Sofosbuvir/Ribavirin therapy for patients experiencing failure of ombitasvir/paritaprevir/ritonavir + ribavirin therapy: Two cases report and review of literature

Table 1 Laboratory findings at baseline, and the treatments and outcomes of the patients

Parameters	Patient 1	Patient 2
Age (yr)	61	50
Sex	Female	Male
BMI (kg/m2)	25.1	29.7
HCV genotype	2a	2a
IFN-based therapy: Outcome	Peginterferon/ribavirin: Intolerance: discontinuation due to erythema and itching	Naive: NA
DAA-based therapy: Outcome	12-wk ombitasvir/paritaprevir/ritonavir plus ribavirin: relapse at PTW8	16-wk ombitasvir/paritaprevir/ritonavir plus ribavirin: breakthrough at the end of treatment
At the start of therapy
HCV RNA (log IU/mL)	4.7	6.9
AST (IU/L)	81	31
ALT (IU/L)	60	31
WBC (cells/μL)	4100	4900
Hemoglobin (g/dL)	11.3	15.5
Platelets (cells/μL)	118000	81000
AFP (ng/mL)	62	13.1
FIB4 index	5.41	3.44
APRI	2.08	1.16
RAVs at baseline1	None	None
IL28B SNP rs12979860	C/T	C/C
Severity of liver disease	Chronic hepatitis	Chronic hepatitis
Treatment and outcome
Sofosbuvir/ribavirin dosage (mg)	400/600	400/800
Achievement of a rapid virological response	Yes	Yes
Adherence to sofosbuvir/ribavirin	100%	100%
Weeks of therapy	12	12
Response	SVR24	SVR24
Concomitant drugs	Amlodipine besilate and eplerenone	None
Adverse events	Itching, chill, dull feeling in the throat, hypertension, cough, and increase of transaminases	Headache, blurring vision and light aversion probably due to recurrence of Vogt-Koyanagi-Harada disease, arthralgia and morning stiffness probably due to the development of rheumatoid arthralgia

¹ RAVs against NS3, NS5A or NS5B. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; AFP: Alpha-fetoprotein; APRI: AST-to-platelet ratio index; BMI: Body mass index; DAA: Direct-acting antiviral agent; HCV: Hepatitis C virus; IFN: Interferon; IL: Interleukin; NA: Not applicable; PTW: Post treatment week; RAVs: Resistance-associated variations; SNP: Single nucleotide polymorphism; SVR: Sustained virological response; WBC: White blood cells.

Table 2 Primers used for the amplification of the NS3, NS5A and NS5B regions of the genotype 2a hepatitis C virus genome

Primer name	Sequence (5’ to 3’)1	Nucleotide position2	Notes
HCV/2a-NS3 region
HC686	GTGGARCCYATYATCTTCAGTC	3263-3284	1st sense
HC687	GYACAGCHGGYGGYGTGCTG	3991-4010	RT and 1st antisense
HC688	TYATCTTCAGTCCGATGGAG	3273-3292	2nd sense
HC689	HGGYGGYGTGCTGTTGTCAC	3984-4003	2nd antisense
HCV/2a-NS5A region
HC694	YGCTTCCAGAGGAAACCACG	6118-6137	1st sense
HC695	AGCCCRACGCWRAACGAGAC	6785-6804	RT and 1st antisense
HC696	ACYCAYTACGTGACGGAGTC	6146-6165	2nd sense
HC697	CWRAACGAGACCTCRTCCCG	6776-6795	2nd antisense
HCV/2a-NS5B region
HC673	TGCTGCTCYATGTCWTACTCC	7661-7681	1st sense
HC669	GARTACCTRGTCATRGCCTCC	8686-8706	RT and 1st antisense
HC674	GCTCYATGTCWTACTCCTGGAC	7665-7686	2nd sense
HC670	CATRGCCTCCGTGAAGRCTC	8676-8695	2nd antisense

¹ R=A/G, D=G/A/T, H=A/C/T, W=A/T and Y=T/C.

² Nucleotide positions are numbered in accordance with the HC-J6 strain (D00944) as the HCV/2a reference. HCV: Hepatitis C virus.