Table 1.
Summary of studies investigating metabolic manifestations of chronic hepatitis C.
| Ref. | The Metabolic Outcome of Interest | Findings |
|---|---|---|
| Adinolfi et al. [99], 2001 | HS and hepatic fibrosis score | HS, and especially the higher grades, is of clinical importance because it showed a higher hepatic fibrosis score than those with a lower grade or without HS. |
| Kumar et al. [93], 2002 | Post-SVR effect on HS | In individuals with HCV genotype 1, regardless of treatment response, there was no change in HS after treatment. SVR significantly reduced HS among individuals infected with genotype 3, whereas there was no improvement in HS among those without an SVR. |
| Perlemuter et al. [94], 2002 | HS mechanism | Hepatitis C virus core protein inhibits MTP activity and VLDL secretion |
| Ishizaka et al. [104], 2002 | Carotid plaque and carotid IMT | There is an association between HCV seropositivity and carotid-artery plaque and carotid IMT was independent of other atherosclerosis risk factors. |
| Asselah et al. [101], 2003 | HS, necroinflammation, and fibrosis | HS does not appear to be a significant predictor of liver fibrosis in people with CHC. A high stage of fibrosis is related with a high grade of necroinflammation. |
| Hézode et al. [91], 2004 | HS and HCV genotype | In patients infected with HCV genotype 3, the severity of HS was independently related to HCV RNA load alone, whereas in individuals infected with HCV genotype 1, it was independently associated to body mass index, total alcohol intake, and histopathologic activity grade (but not viral load). |
| Castéra et al. [92], 2004 | HS and effect of SVR | There is a remarkable improvement in HS in subjects infected with HCV genotype 3, who acquired SVR. |
| Perumalswami et al. [100], 2006 | HS and fibrosis | In patients with CHC, HS was not associated with the presence of or subsequent progression of fibrosis. |
| Fernández-Rodríguez et al. [79], 2006 | HS and cholesterol level in HCV genotype 3 | Besides producing HS, HCV genotype 3 specifically reduces serum cholesterol which then reversed with SVR. |
| Targher et al. [105], 2007 | Carotid IMT | IMT of CHC patients was smaller compared to IMT of NAFLD, but larger in comparison to the IMT of controls |
| Butt et al. [114], 2007 | Coronary artery disease and stroke | The prevalence and likelihood of coronary artery disease and stroke are reduced in HCV-infected individuals. |
| Reddy et al. [90], 2008 | HS and HCV genotype | HS is substantially more prevalent in patients infected with HCV genotype 3 than other genotypes and that successful treatment of HCV genotype 3 infection with interferon plus ribavirin is associated with clearance of HS. |
| Sheridan et al. [31], 2009 | Serum lipid and treatment outcome | Higher apoB-associated cholesterol is associated with improved treatment outcomes in CHC patients receiving antiviral medication. |
| Corey et al. [82], 2009 | post- treatment hyperlipidemia and coronary artery disease | HCV is linked to lower levels of cholesterol and LDL. This hypolipidemia reverse with successful HCV treatment but persists in non-responders. A considerable proportion of successfully treated patients experience LDL and cholesterol rise to levels associated with increased coronary disease risk |
| Butt et al. [109], 2009 | Coronary artery disease | HCV infection is associated with a greater risk of coronary artery disease, even after adjustment for traditional risk factors. |
| Harrison et al. [73], 2010 | Serum lipid, statin use and treatment outcome | Elevated LDL or low HDL levels at baseline, as well as anticipatory statin use, were associated with greater SVR rates. |
| Mostafa et al. [120], 2010 | Lipoprotein profile, insulin resistance, Carotid IMT | The risk of carotid atherosclerosis was considerably elevated in HCV-infected persons, but not in HCV-cleared individuals, compared to uninfected controls. |
| Lee et al. [121], 2010 | Cerebrovascular diseases | HCV infection is linked with a greater risk of cerebrovascular mortality, especially for those with higher serum HCV RNA levels. |
| Corey et al. [68], 2011 | Hypolipidemia | Acute HCV infection results in hypolipidemia characterized by lower LDL, cholesterol and non-HDL cholesterol levels that reverse following infection resolution. |
