- Email: [email protected]
Sa1090 Low Rate of Hepatitis C Virus Reinfection After Sustained Virological Response in Injected Drug Users
AASLD Abstracts
test compared with only 47% Asian cases with positive anti-HCV (Figure 1). For Asian cases, the most common risk factors were blood transfusion (25%), acupuncture (13%), and exposure to dirty needles (8%). Illicit drug use (IDU) and body tattoo were present only in a minority of patients (3% and 4%, respectively) (Figure 2). For non-Asian cases, the most common risk factors were IDU and body tattoo (41% and 33%, respectively). On multiple logistic regression, independent predictors for positive anti-HCV test in Asians were acupuncture/exposure to dirty needles (OR=11.3, p<0.0001), tattoos (OR=10.5, p=0.002), and history of blood transfusion (OR=5.1, p<0.0001). For both Asian and Non-Asian, cases were more likely to have a family history of HCV compared to controls (6% vs. 1% [p<0.0001] and 15% vs. 2% [p=0.02], respectively). Conclusion: Compared to non-Asians, Asians are likely to present without commonly known risk factors for infection with HCV (47%). In addition to well-known risk factors for HCV infection such as blood transfusion and tattoos, acupuncture and exposure to dirty needles are also independent risk factors of HCV infection. Asians coming from endemic areas should be screened for HCV even when commonly known risk factors for Western patients are not present.
cardiovascular related mortality and infection related mortality. Summary risk ratios were computed using the fixed effects or random effects model if there was suggestion of heterogeneity between the studies. Heterogeneity was assessed using the Cochrane's Q and I2 statistics. Publication bias was evaluated using the Begg's and Egger's tests, and visual inspection of corresponding funnel plots. A sensitivity analysis using Duval and Tweedie's “trim-and-fill” method was also performed. Results: A total of eight studies, all of which were cohort studies met the inclusion criteria. The total number of patients was 41,067, with 4,499 being HCV positive. The overall pooled risk ratio for all-cause-mortality was 1.15 with a 95% CI of 1.08-1.22;P<0.001. Liver dysfunction was the leading cause of mortality in HCV patients with an RR of 9.18(95% CI 4.25 -19.83, P<0.001). The sensitivity analysis incorporating hypothetical studies using the Duval and Tweedie “trim-and-fill” method persistently showed a statistically significant result with RRo 6.45(95%CI 3.27-12.72;P<0.001). There was no statistically significant difference in mortality due to cardiovascular and infectious etiologies between the 2 groups with risk ratios of 1.04(95% CI 0.91-1.18) and 1.14(95% CI 0.891.47), respectively. Table 1 summarizes the results of the various outcomes. Conclusion:This study suggests that HCV infection in long term HD patients is associated with an increased risk of mortality. While cardiovascular disorders are known to be the leading cause of mortality in HD patients, liver dysfunctions may be the leading cause in HCV infected HD patients. Management of HCV in HD needs to be considered a priority. Table 1: Summary of pooled effects, heterogeneity and publication bias
* Sensitivity analysis done because of wide confidence interval in liver related mortality showed Liver related mortality by Duval and Tweedie “trim-and-fill” Pooled effect = 6.45 (95% 3.27-12.72), P <0.001
Figure 1. Proportion of patients with any known risk factors, by ethnicities
Sa1089 Proteomic Analysis of ITPA SNP rs1127354 Chronic Hepatitis C (Ch-C) Patients Indicates Differential Regulation of Apoptosis Pathway Components J. Michael Estep, Maria Stepanova, Arian Afendy, Emanuel Petricoin, Ancha Baranova, Zobair M. Younossi Background:Anemia is an important and common side effect of pegylated interferon alfa and ribavirin (PEG-IFN+RBV). The ITPA SNP rs1127354 “T” allele confers protection against RBV-induced anemia in CH-C patients undergoing PEG-IFN/RBV treatment compared to the more common “C” allele. Previously, we have established that the apoptosis pathway components are significantly differentially regulated at the mRNA level during PEG-IFN/ RBV treatment in patients with differing rs1127354 genotypes. Aim: The aim of this study was to investigate proteomic profiles of CH-C patients with different rs1127354 genotypes. Methods: From peripheral blood lymphocyte samples which were collected from 53 CH-C patients, protein lysates were extracted and then used for Reverse Phase Protein Microarray analysis, which quantitatively measured the relative phosphorylation of the signaling molecules. DNA was extracted from whole blood and genotyped for rs1127354 by PCR using tetra-primer refractory PCR method. Pathway analysis was conducted using MetCore GeneGo and Ariadne Pathway Analysis software packages. Results: MetaCore Pathway Analysis indicated the significant differential regulation of the apoptosis pathway (P=2.88*10^-7). Signals for antiapoptotic molecules CD5L, CD247, and STAT3 were increased in the CT group vs. the CC group by 8.4%, 18.3%, and 25.8%, respectively. Furthermore, in the CT group we observed a decrease in expression of 15 apoptosis-related molecules, 10 of which (LCK, IL4, IL1b, IL10, STAT2, PKLR, PRKCZ, PRKCD, RPS6KB1, and JAK1) are considered proapoptotic. Additionally, in the CT group, decreases of IL5 and IL10 signals were observed. IL5 and IL10, known to promote hemolysis, were lower in the heterozygous CT group as compared to the CC by 3% and 9.9% respectively. Conclusions: Proteomic investigations support differential regulation of apoptosis as the mechanism by which ITPA genotype confers protection from PEG-IFN/RBV treatment associated anemia.
Figure 2. Risk exposures in cases and controls, by ethnicities Sa1088
Sa1090
Impact of Chronic Hepatitis C Infection on Mortality in Chronic Hemodialysis Patients: A Meta-Analysis Augustine Salami, Ivo C. Ditah, Vidyasagar Marupakula, Charles O. Jaiyeoba, Zeenat Bhat, Syed-Mohammed Jafri
Low Rate of Hepatitis C Virus Reinfection After Sustained Virological Response in Injected Drug Users Spilios Manolakopoulos, Hariklia Kranidioti, Stylianos Karatapanis, Ioannis Goulis, Efrosini Tsirogianni, Melanie Deutsch, Olga Anagnostou, Dimitrios Margaritopoulos, George V. Papatheodoridis, Dimitrios Pectasides
Background: The prevalence of chronic hepatitis C virus infection (HCV) is significantly higher in hemodialysis (HD) patients. There is accumulating data suggesting that HCV is associated with increased mortality in HD patients. However, this increase is likely confounded by several co-morbidities and incident complications in these patients. While cardiovascular disorders remain the leading cause of death in HD patients, it is unknown whether this is true in HCV positive HD patients. AIM: Evaluate the impact of chronic HCV infection on mortality in hemodialysis patients. Methods: A systematic search of PubMed,Scopus,and Web of Science databases from January 1980 to September 2011 was done. Identified articles were manually reviewed for additional references. Only peer-reviewed articles comparing mortality in HCV positive to HCV negative patients who must have been on hemodialysis for at least six months were eligible for inclusion. Data were abstracted independently by 2 authors. Inter-reviewer discrepancies were resolved by joint review of the original article. Outcome measures evaluated included all-cause mortality, liver disease-related mortality,
AASLD Abstracts
Background and aims The majority of intravenous drug users (IVDUs) are infected with the hepatitis C virus (HCV) and they may be the source of infection of many other subjects due to their risky behavior. Despite the fact that the majority of IVDUs in Greece are infected with HCV genotype 3 and have similar response rates to non-IVDU patients, only a minority of them start antiviral treatment. The risk of reinfection following therapy is one of the main reasons for not initiating antiviral treatment. We evaluated the rate of HCV reinfection in past - current IVDUs following sustained virological response (SVR) having received anti viral treatment in a multidisciplinary program. Methods We analyzed data from a cohort of IVDUs patients with HCV infection attending a multidisciplinary supervised program in three liver Greek Units. Inclusion criteria were: A. chronic hepatitis C infection, b. previous antiviral treatment with development of SVR, c.) at least 12 months interval after end of
S-966
treatment, d. patient willingness to be included in the study. All patients after giving inform consent were evaluated with a minucious questionaring and were retested for HCV RNA. Results Between January 2011and October 2011, 61 patients (49 males/12 females, mean age 37,5 years, range 20-61) were included in the present study. 67,7% had genotype 3a. The mean time between the end of treatment and re-evaluation was 2,5 years (range 1-7). At the day of re-evaluation, 37/61 (60%) patients reported active drug use and 21/37 (56,8%) were injected drug users. 27/61 (43,5%) patients were on methadone / buprenorphine substistution. Only 5/61 (8,1%) cases of reinfection were observed. They were all injected drug users and 4 of whom were infected with another HCV genotype from the initial, while one patient was reinfected with the same (genotype 3a). Two of these 5 patients were lost from the supervised program. Conclusion Our study showed that the rate of reinfection after successful treatment of HCV infection in past or current users is very low. In IVDUs, treatment of hepatitis C is feasible, when a multidisciplinary team is willing to provide the appropriate care.
