AIM: To examine whether vitamin D improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3. METHODS: Fifty patients with chronic HCV genotype 2-3 were randomized co...AIM: To examine whether vitamin D improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3. METHODS: Fifty patients with chronic HCV genotype 2-3 were randomized consecutively into two groups: Treatment group [20 subjects, age 48 ± 14 years, body mass index (BMI) 30 ± 6, 65% male], who received 180 μg pegylated α-interferon-2a plus oral ribavirin 800 mg/d (Peg/RBV), together with oral vitamin D3 (Vitamidyne D drops; 2000 IU/d, 10 drops/d, normal serum level > 32 ng/mL) for 24 wk; and control group (30 subjects, age 45 ± 10 years, BMI 26 ± 3, 60% male), who received identical therapy without vitamin D. HCV RNA was assessed by reverse transcription polymerase chain reaction. Undetectable HCV RNA at 4, 12 and 24 wk after treatment was considered as rapid virological response, complete early virological response, and sustained virological response (SVR), respectively. Biomarkers of in? ammation were measured. RESULTS: The treatment group with vitamin D hadhigher BMI (30 ± 6 vs 26 ± 3, P < 0.02), and high viral load (> 400 000 IU/mL, 65% vs 40%, P < 0.01) than controls. Ninety-fi ve percent of treated patients were HCV RNA negative at week 4 and 12. At 24 wk after treatment (SVR), 19/20 (95%) treated patients and 23/30 (77%) controls were HCV RNA negative (P < 0.001). Baseline serum vitamin D levels were lower at baseline (20 ± 8 ng/mL) and increased after 12 wk vitamin D treatment, to a mean level of (34 ± 11 ng/ mL). Logistic regression analysis identifi ed vitamin D supplement [odds ratio (OR) 3.0, 95% CI 2.0-4.9, P < 0.001], serum vitamin D levels (< 15 or > 15 ng/mL, OR 2.2, P < 0.01), and BMI (< 30 or > 30, OR 2.6, P < 0.01) as independent predictors of viral response. Adverse events were mild and typical of Peg/RBV. CONCLUSION: Low vitamin D levels predicts negative treatment outcome, and adding vitamin D to conventional Peg/RBV therapy for patients with HCV genotype 2-3 signifi cantly improves viral response.展开更多
AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assign...AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assigned(3:1) to receive 24 wk of treatment with d UAL(daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period(immediate treatment arm) or following 12 wk of matching placebo(placebodeferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12(SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin(70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase), and during 24 wk of d UAL in both arms combined.RESULTS In total, 207 patients were randomly assigned to immediate(n = 155) or placebo-deferred(n = 52) treatment. Most patients were Asian(86%), female(59%) and aged < 65 years(90%). Among them, 13% had cirrhosis, 32% had IL28 B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/m L. Among patients in the immediate treatment arm, SVR12 was achieved by 92%(95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate(70%). SVR12 was largely unaffected by cirrhosis(89%), age ≥ 65 years(92%), male sex(90%), baseline HCV RNA ≥ 6 million(89%) or IL28 B non-CC genotypes(96%), although SVR12 was higher among patients without(96%) than among those with(53%) baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H). during the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL. during 24 wk of d UAL therapy(combined arms), the most common adverse events(≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were展开更多
Chronic active hepatitis(CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma.The histological end points of CAH are chronic inflammation,fibrosis and cirr...Chronic active hepatitis(CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma.The histological end points of CAH are chronic inflammation,fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers.The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis,inflammation and cytokine production and liver scaring(fibrosis).The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components.The viral and cellular factors that contribute to liver injury are discussed in this article.Liver injury caused by the viral infection affects many cellular processes such as cell signaling,apoptosis,transcription,DNA repair which in turn induce radical effects on cell survival,growth,transformation and maintenance.The consequence of such perturbations is resulted in the alteration of bile secretion,gluconeogenesis,glycolysis,detoxification and metabolism of carbohydrates,proteins,fat and balance of nutrients.The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury.展开更多
