Is liver biopsy still needed in children with chronic viral hepatitis?

Table 1 Indications for the liver biopsy in children with chronic hepatitis B according to the phase of the infection[21,22,29]

Phase of HBV infection	Immune-tolerant	Immune-active (-clearance)	Immune-inactive	Reactivation/HBeAg-negative chronic hepatitis
HBsAg	Detectable	Detectable	Detectable	Detectable
HBeAg	Detectable	Detectable	Undetectable (anti-HBe positive)	Undetectable (anti-HBe positive)
HBV DNA (IU/mL)/(copies/mL)	> 20000/> 105	> 20000/> 105	< 2000/< 104 or undetectable	> 2000/> 104
ALT	Normal	Persistently elevated	Normal	Normal or elevated
Histopathology: necroinflammation and fibrosis	Minimal or absent	Can develop	Liver inflammation absent or minimal, fibrosis regresses over time	Active liver inflammation +/- fibrosis
Liver biopsy	Generally not indicated	Indicated	Generally not indicated	Indicated, especially if ALT elevated
Antiviral therapy	Generally ineffective, risk of drug resistance; continued monitoring recommended	Should be considered	Continued monitoring recommended	Should be considered if moderate or severe inflammation or fibrosis detected

ALT: Alanine aminotransferase; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen.

Table 2 Liver biopsy findings in children with chronic hepatitis B and C n (%)

Type of infection	Patients (n)	Age,yr (mean ± SD or range)	Grading of necroinflammatory activity			Staging of fibrosis				Ref.
			mean HAI ± SD	Minimal/mild	Moderate/severe	mean ± SD	No/low grade	Severe/cirrhosis	Cirrhosis
HBV	30	12.9 ± 2.5	5.4 ± 3.4	25 (84)	5 (16)	1.7 ± 0.9	24 (80)	6 (20)	1 (3)	Pokorska-Śpiewak et al[52]
HBV	35	10.2 (2.0-20.2)	-	33 (94)	2 (6)	-	28 (80)	7 (20)	2 (7)	Boxall et al[77]
HBV	190	7.5 ± 4.1	6.07 ± 3.22	135 (71)	55 (29)	1.71 ± 0.78	183 (96)	7 (4)	1 (0.5)	Mozer-Lisewska et al[30]
HBV	47	9 (1-17)	-	34 (72)	13 (28)	-	41 (87)	6 (13)	0	Dzierzanowska-Fangrat et al[78]
HCV	30	11.5 ± 3.6	4.2 ± 2.5	29 (97)	1 (3)	1.2 ± 0.9	28 (93)	2 (7)	0	Pokorska-Śpiewak et al[52]
HCV	44	8.6 ± 4.1	-	32 (73)	12 (27)	-	39 (89)	5 (11)	-	Mohan et al[43]
HCV	44	14.5 ± 4.0	-	33 (75)	11 (25)	-	35 (80)	9 (20)	-	Mohan et al[43]
HCV	112	8.6 (1-19)	-	-	-	-	107 (96)	5 (4)	1 (1)	Guido et al[79]
HCV	80	9.1 ± 4.8	-	62 (78)	17 (21)	-	66 (83)	13 (16)	1 (1)	Guido et al[80]
HCV	121	9.8 ± 3.7	5.1	72 (60)	49 (40)	-	114 (94)	7 (6)	2 (2)	Goodman et al[46]
HCV	42	13.4 ± 4.1	-	30 (71)	12 (29)	-	37 (88)	5 (12)	-	Mohan et al[42]
HCV	109	8.8 ± 4.2	3.3 ± 1.5	-	-	1.36 ± 0.5	105 (97)	4 (3)	-	Kage et al[81]
HBV/HCV	10	12.6 ± 2.7	6.2 ± 3.0	7 (70)	3 (30)	1.7 ± 0.8	9 (90)	1 (10)	0	Pokorska-Śpiewak et al[52]

HAI: Histological activity index; HBV: Hepatitis B virus; HCV: Hepatitis C virus.

Table 3 Indications for the antiviral treatment in patients with chronic hepatitis C according to the stage of fibrosis[45]

Stage of fibrosis (METAVIR)	Treatment
Significant fibrosis (F3) or cirrhosis (F4), including decompensated cirrhosis	Should be prioritized
Moderate fibrosis (F2)	Is justified
No or mild liver disease (F0, F1)	Can be deferred

Table 4 Diagnostic performance of the main non-invasive methods used to determine significant liver fibrosis (METAVIR F ≥ 2) and cirrhosis (METAVIR F4) in adult and pediatric patients

Test	Patients (n)	Disease	AUROC		Ref.
			F≥2	F4
Fibrotest	3501	HCV	0.85	-	Poynard et al[82]
Fibrotest	1457	HBV	0.80	-	Poynard et al[82]
Fibrotest	1161	Chronic liver disease	-	0.73	de Lédinghen et al[69]
APRI	6259	HCV	0.77	0.83	Lin et al[83]
APRI	1161	Chronic liver disease	-	0.73	de Lédinghen et al[69]
TE	251	HCV	0.79	0.97	Ziol et al[84]
TE	183	HCV	0.83	0.95	Castéra et al[47]
TE	165	HCV	0.88	0.90	Nitta et al[85]
TE	400	HCV	0.818	0.932	Sporea et al[86]
TE	173	HBV	0.81	0.93	Marcellin et al[87]
TE	175	HBV	0.95	0.98	Zhu et al[88]
TE	1161	Chronic liver disease	-	0.88	de Lédinghen et al[69]
TE	301	HCV	0.815	1.00	Awad et al[89]
ARFI	911	HCV	0.792	0.842	Sporea et al[86]

¹Children. AUROC: Area under the receiver operator characteristic curve; APRI: Aspartate-to-platelet ratio index; ARFI: Acoustic Radiation Force Impulse Imaging; TE: Transient elastography; HCV: Hepatitis C virus.