Participants were classified as advanced fibrosis cases (stage F3-F4) vs. mild controls (F0F2), advanced inflammation (A2-A3) vs. mild (A0-A1/A2), and advanced steatosis (S1-S3) vs. mild (S0). We evaluated the association between total serum testosterone and fibrosis, inflammation and steatosis using logistic regression with adjustment for age, race, diabetes, alcohol abuse, adiposity (BMI 25+), and viral load. Results: Mean age was 56 years with 40% White and 56% African American. (Table 1) Multivariate analyses demonstrated that each 1 ng/ml increase in total serum testosterone was associated with a significantly increased excess risk of advanced fibrosis (21%, p=0.04) and with an increased advanced inflammation risk closely approaching significance (16%, p=0.07). Higher total testosterone was not associated with steatosis risk (8%, p=0.38). The strength of the association between testosterone and advanced liver disease was similar in the current biopsy-based and previous FibroSURE-based studies (21% and 25% excess fibrosis risk and 16% and 15% excess inflammation risk in the current and previous studies). Conclusions: Higher total serum testosterone is associated with increased risk of biopsy-confirmed hepatic fibrosis and inflammation in HCV+ males; this finding supports our earlier FibroSURE-based study results [1]. Larger prospective studies are needed to assess if the association between testosterone and hepatic fibrosis and inflammation is causal in males, and to assess if a similar association exists in HCV+ females. References: [1] White DL, Tavakoli-Tabasi S, Kuzniarek J, Pascua R, Ramsey DJ, El-Serag HB. Higher serum testosterone is associated with increased risk of advanced hepatitis C-related liver disease in males.Hepatology 2011 Aug 19. Sociodemographic and clinical characteristic of 192 chronically HCV-infected male veterans
Sa1091 Hepatitis C (HCV) Antiviral Therapy is Feasible in Patients With Active Substance use (SU) and Mental Illness (MI) and is More Likely to Occur in Those Who Receive Education Class Khurram Bari, Salvador Augustin, Carol A. Eggers, Hashem J. Hashem, Mayur Desai, Martha Shea, Suchat Wongcharatrawee, Joseph K. Lim, Guadalupe Garcia-Tsao
AASLD Abstracts
Many veterans with HCV infection have active SU or MI and these co-morbidities are considered contraindications to antiviral therapy in most centers across the world. The objective of the study was to assess the feasibility of therapy in these patients and to identify predictors and/or barriers to treatment initiation. METHODS: Prospective cohort study of anti-HCV-positive veterans with active SU (use of alcohol and/or illegal substances within 6 months) and/or active MI (undergoing active treatment for MI in the past 6 months). Patients who agreed to have a baseline psychometric evaluation were enrolled in the study. After the initial visit, all patients were given appointments to attend HCV education class (1 hour), baseline psychiatric evaluation, liver biopsy and office visit with provider to discuss therapy and decide on treatment initiation. Patients who decided to undergo therapy (mostly pegylated interferon + ribavirin), were followed until completion of therapy and evaluation of sustained virological response (SVR). RESULTS: From 1/03 to 5/09, 928 patients with active SU/MI were referred to the clinic and 296 were enrolled in the study, of which 69 were excluded (50 genotype non-1, 14 medical contraindications, 5 negative HCV-RNA). We chose to focus this analysis on genotype 1 patients (n=227) since the results would be more relevant to current triple therapy. Median age was 51 years, 99% male, 50% Caucasian, 45% African-American (AA), 5 % Hispanic; median BMI 28, biopsy done in 43% (46% stage 0-1; 54% stage 2-4)]. One hundred and seventy (75%) patients had active MI and 139 (61%) had active SU; 94 (41%) had both. Eighty one (36%) patients initiated HCV therapy. Fifty eight (72%) continued treatment until recommended by provider and 16 patients (16/81=20%) had SVR (rate across the VA is ~25%). On univariate analysis, and taking into account all baseline characteristics, patients who initiated treatment were more likely to have: attended education class, baseline psychiatric evaluation, liver biopsy and prior HCV treatment. AA ethnicity and alcohol + another substance (polySU) were inversely related to treatment initiation. On multivariate analysis, education class (p=0.002, OR=3.1) was the strongest predictor of treatment initiation while AA ethnicity (p=0.023, OR=0.5) and polySU (p=0.057, OR=0.52) were the most significant barriers to starting therapy. Having attended class increased treatment initiation rates in AAs and in polySU patients (Table 1). Patients who attended class were also more likely to have a liver biopsy (52% vs. 85%, p=0.000) CONCLUSION: HCV treatment is feasible in patients with active SU/MI and these co-morbidities should not be a contraindication to therapy. Patient education is the strongest predictor of treatment initiation and increases therapy rates in even harderto-treat subsets of patients (AA, polySU). Effect of education class on treatment rates for African-American and poly SU patients
Logistic regression models for the association between total serum testosterone level and risk of advanced biopsy-confirmed hepatic fibrosis, inflammation, and steatosis
^Chronic alcohol abuse (3+ drinks/day for >=10 years) Sa1093 Inosine Triphosphastase (ITPA) Variants Predict Treatment-Induced Anemia, Ribavirin Dose-Reduction and Need for Erythropoietin Support During Peginterferon/Ribavirin Therapy for Chronic HCV Paul J. Clark, Alessio Aghemo, Elisabetta Degasperi, Enrico Galmozzi, Alexander J. Thompson, Keyur Patel, Maria Grazia Rumi, G. Prati, Massimo Colombo Background: Anemia frequently complicates peginterferon/ribavirin (PEG/RBV) therapy for HCV, and is a persistent challenge in many direct antiviral-based regimens. Better prediction of anemia and the need for ribavirin dose reduction (RBVDR) or erythropoietin (EPO) may enhance patient management. Inosine triphosphatase (ITPA) gene variants are strongly associated with RBV-induced anemia (Fellay 2009) however ITPA's impact in the clinic remains undefined. Methods: 193 patients consecutively treated with PEG/RBV for chronic HCV were genotyped for ITPA (rs1127354 and rs7270101) using Taqman probes. HardyWeinberg equilibrium was present. ITPA deficiency was estimated as previously described (no deficiency/mild/moderate/severe, 0-3). Univariate and multivariate analysis (MVA) considered ITPA association with 4 week (Wk4) Hb measures: Hb decline (mg/dL); Hb < 10 mg/dL and Hb decline >3mg/dL); need for RBVDR and EPO. MVA adjusted for age, female gender, baseline Hb and renal impairment (eGFR >90 ml/min/1.73m2), hepatic fibrosis (>Ishak 3) and starting RBV dose (mg/kg) using backward elimination algorithms. Results: 126 patients had no ITPA deficiency and 67 had some degree of deficiency (n=126/40/24/ 3, ITPA deficiency grade 0/1/2/3 respectively). ITPA deficient patients had less median Hb decline at Wk4 (decline: 3.0/2.2/0.60/0 mg/dL, 0-3 respectively, P< 0.001). ITPA deficient patients were less likely to experience anemia (Hb< 10mg/dL (OR: 0.08, P=0.005) and Hb decline>3mg/dL (OR:0.19, P< 0.001)) at Wk4. ITPA deficiency reduced the odds of RBVDR (18% (12/67) vs. 40% (51/126, OR:0.32, (CI:0.16-0.66), P=0.003)) and need for EPO (OR:0.41, CI:0.20-0.82, P=0.017) throughout treatment. MVA: ITPA (P< 0.001), baseline Hb (P< 0.001), fibrosis (P=0.017), gender (P=0.030) and RBV dose (P=0.034) were associated with Hb decline at Wk4 (R2= 0.45) and the likelihood of a >3mg/dL Hb drop (R2= 0.39). ITPA and baseline Hb were associated with HB decline to < 10mg (R2= 0.31). RBV dose (P< 0.001), ITPA (P=0.021) and baseline Hb (P=0.045), were associated with RBVDR (R2= 0.39). EPO need was associated with baseline Hb (P< 0.001), renal impairment (P=0.001), fibrosis (P=0.002) and ITPA (P=0.020, R2= 0.34). Conclusion: In this clinic-based cohort,
Sa1092 Higher Total Serum Testosterone Level is Associated With Increased Risk of Biopsy-Confirmed Advanced Hepatic Fibrosis and Inflammation but Not Advanced Steatosis in Male Veterans With Chronic Hepatitis C Donna L. White, Linda K. Green, Shahriar Tavakoli-Tabasi, Jill Kuzniarek, David J. Ramsey, Shubhada Sansgiry, Jodi Francis, Hashem El-Serag Background: Chronic liver disease including cirrhosis and HCC are greatly increased (2-4 fold higher) in males than females across a spectrum of risk factors including hepatitis C. We previously reported that higher total serum testosterone was associated with increased risk of FibroSURE determined hepatic fibrosis and inflammation in hepatitis C (HCV) infected males.[1] We performed a confirmatory analysis in 192 HCV+ males with liver biopsy and in addition assessed the association between serum testosterone and steatosis risk. Methods: We prospectively recruited consecutive veterans with chronic HCV in an urban VA HCV clinic (2009-2011). Analyses were restricted to males, ages 20-70, not on interferon, and without sex hormone modifying conditions or medications, decompensation or HCC. An RA administered survey interrogated alcohol and medical history, viremia was confirmed, measurements were taken, and a physician reviewed medical records for contraindications. A single blinded pathologist assessed biopsies using METAVIR and Brunt classifications.
S-967
AASLD Abstracts
test compared with only 47% Asian cases with positive anti-HCV (Figure 1). For Asian cases, the most common risk factors were blood transfusion (25%), acupuncture (13%), and exposure to dirty needles (8%). Illicit drug use (IDU) and body tattoo were present only in a minority of patients (3% and 4%, respectively) (Figure 2). For non-Asian cases, the most common risk factors were IDU and body tattoo (41% and 33%, respectively). On multiple logistic regression, independent predictors for positive anti-HCV test in Asians were acupuncture/exposure to dirty needles (OR=11.3, p<0.0001), tattoos (OR=10.5, p=0.002), and history of blood transfusion (OR=5.1, p<0.0001). For both Asian and Non-Asian, cases were more likely to have a family history of HCV compared to controls (6% vs. 1% [p<0.0001] and 15% vs. 2% [p=0.02], respectively). Conclusion: Compared to non-Asians, Asians are likely to present without commonly known risk factors for infection with HCV (47%). In addition to well-known risk factors for HCV infection such as blood transfusion and tattoos, acupuncture and exposure to dirty needles are also independent risk factors of HCV infection. Asians coming from endemic areas should be screened for HCV even when commonly known risk factors for Western patients are not present.
cardiovascular related mortality and infection related mortality. Summary risk ratios were computed using the fixed effects or random effects model if there was suggestion of heterogeneity between the studies. Heterogeneity was assessed using the Cochrane's Q and I2 statistics. Publication bias was evaluated using the Begg's and Egger's tests, and visual inspection of corresponding funnel plots. A sensitivity analysis using Duval and Tweedie's “trim-and-fill” method was also performed. Results: A total of eight studies, all of which were cohort studies met the inclusion criteria. The total number of patients was 41,067, with 4,499 being HCV positive. The overall pooled risk ratio for all-cause-mortality was 1.15 with a 95% CI of 1.08-1.22;P<0.001. Liver dysfunction was the leading cause of mortality in HCV patients with an RR of 9.18(95% CI 4.25 -19.83, P<0.001). The sensitivity analysis incorporating hypothetical studies using the Duval and Tweedie “trim-and-fill” method persistently showed a statistically significant result with RRo 6.45(95%CI 3.27-12.72;P<0.001). There was no statistically significant difference in mortality due to cardiovascular and infectious etiologies between the 2 groups with risk ratios of 1.04(95% CI 0.91-1.18) and 1.14(95% CI 0.891.47), respectively. Table 1 summarizes the results of the various outcomes. Conclusion:This study suggests that HCV infection in long term HD patients is associated with an increased risk of mortality. While cardiovascular disorders are known to be the leading cause of mortality in HD patients, liver dysfunctions may be the leading cause in HCV infected HD patients. Management of HCV in HD needs to be considered a priority. Table 1: Summary of pooled effects, heterogeneity and publication bias
* Sensitivity analysis done because of wide confidence interval in liver related mortality showed Liver related mortality by Duval and Tweedie “trim-and-fill” Pooled effect = 6.45 (95% 3.27-12.72), P <0.001
Figure 1. Proportion of patients with any known risk factors, by ethnicities
Sa1089 Proteomic Analysis of ITPA SNP rs1127354 Chronic Hepatitis C (Ch-C) Patients Indicates Differential Regulation of Apoptosis Pathway Components J. Michael Estep, Maria Stepanova, Arian Afendy, Emanuel Petricoin, Ancha Baranova, Zobair M. Younossi Background:Anemia is an important and common side effect of pegylated interferon alfa and ribavirin (PEG-IFN+RBV). The ITPA SNP rs1127354 “T” allele confers protection against RBV-induced anemia in CH-C patients undergoing PEG-IFN/RBV treatment compared to the more common “C” allele. Previously, we have established that the apoptosis pathway components are significantly differentially regulated at the mRNA level during PEG-IFN/ RBV treatment in patients with differing rs1127354 genotypes. Aim: The aim of this study was to investigate proteomic profiles of CH-C patients with different rs1127354 genotypes. Methods: From peripheral blood lymphocyte samples which were collected from 53 CH-C patients, protein lysates were extracted and then used for Reverse Phase Protein Microarray analysis, which quantitatively measured the relative phosphorylation of the signaling molecules. DNA was extracted from whole blood and genotyped for rs1127354 by PCR using tetra-primer refractory PCR method. Pathway analysis was conducted using MetCore GeneGo and Ariadne Pathway Analysis software packages. Results: MetaCore Pathway Analysis indicated the significant differential regulation of the apoptosis pathway (P=2.88*10^-7). Signals for antiapoptotic molecules CD5L, CD247, and STAT3 were increased in the CT group vs. the CC group by 8.4%, 18.3%, and 25.8%, respectively. Furthermore, in the CT group we observed a decrease in expression of 15 apoptosis-related molecules, 10 of which (LCK, IL4, IL1b, IL10, STAT2, PKLR, PRKCZ, PRKCD, RPS6KB1, and JAK1) are considered proapoptotic. Additionally, in the CT group, decreases of IL5 and IL10 signals were observed. IL5 and IL10, known to promote hemolysis, were lower in the heterozygous CT group as compared to the CC by 3% and 9.9% respectively. Conclusions: Proteomic investigations support differential regulation of apoptosis as the mechanism by which ITPA genotype confers protection from PEG-IFN/RBV treatment associated anemia.
