Consensus on management of hepatitis C virus infection in resource-limited Ukraine and Commonwealth of Independent States regions

Table 1 Definitions of the grading of the recommendations

Grading	Definition
Preferred	Treatment can be used in most patients and recommendation is based on optimal efficacy, favorable tolerability, toxicity profiles, treatment duration, and pill burden
Alternative	Treatment can be the one that is effective but with potential disadvantages/limitations in certain patient populations or with less supporting data as compared with the recommended regimens; in certain situations, an alternative regimen may be an optimal regimen for a specific patient population
Not recommended	Treatment is clearly inferior compared with the recommended or alternative regimens because of factors such as lower efficacy, unfavorable tolerability, toxicity, longer duration, and/or higher pill burden. Unless otherwise indicated, such regimens should not be administered in HCV-infected patients

HCV: Hepatitis C virus.

Table 2 Direct-acting antivirals available in Ukraine and specific Commonwealth of Independent States countries

Country	SOF	LDV/SOF	DCV
Uzbekistan	√	√	√
Ukraine	√	√
Belarus	√	√	√
Kazakhstan	√	√	√

SOF: Sofosbuvir; DCV: Daclatasvir; LDV: Ledipasvir.

Table 3 Recommended treatment regimens for hepatitis C virus GT1 infection

Recommendation category	Treatment option/s	Treatment regimens
Preferred	LDV + SOF ± RBV	LDV + SOF for 12 wk
		In treatment-naïve patients having HCV RNA < 6 million IU/mL in whom cirrhosis has been conclusively ruled out by transient elastography (FibroScan) or biopsy: LDV + SOF for 8 wk
		In treatment-experienced cirrhotic patients/patients with decompensated liver disease/postliver transplant patients: LDV + SOF + RBV for 12 wk (or) LDV + SOF for 24 wk if RBV is ineligible
Alternative	SOF + DCV ± RBV	SOF + DCV for 12 wk (addition of RBV may be considered if cirrhosis has not been conclusively ruled out)
		In patients with compensated cirrhosis: SOF + DCV ± weight-based RBV for 24 wk
		In patients with decompensated cirrhosis: SOF + DCV + RBV for 12 wk (or) SOF + DCV for 24 wk if RBV is ineligible
Not recommended	Due to the advent of newer DAAs, pegylated interferon, boceprevir, and telaprevir-based regimens are not recommended.

SOF: Sofosbuvir; LDV: Ledipasvir; DAAs: Direct-acting antivirals; DCV: Daclatasvir; RBV: Ribavirin; RNA: Ribonucleic acid.

Table 4 Recommended preferred treatment regimens for hepatitis C virus GT2 infection

Recommendation category	Treatment option(s)	Treatment regimen
Preferred	SOF + DCV ± RBV	SOF + DCV for 12 wk in noncirrhotics
		In decompensated cirrhosis and previous failures:
		SOF + DCV + RBV for 12 wk
	SOF + RBV	SOF + RBV for 12 wk in noncirrhotics
		To be extended to 24 wk in cirrhotics and treatment failures (Data are not available for patients with decompensated cirrhosis.)
		Should be considered as an alternative regimen when DCV is not available
Not recommended	Due to the advent of newer DAAs, pegylated interferon, boceprevir, and telaprevir-based regimens are not recommended.

DAAs: Direct-acting antivirals; DCV: Daclatasvir; RBV: Ribavirin; SOF: Sofosbuvir.

Table 5 Recommended treatment regimens for hepatitis C virus GT3 infection

Recommendation category	Treatment option(s)	Treatment regimen
Preferred	SOF + DCV ± RBV	SOF + DCV for 12 wk (addition of RBV may be considered if cirrhosis has not been conclusively ruled out)
		In patients with compensated cirrhosis
		Treatment-naïve patients: SOF + DCV + RBV for 24 wk if patients can tolerate ribavirin well, if not SOF+DCV for 24 wk
		Treatment-experienced patients: SOF + DCV + RBV for 24 wk if patients tolerated ribavirin well, if not SOF + DCV for 24 wk
		In patients with decompensated cirrhosis:
		SOF + DCV + RBV for 12 wk
		If RBV is ineligible: SOF + DCV for 24 wk
Alternative	SOF + RBV	SOF + RBV for 24 wk (should be considered only when preferred regimens are not available)
	LDV + SOF + RBV	LDV + SOF + RBV for 12 wk (should be considered only when preferred regimens are not available)
Not recommended	Due to the advent of newer DAAs, pegylated interferon, boceprevir, and telaprevir-based regimens are not recommended.

