legend: 1: No active intervention; 2: Glucocorticosteroids; 3: Glucocorticosteroids plus anti‐TNF; 4: Glucocorticosteroids plus metadoxine; 5: Glucocorticosteroids plus N‐acetyl cysteine; 6: Glucocorticosteroids plus pentoxifylline; 7: Pentoxifylline; 8: Pentoxifylline plus metadoxine. Abbreviations: TNF = tumour necrosis factor.
25
25
Forest plot of adverse events (proportion) (network meta‐analysis estimates and direct comparisons when available): Both fixed‐effect model and random‐effects model for other interventions compared to no intervention are provided. The direct estimates and network meta‐analysis estimates appear similar. There was no evidence of any differences in any other interventions versus no intervention using the random‐effects model. Abbreviations: GSF = granulocyte stimulating factor.
26
26
The top figure shows the surface area under the curve constructed on the basis of the ranking probabilities. The bottom figure shows the probability of each intervention being best, second best, third best, and so on. No active intervention appears to be the top‐ranking intervention, while GSF plus pentoxifylline appears to be the worst‐ranking intervention. Legend: 1: No active intervention; 2: GSF plus pentoxifylline; 3: N‐acetyl cysteine 4: Pentoxifylline. Abbreviations: GSF = granulocyte stimulating factor.
27
27
IF (Inconsistency Factor) plots of adverse events (number) in which direct and indirect estimates were available. There appears to be inconsistency in several loops as the confidence intervals do not overlap 1. The loops in which the confidence intervals did not overlap 1 are: no intervention ‐ pentoxifylline ‐ pentoxifylline plus glucocorticosteroids (confidence intervals: 0.44 to 0.74), no intervention ‐ glucocorticosteroids ‐ pentoxifylline plus glucocorticosteroids (confidence intervals: 0.38 to 0.64), no intervention ‐ glucocorticosteroids ‐ pentoxifylline (0.00 to 0.68), glucocorticosteroids ‐ pentoxifylline‐ metadoxine plus pentoxifylline (0.00 to 0.39), and glucocorticosteroids ‐ metadoxine plus glucocorticosteroids ‐ pentoxifylline (0.00 to 0.39).
28
28
Forest plot of adverse events (number) (network meta‐analysis estimates and direct comparisons when available): Both fixed‐effect model and random‐effects model for other interventions compared to no intervention are provided. The direct estimates and network meta‐analysis estimates are similar. Based on the network meta‐analysis, it appears that glucocorticosteroids, pentoxifylline, and pentoxifylline plus glucocorticosteroids have more adverse events compared with no intervention. Abbreviations: GSF = granulocyte stimulating factor; TNF = tumour necrosis factor; SAMe = S‐adenosyl methionine.
29
29
The top figure shows the surface area under the curve constructed on the basis of the ranking probabilities. The bottom figure shows the probability of each intervention being best, second best, third best, and so on. None of the interventions seems to be clearly better than others, although GSF plus pentoxifylline appears to be the worst‐ranking intervention.
 
