Research Article
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Tedavi ile Remisyona Giren Kronik Hepati B Hastalarında Persistan ALT Yüksekliği

Year 2017, Volume: 14 Issue: 2, 87 - 94, 31.08.2017

Abstract

Amaç: Amacımız, anti viral tedavi ile remisyona giren kronik hepatit B (KHB) hastalarında persistan ALT yüksekliğinin
nedenini araştırmaktır.
Materyal Metod: Persistan ALT yüksekliği olan 10 hasta çalışmaya alınarak tedavi öncesi HBV-DNA değerleri, serolojik
testleri, ALT, AST düzeyleri, histopatolojik olarak fibroz derecesi, ultrasonografisi, kullanmakta olduğu anti viral ilaçlar
incelendi. Bu hastalarda tedavi başlangıcından itibaren geçen süre değerlendirildiği sırada hastaların yine HBV-DNA, seroloji, biyokimyasal testler, diğer karaciğer fonksiyon testleri, serum kolesterol ve trigliserid düzeyleri, karaciğer ultrasonografisi,
otoimmün tetkikleri ve muhtemel diğer hepatit nedenleri araştırıldı.
Bulgular: Tamamı erkek 10 hastanın tedavi başında HBV-DNA değerleri 104
-108
kopya/ml arasında ve hastaların beşinde
HBeAg serokonversiyonu vardı. Tedavi ile virolojik yanıta bakıldığında hastalardan sadece birisinde HBV-DNA 244 IU/ml
iken, geri kalan kısmında negatifleşti. Ve hastaların tümünde HBeAg serokonversiyonu oluştu. Hastaların beşinde ALT
değerlerinde tedavi öncesine göre yükselme olduğu; bir hastada ALT değerinin aynı kaldığı, geri kalan 4 hastada da ALT
değerlerinde düşme olmakla beraber normale gelmediği görülmektedir. Karaciğer USG incelendiğinde iki hastada grade I
hepatosteatoz dışında başka bir patoloji tespit edilmedi. Diğer viral hepatit etkenleri ve otoimmun hepatit markerları negatif
olup karaciğer fonksiyon testleri ve alfa feto protein (AFP) de normal idi. Hastaların hikâyesinde ilacı bırakma, alkol ve madde
(drug use) kullanımı veya neden olabilecek başka bir ilaç kullanımı da söz konusu değildi.Hastaların kullandığı antiviral
ilaçlara bakıldığında dört hastanın entekavir, dört hastanın tenofovir, bir hastanın entekavir + tenofovir, bir hastanın telbivudin
ve bir hastanın da pegile interferon alfa kullandığı görüldü.
Sonuç: KHB hastaları, tedavi ile virolojik ve serolojik olarak remisyonda olsalar bile ALT yüksekliği devam edebilir. Bu
durum, nedeni tam olarak bilinmeyen ve aydınlatılması gereken bir sorun olarak karşımızda durmaktadır

References

  • 1. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(6):1264–73.
  • 2. Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. Journal of hepatology., (2008); 48 (2): 335–352
  • 3. Bonilla Guerrero R, Roberts L.R. The role of hepatitis B virus integrations in the pathogenesis of human hepatocellular carcinoma. Journal of hepatology. (2005);42 (5):760–777
  • 4. Bosch F.X, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. (2004);127(5 ): 15-16.
  • 5. Ke W, Zhang C, Liu L, Gao Y, Yao Z, Ye X et al. Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China. Hepatol Int. 2016;10(6): 924-936.
  • 6. Kim JH, Sinn DH, Kim K, Kim H, Gwak GY, Paik YH, et al. Lamivudine versus Entecavir for Newly Diagnosed Hepatitis B Virus-Related Hepatocellular Carcinoma. Gut Liver. 2016;10(6): 939-947.
  • 7. Runyon BA; AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009 Jun;49(6):2087-107.doi: 10.1002/hep.22853
  • 8. Turkish guide of chronic hepatitis B 2015 (Türkiye Kronik Viral Hepatit Tanı Ve Tedavi Rehberi 2015) (in Turkish)
  • 9. Papatheodoridis G, Vlachogiannakos I, Cholongitas E, Wursthorn K, Thomadakis C, Touloumi G, Petersen J. Discontinuation of oral antivirals in chronic hepatitis B: A systematic review. Hepatology. 2016;63(5):1481-1492.
  • 10. Tacke F, Kroy DC. Treatment for hepatitis B in patients with drug resistance. Ann Transl Med. 2016;4(18):334.
  • 11. Cho JY, Sohn W, Sinn DH, Gwak GY, Paik YH, Choi MS, et al. Long-term real-world entecavir therapy in treatment-naïve hepatitis B patients: base-line hepatitis B virus DNA and hepatitis B surface antigen levels predict virologic response. Korean J Intern Med. 2016; doi: 10.3904/kjim.2016.096.
  • 12. Ke W, Zhang C, Liu L, Gao Y, Yao Z, Ye X, Zhou S, Yang Y. Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China. Hepatology International. 2016;10 (6):924–936.
  • 13. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBVStudy Group. Risk of hepatocellular carcinoma across a biological gradient ofserum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73.
  • 14. Raj V. Treatment of hepatitis B. Clin Cornerstone. 2001;3(6):24-36.
  • 15. Chen CF, Lee WC, Yang HI, Chang HC, Jen CL, Iloeje UH, et al. Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma. Gastroenterology. 2011 Oct;141(4):1240- 1248.

