Review
Copyright ©The Author(s) 2021.
World J Gastroenterol. May 28, 2021; 27(20): 2474-2494
Published online May 28, 2021. doi: 10.3748/wjg.v27.i20.2474
Table 1 Pediatric studies of different combinations of direct-acting antivirals
Drug regimen
Age range in yr
Sample size
Genotype(s)
Number of patients with SVR12, %
Ref.
Sofosbuvir/ledipasvir12-17100198/100 (98)Balistreri et al[25]
6-11921, 3, 491/92 (99)Murray et al[26]
3-534 1, 433/34 (97)Schwarz et al[27]
Sofosbuvir plus ribavirin12-17522, 351/52 (98)Wirth et al[33]
6-114141/41 (100)Rosenthal et al[34]
3-51312/13 (92)Rosenthal et al[34]
Sofosbuvir/velpatasvir12-171021, 2, 3, 497/102 (95)Sokal et al[35]
6-117368/73 (93)Sokal et al[35]
3-54134/41 (83)Sokal et al[35]
Glecaprevir/pibrentasvir12-17471, 2, 3, 447/47 (100)Jonas et al[36]
6-113231/32 (97)Jonas et al[37]
3-51615/16 (96)Jonas et al[37]
Ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin12-17381, 438/38 (100)Leung et al[134]
6-1126125/26 (95)Rosenthal et al[135]
Elbasvir/grazoprevir12-17221, 422/22 (100)Wirth et al[136]
6-111717/17 (100)Wirth et al[136]
3-51818/18 (100)Wirth et al[136]
Sofosbuvir/velpatasvir/voxilaprevir12-17211, 2, 3, 421/21 (100)Bansal et al[137]
Sofosbuvir plus daclatasvir15-1713413/13 (100)El-Sayed et al[138]
13-171010/10 (100)El-Shabrawi et al[139]
12-173029/29 (100)Yakoot et al[140]
8-17401, 439/39 (100)Abdel Ghaffar et al[141]
7-1314314/14 (100)Padhi et al[57]
Table 2 Direct-acting antiviral regimens approved for treatment of chronic hepatitis C virus infection in children and adolescents
Regimen
Genotype and duration of treatment
Formulations
Dosage
Sofosbuvir/ledipasvirGT 1, 4, 5, 6: 12 wkTablet (FDC) 400/90 mg> 35 kg: 400/90 mg/d
GT 1, treatment-experienced, cirrhosis: 24 wk17-35 kg: 200/45 mg/d
< 17 kg, older than 3 yr of age: 150/33.75 mg/d
Tablet (FDC) 200/45 mg
Pellets 200/45 mg and 150/33.75
Sofosbuvir + ribavirinGT 2: 12 wkSofosbuvir: tablet 400 mgSofosbuvir: > 35 kg: 400 mg/d
GT 3: 24 wk17-35 kg: 200 mg/d
Tablet 100 mg< 17 kg, older than 3 yr of age: 200 mg if ≥ 17 kg
Capsules 50 mg containing granules
150 mg/d if < 17 kg. Ribavirin: 15 mg/kg per day in two divided doses
Sofosbuvir/velpatasvirAll GTs: 12 wkdecompensated cirrhosis: 12 wk + ribavirinTablet (FDC) 400/100 mg> 30 kg: 400/100 mg/d
17-30 kg, older than 6 yr of age: 200/50 mg/d. Ribavirin: 15 mg/kg per day in two divided doses
Tablet (FDC) 200/50 mg
Glecaprevir/pibrentasvirAll GTs: 8 wkTablet (FDC) 100/40 mg/d12-17 yr or > 45 kg: 300/120 mg/d
All GTs, cirrhosis: 12 wk
GT 3 treatment-experienced: 16 wk
Table 3 Antiviral drugs approved for adolescents and children with chronic hepatitis B virus infection
Drug
Use in children
Dose
Formulation
Interferon-α-2b≥ 1 yr6 million IU/m2 3 times a weekSubcutaneous injections
