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Safety and Efficacy of Hepatitis B Vaccination in Cirrhosis of Liver

Safety and Efficacy of Hepatitis B Vaccination in Cirrhosis of Liver Hindawi Publishing Corporation Advances in Virology Volume 2013, Article ID 196704, 5 pages http://dx.doi.org/10.1155/2013/196704 Research Article Safety and Efficacy of Hepatitis B Vaccination in Cirrhosis of Liver 1 2 1 1 D. Ajith Roni, Rama Mohan Pathapati, A. Sathish Kumar, Lalit Nihal, 1 2 K. Sridhar, and Sujith Tumkur Rajashekar Medical Gastroenterology, Narayana Medical College Hospital, Nellore, Andhra Pradesh 524002, India Clinical Pharmacology, Narayana Medical College Hospital, Nellore, Andhra Pradesh 524002, India Correspondence should be addressed to Rama Mohan Pathapati; pill4ill@yahoo.co.in Received 14 March 2013; Accepted 7 May 2013 Academic Editor: Masao Matsuoka Copyright © 2013 D. Ajith Roni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction. Patients with chronic liver disease (CLD) are more likely to have severe morbidity and fatality rate due to superimposed acute or chronic hepatitis B (HBV) infection. eTh literature has shown that hepatitis B vaccines are safe and eeff ctive in patients with CLD, but the data in cirrhosis liver is lacking. We assessed the safety and immunogenicity of HBV vaccine in patients with cirrhosis liver. Methods. CTP classes A and B CLD patients negative for hepatitis B surface antigen and antibody to hepatitis B core antigen were included. All patients received three doses of hepatitis B vaccine 20 mcg intramuscularly at 0, 30, and 60 days. Anti-HBs antibody was measured aer ft 120 days. Results.52patientswithmeanage47.48±9.37 years were studied. Response rates in CTP classes A and B were 88% and 33.3%. We observed that the alcoholic chronic liver disease had less antibody response (44%) than other causes of chronic liver disease such as cryptogenic 69% and HCV 75%. Conclusions. Patients with cirrhosis liver will have low antibody hepatitis B titers compared to general population. As the age and liver disease progress, the response rate for hepatitis B vaccination will still remain to be weaker. 1. Introduction recommended HBV vaccination for these patients [18, 19]. The immune response to HBV vaccines among patients with Globally, chronic HBV infection affects over 350 million peo- CLD varies from 70% to 90%. Hence in evaluating HBV ple, and up to 40% of these cases may progress to cirrhosis, vaccination in patients with cirrhosis liver, three questions liver failure, or hepatocellular carcinoma [1]. Chronic liver need to be answered: (1) who needs vaccination? And (2) disease [CLD] contributes to approximately 400000 hospital- is the vaccination safe? and (3) is it eeff ctive? Answering izations and nearly 30,000 deaths annually worldwide [2, 3]. these questions will provide an eeff ctive strategy for applying When compared with patients without liver disease, patients HBVvaccinesinCLD.Tothispurpose we studiedthe safety with CLD are more likely to have severe complications and and immunogenicity of 3 doses of 20𝜇 g of HBV vaccine in also severe fatality rate due to superimposed acute or chronic patients with cirrhosis liver. HBV infection. Both acute and chronic coinfections with HBVcan be preventedbyHBV vaccination [4, 5]. Strong 2. Methods epidemiological evidence suggests an increased occurrence of fulminant liver failure, cirrhosis and hepatocellular car- This prospective open label study was conducted in the cinoma in patients with HBV, and HCV coinfection [6, 7]. department of medical gastroenterology. Institutional ethics HBV vaccination is safe and well tolerated and has high committee approved the study protocol. Informed consent seroconversion rates in patients with mild to moderate CLD was obtained from study participants. Patients with CLD but has reduced efficacy in advanced liver disease and aer ft of CTPclass Aand Bwereenrolledinthe study. Both liver transplantation [8–17]. To minimize the occurrence male and female patients between 18 and 60 years who of HBV infection in CLD, a variety of organizations have were serologically negative for hepatitis B surface antigen, 2 Advances in Virology antibody to hepatitis B core antigen and have no history of hepatitis B vaccination were included. Patients with CTP class-C, having malignancy, acute liver disease, HIV, receiv- ing immunosuppressive medications and life expectancy less than 120 days were excluded. All patients received three doses of HBV vaccine (Shanvac, M/s Shantha Biotech) 20 mcg intramuscularly over the deltoid region during all the three visits at 0, 30, and 60 days. A 5 mL of blood was collected in a plain vacutainer tube, the serum was separated, and the