Metabolic and cardiovascular complications after virological cure in hepatitis C: What awaits beyond

Table 1 Summary of studies investigated cardiometabolic manifestations of chronic hepatitis C after viral cure

Ref.	Antiviral regimen	The studied HCV-associated cardiometabolic manifestations	Post SVR outcomes
Fernández-Rodríguez et al[28], 2006	NA1	Lipid disturbances. Hepatic steatosis	Hypercholesterolemia in patients with genotype 3
			No change in genotype 3 non-responders and in patients with genotype 1 regardless of response
			Decrease in steatosis
Giordanino et al[71], 2008	IFN monotherapy or Peg-IFN + RBV (24-48 wk)	Glucose abnormalities (IFG or DM)	No significant reduction in the risk of glucose intolerance in long-term responders and non-responders
Arase et al[70], 2009	IFN monotherapy or IFN + RBV2	DM	Decreased incidence of DM in sustained responders. However, its development is associated with advanced liver disease
Corey et al[18], 2009	NA1	Lipid abnormalities	Increased LDL and total cholesterol from baseline compared to non-responders
		Risk of CVD	Increased CVD risk profile
Conjeevaram et al[67], 2011	Peg-IFN + RBV (24-48 wk)	IR	Decreased IR
		Obesity	Decreased in BMI
Kuo et al[27], 2011	Peg-IFN + RBV (24 wk)	Change in serum lipid	Total cholesterol and triglycerides levels significantly increased
			No evident change in lipid profile occurred in non-SVR group
Aghemo et al[68], 2012	Peg-IFN + RBV2	IR in non-diabetic CHC patients	Baseline and posttreatment HOMA-IR values were similar in SVR patients
			Significant increase in HOMA-IR was noted in non-SVR patients
Clark et al[25], 2012	Albinterferon α-2b + RBV	Lipid abnormalities in genotypes 2,3	Hypercholesterolemia
Thompson et al[66], 2012	Albinterferon α-2b vs Peg-IFN + RBV (24-48 wk)	IR in genotypes 1,2,3	Reduced IR in genotype 1 responders
			No change in genotype 1 non-responders and genotype 2 and 3 regardless of the response
Chang et al[29], 2014	eg-IFN + RBV (24/48 wk)	Lipids and IR in genotypes 2, 3	Increased total cholesterol and triglycerides in sustained responders
			Decreased HOMA-IR in patients with SVR and baseline IR
			High HOMA-IR was found in patients without baseline IR (only in genotype 1)
Hsu et al[88], 2015	Peg-IFN + RBV (16-48 wk)	Acute coronary syndrome and ischemic stroke	Improvement in both studied circulatory outcomes
Innes et al[89], 2015	NA1	CVD	Reduced hazard and absolute risk for CVD
Meissner et al[24], 2015	SOF + RBV (24 wk)	Lipid disturbances in genotype 1	Increased LDL level and particle size and decreased triglycerides concentration and VLDL particle size irrespective to treatment response
			Increased intrahepatic lipid-related genes in sustained responders
Leone et al[72], 2016	IFN-based regimen	DM and CVD	No significant risk reduction in DM and CVD in SVR group as opposed to non SVR
Yair-Sabag et al[39], 2016	Peg-IFN + RBV (24-48 wk)	IFG and DM. Triglycerides. Hepatic steatosis	Lower IFG and DM, and higher triglycerides in sustained responders
			Improvement in hepatic steatosis
Chang et al[16], 2017	NA1	Cardiovascular complications	An increased adipokine PAI-1 in SVR group, which accelerates cardiovascular risk, especially in vulnerable cases
Mahale et al[69], 2018	IFN-based regimen2	DM and CVD	Antiviral therapy associated with lower risk of DM and stroke whereas no significant effect on CVD
Nahon et al[90], 2017	Peg-IFN + RBV (16-48 wk) or combination therapies3	CVD	Lower risk of CVD in SVR subjects in comparison to non SVR
Stine et al[74], 2017	DAAs2,3	DM in genotypes 1, 2, 3	Glycosylated hemoglobin was not affected in known diabetic patients
			1/3 of patients required escalation of anti-diabetic therapy during antiviral treatment
Carvalho et al[11], 2018	SOF + LDV ± RBV (group 1) vs Peg-IFN + RBV (group 2)	Lipid levels. Serum glucose. IR	While total cholesterol increased in both groups, triglycerides levels decreased in group 1 and increased in group 2
			LDL elevated in group 1 and No change in group 2
			No significant variation in serum glucose
			Significant increase in HOMA-IR only in group 2
Kawagishi et al[17], 2018	DAAs3	Hepatic steatosis. Lipid abnormalities	Decrease in CAP and LDL in patients with high baseline values
			Elevated sdLDL in patients who had dyslipidemia and hepatic steatosis at 24 wk
Li et al[73], 2018	DAAs4	DM	Lower risk of DM in SVR patients than in treatment failure group
Noureddin et al[46], 2018	DAAs3	Hepatic steatosis and fibrosis	High prevalence of fatty liver
			Although fibrosis has been reduced in patients with and without steatosis compared to baseline, patients with steatosis continued to have clinically significant liver stiffness
Li et al[10], 2019	IFN + RBV (48 wk)	Serum glucose level and IR	Reduced glucose level
			Improved IR
Butt et al[87], 2019	IFN + RBV2,3. DAAs2,3	CVD	Lower incidence in treatment group, compared to controls
			DAAs showed greater risk reduction than interferon-based regimen
			SVR associated with decreased CVD risk
Abdo et al[75], 2020	SOF + DCV (12-24 wk)	Glycemic status, IR, and lipid profile in CHC patients with DM	Improvement of glycemic state and HOMA-IR
			Global worsening of lipid profile
Graf et al[45], 2020	DAAs3	IR, lipid perturbations, body weight changes, and hepatic steatosis	Lower HOMA-IR compared to baseline
			Higher total cholesterol, LDL, and HDL
			Higher CAP relative to baseline
			BMI did not significantly change over time
Huang et al[31], 2020	DAAs4	Lipids and cardiovascular events	Increased total cholesterol and LDL
			Higher cardio-cerebral diseases

¹No data available on antiviral therapy.

²Data on course of treatment is not available.

³Various regimens were used.

⁴No data available neither on types of direct acting antiviral agents nor on treatment duration. BMI: Body mass index; CAP: Controlled attenuation parameter; CHC: Chronic hepatitis C; CVD: Cardiovascular disease; DAAs: Direct acting antiviral agents; DCV: Daclatasvir; DM: Diabetes mellitus; HDL: High density lipoprotein cholesterol; HOMA-IR: Homeostatic model assessment of insulin resistance; IFG: Impaired fasting glucose; IFN: Interferon; IR: Insulin resistance; LDL: Low-density lipoprotein cholesterol; LDV: Ledipasvir; NA: Not available; PAI-1: Plasminogen activator inhibitor-1; Peg-IFN: Pegylated interferon; RBV: Ribavirin; sdLDL: Small-dense low-density lipoprotein; SOF: Sofosbuvir; SVR: Sustained virologic response; VLDL: Very low-density lipoprotein cholesterol; HCV: Hepatitis C virus.