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Cochrane Database of Systematic Reviews

Administración de suplementos de vitamina D para las hepatopatías crónicas en adultos

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Información

DOI:
https://doi.org/10.1002/14651858.CD011564.pub2Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 03 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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Contraer

Autores

  • Goran Bjelakovic

    Correspondencia a: Department of Internal Medicine, Medical Faculty, University of Nis, Nis, Serbia

    [email protected]

    Clinic of Gastroenterology and Hepatology, Clinical Centre Nis, Nis, Serbia

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

  • Dimitrinka Nikolova

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

  • Marko Bjelakovic

    Medical Faculty, University of Nis, Nis, Serbia

  • 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

GB: initiated the review; drafted the protocol; performed the literature search, data extraction, and statistical analyses; and drafted the review.
DN: revised the protocol, performed data extraction, and revised the review.
MB: joined the team of authors at the review stage, performed data extraction, and revised the review.
CG: revised the protocol, acted as arbiter for disagreements, and revised the review.

Sources of support

Internal sources

  • Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark.

External sources

  • Ministry of Education, Science and Technological Development of the Republic of Serbia, Project 41018, Serbia.

  • Medical Faculty, University of Nis, Project 24, Serbia.

Declarations of interest

None known.

Acknowledgements

We thank Marija Bjelakovic for her work on the review.

Cochrane Review Group funding acknowledgement: the Danish State is the largest single funder of The Cochrane Hepato‐Biliary Group through its investment in The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, 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: Tony Bruns, Germany; Sohail Mushtaq, UK.
Contact and sign‐off editor: Vanja Giljaca, UK.

Version history

Published

Title

Stage

Authors

Version

2021 Aug 25

Vitamin D supplementation for chronic liver diseases in adults

Review

Milica Bjelakovic, Dimitrinka Nikolova, Goran Bjelakovic, Christian Gluud

https://doi.org/10.1002/14651858.CD011564.pub3

2017 Nov 03

Vitamin D supplementation for chronic liver diseases in adults

Review

Goran Bjelakovic, Dimitrinka Nikolova, Marko Bjelakovic, Christian Gluud

https://doi.org/10.1002/14651858.CD011564.pub2

2015 Mar 04

Vitamin D supplementation for chronic liver diseases in adults

Protocol

Goran Bjelakovic, Dimitrinka Nikolova, Marija Bjelakovic, Christian Gluud

https://doi.org/10.1002/14651858.CD011564

Differences between protocol and review

  • Types of outcome measures. Primary outcomes. We followed new recommendations from Cochrane, and changed primary outcomes to: all‐cause mortality, liver‐related mortality, and serious adverse events.

  • Types of outcome measures. Secondary outcomes. We followed new recommendations from Cochrane, and changed secondary outcomes to: liver‐related morbidity, health‐related quality of life, and non‐serious adverse events. We moved the other planned secondary outcomes: vitamin D status, bone mineral density, biochemical indices, failure of virological response, and acute cellular rejection in liver transplant recipients under 'Exploratory outcomes'. We added alkaline phosphatase, triglyceride, cholesterol, and calcium to exploratory outcome 'biochemical indices' to be able to analyse the effect of vitamin D supplementation on the broader spectrum of biochemical indices.

  • Data synthesis. We considered a P value of 0.025 or less, two‐tailed, as statistically significant if the required information size was reached due to our three primary outcomes (Jakobsen 2014).

  • Data synthesis. In our Trial Sequential Analysis, the diversity‐adjusted required information size was based on the event proportion in the control group; assumption of a plausible relative risk reduction; a risk of type I error of 2.5%; a risk of type II error of 10%; and the observed diversity of the included trials in the meta‐analysis (Jakobsen 2014; Wetterslev 2017).

  • Marko Bjelakovic joined the team of authors during the preparation of the review and Marija Bjelakovic left the team of authors during the preparation of the review.

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 some of our protocols and reviews as they share at least three common authors.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Adult; 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 item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

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

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

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

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Funnel plot of comparison: 1 Vitamin D versus placebo or no intervention, outcome: 1.1 All‐cause mortality.
Figuras y tablas -
Figure 4

Funnel plot of comparison: 1 Vitamin D versus placebo or no intervention, outcome: 1.1 All‐cause mortality.

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Trial Sequential Analysis on all‐cause mortality up to 1.4‐year follow‐up in 15 vitamin D trials, based on mortality rate in the control group of 10%, a relative risk reduction of 28% in the intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 6396 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundary 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).
Figuras y tablas -
Figure 5

Trial Sequential Analysis on all‐cause mortality up to 1.4‐year follow‐up in 15 vitamin D trials, based on mortality rate in the control group of 10%, a relative risk reduction of 28% in the intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 6396 participants. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundary 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).