| Adinolfi et al. [103], 2012 | Carotid atherosclerosis, HS | CHC patients had a greater prevalence of carotid atherosclerosis than controls.CHC with HS had a higher prevalence of carotid atherosclerosis than NAFLD patients. |
| Petta et al. [106], 2012 | Carotid atherosclerosis | Severe hepatic fibrosis is associated with an increased risk of early carotid atherosclerosis in HCV genotype 1 patients. |
| Liao et al. [111], 2012 | Stroke | CHC infection was independently associated with increased risk of stroke after controlling for conventional stroke risk factors. |
| Lambert et al. [70], 2013 | Serum lipids abnormalities | Patients with HCV have increased lipogenesis but decreased cholesterol production compared to healthy people. |
| Hsu et al. [112], 2013 | Stroke and Post-SVR | Interferon-based therapy may decrease stroke risk in CHC patients, independent of other confounders. |
| Adinolfi et al. [113], 2013 | Ischemic stroke. | HCV infection is associated with an increased risk of ischemic stroke. |
| Chang et al. [80], 2014 | Post-SVR changes in cholesterol, triglycerides, HDL, LDL, ApoB. | Significant post-therapeutic elevation in cholesterol, triglyceride, HDL, LDL, ApoA1 and ApoB were reported in patients with SVR but not in those without. Although the pre-treatment lipid profiles of genotype1 and genotype 2 patients were indifferent, genotype 1 had greater post-treatment triglyceride/HDL ratios and triglyceride levels than genotype2 individuals. |
| Lin et al. [108], 2014 | Ischemic heart disease | HCV seropositivity was an independent risk apart from conventional factors for ischemic heart disease. |
| Foka et al. [7], 2014 | SVR, Persistent lipid abnormalities | It has been shown that ANGPTL-3 modulation by the viral core protein through a process that may be linked to deregulated glycolysis, enhanced hepatic lipogenesis, and a steatotic phenotype in hepatocellular adenomas may contribute to persistent HCV manifestations and the development of HCC. |
| Morales et al. [76], 2016 | Sofosbuvir and lipid profile alterations | Post-therapy, eradication of HCV with a Sofosbuvir regimen led to a significant increase in LDL and total cholesterol. |
| Afsari et al. [98], 2017 | HS and fibrosis | HS is independently related to fibrosis in patients infected with HCV. |
| Lacerda et al. [77], 2018 | Lipid changes post-SVR | After an effective treatment, CHC patients experienced a restoration of lipid metabolism. |
| Cacoub et al. [118], 2018 | Subclinical atherosclerosis and cardiovascular disease | SVR was associated with a decreased rate of major cardiovascular events. |
| Driedger et al. [78], 2019 | Serum cholesterol and triglycerides changes after SVR | Serum cholesterol and triglycerides levels were elevated after achieving SVR |
| Peleg et al. [102], 2019 | HS and advanced fibrosis | HCV patients with HS did not have increased incidence of advanced fibrosis or cirrhosis. |
| Butt et al. [119], 2019 | Cardiovascular events and DAAs | There is a substantial benefit of HCV treatment on the incidence and risk of future cardiovascular events. |
| Huang et al. [122], 2020 | Lipid profile, cardio-cerebrovascular events | Serum lipid levels were augmented after HCV eradication, and it was associated with increased risk of cardio-cerebrovascular diseases. |
| Wu et al. [110], 2021 | Acute coronary syndrome | There was no statistically significant correlation between HCV infection and hospitalization for acute coronary syndrome. |
| Valiakou et al. [8], 2021 | SVR and persistent lipid abnormalities | In individuals with advanced liver fibrosis who attained viral clearance in vitro, the levels of ANGPTL-3 remained unaltered. As a result, ANGPTL-3 may be a component of the residual HCV molecular fingerprint, which may contribute to the ongoing dysregulation of lipid metabolism in those who have been cured and may predispose some of them to development of HCC. |
ANGPTL-3: Angiopoietin-like protein-3; CHC: Chronic hepatitis C; HCV: Hepatitis C virus; HS: Hepatic steatosis; IMT: Intima-media thickness; HDL: High density lipoprotein; LDL: Low density lipoprotein, VLDL: Very low density lipoprotein; SVR: Sustained virological response.