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IL28β Genotype in HCV Infected Indian Subjects—A Preliminary Study
Abstracts
Results: Of 74 patients screened, 48 patients included. (M:F = 22:26), mean age: 16–52 years median; 22 ± 9 years). Mean documented duration of viremia was 6 months to 12.5 years (median 6.23 ± 2 years). No correlation was observed between serum HBV DNA viral load and HBsAg titers (r = 0.32, p = 0.04) HBeAg positivity correlated with high viral load p = 0.03, r = 0.64), but not with HBsAg titers (p = 0.03, r = 0.34). SGPT has no correlation either with HBsAg titers (p = 0.02, r = 0.31) or viral load. Conclusion: There is no correlation between HBsAg titers and HBV DNA viral load in treatment naïve chronic hepatitis B infection without cirrhosis. The contradiction of pretreatment absence of correlation between HBsAg titers and viral load and on treatment projected HBsAg titer correlation to treatment response needs to be addressed by further studies. Conflict of Interest: None
Serum Neopterin Levels and Viral Load Among Hepatitis C Positive Recipients of Living Donor Renal Transplants S Justa, RW Minz, M Minz, S Anand, A Sharma Department of Immunopathology; Department of Renal Transplant Surgery; Post Graduate Institute of Medical Education and Research, Chandigarh, India Background and Aim: Neopterin belongs to the group of compounds known as pteridines. Increased concentration of neopterin has been reported in conditions causing stimulation of cellular immunity, such as viral infections and allograft rejection. The aim of this study was to assess the dynamics of serum neopterin during the first 6 months post transplantation among HCV-positive (group I) and negative (group II) recipients of living donor renal transplantation (LDRT). Methods: Twenty two group I and 10 group II patients were serially monitored for serum neopterin levels by ELISA. Group I patients were monitored at three time points i.e. pre-transplantation, day 10 and 6 months post-transplantation. Group II patients were monitored at two time points i.e. day 10 and 6 months post-transplantation. HCV serum viral load was monitored among group I patients by quantitative real time PCR. The histological changes occurring within the first 6 months post transplantation among the study groups were evaluated using Banff classification. Results: There was a significant increase in serum neopterin as well as neopterin to creatinine ratio on day 10 as well as 6-month posttransplantation in comparison to pre-transplantation levels among group I patients. Serum neopterin levels failed to show any association with either HCV viral load or allograft rejection. Conclusion: We did not find any association between neopterin and rejection episodes during the first 6 months post transplantation. Serum neopterin thus failed to delineate a low-risk population which might be spared invasive diagnostic procedures such as protocol biopsy. Nonetheless, our data suggests the use of serum neopterin levels as a possible, surrogate marker of cellular immune response to viral infection after transplantation. Conflict of Interest: None
IL28b Genotype in HCV Infected Indian Subjects—A Preliminary Study SS Prasad*, PN Rao**, RM Mukherjee*, K Ashwini*, P Balkumar Reddy*, DN Reddy** Asian Healthcare Foundation, **Asian Institute of Gastroenterology, Somajiguda, Hyderabad
*
Introduction: It is well known that many patients will not be cured by standard treatment for HCV. A recent study reported that host IL28β polymorphism plays a significant role in clearance of HCV. Thus the present study is aimed to determine an association between host genotype and SVR in HCV patients. Materials and Methods: The study includes 38 patients, who are under standard treatment for HCV. A 3 mL of peripheral blood sample was processed for DNA isolation. PCR-direct sequencing method is employed for genotyping of IL28β polymorphism. The genotyping of HCV is done by reverse hybridization and quantification by RT-PCR. The project is approved by Institutional Ethics Committee and an informed consent was obtained from all the study patients. Results: The average age of patients was 51.6 years. Among them, 8 patients were females. A 21% (n = 8) of them are genotype 1, 42% (n = 16) genotype 2, 11% (n = 4) genotype 3 and for remaining viral genotype has not been done. The distribution of host genotype of IL28β polymorphism (rs129798760) as follows: CC genotype is observed in 74%, CT genotype is observed in 21%, TT genotype is observed in 5% of study patients. A total of 11 cases were discontinued for the treatment due to personal reasons and in 15 cases SVR results are awaited. However, 12 patients have completed the treatment and they were analyzed for the role of host genotype (IL28β) with SVR. Among these
© 2011, INASL
4
Abstracts