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Trial Sequential Analysis on rapid virological response in the two vitamin D trials was performed based on a mortality rate in the control group of 5%, a relative risk reduction (RRR) of 30% in the intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 11958 participants. The cumulative Z‐curve crossed the conventional monitoring boundary for benefit. The trial sequential monitoring boundary is ignored due to little information use (1.56%).
Figuras y tablas -
Figure 6

Trial Sequential Analysis on rapid virological response in the two vitamin D trials was performed based on a mortality rate in the control group of 5%, a relative risk reduction (RRR) of 30% in the intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 11958 participants. The cumulative Z‐curve crossed the conventional monitoring boundary for benefit. The trial sequential monitoring boundary is ignored due to little information use (1.56%).

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Trial Sequential Analysis on early virological response in the two vitamin D trials was performed based on a mortality rate in the control group of 5%, a relative risk reduction (RRR) of 30% in the intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 11958 participants. The cumulative Z‐curve crossed the conventional monitoring boundary for benefit. The trial sequential monitoring boundary is ignored due to little information use (1.17%).
Figuras y tablas -
Figure 7

Trial Sequential Analysis on early virological response in the two vitamin D trials was performed based on a mortality rate in the control group of 5%, a relative risk reduction (RRR) of 30% in the intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 11958 participants. The cumulative Z‐curve crossed the conventional monitoring boundary for benefit. The trial sequential monitoring boundary is ignored due to little information use (1.17%).

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Trial Sequential Analysis on sustained virological response in the five vitamin D trials was performed based on a mortality rate in the control group of 5%, a relative risk reduction (RRR) of 30% in the intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 69798 participants. The trial sequential monitoring boundary is ignored due to little information use (0.45%).
Figuras y tablas -
Figure 8

Trial Sequential Analysis on sustained virological response in the five vitamin D trials was performed based on a mortality rate in the control group of 5%, a relative risk reduction (RRR) of 30% in the intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 69798 participants. The trial sequential monitoring boundary is ignored due to little information use (0.45%).

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Trial Sequential Analysis on acute cellular rejection in the one vitamin D trial was performed based on a mortality rate in the control group of 5%, a relative risk reduction (RRR) of 30% in the intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 11958 participants. The cumulative Z‐curve did not cross the conventional monitoring boundary. The trial sequential monitoring boundary is ignored due to little information use (0.84%).
Figuras y tablas -
Figure 9

Trial Sequential Analysis on acute cellular rejection in the one vitamin D trial was performed based on a mortality rate in the control group of 5%, a relative risk reduction (RRR) of 30% in the intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 11958 participants. The cumulative Z‐curve did not cross the conventional monitoring boundary. The trial sequential monitoring boundary is ignored due to little information use (0.84%).

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Comparison 1 Vitamin D versus placebo or no intervention, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 1.1

Comparison 1 Vitamin D versus placebo or no intervention, Outcome 1 All‐cause mortality.

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Comparison 1 Vitamin D versus placebo or no intervention, Outcome 2 All‐cause mortality ('best‐worst' case and 'worst‐best' case scenarios).
Figuras y tablas -
Analysis 1.2

Comparison 1 Vitamin D versus placebo or no intervention, Outcome 2 All‐cause mortality ('best‐worst' case and 'worst‐best' case scenarios).

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Comparison 1 Vitamin D versus placebo or no intervention, Outcome 3 Liver‐related mortality.
Figuras y tablas -
Analysis 1.3

Comparison 1 Vitamin D versus placebo or no intervention, Outcome 3 Liver‐related mortality.

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Comparison 1 Vitamin D versus placebo or no intervention, Outcome 4 Serious adverse events.
Figuras y tablas -
Analysis 1.4

Comparison 1 Vitamin D versus placebo or no intervention, Outcome 4 Serious adverse events.

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Comparison 1 Vitamin D versus placebo or no intervention, Outcome 5 Non‐serious adverse events.
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Analysis 1.5

Comparison 1 Vitamin D versus placebo or no intervention, Outcome 5 Non‐serious adverse events.

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Comparison 1 Vitamin D versus placebo or no intervention, Outcome 6 Failure of rapid virological response.
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Analysis 1.6

Comparison 1 Vitamin D versus placebo or no intervention, Outcome 6 Failure of rapid virological response.

