Hepatitis E in solid organ transplant recipients: A systematic review and meta-analysis

Table 1 Subgroup analyses of all variables

Subgroup	n (%)	Incidence (%)	95%CI
Year
< 2015	10	17.1	9.9-27.9
≥ 2015	8	26.8	19.5-35.7	Q = 2.248, P = 0.134
Country
High-income	16	18.9	13.1-26.4
Middle-income	2	41.8	37.6-46.1	Q = 22.375, P < 0.001c
Study type
Prospective	6	22.3	13.4-34.7
Retrospective	12	20.3	12.8-30.7	Q = 0.077, P = 0.782
Sample size
n < 400	14	25.4	18.9-33.1
n ≥ 400	4	10.4	3.2-28.8	Q = 2.613, P = 0.106
Mean age
≤ 50 yr	3	17.7	5.4-44.8
> 50 yr	10	20.2	13.4-29.3	Q = 0.051, P = 0.821
Male proportion
≤ 65%	7	16.0	7.7-30.4
> 65%	5	23.0	12.5-38.5	Q = 0.631, P = 0.427
Diagnostic test
More than one marker	11	25.9	19-34.4
Single marker	7	14.1	5.5-31.5	Q = 1.806, P = 0.179
Antibody assay
Wantai assay	8	28.4	21.4-36.6
Other assays	6	12.3	7.7-19.1	Q = 10.134, P = 0.001b
Follow-up
≤ 12 mo	7	23.8	23.8
> 12 mo	4	26.8	26.8	Q = 0.072, P = 0.789

^bP < 0.01.

^cP < 0.001. CI: Confidence interval; n: Number of studies.

