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 li...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.展开更多
AIM:To identify factors associated with prognosis of hepatocellular carcinoma(HCC) after initial therapy.METHODS:A total of 377 HCC patients who were newly treated at Katsushika Medical Center,Japan from January 2000 ...AIM:To identify factors associated with prognosis of hepatocellular carcinoma(HCC) after initial therapy.METHODS:A total of 377 HCC patients who were newly treated at Katsushika Medical Center,Japan from January 2000 to December 2009 and followed up for > 2 years,or died during follow-up,were enrolled.The factors related to survival were first analyzed in 377 patients with HCC tumor stage T1-T4 using multivariate Cox proportional hazards regression analysis.A similar analysis was performed in 282 patients with tumor stage T1-T3.Additionally,factors associated with the period between initial and subsequent therapy were examined in 144 patients who did not show local recurrence.Finally,214 HCC stage T1-T3 patients who died during the observation period were classified into four groups according to their alcohol consumption and postprandial glucose levels,and differences in their causes of death were examined.RESULTS:On multivariate Cox proportional hazards regression analysis,the following were significantly associated with survival:underlying liver disease stage [non-cirrhosis/Child-Pugh A vs B/C,hazard ratio(HR):0.603,95% CI:0.417-0.874,P = 0.0079],HCC stage(T1/T2 vs T3/T4,HR:0.447,95% CI:0.347-0.576,P < 0.0001),and mean postprandial plasma glucose after initial therapy(< 200 vs ≥ 200 mg/dL,HR:0.181,95% CI:0.067-0.488,P = 0.0008).In T1-T3 patients,uninterrupted alcohol consumption after initial therapy(no vs yes,HR:0.641,95% CI:0.469-0.877,P = 0.0055) was significant in addition to underlying liver disease stage(non-cirrhosis/Child-Pugh A vs B/C,HR:0649,95% CI:0.476-0.885,P = 0.0068),HCC stage(T1 vs T2/T3,HR:0.788,95% CI:0.653-0.945,P = 0.0108),and mean postprandial plasma glucose after initial therapy(< 200 mg/dL vs ≥ 200 mg/dL,HR:0.502,95% CI:0.337-0.747,P = 0.0005).In patients without local recurrence,time from initial to subsequent therapy for newly emerging HCC was significantly longer in the "postprandial glucose within 200 mg/dL group" than the "postprandial glucose > 200 mg/dL group"(log-rank test,P < 0.05),whereas there was no difference in the period between the "non-alcohol group"(patients who did not drink regularly or those who could reduce their daily consumption to < 20 g) and the "continuation group"(drinkers who continued to drink > 20 g daily).Of 214 T1-T3 patients who died during the observation period,death caused by other than HCC progression was significantly more frequent in "group AL"(patients in the continuation and postprandial glucose within 200 mg/dL groups) than "group N"(patients in the non-alcohol and postprandial glucose within 200 mg/dL groups)(P = 0.0016).CONCLUSION:This study found that abstinence from habitual alcohol consumption and intensive care for diabetes mellitus were related to improved prognosis in HCC patients.展开更多
AIM:To construct formulae for predicting the likelihood of ribavirin-induced anemia in pegylated interferon plus ribavirin for chronic hepatitis C.METHODS:Five hundred and sixty-one Japanese patients with hepatitis C ...AIM:To construct formulae for predicting the likelihood of ribavirin-induced anemia in pegylated interferon plus ribavirin for chronic hepatitis C.METHODS:Five hundred and sixty-one Japanese patients with hepatitis C virus genotype 1b who had received combination treatment were enrolled and assigned randomly to the derivation and confirmatory groups.Single nucleotide polymorphisms at or nearby ITPA were genotyped by real-time detection polymerase chain reaction.Factors influencing significant anemia(hemoglobin concentration < 10.0 g/dL at week 4 of treatment) and significant hemoglobin decline(declining concentrations > 3.0 g/dL at week 4) were analyzed using multiple regression analyses.Prediction formulae were constructed by significantly independent factors.RESULTS:Multivariate analysis for the derivation group identified four independent factors associated with significant hemoglobin decline:hemoglobin decline at week 2 [P = 3.29 × 10-17,odds ratio(OR) = 7.54(g/dL)],estimated glomerular filtration rate [P = 2.16 × 10-4,OR = 0.962(mL/min/1.73 m 2)],rs1127354(P = 5.75 × 10-4,OR = 10.94) and baseline hemoglobin [P = 7.86 × 10-4,OR = 1.50(g/dL)].Using the model constructed by these factors,positive and negative predictive values and predictive accuracy were 79.8%,88.8% and 86.2%,respectively.For the confirmatory group,they were 83.3%,91.0% and 88.3%.These factors were closely correlated with significant anemia.However,the model could not be constructed,because no patients with rs1127354 minor genotype CA/AA had significant anemia.CONCLUSION:Reliable formulae for predicting the likelihood of ribavirin-induced anemia were constructed.Such modeling may be useful in developing individual tailoring and optimization of ribavirin dosage.展开更多
