Hepatitis C virus (HCV) infection is associated with serum lipid abnormalities, which partly normalize following direct-acting antiviral (DAA) therapy. Here, associations of serum triglycerides (TGs) with viral genotype and markers of liver disease severity were evaluated in patients with chronic HCV. 

The study included the serum of 177 patients with chronic HCV. TGs were quantified by flow injection analysis Fourier transform mass spectrometry. Laboratory values and noninvasive scores for liver fibrosis assessment were determined. The nonparametric Kruskal‒Wallis test, one-way ANOVA, multiple linear regression and Student’s t test were used as appropriate. P values were adjusted for multiple comparisons.

HCV-infected women had lower serum TGs than men, and thus, a sex-specific analysis was performed. None of the 46 TG species analyzed differed in the serum of female patients with and without liver cirrhosis. In contrast, in the serum of male patients with liver cirrhosis, TGs with 53, 56 and 58 carbon atoms and three to eight double bonds were diminished. These polyunsaturated TGs were also low in males with a high fibrosis-4 score. TGs with 7 or 8 double bonds negatively correlated with the model of end-stage liver disease score in males. In addition, TGs with 49, 51 and 53 carbon atoms were reduced in male patients infected with genotype 3a in comparison to genotype 1a. TGs with 56 carbon atoms were lower in genotype 3a-infected males than in genotype 1b-infected males. TGs did not differ in females by genotype. Genotype 3-related changes disappeared at the end of therapy with DAAs. Overall, the levels of serum TGs did not change during DAA therapy in either sex. Consequently, the serum TGs of males with liver cirrhosis were lower than those of males without cirrhosis at the end of therapy. Such a difference was not apparent in females.

The decline in TGs observed only in male patients with liver cirrhosis and male patients infected with genotype 3 illustrates sex-specific changes in lipid metabolism in chronic HCV.

The online version contains supplementary material available at 10.1186/s12944-022-01715-w.

• Direct acting antivirals
• Fibrosis-4 score
• Genotype
• Liver cirrhosis
• Polyunsaturated triglycerides

Introduction: Chronic liver disease (CLD) is a term used to describe a wide spectrum of disorders, including idiopathic, infectious, genetic, drug-induced, toxin-induced, and autoimmune disorders. The common consequence of chronic damage to the liver is cirrhosis. Cirrhotic patients are further classified by their severity based on the Child-Pugh scoring system. Currently, Child-Pugh scoring consists of ascites, hepatic encephalopathy (HE), prothrombin time, serum albumin level, and total bilirubin level. Lipid panel in CLD is a great marker in determining the severity of CLD.

Method and methodology: It was a descriptive cross-sectional study conducted at a tertiary care hospital. A sample size of 122 was calculated by using a RaoSoft Digital Sample Size Calculator (RaoSoft, Inc., Seattle, WA) in which we used 5% as a margin of error, 95% as confidence interval (CI), 178 as population size, and response distribution as 50%. Non-complicated CLD patients having age in between 15 and 80 years with no cirrhotic complications including HE, spontaneous bacterial peritonitis, hepato-pumonary, or hepato-renal syndrome were included in our study; the rest of the CLD patients were excluded from our study.

Results: The mean age of the study population was 47.09 ± 12.30 years with more than half of the patients lying among the age group 25-50 years. The study population included 76% of males (n=93) and 24% of females (n=29), with a mean age of females higher than the males. Diabetes mellitus (58.19%) was the most frequent comorbidity associated with CLD in subjects included in our study. Parameters of lipid panel were decreased exponentially as the severity of CLD increases from Child score A to C. Total cholesterol, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), high-density lipoprotein (HDL), and triglyceride (TG) level decreased as the severity increases in our study. The mean model for end-stage liver disease (MELD) score increased as per hypothesized as the severity increases from Child score A to Child score C, respectively.

Conclusion: Our study concluded that as the severity of CLD increases from Child class A to Child class C, the lipid panel profile decreases exponentially which proved the idea that had been hypothesized at the beginning of our study.

