Expert opinion on the management of hepatitis C infection in Kuwait

Figures & data

Table 1 Scoring criteria developed by the KHC

	Notes	Grading
Evidence quality
High	Data derived from multiple randomized clinical trials or equivalent (Phase III studies)	A
Moderate	Data derived from a single randomized trial, nonrandomized studies, meta-analyses, or equivalent	B
Low	Expert opinion, case studies, or standard of care	C
Relevance
Strongly relevant to Kuwaiti practice	Favorable opinion of procedure/therapy based on relevance to Kuwaiti clinical practice and local HCV patient population (eg, evidence focuses on genotype 4, which is more prevalent in Kuwait)	1
Weakly relevant to Kuwait practice	Inconclusive or poor opinion of procedure/therapy based on relevance to routine Kuwaiti clinical practice or typical Kuwaiti population with HCV	2

Abbreviations: KHC, Kuwait Hepatology Club; HCV, hepatitis C virus.

Table 2 Workshop: Kuwait standard of practice for diagnostics tests

First-line test	Frequency of retesting	Confirmatory test	Frequency of retesting
Acute
Anti-HCV antibody (A1)	6–12 weeks (in general population)	Anti-HCV antibody	6 weeks after diagnosis
HCV RNA quantitative test	12 weeks	HCV RNA quantitative test	After 12 weeks, if negative
Anti-HCV + HCV RNA	12 weeks (in immunocompromised patients)	None, if both are positive
Chronic
Anti-HCV antibody	24 weeks	HCV RNA quantitative test	Before therapy
HCV RNA quantitative test
Anti-HCV + HCV RNA		HCV RNA quantitative test	12 weeks, only if anti-HCV antibody was positive and RNA was negative

Abbreviation: HCV, hepatitis C virus.

Table 3 Therapies currently available in Kuwait

Regimensa	Name
PrO	Paritaprevir (75 mg)/ritonavir (50 mg) + ombitasvir (12.5 mg)
PrOD	Paritaprevir (75 mg)/ritonavir (50 mg) + ombitasvir (12.5 mg)/dasabuvir (250 mg)
SOF/LDV	SOF (400 mg) and LDV (90 mg)
DAC/SOF	DAC (60 mg)/SOF (400 mg)

Note:

a These regimens may be administered with or without ribavirin depending on prior therapy experience, genotype status, or underlying demographic characteristics and comorbidities.

Abbreviations: DAC, daclatasvir; LDV, ledipasvir; PrO, paritaprevir/ritonavir-ombitasvir; PrOD, PrO and dasabuvir; SOF, sofosbuvir.

Table 4 Summary of KHC treatment suggestions for GT1, GT4, and special populations