Background:Hepatitis C virus(HCV)genotype 3,particularly subtype 3b,is increasing in prevalence and distribution in China.This study evaluated the prevalence,regional distribution,clinical characteristics,host factors...Background:Hepatitis C virus(HCV)genotype 3,particularly subtype 3b,is increasing in prevalence and distribution in China.This study evaluated the prevalence,regional distribution,clinical characteristics,host factors,treatment outcomes,and disease progression of patients with HCV genotype 3 in China.Methods:A 5-year follow-up was preceded by a cross-sectional study.Treatment choices were at the discretion of treating physicians.Estimated infection time to overall-disease-progression(defined by≥1 of:newly diagnosed cirrhosis;cirrhosis at baseline,Child-Turcotte-Pugh score increased 2 points or more;progression from compensated cirrhosis to decompensated cirrhosis;hepatocellular carcinoma;liver transplantation;or death)was calculated using the Kaplan-Meier method.Cox regression analyses were conducted to evaluate the risk factors for disease progression.Results:The cross-sectional study enrolled 997 patients,including 91 with HCV genotype 3 infection.Among them,subtype 3b(57.1%)was more dominant than subtype 3a(38.5%).Five hundred and twelve patients were included into the follow-up phase.Among patients analyzed for estimated infection time to overall-disease-progression,52/304(17.1%)patients with HCV genotype 1 and 4/41(9.8%)with HCV genotype 3(4/26 with genotype 3b,0/13 with genotype 3a,and 0/2 with undefined subtype of genotype 3)experienced overall-disease-progression.Patients with HCV genotype 3 were younger than those with genotype 1(mean age:39.5±8.7 vs.46.9±13.6 years)and demonstrated more rapid disease progression(mean estimated infection time to overall-disease-progression 27.1 vs.35.6 years).Conclusions:HCV genotype 3,specifically subtype 3b,is associated with more rapid progression of liver disease.Further analysis to compare HCV subtype 3a and 3b is needed in high prevalence regions.展开更多
Hepatitis C virus(HCV) infection is a common chronic liver disease worldwide.Non-alcoholic fatty liver disease and insulin resistance(IR) are the major determinants of fibrosis progression and response to antiviral th...Hepatitis C virus(HCV) infection is a common chronic liver disease worldwide.Non-alcoholic fatty liver disease and insulin resistance(IR) are the major determinants of fibrosis progression and response to antiviral therapy.The pathogenetic link between IR and chronic HCV infection is complex,and is associated with HCV genotype.Liver steatosis is the most common in the patients infected with genotype 3 virus,possibly due to direct effects of genotype 3 viral proteins.To the contrary,hepatic steatosis in the patients infected with other genotypes is thought to be mostly due to the changes in host metabolism,involving IR.In HCV genotype 3,liver steatosis correlates with viral load,reverts after reaching the sustained virologic response and reoccurs in the relapsers.A therapeutic strategy to improve IR and liver steatosis and subsequently the response to antiviral treatment in these patients is warranted.展开更多
BACKGROUND Hepatitis C virus(HCV)is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality.Chronic infection leads to cirrhosis in a large proportion of...BACKGROUND Hepatitis C virus(HCV)is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality.Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma(HCC)in people with cirrhosis.Of the 6 HCV genotypes(G1-G6),genotype-3 accounts for 17.9%of infections.HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis.AIM To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings.Consequently,we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023.METHODS This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations.We searched Web of Science,Medline,EMBASE,and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings,1946-2023.RESULTS Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates.Three thousand eight hundred and eighty-four records were screened with 3514 excluded.Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis.Of the seven studies,three studies were retrospective case-control trials,two retrospective cohort studies,one a prospective cohort study and one a cross-sectional study design.All were based in hospital settings with four in Pakistan,two in South Korea and one in the United States.The total number of participants were 9621 of which 167 developed HCC(1.7%).All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age(five-studies),with two studies each showing male sex,high alpha feto-protein,directly-acting antivirals treatment and achievement of sustained virologic res展开更多
丙型肝炎病毒（hepatitis C virus，HCV）感染呈全球性流行，不同性别、年龄、种族人群均对丙型肝炎病毒易感。丙型肝炎病毒常常可导致慢性感染，是全世界慢性肝病主要病因之一。慢性丙型肝炎病毒感染常呈持续很多年的进展性病程，并最...丙型肝炎病毒（hepatitis C virus，HCV）感染呈全球性流行，不同性别、年龄、种族人群均对丙型肝炎病毒易感。丙型肝炎病毒常常可导致慢性感染，是全世界慢性肝病主要病因之一。慢性丙型肝炎病毒感染常呈持续很多年的进展性病程，并最终导致肝硬化、肝细胞癌以及需要进行肝移植的终末期肝病。本文就基因3型丙型肝炎病毒感染及其抗病毒治疗作一阐述。展开更多
Background Previous serological studies of human bocavirus(HBoV)1 could not exclude cross-reactivity with the other three HBoVs,particularly HBoV2.Methods To search for genotype-specific antibodies against HBoV1 and H...Background Previous serological studies of human bocavirus(HBoV)1 could not exclude cross-reactivity with the other three HBoVs,particularly HBoV2.Methods To search for genotype-specific antibodies against HBoV1 and HBoV2,the divergent regions(DRs)located on the major capsid protein VP3 were defined through viral amino acid alignment and structure prediction.DR-deduced peptides were used as antigens to harvest corresponding anti-DR rabbit sera.To determine their genotype specificities for HBoV1 and HBoV2,these sera samples were used as antibodies against the antigens VP3 of HBoV1 and HBoV2(expressed in Escherichia coli)in western blotting(WB),enzyme-linked immunosorbent assay(ELISA),and bio-layer interferometry(BLI)assays.Subsequently,the antibodies were evaluated with clinical specimens from pediatric patients with acute respiratory tract infection by indirect immunofluorescence assay(IFA).Results There were four DRs(DR1–4)located on VP3 with different secondary and tertiary structures between HBoV1 and HBoV2.Regarding the reactivity with VP3 of HBoV1 or HBoV2 in WB and ELISA,high intra-genotype cross-reactivity of anti-HBoV1 or HBoV2 DR1,DR3,and DR4,but not anti-DR2,was observed.Genotype-specific binding capacity of anti-DR2 sera was confirmed by BLI and IFA,in which only anti-HBoV1 DR2 antibody reacted with HBoV1-positive respiratory specimens.Conclusion Antibodies against DR2,located on VP3 of HBoV1 or HBoV2,were genotype specific for HBoV1 and HBoV2,respectively.展开更多
Single nucleotide polymorphisms near the interleukin28B(IL-28B)gene have been identified as strong predictors of both spontaneous or Peg-interferon(Peg-IFN)and ribavirin(RBV)induced clearance of hepatitis C virus(HCV)...Single nucleotide polymorphisms near the interleukin28B(IL-28B)gene have been identified as strong predictors of both spontaneous or Peg-interferon(Peg-IFN)and ribavirin(RBV)induced clearance of hepatitis C virus(HCV).Several studies have shown that,in patients with genotype 1(GT-1),rs12979860 C/C and rs8099917T/T substitutions are associated with a more than twofold increase in sustained virological response rate to Peg-IFN and RBV treatment.Although new treatment regimens based on combination of DAA with or without IFN are in the approval phase,until combination regimens with a backbone of Peg-IFN will be used,we can expect that IL28B holds its importance.The clinical relevance of IL28B genotyping in treatment of patients infected with HCV genotype 2(GT-2)and 3(GT-3)remains controversial.Therefore,after a careful examination of the available literature,we analyzed the impact of IL28B in GT-2 and-3.Simple size of the studies and GT-2 and GT-3 proportion were discussed.An algorithm for the practical use of IL28B in these patients was suggested at the aim of optimizing treatment.展开更多
Hepatitis C virus(HCV) infection is one of the most common causes of chronic liver disease and the main indication for liver transplantation worldwide. As promising specific treatments have been introduced for genotyp...Hepatitis C virus(HCV) infection is one of the most common causes of chronic liver disease and the main indication for liver transplantation worldwide. As promising specific treatments have been introduced for genotype 1, clinicians and researchers are now focusing on patients infected by non-genotype 1 HCV, particularly genotype 3. Indeed, in the golden era of direct-acting antiviral drugs, genotype 3 infections are no longer considered as easy to treat and are associated with higher risk of developing severe liver injuries, such as cirrhosis and hepatocellular carcinoma. Moreover, HCV genotype 3 accounts for 40% of all HCV infections in Asia and is the most frequent genotype among HCV-positive injecting drug users in several countries. Here, we review recent data on HCV genotype 3 infection/treatment, including clinical aspects and the underlying genotype-specific molecular mechanisms.展开更多
文摘AIM: To examine whether vitamin D improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3. METHODS: Fifty patients with chronic HCV genotype 2-3 were randomized consecutively into two groups: Treatment group [20 subjects, age 48 ± 14 years, body mass index (BMI) 30 ± 6, 65% male], who received 180 μg pegylated α-interferon-2a plus oral ribavirin 800 mg/d (Peg/RBV), together with oral vitamin D3 (Vitamidyne D drops; 2000 IU/d, 10 drops/d, normal serum level > 32 ng/mL) for 24 wk; and control group (30 subjects, age 45 ± 10 years, BMI 26 ± 3, 60% male), who received identical therapy without vitamin D. HCV RNA was assessed by reverse transcription polymerase chain reaction. Undetectable HCV RNA at 4, 12 and 24 wk after treatment was considered as rapid virological response, complete early virological response, and sustained virological response (SVR), respectively. Biomarkers of in? ammation were measured. RESULTS: The treatment group with vitamin D hadhigher BMI (30 ± 6 vs 26 ± 3, P < 0.02), and high viral load (> 400 000 IU/mL, 65% vs 40%, P < 0.01) than controls. Ninety-fi ve percent of treated patients were HCV RNA negative at week 4 and 12. At 24 wk after treatment (SVR), 19/20 (95%) treated patients and 23/30 (77%) controls were HCV RNA negative (P < 0.001). Baseline serum vitamin D levels were lower at baseline (20 ± 8 ng/mL) and increased after 12 wk vitamin D treatment, to a mean level of (34 ± 11 ng/ mL). Logistic regression analysis identifi ed vitamin D supplement [odds ratio (OR) 3.0, 95% CI 2.0-4.9, P < 0.001], serum vitamin D levels (< 15 or > 15 ng/mL, OR 2.2, P < 0.01), and BMI (< 30 or > 30, OR 2.6, P < 0.01) as independent predictors of viral response. Adverse events were mild and typical of Peg/RBV. CONCLUSION: Low vitamin D levels predicts negative treatment outcome, and adding vitamin D to conventional Peg/RBV therapy for patients with HCV genotype 2-3 signifi cantly improves viral response.
文摘AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assigned(3:1) to receive 24 wk of treatment with d UAL(daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period(immediate treatment arm) or following 12 wk of matching placebo(placebodeferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12(SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin(70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase), and during 24 wk of d UAL in both arms combined.RESULTS In total, 207 patients were randomly assigned to immediate(n = 155) or placebo-deferred(n = 52) treatment. Most patients were Asian(86%), female(59%) and aged < 65 years(90%). Among them, 13% had cirrhosis, 32% had IL28 B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/m L. Among patients in the immediate treatment arm, SVR12 was achieved by 92%(95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate(70%). SVR12 was largely unaffected by cirrhosis(89%), age ≥ 65 years(92%), male sex(90%), baseline HCV RNA ≥ 6 million(89%) or IL28 B non-CC genotypes(96%), although SVR12 was higher among patients without(96%) than among those with(53%) baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H). during the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL. during 24 wk of d UAL therapy(combined arms), the most common adverse events(≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were
文摘Chronic active hepatitis(CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma.The histological end points of CAH are chronic inflammation,fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers.The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis,inflammation and cytokine production and liver scaring(fibrosis).The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components.The viral and cellular factors that contribute to liver injury are discussed in this article.Liver injury caused by the viral infection affects many cellular processes such as cell signaling,apoptosis,transcription,DNA repair which in turn induce radical effects on cell survival,growth,transformation and maintenance.The consequence of such perturbations is resulted in the alteration of bile secretion,gluconeogenesis,glycolysis,detoxification and metabolism of carbohydrates,proteins,fat and balance of nutrients.The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury.