Pegylated interferon-α-2a≥ 3 yr180 µg/1.73 m2 once a week Subcutaneous injections
Lamivudine≥ 3 yr3 mg/kg daily (max 100 mg)Oral solution (5 mg/mL)
tablets (100 mg)
Entecavir≥ 2 yr10-30 kg: 0.015 mg/kg daily (max 0·5 mg)Oral solution (0.05 mg/mL)
tablets (0.5 mg and 1 mg)
Adefovir ≥ 12 yr10 mg dailyTablets (10 mg)
Tenofovir disoproxil fumarate≥ 12 yr (FDA)300 mg dailyOral powder (40 mg per 1 g)
≥ 2 yr (EMA)tablets (150, 200, 250 and 300 mg)
Tenofovir alafenamide≥ 12 yr (EMA)25 mg dailyTablets (25 mg)
Table 4 Summary of results of clinical trials of hepatitis B antiviral therapy in children

Interferon-α-2b
Lamivudine
Adefovir
Tenofovir DF
Entecavir
Pegylated interferon-α-2a
Number treated14419117352120101
Duration of treatment in wk245248724848
Age, median (range)5 (1-17)9 (2-17)1115.5 (12-17)12 (2-17)11 (3-7)
Virological response as HBeAg negative HBV DNA undetectable (% treated vs placebo)26 (vs 11)23 (vs 13)10.6 (vs 0)21.2 (vs 0)24.2 (vs 3.3)19.8 (vs 2)
HBsAg negative (% treated vs placebo)10 (vs 1)2 (vs 0)0.8 (vs 0)1.9 (vs 0)5.8 (vs 0)8.9 (0)
Ref.Sokal et al[97]Jonas et al[98]Jonas et al[99]Murray et al[100]Jonas et al[101]Wirth et al[102]
Table 5 Investigational drugs for chronic hepatitis B infection
Class
Compound
Mechanism
Known side effects
Route
Status
Ref.
Entry inhibitorsBulevirtideBlocks entry via interaction with NTCPInjection site reactions, cholestasisSubcutaneous (iv)Approved for CHD (HBV/HDV) Phase II for HBeAg-CHBEuropean Association for the Study of the Liver[117] and Bogomolov et al[118]
Capsid assembly modulatorsJNJ-56136379Prevents encapsidation of pgRNA Prevents formation of cccDNAHypertransaminasemiaOralPhase II for CHB ± NAZoulim et al[105]
Capsid assembly modulatorsABI-H0731 (Vebicorvir)Prevents packaging of pgRNA into capsidsSkin rash, dizzinessOralPhase II for CHB ± NAYuen et al[106]
HBsAg secretion inhibitorsREP-2139Inhibits the secretion of HBsAg subviral particlesFever, chills, hypertransaminasemia, leukopeniaivPhase II for CHB + NA Phase II for CHD + peg-IFN-αBazinet et al[109,110]
HBsAg secretion inhibitorsREP-2165Inhibits the secretion of HBsAg subviral particlesFever, chills, hypertransaminasemia, leukopeniaivPhase II for CHD + peg-IFN-αBazinet et al[110]
RNA interferenceJNJ-3989Silences the mRNA viral transcripts reducing HBsAg-ivPhase II for CHBYuen et al[111] and Gane et al[112]
RNA interferenceVIR-2218Silences the mRNA viral transcripts reducing HBsAg-ivPhase II for CHBVIR Biotechnology[113]
RIG-1 agonistInarigivir (SB9200)Activates PRR RIG-1 and IFN-I responseHeadache, dizziness, UTI, ILI, GI symptoms, hypertransaminasemiaOralPhase II for CHB + NAYuen et al[114]
Immune modifierSelgantolimod (GS-9688)TLR8 agonistNausea, vomiting, chills, headache, UTIOralPhase II for CHB + NAGane et al[116]