- Email: [email protected]
Sa1006 Factors Predicting Progression of Hepatitis C Associated Fibrosis: A Decade Long Follow-up
Sa1004
Sa1006
The Impact of HIV/HCV Co-Infection and the Progression of Liver Fibrosis - a Meta-Analysis Sailajah Janarthanan, Ivo C. Ditah, Douglas G. Adler
Factors Predicting Progression of Hepatitis C Associated Fibrosis: A Decade Long Follow-up Britt Christensen, Alexander J. Thompson, Sally Bell, David M. Iser, Tin Nguyen, Paul Desmond
AASLD Abstracts
Background Data from epidemiological studies suggests that HIV co-infection influences the progression of HCV related liver diseases. However, these finding have not been consistently reported across all studies and some have been criticized for lack of power. The aim of this study was to perform a meta-analysis to determine whether HIV co-infection accelerates the onset of liver fibrosis/cirrhosis in HCV treatment naïve HIV/HCV co-infected patients. Methods We conducted a comprehensive search for studies published up to April 2010. Only studies that compared liver fibrosis/cirrhosis in HCV/HIV co-infected to HCV only infected patients were eligible for analysis. Liver fibrosis or cirrhosis diagnosis was based on histology of liver biopsy or radiology. Reviews of each study were conducted and references were reviewed. The adjusted risk estimates were extracted by two independent authors and summarized using random effects meta-analysis with STATA 9. Results 9 combined casecontrol and cohort studies were eligible for analysis. Among all studies, there was about a seven fold increase in the incidence of liver fibrosis/cirrhosis in HCV/HIV co-infected patients compared to HCV only patients. The overall summary risk estimate for liver fibrosis/cirrhosis was RR 1.67; 95% CI 1.21 to 2.30 (P < 0.001). There was evidence of publication bias among the different studies included. Due to the statistically identified heterogeneity among the studies, we did a random effects meta-analysis. Conclusion Our meta-analysis results show that in treatment naïve patients HIV co-infection accelerates the early onset of liver fibrosis/cirrhosis in HCV infected patients. HIV/HCV co-infected patients may require a more aggressive management approach.
Predictors of progression of liver fibrosis over long periods of time in chronic hepatitis C (CHC) are poorly defined. Our aim was to assess liver fibrosis progression in a wellcharacterized cohort in long-term follow-up (>10ys) and explore factors associated with progression. Methods: CHC patients who had a base-line (B/L) liver biopsy pre-2001 and follow-up (F/U) biopsy/fibroscan (FS) more than 10 years later were identified. Fibrosis (F) was categorised as mild-moderate for biopsy METAVIR stage F0-2 or FS score ≤ 9.5 KPa and advanced for biopsy METAVIR stage F3-4 or FS score > 9.5 KPa. Demographic, clinical, histological and biochemical data were collected. The primary outcome was F progression as defined by an increase from mild-moderate fibrosis at B/L biopsy (F0-2) to advanced fibrosis at F/U biopsy/FS (F3-4/FS>9.5). Variables influencing F progression examined using McNemar's test and logistic regression were viral eradication (SVR), age, gender, duration and mode of infection, HCV genotype (HCV-1 vs non-1), BMI and ALT. Results: 58 patients were identified: 67% male, 85% Caucasian, 68% HCV-1, 25% HCV-3. IVDU (47%) and blood transfusion (16%) were the predominant modes of exposure. At B/L, median age was 39 [range 23-69] and estimated duration of infection was 18 years [range 3-44]. 83% (n= 48) had mild-moderate fibrosis and 17% (n=10) had advanced fibrosis. All patients had repeat fibrosis assessment after a median interval of 13 years [range 10-19]: FS 81% (n= 47) and biopsy 19% (n=11). At F/U 62% (n=36) had mild-moderate fibrosis and 38% (n= 22) advanced fibrosis. 12 patients had F progression. 53 patients received antiviral treatment during the study and 28% (n=16) attained SVR. In patients who attained SVR, 2/16 (13%) progressed to advanced fibrosis, 12/16 (75%) demonstrated no change in fibrosis and 2/16 (13%) regressed to mild-moderate fibrosis (comparison B/L and F/U, p=1.0, McNemar's Test). In patients who remained viraemic during F/U, 11/36 (31%) progressed to advanced fibrosis, 23/36 (64%) demonstrated no change in fibrosis and 1/36 (3%) regressed to mildmoderate fibrosis (p=0.0063, McNemar's Test). On univariate analysis of patients with mildmoderate fibrosis at B/L (n=48), higher ALT was associated with advanced fibrosis at F/U (OR 1.02, 95% CI [1.004, 1.031], p=0.011). In addition there was a trend between increased years of infection and increased F-progression (OR 1.10, 95% CI [0.99, 1.23], p=0.074). There was no association noted between F-progession and patient age (p=0.19), exposure (p=0.50), viral load (p=0.77), gender (p=1) and BMI (p=0.82). Conclusion: HCV causes progressive fibrosis over long periods of time. Viral eradication reduces the risk of F progression, supporting use of antiviral therapy. High ALT in patients with long-standing CHC should increase the index of suspicion for advanced fibrosis.