analysis for anti-Hbc total and titer for anti-Hbs was done on thesameday of thecollectionofsamples.Blood analysis for anti-Hbc total and titer for anti-HBs was done with chemi- luminescence analyzer-Access 2 Immunoassay analyzer, and ALD CR HCV BC AI WD Beckmancoulter.Anti-HBs antibody wasmeasuredaeft r120 Figure 1: ALD: alcoholic liver disease; CR: cryptogenic hepatitis; days, and according to antibody titers patients were classified HCV: hepatitis C virus; BC: budd chiarri; AI: autoimmune hepatitis; into good responders, poor responders, and nonresponders. and WD: wilson’s Disease. Good responders were defined as those having the anti-HBs titer were> or =100 mUI/mL, poor responders having anti- HBs titer between 10 and 99 mUI/mL, and nonresponders having anti-HBs titer<10 mUI/mL. The secondary outcome was to assess the safety of HBV vaccination in CLD. Patients reported adverse events; infusion site reactions and routine laboratory parameters were considered safety markers of the study. 2.1. Statistical Analysis. Data was entered into excel spread- sheet 2007 and analyzed by using the GraphPad Prism Software version 4. All the continuous data will be expressed as mean± SD. Categorical data was expressed as numbers and percentages. Chi-square test was used to detect differences between groups. A two-tailed𝑃 value< 0.05 was considered <10 10–100 >100 statistically significant. Figure 2: Antibody response shown in percentages aeft r adminis- tration of HBV vaccine in chronic liver disease patients. 3. Results 52 patients received 3 doses of HBV vaccine; the mean age of patients was47.48±9.37 years. eTh re were 37 males and nonresponders were 9/37 (24%) in males and 2/15 (13%) in 15 females. 30 patients were less than 50 years of age and 22 females (𝑃 value 0.43). were more than 50 years. 25 patients were in CTP class A When we were individually analyzing the vaccine and the rest 27 were in CTP class B. eTh reasons for CLD response across different etiologies, we found that in 27 of were alcohol 27/52 (52%), cryptogenic 13/52 (25%), hepatitis the patients with alcohol induced CLD, 12/27 (44%) had C 8/52 (15%), and others 4/52 (8%). (Figure 1). In this study good response, 7/27 (26%) had poor response, and 8/27 31/52 (60%) were good responders, 10/52 (19%) were of poor (30%) were non responders and in 8 patients with HCV responders and 11/52 (21%) were nonresponders. (Figure 2). related CLD 6/8 (76%) were good responders, 1/8 (12%) Patient characteristics and clinical profiles were shown in poor responders, and 1/8 (12%) were nonresponders. Overall Table 1. response rates in 52 patients were as follows: 31/52 (60%) Among the patients who were less than 50 years of age, had good response, 10/52 (19%) had poor response, and 11/52 21/30 (70%) of them were good responders, 6/30 (20%) were (21%) were nonresponders. (𝑃=0.36 ). poor responders, and 3/30 (10%) were nonresponders. In We also compared response rates with the child scores; patients more than 50 years, 9/22 (40%) were good respon- outof25patientswho were childAscore, 22/25(88%)were ders, 5/22 (23%) were poor responders, and 8/22 (36%) were good responders, 1/25 (40%) were poor responders, and 2/25 nonresponders. On comparing the responders rate between (8%) were nonresponders and in child B class only 9/27 the age groups, patients in age group less than 50 years had (33%) had good antibody response and 9/27 (33%) had poor significant responder rates (70%) than patients with age more response, 9/27 (33%) were nonresponders (𝑃 < 0.0001 ). than 50 years. (40%) (𝑃=0.03 ). None of our patients had sueff red significant systemic or We observed that 20/37 (54%) of the males and 11/15 local adverse reactions. All patients complained of pain and (74%) of the females were good responders, 8/37 (22%) redness during vaccine administration. No other adverse males and 2/15 (13%) females were poor responderss and events were observed. (IU/mL) (%) Advances in Virology 3 Table 1: Patient characteristics, clinical profiles, and immunological outcomes. Antibody titers Partial Nonresponders Responders 226.88± 164 Total responders 𝑃 value [<10 IU/mL] [>100 IU/mL] [IU/mL] [10–100 IU/mL] Age group 47.48± 9.37 [years] <50 30 3 [10%] 6 [20%] 21 [70%] 0.03 >50 22 8 [36%] 5 [23%] 9 [41%] Total 52 11 [21%] 11 [21%] 30 [58%] Gender Female 15 2 [13%] 2 [13%] 11 [74%] 0.43 Male 37 9 [24%] 8 [22%] 20 [54%] Total 52 11 [21%] 10 [19%] 31 [60%] Etiology Alcohol 27 8 [30%] 7 [26%] 12 [44%] Hepatitis C 8 1 [12%] 1 [12%] 6 [76%] 0.36 Cryptogenic 13 2 [15%] 2 [15%] 9 [70%] Others 4 0 0 4 [100%] Total 52 11 [21%] 10 [19%] 31 [60%] Child’s class A 25 2 [8%] 1 [4%] 22 [88%] <0.0001 B 27 9 [33.3%] 9 [33.3%] 9 [33.3%] Total 52 11 [21%] 10 [19%] 31 [60%] 4. Discussion in our study. In chronic ALD patients the response rates observed by Mendenhall et al., Bronowicki et al., and Rosman Vaccination with HBV vaccine is extremely safe in general et al. [23–25]were18%,69%,and 46%, respectively.The population andinpatientswithchronic liverdisease.The previous studies had included only fewer cirrhotic patients. immunogenicity rates of vaccination in general population In our study the good responders in patients with alcoholic are>90% whereas in CLD it varied from 18% to 100%. In inducedcirrhosis were only 44%, andall thepatientswere thepresent study, theresponsetostandardHBV vaccination with childAor childBcirrhosiswhencomparedtoprevious with a dose of 20𝜇 gat0,1,and 2monthsincirrhosis of liver studies in the literature. with various etiologies was evaluated and compared. We eTh se observations suggest that if we are vaccinating found that good responders were only 60%, poor responders at an earlier age (<50 years) and also at an early stage 19% percent, and nonresponders 21%. When we analyzed the of chronic liver disease (child A), the immunogenicity of various aetiologies of CLD and the vaccine response rate, we hepatitis B vaccination is superior as compared to patients observed that the patients with alcoholic chronic liver disease with age more than 50 years and with child B cirrhosis (ALD) had poor antibody response (44%) as compared to liver. eTh se observations suggest that if the patient is having other aetiologies of chronic liver disease such as cryptogenic advanced cirrhosis liver or in the age group of more than (69%) and HCV (75%) related liver disease. Severity of the 50 years, it is always better to try different regimens like chronic liver disease predicts the response rate; the good 40 ug or 80 ug of hepatitis vaccination or other routes of responders were in CTP class A (88%) as compared to CTP vaccine administrations like multiple intradermal dose. And class B (33.3%). It was observed that apart from severity of theliteraturesearchhad shownthatthe safety profile of these liverdisease,the ageofthe patients also hadcontributed to higher doses was comparable with that of normal dose. er Th e antibody response; patients less than 50 years had a higher were only few studies having data on multiple intradermal rate of response with hepatitis B vaccination than patients dose of hepatitis B vaccination in chronic liver disease, but above 50 years. it has not been yet approved in vaccination schedule. Studies conducted by Lee et al., Wiedmann et al. and Keeeff and Krause [ 20–22]inCLD patients with HCVwho 5. Study Limitations hadreceived20ugshowedresponserates of 100%,89%,and 69%, respectively. However these studies did not include any We had evaluated only using standard dose of hepatitis B vac- patients with cirrhosis liver. In our study the good responders cine (Shanvac, M/s Shantha biotech) in patients with cirrhosis in patients with HCV related cirrhosis liver were 76%. How- liver of CTP classes A and B only and had excluded CTP ever a fewer number of patients with HCV had participated class C patients. However we have not compared the efficacy 4 Advances in Virology of Shanvac HBV vaccine with other available vaccines in [8] S. Chlabicz and A. Grzeszczuk, “Hepatitis B virus vaccine for patients with hepatitis C virus infection,” Infection,vol.28, no. themarket. Ourstudy populationswerediversiefi dand the 6, pp. 341–345, 2000. subjects included in the different etiologic groups were small. We should have attempted with higher dose and/or weekly [9] S.D.Lee,C.Y.Chan, M. I. Yu,R.H.Lu, F. Y. Chang, andK.J. Lo, “Hepatitis B vaccination in patients with chronic hepatitis intradermal doses as per the evidence from the literature of C,” Journal of Medical Virology,vol.59, pp.463–468,1999. patients with chronic kidney disease. Additionally long-term persistence of antibody titers, the frequency of estimating the [10] M. Wiedmann, U. G. Liebert, U. Oesen et al., “Decreased immunogenicity of recombinant hepatitis B vaccine in chronic postvaccination anti-Hbs titer, and the need for booster dose hepatitis C,” Hepatology,vol.31, no.1,pp. 230–234, 2000. of hepatitis B vaccine were not evaluated due to technical and financial constraints. Another limitation of our study is that [11] A. S. Rosman, P. Basu, K. Galvin, and C. S. Lieber, “Efficacy of a high and accelerated dose of hepatitis B vaccine in alcoholic all the patients received the same quantity of HBV vaccine patients: a randomized clinical trial,” American Journal of (20𝜇 g), and thus comparisons between high and low doses Medicine,vol.103,no. 3, pp.217–222,1997. cannot be anticipated. [12] E. B. Keeffe and D. S. Krause, “Hepatitis B vaccination of patients with chronic liver disease,” Liver Transplantation,vol. 6. Conclusions 4, pp. 437–439, 1998. [13] C. Mendenhall, G. A. Roselle, L. A. Lybecker et al., “Hepatitis B Patients with cirrhosis liver when compared to general vaccination: response of alcoholic with and without liver injury,” population will have low postimmunization antibody titres Digestive Diseases and Sciences,vol.33, pp.263–269,1998. against hepatitis B. As the age and the stage of liver disease [14] J. P. Bronowicki, F. Weber-Larivaille, J. P. Gut, M. Doo ff el ¨ , progress, the immunogenicity of standard dose of hepatitis and D. Vetter, “Comparison of immunogenicity of anti-HBV Bvaccination againsthepatitis Binfection will stillremain vaccination end serovaccination in alcoholic patients with weak. Hence all the cirrhotics with non-HBV etiologies cirrhosis,” Gastroenterologie Clinique et Biologique,vol.21, no. should be initiated on hepatitis B vaccination protocol at the 11, pp.848–853,1997. time of diagnosis to achieve better protection against HBV. [15] E. Villeneuve, J. Vincelette, and J. P. Villeneuve, “Ineffectiveness If the patient had not achieved seroconversion with stan- of hepatitis B vaccination in cirrhotic patients waiting for liver dard universal dose of hepatitis B vaccine, reimmunization transplantation,” Canadian Journal of Gastroenterology,vol.14, with ahigherdoseofhepatitis Bvaccine schedule or with pp.59B–62B,2000. multiple intradermal route of vaccination may be considered. [16] M. Dominguez, R. Barcena, M. Garcia, A. Lopez-Sanroman, Further studies are needed to assess the antibody titres by and J. Nuno, “Vaccination against hepatitis B virus in cirrhotic considering type of vaccine, the dose to be administered, the patients on liver transplant waiting list,” Liver Transplantation, route of administration, the frequency of antibody testing, vol. 6, pp. 440–442, 2000. and the requirement for booster dose. [17] M. Arslan,R.H.Wiesner,C.Sievers,K.Egan, andN.N.Zein, “Double-dose accelerated hepatitis B vaccine in patients with end-stage liver disease,” Liver Transplantation,vol.7,no. 4, pp. References 314–320, 2001. [18] Centers for Disease Control and Prevention, “Recommenda- [1] A. S. Lok, “Chronic hepatitis B,” eTh New England Journal of tions and reports: hepatitis A and B vaccines,” Morbidity and Medicine,vol.346,no. 22,pp. 1682–1683, 2002. Mortality Weekly Report,vol.52, pp.34–36,2003. [2] L.J.Kozak,M.F.Owings, andM.J.Hall, “NationalHospital [19] National Institutes of Health, “National Institutes of Health Discharge Survey: 2001 annual summary with detailed diagno- Consensus Development Conference Statement: management sis and procedure data,” Vital and Health Statistics,vol.13, no. of hepatitis C: 2002—June 10-12, 2002,” Hepatology,vol.36, 156, pp. 1–198, 2004. supplement 1, pp. S3–S20, 2002. [3] E.Arias,R.N.Anderson, H. C. Kung,S.L.Murphy, andK.D. [20] S. D. Lee, C. Y. Chan,M.I.Yu, R. H. Lu,F.Y.Chang,and K. J. Kochanek, “Deaths: final data for 2001,” National Vital Statistics Lo, “Hepatitis B vaccination in patients with chronic hepatitis Reports,vol.52, no.3,pp. 1–115,2003. C,” Journal of Medical Virology,vol.59, pp.463–468,1999. [4] R.S.Ko,“ ff Risksassociatedwithhepatitis Aand hepatitisBin [21] M. Wiedmann, U. G. Liebert, U. Oesen et al., “Decreased immu- patients with hepatitis C,” Journal of Clinical Gastroenterology, nogenicity of recombinant hepatitis B vaccine in chronic hep- vol. 33,no. 1, pp.20–26,2001. atitis C,” Hepatology,vol.31, no.1,pp. 230–234, 2000. [5] G. Reiss and E. B. Keeffe, “Review article: hepatitis vaccination [22] E. B. Keeffe and D. S. Krause, “Hepatitis B vaccination of in patients with chronic liver disease,” Alimentary Pharmacology patients with chronic liver disease,” Liver Transplantation,vol. & er Th apeutics ,vol.19, pp.715–727,2004. 4, pp. 437–439, 1998. [6] A. Alberti, P. Pontisso, L. Chemello et al., “eTh interaction bet- [23] A. S. Rosman, P. Basu, K. Galvin, and C. S. Lieber, “Efficacy of ween hepatitis B virus and hepatitis C virus in acute and chronic a high and accelerated dose of hepatitis B vaccine in alcoholic liver disease,” JournalofHepatology, Supplement,vol.22, no.1, patients: a randomized clinical trial,” American Journal of pp. 38–41, 1995. Medicine,vol.103,no. 3, pp.217–222,1997. [7] L. Benvegnu, G. Fattovich, F. Noventa et al., “Concurrent hepati- [24] C. Mendenhall,G.A.Roselle,L.A.Lybeckeretal.,“HepatitisB tis B and C virus infection and risk of hepatocellular carcinoma vaccination. Response of alcoholic with and without liver in cirrosis. A Prospective Study,” Cancer,vol.74, pp.2442–2448, injury,” Digestive Diseases and Sciences, vol. 33, pp. 263–269, 1994. 1998. Advances in Virology 5 [25] J. P. Bronowicki, F. Weber-Larivaille, J. P. Gut, M. Doo ff el ¨ , and D. Vetter, “Comparison of immunogenicity of anti-HBV vacci- nation end serovaccination in alcoholic patients with cirrhosis,” Gastroenterologie Clinique et Biologique, vol. 21, no. 11, pp. 848– 853, 1997. 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Safety and Efficacy of Hepatitis B Vaccination in Cirrhosis of Liver

