Tenofovir (all routes except local)

Maternal liver disorder / failure during pregnancy

R analysis
id Study   Lib. in paper Exposition period    Study type 
 Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S5628
R14040		 Sibiude, 2019 Maternal Liver Enzyme Elevation (Grade 1–4) during pregnancy during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes Control group: non-TDF (mix or unspecified regimens) Exposed group: TDF (mix or unspecified regimens) Indication: HIV 1.00 [0.50;1.80] -/-   -/- - -
ref
S5134
R13377		 Floridia, 2018 Maternal Cholestasis/liver function tests abnormalities during pregnancy (anytime or not specified) cohort exposed to other treatment, sick Adjustment: No Control group: Abacavir/Lamivudine-based Exposed group: TDF/emtricitabine-based Indication: HIV 0.91 [0.58;1.42] 75/661   31/252 106 661
ref
S5304
R13753		 Jourdain a, 2018 Maternal acute hepatic exacerbation (alanine aminotransferase level of >300 IU per liter) 3rd trimester randomized controlled trial unexposed, sick Adjustment: Randomisation Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 1.89 [0.62;5.76] C 9/154   5/157 14 154
ref
S5321
R13791		 Lin, 2018 Intrahepatic cholestasis of pregnancy 3rd trimester randomized controlled trial unexposed, sick Adjustment: Randomisation Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 1.06 [0.30;3.71] C 6/59   5/52 11 59
ref
S5290
R13647		 Seo, 2018 Maternal severe postpartum hepatitis (ALT levels > 5-fold the upper limit of normal, 40 IU/L)) 3rd trimester retrospective cohort exposed to other treatment, sick Adjustment: No Control group: telbivudine Exposed group: TDF (only) Indication: CHB 3.71 [0.74;18.73] C 4/11   4/30 8 11
ref
S5259
R13601		 Pan, 2016 Interhepatic cholestasis of pregnancy late pregnancy randomized controlled trial unexposed, sick Adjustment: Randomisation Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 1.56 [0.26;9.57] C 3/97   2/100 5 97
ref
S5262
R13629		 Chen, 2015 Maternal elevation of aminotransferase levels (> 5x ULN) at least once late pregnancy prospective cohort unexposed, sick Adjustment: No Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 0.23 [0.05;1.17] C 2/62   7/56 9 62
ref
Total 7 studies 1.05 [0.71;1.55] 153 1,044
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

StudyTE95% CIn casesn exposedweightROBABCDEF Sibiude, 2019Sibiude, 2019 1.00[0.50; 1.80]--26%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Floridia, 2018Floridia, 2018 0.91[0.58; 1.42]10666139%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Jourdain a, 2018Jourdain a, 2018 1.89[0.62; 5.76]1415411%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Lin, 2018Lin, 2018 1.06[0.30; 3.71]11599%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Seo, 2018Seo, 2018 3.71[0.74; 18.73]8115%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Pan, 2016Pan, 2016 1.56[0.26; 9.57]5974%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Chen, 2015Chen, 2015 0.23[0.05; 1.17]9625%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (7 studies) I2 = 18% 1.05[0.71; 1.55]1531,0440.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.95[0.52; 1.71]12373447%NASibiude, 2019 Floridia, 2018 Seo, 2018 Chen, 2015 4 case control studiescase control studies 0 RCTRCT 1.48[0.69; 3.16]303100%NAJourdain a, 2018 Lin, 2018 Pan, 2016 3 Type of controls unexposed, sickunexposed, sick 1.01[0.42; 2.39]3937234%NAJourdain a, 2018 Lin, 2018 Pan, 2016 Chen, 2015 4 exposed to other treatment, sickexposed to other treatment, sick 1.05[0.66; 1.66]11467226%NASibiude, 2019 Floridia, 2018 Seo, 2018 3 Tags Adjustment   - No  - No 0.92[0.29; 2.96]12373464%NAFloridia, 2018 Seo, 2018 Chen, 2015 3   - Randomisation  - Randomisation 1.48[0.69; 3.16]303100%NAJourdain a, 2018 Lin, 2018 Pan, 2016 3   - Yes  - Yes 1.00[0.53; 1.90]-- -NASibiude, 2019 1 Control group   - Abacavir/Lamivudine-based  - Abacavir/Lamivudine-based 0.91[0.58; 1.42]106661 -NAFloridia, 2018 1   - non-TDF (mix or unspecified regimens)  - non-TDF (mix or unspecified regimens) 1.00[0.53; 1.90]-- -NASibiude, 2019 1   - telbivudine  - telbivudine 3.71[0.74; 18.73]811 -NASeo, 2018 1   - Unexposed, sick  - Unexposed, sick 1.01[0.42; 2.39]3937234%NAJourdain a, 2018 Lin, 2018 Pan, 2016 Chen, 2015 4 Exposed group   - TDF (mix or unspecified regimens)  - TDF (mix or unspecified regimens) 1.00[0.53; 1.90]-- -NASibiude, 2019 1   - TDF (only)  - TDF (only) 1.25[0.55; 2.86]4738339%NAJourdain a, 2018 Lin, 2018 Seo, 2018 Pan, 2016 Chen, 2015 5   - TDF/emtricitabine-based  - TDF/emtricitabine-based 0.91[0.58; 1.42]106661 -NAFloridia, 2018 1 Indication   - CHB  - CHB 1.25[0.55; 2.86]4738339%NAJourdain a, 2018 Lin, 2018 Seo, 2018 Pan, 2016 Chen, 2015 5   - HIV  - HIV 0.94[0.65; 1.36]1066610%NASibiude, 2019 Floridia, 2018 2 All studiesAll studies 1.05[0.71; 1.55]1531,04418%NASibiude, 2019 Floridia, 2018 Jourdain a, 2018 Lin, 2018 Seo, 2018 Pan, 2016 Chen, 2015 70.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.22.21.1090.000Sibiude, 2019Floridia, 2018Jourdain a, 2018Lin, 2018Seo, 2018Pan, 2016Chen, 2015

Asymetry test p-value = 0.5869 (by Egger's regression)

slope=-0.1785 (0.3856); intercept=0.5235 (0.9022); t=0.5803; p=0.5869

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 0.90[0.41; 1.99]4346927%NAJourdain a, 2018 Lin, 2018 Pan, 2016 Pan, 2016 Chen, 2015 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.05[0.66; 1.66]11467226%NASibiude, 2019 Floridia, 2018 Seo, 2018 30.510.01.0