Table 2 Characteristics of studies included in the systematic review

Ref.	Country	Type	n (%)	Organ	Age	Male	White	HEV	Confirmed test	Acute HEV	Death	Outcome	Follow-up
Kamar et al[19], 2011	Monaco	R	85	UD	-	-	-	65.9% (total; 56/85). 32.1% (18/85) had clearance. 0% (0/18) reactivation	Persistently elevated LFTs and positive HEV-RNA	0%	-	Factors associated with chronic HEV infection: Tacrolimus (OR 1.89; 1.49-1.97). Low platelet (OR 1.02; 1.00-1.10)	6 mo
Legrand-Abravanel et al[35], 2011	France	R	700	Liver (n = 171), kidney (n = 529)	52	65.6%	-	15.1% (total; 106/700). 14.6% (25/171) for LTx. 15.3% (81/529 for KTx. 5.6% (de novo; 34/601). 0% (0/17) reactivation	Positive HEV IgG, IgM (Adaltis assay) or HEV-RNA	2.8% (17/611). 2.7% (4/150) for LTx. 2.8% (13/461) for KTx	-	-	22 mo
Pischke et al[22], 2012	Germany	P	274	Heart	57	80%	-	12.8% (total; 35/274). 7.3% (de novo; 20/274)	Positive HEV IgG (MP assay) or HEV-RNA	-	-	Heart transplant recipients had significantly higher seroprevalence of HEV-IgG than healthy individuals	8 mo
Crossan et al[21], 2014	Scotland	P	317	UD	56.4	93.4%	-	14.2% (total; 45/317)	Positive HEV IgG or IgM (Wantai assay)	0.9% (3/317)	-	Factors associated with chronic HEV infection: HBV coinfection (OR 7.4; 1.4-37). IgG positive is associated with HCC (OR 2.3; 1.1-4.8)	-
Mallet et al[36], 2013	France	R	267	Liver	-	-	-	31% (total; 83/267)	Positive HEV IgG (Wantai assay)	-	-	-	-
Pischke et al[37], 2014	Germany	R	95	Lung	-	-	-	5.3% (total; 5/95)	Positive HEV IgG (MP assay)	-	-	-	-
Riezebos-Brilman et al[38], 2013	Netherlands	R	468	Lung	40	60%	-	2.1% (total; 10/468)	Positive HEV-RNA	-	0.4%	-	6.5 mo
Abravanel et al[39], 2014	France	P	263	Liver (n = 52), kidney (n = 211)	53	64.3%	-	38.4% (total; 101/263). 42.3% for LTx (22/52). 37.4% for KTx (79/211). 1.9% (de novo; 3/162)	Positive HEV IgG, IgM (Wantai assay) or HEV-RNA	-	-	-	12 mo
Buffaz et al[40], 2014	France	R	206	Liver	41.1	63.0%	-	36.4% (total; 75/206). 5.3% (de novo; 11/206)	Positive post-transplant HEV IgG, IgM (Wantai assay) or HEV-RNA	-	-	-	32.8 mo
Riveiro-Barciela et al[20], 2014	Spain	R	625	Liver (n = 332), kidney (n = 296), dual (n = 6)	54.5	60.8%	-	5.8% (total; 36/625). 3.7% (11/296) for KTx. 7.4% (25/332) for LTx	Positive HEV IgG (MP assay)	-	-	Risk factors associated with HEV infection: Cirrhosis (OR 7.6; 4.4-13.1). Liver transplantation (OR 3.1; 1.8-5.4). HIV infection (OR 2.4; 1.3-4.4)	-
De Nicola et al[41], 2015	Italy	R	79	Liver	55	-	-	33% (total; 26/79). 5.7% (de novo; 3/53)	Positive HEV IgG, IgM (Wantai assay), HEV-RNA	0%	-	-	12 mo
Magnusson et al[42], 2015	Sweden	P	62	Lung	55	37.5%	100%	14.8% (total; 8/54). De novo N/A	Positive HEV IgG (recomWell assay)	25% (2/8)	17.8%	-	12 mo
Sherman et al[43], 2017	United States	P	171	Liver (n = 70), kidney (n = 101)	-	-	-	19.9% (total; 34/171). 21.4% (15/70) for LTx. 18.8% (19/101) for KTx	Positive HEV IgG (Wantai assay)	5.5% (3/55) for LTx. 0% for KTx	-	HIV-infected transplant recipients	24 mo
Erken et al[17], 2018	Netherlands	R	677	Kidney	-	-	-	0.7% (de novo; 2/300)	Positive HEV-RNA	-	-	Subjects are patients with ALT elevations	-
Reekie et al[18], 2018	United Kingdom	R	611	Liver (n = 262), kidney (n = 349)	-	-	-	0.5% (total; 3/611)	Positive HEV-RNA	-	-	-	36 mo
Samala et al[44], 2018	United States	R	232	Liver (n = 208), kidney (n = 10), both (n = 10), intestine (n = 4)	58	65%	70%	19.4% (total; 45/232)	Positive IgG, IgM (Wantai assay) or HEV-RNA	-	-	HEV seroprevalence was associated with older age and patients with the diagnosis of alcohol- or NAFLD-associated liver failure	-
Darstein et al[45], 2020	Germany	R	74	Liver	55	62.2%	-	28.8% (total; 21/73)	Positive HEV IgG (recomWell assay) or HEV-RNA	-	-	-	-
Komolmit et al[46], 2020	Thailand	P	108	Liver	58	69%	0%	44% (total; 48/108)	Positive IgG, IgM (Wantai assay) or HEV-RNA	2% (1/48)	0.9%	-	12 mo
Wang et al[23], 2020	China	R	408	Liver	50	81.1%	0%	41.2% (total; 168/408). 16.9% (de novo; 69/408)	Positive HEV-RNA more than 6 months	13.7% (56/408)	-	Alcoholic cirrhosis (OR 5.324; 1.36-20.98). Liver failure (OR 23.76; 2.78-203.08). Graft rejection (OR 0.217; 0.06-0.74)	13.7 mo
Zanotto et al[47], 2020	Italy	R	120	Liver	-	-	-	19.2% (total; 23/120)	Positive HEV IgG, IgM (N/A assay) or HEV-RNA	-	-	-	-

UD: Undifferentiated; HEV: Hepatitis E virus; LFTs: Liver function test; OR: Odds ratio; LTx: Liver transplant; IgG: Immunoglobulin G; MC: Multicenter; IgM: Immunoglobulin M; KTx: Kidney transplant; HCC: Hepatocellular carcinoma; HIV: Human immunodeficiency virus; ALT: Alanine aminotransferase; R: Retrospective; NAFLD: Non-alcoholic fatty liver disease; MP: Methylparaben.