	Preferred	Alternative		Not recommended
GT1 (regimens are listed alphabetically, SVR12 rates are included as percentages)
Treatment naive
GT1a (noncirrhotic)	DAC/SOF × 12 weeks (A1): 98%^Citation22			SOF + RBV × 24 weeks (A1); PEG/RBV + PIs (SOF, TPV, and BOC) × 48 weeks (A1); monotherapy (PEG or RBVb)
	PrOD + RBV × 12 weeks (A1): >95%^Citation14
	SIM/SOF × 12 weeksa (B2): 95%^Citation23
	SOF/LDV × 12 weeks (A1): 97%^Citation19
GT1a (comp cirrhotic)a	SOF/LDV × 12 weeks (A1): 96%^Citation21	PrOD + RBV × 12 weeks (A1): >80%^Citation18		(A1)
		SIM/SOF ± RBV × 24 weeksa (B2): 96%^Citation23
		DAC/SOF ± RBV × 24 weeks (A1): 82% (decomp)^Citation16
GT1b (noncirrhotic)	DAC/SOF × 12 weeks (A1): 100%^Citation22
	PrOD × 12 weeks (A1): 99%^Citation15
	SOF/LDV × 12 weeks (A1): 87%^Citation20
	SIM/SOF × 12 weeksa (B2): 95%^Citation24
GT1b (comp cirrhotic)	PrOD × 12 weeks (A1): 100%^Citation16	SIM/SOF ± RBV × 24 weeksa (B2)
	SOF/LDV × 12 weeks (A1): 96%^Citation21	SOF/DAC ± RBV × 24 weeks (A1)
Treatment experience with PEG/RBV
GT1a PEG/RBV experienced (noncirrhotic)	DAC/SOF × 12 weeks (A1): 81.6%^Citation16
	PrOD + RBV × 12 weeks (A1): 96%^Citation17
	SIM/SOF × 12 weeksa (B2): 96%^Citation25
	SOF/LDV × 12 weeks (A1): 94%^Citation20
GT1a PEG/RBV experienced (comp cirrhotic)	SOF/LDV × 24 weeks (A1): 97%^Citation17	PrOD + RBV × 24 weeks (A1): >95%^Citation17
	SOF/LDV + RBV × 12 weeks (A1): 96%^Citation17	SIM/SOF ± RBV × 24 weeksa (B2): 80%^Citation16
		SOF/DAC ± RBV × 24 weeks (A1)
GT1b PEG/RBV experienced (noncirrhotic)	DAC/SOF × 12 weeks (A1): 82.6%
	PrOD × 12 weeks (A1): 100%^Citation40
	SIM/SOF × 12 weeksa (B2): 95%^Citation25
	SOF/LDV × 12 weeks (A1): 98%^Citation20
GT1b PEG/RBV experienced (comp cirrhotic)	PrOD × 12 weeks (A1): 100%^Citation16	SIM/SOF ± RBV × 24 weeksa (B2): 76%^Citation16
	SOF/LDV + RBV × 12 weeks (A1): 96%^Citation21	SOF/DAC ± RBV × 24 weeks (A1)
	SOF/LDV × 24 weeks (A1): 97%^Citation21
Treatment experience with SOF + RBV
GT1 SOF + RBV experienced (noncirrhotic)	SOF/LDV + RBV × 12 weeks (A1): 100%^Citation20
GT1 SOF + RBV experienced (cirrhotic)	SOF/LDV + RBV × 24 weeks (A1): 97%^Citation21
Treatment experience with PI-based regimen
GT1 PI + PR experienced (noncirrhotic)	DAC/SOF × 12 weeks (A1): 82.6%^Citation16 SOF/LDV × 12 weeks (A1): 98%^Citation20			IFN-free regimen including SIM or paritaprevir (A1); PEG/RBV alone (A1); SIM + PEG/RBV (A1); SOF + PEG/RBV (A1); TPV + PEG/RBV (A1); BOC + PEG/RBV (A1); monotherapy with PEG, RBV, DAA (A1)
GT1 PI + PR experienced (cirrhotic)	DAC/SOF ± RBV × 24 weeks (A1): 97.1%^Citation16
	SOF/LDV + RBV × 12 weeks (A1): >80%^Citation20
	SOF/LDV × 24 weeks (A1): 100%^Citation20
Treatment experience with SIM/SOF
GT1 SIM/SOF experienced (noncirrhotic)	RAV testing and treat according to resultsc
	SOF-based dual treatment + RBV × 24 weeks
	SOF-based triple/quadruple treatment × 12–24 weeks + RBV
GT1 SIM/SOF experienced (cirrhotic or in immediate need of treatment)	RAV testing and treat according to resultsc
	SOF-based dual treatment + RBV × 24 weeks
	SOF-based triple/quadruple treatment × 12–24 weeks + RBV
GT1	NS3/NS5A RAV testing and treat according to results
	SOF-based dual treatment + RBV × 24 weeks
	SOF-based triple/quadruple treatment × 12–24 weeks + RBV
GT4
GT4 (noncirrhotic, comp cirrhotic)	PrO + RBV × 12 weeks (A1): 100%^Citation37 SOF/LDV × 12 weeks (B1): 94%^Citation38			PEG/RBV ± SIM × 24–48 weeks (A1); SOF/RBV + PEG × 12 weeks (A1); monotherapy (PEG or RBV or DAA) (A1); TPV- or BOC- based regimens (A1)
GT4 PR experienced (noncirrhotic)	PrO + RBV × 12 weeks (A1): 100%^Citation37			PEG-IFN/RBV with or without TPV or BOC (A1); monotherapy (A1) with PEG-IFN, RBV, or DAA
	SOF/LDV × 12 weeks (A1): 94%^Citation38
GT4 PR experienced (comp cirrhotic)	PrO + RBV × 12 weeks (A1): 96%^Citation35,Citation36
	SOF/LDV + RBV × 12 weeks (A1): 95%^Citation39
	SOF/LDV × 24 weeks (A1)
Unique patient population in GT1 and GT4 patients: decompensated cirrhosis (CTP B or C)
GT1 or GT4 (CTP B or C)	DAC/SOF + RBV × 12 weeksd (A1): 83%^Citation41			IFN-based treatment (A1); monotherapy PEG-IFN, RBV, or DAA (A1); TPV, BOC, or SIM-based PrOD (A1)
	SOF/LDV + RBV × 12 weeks (A1): 87% (B) and 86% (C)^Citation42
GT1 or GT4 RBV ineligible	DAC/SOF × 24 weeksd(A1)
	SOF/LDV × 24 weeks (A1)
GT1 or GT4 (SOF experienced)	SOF/LDV + RBV × 24 weeks (A1)
Unique patient population in GT1 and GT4 patients: liver transplante
GT1 or GT4 in allograft, comp cirrhotic, naive, and experienced	DAC/SOF + RBV × 12 weeks (A1): 87%^Citation44 and 94%^Citation41
	SOF/LDV + RBV × 12 weeks (A1): 96%^Citation45
GT1 or GT4 in allograft comp cirrhotic, naive, RBV ineligible	DAC/SOF × 24 weeks (A1)
	SOF/LDV × 24 weeks (A1)
GT1 or GT4 in allograft, decompensated (CTP class B and C) naive and experienced	SOF/LDV + RBV × 12 weeks (A1)
GT1 in allograft, including comp cirrhotic			SOF/SIM ± RBV × 12 weeks (B2)
GT1 in allograft, including F0–F2			PrOD + RBV × 24 weeks (A1)
HCV in allograft with comp cirrhotic				PEG-IFN (A1); monotherapy PEG-IFN, RBV, or DAA (A1); TPV and BOC (A1)
HCV in allograft with decompensated cirrhosis				PEG-IFN (A1); SIM (B2); PrOD or PrO or RBV (A1); monotherapy PEG-IFN, RBV, and DAA (A1); TPV and BOC (A1)
Unique patient population in GT1 and GT4 patients: renal impairment
Severe CKD (creatinine clearance <30 mL/min or end-stage renal disease)	GT1b: PrOD (no D for GT4) × 12 weeks (A1): 90%^Citation46		GT1a: PrOD + RBV × 12 weeks (A1)
Mild or moderate CKD (creatinine clearance 30–80 mL/min)	No dosage adjustment needed for: PrOD/PrO (A1), SIM (A1), or SOF (A1)