AIM: To investigate how hepatitis C virus(HCV) G1 b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV...AIM: To investigate how hepatitis C virus(HCV) G1 b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1 b infection(active HCV group) and 91 with cleared HCV infection(SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using Lipo SEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1 b infection and the lipoprotein particle number was determined by multiple linear regression analysis.RESULTS: The median number of low-density lipoprotein(LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range(IQR): 444 nmol/L] than in the SVR group(1363 nmol/L, IQR: 472 nmol/L, P < 0.001), as was that of highdensity lipoprotein(HDL) particles(14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein(VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium(median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small(median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles(median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1 b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.CONCLUSION: HCV G1 b infection decreases the numbers of medium, small, and very small LDL particles.展开更多
AIM To investigate the influence of interferon-free antivirus therapy on lipid profiles in chronic hepatitis C virus genotype 1b(HCV1b) infection.METHODS Interferon-free antiviral agents were used to treat 276 patient...AIM To investigate the influence of interferon-free antivirus therapy on lipid profiles in chronic hepatitis C virus genotype 1b(HCV1b) infection.METHODS Interferon-free antiviral agents were used to treat 276 patients with chronic HCV1 b infection, and changes in serum lipids of those who achieved sustained virologic response(SVR) were examined. The treatment regimen included 24 wk of daclatasvir plus asunaprevir(DCV + ASV) or 12 wk of sofosbuvir plus ledipasvir(SOF + LDV). SVR was achieved in 121(85.8%) of 141 patients treated with DCV + ASV and 132(97.8%) of 135 patients treated with SOF + LDV. In the two patient groups(DCV + ASV-SVR and SOF + LDV-SVR), serum total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), and triglycerides were measured at baseline during treatment and at 4 and 12 wk after treatment. Then, longitudinal changes in lipid profiles were analyzed.RESULTS Serum levels of TC, LDL-C, and HDL-C were significantly increased throughout the observation period in both the DCV + ASV-SVR and SOF + LDV-SVR groups. During antivirus treatment, the increases in TC and LDL-C were significantly greater in the SOF + LDVSVR group than in the DCV + ASV-SVR group(P < 0.001). At 4 and 12 wk after the therapy, serum levels of TC and LDL-C were similar between the two groups and were significantly greater than those at baseline. Approximately 75%-80% of the increase in TC was derived from an increased LDL-C. In multiple regression analysis, the difference in therapy protocol(DCA + ASV or SOF + LDV) was an independent predictor that was significantly associated with the increase in TC and LDL-C at 4 wk of therapy.CONCLUSION Serum cholesterol significantly increased during SOF + LDV treatment. After treatment, HCV elimination was associated with a similar increase in cholesterol regardless of the therapy protocol.展开更多
AIM: To evaluate interferon-λ3(IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin(Peg-IFNα/RBV) therapy for genotype 2(G2) chronic hepatitis C.METHODS: Between January 2006 and June 2012,...AIM: To evaluate interferon-λ3(IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin(Peg-IFNα/RBV) therapy for genotype 2(G2) chronic hepatitis C.METHODS: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus(HCV) were treated with responseguided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response(RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype(TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV subgenotype 2a or 2b.RESULTS: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response(SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate(96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5%(P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups(80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR(OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.CONCLUSION: In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.展开更多
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...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/m L vs 2.40 ± 1.00 μg/m L, 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/m L vs 28.14 ± 9.94 μg/m L, P = 0.001) and high-density lipoprotein(HDL)(mean ± SD, 25.9 ± 7.34 μg/m L vs 17.17 ± 4.82 μg/m L, P < 0.001) were significantly higher in patientswith 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.展开更多
文摘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.
