Title: Seropositivity of Hepatitis and Cancer Management-Review and Recommendations

Authors: Prof. Subbiah Shanmugam, Prof. Sujay Susikar, Rajeswaran Ayyanar

 DOI: https://dx.doi.org/10.18535/jmscr/v8i1.76

Abstract

Background: Hepatitis virus reactivation is one of the troublesome and preventable causes of mortality and morbidity in oncology patients. It causes significant morbidity either directly as liver injury or indirectly by delaying   chemotherapy or definitive treatment. We started the research to find the cause of hepatitis virus (hepatitis B & hepatitis C) positivity, on subsequent admissions in patients who were previously negative by the same serological test. We conducted the research to find out the possible mode of acquisition of hepatitis virus

Objectives

  1. To emphasize the importance of serological test during every admission  particularly in a cancer ward and to standardize the protocol
  2. Preventing hepatitis virus reactivation related morbidity and mortality.
  3. To ensure safety of patients and medical personal.
  4. To enhance safety during blood transfusion.

Materials and Methods: Patients admitted during the period of January 2017 to March2 019 in department of surgical oncology, government Royapettah hospital who were negative for hepatitis B virus (HBV) /hepatitis C virus (HCV) on first or initial admission and treated after that with blood transfusion, chemotherapy, interventional procedures were included. Patients who became positive on routine serology were reaffirmed by specific tests like ELISA, RNA/DNA tests. Along with that liver function test, radiological assessment of liver was done and morbidity and mortality   recorded.

Results: Among the seroconverted patients, 60(68%) were found to be positive for HBV and 26(29.5%) were HCV positive. Two patients were (2.27%) positive for both HBV&HCV.  We found seroconversion   in 38 patients. Female to male ratio was 1:0.9. In our study we found that 79% patients were between the age of 30 to 60. We noted that 32 (84.2%) patients with seroconversion was post chemotherapy. There were 11 patients (28 %) who got blood transfusion. In patients with seroconversion   Adriamycin, CDDP, 5-FU based chemotherapy was used in 9,19,9 patients respectively. Musculoskeletal sarcoma and GIT cancers were most frequent among the seroconverted patients. During our hospital admissions 3 patients died of acute fulminant hepatic failure (mortality rate of 39 per 1000/year), 1 patient required ICU admission and recovered.  Half (n=19) of patients having fibro scan above 12.5 kilopascals probably indicating that these patients were in a chronic hepatitis state.

Conclusion: In our study we frequently encountered patients who were seropositive after treatment. It was found to be related to chemotherapy induced immunosuppression causing hepatitis virus reactivation.

We used rapid card test to detect HBV and HCV antibody, which has very low sensitivity and not recommended for routine screening. Sensitivity and specificity of third generation EIA is 99% and is recommended for routine screening (32).

As an oncologist it is important to be aware about this potential life threatening and treatable condition. Timely administration of antiviral prophylaxis will reduce the viral reactivation related fulminant hepatic failure and death.

  1. The serological tests recommended to detect HBV, in descending order are HBV-DNA, HBs Ag and HB e Ag 
  2. For HCV it is ideal to do HCV antibody as a screening test, followed by EIA and HCV RNA as a confirmative test.

Keywords: Hepatitis, HBV and HCV reactivation, chemotherapy induced hepatitis virus reactivation.