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Hindawi Publishing Corporation
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Copyright © 2013 D. Ajith Roni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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10.1155/2013/196704
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Abstract

Hindawi Publishing Corporation Advances in Virology Volume 2013, Article ID 196704, 5 pages http://dx.doi.org/10.1155/2013/196704 Research Article Safety and Efficacy of Hepatitis B Vaccination in Cirrhosis of Liver 1 2 1 1 D. Ajith Roni, Rama Mohan Pathapati, A. Sathish Kumar, Lalit Nihal, 1 2 K. Sridhar, and Sujith Tumkur Rajashekar Medical Gastroenterology, Narayana Medical College Hospital, Nellore, Andhra Pradesh 524002, India Clinical Pharmacology, Narayana Medical College Hospital, Nellore, Andhra Pradesh 524002, India Correspondence should be addressed to Rama Mohan Pathapati; pill4ill@yahoo.co.in Received 14 March 2013; Accepted 7 May 2013 Academic Editor: Masao Matsuoka Copyright © 2013 D. Ajith Roni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction. Patients with chronic liver disease (CLD) are more likely to have severe morbidity and fatality rate due to superimposed acute or chronic hepatitis B (HBV) infection. eTh literature has shown that hepatitis B vaccines are safe and eeff ctive in patients with CLD, but the data in cirrhosis liver is lacking. We assessed the safety and immunogenicity of HBV vaccine in patients with cirrhosis liver. Methods. CTP classes A and B CLD patients negative for hepatitis B surface antigen and antibody to hepatitis B core antigen were included. All patients received three doses of hepatitis B vaccine 20 mcg intramuscularly at 0, 30, and 60 days. Anti-HBs antibody was measured aer ft 120 days. Results.52patientswithmeanage47.48±9.37 years were studied. Response rates in CTP classes A and B were 88% and 33.3%. We observed that the alcoholic chronic liver disease had less antibody response (44%) than other causes of chronic liver disease such as cryptogenic 69% and HCV 75%. Conclusions. Patients with cirrhosis liver will have low antibody hepatitis B titers compared to general population. As the age and liver disease progress, the response rate for hepatitis B vaccination will still remain to be weaker. 1. Introduction recommended HBV vaccination for these patients [18, 19]. The immune response to HBV vaccines among patients with Globally, chronic HBV infection affects over 350 million peo- CLD varies from 70% to 90%. Hence in evaluating HBV ple, and up to 40% of these cases may progress to cirrhosis, vaccination in patients with cirrhosis liver, three questions liver failure, or hepatocellular carcinoma [1]. Chronic liver need to be answered: (1) who needs vaccination? And (2) disease [CLD] contributes to approximately 400000 hospital- is the vaccination safe? and (3) is it eeff ctive? Answering izations and nearly 30,000 deaths annually worldwide [2, 3]. these questions will provide an eeff ctive strategy for applying When compared with patients without liver disease, patients HBVvaccinesinCLD.Tothispurpose we studiedthe safety with CLD are more likely to have severe complications and and immunogenicity of 3 doses of 20𝜇 g of HBV vaccine in also severe fatality rate due to superimposed acute or chronic patients with cirrhosis liver. HBV infection. Both acute and chronic coinfections with HBVcan be preventedbyHBV vaccination [4, 5]. Strong 2. Methods epidemiological evidence suggests an increased occurrence of fulminant liver failure, cirrhosis and hepatocellular car- This prospective open label study was conducted in the cinoma in patients with HBV, and HCV coinfection [6, 7]. department of medical gastroenterology. Institutional ethics HBV vaccination is safe and well tolerated and has high committee approved the study protocol. Informed consent seroconversion rates in patients with mild to moderate CLD was obtained from study participants. Patients with CLD but has reduced efficacy in advanced liver disease and aer ft of CTPclass Aand Bwereenrolledinthe study. Both liver transplantation [8–17]. To minimize the occurrence male and female patients between 18 and 60 years who of HBV infection in CLD, a variety of organizations have were serologically negative for hepatitis B surface antigen, 2 Advances in Virology antibody to hepatitis B core antigen and have no