Scolaris Content Display Scolaris Content Display

Ejercicio físico para los pacientes con cirrosis

Appendices

Appendix 1. Search strategies

Database

Time span

Search strategy

Cochrane Hepato‐Biliary Group Controlled Trials Register

February 2018

(exercise* or physical activit* or training or (oxygen and (uptake or consumption))) AND cirrho*

Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library

2018, Issue 1

#1 MeSH descriptor: [Exercise] explode all trees

#2 exercise* or physical activit* or training or (oxygen and (uptake or consumption))

#3 #1 or #2

#4 MeSH descriptor: [Liver Cirrhosis] explode all trees

#5 cirrho*

#6 #4 or #5

#7 #3 and #6

MEDLINE Ovid

1946 to February 2018

1. exp Exercise/

2. (exercise* or physical activit* or training or (oxygen and (uptake or consumption))).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier]

3. 1 or 2

4. exp Liver Cirrhosis/

5. cirrho*.mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier]

6. 4 or 5

7. 3 and 6

8. (random* or blind* or placebo* or meta‐analys*).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier]

9. 7 and 8

Embase Ovid

1974 to February 2018

1. exp exercise/

2. (exercise* or physical activit* or training or (oxygen and (uptake or consumption))).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]

3. 1 or 2

4. exp liver cirrhosis/

5. cirrho*.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]

6. 4 or 5

7. 3 and 6

8. (random* or blind* or placebo* or meta‐analys*).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]

9. 7 and 8

LILACS (Bireme)

1982 to February 2018

(exercise$ or physical activit$ or training or (oxygen and (uptake or consumption))) [Words] and cirrho$ [Words]

Science Citation Index Expanded (Web of Science)

1900 to February 2018

#5 #4 AND #3

#4 TS=(random* or blind* or placebo* or meta‐analys*)

#3 #2 AND #1

#2 TS=(cirrho*)

#1 TS=(exercise* or physical activit* or training or (oxygen and (uptake or consumption)))

Conference Proceedings Citation Index – Science (Web of Science)

1990 to February 2018

#5 #4 AND #3

#4 TS=(random* or blind* or placebo* or meta‐analys*)

#3 #2 AND #1

#2 TS=(cirrho*)

#1 TS=(exercise* or physical activit* or training or (oxygen and (uptake or consumption)))

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 trials
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Figure 2

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

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study
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Figure 3

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

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Comparison 1 Exercise versus control, Outcome 1 All‐cause mortality.
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Analysis 1.1

Comparison 1 Exercise versus control, Outcome 1 All‐cause mortality.

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Comparison 1 Exercise versus control, Outcome 2 Serious adverse events.
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Analysis 1.2

Comparison 1 Exercise versus control, Outcome 2 Serious adverse events.

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Comparison 1 Exercise versus control, Outcome 3 Health‐related quality of life.
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Analysis 1.3

Comparison 1 Exercise versus control, Outcome 3 Health‐related quality of life.

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Comparison 1 Exercise versus control, Outcome 4 Non‐serious adverse events.
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Analysis 1.4

Comparison 1 Exercise versus control, Outcome 4 Non‐serious adverse events.

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Comparison 1 Exercise versus control, Outcome 5 Anthropometric measurements: lean body mass (kg).
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Analysis 1.5

Comparison 1 Exercise versus control, Outcome 5 Anthropometric measurements: lean body mass (kg).

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Comparison 1 Exercise versus control, Outcome 6 Anthropometric measurements: mid‐arm circumference (cm).
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Analysis 1.6

Comparison 1 Exercise versus control, Outcome 6 Anthropometric measurements: mid‐arm circumference (cm).

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Comparison 1 Exercise versus control, Outcome 7 Anthropometric measurements: thigh circumference (cm).
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Analysis 1.7

Comparison 1 Exercise versus control, Outcome 7 Anthropometric measurements: thigh circumference (cm).

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Comparison 1 Exercise versus control, Outcome 8 Anthropometric measurements: body mass index (kg/m2).
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Analysis 1.8

Comparison 1 Exercise versus control, Outcome 8 Anthropometric measurements: body mass index (kg/m2).

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Comparison 1 Exercise versus control, Outcome 9 Physical fitness: peak oxygen uptake (mL/kg/minute).
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Analysis 1.9

Comparison 1 Exercise versus control, Outcome 9 Physical fitness: peak oxygen uptake (mL/kg/minute).

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Comparison 1 Exercise versus control, Outcome 10 Physical fitness: 6‐Minute Walk Test (m in total).
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Analysis 1.10

Comparison 1 Exercise versus control, Outcome 10 Physical fitness: 6‐Minute Walk Test (m in total).

