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Copyright ©The Author(s) 2021.
World J Gastroenterol. Jan 21, 2022; 28(3): 290-309
Published online Jan 21, 2022. doi: 10.3748/wjg.v28.i3.290
Table 1 Risk factors of de novo hepatitis B infection in children after liver transplantation
Risk factors
Positive anti-HBc donor[40]
Positive-intrahepatic HBV DNA[40]
Liver graft HBV DNA > 1000 copies[40]
Intraoperative fresh-frozen plasma transfusion > 400 mL[40]
Positive-anti-HBc recipients[40]
Pre-operative anti-HBs < 1000 mIU/mL[40,43,48]
Post-operative anti-HBs < 100-200 mIU/mL[48,53]
Hepatitis B surface mutation (within the “a” determinant region[54])
Table 2 Antiviral agents for hepatitis B infection in children[44]
Medication
Licensing
Dose and duration
HBsAg loss (%)
Resistance (%)
IFN-α-2b≥ 1 yr 6 million IU/m2 three times weekly for 6 mo1-20
Lamivudine≥ 2 yr3 mg/kg daily for ≥ 1 yr019-64
Entecavir≥ 2 yr0.25-0.5 mg daily for ≥ 1 yr 0.520.7-1.2
Tenofovir dipovaxil fumarate≥ 12 yr300 mg daily for ≥ 1 yr 0.020
Adefovir≥ 12 yr10 mg daily for ≥ 1 yr 00.9-20
Table 3 Recommended direct-acting antiviral regimens for children who are naïve to or experienced with direct-acting antiviral therapy[101,102]
Age
Genotype
No cirrhosis/ cirrhosis
Recommended regimens of DAAs
Duration (wk)
12-17 yrPan-genotypesNo cirrhosisSofosbuvir 400 mg/ velpatasvir 100 mg 12
Compensated cirrhosis (Child-Pugh A)Glecaprevir 300 mg/pibrentasvir 120 mg8-12
12-17 yr or BW ≥ 35 kg 1, 4, 5, 6No cirrhosisSofosbuvir 400 mg/ledipasvir 90 mg12
Compensated cirrhosis (Child-Pugh A)Sofosbuvir 200 mg/velpatasvir 50 mg (BW ≥ 17 kg)
3-11 yr Pan-genotypesNo cirrhosisSofosbuvir 150 mg/velpatasvir 37.5 mg (BW < 17 kg)12
Compensated cirrhosis (Child-Pugh A)Glecaprevir 250 mg/pibrentasvir 100 mg (BW 30-44 kg); Glecaprevir 200 mg/pibrentasvir 80 mg (BW 20-29 kg); Glecaprevir 150 mg/pibrentasvir 60 mg (BW 12-19 kg)12; 8-16; 8-16; 8-16;
Table 4 Studies of children infected with hepatitis E virus after liver transplantation
Ref.
Year
Country
Participants
Seroprevalence of HEV infection
Methods
Comments
HEV IgM/G
HEV RNA
1[130]2012CanadaGr 1; N: 66 with normal LFT, aged 13.7 yr (1.8-25.5); Gr 2; N: 14 with transaminitis, aged 17.4 yr (5.9-19.8)Gr 1: 10/66 (15%) with IgG +, none had IgM, HEV RNA +; Gr 2: 12/14 (86%) with IgG+; 9/12 (75%) with IgM+; 1/12 (0.8%) with HEV RNA +Feldan Bio Inc, Saint-AugustinSerum nested RT-qPCRAll in Gr 2 showed a trend toward chronic hepatitis and fibrosis; An 8-yr-old girl had chronic HEV infection (genotype 3) for > 10 yr and developed cirrhosis
2[131]2012GermanyN: 41 liver-transplanted children, aged 8.8 ± 4.2 yr2/41 (4.9%) IgG +0/41 stool HEV RNA +MikrogenStool RT-qPCRNo case with chronic HEV infection
3[132]2013GermanyN: 22 liver-transplanted children, aged 6.7 yr (1.4-17.2) 1/22 (0.45%) IgG + by Wantai assay and HEV RNA + in serumWantai assaySerum or stool PCR10-year-old boy with HEV infection that had persistent transaminitis after 2-mo immunosuppressive reduction. Ribavirin 15 mg/kg/d was started for 6 mo. Normal LFT and undetectable serum and stool HEV RNA at day 42 of treatment.
4[139]2014BrazilOne liver-transplanted child: case reportHEV IgG/IgM and HEV RNA in serum and liver tissue at 6-10 yr after liver transplantationMikrogenLiver and serum RT-PCRA 4-yr-old girl with transaminitis from ACR at 6 yr after LT, had transaminitis off and on and HEV IgG/IgM and HEV RNA was detected 9-10 yr after LT. Chronic HEV infection was successful treatment with ribavirin for 10 mo.
5[133]2015France84 liver-transplanted children, aged 12.3 yr8/84 (8.3%) HEV IgG+Wantai assayCeeram Tools® kit for HEV-RNA detectionNone had HEV IgM/RNA +; No case of chronic infection
6[140]2020France80 liver-transplanted children, aged 3.5 ± 4 yr6/80 (8%) with HEV IgG+Wantai assayCeeram Tools® kit for HEV-RNA detectionNone had HEV IgM/RNA +; No case of chronic infection; 4/6 had undetectable HEV IgG after follow-up (3-42 mo)
72021Thailand30 liver-transplanted children with transaminitis, aged 1.2-17.6 yr14/30 (45.2%) with HEV IgG+, 4 (13%) with HEV IgM+ and one case with HEV RNA in stoolEuroimmun kit Stool PCRAll of them had persistence of HEV IgM from 5 to 44 mo and transaminitis from 4 to 30 mo before HEV testing. The previous treatment included graft rejection, de novo autoimmune hepatitis and CMV viremia.
Table 5 Diagnostic tests for hepatitis E infection[144,145]
Detection
Technique
Specimen
Virus or its components (direct method)HEV nucleic acid: (1) RT-PCR; (2) Realtime RT-PCR; and (3) Loop-mediated isothermal amplification assay. HEV RNA: (1) In situ hybridization; (2) HEV viral protein (antigen); (3) EIA; and (4) IHC.Serum, stool, bile, liver tissue
Host immune response (indirect method)Specific anti-HEV antibodies (IgM and IgG) (sensitivity 72%-98% and specificity 78%-96%): (1) Indirect EIA; (2) Immunochromatographic assays; (3) Double-antigen sandwich-based EIAs; (4) μ capture EIAs for IgM anti-HEV; (5) Specific cellular immune response; and (6) ELISpot assays.Serum, peripheral blood mononuclear cells