DAAs: Direct-acting antivirals; DCV: Daclatasvir; LDV: Ledipasvir; RBV: Ribavirin; SOF: Sofosbuvir.

Table 6 Recommended treatment regimens for hepatitis C virus GT4 infection

Recommendation category	Treatment option(s)	Treatment regimen
Preferred	LDV + SOF ± RBV	LDV + SOF for 12 wk [Addition of RBV may be considered based on the physician’s discretion in treating difficult-to-treat patients (treatment-experienced patients, patients with cirrhosis)].
		In case of previous SOF treatment failure: LDV + SOF + RBV for 12 wk
Alternative	SOF + DCV ± RBV	SOF + DCV for 12 wk (Addition of RBV may be considered if cirrhosis has not been conclusively ruled out.)
		Cirrhosis of any class: SOF + DCV + RBV for 12 wk
		If RBV is ineligible, SOF + DCV for 24 wk
Not recommended	Due to the advent of newer DAAs, pegylated interferon, boceprevir, and telaprevir-based regimens are not recommended.

DAAs: Direct-acting antivirals; DCV: Daclatasvir; LDV: Ledipasvir; RBV: Ribavirin; SOF: Sofosbuvir.

Table 7 Recommended treatment regimens for hepatitis C virus GT5 or GT6 infections

Recommendation category	Treatment option(s)	Treatment regimen
Preferred	LDV + SOF ± RBV	LDV + SOF for 12 wk [Addition of RBV may be considered based on the physician’s discretion in treating difficult-to-treat patients (treatment-experienced patients, patients with cirrhosis)].
		In case of previous SOF treatment failure: LDV + SOF + RBV for 12 wk
Alternative	SOF + DCV ± RBV	SOF + DCV for 12 wk (Addition of RBV may be considered if cirrhosis has not been conclusively ruled out.)
		Cirrhosis of any class: SOF + DCV + RBV for 12 wk
		If RBV is ineligible, SOF + DCV for 24 wk
Not recommended	Due to the advent of newer DAAs, pegylated interferon, boceprevir, and telaprevir-based regimens are not recommended.

DAAs: Direct-acting antivirals; DCV: Daclatasvir; LDV: Ledipasvir; RBV: Ribavirin; SOF: Sofosbuvir.

Table 8 On- and posttreatment assessments during the management of hepatitis C virus infection

Assessments	Expert recommendations
On-treatment	In patients with cirrhosis, CBC, creatinine level, estimated GFR, and hepatic function panel may be repeated after 4 wks
	All patients on RBV should have CBC done at four and 8 wk to monitor for hemolysis
	HCV RNA testing (qualitative/quantitative) may not be required, as there are no current recommendations for response-guided therapy. Testing at the end of treatment is mandatory
	Assessment of potential drug-drug interactions with concomitant medications is recommended
	A periodic review of therapy compliance and the general condition of the patient is recommended
Posttreatment	SVR should be assessed at 12 wk or 24 wk after the end of treatment
	In patients who have failed therapy:
	Disease progression (hepatic function panel, CBC, and INR) should be assessed once in 6-12 mo
	In patients with advanced fibrosis (Metavir stages F3 or F4), screening for hepatocellular carcinoma with ultrasound is recommended every 6 mo
	Endoscopic screening for esophageal varices is recommended in cirrhotic patients
	In patients who achieve SVR:
	In patients with advanced fibrosis (Metavir stage F3 or F4), screening for hepatocellular carcinoma with ultrasound is recommended in every 6 mo
	Endoscopic screening for esophageal varices is recommended in cirrhotic patients with pretreatment varices or portal hypertensive gastropathy
	AFP as a screening test for HCC is recommended in cirrhotic patients

CBC: Complete blood count; GFR: Glomerular filtration rate; RBV: Ribavirin; RNA: Ribonucleic acid; SVR: Sustained virologic response; AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma.