AIM:To investigate retrospectively the long-term efficacy of various treatment strategies using adefovir dipivoxil(adefovir) in patients with lamivudine-resistant chronic hepatitis B.METHODS:We included 154 consecutiv...AIM:To investigate retrospectively the long-term efficacy of various treatment strategies using adefovir dipivoxil(adefovir) in patients with lamivudine-resistant chronic hepatitis B.METHODS:We included 154 consecutive patients in two treatment groups:the "add-on" group(n = 79),in which adefovir was added to ongoing lamivudine treatment due to lamivudine resistance,and the "switch/combination" group(n = 75),in which lamivudine was first switched to adefovir and then re-added later as needed.The "switch/combination" group was then divided into two subgroups depending on whether participants followed(group A,n = 30) or violated(group B,n = 45) a proposed treatment strategy that determined whether to add lamivudine based on the serum hepatitis B virus(HBV) DNA levels(< 60 IU/mL or not) after 6 mo of treatment(roadmap concept).RESULTS:The cumulative probability of virologic response(HBV DNA < 60 IU/mL) was higher in group A than in the "add-on" group and in group B(P < 0.001).In contrast,the cumulative probability of virologic breakthrough was lower in the "add-on" group than in group B(P = 0.002).Furthermore,the risk of virologic breakthrough in the multivariate analysis was significantly lower in the "add-on" group than in group A(hazard ratio = 0.096;95%CI,0.015-0.629;P = 0.015).CONCLUSION:The selective combination of adefovir with lamivudine based upon early treatment responses increased the odds of virologic breakthrough relative to the use of uniform combination therapy from the beginning of treatment.展开更多
Hepatitis C is the most common indication for orthotopic liver transplantation in the United States. Unfortunately, hepatitis C recurs universally in the transplanted liver and is the major cause of decreased graft an...Hepatitis C is the most common indication for orthotopic liver transplantation in the United States. Unfortunately, hepatitis C recurs universally in the transplanted liver and is the major cause of decreased graft and patient survival. The combination therapy of interferon and ribavirin has been shown to be the most effective therapy for recurrent hepatitis C. However, pre-and post-transplant hypersplenism often precludes patients from receiving the antiviral therapy. Splenectomy and partial splenic embolization are the two invasive modalities that can correct the cytopenia associated with hypersplenism. In this report we review the two treatment options, their associated outcomes and complications.展开更多
AIM:To analyze the association of three IL28B single nucleotide polymorphisms with response to therapy in Chilean patients infected with hepatitis C virus CV.METHODS:We studied two groups of patients with chronic CV i...AIM:To analyze the association of three IL28B single nucleotide polymorphisms with response to therapy in Chilean patients infected with hepatitis C virus CV.METHODS:We studied two groups of patients with chronic CV infection genotype 1,under standard combined treatment with pegylated interferon plus ribavirin.One group consisted of 50 patients with sustained virological response,whereas the second group consisted of 49 null responders.In order to analyze the IL28B single nucleotide polymorphisms rs12979860,rs12980275 and rs8099917,samples were used for polymerase chain reaction amplification,and the genotyping was performed by restriction fragment lengthpolymorphism.RESULTS:The IL28B rs12979860 CC,rs12980275 AA and rs8099917 TT genotypes were much more frequently found in patients with sustained virological response compared to null responders 38%,44% and 50% vs 2%,8.2% and 8.2%,respectively.These differences were highly significant in all three cases(P < 0.0001.CONCLUSION:The three IL28B polymorphisms studied are strongly associated with sustained virological response to therapy in Chilean patients with chronic CV genotype 1.展开更多
AIM:To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B(CHB) patients with decompensated cirrhosis.METHODS:Thirty HBeAg positive CHB patients with decompensated cirrhosis ...AIM:To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B(CHB) patients with decompensated cirrhosis.METHODS:Thirty HBeAg positive CHB patients with decompensated cirrhosis were enrolled in the study.All of the patients were given 48 wk combination therapy with lamivudine(LAM) and adefovir dipivoxil(ADV) .Briefly,10 patients were given the de novo combination therapy with LAM and ADV,whereas the other 20 patients received ADV in addition to LAM after hepatitis B virus(HBV) genetic mutation.RESULTS:Serum alanine aminotransferase and total bilirubin were both improved in the two groups at 4,12,24 and 48 wk after treatment.Serum albumin was also improved at 24 and 48 wk after combination therapy in both groups.The serum HBV DNA level wasstill detectable in every patient in the two groups at 4 and 12 wk after combination treatment.However,in the de novo combination group,serum HBV DNA levels in 4(40%) and 9(90%) patients was decreased to below 1×10 3 copies/mL at 24 and 48 wk after the combination treatment,respectively.In parallel,serum HBV DNA levels in 2(20%) and 8(40%) patients in the add-on combination group became undetectable at 24 and 48 wk after combination treatment,respectively.Furthermore,6(60%) patients in the de novo combination group achieved HBeAg seroconversion after 48 wk treatment,whereas only 4(20%) patients in the add-on combination group achieved seroconversion.Child-Pugh score of patients in the de novo combination group was better than that of patients in the add-on combination group after 48 wk treatment.Moreover,patients in the de novo combination group had a significantly decreased serum creatinine level and elevated red blood cell counts.CONCLUSION:De novo combination therapy with LAM and ADV was better than add-on combination therapy in terms of Child-Pugh score,virus inhibition and renal function.展开更多
Pure red cell aplasia (PRCA) is a rare hematological disorder which is characterized by severe anemia,reticulocytopenia and almost complete absence of erythroid precursors in bone marrow.The pathophysiology of PRCA ma...Pure red cell aplasia (PRCA) is a rare hematological disorder which is characterized by severe anemia,reticulocytopenia and almost complete absence of erythroid precursors in bone marrow.The pathophysiology of PRCA may be congenital or acquired.To our knowledge,there is only one case report in the English literature of PRCA after pegylated interferon combination therapy for chronic hepatitis C.We report a second case of PRCA after pegylated interferon combination treatment for chronic hepatitis C.The diagnosis of PRCA was confirmed by the typical findings of bone marrow biopsy.The possible etiologies of our case are also discussed in this paper.展开更多
AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Althou...AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNA- dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear. METHODS: HCV quasispecies were studied by clon- ing and sequencing of sequential isolates from patients infected by HCV genotype 1b. Patients were treated by IFN-α2b for 3 mo followed by IFN-α2b alone or com- bined IFN-R therapy for 9 additional months. Patients were categorized intro two groups based on their re- sponse to the treatments: 7 with sustained virological re- sponse (SVR) (quasispecies = 150) and 3 non-respond- ers (NR) to IFN-R (quasispecies = 106). RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispe- cies during therapy. Analysis of amino acids substitu- tions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate thetwo groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients. CONCLUSION: These results suggest that detailed mo- lecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection.展开更多
AIM: To investigate the efficacy and safety of combined antiviral and immunosuppressant therapy in adult hepatitis B virus-associated glomerulonephritis (HBVGN) patients. METHODS: A computerized literature search was ...AIM: To investigate the efficacy and safety of combined antiviral and immunosuppressant therapy in adult hepatitis B virus-associated glomerulonephritis (HBVGN) patients. METHODS: A computerized literature search was carried out in the PubMed database, Embase, the Cochrane Library, Chinese BioMedical Literature on disc, Chinese Medical Current Contents, Chinese National Knowledge Infrastructure, Wanfang and VIP (Chinese Technological Journal of Database) to collect articles between June 1980 and December 2010 on therapy with immunosuppressants, e.g., glucorticosteroids, mycophenolate mofetil and leflunomide, combined with antivirals, e.g., interferon, lamivudine, entecavir and adefovir dipivoxil, in adult HBV-GN patients. The primary outcomes were remission of proteinuria, clearanceof HBV e-antigen, and elevation of serum albumin. The secondary outcomes were blood levels of alanine aminotransferase, serum creatinine, and HBV-DNA titer. Meta-analysis was performed using Review Manager 5.1. Fixed or random effect models were employed to combine the results after a heterogeneity test. The effects of the combined therapy were analyzed for different doses of glucorticosteroid and different types of HBV-GN. RESULTS: Twelve clinical trials with 317 patients were included. A significantly higher incidence of HBV-GN was found in male patients (relative risk = 2.40, 95% CI: 1.98-2.93). Combined therapy reduced the proteinuria significantly with a mean difference of 4.19 (95% CI: 3.86-4.53) and increased the serum albumin concentration significantly with a mean difference of -11.95 (95% CI: -12.97-10.93) without significant alterations of liver function (mean difference: 4.62, 95% CI: -2.55-11.79) and renal function (mean difference: 10.29, 95% CI: 0.14-20.45). No signif icant activation of HBV-DNA replication occurred (mean difference: 0.12, 95% CI: -0.37-0.62). There was no significant difference between the high dose glucorticosteroid group and the low dose glucorticosteroid group in terms of proteinuria remission (P = 0.76) and between different pathological types of HBV-GN [membranous glomerulonephritis (MN) vs mesangial proliferative glomerulonephritis, P = 0.68; MN vs membranoproliferative glomerulonephritis, P = 0.27]. CONCLUSION: Combined antiviral and immunosuppressant therapy can improve the proteinuria in HBVGN patients without altering HBV replication or damaging liver and renal functions.展开更多
A contrast study on the effects of manual acupuncture and electroacupuncture wasconducted in 60 cases of chronic hepatitis B carriers.The results demonstrated that theimmunological functions,both cellular and humoral,...A contrast study on the effects of manual acupuncture and electroacupuncture wasconducted in 60 cases of chronic hepatitis B carriers.The results demonstrated that theimmunological functions,both cellular and humoral,were markedly regulated asevidenced by the negative turnover rates of HBsAg,HBeAg,anti-HBc and HBcAg,as wellas the positive turnover rate of anti-HBe.展开更多
基金Supported by A grant from the Korea Healthcare Technology R and D project,Ministry of Health and Welfare,South Korea,No. R06050496
文摘AIM:To investigate retrospectively the long-term efficacy of various treatment strategies using adefovir dipivoxil(adefovir) in patients with lamivudine-resistant chronic hepatitis B.METHODS:We included 154 consecutive patients in two treatment groups:the "add-on" group(n = 79),in which adefovir was added to ongoing lamivudine treatment due to lamivudine resistance,and the "switch/combination" group(n = 75),in which lamivudine was first switched to adefovir and then re-added later as needed.The "switch/combination" group was then divided into two subgroups depending on whether participants followed(group A,n = 30) or violated(group B,n = 45) a proposed treatment strategy that determined whether to add lamivudine based on the serum hepatitis B virus(HBV) DNA levels(< 60 IU/mL or not) after 6 mo of treatment(roadmap concept).RESULTS:The cumulative probability of virologic response(HBV DNA < 60 IU/mL) was higher in group A than in the "add-on" group and in group B(P < 0.001).In contrast,the cumulative probability of virologic breakthrough was lower in the "add-on" group than in group B(P = 0.002).Furthermore,the risk of virologic breakthrough in the multivariate analysis was significantly lower in the "add-on" group than in group A(hazard ratio = 0.096;95%CI,0.015-0.629;P = 0.015).CONCLUSION:The selective combination of adefovir with lamivudine based upon early treatment responses increased the odds of virologic breakthrough relative to the use of uniform combination therapy from the beginning of treatment.
文摘Hepatitis C is the most common indication for orthotopic liver transplantation in the United States. Unfortunately, hepatitis C recurs universally in the transplanted liver and is the major cause of decreased graft and patient survival. The combination therapy of interferon and ribavirin has been shown to be the most effective therapy for recurrent hepatitis C. However, pre-and post-transplant hypersplenism often precludes patients from receiving the antiviral therapy. Splenectomy and partial splenic embolization are the two invasive modalities that can correct the cytopenia associated with hypersplenism. In this report we review the two treatment options, their associated outcomes and complications.
基金Supported by The grant OAIC 394/10(to M.V.)from Hospital Clínico Universidad de Chile
文摘AIM:To analyze the association of three IL28B single nucleotide polymorphisms with response to therapy in Chilean patients infected with hepatitis C virus CV.METHODS:We studied two groups of patients with chronic CV infection genotype 1,under standard combined treatment with pegylated interferon plus ribavirin.One group consisted of 50 patients with sustained virological response,whereas the second group consisted of 49 null responders.In order to analyze the IL28B single nucleotide polymorphisms rs12979860,rs12980275 and rs8099917,samples were used for polymerase chain reaction amplification,and the genotyping was performed by restriction fragment lengthpolymorphism.RESULTS:The IL28B rs12979860 CC,rs12980275 AA and rs8099917 TT genotypes were much more frequently found in patients with sustained virological response compared to null responders 38%,44% and 50% vs 2%,8.2% and 8.2%,respectively.These differences were highly significant in all three cases(P < 0.0001.CONCLUSION:The three IL28B polymorphisms studied are strongly associated with sustained virological response to therapy in Chilean patients with chronic CV genotype 1.
基金Supported by Glorious Funds from Chinese foundation for hepatitis prevention and control,No.GHF2010205
文摘AIM:To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B(CHB) patients with decompensated cirrhosis.METHODS:Thirty HBeAg positive CHB patients with decompensated cirrhosis were enrolled in the study.All of the patients were given 48 wk combination therapy with lamivudine(LAM) and adefovir dipivoxil(ADV) .Briefly,10 patients were given the de novo combination therapy with LAM and ADV,whereas the other 20 patients received ADV in addition to LAM after hepatitis B virus(HBV) genetic mutation.RESULTS:Serum alanine aminotransferase and total bilirubin were both improved in the two groups at 4,12,24 and 48 wk after treatment.Serum albumin was also improved at 24 and 48 wk after combination therapy in both groups.The serum HBV DNA level wasstill detectable in every patient in the two groups at 4 and 12 wk after combination treatment.However,in the de novo combination group,serum HBV DNA levels in 4(40%) and 9(90%) patients was decreased to below 1×10 3 copies/mL at 24 and 48 wk after the combination treatment,respectively.In parallel,serum HBV DNA levels in 2(20%) and 8(40%) patients in the add-on combination group became undetectable at 24 and 48 wk after combination treatment,respectively.Furthermore,6(60%) patients in the de novo combination group achieved HBeAg seroconversion after 48 wk treatment,whereas only 4(20%) patients in the add-on combination group achieved seroconversion.Child-Pugh score of patients in the de novo combination group was better than that of patients in the add-on combination group after 48 wk treatment.Moreover,patients in the de novo combination group had a significantly decreased serum creatinine level and elevated red blood cell counts.CONCLUSION:De novo combination therapy with LAM and ADV was better than add-on combination therapy in terms of Child-Pugh score,virus inhibition and renal function.
文摘Pure red cell aplasia (PRCA) is a rare hematological disorder which is characterized by severe anemia,reticulocytopenia and almost complete absence of erythroid precursors in bone marrow.The pathophysiology of PRCA may be congenital or acquired.To our knowledge,there is only one case report in the English literature of PRCA after pegylated interferon combination therapy for chronic hepatitis C.We report a second case of PRCA after pegylated interferon combination treatment for chronic hepatitis C.The diagnosis of PRCA was confirmed by the typical findings of bone marrow biopsy.The possible etiologies of our case are also discussed in this paper.
基金Supported by a grant from l’Agence National de la Recherche sur le Sida (ANRS grant 2001/011)
文摘AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNA- dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear. METHODS: HCV quasispecies were studied by clon- ing and sequencing of sequential isolates from patients infected by HCV genotype 1b. Patients were treated by IFN-α2b for 3 mo followed by IFN-α2b alone or com- bined IFN-R therapy for 9 additional months. Patients were categorized intro two groups based on their re- sponse to the treatments: 7 with sustained virological re- sponse (SVR) (quasispecies = 150) and 3 non-respond- ers (NR) to IFN-R (quasispecies = 106). RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispe- cies during therapy. Analysis of amino acids substitu- tions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate thetwo groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients. CONCLUSION: These results suggest that detailed mo- lecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection.
基金Supported by National Natural Science Foundation, No. 81072914Major Project Foundation of National Science and Technology, No. 2010ZX9102-204Traditional Chinese Medicine Research Grant for Military Organization, No. 10ZYZ255
文摘AIM: To investigate the efficacy and safety of combined antiviral and immunosuppressant therapy in adult hepatitis B virus-associated glomerulonephritis (HBVGN) patients. METHODS: A computerized literature search was carried out in the PubMed database, Embase, the Cochrane Library, Chinese BioMedical Literature on disc, Chinese Medical Current Contents, Chinese National Knowledge Infrastructure, Wanfang and VIP (Chinese Technological Journal of Database) to collect articles between June 1980 and December 2010 on therapy with immunosuppressants, e.g., glucorticosteroids, mycophenolate mofetil and leflunomide, combined with antivirals, e.g., interferon, lamivudine, entecavir and adefovir dipivoxil, in adult HBV-GN patients. The primary outcomes were remission of proteinuria, clearanceof HBV e-antigen, and elevation of serum albumin. The secondary outcomes were blood levels of alanine aminotransferase, serum creatinine, and HBV-DNA titer. Meta-analysis was performed using Review Manager 5.1. Fixed or random effect models were employed to combine the results after a heterogeneity test. The effects of the combined therapy were analyzed for different doses of glucorticosteroid and different types of HBV-GN. RESULTS: Twelve clinical trials with 317 patients were included. A significantly higher incidence of HBV-GN was found in male patients (relative risk = 2.40, 95% CI: 1.98-2.93). Combined therapy reduced the proteinuria significantly with a mean difference of 4.19 (95% CI: 3.86-4.53) and increased the serum albumin concentration significantly with a mean difference of -11.95 (95% CI: -12.97-10.93) without significant alterations of liver function (mean difference: 4.62, 95% CI: -2.55-11.79) and renal function (mean difference: 10.29, 95% CI: 0.14-20.45). No signif icant activation of HBV-DNA replication occurred (mean difference: 0.12, 95% CI: -0.37-0.62). There was no significant difference between the high dose glucorticosteroid group and the low dose glucorticosteroid group in terms of proteinuria remission (P = 0.76) and between different pathological types of HBV-GN [membranous glomerulonephritis (MN) vs mesangial proliferative glomerulonephritis, P = 0.68; MN vs membranoproliferative glomerulonephritis, P = 0.27]. CONCLUSION: Combined antiviral and immunosuppressant therapy can improve the proteinuria in HBVGN patients without altering HBV replication or damaging liver and renal functions.
文摘A contrast study on the effects of manual acupuncture and electroacupuncture wasconducted in 60 cases of chronic hepatitis B carriers.The results demonstrated that theimmunological functions,both cellular and humoral,were markedly regulated asevidenced by the negative turnover rates of HBsAg,HBeAg,anti-HBc and HBcAg,as wellas the positive turnover rate of anti-HBe.