• chronic liver disease
• correlation
• descriptive
• lipid panel
• tertiary care

• cardiology
• epidemiology
• infectious diseases

• Adult
• Aged
• Bayes Theorem
• Canada/epidemiology
• Cross-Sectional Studies
• Female
• Heart Disease Risk Factors
• Hepatitis C/epidemiology
• Humans
• Male
• Middle Aged

• Public Health Agency of Canada

• chronic hepatitis c virus
• compensated liver cirrhosis
• inflammatory marker levels

• Alanine Transaminase/blood
• Aspartate Aminotransferases/blood
• Biomarkers/blood
• Case-Control Studies
• China/epidemiology
• Fatty Liver/blood
• Fatty Liver/diagnosis
• Fatty Liver/epidemiology
• Female
• Hepacivirus/isolation & purification
• Hepatitis C, Chronic/blood
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/epidemiology
• Humans
• Lipoproteins/blood
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/epidemiology
• Liver Cirrhosis/etiology
• Lymphocyte Count/methods
• Male
• Middle Aged
• Platelet Count/methods
• Risk Factors

The role of hepatitis C virus (HCV) infection in increasing the risk of cardiovascular disease (CVD) is controversial. The objective of the present study is to estimate the 10-year risk of CVD in HCV- positive subjects and describe their profile of cardiometabolic risk markers compared to HCV-negative subjects. We conducted a cross-sectional study to estimate 10-year CVD risk, calculated using the Framingham Risk Score (FRS), in participants from the Canadian Health Measures Survey (CHMS; 2007–2015, n = 10,115) and the US-National Health and Nutrition Examination Survey (NHANES; 2007–2016, n = 16,668). Subjects included in our analysis were aged 30 to 74 years with no prior history of CVD. FRS estimates, sociodemographic and cardiometabolic risk factors were compared between HCV- positive and -negative subjects in the two surveys. HCV-positive subjects had a distinct sociodemographic profile compared to their HCV-negative counterparts. Cardiometabolic risk factors, inflammatory markers and serum levels of micronutrients were comparable between the two survey populations, both in HCV-positive and -negative subjects. The average FRS in HCV-positive patients was in the range of “intermediate” 10-year CVD risk (i.e., 10–20%) and was significantly higher (P<0.01) than their HCV-negative counterparts who were within the “low” 10-year CVD risk range (i.e., ≤10%). Using a multivariable linear regression model adjusted for ethnicity, number of metabolic syndrome components and BMI, HCV infection was significantly associated with a 2.5–3.5% absolute risk increase of 10-year CVD (P<0.01). The results of the present study suggest a potential association between HCV infection and risk of subclinical and clinical CVD. The expansion of anti-HCV therapy may also contribute to reduced CVD risk and burden in patients with chronic HCV infection and should be explored further in other datasets and population modelling studies.

• Adult
• Biomarkers/blood
• Body Mass Index
• Canada/epidemiology
• Cardiovascular Diseases/blood
• Cardiovascular Diseases/epidemiology
• Cardiovascular Diseases/etiology
• Cardiovascular Diseases/therapy
• Female
• Hepacivirus
• Hepatitis C, Chronic/blood
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/epidemiology
• Hepatitis C, Chronic/therapy
• Humans
• Male
• Middle Aged
• Models, Biological
• Risk Factors
• United States/epidemiology

• Public Health Agency of Canada

• apolipoprotein
• direct-acting antiviral agent
• hepatitis C virus
• lipoprotein metabolism

• Apolipoprotein B
• Cholesterol
• Fatty liver
• Hepatitis C virus
• Liver cirrhosis
• Low-density lipoprotein
• Triglycerides

AIM: To determine the significance of cholesteryl ester transfer protein (CETP) in lipoprotein abnormalities in chronic hepatitis C virus (HCV) infection.

METHODS: We evaluated the significance of the serum concentration of CETP in 110 Japanese patients with chronic HCV infection. Fifty-five patients had active HCV infection, and HCV eradication had been achieved in 55. The role of CETP in serum lipoprotein abnormalities, specifically, in triglyceride (TG) concentrations in the four major classes of lipoproteins, was investigated using Pearson correlations in conjunction with multiple regression analysis and compared them between those with active HCV infection and those in whom eradication had been achieved.