Figure 2. Risk exposures in cases and controls, by ethnicities Sa1088
Sa1090
Impact of Chronic Hepatitis C Infection on Mortality in Chronic Hemodialysis Patients: A Meta-Analysis Augustine Salami, Ivo C. Ditah, Vidyasagar Marupakula, Charles O. Jaiyeoba, Zeenat Bhat, Syed-Mohammed Jafri
Low Rate of Hepatitis C Virus Reinfection After Sustained Virological Response in Injected Drug Users Spilios Manolakopoulos, Hariklia Kranidioti, Stylianos Karatapanis, Ioannis Goulis, Efrosini Tsirogianni, Melanie Deutsch, Olga Anagnostou, Dimitrios Margaritopoulos, George V. Papatheodoridis, Dimitrios Pectasides
Background: The prevalence of chronic hepatitis C virus infection (HCV) is significantly higher in hemodialysis (HD) patients. There is accumulating data suggesting that HCV is associated with increased mortality in HD patients. However, this increase is likely confounded by several co-morbidities and incident complications in these patients. While cardiovascular disorders remain the leading cause of death in HD patients, it is unknown whether this is true in HCV positive HD patients. AIM: Evaluate the impact of chronic HCV infection on mortality in hemodialysis patients. Methods: A systematic search of PubMed,Scopus,and Web of Science databases from January 1980 to September 2011 was done. Identified articles were manually reviewed for additional references. Only peer-reviewed articles comparing mortality in HCV positive to HCV negative patients who must have been on hemodialysis for at least six months were eligible for inclusion. Data were abstracted independently by 2 authors. Inter-reviewer discrepancies were resolved by joint review of the original article. Outcome measures evaluated included all-cause mortality, liver disease-related mortality,
AASLD Abstracts
Background and aims The majority of intravenous drug users (IVDUs) are infected with the hepatitis C virus (HCV) and they may be the source of infection of many other subjects due to their risky behavior. Despite the fact that the majority of IVDUs in Greece are infected with HCV genotype 3 and have similar response rates to non-IVDU patients, only a minority of them start antiviral treatment. The risk of reinfection following therapy is one of the main reasons for not initiating antiviral treatment. We evaluated the rate of HCV reinfection in past - current IVDUs following sustained virological response (SVR) having received anti viral treatment in a multidisciplinary program. Methods We analyzed data from a cohort of IVDUs patients with HCV infection attending a multidisciplinary supervised program in three liver Greek Units. Inclusion criteria were: A. chronic hepatitis C infection, b. previous antiviral treatment with development of SVR, c.) at least 12 months interval after end of
S-966
treatment, d. patient willingness to be included in the study. All patients after giving inform consent were evaluated with a minucious questionaring and were retested for HCV RNA. Results Between January 2011and October 2011, 61 patients (49 males/12 females, mean age 37,5 years, range 20-61) were included in the present study. 67,7% had genotype 3a. The mean time between the end of treatment and re-evaluation was 2,5 years (range 1-7). At the day of re-evaluation, 37/61 (60%) patients reported active drug use and 21/37 (56,8%) were injected drug users. 27/61 (43,5%) patients were on methadone / buprenorphine substistution. Only 5/61 (8,1%) cases of reinfection were observed. They were all injected drug users and 4 of whom were infected with another HCV genotype from the initial, while one patient was reinfected with the same (genotype 3a). Two of these 5 patients were lost from the supervised program. Conclusion Our study showed that the rate of reinfection after successful treatment of HCV infection in past or current users is very low. In IVDUs, treatment of hepatitis C is feasible, when a multidisciplinary team is willing to provide the appropriate care.