文摘AIM:To identify factors associated with prognosis of hepatocellular carcinoma(HCC) after initial therapy.METHODS:A total of 377 HCC patients who were newly treated at Katsushika Medical Center,Japan from January 2000 to December 2009 and followed up for > 2 years,or died during follow-up,were enrolled.The factors related to survival were first analyzed in 377 patients with HCC tumor stage T1-T4 using multivariate Cox proportional hazards regression analysis.A similar analysis was performed in 282 patients with tumor stage T1-T3.Additionally,factors associated with the period between initial and subsequent therapy were examined in 144 patients who did not show local recurrence.Finally,214 HCC stage T1-T3 patients who died during the observation period were classified into four groups according to their alcohol consumption and postprandial glucose levels,and differences in their causes of death were examined.RESULTS:On multivariate Cox proportional hazards regression analysis,the following were significantly associated with survival:underlying liver disease stage [non-cirrhosis/Child-Pugh A vs B/C,hazard ratio(HR):0.603,95% CI:0.417-0.874,P = 0.0079],HCC stage(T1/T2 vs T3/T4,HR:0.447,95% CI:0.347-0.576,P < 0.0001),and mean postprandial plasma glucose after initial therapy(< 200 vs ≥ 200 mg/dL,HR:0.181,95% CI:0.067-0.488,P = 0.0008).In T1-T3 patients,uninterrupted alcohol consumption after initial therapy(no vs yes,HR:0.641,95% CI:0.469-0.877,P = 0.0055) was significant in addition to underlying liver disease stage(non-cirrhosis/Child-Pugh A vs B/C,HR:0649,95% CI:0.476-0.885,P = 0.0068),HCC stage(T1 vs T2/T3,HR:0.788,95% CI:0.653-0.945,P = 0.0108),and mean postprandial plasma glucose after initial therapy(< 200 mg/dL vs ≥ 200 mg/dL,HR:0.502,95% CI:0.337-0.747,P = 0.0005).In patients without local recurrence,time from initial to subsequent therapy for newly emerging HCC was significantly longer in the "postprandial glucose within 200 mg/dL group" than the "postprandial glucose > 200 mg/dL group"(log-rank test,P < 0.05),whereas there was no difference in the period between the "non-alcohol group"(patients who did not drink regularly or those who could reduce their daily consumption to < 20 g) and the "continuation group"(drinkers who continued to drink > 20 g daily).Of 214 T1-T3 patients who died during the observation period,death caused by other than HCC progression was significantly more frequent in "group AL"(patients in the continuation and postprandial glucose within 200 mg/dL groups) than "group N"(patients in the non-alcohol and postprandial glucose within 200 mg/dL groups)(P = 0.0016).CONCLUSION:This study found that abstinence from habitual alcohol consumption and intensive care for diabetes mellitus were related to improved prognosis in HCC patients.