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Comparison 1 Exercise versus control, Outcome 11 Blood glucose (mmol/L).
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Analysis 1.11

Comparison 1 Exercise versus control, Outcome 11 Blood glucose (mmol/L).

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Comparison 1 Exercise versus control, Outcome 12 Serum albumin (g/L).
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Analysis 1.12

Comparison 1 Exercise versus control, Outcome 12 Serum albumin (g/L).

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Comparison 1 Exercise versus control, Outcome 13 Serum creatinine (µmol/L).
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Analysis 1.13

Comparison 1 Exercise versus control, Outcome 13 Serum creatinine (µmol/L).

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Comparison 1 Exercise versus control, Outcome 14 Ammonia (µmol/L).
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Analysis 1.14

Comparison 1 Exercise versus control, Outcome 14 Ammonia (µmol/L).

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Summary of findings for the main comparison. Exercise compared to no exercise for people with cirrhosis

Exercise compared to no exercise for people with cirrhosis

Patient or population: people with Child‐Pugh stage A or B cirrhosis
Setting: outpatients
Intervention: 8–14 weeks of physical exercise (aerobic 3 RCTs; resistance 1 RCT; or a combination of aerobic and resistance training 2 RCTs)
Comparison: sham exercise (supervised relaxation 1 RCT) or no exercise (5 RCTs)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Qualityof the evidence
(GRADE)

Comments

Risk with no exercise

Risk with exercise

All‐cause mortality
Follow‐up: range 8–14 weeks

Study population

RR 0.19
(0.01 to 3.73)

173
(6 RCTs)

⊕⊕⊕⊝
Moderatea

24 per 1000

5 per 1000
(0 to 89)

Serious adverse events
Follow‐up: range 8–14 weeks

Study population

RR 0.61
(0.19 to 1.94)

173
(6 RCTs)

⊕⊕⊝⊝
Lowb

—

155 per 1000

94 per 1000
(29 to 300)

Health‐related quality of life ‐ CLDQ (total score 1–7, high score corresponds to a better HRQoL)
Follow‐up: range 8–14 weeks

The mean quality of life ‐ CLDQ (total score) ranged from 5.03 to 5.39

MD 0.11 higher
(0.44 lower to 0.67 higher)

—

81
(3 RCTs)

⊕⊕⊝⊝
Lowb

—

Anthropometric measurements: mid‐arm circumference (cm)
Follow‐up: range 12–13 weeks

The mean mid‐arm circumference (cm) ranged from 27.1 to 31.5

MD 2.61 higher
(0.36 higher to 4.85 higher)

—

72
(3 RCTs)

⊕⊕⊝⊝
Lowb

—

Anthropometric measurements: mid‐thigh circumference (cm)
Follow‐up: range 8–13 weeks

The mean mid‐thigh circumference (cm) ranged from 51.8 to 54.6

MD 1.76 higher
(0.26 lower to 3.77 higher)

—

128
(5 RCTs)

⊕⊕⊝⊝
Lowb

—

Physical fitness: peak exercise oxygen uptake (mL/kg/minute)
Follow‐up: range 8–14 weeks

The mean peak exercise oxygen uptake (mL/kg/minute) ranged from 21.2 to 26.1

MD 0.3 higher
(2.74 lower to 3.35 higher)

—

100
(4 RCTs)

⊕⊕⊝⊝
Lowb

—

Physical fitness: 6‐Minute Walk Test (min in total)
Follow‐up: range 8–13 weeks

The mean 6‐Minute Walk Test (min in total) ranged from 309 to 546

MD 56.06 higher
(9.14 lower to 121.26 higher)

—

105
(4 RCTs)

⊕⊝⊝⊝
Very lowc

—

*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; CLDQ: Chronic Liver Disease Questionnaire; HRQoL: health‐related quality of life; MD: mean difference; RCT: randomised clinical trial; RR: risk ratio

GRADE Working Group grades of evidence
High quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aDowngraded one level due to serious imprecision (insufficient statistical power).
bDowngraded two levels due to within‐trial risk of bias (lack of trials with a low risk of bias, one level) and serious imprecision (insufficient statistical power, one level).
cDowngraded three levels due to within‐trial risk of bias (lack of trials with a low risk of bias, one level); inconsistency (between‐trial heterogeneity identified although only four trials were included, one level); and very serious imprecision (insufficient statistical power, one level).