Notes:

a For cirrhotic patients, some regimens are classified as alternative regimens because they have longer duration, potentially reduced efficacy, and/or limited supporting data compared with the preferred regimens.

b Low-dose RBV (600–800 mg) can be used with patients who have an initial hemoglobin value of <11 g/dL (evidence rating: C1).

c The KHC voted that there was no need to defer treatment in GT1 SIM/SOF-experienced noncirrhotic patients. SOF/LDV may be given. The KHC was divided on whether to wait for FibroScan results before SOF/LDV could be administered.

d Dose-adjust cytochrome P450 3A/4 inducers.

e The KHC stated that not enough postliver transplant patients are seen in Kuwait.

Abbreviations: BOC, boceprevir; DAA, direct-acting antiviral agent; DAC, daclatasvir; GT, genotype; HCV, hepatitis C virus; IFN, interferon; KHC, Kuwait Hepatology Club; LDV, ledipasvir; NS, nonstructural; CKD, chronic kidney disease; CTP, Child–Turcotte–Pugh; PEG, PEGylated; PIs, protease inhibitors; PR, PEG-IFN and RBV; PrO, paritaprevir/ritonavir-ombitasvir; PrOD, PrO and dasabuvir; RAV, resistance-associated variants; RBV, ribavirin; SIM, simeprevir; SOF, sofosbuvir; SVR, sustained virologic response; TPV, telaprevir.