基金Supported by Clinical Research Funds from Division of Gastroenterology and Hepatology,Katsushika Medical Center,The Jikei University School of Medicine
文摘AIM:To construct formulae for predicting the likelihood of ribavirin-induced anemia in pegylated interferon plus ribavirin for chronic hepatitis C.METHODS:Five hundred and sixty-one Japanese patients with hepatitis C virus genotype 1b who had received combination treatment were enrolled and assigned randomly to the derivation and confirmatory groups.Single nucleotide polymorphisms at or nearby ITPA were genotyped by real-time detection polymerase chain reaction.Factors influencing significant anemia(hemoglobin concentration < 10.0 g/dL at week 4 of treatment) and significant hemoglobin decline(declining concentrations > 3.0 g/dL at week 4) were analyzed using multiple regression analyses.Prediction formulae were constructed by significantly independent factors.RESULTS:Multivariate analysis for the derivation group identified four independent factors associated with significant hemoglobin decline:hemoglobin decline at week 2 [P = 3.29 × 10-17,odds ratio(OR) = 7.54(g/dL)],estimated glomerular filtration rate [P = 2.16 × 10-4,OR = 0.962(mL/min/1.73 m 2)],rs1127354(P = 5.75 × 10-4,OR = 10.94) and baseline hemoglobin [P = 7.86 × 10-4,OR = 1.50(g/dL)].Using the model constructed by these factors,positive and negative predictive values and predictive accuracy were 79.8%,88.8% and 86.2%,respectively.For the confirmatory group,they were 83.3%,91.0% and 88.3%.These factors were closely correlated with significant anemia.However,the model could not be constructed,because no patients with rs1127354 minor genotype CA/AA had significant anemia.CONCLUSION:Reliable formulae for predicting the likelihood of ribavirin-induced anemia were constructed.Such modeling may be useful in developing individual tailoring and optimization of ribavirin dosage.
文摘AIM: To investigate how hepatitis C virus(HCV) G1 b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1 b infection(active HCV group) and 91 with cleared HCV infection(SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using Lipo SEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1 b infection and the lipoprotein particle number was determined by multiple linear regression analysis.RESULTS: The median number of low-density lipoprotein(LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range(IQR): 444 nmol/L] than in the SVR group(1363 nmol/L, IQR: 472 nmol/L, P < 0.001), as was that of highdensity lipoprotein(HDL) particles(14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein(VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium(median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small(median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles(median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1 b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.CONCLUSION: HCV G1 b infection decreases the numbers of medium, small, and very small LDL particles.
文摘AIM To investigate the influence of interferon-free antivirus therapy on lipid profiles in chronic hepatitis C virus genotype 1b(HCV1b) infection.METHODS Interferon-free antiviral agents were used to treat 276 patients with chronic HCV1 b infection, and changes in serum lipids of those who achieved sustained virologic response(SVR) were examined. The treatment regimen included 24 wk of daclatasvir plus asunaprevir(DCV + ASV) or 12 wk of sofosbuvir plus ledipasvir(SOF + LDV). SVR was achieved in 121(85.8%) of 141 patients treated with DCV + ASV and 132(97.8%) of 135 patients treated with SOF + LDV. In the two patient groups(DCV + ASV-SVR and SOF + LDV-SVR), serum total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), and triglycerides were measured at baseline during treatment and at 4 and 12 wk after treatment. Then, longitudinal changes in lipid profiles were analyzed.RESULTS Serum levels of TC, LDL-C, and HDL-C were significantly increased throughout the observation period in both the DCV + ASV-SVR and SOF + LDV-SVR groups. During antivirus treatment, the increases in TC and LDL-C were significantly greater in the SOF + LDVSVR group than in the DCV + ASV-SVR group(P < 0.001). At 4 and 12 wk after the therapy, serum levels of TC and LDL-C were similar between the two groups and were significantly greater than those at baseline. Approximately 75%-80% of the increase in TC was derived from an increased LDL-C. In multiple regression analysis, the difference in therapy protocol(DCA + ASV or SOF + LDV) was an independent predictor that was significantly associated with the increase in TC and LDL-C at 4 wk of therapy.CONCLUSION Serum cholesterol significantly increased during SOF + LDV treatment. After treatment, HCV elimination was associated with a similar increase in cholesterol regardless of the therapy protocol.
文摘AIM: To evaluate interferon-λ3(IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin(Peg-IFNα/RBV) therapy for genotype 2(G2) chronic hepatitis C.METHODS: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus(HCV) were treated with responseguided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response(RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype(TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV subgenotype 2a or 2b.RESULTS: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response(SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate(96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5%(P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups(80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR(OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.CONCLUSION: In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.
文摘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/m L vs 2.40 ± 1.00 μg/m L, 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/m L vs 28.14 ± 9.94 μg/m L, P = 0.001) and high-density lipoprotein(HDL)(mean ± SD, 25.9 ± 7.34 μg/m L vs 17.17 ± 4.82 μg/m L, P < 0.001) were significantly higher in patientswith 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.