history of hepatitis B vaccination were included. Patients with CTP class-C, having malignancy, acute liver disease, HIV, receiv- ing immunosuppressive medications and life expectancy less than 120 days were excluded. All patients received three doses of HBV vaccine (Shanvac, M/s Shantha Biotech) 20 mcg intramuscularly over the deltoid region during all the three visits at 0, 30, and 60 days. A 5 mL of blood was collected in a plain vacutainer tube, the serum was separated, and the analysis for anti-Hbc total and titer for anti-Hbs was done on thesameday of thecollectionofsamples.Blood analysis for anti-Hbc total and titer for anti-HBs was done with chemi- luminescence analyzer-Access 2 Immunoassay analyzer, and ALD CR HCV BC AI WD Beckmancoulter.Anti-HBs antibody wasmeasuredaeft r120 Figure 1: ALD: alcoholic liver disease; CR: cryptogenic hepatitis; days, and according to antibody titers patients were classified HCV: hepatitis C virus; BC: budd chiarri; AI: autoimmune hepatitis; into good responders, poor responders, and nonresponders. and WD: wilson’s Disease. Good responders were defined as those having the anti-HBs titer were> or =100 mUI/mL, poor responders having anti- HBs titer between 10 and 99 mUI/mL, and nonresponders having anti-HBs titer<10 mUI/mL. The secondary outcome was to assess the safety of HBV vaccination in CLD. Patients reported adverse events; infusion site reactions and routine laboratory parameters were considered safety markers of the study. 2.1. Statistical Analysis. Data was entered into excel spread- sheet 2007 and analyzed by using the GraphPad Prism Software version 4. All the continuous data will be expressed as mean± SD. Categorical data was expressed as numbers and percentages. Chi-square test was used to detect differences between groups. A two-tailed𝑃 value< 0.05 was considered <10 10–100 >100 statistically significant. Figure 2: Antibody response shown in percentages aeft r adminis- tration of HBV vaccine in chronic liver disease patients. 3. Results 52 patients received 3 doses of HBV vaccine; the mean age of patients was47.48±9.37 years. eTh re were 37 males and nonresponders were 9/37 (24%) in males and 2/15 (13%) in 15 females. 30 patients were less than 50 years of age and 22 females (𝑃 value 0.43). were more than 50 years. 25 patients were in CTP class A When we were individually analyzing the vaccine and the rest 27 were in CTP class B. eTh reasons for CLD response across different etiologies, we found that in 27 of were alcohol 27/52 (52%), cryptogenic 13/52 (25%), hepatitis the patients with alcohol induced CLD, 12/27 (44%) had C 8/52 (15%), and others 4/52 (8%). (Figure 1). In this study good response, 7/27 (26%) had poor response, and 8/27 31/52 (60%) were good responders, 10/52 (19%) were of poor (30%) were non responders and in 8 patients with HCV responders and 11/52 (21%) were nonresponders. (Figure 2). related CLD 6/8 (76%) were good responders, 1/8 (12%) Patient characteristics and clinical profiles were shown in poor responders, and 1/8 (12%) were nonresponders. Overall Table 1. response rates in 52 patients were as follows: 31/52 (60%) Among the patients who were less than 50 years of age, had good response, 10/52 (19%) had poor response, and 11/52 21/30 (70%) of them were good responders, 6/30 (20%) were (21%) were nonresponders. (𝑃=0.36 ). poor responders, and 3/30 (10%) were nonresponders. In We also compared response rates with the child scores; patients more than 50 years, 9/22 (40%) were good respon- outof25patientswho were childAscore, 22/25(88%)were ders, 5/22 (23%) were poor responders, and 8/22 (36%) were good responders, 1/25 (40%) were poor responders, and 2/25 nonresponders. On comparing the responders rate between (8%) were nonresponders and in child B class only 9/27 the age groups, patients in age group less than 50 years had (33%) had good antibody response and 9/27 (33%) had poor significant responder rates (70%) than patients with age more response, 9/27 (33%) were nonresponders (𝑃 < 0.0001 ). than 50 years. (40%) (𝑃=0.03 ). None of our patients had sueff red significant systemic or We observed that 20/37 (54%) of the males and 11/15 local adverse reactions. All patients complained of pain and (74%) of the females were good responders, 8/37 (22%) redness during vaccine administration. No other adverse males and 2/15 (13%) females were poor responderss and events were observed. (IU/mL) (%) Advances in Virology 3 Table 1: Patient characteristics, clinical profiles, and immunological outcomes. Antibody titers Partial Nonresponders Responders 226.88± 164 Total responders 𝑃 value [<10 IU/mL] [>100 IU/mL] [IU/mL] [10–100 IU/mL] Age group 47.48± 9.37 [years] <50 30 3 [10%] 6 [20%] 21 [70%] 0.03 >50 22 8 [36%] 5 [23%] 9 [41%] Total 52 11 [21%] 11 [21%] 30 [58%] Gender Female 15 2 [13%] 2 [13%] 11 [74%] 0.43 Male 37 9 [24%] 8 [22%] 20 [54%] Total 52 11 [21%] 10 [19%] 31 [60%] Etiology Alcohol 27 8 [30%] 7 [26%] 12 [44%] Hepatitis C 8 1 [12%] 1 [12%] 6 [76%] 0.36 Cryptogenic 13 2 [15%] 2 [15%] 9 [70%] Others 4 0 0 4 [100%] Total 52 11 [21%] 10 [19%] 31 [60%] Child’s class A 25 2 [8%] 1 [4%] 22 [88%] <0.0001 B 27 9 [33.3%] 9 [33.3%] 9 [33.3%] Total 52 11 [21%] 10 [19%] 31 [60%] 4. Discussion in our study. In chronic ALD patients the response rates observed by Mendenhall et al., Bronowicki et al., and Rosman Vaccination with HBV vaccine is extremely safe in general et al. [23–25]were18%,69%,and 46%, respectively.The population andinpatientswithchronic liverdisease.The previous studies had included only fewer cirrhotic patients. immunogenicity rates of vaccination in general population In our study the good responders in patients with alcoholic are>90% whereas in CLD it varied from 18% to 100%. In inducedcirrhosis were only 44%, andall thepatientswere thepresent study, theresponsetostandardHBV vaccination with childAor childBcirrhosiswhencomparedtoprevious with a dose of 20𝜇 gat0,1,and 2monthsincirrhosis of liver studies in the literature. with various etiologies was evaluated and compared. We eTh se observations suggest that if we are vaccinating found that good responders were only 60%, poor responders at an earlier age (<50 years) and also at an early stage 19% percent, and nonresponders 21%. When we analyzed the of chronic liver disease (child A), the immunogenicity of various aetiologies of CLD and the vaccine response rate, we hepatitis B vaccination is superior as compared to patients observed that the patients with alcoholic chronic liver disease with age more than 50 years and with child B cirrhosis (ALD) had poor antibody response (44%) as compared to liver. eTh se observations suggest that if the patient is having other aetiologies of chronic liver disease such as cryptogenic advanced cirrhosis liver or in the age group of more than (69%) and HCV (75%) related liver disease. Severity of the 50 years, it is always better to try different regimens like chronic liver disease predicts the response rate; the good 40 ug or 80 ug of hepatitis vaccination or other routes of responders were in CTP class A (88%) as compared to CTP vaccine administrations like multiple intradermal dose. And class B (33.3%). It was observed that apart from severity of theliteraturesearchhad shownthatthe safety profile of these liverdisease,the ageofthe patients also hadcontributed to higher doses was comparable with that of normal dose. er Th e antibody response; patients less than 50 years had a higher were only few studies having data on multiple intradermal rate of response with hepatitis B vaccination than patients dose of hepatitis B vaccination in chronic liver disease, but above 50 years. it has not been yet approved in vaccination schedule. Studies conducted by Lee et al., Wiedmann et al. and Keeeff and Krause [ 20–22]inCLD patients with HCVwho 5. Study Limitations hadreceived20ugshowedresponserates of 100%,89%,and 69%, respectively. However these studies did not include any We had evaluated only using standard dose of hepatitis B vac- patients with cirrhosis liver. In our study the good responders cine (Shanvac, M/s Shantha biotech) in patients with cirrhosis in patients with HCV related cirrhosis liver were 76%. How- liver of CTP classes A and B only and had excluded CTP ever a fewer number of patients with HCV had participated class C patients. However we have not compared the efficacy 4 Advances in Virology of Shanvac HBV vaccine with other available vaccines in [8] S. Chlabicz and A. Grzeszczuk, “Hepatitis B virus vaccine for patients with hepatitis C virus infection,” Infection,vol.28, no. themarket. Ourstudy populationswerediversiefi dand the 6, pp. 341–345, 2000. subjects included in the different etiologic groups were small. We should have attempted with higher dose and/or weekly [9] S.D.Lee,C.Y.Chan, M. I. Yu,R.H.Lu, F. Y. Chang, andK.J. Lo, “Hepatitis B vaccination in patients with chronic hepatitis intradermal doses as per the evidence from the literature of C,” Journal of Medical Virology,vol.59, pp.463–468,1999. patients with chronic kidney disease. Additionally long-term persistence of antibody titers, the frequency of estimating the [10] M. Wiedmann, U. G. Liebert, U. Oesen et al., “Decreased immunogenicity of recombinant hepatitis B vaccine in chronic postvaccination anti-Hbs titer, and the need for booster dose hepatitis C,” Hepatology,vol.31, no.1,pp. 230–234, 2000. of hepatitis B vaccine were not evaluated due to technical and financial constraints. Another limitation of our study is