Hepatitis C virus infection: Are there still specific problems with genotype 3?

Table 1 Reported prevalence of hepatitis C virus genotype 3

Country, Region	Viremic population	Genotype 3 prevalence	Ref.
Asia
India	6026 (3157-7174)	54.4%	[8]
	8666 (5150-15449)	64.0%	[14]
Malaysia	237 (47-1216)	58.6%	[8]
Pakistan	7039 (1728-10524)	79.0%	[8]
Thailand	925 (633-1259)	44.2%	[8]
Thailand, North		23%/16% (3a/3b)	[17]
Thailand, South		38%/14% (3a/3b)	[17]
Europe, Western
Denmark	21 (14-21)	43.0%	[8]
Finland	22 (16-27)	46.0%	[8,14]
Norway	29 (25-37)	28.1%	[8]
	22 (18-28)	50.0%	[14]
United Kingdom	210 (125-428)	43.8%	[8]
Middle East
Turkey	434 (274-959)	4.9%	[8]
Turkey, province of Kahramanmaras		46.0%	[16]
Australasia
Australia	234 (169-260)	36.8%	[8]
New Zealand	50 (27-72)	35.0%	[8,14]

Table 2 Factors associated with poor response to pegylated interferon α/RVB in hepatitis C virus GT-3- infected patients

Factors	Study design	Number of patients	Characteristics	Ref.	Comments
Viral factors
High baseline viral load (> 8 × 105 UI/mL)	Prospective	426 (all GT-3)	223 patients with viral load > 8 × 105 UI/mL	[56]	Combined with non-RVR
High baseline viral load (> 6 × 105 UI/mL)	Retrospective	107 (all GT-3)	45 non-SVR/62 SVR	[71]	Combined with advanced fibrosis
High baseline quasi- species complexity and diversity	Retrospective	10 (all GT-3)		[58]
Mutations in NS5A	Prospective	49 (all GT-3)	25 non-SVR/24 SVR	[62]	Significant mutations at positions 2309 (Ala to Ser) and 2326 (Gly to Ala)
Host factors
Fibrosis/Cirrhosis	Prospective	91 (all GT-3)	17 cirrhotic/74 non-cirrhotic	[63]	Also associated with increased risk of post-treatment relapse
	Retrospective	604 (all GT-3)	145 cirrhotic/459 non-cirrhotic	[64]	Response not affected by ethnicity
	Retrospective	180	108 GT-3/72 GT-2	[66]	Lack of SVR associated with fibrosis and GT-3
	Retrospective	107 (all GT-3)	45 non-SVR/62 SVR	[71]	Combined with high baseline viral load
Steatosis	Prospective	224	182 GT-3/42 GT-2	[69]	Lower SVR in GT-3
	Retrospective	932	505 GT-3/427 GT-2	[70]	Associated with higher relapse rates in GT-3 patients who had RVR
Ethnicity	Retrospective	103	66 Caucasians/38 Asians	[74]	Poor response could reflect more advanced liver disease at baseline in Asian patients
	Retrospective	604 (all GT-3)	305 non-Asians/299 South Asians	[64]	No correlation between ethnicity and treatment relapse
IFNL3 gene polymorphisms	Retrospective	107 (all GT-3)	45 non-SVR/62 SVR	[71]	No correlation between IFNL3 polymorphisms and SVR
	Prospective	293 HCV RNA- positive	65.87% GT-3/32.08% GT-1	[78]	CC and TT alleles strongly associated with SVR in GT-3 patients
Intrahepatic ISG15 expression/IFNL4 gene polymorphisms	Retrospective	92	36 GT-3/56 GT-1	[79]	In GT-3, low ISG15 expression and good-responder IFNL4 genotype associated with high SVR rates

GT: Genotype; SVR: Sustained virologic response; RVR: Rapid virologic response; NS5A: Non-structural 5A protein; IFNL: Interferon lambda; ISG: Interferon-stimulated gene; HCV: Hepatitis C virus.

Table 3 Overview of direct-acting antiviral-containing treatments for hepatitis C virus genotype-3-infected patients

Drug combination	Recommendations1	Duration	Ref.
IFN-containing treatment
PEG-IFN/RBV and SOF	For treatment-experienced patients, with or without cirrhosis	12 wk	[97]
PEG-IFN/RBV and DCV	Not yet recommended	12 or 16 wk	[98]
IFN-free treatment
SOF and RBV	Suboptimal in treatment-experienced cirrhotic patients	24 wk	[99,100]
SOF and DCV	For patients without cirrhosis	12 wk	[101]
SOF/DCV and RBV	For treatment-naive and treatment-experienced patients with cirrhosis	24 wk	[102]
SOF/ledipasvir (single-tablet regimen)	Not yet recommended	12 wk	[104]
Promising therapeutic option
GS-5816/SOF ± RBV	Under evaluation	12 wk	[107,108]

¹According to the EASL Clinical Practice Guidelines in April 2015[10].