Sa1005 Development and Preliminary Clinical Evaluation of an Novel Biosensor-Based Microarray (BBM) Assay for Detection of Rs8099917 and Rs12979860 for HCV Individual Therapy Jiawu Song, Peiyuan Li, Xiaojun Zhou, Lan Yao, Bo Guo, Jiangnan Ren Aim: The goal of our study is to develop a novel and promised clinical biosensor-based assay which can simultaneously detect the single nucleotide polymorphisms (SNPs) of rs12979860 and rs8099917 on IL28B which were defined as most important for hepatitis C virus therapy , and evaluate the specificity and sensitivity of the novel assay by both genotype-specificity plasmids and clinical samples. Methods: A set of four kinds of probes specific for rs8099917 or rs12979860 were designed and arrayed on a biosensor microarray. Two sets primers were be used in the same tube the PCR system to amplify two fragments incorporating rs12979860 or rs8099917. The plasmids with different alleles of these two SNPs were generated and be successful amplified and then be sent for reverse hybridization with BBM assay to test the good concordance of all the haplotypes of these two SNPs. The 40 clinical blood samples, of which is 10 for non HCV infected, and 30 for HCV infected patients were applied for evaluation the concordance of BBM with sequencing .Every amplicons of these 40 patients were be tested by BBM and sequencing for evaluation the specificity of the BBM assay. Ten HCV-infected blood samples and their corresponding dilution will be prepared for the confirmation of the sensitivity of the BBM assay. The results were caculated separately by rs12979860 orrs8099917 genotype and Kappa analysis were used to test the accordance between BBM assay and direct sequencing in detecting the two SNPs. Result: The PCR system successfully developed in amplified these two fragment in one tube in this assay. All the halplotypes of rs12979860 and rs8099917 plasmids determined by BBM assay were easily be identified(fig.1), and were full accordant with known synthetic plasmids(concordance was 100%, Kappa=1). Meantime, the accordance ration between direct sequencing and BBM assay for the detection of rs12979860and rs8099917 of clinical blood samples was up to 92.5%(Kappa=0.85>0.75)(table1) and 95%(Kappa=0.88>0.75), respectively. And all of these were suggest that the BBM is a promised clinical assay for these two IL28B SNPs genotyping. Finally a total of 30 blood samples with white blood white cell count ranging from ~10E3 ~10E4 per miniliter (ml) were all detected by BBM assay. Conclusion: Our study demonstrated that BBM assay is a specificity is same as seqeuencing,and also is a simple, rapid, sensitive assay for these two SNPs genotyping. And its high specificity and easy performing as well as time saving make it will be a promised clinical assay for clinical application. The rs12979860 polymorphism of Clinical blood samples
Sa1007 A Survey to Determine Hepatitis C Awareness Among Physicians at a Community Hospital Thimmaiah G. Theethira, Rani Chikkanna, Tushar Gohel The hepatitis C virus (HCV) is a major public health problem and a leading cause of chronic liver disease. An estimated 180 million people are infected worldwide. In the United States (U.S.), the prevalence of HCV infection (HCVI) between the years 1999 and 2002 was 1.6%, equating to about 4.1 million persons positive for antibody to hepatitis C (anti-HCV). The optimal approach to detecting HCVI is to screen persons for a history of risk of exposure to the virus, and to test selected individuals who have an identifiable risk factor. We undertook a survey consisting of a brief questionnaire relating to hepatitis C diagnosis and management to determine the awareness of HCVI among physicians practicing in a community hospital setting. Results: A total of 83 physicians including residents and teaching faculty members responded to the survey from a total of 100 questionnaires distributed. 41 (49.3%) of the respondents were attending physicians, 15 (18%) interns, 14(16.8%) second year residents and 13 (15.6%) third year residents. Most (63.8%) of the responding physicians were from the department of Internal Medicine , with the remaining from Family Practice (18%), Gastroenterology (3.6%) and other Internal Medicine sub specialties (14.5%). A majority (77%) of the physicians indicated that they saw fewer than 10 patients with hepatitis C per year. 20 (24%) responding physicians indicated that they were able to attend at least one CME regarding HCVI each year. 35 (42%) physicians indicated that they routinely looked for tattoos during physical examination. More than half (66.2%) of the responding physicians enquired about a history of intravenous drug use during history taking. Among physicians who actually documented intravenous drug use, 63.8 % of them ordered a hepatitis C screening panel. 52(62.6%) of the physicians felt that they would seek ID/ Hepatology consult when they encountered patients with HCVI and normal transaminases. Only 3(3.6) of the physicians were able to accurately enumerate all the prognostic factors affecting a sustained virologic response to hepatitis C treatment. Conclusion: As the ‘‘gatekeepers'' to the health care system in the United States, primary care physicians must be able to identify patients at risk for hepatitis C and institute proper diagnostic testing and referral. Fewer than half of the responding physicians were actually able to correctly identify patients for screening and evaluate them for hepatitis C infection. The survey results indicated that knowledge about HCV infection among primary care physicians was less than desirable and had scope for improvement. Training level of the respondents
Work up for chronic Hepatitis C virus infection
The halplotypes of rs12979860 and rs8099917 Determined by BBM assay
AASLD Abstracts
S-944
Sa1006
The Impact of HIV/HCV Co-Infection and the Progression of Liver Fibrosis - a Meta-Analysis Sailajah Janarthanan, Ivo C. Ditah, Douglas G. Adler
Factors Predicting Progression of Hepatitis C Associated Fibrosis: A Decade Long Follow-up Britt Christensen, Alexander J. Thompson, Sally Bell, David M. Iser, Tin Nguyen, Paul Desmond
AASLD Abstracts
Background Data from epidemiological studies suggests that HIV co-infection influences the progression of HCV related liver diseases. However, these finding have not been consistently reported across all studies and some have been criticized for lack of power. The aim of this study was to perform a meta-analysis to determine whether HIV co-infection accelerates the onset of liver fibrosis/cirrhosis in HCV treatment naïve HIV/HCV co-infected patients. Methods We conducted a comprehensive search for studies published up to April 2010. Only studies that compared liver fibrosis/cirrhosis in HCV/HIV co-infected to HCV only infected patients were eligible for analysis. Liver fibrosis or cirrhosis diagnosis was based on histology of liver biopsy or radiology. Reviews of each study were conducted and references were reviewed. The adjusted risk estimates were extracted by two independent authors and summarized using random effects meta-analysis with STATA 9. Results 9 combined casecontrol and cohort studies were eligible for analysis. Among all studies, there was about a seven fold increase in the incidence of liver fibrosis/cirrhosis in HCV/HIV co-infected patients compared to HCV only patients. The overall summary risk estimate for liver fibrosis/cirrhosis was RR 1.67; 95% CI 1.21 to 2.30 (P < 0.001). There was evidence of publication bias among the different studies included. Due to the statistically identified heterogeneity among the studies, we did a random effects meta-analysis. Conclusion Our meta-analysis results show that in treatment naïve patients HIV co-infection accelerates the early onset of liver fibrosis/cirrhosis in HCV infected patients. HIV/HCV co-infected patients may require a more aggressive management approach.