that [11] A. S. Rosman, P. Basu, K. Galvin, and C. S. Lieber, “Efficacy of a high and accelerated dose of hepatitis B vaccine in alcoholic all the patients received the same quantity of HBV vaccine patients: a randomized clinical trial,” American Journal of (20𝜇 g), and thus comparisons between high and low doses Medicine,vol.103,no. 3, pp.217–222,1997. cannot be anticipated. [12] E. B. Keeffe and D. S. Krause, “Hepatitis B vaccination of patients with chronic liver disease,” Liver Transplantation,vol. 6. Conclusions 4, pp. 437–439, 1998. [13] C. Mendenhall, G. A. Roselle, L. A. Lybecker et al., “Hepatitis B Patients with cirrhosis liver when compared to general vaccination: response of alcoholic with and without liver injury,” population will have low postimmunization antibody titres Digestive Diseases and Sciences,vol.33, pp.263–269,1998. against hepatitis B. As the age and the stage of liver disease [14] J. P. Bronowicki, F. Weber-Larivaille, J. P. Gut, M. Doo ff el ¨ , progress, the immunogenicity of standard dose of hepatitis and D. Vetter, “Comparison of immunogenicity of anti-HBV Bvaccination againsthepatitis Binfection will stillremain vaccination end serovaccination in alcoholic patients with weak. Hence all the cirrhotics with non-HBV etiologies cirrhosis,” Gastroenterologie Clinique et Biologique,vol.21, no. should be initiated on hepatitis B vaccination protocol at the 11, pp.848–853,1997. time of diagnosis to achieve better protection against HBV. [15] E. Villeneuve, J. Vincelette, and J. P. Villeneuve, “Ineffectiveness If the patient had not achieved seroconversion with stan- of hepatitis B vaccination in cirrhotic patients waiting for liver dard universal dose of hepatitis B vaccine, reimmunization transplantation,” Canadian Journal of Gastroenterology,vol.14, with ahigherdoseofhepatitis Bvaccine schedule or with pp.59B–62B,2000. multiple intradermal route of vaccination may be considered. [16] M. Dominguez, R. Barcena, M. Garcia, A. Lopez-Sanroman, Further studies are needed to assess the antibody titres by and J. Nuno, “Vaccination against hepatitis B virus in cirrhotic considering type of vaccine, the dose to be administered, the patients on liver transplant waiting list,” Liver Transplantation, route of administration, the frequency of antibody testing, vol. 6, pp. 440–442, 2000. and the requirement for booster dose. [17] M. Arslan,R.H.Wiesner,C.Sievers,K.Egan, andN.N.Zein, “Double-dose accelerated hepatitis B vaccine in patients with end-stage liver disease,” Liver Transplantation,vol.7,no. 4, pp. References 314–320, 2001. [18] Centers for Disease Control and Prevention, “Recommenda- [1] A. S. Lok, “Chronic hepatitis B,” eTh New England Journal of tions and reports: hepatitis A and B vaccines,” Morbidity and Medicine,vol.346,no. 22,pp. 1682–1683, 2002. Mortality Weekly Report,vol.52, pp.34–36,2003. [2] L.J.Kozak,M.F.Owings, andM.J.Hall, “NationalHospital [19] National Institutes of Health, “National Institutes of Health Discharge Survey: 2001 annual summary with detailed diagno- Consensus Development Conference Statement: management sis and procedure data,” Vital and Health Statistics,vol.13, no. of hepatitis C: 2002—June 10-12, 2002,” Hepatology,vol.36, 156, pp. 1–198, 2004. supplement 1, pp. S3–S20, 2002. [3] E.Arias,R.N.Anderson, H. C. Kung,S.L.Murphy, andK.D. [20] S. D. Lee, C. Y. Chan,M.I.Yu, R. H. Lu,F.Y.Chang,and K. J. Kochanek, “Deaths: final data for 2001,” National Vital Statistics Lo, “Hepatitis B vaccination in patients with chronic hepatitis Reports,vol.52, no.3,pp. 1–115,2003. C,” Journal of Medical Virology,vol.59, pp.463–468,1999. [4] R.S.Ko,“ ff Risksassociatedwithhepatitis Aand hepatitisBin [21] M. Wiedmann, U. G. Liebert, U. Oesen et al., “Decreased immu- patients with hepatitis C,” Journal of Clinical Gastroenterology, nogenicity of recombinant hepatitis B vaccine in chronic hep- vol. 33,no. 1, pp.20–26,2001. atitis C,” Hepatology,vol.31, no.1,pp. 230–234, 2000. [5] G. Reiss and E. B. Keeffe, “Review article: hepatitis vaccination [22] E. B. Keeffe and D. S. Krause, “Hepatitis B vaccination of in patients with chronic liver disease,” Alimentary Pharmacology patients with chronic liver disease,” Liver Transplantation,vol. & er Th apeutics ,vol.19, pp.715–727,2004. 4, pp. 437–439, 1998. [6] A. Alberti, P. Pontisso, L. Chemello et al., “eTh interaction bet- [23] A. S. Rosman, P. Basu, K. Galvin, and C. S. Lieber, “Efficacy of ween hepatitis B virus and hepatitis C virus in acute and chronic a high and accelerated dose of hepatitis B vaccine in alcoholic liver disease,” JournalofHepatology, Supplement,vol.22, no.1, patients: a randomized clinical trial,” American Journal of pp. 38–41, 1995. 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