Participants were classified as advanced fibrosis cases (stage F3-F4) vs. mild controls (F0F2), advanced inflammation (A2-A3) vs. mild (A0-A1/A2), and advanced steatosis (S1-S3) vs. mild (S0). We evaluated the association between total serum testosterone and fibrosis, inflammation and steatosis using logistic regression with adjustment for age, race, diabetes, alcohol abuse, adiposity (BMI 25+), and viral load. Results: Mean age was 56 years with 40% White and 56% African American. (Table 1) Multivariate analyses demonstrated that each 1 ng/ml increase in total serum testosterone was associated with a significantly increased excess risk of advanced fibrosis (21%, p=0.04) and with an increased advanced inflammation risk closely approaching significance (16%, p=0.07). Higher total testosterone was not associated with steatosis risk (8%, p=0.38). The strength of the association between testosterone and advanced liver disease was similar in the current biopsy-based and previous FibroSURE-based studies (21% and 25% excess fibrosis risk and 16% and 15% excess inflammation risk in the current and previous studies). Conclusions: Higher total serum testosterone is associated with increased risk of biopsy-confirmed hepatic fibrosis and inflammation in HCV+ males; this finding supports our earlier FibroSURE-based study results [1]. Larger prospective studies are needed to assess if the association between testosterone and hepatic fibrosis and inflammation is causal in males, and to assess if a similar association exists in HCV+ females. References: [1] White DL, Tavakoli-Tabasi S, Kuzniarek J, Pascua R, Ramsey DJ, El-Serag HB. Higher serum testosterone is associated with increased risk of advanced hepatitis C-related liver disease in males.Hepatology 2011 Aug 19. Sociodemographic and clinical characteristic of 192 chronically HCV-infected male veterans
Sa1091 Hepatitis C (HCV) Antiviral Therapy is Feasible in Patients With Active Substance use (SU) and Mental Illness (MI) and is More Likely to Occur in Those Who Receive Education Class Khurram Bari, Salvador Augustin, Carol A. Eggers, Hashem J. Hashem, Mayur Desai, Martha Shea, Suchat Wongcharatrawee, Joseph K. Lim, Guadalupe Garcia-Tsao
AASLD Abstracts
Many veterans with HCV infection have active SU or MI and these co-morbidities are considered contraindications to antiviral therapy in most centers across the world. The objective of the study was to assess the feasibility of therapy in these patients and to identify predictors and/or barriers to treatment initiation. METHODS: Prospective cohort study of anti-HCV-positive veterans with active SU (use of alcohol and/or illegal substances within 6 months) and/or active MI (undergoing active treatment for MI in the past 6 months). Patients who agreed to have a baseline psychometric evaluation were enrolled in the study. After the initial visit, all patients were given appointments to attend HCV education class (1 hour), baseline psychiatric evaluation, liver biopsy and office visit with provider to discuss therapy and decide on treatment initiation. Patients who decided to undergo therapy (mostly pegylated interferon + ribavirin), were followed until completion of therapy and evaluation of sustained virological response (SVR). RESULTS: From 1/03 to 5/09, 928 patients with active SU/MI were referred to the clinic and 296 were enrolled in the study, of which 69 were excluded (50 genotype non-1, 14 medical contraindications, 5 negative HCV-RNA). We chose to focus this analysis on genotype 1 patients (n=227) since the results would be more relevant to current triple therapy. Median age was 51 years, 99% male, 50% Caucasian, 45% African-American (AA), 5 % Hispanic; median BMI 28, biopsy done in 43% (46% stage 0-1; 54% stage 2-4)]. One hundred and seventy (75%) patients had active MI and 139 (61%) had active SU; 94 (41%) had both. Eighty one (36%) patients initiated HCV therapy. Fifty eight (72%) continued treatment until recommended by provider and 16 patients (16/81=20%) had SVR (rate across the VA is ~25%). On univariate analysis, and taking into account all baseline characteristics, patients who initiated treatment were more likely to have: attended education class, baseline psychiatric evaluation, liver biopsy and prior HCV treatment. AA ethnicity and alcohol + another substance (polySU) were inversely related to treatment initiation. On multivariate analysis, education class (p=0.002, OR=3.1) was the strongest predictor of treatment initiation while AA ethnicity (p=0.023, OR=0.5) and polySU (p=0.057, OR=0.52) were the most significant barriers to starting therapy. Having attended class increased treatment initiation rates in AAs and in polySU patients (Table 1). Patients who attended class were also more likely to have a liver biopsy (52% vs. 85%, p=0.000) CONCLUSION: HCV treatment is feasible in patients with active SU/MI and these co-morbidities should not be a contraindication to therapy. Patient education is the strongest predictor of treatment initiation and increases therapy rates in even harderto-treat subsets of patients (AA, polySU). Effect of education class on treatment rates for African-American and poly SU patients