基金This work was supported by grants from the China National Science and Technology Major Project for Infectious Diseases Control during the 12th and 13th Five-Year Plan Period(Nos.2017ZX10202202,2012ZX10002003,2012ZX10002005)the Beijing Natural Science Foundation(No.7182174)the National Natural Science Foundation of China(No.81870406),and from the Bristol-Myers Squibb。
文摘Background:Hepatitis C virus(HCV)genotype 3,particularly subtype 3b,is increasing in prevalence and distribution in China.This study evaluated the prevalence,regional distribution,clinical characteristics,host factors,treatment outcomes,and disease progression of patients with HCV genotype 3 in China.Methods:A 5-year follow-up was preceded by a cross-sectional study.Treatment choices were at the discretion of treating physicians.Estimated infection time to overall-disease-progression(defined by≥1 of:newly diagnosed cirrhosis;cirrhosis at baseline,Child-Turcotte-Pugh score increased 2 points or more;progression from compensated cirrhosis to decompensated cirrhosis;hepatocellular carcinoma;liver transplantation;or death)was calculated using the Kaplan-Meier method.Cox regression analyses were conducted to evaluate the risk factors for disease progression.Results:The cross-sectional study enrolled 997 patients,including 91 with HCV genotype 3 infection.Among them,subtype 3b(57.1%)was more dominant than subtype 3a(38.5%).Five hundred and twelve patients were included into the follow-up phase.Among patients analyzed for estimated infection time to overall-disease-progression,52/304(17.1%)patients with HCV genotype 1 and 4/41(9.8%)with HCV genotype 3(4/26 with genotype 3b,0/13 with genotype 3a,and 0/2 with undefined subtype of genotype 3)experienced overall-disease-progression.Patients with HCV genotype 3 were younger than those with genotype 1(mean age:39.5±8.7 vs.46.9±13.6 years)and demonstrated more rapid disease progression(mean estimated infection time to overall-disease-progression 27.1 vs.35.6 years).Conclusions:HCV genotype 3,specifically subtype 3b,is associated with more rapid progression of liver disease.Further analysis to compare HCV subtype 3a and 3b is needed in high prevalence regions.
文摘Hepatitis C virus(HCV) infection is a common chronic liver disease worldwide.Non-alcoholic fatty liver disease and insulin resistance(IR) are the major determinants of fibrosis progression and response to antiviral therapy.The pathogenetic link between IR and chronic HCV infection is complex,and is associated with HCV genotype.Liver steatosis is the most common in the patients infected with genotype 3 virus,possibly due to direct effects of genotype 3 viral proteins.To the contrary,hepatic steatosis in the patients infected with other genotypes is thought to be mostly due to the changes in host metabolism,involving IR.In HCV genotype 3,liver steatosis correlates with viral load,reverts after reaching the sustained virologic response and reoccurs in the relapsers.A therapeutic strategy to improve IR and liver steatosis and subsequently the response to antiviral treatment in these patients is warranted.
基金Supported by the Clinical Research Fellowship Grant from the Wellcome Trust,United Kingdom,No.227516/Z/23/Z.
文摘BACKGROUND Hepatitis C virus(HCV)is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality.Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma(HCC)in people with cirrhosis.Of the 6 HCV genotypes(G1-G6),genotype-3 accounts for 17.9%of infections.HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis.AIM To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings.Consequently,we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023.METHODS This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations.We searched Web of Science,Medline,EMBASE,and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings,1946-2023.RESULTS Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates.Three thousand eight hundred and eighty-four records were screened with 3514 excluded.Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis.Of the seven studies,three studies were retrospective case-control trials,two retrospective cohort studies,one a prospective cohort study and one a cross-sectional study design.All were based in hospital settings with four in Pakistan,two in South Korea and one in the United States.The total number of participants were 9621 of which 167 developed HCC(1.7%).All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age(five-studies),with two studies each showing male sex,high alpha feto-protein,directly-acting antivirals treatment and achievement of sustained virologic res
文摘丙型肝炎病毒（hepatitis C virus，HCV）感染呈全球性流行，不同性别、年龄、种族人群均对丙型肝炎病毒易感。丙型肝炎病毒常常可导致慢性感染，是全世界慢性肝病主要病因之一。慢性丙型肝炎病毒感染常呈持续很多年的进展性病程，并最终导致肝硬化、肝细胞癌以及需要进行肝移植的终末期肝病。本文就基因3型丙型肝炎病毒感染及其抗病毒治疗作一阐述。
基金supported by the Beijing Natural Science Foundation(7192029)the National Natural Science Foundation of China(82172277)the Beijing Municipal Commission of Health(2060399 PXM2017_026268_00005_00254486).