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Comparison 1 Vitamin D versus placebo or no intervention, Outcome 7 Failure of early virological response.
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Analysis 1.7

Comparison 1 Vitamin D versus placebo or no intervention, Outcome 7 Failure of early virological response.

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Comparison 1 Vitamin D versus placebo or no intervention, Outcome 8 Failure of sustained virological response.
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Analysis 1.8

Comparison 1 Vitamin D versus placebo or no intervention, Outcome 8 Failure of sustained virological response.

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Comparison 1 Vitamin D versus placebo or no intervention, Outcome 9 Acute cellular rejection in liver transplant recipients.
Figuras y tablas -
Analysis 1.9

Comparison 1 Vitamin D versus placebo or no intervention, Outcome 9 Acute cellular rejection in liver transplant recipients.

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Comparison 1 Vitamin D versus placebo or no intervention, Outcome 10 Vitamin D status (ng/mL).
Figuras y tablas -
Analysis 1.10

Comparison 1 Vitamin D versus placebo or no intervention, Outcome 10 Vitamin D status (ng/mL).

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Comparison 1 Vitamin D versus placebo or no intervention, Outcome 11 Biochemical indices.
Figuras y tablas -
Analysis 1.11

Comparison 1 Vitamin D versus placebo or no intervention, Outcome 11 Biochemical indices.

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Summary of findings for the main comparison. Vitamin D compared to placebo or no intervention for chronic liver diseases in adults

Vitamin D compared to placebo or no intervention for chronic liver diseases in adults

Patient or population: adults with chronic liver diseases.
Setting: inpatients and outpatients from Austria, China, Egypt, Iran, Israel, Italy, Japan, USA.
Intervention: vitamin D
Comparison: placebo or no intervention

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(trials)

Quality of the evidence
(GRADE)

Comments

Risk with placebo or no intervention

Risk with vitamin D

All‐cause mortality at the end of follow‐up

Follow‐up: 0.1 to 1.4, mean 0.6 years

Study population

OR 0.70
(0.09 to 5.38)

1034
(15 RCTs)

⊕⊝⊝⊝
Very low1,2,3

Trial Sequential Analyses‐adjusted CI was 0.00 to 2534.

4 per 1.000

3 per 1.000
(0 to 21)

Liver‐related mortality

Follow‐up: mean 1 year

Study population

RR 1.62
(0.08 to 34.66)

18
(1 RCT)

⊕⊝⊝⊝
Very low1,3

Due to few data, we did not conduct Trial Sequential Analysis which would only have revealed larger imprecision.

0 per 1.000

0 per 1.000
(0 to 0)

Serious adverse events ‐ hypercalcaemia

Follow‐up: mean 1 year

Study population

RR 5.00
(0.25 to 100.80)

76
(1 RCT)

⊕⊝⊝⊝
Very low1,3

Due to few data, we did not conduct Trial Sequential Analysis which would only have revealed larger imprecision.

0 per 1.000

0 per 1.000
(0 to 0)

Serious adverse events ‐ myocardial infarction

Follow‐up: 0.2 to 1, mean 0.6 years

Study population

RR 0.75
(0.08 to 6.81)

86
(2 RCTs)

⊕⊝⊝⊝
Very low1,3

Due to few data, we did not conduct Trial Sequential Analysis which would only have revealed larger imprecision.

25 per 1.000

19 per 1.000
(2 to 170)

Serious adverse events ‐ thyroiditis

Follow‐up: mean 0.2 years

Study population

RR 0.33
(0.01 to 7.91)

68
(1 RCT)

⊕⊝⊝⊝
Very low1,3

Due to few data, we did not conduct Trial Sequential Analysis which would only have revealed larger imprecision.

29 per 1.000

10 per 1.000
(0 to 233)

Failure of sustained virological response

Follow‐up: 0.3 to 1.4, mean 0.9 years

Study population

RR 0.59
(0.28 to 1.21)

422
(5 RCTs)

⊕⊝⊝⊝

Very low

1,2,3,6

The trial sequential monitoring boundary is ignored due to little information use (0.6%).

465 per 1.000

275 per 1.000
(130 to 563)

Acute cellular rejection in liver transplant recipients

Follow‐up: mean 0.08 years

Study population

RR 0.33
(0.04 to 2.62)

75
(1 RCT)

⊕⊝⊝⊝

Very low

1,3,7

The trial sequential monitoring boundary is ignored due to little information use (0.84%).

120 per 1.000

40 per 1.000
(5 to 314)

*The risk in the intervention group (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; RR: Risk ratio; RCT: randomised clinical trial; OR: Odds 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.