 Legend: 1: No active intervention; 2: Glucocorticosteroids; 3: Glucocorticosteroids plus anti‐TNF; 4: Glucocorticosteroids plus metadoxine; 5: Glucocorticosteroids plus N‐acetyl cysteine; 6: Glucocorticosteroids plus pentoxifylline; 7: Glucocorticosteroids plus SAMe; 8: GSF plus pentoxifylline; 9: N‐acetyl cysteine; 10: Pentoxifylline; 11: Pentoxifylline plus metadoxine. Abbreviations: GSF = granulocyte stimulating factor; TNF = tumour necrosis factor; SAMe = S‐adenosyl methionine.
1.1
1.1. Analysis
Comparison 1 Alcoholic hepatitis (all), Outcome 1 Mortality at maximal follow‐up.
1.2
1.2. Analysis
Comparison 1 Alcoholic hepatitis (all), Outcome 2 Mortality (30‐days).
1.3
1.3. Analysis
Comparison 1 Alcoholic hepatitis (all), Outcome 3 Mortality (90‐days).
1.4
1.4. Analysis
Comparison 1 Alcoholic hepatitis (all), Outcome 4 Serious adverse events (proportion).
1.5
1.5. Analysis
Comparison 1 Alcoholic hepatitis (all), Outcome 5 Serious adverse events (number).
1.6
1.6. Analysis
Comparison 1 Alcoholic hepatitis (all), Outcome 6 Liver transplantation.
1.7
1.7. Analysis
Comparison 1 Alcoholic hepatitis (all), Outcome 7 Decompensated cirrhosis.
1.8
1.8. Analysis
Comparison 1 Alcoholic hepatitis (all), Outcome 8 Cirrhosis.
1.9
1.9. Analysis
Comparison 1 Alcoholic hepatitis (all), Outcome 9 Adverse events (proportion).
1.10
1.10. Analysis
Comparison 1 Alcoholic hepatitis (all), Outcome 10 Adverse events (number).
2.1
2.1. Analysis
Comparison 2 Severe alcoholic hepatitis, Outcome 1 Mortality at maximal follow‐up.
2.2
2.2. Analysis
Comparison 2 Severe alcoholic hepatitis, Outcome 2 Mortality (30 days).
2.3
2.3. Analysis
Comparison 2 Severe alcoholic hepatitis, Outcome 3 Mortality (90 days).
2.4
2.4. Analysis
Comparison 2 Severe alcoholic hepatitis, Outcome 4 Serious adverse events (proportion).
2.5
2.5. Analysis
Comparison 2 Severe alcoholic hepatitis, Outcome 5 Serious adverse events (number).
2.6
2.6. Analysis
Comparison 2 Severe alcoholic hepatitis, Outcome 6 Liver transplantation.
2.7
2.7. Analysis
Comparison 2 Severe alcoholic hepatitis, Outcome 7 Decompensated cirrhosis.
2.8
2.8. Analysis
Comparison 2 Severe alcoholic hepatitis, Outcome 8 Adverse events (proportion).
2.9
2.9. Analysis
Comparison 2 Severe alcoholic hepatitis, Outcome 9 Adverse events (number).
3.1
3.1. Analysis
Comparison 3 Alcohol‐related liver disease (others), Outcome 1 Mortality at maximal follow‐up.
3.2
3.2. Analysis
Comparison 3 Alcohol‐related liver disease (others), Outcome 2 Mortality (30 days).
3.3
3.3. Analysis
Comparison 3 Alcohol‐related liver disease (others), Outcome 3 Mortality (90 days).
3.4
3.4. Analysis
Comparison 3 Alcohol‐related liver disease (others), Outcome 4 Serious adverse events (proportion).
3.5
3.5. Analysis
Comparison 3 Alcohol‐related liver disease (others), Outcome 5 Liver transplantation.
3.6
3.6. Analysis
Comparison 3 Alcohol‐related liver disease (others), Outcome 6 Decompensated cirrhosis.
3.7
3.7. Analysis
Comparison 3 Alcohol‐related liver disease (others), Outcome 7 Hepatocellular carcinoma.
3.8
3.8. Analysis
Comparison 3 Alcohol‐related liver disease (others), Outcome 8 Adverse events (proportion).
3.9
3.9. Analysis
Comparison 3 Alcohol‐related liver disease (others), Outcome 9 Adverse events (number).
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Update of

  • doi: 10.1002/14651858.CD011646

References

References to studies included in this review

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Higuera de la Tijera 2015 {published data only}
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Kim 2012 {published data only}
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Nguyen‐Khac 2011 {published data only}
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Achord 1987 {published data only}
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Nasrallah 1980 {published data only}
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Naveau 1986 {published data only}
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Panos 1990 {published data only}
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Ramond 1992a {published data only}
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Simon 1988 {published data only}
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Spahr 2008 {published data only}
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References to other published versions of this review

Gurusamy 2015
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