RESULTS: The serum CETP levels of patients with active HCV infection were significantly higher than those of patients in whom HCV eradication was achieved (mean ± SD, 2.84 ± 0.69 μg/mL vs 2.40 ± 1.00 μg/mL, P = 0.008). In multiple regression analysis, HCV infection status (active or eradicated) was an independent factor significantly associated with the serum CETP level. TG concentrations in low-density lipoprotein (mean ± SD, 36.25 ± 15.28 μg/mL vs 28.14 ± 9.94 μg/mL, P = 0.001) and high-density lipoprotein (HDL) (mean ± SD, 25.9 ± 7.34 μg/mL vs 17.17 ± 4.82 μg/mL, P < 0.001) were significantly higher in patients with active HCV infection than in those in whom HCV eradication was achieved. The CETP level was strongly correlated with HDL-TG in patients with active HCV infection (R = 0.557, P < 0.001), whereas CETP was not correlated with HDL-TG in patients in whom HCV eradication was achieved (R = -0.079, P = 0.56).

CONCLUSION: Our results indicate that CETP plays a role in abnormalities of lipoprotein metabolism in patients with chronic HCV infection.

• Hepatitis C virus
• Cholesteryl ester transfer protein
• High-density lipoprotein triglyceride
• Case control study
• Lipoprotein metabolism

The Hepatitis C virus (HCV) infection exhibits a high global prevalence frequently associated with hepatocellular carcinoma, taking years to develop. Despite the standardization of highly sensitive HCV quantitative RT-PCR (qRT-PCR) detection methods, false-negative diagnoses may be generated with current methods, mainly due to the presence of PCR inhibitors and/or low viral loads in the patient’s sample. These false-negative diagnoses impact both public health systems, in developing countries, and an in lesser extent, in developed countries, including both the risk of virus transmission during organ transplantation and/or blood transfusion and the quality of the antiviral treatment monitoring. To adopt an appropriate therapeutic strategy to improve the patient’s prognosis, it is urgent to increase the HCV detection sensitivity. Based upon previous studies on HBV, we worked on the capacity of the scavenger acute phase protein, Apolipoprotein H (ApoH) to interact with HCV. Using different approaches, including immunoassays, antibody-inhibition, oxidation, ultracentrifugation, electron microscopy and RT-PCR analyses, we demonstrated specific interactions between HCV particles and ApoH. Moreover, when using a two-step HCV detection process, including capture of HCV by ApoH-coated nanomagnetic beads and a home-made real-time HCV-RT-PCR, we confirmed the presence of HCV for all samples from a clinical collection of HCV-seropositive patients exhibiting an RT-PCR COBAS® TaqMan® HCV Test, v2.0 (COBAS)-positive result. In contrast, for HCV-seropositive patients with either low HCV-load as determined with COBAS or exhibiting HCV-negative COBAS results, the addition of the two-step ApoH-HCV-capture and HCV-detection process was able to increase the sensitivity of HCV detection or more interestingly, detect in a genotype sequence-independent manner, a high-proportion (44%) of HCV/RNA-positive among the COBAS HCV-negative patients. Thus, the immune interaction between ApoH and HCV could be used as a sample preparation tool to enrich and/or cleanse HCV patient’s samples to enhance the detection sensitivity of HCV and therefore significantly reduce the numbers of false-negative HCV diagnosis results.

Hepatitis C virus (HCV) is a hepatotrophic virus and a major cause of chronic liver disease, including hepatocellular carcinoma, worldwide. The life cycle of HCV is closely associated with the metabolism of lipids and lipoproteins. The main function of lipoproteins is transporting lipids throughout the body. Triglycerides, free cholesterol, cholesteryl esters, and phospholipids are the major components of the transported lipids. The pathway of HCV assembly and secretion is closely linked to lipoprotein production and secretion, and the infectivity of HCV particles largely depends on the interaction of lipoproteins. Moreover, HCV entry into hepatocytes is strongly influenced by lipoproteins. The key lipoprotein molecules mediating these interactions are apolipoproteins. Apolipoproteins are amphipathic proteins on the surface of a lipoprotein particle, which help stabilize lipoprotein structure. They perform a key role in lipoprotein metabolism by serving as receptor ligands, enzyme co-factors, and lipid transport carriers. Understanding the association between the life cycle of HCV and lipoprotein metabolism is important because each step of the life cycle of HCV that is associated with lipoprotein metabolism is a potential target for anti-HCV therapy. In this article, we first concisely review the nature of lipoprotein and its metabolism to better understand the complicated interaction of HCV with lipoprotein. Then, we review the outline of the processes of HCV assembly, secretion, and entry into hepatocytes, focusing on the association with lipoproteins. Finally, we discuss the clinical aspects of disturbed lipid/lipoprotein metabolism and the significance of dyslipoproteinemia in chronic HCV infection with regard to abnormal apolipoproteins.