Logistic regression models for the association between total serum testosterone level and risk of advanced biopsy-confirmed hepatic fibrosis, inflammation, and steatosis
^Chronic alcohol abuse (3+ drinks/day for >=10 years) Sa1093 Inosine Triphosphastase (ITPA) Variants Predict Treatment-Induced Anemia, Ribavirin Dose-Reduction and Need for Erythropoietin Support During Peginterferon/Ribavirin Therapy for Chronic HCV Paul J. Clark, Alessio Aghemo, Elisabetta Degasperi, Enrico Galmozzi, Alexander J. Thompson, Keyur Patel, Maria Grazia Rumi, G. Prati, Massimo Colombo Background: Anemia frequently complicates peginterferon/ribavirin (PEG/RBV) therapy for HCV, and is a persistent challenge in many direct antiviral-based regimens. Better prediction of anemia and the need for ribavirin dose reduction (RBVDR) or erythropoietin (EPO) may enhance patient management. Inosine triphosphatase (ITPA) gene variants are strongly associated with RBV-induced anemia (Fellay 2009) however ITPA's impact in the clinic remains undefined. Methods: 193 patients consecutively treated with PEG/RBV for chronic HCV were genotyped for ITPA (rs1127354 and rs7270101) using Taqman probes. HardyWeinberg equilibrium was present. ITPA deficiency was estimated as previously described (no deficiency/mild/moderate/severe, 0-3). Univariate and multivariate analysis (MVA) considered ITPA association with 4 week (Wk4) Hb measures: Hb decline (mg/dL); Hb < 10 mg/dL and Hb decline >3mg/dL); need for RBVDR and EPO. MVA adjusted for age, female gender, baseline Hb and renal impairment (eGFR >90 ml/min/1.73m2), hepatic fibrosis (>Ishak 3) and starting RBV dose (mg/kg) using backward elimination algorithms. Results: 126 patients had no ITPA deficiency and 67 had some degree of deficiency (n=126/40/24/ 3, ITPA deficiency grade 0/1/2/3 respectively). ITPA deficient patients had less median Hb decline at Wk4 (decline: 3.0/2.2/0.60/0 mg/dL, 0-3 respectively, P< 0.001). ITPA deficient patients were less likely to experience anemia (Hb< 10mg/dL (OR: 0.08, P=0.005) and Hb decline>3mg/dL (OR:0.19, P< 0.001)) at Wk4. ITPA deficiency reduced the odds of RBVDR (18% (12/67) vs. 40% (51/126, OR:0.32, (CI:0.16-0.66), P=0.003)) and need for EPO (OR:0.41, CI:0.20-0.82, P=0.017) throughout treatment. MVA: ITPA (P< 0.001), baseline Hb (P< 0.001), fibrosis (P=0.017), gender (P=0.030) and RBV dose (P=0.034) were associated with Hb decline at Wk4 (R2= 0.45) and the likelihood of a >3mg/dL Hb drop (R2= 0.39). ITPA and baseline Hb were associated with HB decline to < 10mg (R2= 0.31). RBV dose (P< 0.001), ITPA (P=0.021) and baseline Hb (P=0.045), were associated with RBVDR (R2= 0.39). EPO need was associated with baseline Hb (P< 0.001), renal impairment (P=0.001), fibrosis (P=0.002) and ITPA (P=0.020, R2= 0.34). Conclusion: In this clinic-based cohort,
Sa1092 Higher Total Serum Testosterone Level is Associated With Increased Risk of Biopsy-Confirmed Advanced Hepatic Fibrosis and Inflammation but Not Advanced Steatosis in Male Veterans With Chronic Hepatitis C Donna L. White, Linda K. Green, Shahriar Tavakoli-Tabasi, Jill Kuzniarek, David J. Ramsey, Shubhada Sansgiry, Jodi Francis, Hashem El-Serag Background: Chronic liver disease including cirrhosis and HCC are greatly increased (2-4 fold higher) in males than females across a spectrum of risk factors including hepatitis C. We previously reported that higher total serum testosterone was associated with increased risk of FibroSURE determined hepatic fibrosis and inflammation in hepatitis C (HCV) infected males.[1] We performed a confirmatory analysis in 192 HCV+ males with liver biopsy and in addition assessed the association between serum testosterone and steatosis risk. Methods: We prospectively recruited consecutive veterans with chronic HCV in an urban VA HCV clinic (2009-2011). Analyses were restricted to males, ages 20-70, not on interferon, and without sex hormone modifying conditions or medications, decompensation or HCC. An RA administered survey interrogated alcohol and medical history, viremia was confirmed, measurements were taken, and a physician reviewed medical records for contraindications. A single blinded pathologist assessed biopsies using METAVIR and Brunt classifications.
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AASLD Abstracts