12 patients, 9 were of CC genotype and 3 were CT. Finally 8 (66.66%) patients with CC genotype and 1 (8.33%) patient with CT genotype have achieved SVR besides 1 (8.33%) patient with CC genotype and 2 (16.66%) patients with CT genotype have not achieved SVR. Limitations: Small sample size and association of host genotype (IL28β) with the SVR of different viral genotypes is not classified. Conflict of Interest: None
Prevalence of Coinfection of Hepatitis B in HIV-infected Patients of North Kerala TM Ramachandran*, G Ayyappan**, N Sona†, K Soopy‡, T Varghese¶ Additional Professor of Gastroenterology, **Senior Resident, Department of Gastroenterology and Presenting Author, †Senior Medical Officer, ART Center, Associate Professor of Medicine, ¶Professor and Head of Gastroenterology, Medical College, Calicut
*
‡
Background: Patients with HIV infection are likely to have high risk of HBV infection which share the same route of transmission with HIV. HBV coinfection has been shown to decrease the life expectancy in the HIV-infected patients and also influences the management of these patients. There are no studies from Kerala regarding the prevalence of hepatitis B coinfection in HIV-infected patients. Aim: To assess the prevalence of hepatitis B coinfection in HIV-infected patients in North Kerala. Materials and Methods: HIV-infected patients attending the ART Clinic, Medical College, Calicut from December 2009 to December 2010 were screened for hepatitis B infection using HBsAg ELISA test. History regarding risk factors was taken. LFT was done for all patients. Results: Five hundred and twenty six HIV-positive patients were screened (male 317, M:F = 1.5). Mean age was 39.1 (range 20–85) years. History of high-risk sexual behavior was present in 376/526 (71.4%), prior surgery and blood transfusions in 66/526 (12.5%) and 35/526 (6.6%). History of i.v. drug abuse in 8/526 (1.5%). 489/526 (93.1%) of patients were on anti-retroviral therapy. Mean bilirubin level was 0.54 mg/dL. Mean albumin level was 3.6 g/dL. ALT was elevated in 321/526 (61%) of patients. 6/526 patients (1.14%) were found to be HBsAg positive (males – 4). Intravenous drug abuse was present in 1/6 (16.6%) and high risk sexual behavior in 3/6 (50%). ALT elevation was present in 4/6 (66.6%) of HBsAg positive patients. Conclusion: The prevalence of hepatitis B infection in HIV-infected patients of North Kerala is 1.14%. The prevalence is low compared to other regions of India. However the prevalence of HBV infection was 2-fold higher in this high-risk group when compared to our general population (0.52%). The LFT abnormalities seen in HIV patients need to be evaluated by further studies. Conflict of Interest: None
Adverse Outcome in Lamivudine Resistant HBV-related Cirrhotic Patient Co-infected with HIV R Maheswari, R Rai, R Trimukhe Department of Medicine, NSCB Medical College, Jabalpur Background: An estimated 360 million persons worldwide are chronically infected with HIV; nearly 10% of them are co-infected with chronic HBV. These individuals tend to have higher levels of HBV DNA, lower rates of spontaneous HBeAg seroconversion, more severe liver disease and increased rates of liver related mortality. Until few years lamivudine was frequently prescribed for chronic HBV infection and as component of HAART. However lamivudine was frequently associated with development of resistance, more so in patients with HIV co-infection and is associated with adverse outcomes. Aim: To describe the clinical sequel of lamivudine resistance in HBV-related cirrhotic patient co-infected with HIV on HAART. Methods: A HIV co-infected HBV related HBe-Ag-negative cirrhotic patient was followed for 2 years on HAART (Stauvudine/ Lamivudine-300 mg daily/Efavirenz). Routine hematological, biochemical tests, LFT, PT, HBV-DNA and radiological investigations were done on follow-up. Results: A 40-year-old male, non-alcoholic, presented on July 2010 with oral candidiasis, appetite loss and fever for 3 months. Two years back he had raised bilirubin (4 mg/dL), ALT: 144U/L, HBV-DNA: 27160 IU/mL and CD4 count: 300 cells/cumm. Anti-HCV and HDV RNA were negative. After 1 year he had normal bilirubin and ALT; HBV-DNA: 266 IU/mL and CD4 count: 410 cells/cumm. In July 2010 there was a virological breakthrough (HBV-DNA: 34258 IU/mL) with bilirubin: 3 mg/dL, ALT levels: 345 U/L and CD4 count: 278 cells/cumm. This patient probably developed lamivudine resistance. Tenofovir was added but patient died after 2 months. Conclusion: Few years back patients with HBV HIV co-infection in resource constrained settings received lamivudine as the only drug active against HBV and as a part of HAART which has led to emergence of lamivudine-resistant HBV. Despite newly licensed drug like tenofovir for HBV; treatment of co-infection is difficult especially when there is suspected failure of HAART and has to be addressed. Conflict of Interest: None