References

  1. Dai MS, Chao TY, Kao WY, Shyu RY, Liu TM. Delayed hepatitis B 231 Venessa Pattullo. HBV reactivation with immunosuppression virus reactivation after cessation of preemptive lamivudine in lym­phoma patients treated with rituximab plus CHOP. Ann Hematol 2004;83:769-774.
  2. Hsu C, Hsiung CA, Su IJ, Hwang WS, Wang MC, Lin SF, et al. A re­visit of prophylactic lamivudine for chemotherapy-associated hepa­titis B reactivation in non-Hodgkin’s lymphoma: a randomized trial. Hepatology 2008;47:844-853.
  3. Lok AS, Liang RH, Chiu EK, Wong KL, Chan TK, Todd D. Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. Gastroenterology 1991;100:182-188.
  4. Liaw YF, Sheen IS, Chen TJ, Chu CM, Pao CC. Incidence, determi­nants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. Hepatology 1991;13:627-631.
  5. Bréchot C, Degos F, Lugassy C, Thiers V, Zafrani S, Franco D, et al. Hepatitis B virus DNA in patients with chronic liver disease and negative tests for hepatitis B surface antigen. N Engl J Med 1985;312:270-276.
  6. Chemin I, Jeantet D, Kay A, Trépo C. Role of silent hepatitis B virus in chronic hepatitis B surface antigen(-) liver disease. Antiviral Res 2001;52:117-123.
  7. Perrillo RP, Gish R, Falck-Ytter YT. American gastroenterological association institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug 235 enessa Pattullo.HBV reactivation with immunosuppression http://www.e-cmh.org http://dx.doi.org/10.3350/cmh.2016.0024 therapy. Gastroenterology 2015;148:221-244 e3.
  8. Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT. American gastroenterological association institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology 2015;148:215- 219.
  9. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C  virus infection. J Hepatol. 2014;61(suppl 1):S45-S57.
  10. Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013;57: 1333-1342.
  11. Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT. American gastroenterological association institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology 2015;148:215- 219.
  12. .Markovic S, Drozina G, Vovk M, Fidler-Jenko M. Reactivation of hepatitis B but not hepatitis C in patients with malignant lymphoma and immunosuppressive therapy. A prospective study in 305 patients. Hepatogastroenterology 1999;46:2925-2930.
  13. Torres HA, Davila M. Reactivation of hepatitis B virus and hepatitis  C virus in patients with cancer. Nat Rev Clin Oncol 2012; 9:156-166.
  14. Vento S, Cainelli F, Longhi MS. Reactivation of replication of hepatitis B and C viruses after immunosuppressive therapy: an unresolved issue. Lancet Oncol 2002;3:333-340.
  15. Lok AS, Ward JW, Perrillo RP, McMahon BJ, Liang TJ. Reactivation of hepatitis B during immunosuppressive therapy: potentially fatal yet preventable. Ann Intern Med 2012;156:743-745.
  16. Mahale P, Kontoyiannis DP, Chemaly RF, Jiang Y, Hwang JP, Davila M, et al. Acute exacerbation and reactivation of chronic hepatitis C virus infection in cancer patients. J Hepatol 2012;57: 1177-1185.
  17. Fujii Y, Kaku K, Tanaka M, Yosizaki M, Kaneko T, Matumoto Hepatitis C virus infection in patients with leukemia. Am J Hematol 1994;46:278-282.
  18. Zuckerman E, Zuckerman T, Douer D, Qian D, Levine AM. Liver dysfunction in patients infected with hepatitis C virus undergoing chemotherapy for hematologic malignancies. Cancer1998;83:1224-1230.
  19. Vento S, Cainelli F, Mirandola F, Cosco L, Di Perri G, Solbiati M, et al. Fulminant hepatitis on withdrawal of chemotherapy in carriers of hepatitis C virus. Lancet 1996;347:92-93.
  20. Evans AT, Loeb KR, Shulman HM, Hassan S, Qiu WC, Hockenbery DM, et al. Fibrosing cholestatic hepatitis C after hematopoietic cell transplantation: report of 3 fatal cases. Am J Surg Pathol 2015;39:212-220.
  21. Lok AS, Ward JW, Perrillo RP, McMahon BJ, Liang TJ. Reactivation of hepatitis B during immunosuppressive therapy: potentially fatal yet preventable. Ann Intern Med 2012;156:743-745.
  22. Lok AS, Liang RH, Chiu EK, Wong KL, Chan TK, Todd D. Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. Gastroenterology 1991;100:182-188.
  23. Loomba R, Rowley A, Wesley R, Liang TJ, Hoofnagle JH, Pucino F, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 2008;148:519-528.
  24. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C  virus infection. J Hepatol. 2014;61(suppl 1):S45-S57.
  25. Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates  of age-specific antibody to HCV seroprevalence. Hepatology. 2013;57: 1333-1342. 
  26. Sievert W, Altraif I, Razavi HA, et al. A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt Liver Int. 2011;31(suppl 2):61-80.
  27. Stanaway JD, Flaxman AD, Naghavi M, et al. The global burden of viral hepatitis from 1990 to 2013: findings from the  Global Burden of Disease Study 2013. Lancet.  2016;388:1081-1088.
  28. Torres HA, Mahale P, Blechacz B, et al.Effect of hepatitis C virus infection inpatients with cancer: addressing a neglected population. J Natl Compr Canc Netw. 2015;13:41-50.
  29. Torres HA, Economides MP, Kyvernitakis A, et al. Sofosbuvir-based therapy in patients with chronic hepatitis C virus infection and malignancies—a prospective  observational study of 143 patients. The 53rd Annual Meeting of American Society  of Clinical Oncology (ASCO), June 2–6,2017. Chicago, IL. Abstract e18152.
  30. Silvestri F, Pipan C, Barillari G, et al. Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders. Blood. 1996;87:4296-4301.
  31. Oguz A, Aykas F, Unal D, et al. Hepatitis B and C seroprevalence in solid tumors—necessity for  screening during chemotherapy. Asian Pac J Cancer Prev. 2014;15:1411-1414.
  32. Alborino F, Burighel A, Tiller FW, et al. Multicenter evaluation of a fully automated third-eneration anti-HCV antibody screening test with excellent sensitivity and specificity. Med Microbiol Immunol 2000; 200:77-83.
  33. Chevaliez S, Rodriguez C, Pawlotsky JM. New virologic  tools for management of chronic hepatitis B and C. Gastroenterology 2012; 142:1303-13 e1.

Corresponding Author

Prof. Sujay Susikar

Associate Professor, Department of Surgical Oncology, Government Royapettah Hospital, Chennai, India