Table 5 Summary of KHC treatment suggestions for genotypes 2, 3, 5, and 6

	Preferred	Alternative	Not recommended
GT2: treatment naive
GT2 (noncirrhotic)	DAC/SOF (400 mg) × 12 weeks (no RBV for RBV-intolerant patients) (A1): 92%^Citation22		PEG-IFN and RBV for 24 weeks (A1); monotherapy with PEG-IFN, RBV, or a direct-acting antiviral (A1); TPV-, BOC-, or LDV-containing regimens (A1)
	SOF/RBV × 12 weeks (A1): 97%^Citation16
GT2 (comp cirrhotic)	DAC/SOF (400 mg) × 16–24 weeks (RBV-intolerant patients) (A1): 100%^Citation22
	SOF/RBV × 16–24 weeks (A1): 100%^Citation16
GT2: treatment experienced
GT2 PEG-IFN/RBV experienced	DAC/SOF (400 mg) × 12 weeks (A1): 92%^Citation22		PEG-IFN and ± TPV or BOC, LDV/SOF (A1); monotherapy with PEG-IFN, RBV, or a direct-acting antiviral (A1)
	SOF/RBV × 12 weeks (A1): 91%^Citation45
GT2 PEG-IFN/RBV experienced (comp cirrhosis)	DAC/SOF (400 mg) × 16–24 weeks (RBV-intolerant patients) (A1)	SOF (400 mg) + RBV + PEG-IFN × 12 weeks (A1)
	SOF/RBV × 16–24 weeks (A1): 79%^Citation45
GT2 SOF/RBV experienced	DAC/SOF (400 mg) × 24 weeks (RBV-intolerant patients) (A1): 100%^Citation30
	SOF/RBV + PEG-IFN × 12 weeks (A1)
GT2: treatment-naive and treatment-experienced patients with HCV infection in the allograft, including those with
compensated cirrhosis
GT2	DAC/SOF + RBV (600 mg) × 12 weeks (A1)		Regimens containing PEG-IFN (A1); monotherapy with PEG-IFN, RBV, or a DAA (A1)
	SOF + RBV × 24 weeks (A1)
GT2 RBV intolerant or ineligible	DAC/SOF × 24 weeks (A1)
GT3 patients: treatment-naive and treatment-experienced patients including those with compensated cirrhosis
GT3	DAC/SOF (400 mg) ± RBV × 12 weeks (A1): 97%	SOF (400 mg) + RBV + PEG-IFN × 24 weeks (DAC and IFN ineligible) (A1)	PEG-IFN and RBV for 24–48 weeks (A1); monotherapy with PEG-IFN, RBV, or a direct-acting antiviral (A1); TPV-, BOC-, or SIM-based regimens (A1)
	SOF (400 mg) + RBV + PEG-IFN × 12 weeks (A1): 56%^Citation16
GT3 (cirrhosis)	DAC/SOF (400 mg) ± RBV × 24 weeks: 58%
	SOF (400 mg) + RBV + PEG-IFN × 12 weeks (A1)
GT3 (PEG-IFN/RBV experienced)	DAC/SOF × 12 weeks (A1)		PEG-IFN + RBV × 24–48 weeks (A1); monotherapy with PEG-IFN, RBV, or a direct-acting antiviral (A1); TPV-, BOC-, or SIM-based regimens (A1)
	SOF + RBV + PEG-IFN × 12 weeks (A1): 83%^Citation16
GT3 (PEG-IFN/RBV experienced, comp cirrhosis)	DAC/SOF + RBV × 24 weeks (A1)
	SOF + RBV + PEG-IFN × 12 weeks (A1): 83%^Citation16
GT3 SOF/RBV experienced	DAC/SOF (400 mg) + RBV × 24 weeks (IFN-intolerant patients) (A1)
	SOF/RBV + PEG-IFN × 12 weeks (A1): 93%^Citation16
Genotype 2 or 3 treatment-naive and -experienced patients with HCV genotype 2 infection in the allograft who have compensated cirrhosis
GT2, GT3 (comp cirrhosis)	DAC/SOF (400 mg) ± RBV × 12 weeks (A1)		Regimens containing PEG-IFN (A1); monotherapy with PEG-IFN, RBV, or a direct-acting antiviral (A1); TPV-, BOC-, GZP-, or EBV-based regimen (A1)
	SOF (400 mg) + RBV + PEG-IFN × 24 weeks (A1)
GT2, GT3 (PEG-IFN/RBV experienced, comp cirrhosis)	DAC/SOF (400 mg) × 24 weeks (A1)
Genotype 2 or 3 patients who have decompensated cirrhosis (moderate or severe hepatic impairment; CTP class B or C) and who may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma
GT2, GT3	DAC/SOF + RBV (600 mg) × 12 weeks (A1)		Any IFN-based therapy (A1); monotherapy with PEG-IFN, RBV, or a direct-acting antiviral (A1); paritaprevir-, ombitasvir-, or dasabuvir-based regimens (A1); TPV-, BOC-, SIM-, GZP- or EBV-based regimens (A1)
Genotype 2 or 3 patients: treatment-naive and treatment-experienced liver transplant recipients with decompensated cirrhosis (CTP class B or C) who have HCV genotype 2 or 3 infection in the allograft
GT2	SOF + RBV (initial 600 mg increase monthly by 200 mg/day as tolerated; 1000 mg [<75 kg] to 1200 mg [>75 kg]) × 24 weeksa (A1)		Regimens containing PEG-IFN; regimens containing SIM; fixed-dose combination of paritaprevir, ritonavir, and ombitasvir plus twice-daily dasabuvir and RBV; monotherapy with PEG-IFN, RBV, or a DAA; TPV-, BOC-, GZP-, and EBV-based regimens
GT3	SOF + RBV (initial 600 mg, increase as tolerated; 1000 mg [<75 kg] to 1200 mg [>75 kg]) × 24 weeksb (A1)
Genotype 2 or 3 patients: treatment-naive and treatment-experienced liver transplant recipients with decompensated cirrhosis(CTP class B or C) who have HCV genotype 3 infection in the allograft
GT2	SOF + RBV (initial 600 mg increase monthly by 200 mg/day as tolerated; 1000 mg [<75 kg] to 1200 mg [>75 kg]) × 24 weeksa (A1)		No available data
GT3	SOF + RBV (initial 600 mg, increase as tolerated) × 24 weeksb (A1)
Genotype 5 and 6 patients: very few patients of these genotypes are seen in Kuwait
GT5, GT6	SOF/LDV × 12 weeks: 93% (GT5)^Citation39,c		No available data