© 2011, INASL
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Results: Of 74 patients screened, 48 patients included. (M:F = 22:26), mean age: 16–52 years median; 22 ± 9 years). Mean documented duration of viremia was 6 months to 12.5 years (median 6.23 ± 2 years). No correlation was observed between serum HBV DNA viral load and HBsAg titers (r = 0.32, p = 0.04) HBeAg positivity correlated with high viral load p = 0.03, r = 0.64), but not with HBsAg titers (p = 0.03, r = 0.34). SGPT has no correlation either with HBsAg titers (p = 0.02, r = 0.31) or viral load. Conclusion: There is no correlation between HBsAg titers and HBV DNA viral load in treatment naïve chronic hepatitis B infection without cirrhosis. The contradiction of pretreatment absence of correlation between HBsAg titers and viral load and on treatment projected HBsAg titer correlation to treatment response needs to be addressed by further studies. Conflict of Interest: None
Serum Neopterin Levels and Viral Load Among Hepatitis C Positive Recipients of Living Donor Renal Transplants S Justa, RW Minz, M Minz, S Anand, A Sharma Department of Immunopathology; Department of Renal Transplant Surgery; Post Graduate Institute of Medical Education and Research, Chandigarh, India Background and Aim: Neopterin belongs to the group of compounds known as pteridines. Increased concentration of neopterin has been reported in conditions causing stimulation of cellular immunity, such as viral infections and allograft rejection. The aim of this study was to assess the dynamics of serum neopterin during the first 6 months post transplantation among HCV-positive (group I) and negative (group II) recipients of living donor renal transplantation (LDRT). Methods: Twenty two group I and 10 group II patients were serially monitored for serum neopterin levels by ELISA. Group I patients were monitored at three time points i.e. pre-transplantation, day 10 and 6 months post-transplantation. Group II patients were monitored at two time points i.e. day 10 and 6 months post-transplantation. HCV serum viral load was monitored among group I patients by quantitative real time PCR. The histological changes occurring within the first 6 months post transplantation among the study groups were evaluated using Banff classification. Results: There was a significant increase in serum neopterin as well as neopterin to creatinine ratio on day 10 as well as 6-month posttransplantation in comparison to pre-transplantation levels among group I patients. Serum neopterin levels failed to show any association with either HCV viral load or allograft rejection. Conclusion: We did not find any association between neopterin and rejection episodes during the first 6 months post transplantation. Serum neopterin thus failed to delineate a low-risk population which might be spared invasive diagnostic procedures such as protocol biopsy. Nonetheless, our data suggests the use of serum neopterin levels as a possible, surrogate marker of cellular immune response to viral infection after transplantation. Conflict of Interest: None
IL28b Genotype in HCV Infected Indian Subjects—A Preliminary Study SS Prasad*, PN Rao**, RM Mukherjee*, K Ashwini*, P Balkumar Reddy*, DN Reddy** Asian Healthcare Foundation, **Asian Institute of Gastroenterology, Somajiguda, Hyderabad
*
Introduction: It is well known that many patients will not be cured by standard treatment for HCV. A recent study reported that host IL28β polymorphism plays a significant role in clearance of HCV. Thus the present study is aimed to determine an association between host genotype and SVR in HCV patients. Materials and Methods: The study includes 38 patients, who are under standard treatment for HCV. A 3 mL of peripheral blood sample was processed for DNA isolation. PCR-direct sequencing method is employed for genotyping of IL28β polymorphism. The genotyping of HCV is done by reverse hybridization and quantification by RT-PCR. The project is approved by Institutional Ethics Committee and an informed consent was obtained from all the study patients. Results: The average age of patients was 51.6 years. Among them, 8 patients were females. A 21% (n = 8) of them are genotype 1, 42% (n = 16) genotype 2, 11% (n = 4) genotype 3 and for remaining viral genotype has not been done. The distribution of host genotype of IL28β polymorphism (rs129798760) as follows: CC genotype is observed in 74%, CT genotype is observed in 21%, TT genotype is observed in 5% of study patients. A total of 11 cases were discontinued for the treatment due to personal reasons and in 15 cases SVR results are awaited. However, 12 patients have completed the treatment and they were analyzed for the role of host genotype (IL28β) with SVR. Among these
© 2011, INASL
4
Abstracts