文摘Background Previous serological studies of human bocavirus(HBoV)1 could not exclude cross-reactivity with the other three HBoVs,particularly HBoV2.Methods To search for genotype-specific antibodies against HBoV1 and HBoV2,the divergent regions(DRs)located on the major capsid protein VP3 were defined through viral amino acid alignment and structure prediction.DR-deduced peptides were used as antigens to harvest corresponding anti-DR rabbit sera.To determine their genotype specificities for HBoV1 and HBoV2,these sera samples were used as antibodies against the antigens VP3 of HBoV1 and HBoV2(expressed in Escherichia coli)in western blotting(WB),enzyme-linked immunosorbent assay(ELISA),and bio-layer interferometry(BLI)assays.Subsequently,the antibodies were evaluated with clinical specimens from pediatric patients with acute respiratory tract infection by indirect immunofluorescence assay(IFA).Results There were four DRs(DR1–4)located on VP3 with different secondary and tertiary structures between HBoV1 and HBoV2.Regarding the reactivity with VP3 of HBoV1 or HBoV2 in WB and ELISA,high intra-genotype cross-reactivity of anti-HBoV1 or HBoV2 DR1,DR3,and DR4,but not anti-DR2,was observed.Genotype-specific binding capacity of anti-DR2 sera was confirmed by BLI and IFA,in which only anti-HBoV1 DR2 antibody reacted with HBoV1-positive respiratory specimens.Conclusion Antibodies against DR2,located on VP3 of HBoV1 or HBoV2,were genotype specific for HBoV1 and HBoV2,respectively.
文摘Single nucleotide polymorphisms near the interleukin28B(IL-28B)gene have been identified as strong predictors of both spontaneous or Peg-interferon(Peg-IFN)and ribavirin(RBV)induced clearance of hepatitis C virus(HCV).Several studies have shown that,in patients with genotype 1(GT-1),rs12979860 C/C and rs8099917T/T substitutions are associated with a more than twofold increase in sustained virological response rate to Peg-IFN and RBV treatment.Although new treatment regimens based on combination of DAA with or without IFN are in the approval phase,until combination regimens with a backbone of Peg-IFN will be used,we can expect that IL28B holds its importance.The clinical relevance of IL28B genotyping in treatment of patients infected with HCV genotype 2(GT-2)and 3(GT-3)remains controversial.Therefore,after a careful examination of the available literature,we analyzed the impact of IL28B in GT-2 and-3.Simple size of the studies and GT-2 and GT-3 proportion were discussed.An algorithm for the practical use of IL28B in these patients was suggested at the aim of optimizing treatment.
基金Supported by Agence Nationale de la Recherche sur le SIDA et les Hépatites Virales
文摘Hepatitis C virus(HCV) infection is one of the most common causes of chronic liver disease and the main indication for liver transplantation worldwide. As promising specific treatments have been introduced for genotype 1, clinicians and researchers are now focusing on patients infected by non-genotype 1 HCV, particularly genotype 3. Indeed, in the golden era of direct-acting antiviral drugs, genotype 3 infections are no longer considered as easy to treat and are associated with higher risk of developing severe liver injuries, such as cirrhosis and hepatocellular carcinoma. Moreover, HCV genotype 3 accounts for 40% of all HCV infections in Asia and is the most frequent genotype among HCV-positive injecting drug users in several countries. Here, we review recent data on HCV genotype 3 infection/treatment, including clinical aspects and the underlying genotype-specific molecular mechanisms.
