Fibrosis regression following hepatitis C antiviral therapy

Table 2 Studies illustrating hepatic histological changes following hepatitis C virus clearance with direct acting antiviral therapy

Ref.	Therapy	n	Follow-up	Scores utilized	Outcome
Shiratori et al[29], 2000	INF-based	487	Median of 3.7 yr apart (range, 1 to 10 yr)	Criteria of Desmet and colleagues (F0 to F4) and those of the French METAVIR Cooperative Study Group (A0 to A3)	- A mean reduction in fibrosis score of -0.60+/-0.07 at less than 3 yr of follow-up and -0.88+/-0.08 at 3 yr or more of follow-up; - Reversal of cirrhosis among 11 CHC patients; - Seven patients decreased their level of fibrosis from F4 to F2 and four from F4 to F3
Poynard et al[30], 2002	INF-based	1030	20 mo mean duration between the biopsies	METAVIR scoring system	- Reversal and/or regression of cirrhosis occurred in 49% of patients where 15% regressed to stage 3, 16% reversed to stage 2, 15% reversed to stage 1 and 2% reversed to stage 0; - Fibrosis worsened in 15%
Maylin et al[31], 2008	INF-based	126	3.27 yr	METAVIR scoring system	- Fibrosis stage was improved in 56%, stable in 32%, progressed in 12%; - Regression of cirrhosis was observed in 64% patients; - No cirrhosis decompensation was observed, and 3 patients developed HCC
George et al[32], 2009	INF-based	49	5 yr	METAVIR scoring system	- 82% had a decrease in fibrosis score, and 92% had a decrease in combined inflammation score; - Two patients with pretreatment cirrhosis developed HCC and one died; - All the other patients with pretreatment cirrhosis or advanced fibrosis had improved fibrosis scores on long-term follow-up biopsy
D’Ambrosio et al[33], 2012	INF-based	38	61 mo	METAVIR scoring system, and the area of fibrosis was measured using morphometry	- Reversal of cirrhosis in 23.6% of the patients, regression of cirrhosis in 61%; regression of fibrosis in 36% of CHC patients
Enomoto et al[34], 2018	DAA	20 paired biopsy specimen	41 ± 20 wk	Knodell scoring system and the METAVIR scoring system	- The inflammation grade significantly regressed, but the fibrosis stage did not; - Histological improvement, defined as a ≥ 2-point decrease in the Knodell inflammatory score and no worsening of the fibrosis, was found 55% patients.
Pan et al[35], 2018	INF-based/DAA	15	3 yr	METAVIR and Batts - Ludwig grading systems	- 13 of patients had improved liver stiffness (to < 9.5 kPa)
Chu et al[36], 2019	INF-based	31	93 mo	METAVIR scoring system and HAI	- Fibrosis regression, stable, and progression were 19%, 45%, and 36%; - A total of 71% of patients achieved inflammation improvement, whereas 6% and 23% of patients had stable disease and disease-progression, respectively
Cheng et al[37], 2021	DAA	21	6 mo	METAVIR fibrosis score and HAI	- Fibrosis scores improved in 61.9% of the patients; - 24.8% stable course; - 14.3% progression of fibrosis

DAA: Direct acting antiviral; INF: Interferon; HAI: Histological Activity Index; HCC: Hepatocellular carcinoma; CHC: Chronic hepatitis C.