1 Downgraded one level due to risk of bias: all trials were at high risk of bias.
2 Downgraded one level due to inconsistency of evidence: intertrial heterogeneity was significant.
3 Downgraded one level due to imprecision of evidence: Trial Sequential Analysis of vitamin D trials shows that we had insufficient information.
4 Downgraded one level due to indirectness of evidence: rapid virological response is a surrogate outcome.
5 Downgraded one level due to indirectness of evidence: early virological response is a surrogate outcome.
6 Downgraded one level due to indirectness of evidence: sustained virological response is a surrogate outcome.
7 Downgraded one level due to indirectness of evidence: acute cellular rejection is a surrogate outcome.

Figuras y tablas -
Summary of findings for the main comparison. Vitamin D compared to placebo or no intervention for chronic liver diseases in adults
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Table 1. Characteristics of included trials (I)

Study ID

Protocol

Design

Groups

Bias
risk

Blinding

Participants
(n)

Women
(%)

Mean
age (years)

Abu‐Mouch 2011

Yes

Parallel

2

High

NI

72

44

47

Atsukawa 2016

No

Parallel

2

High

NI

115

50

64

Barchetta 2016

Yes

Parallel

2

High

PL

65

35

59

Esmat 2015

No

Parallel

2

High

NI

101

25

40

Foroughi 2016

Yes

Parallel

2

High

PL

60

52

48

Lorvand Amiri 2016

Yes

Parallel

3

High

PL

120

38

41

Mobarhan 1984

No

Parallel

3

High

NI

18

0

61

Nimer 2012

No

Parallel

2

High

NI

50

58

47

Pilz 2016

Yes

Parallel

2

High

PL

36

25

61

Sharifi 2014

No

Parallel

2

High

PL

60

51

60

Shiomi 1999a

No

Parallel

2

High

NI

76

66

61

Shiomi 1999b

No

Parallel

2

High

NI

34

100

56

Vosoghinia 2016

Yes

Parallel

2

High

NI

68

13

42

Xing 2013

No

Parallel

3

High

PL

75

17

48

Yokoyama 2014

No

Parallel

2

High

NI

84

49

59

n: number of participants; NI: no intervention; PL: placebo.
Figuras y tablas -
Table 1. Characteristics of included trials (I)
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Table 2. Characteristics of included trials (II)

Study ID

Participants

Outcome measures

Sponsor

Country

Abu‐Mouch 2011

Chronic hepatitis C genotype 1

Sustained virological response

No information

Israel

Atsukawa 2016

Chronic hepatitis C genotype 1

Sustained virological response

No information

Japan

Barchetta 2016

NAFLD

Liver steatosis, liver function

No

Italy

Esmat 2015

Chronic hepatitis C genotype 4

Sustained virological response

No information

Egypt

Foroughi 2016

NAFLD

Liver steatosis, liver function

No

Iran

Lorvand Amiri 2016

NAFLD

Liver function, body fat

No

Iran

Mobarhan 1984

Liver cirrhosis

Bone mineral density

Yes

USA

Nimer 2012

Chronic hepatitis C genotype 2 or 3

Sustained virological response

No information

Israel

Pilz 2016

Liver cirrhosis

Vitamin D status, liver function

No

Austria

Sharifi 2014

NAFLD

Liver function, insulin resistance index

No

Iran

Shiomi 1999a

Liver cirrhosis

Bone mineral density

No information

Japan

Shiomi 1999b

Primary biliary cirrhosis

Bone mineral density

No information

Japan

Vosoghinia 2016

Chronic hepatitis C genotype 1,2,3,4

Early virological response

No

Iran

Xing 2013

Liver transplant recipients

Acute cellular rejection rate

No

China

Yokoyama 2014

Chronic hepatitis C genotype 1

Sustained virological response

No information

Japan

NAFLD: non‐alcoholic fatty liver disease.
Figuras y tablas -
Table 2. Characteristics of included trials (II)
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Table 3. Characteristics of included studies (III)

Study ID

Vitamin

Calcium
(mg)

Regimen*

Treatment
(weeks)

Follow‐up
(weeks)

Cointervention

D3
(IU)

D2
(IU)

25(OH)D
(IU)

1,25(OH)2D
(µg)