Notes:

a With consideration of the patient’s creatinine clearance rate and hemoglobin level for up to 48 weeks.

b No dose adjustment is required for tacrolimus or cyclosporine with SOF–RBV, SOF–LDV, or SOF–DAC. Because of high plasma concentrations of SIM, the concomitant use of SIM and cyclosporine A is not recommended in liver transplant recipients. No SIM dose changes are required with tacrolimus and sirolimus, but the patient’s blood concentrations should be monitored regularly. When using the combination of ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir, the tacrolimus dose must be adjusted to 0.5 mg once weekly or to 0.2 mg every 3 days, whereas the cyclosporine A dose must be adjusted to one-fifth of the daily dose given prior to HCV treatment once daily; prednisone use at doses ≤5 mg/day is permitted, but mTOR inhibitors are not recommended.

c The KHC generally agreed with AASLD recommendation for the treatment of these patients. Currently, SOF/LDV is the only option available in Kuwait. Other AASLD-approved treatments are not approved yet.

Abbreviations: AASLD, American Association for the Study of Liver Diseases; BOC, boceprevir; CTP, Child–Turcotte–Pugh; DAC, daclatasvir; EBV, elbasvir; GT, genotype; GZP, grazoprevir; HCV, hepatitis C virus; IFN, interferon; KHC, Kuwait Hepatology Club; LDV, ledipasvir; PEG, PEGylated; RBV, ribavirin; SIM, simeprevir; SOF, sofosbuvir; TPV, telaprevir.

Table 6 Common barriers to HCV treatment and potential strategies to address these barriers

Barrier	Strategy
Contraindications to treatment (eg, comorbidities, substance abuse, and psychiatric disorders)	Counseling and education
	Referral to services (eg, psychiatry and opioid substitution therapy)
	Optimize treatment with simpler and less-toxic regimens
Competing priority and loss to follow-up	Conduct counseling and education
	Engage case managers and patient navigators (HIV model)
	Colocalize services (eg, primary care, medical homes, and drug treatment)
Long treatment duration and adverse effects	Optimize treatment with simpler and better tolerated regimens
	Education and monitoring
	Directly observed therapy (tuberculosis model)
Lack of access to treatment (high cost, lack of insurance, geographic distance, and lack of availability of specialists)	Participate in models of care involving close collaboration between primary care practitioners and specialists
	Pharmaceutical patient assistance programs
	Colocalize services (primary care, medical homes, and drug treatment)
Lack of practitioner expertise	Collaboration with specialists (eg, via Project ECHO-like models and telemedicine)
	Develop accessible and clear HCV treatment guidelines
	Develop electronic health record performance measures and clinical decision support tools (eg, pop-up reminders and standing orders)

Abbreviations: ECHO, Extension for Community Health Outcomes; HCV, hepatitis C virus.

Figure 1 Proposed initiatives to contain the transmission of HCV.

Abbreviations: HCV, hepatitis C virus; STD, sexually transmitted diseases; PWIDS, people who inject drugs.

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