Figuras y tablas -
Summary of findings for the main comparison. Exercise compared to no exercise for people with cirrhosis
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Table 1. Serious adverse events

Trial

Number of participants

Intervention group

Control group

Aamann 2018

37

5 participants:

  • ascites requiring paracentesis (2)

  • commotio (1)

  • prostate cancer (1)

  • inflammatory bowel disease requiring colectomy (1)

8 participants:

  • pneumonia (1)

  • stroke (1)

  • fractured foot (1)

  • broken osteosynthesis (1)

  • spontaneous bacterial peritonitis with septic shock (1)

  • fever of unknown origin (1)

  • acute‐on‐chronic liver failure (2)

Krüger 2018

37

None

None

Macías‐Rodríguez 2016

26

3 participants:

  • bleeding NSAID‐induced duodenal ulcer (1)

  • perianal abscess (1)

  • severe hypertension (1)

None

Román 2014

20

1 participant:

  • hepatocellular carcinoma (1)

3 participants:

  • variceal bleeding (1)

  • septic shock due to urinary tract infection (1)

  • fever of unknown origin (1)

Román 2016

25

None

2 participants:

  • hepatocellular carcinoma (1)

  • breast cancer (adenocarcinoma) (1)

Zenith 2014

19

None

None

NSAID: non‐steroidal anti‐inflammatory drug
Figuras y tablas -
Table 1. Serious adverse events
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Comparison 1. Exercise versus control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

6

173

Risk Ratio (M‐H, Random, 95% CI)

0.19 [0.01, 3.73]

2 Serious adverse events Show forest plot

6

173

Risk Ratio (M‐H, Random, 95% CI)

0.61 [0.19, 1.94]

3 Health‐related quality of life Show forest plot

5

Mean Difference (IV, Random, 95% CI)

Subtotals only

3.1 Chronic Liver Disease Questionnaire (total score)

3

81

Mean Difference (IV, Random, 95% CI)

0.11 [‐0.44, 0.67]

3.2 EuroQol‐Visual Analogue Scale (total score)

2

56

Mean Difference (IV, Random, 95% CI)

3.11 [‐24.03, 30.24]

3.3 36‐item Short Form (Mental Component Summary)

2

51

Mean Difference (IV, Random, 95% CI)

2.26 [‐3.84, 8.37]

4 Non‐serious adverse events Show forest plot

6

173

Risk Ratio (M‐H, Random, 95% CI)

1.97 [0.53, 7.33]

5 Anthropometric measurements: lean body mass (kg) Show forest plot

4

Mean Difference (IV, Random, 95% CI)

Subtotals only

5.1 Dual‐energy x‐ray absorptiometry (DXA) – lean leg mass (kg)

1

22

Mean Difference (IV, Random, 95% CI)

0.46 [‐2.92, 3.84]

5.2 Ultrasound – mean compression index (cm/m2)

2

56

Mean Difference (IV, Random, 95% CI)

0.07 [‐0.03, 0.17]

5.3 Bioimpedance – dry lean (kg)

1

34

Mean Difference (IV, Random, 95% CI)

2.30 [‐0.73, 5.33]

6 Anthropometric measurements: mid‐arm circumference (cm) Show forest plot

3

72

Mean Difference (IV, Random, 95% CI)

2.61 [0.36, 4.85]

7 Anthropometric measurements: thigh circumference (cm) Show forest plot

5

128

Mean Difference (IV, Random, 95% CI)

1.76 [‐0.26, 3.77]

8 Anthropometric measurements: body mass index (kg/m2) Show forest plot

6

154

Mean Difference (IV, Random, 95% CI)

0.97 [‐0.48, 2.42]

9 Physical fitness: peak oxygen uptake (mL/kg/minute) Show forest plot

4

100

Mean Difference (IV, Random, 95% CI)

0.30 [‐2.74, 3.35]

10 Physical fitness: 6‐Minute Walk Test (m in total) Show forest plot

4

105

Mean Difference (IV, Random, 95% CI)

56.06 [‐9.14, 121.26]

11 Blood glucose (mmol/L) Show forest plot

2

59

Mean Difference (IV, Random, 95% CI)

0.27 [‐0.54, 1.08]

12 Serum albumin (g/L) Show forest plot

6

155

Mean Difference (IV, Random, 95% CI)

0.05 [‐1.48, 1.59]

13 Serum creatinine (µmol/L) Show forest plot

4

99

Mean Difference (IV, Random, 95% CI)

‐1.54 [‐8.03, 4.95]

14 Ammonia (µmol/L) Show forest plot

3

73

Mean Difference (IV, Random, 95% CI)

8.39 [‐4.20, 20.97]
Figuras y tablas -
Comparison 1. Exercise versus control
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