Abu‐Mouch 2011

2000

‐

‐

‐

‐

Daily

48

72

PEG‐INF, RBV

Atsukawa 2016

2000

‐

‐

‐

‐

Daily

16

16

PEG‐INF, RBV, SP

Barchetta 2016

2000

‐

‐

‐

‐

Daily

24

24

‐

Esmat 2015

2143

‐

‐

‐

‐

Weekly

48

72

PEG‐INF, RBV

Foroughi 2016

7143

‐

‐

‐

‐

Weekly

10

10

‐

Lorvand Amiri 2016

1000

‐

‐

‐

500

Daily

10

12

‐

Mobarhan 1984

‐

17,857

2400

‐

‐

Daily

52

52

‐

Nimer 2012

2000

‐

‐

‐

‐

Daily

24

48

PEG‐INF, RBV

Pilz 2016

2800

‐

‐

‐

‐

Daily

8

8

‐

Sharifi 2014

3571

‐

‐

‐

‐

Twice a week

16

16

‐

Shiomi 1999a

‐

‐

‐

1

‐

Daily

52

52

‐

Shiomi 1999b

‐

‐

‐

1

‐

Daily

52

52

‐

Vosoghinia 2016

1600

‐

‐

‐

‐

Daily

12

12

PEG‐INF, RBV

Xing 2013

‐

‐

‐

0.25

1000

Daily

4

4

‐

Yokoyama 2014

1000

‐

‐

‐

‐

Daily

16

24

PEG‐INF, RBV

* Vitamin D was administered orally in all trials.
1,25(OH)2D: calcitriol; 25(OH)D: calcidiol; PEG‐INF: pegylated‐interferon; RBV: ribavirin; SP: simeprevir.

Figuras y tablas -
Table 3. Characteristics of included studies (III)
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Comparison 1. Vitamin D versus placebo or no intervention

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

15

1034

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.70 [0.09, 5.38]

2 All‐cause mortality ('best‐worst' case and 'worst‐best' case scenarios) Show forest plot

15

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

2.1 'Best‐worst' case scenario

15

1034

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.11 [0.05, 0.24]

2.2 'Worst‐best' case scenario

15

1034

Peto Odds Ratio (Peto, Fixed, 95% CI)

7.80 [3.67, 16.57]

3 Liver‐related mortality Show forest plot

1

18

Risk Ratio (M‐H, Random, 95% CI)

1.62 [0.08, 34.66]

4 Serious adverse events Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4.1 Hypercalcaemia

1

76

Risk Ratio (M‐H, Random, 95% CI)

5.0 [0.25, 100.80]

4.2 Myocardial infarction

2

86

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.08, 6.81]

4.3 Thyroiditis

1

68

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 7.91]

5 Non‐serious adverse events Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 Glossitis

1

65

Risk Ratio (M‐H, Random, 95% CI)

3.70 [0.16, 87.58]

6 Failure of rapid virological response Show forest plot

2

187

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.52, 0.94]

7 Failure of early virological response Show forest plot

2

140

Risk Ratio (M‐H, Random, 95% CI)

0.10 [0.03, 0.33]

8 Failure of sustained virological response Show forest plot

5

422

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.28, 1.21]

9 Acute cellular rejection in liver transplant recipients Show forest plot

1

75

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.04, 2.62]

10 Vitamin D status (ng/mL) Show forest plot

6

424

Mean Difference (IV, Random, 95% CI)

17.24 [12.46, 22.02]

11 Biochemical indices Show forest plot

6

Mean Difference (IV, Random, 95% CI)

Subtotals only

11.1 Aspartate aminotransferase (IU/L)

6

313

Mean Difference (IV, Random, 95% CI)

‐1.40 [‐2.88, 0.08]

11.2 Alanine aminotransferase (IU/L)

6

313

Mean Difference (IV, Random, 95% CI)

‐0.52 [‐5.10, 4.06]

11.3 Alkaline phosphatases (IU/L)

2

96

Mean Difference (IV, Random, 95% CI)

7.39 [‐39.89, 54.67]

11.4 Gamma‐glutamyl transpeptidase (IU/L)

2

101

Mean Difference (IV, Random, 95% CI)

3.64 [0.33, 6.96]

11.5 Albumin (g/L)

2

48

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐0.40, 0.20]

11.6 Bilirubin (mg/dL)

2

48

Mean Difference (IV, Random, 95% CI)

0.38 [0.21, 0.55]

11.7 Triglyceride (mg/dL)

2

115

Mean Difference (IV, Random, 95% CI)

23.69 [‐13.90, 61.27]

11.8 Cholesterol (mg/dL)

1

55

Mean Difference (IV, Random, 95% CI)

2.75 [‐4.75, 10.25]

11.9 Calcium (mg/dL)

2

72

Mean Difference (IV, Random, 95% CI)

2.01 [‐0.53, 4.56]
Figuras y tablas -
Comparison 1. Vitamin D versus placebo or no intervention
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