Predictors of progression of liver fibrosis over long periods of time in chronic hepatitis C (CHC) are poorly defined. Our aim was to assess liver fibrosis progression in a wellcharacterized cohort in long-term follow-up (>10ys) and explore factors associated with progression. Methods: CHC patients who had a base-line (B/L) liver biopsy pre-2001 and follow-up (F/U) biopsy/fibroscan (FS) more than 10 years later were identified. Fibrosis (F) was categorised as mild-moderate for biopsy METAVIR stage F0-2 or FS score ≤ 9.5 KPa and advanced for biopsy METAVIR stage F3-4 or FS score > 9.5 KPa. Demographic, clinical, histological and biochemical data were collected. The primary outcome was F progression as defined by an increase from mild-moderate fibrosis at B/L biopsy (F0-2) to advanced fibrosis at F/U biopsy/FS (F3-4/FS>9.5). Variables influencing F progression examined using McNemar's test and logistic regression were viral eradication (SVR), age, gender, duration and mode of infection, HCV genotype (HCV-1 vs non-1), BMI and ALT. Results: 58 patients were identified: 67% male, 85% Caucasian, 68% HCV-1, 25% HCV-3. IVDU (47%) and blood transfusion (16%) were the predominant modes of exposure. At B/L, median age was 39 [range 23-69] and estimated duration of infection was 18 years [range 3-44]. 83% (n= 48) had mild-moderate fibrosis and 17% (n=10) had advanced fibrosis. All patients had repeat fibrosis assessment after a median interval of 13 years [range 10-19]: FS 81% (n= 47) and biopsy 19% (n=11). At F/U 62% (n=36) had mild-moderate fibrosis and 38% (n= 22) advanced fibrosis. 12 patients had F progression. 53 patients received antiviral treatment during the study and 28% (n=16) attained SVR. In patients who attained SVR, 2/16 (13%) progressed to advanced fibrosis, 12/16 (75%) demonstrated no change in fibrosis and 2/16 (13%) regressed to mild-moderate fibrosis (comparison B/L and F/U, p=1.0, McNemar's Test). In patients who remained viraemic during F/U, 11/36 (31%) progressed to advanced fibrosis, 23/36 (64%) demonstrated no change in fibrosis and 1/36 (3%) regressed to mildmoderate fibrosis (p=0.0063, McNemar's Test). On univariate analysis of patients with mildmoderate fibrosis at B/L (n=48), higher ALT was associated with advanced fibrosis at F/U (OR 1.02, 95% CI [1.004, 1.031], p=0.011). In addition there was a trend between increased years of infection and increased F-progression (OR 1.10, 95% CI [0.99, 1.23], p=0.074). There was no association noted between F-progession and patient age (p=0.19), exposure (p=0.50), viral load (p=0.77), gender (p=1) and BMI (p=0.82). Conclusion: HCV causes progressive fibrosis over long periods of time. Viral eradication reduces the risk of F progression, supporting use of antiviral therapy. High ALT in patients with long-standing CHC should increase the index of suspicion for advanced fibrosis.
