Impact of direct-acting antiviral regimens on hepatic and extrahepatic manifestations of hepatitis C virus infection

Table 1 Current diagnostic and tools to assess liver disease stages and severity in hepatitis C virus infected patients

Diagnostic tool	Early fibrosis stages (METAVIR less than F2)	Fibrosis 2	Fibrosis 3	Compensated cirrhosis	Decompensated cirrhosis	Ref.
HCV antibody	Positive	Positive	Positive	Positive	Positive	AASLD and IDSA[30]
Quantitative HCV RNA (viral load)	Positive	Positive	Positive	Positive	Positive
Platelet count < 150000/mm3)	Normal	Normal	Normal	< 150000/mm3	< 150000/mm3
Total and direct bilirubin, ALT & AST	Normal/elevated	Normal/elevated	Normal/elevated	Elevated	Elevated
Child- Pugh	--------	--------	--------	Class A (scores 5-6)	Class B (scores 7-9); Class C (scores 10-15)
FIB-4 Score	< 1.45	≥ 1.45 but < 2.67	≥ 2.67 but < 3.25	≥ 3.25	> 3.25	Filozof et al[31]
Fibroscan by transient elastography	5.3 kPa	7.4 kPa	9.1 kPa	13.2 kPa	13.2 kPa	Platon et al[32]
Fibro test	< 0.48	0.48 - 0.58	> 0.58 but < 0.74	> 0.74	> 0.74	Laboratory Corporation of America[33]
Enhanced liver fibrosis test	< 7.7	7.7	9.8	11.3	11.3	Lichtinghagen et al[34]
Aspartate aminotransferase to platelet ratio index	< 0.77	0.77	0.77	≥ 0.83	≥ 0.83	Lin et al[35]
Liver nodularity and/or splenomegaly	Negative	Negative	Negative	Positive	Positive	AASLD and IDSA[30]
Prior liver biopsy	F0: No fibrosis; F1: Portal fibrosis without septa	F2: Portal Fibrosis with few septa	F3: Numerous septa without cirrhosis	F4: Cirrhosis	F4: Cirrhosis

HCV: Hepatitis C virus.

Table 2 Recommended direct-acting antiviral regimens for treatment of hepatitis C virus infection according to AASL/ADSA 2021

Treatment	No cirrhosis		Compensated cirrhosis		Decompensated cirrhosis
	Naïve HCV infected patient	Previously treated patients	Naïve HCV infected patients	Previously treated patients
Sofosbuvir (400 mg)/Velpatasvir (100 mg)	12 wk	Sofosbuvir (400 mg)/Velpatasvir (100 mg)/Voxilapevir (100 mg), 12 wk, for all genotypes. ALTERNATIVE: Glecaprevir (300 mg)/Pibrentasvir (120 mg), but not recommended for genotype 3 with Sofosbuvir/NS5A inhibitor	For genotypes 1, 2, 4, 5, and 6 & genotype 3 with NS5A-RAS Y93H negative, 12 wk, but not recommended for genotype 3 with NS5A-RAS Y93H positivity	Sofosbuvir (400 mg)/Velpatasvir (100 mg)/Voxilapevir (100 mg), 12 wk, for genotypes 1, 2, 4, 5, and 6; for genotype 3, 12 wk in addition to weight-based Ribavirin. ALTERNATIVE: Glecaprevir (300 mg)/Pibrentasvir (120 mg), but not recommended for genotype 3 with Sofosbuvir/NS5A inhibitor	Patients with HCV infection who have decompensated cirrhosis, i.e., Child-Pugh class B or class C, should be referred to a medical practitioner with expertise in that condition, ideally in a liver transplant center
Glecaprevir (300 mg)/Pibrentasvir (120 mg)	8 wk	16 wk in addition to Sofosbuvir (400 mg) + weight-based Ribavirin ALTERNATIVE: 12 wk of Sofosbuvir (400 mg)/Velpatasvir (100 mg)/Voxilapevir (100 mg)	8 wk	16 wk in addition to Sofosbuvir (400 mg) + weight-based Ribavirin. ALTERNATIVE: 12 wk of Sofosbuvir (400 mg)/Velpatasvir (100 mg)/Voxilapevir (100 mg) in addition to weight-based Ribavirin
Elbasvir (50 mg)/Grazoprevir (100 mg)	12 wk for genotype 1b	12 wk Sofosbuvir (400 mg)/Velpatasvir (100 mg)/Voxilapevir (100 mg). However, Glecaprevir/Pibrentasvir for 16 wk is not recommended as an alternative for this group of patients	12 wk for genotype 1B	NA

HCV: Hepatitis C virus; RAS: Resistance-associated substitutions; NA: Not applicable