Fibrosis regression following hepatitis C antiviral therapy

Table 1 Studies illustrating outcome of liver fibrosis following hepatitis C virus clearance with direct-acting antivirals therapy

Ref.	Therapy	n	Follow-Up	Method of fibrosis assessment	Outcome
Knop et al[14], 2016	DAA	54	24 wk	TE, ARFI	- 88% achieved an improvement of LS values at FU24; - 46% showed reduction in liver stiffness higher than 30% at FU24
Bachofner et al[15], 2016	DAA	392	18 mo	TE, FIB-4 and APRI scores, histopathological results were recorded if available	- Overall TE values of the included patients significantly decreased (regression of 32.4%); - Median FIB-4 and APRI values significantly decreased from 2.54 and 1.10 to 1.80 and 0.43
Dolmazashvili et al[16], 2017	INF-based/DAA	304	24 wk	TE	- 65.1% achieved at least a 20% reduction in LS; - Overall proportion of patients with stage F4 decreased from 56.6% to 36.5%
Pietsch et al[17], 2018	DAA	143	24 and 96 wk	TE, FIB-4 and APRI	-A short-term reduction in LS until FU24 was seen in almost every patient regardless of stage of liver disease; -Further regression was seen in patients with early cirrhosis but not in individuals with cirrhosis and impaired liver function; -Progression of LS values occurred despite viral clearance in about one-sixth of the patients (17%)
Hedenstierna et al[18], 2018	DAA	269	7.7 yr	TE	- A majority improved their fibrosis stage after SVR; - 24% had persisting advanced fibrosis with a LS level of ≥ 9.5 kPa
Lledó et al[19], 2018	DAA	260	SVR12	TE	Significant fibrosis regression in 40% of the cohort patients more pronounced in patients with baseline advanced fibrosis and cirrhosis
Soliman et al[20], 2020	DAA/ INF-based	180 DAA/ 180 INF-based	at SVR12, 6 mo and 1 yr	TE	Reduction in fibrosis was reported in; 46.7% and 49.3% of patients with moderate fibrosis, and 89% and 78.7% of patients with advanced fibrosis after one yr of INF containing and INF free DAAs regimens respectively
Shiha et al[21], 2020	DAA	2326	12-45 mo	TE, and (FIB-4, FIB-5 and APRI)	- In cirrhotic patients, 21.8% showed reversal of cirrhosis, 27.4% showed fibrosis regression while 50.8% remained stationary; - About 26.5% of F3 patients showed reversal of fibrosis, 31.5% showed fibrosis regression and 30.6% remained stationary while 11.4% progressed to F4
Hablass et al[22], 2021	DAA	137	12 mo	TE, and FIB-4	In all patients, the FIB-4 and TE values after HCV elimination was significantly lower than its mean values at baseline
El-Kady et al[23], 2021	DAA	300	2 yr	TE	Both HCV treatment regimens showed improvement in liver fibrosis
Zakareya et al[13], 2021	DAA	655	1, 3, and 5 yr	TE	There was an overall significant regression of liver stiffness in all patients after sustained HCV eradication
Agwa et al[24], 2022	DAA	1230	12 and 48 wk	TE, FIB-4	- 42.7% F4 patients improved and became (190) F3, (90) F2, and (220) F1; - 40 of 60 F3 patients improved and became (10) F2 and (30) F1; - 28.4% off the treated patients transited from significant fibrosis (≥ F3) to non-significant fibrosis (≤ F2)
Hassanin et al[25], 2022	DAA	162	48 wk	TIMP-1, FIB-4 and TE	Liver ‎fibrosis was improved as evidenced by significant decline in serum level of ‎TIMP-1, significant improvement in Fib-4 score, and significant decline in LSM
Thanapirom et al[26], 2022	DAA	89	1 yr	TE, SWE, and MRE	Viral eradication resulted in the reduction of LS values as evaluated by three elastography techniques
Rosato et al[27], 2022	DAA	516	24 mo	TE	- LS significantly decreased till SVR with a progressive reduction until 24 mo; - Only patients with steatosis and those who developed HCC did not experience a late improvement in LS
Yoo et al[28], 2022	DAA	112	48, 96 and 144 wk	TE, FIB-4 and APRI	LS value in patients achieving SVR signifcantly decreased over time (19.4 ± 12.9 kPa [baseline], 13.9 ± 9.1 kPa [48 wk], 11.7 ± 8.2 kPa [96 wk], 10.09 ± 6.23 [144 wk]

DAA: Direct acting antiviral; INF: Interferon; TE: Transient elastography; ARFI: Acoustic Radiation Force Impulse; LSM: Liver stiffness measurement; SWE: Shear wave elastography; MRE: Magnetic resonance elastography; SVR: Sustained virological response; HCC: Hepatocellular carcinoma; TIMP-1: Tissue inhibitor of metalloproteinases-1.