Sa1005 Development and Preliminary Clinical Evaluation of an Novel Biosensor-Based Microarray (BBM) Assay for Detection of Rs8099917 and Rs12979860 for HCV Individual Therapy Jiawu Song, Peiyuan Li, Xiaojun Zhou, Lan Yao, Bo Guo, Jiangnan Ren Aim: The goal of our study is to develop a novel and promised clinical biosensor-based assay which can simultaneously detect the single nucleotide polymorphisms (SNPs) of rs12979860 and rs8099917 on IL28B which were defined as most important for hepatitis C virus therapy , and evaluate the specificity and sensitivity of the novel assay by both genotype-specificity plasmids and clinical samples. Methods: A set of four kinds of probes specific for rs8099917 or rs12979860 were designed and arrayed on a biosensor microarray. Two sets primers were be used in the same tube the PCR system to amplify two fragments incorporating rs12979860 or rs8099917. The plasmids with different alleles of these two SNPs were generated and be successful amplified and then be sent for reverse hybridization with BBM assay to test the good concordance of all the haplotypes of these two SNPs. The 40 clinical blood samples, of which is 10 for non HCV infected, and 30 for HCV infected patients were applied for evaluation the concordance of BBM with sequencing .Every amplicons of these 40 patients were be tested by BBM and sequencing for evaluation the specificity of the BBM assay. Ten HCV-infected blood samples and their corresponding dilution will be prepared for the confirmation of the sensitivity of the BBM assay. The results were caculated separately by rs12979860 orrs8099917 genotype and Kappa analysis were used to test the accordance between BBM assay and direct sequencing in detecting the two SNPs. Result: The PCR system successfully developed in amplified these two fragment in one tube in this assay. All the halplotypes of rs12979860 and rs8099917 plasmids determined by BBM assay were easily be identified(fig.1), and were full accordant with known synthetic plasmids(concordance was 100%, Kappa=1). Meantime, the accordance ration between direct sequencing and BBM assay for the detection of rs12979860and rs8099917 of clinical blood samples was up to 92.5%(Kappa=0.85>0.75)(table1) and 95%(Kappa=0.88>0.75), respectively. And all of these were suggest that the BBM is a promised clinical assay for these two IL28B SNPs genotyping. Finally a total of 30 blood samples with white blood white cell count ranging from ~10E3 ~10E4 per miniliter (ml) were all detected by BBM assay. Conclusion: Our study demonstrated that BBM assay is a specificity is same as seqeuencing,and also is a simple, rapid, sensitive assay for these two SNPs genotyping. And its high specificity and easy performing as well as time saving make it will be a promised clinical assay for clinical application. The rs12979860 polymorphism of Clinical blood samples
Sa1007 A Survey to Determine Hepatitis C Awareness Among Physicians at a Community Hospital Thimmaiah G. Theethira, Rani Chikkanna, Tushar Gohel The hepatitis C virus (HCV) is a major public health problem and a leading cause of chronic liver disease. An estimated 180 million people are infected worldwide. In the United States (U.S.), the prevalence of HCV infection (HCVI) between the years 1999 and 2002 was 1.6%, equating to about 4.1 million persons positive for antibody to hepatitis C (anti-HCV). The optimal approach to detecting HCVI is to screen persons for a history of risk of exposure to the virus, and to test selected individuals who have an identifiable risk factor. We undertook a survey consisting of a brief questionnaire relating to hepatitis C diagnosis and management to determine the awareness of HCVI among physicians practicing in a community hospital setting. Results: A total of 83 physicians including residents and teaching faculty members responded to the survey from a total of 100 questionnaires distributed. 41 (49.3%) of the respondents were attending physicians, 15 (18%) interns, 14(16.8%) second year residents and 13 (15.6%) third year residents. Most (63.8%) of the responding physicians were from the department of Internal Medicine , with the remaining from Family Practice (18%), Gastroenterology (3.6%) and other Internal Medicine sub specialties (14.5%). A majority (77%) of the physicians indicated that they saw fewer than 10 patients with hepatitis C per year. 20 (24%) responding physicians indicated that they were able to attend at least one CME regarding HCVI each year. 35 (42%) physicians indicated that they routinely looked for tattoos during physical examination. More than half (66.2%) of the responding physicians enquired about a history of intravenous drug use during history taking. Among physicians who actually documented intravenous drug use, 63.8 % of them ordered a hepatitis C screening panel. 52(62.6%) of the physicians felt that they would seek ID/ Hepatology consult when they encountered patients with HCVI and normal transaminases. Only 3(3.6) of the physicians were able to accurately enumerate all the prognostic factors affecting a sustained virologic response to hepatitis C treatment. Conclusion: As the ‘‘gatekeepers'' to the health care system in the United States, primary care physicians must be able to identify patients at risk for hepatitis C and institute proper diagnostic testing and referral. Fewer than half of the responding physicians were actually able to correctly identify patients for screening and evaluate them for hepatitis C infection. The survey results indicated that knowledge about HCV infection among primary care physicians was less than desirable and had scope for improvement. Training level of the respondents
Work up for chronic Hepatitis C virus infection
The halplotypes of rs12979860 and rs8099917 Determined by BBM assay
AASLD Abstracts
S-944