12 patients, 9 were of CC genotype and 3 were CT. Finally 8 (66.66%) patients with CC genotype and 1 (8.33%) patient with CT genotype have achieved SVR besides 1 (8.33%) patient with CC genotype and 2 (16.66%) patients with CT genotype have not achieved SVR. Limitations: Small sample size and association of host genotype (IL28β) with the SVR of different viral genotypes is not classified. Conflict of Interest: None
Prevalence of Coinfection of Hepatitis B in HIV-infected Patients of North Kerala TM Ramachandran*, G Ayyappan**, N Sona†, K Soopy‡, T Varghese¶ Additional Professor of Gastroenterology, **Senior Resident, Department of Gastroenterology and Presenting Author, †Senior Medical Officer, ART Center, Associate Professor of Medicine, ¶Professor and Head of Gastroenterology, Medical College, Calicut
*
‡
Background: Patients with HIV infection are likely to have high risk of HBV infection which share the same route of transmission with HIV. HBV coinfection has been shown to decrease the life expectancy in the HIV-infected patients and also influences the management of these patients. There are no studies from Kerala regarding the prevalence of hepatitis B coinfection in HIV-infected patients. Aim: To assess the prevalence of hepatitis B coinfection in HIV-infected patients in North Kerala. Materials and Methods: HIV-infected patients attending the ART Clinic, Medical College, Calicut from December 2009 to December 2010 were screened for hepatitis B infection using HBsAg ELISA test. History regarding risk factors was taken. LFT was done for all patients. Results: Five hundred and twenty six HIV-positive patients were screened (male 317, M:F = 1.5). Mean age was 39.1 (range 20–85) years. History of high-risk sexual behavior was present in 376/526 (71.4%), prior surgery and blood transfusions in 66/526 (12.5%) and 35/526 (6.6%). History of i.v. drug abuse in 8/526 (1.5%). 489/526 (93.1%) of patients were on anti-retroviral therapy. Mean bilirubin level was 0.54 mg/dL. Mean albumin level was 3.6 g/dL. ALT was elevated in 321/526 (61%) of patients. 6/526 patients (1.14%) were found to be HBsAg positive (males – 4). Intravenous drug abuse was present in 1/6 (16.6%) and high risk sexual behavior in 3/6 (50%). ALT elevation was present in 4/6 (66.6%) of HBsAg positive patients. Conclusion: The prevalence of hepatitis B infection in HIV-infected patients of North Kerala is 1.14%. The prevalence is low compared to other regions of India. However the prevalence of HBV infection was 2-fold higher in this high-risk group when compared to our general population (0.52%). The LFT abnormalities seen in HIV patients need to be evaluated by further studies. Conflict of Interest: None
Adverse Outcome in Lamivudine Resistant HBV-related Cirrhotic Patient Co-infected with HIV R Maheswari, R Rai, R Trimukhe Department of Medicine, NSCB Medical College, Jabalpur Background: An estimated 360 million persons worldwide are chronically infected with HIV; nearly 10% of them are co-infected with chronic HBV. These individuals tend to have higher levels of HBV DNA, lower rates of spontaneous HBeAg seroconversion, more severe liver disease and increased rates of liver related mortality. Until few years lamivudine was frequently prescribed for chronic HBV infection and as component of HAART. However lamivudine was frequently associated with development of resistance, more so in patients with HIV co-infection and is associated with adverse outcomes. Aim: To describe the clinical sequel of lamivudine resistance in HBV-related cirrhotic patient co-infected with HIV on HAART. Methods: A HIV co-infected HBV related HBe-Ag-negative cirrhotic patient was followed for 2 years on HAART (Stauvudine/ Lamivudine-300 mg daily/Efavirenz). Routine hematological, biochemical tests, LFT, PT, HBV-DNA and radiological investigations were done on follow-up. Results: A 40-year-old male, non-alcoholic, presented on July 2010 with oral candidiasis, appetite loss and fever for 3 months. Two years back he had raised bilirubin (4 mg/dL), ALT: 144U/L, HBV-DNA: 27160 IU/mL and CD4 count: 300 cells/cumm. Anti-HCV and HDV RNA were negative. After 1 year he had normal bilirubin and ALT; HBV-DNA: 266 IU/mL and CD4 count: 410 cells/cumm. In July 2010 there was a virological breakthrough (HBV-DNA: 34258 IU/mL) with bilirubin: 3 mg/dL, ALT levels: 345 U/L and CD4 count: 278 cells/cumm. This patient probably developed lamivudine resistance. Tenofovir was added but patient died after 2 months. Conclusion: Few years back patients with HBV HIV co-infection in resource constrained settings received lamivudine as the only drug active against HBV and as a part of HAART which has led to emergence of lamivudine-resistant HBV. Despite newly licensed drug like tenofovir for HBV; treatment of co-infection is difficult especially when there is suspected failure of HAART and has to be addressed. Conflict of Interest: None
© 2011, INASL
5