• Hepatitis C virus
• Apolipoprotein
• Lipo-viral particle
• Dyslipoproteinemia
• Lipoprotein

• Animals
• Hepacivirus/growth & development
• Hepacivirus/metabolism
• Hepacivirus/pathogenicity
• Hepatitis C, Chronic/diagnosis
• Hepatitis C, Chronic/metabolism
• Hepatitis C, Chronic/virology
• Humans
• Lipoproteins/metabolism
• Liver/metabolism
• Liver/virology
• Virus Internalization

Reduced low-density lipoprotein (LDL) cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV) infection. However, abnormality in serum triglyceride (TG) has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b) infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL), LDL, and high-density lipoprotein (HDL). Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles.

• VLDL sub-fractions
• chronic hepatitis C (CHC)
• hepatitis C virus (HCV)
• lipoprotein
• triglyceride (TG)
• very-low-density lipoprotein (VLDL)

• Antiviral Agents/therapeutic use
• Biomarkers
• Female
• Genotype
• Hepacivirus/genetics
• Hepatitis C, Chronic/blood
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/virology
• Humans
• Lipoproteins/blood
• Lipoproteins, VLDL
• Liver Cirrhosis/blood
• Liver Cirrhosis/etiology
• Liver Cirrhosis/pathology
• Male
• Treatment Outcome
• Triglycerides/blood

The mechanisms that regulate disease progression during hepatitis C virus (HCV) infection and the response to treatment are not clearly identified. Numerous studies have demonstrated that a strong host immune response against HCV favors HCV clearance. In addition, genetic factors and metabolic machinery, particularly cholesterol modulation, are involved in HCV infection. It is likely that the interplay between all of these factors contributes to the outcome of HCV infection. In recent years, the world has experienced its largest epidemic of obesity. Mexico and the United States are the leading sufferers from this epidemic at the global level. Obesity is associated with the development of numerous pathologies including hypercholesterolemia which is one of the eight most important risk factors for mortality in Mexico. This may be related to the course of HCV infection in this population. Here, we focus on the urgent need to study the progression of HCV infection in relation to ethnic characteristics. Discoveries are discussed that hold promise in identifying immune, metabolic and genetic factors that, in conjunction, could be therapeutic targets or predictors of the progression of HCV infection.

• Hepatitis C virus
• Immune response
• Lipids
• Metabolism
• Genetics

• Animals
• Antiviral Agents/therapeutic use
• Disease Progression
• Fatty Liver/immunology
• Hepacivirus
• Hepatitis C/genetics
• Hepatitis C/immunology
• Humans
• Hypercholesterolemia/complications
• Hypercholesterolemia/virology
• Immunity, Innate
• Lipid Metabolism
• Mexico
• Obesity/complications
• Risk Factors
• United States

• Adult
• Cholesterol/blood
• Cholesterol, HDL/blood
• Cholesterol, LDL/blood
• Cholesterol, VLDL/blood
• Comorbidity
• Diabetes Mellitus, Type 2/epidemiology
• Fatty Liver/blood
• Fatty Liver/epidemiology
• Female
• Genotype
• Hepacivirus/genetics
• Hepacivirus/physiology
• Hepatitis C/epidemiology
• Humans
• Liver Diseases, Alcoholic/blood
• Liver Diseases, Alcoholic/epidemiology
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease
• Particle Size
• Prospective Studies
• Triglycerides/blood
• Virus Replication/physiology

• albumin
• ghrelin
• gut hormone
• hepatitis C virus
• liver cirrhosis