Persistent ALT Elevation in Chronic Hepatitis B Patients Entering to Remission with Treatment

Year 2017, Volume: 14 Issue: 2, 87 - 94, 31.08.2017

Abstract

Aim: Our aim is to investigate the reason for persistent ALT elevation in chronic Hepatitis B (CHB) patients entering into

remission with antiviral treatment.

Material Method: 10 patients with persistent ALT elevation were included in the study and their pre-treatment HBV-DNA

values, serological tests, ALT, AST titers, liver fibrosis degree, ultrasonography (USG) and antiviral medicines they were

taking were analyzed. While the time passed since the beginning of the treatment in these patients was evaluated, their HBVDNA,

serology, bio-chemical tests, other liver functions tests, serum cholesterol and triglyceride levels, liver USG,

autoimmune tests and possible other hepatitis reasons were searched again.

Results: At the beginning of the treatment, HBV-DNA values of the 10 patients, all of whom were male, were between 104

-108

copy/ml and 5 of the patients had HBeAg seroconversion. Considering virological response with treatment, HBV-DNA was

244 IU/ml in only one of the patients whereas it was negative in the rest and HBeAg seroconversion occurred in all the

patients. It was realized that there was an increase in ALT values of five patients compared to pretreatment; ALT value

remained the same in one of the patients and ALT values of the remaining four patients did not decrease to normal despite a

decline. When liver USG was analyzed, no other pathology was determined except for the grade I hepatosteatosis in two

patients. Other viral hepatitis agents and autoimmune hepatitis markers were negative, and liver functions tests and alphafetoprotein

(AFP) were normal. In the patients’ stories, there was no reference to quitting medicines, alcohol and drug use or

taking other medicines that could be a cause. Considering the antiviral medicines the patients took, it was observed that four of

the patients took entecavir, four of them took tenofovir, one took entecavir + tenofovir, one took telbivudin and one took PegInterferon.


Conclusion: ALT elevation of CHB patients may continue even if they are virologically and serologically in remission with

treatment. This situation faces us as a problem which has no precisely known reason and needs highlighting. 

References

  • 1. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(6):1264–73.
  • 2. Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. Journal of hepatology., (2008); 48 (2): 335–352
  • 3. Bonilla Guerrero R, Roberts L.R. The role of hepatitis B virus integrations in the pathogenesis of human hepatocellular carcinoma. Journal of hepatology. (2005);42 (5):760–777
  • 4. Bosch F.X, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. (2004);127(5 ): 15-16.
  • 5. Ke W, Zhang C, Liu L, Gao Y, Yao Z, Ye X et al. Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China. Hepatol Int. 2016;10(6): 924-936.
  • 6. Kim JH, Sinn DH, Kim K, Kim H, Gwak GY, Paik YH, et al. Lamivudine versus Entecavir for Newly Diagnosed Hepatitis B Virus-Related Hepatocellular Carcinoma. Gut Liver. 2016;10(6): 939-947.
  • 7. Runyon BA; AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009 Jun;49(6):2087-107.doi: 10.1002/hep.22853
  • 8. Turkish guide of chronic hepatitis B 2015 (Türkiye Kronik Viral Hepatit Tanı Ve Tedavi Rehberi 2015) (in Turkish)
  • 9. Papatheodoridis G, Vlachogiannakos I, Cholongitas E, Wursthorn K, Thomadakis C, Touloumi G, Petersen J. Discontinuation of oral antivirals in chronic hepatitis B: A systematic review. Hepatology. 2016;63(5):1481-1492.
  • 10. Tacke F, Kroy DC. Treatment for hepatitis B in patients with drug resistance. Ann Transl Med. 2016;4(18):334.
  • 11. Cho JY, Sohn W, Sinn DH, Gwak GY, Paik YH, Choi MS, et al. Long-term real-world entecavir therapy in treatment-naïve hepatitis B patients: base-line hepatitis B virus DNA and hepatitis B surface antigen levels predict virologic response. Korean J Intern Med. 2016; doi: 10.3904/kjim.2016.096.
  • 12. Ke W, Zhang C, Liu L, Gao Y, Yao Z, Ye X, Zhou S, Yang Y. Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China. Hepatology International. 2016;10 (6):924–936.
  • 13. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBVStudy Group. Risk of hepatocellular carcinoma across a biological gradient ofserum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73.
  • 14. Raj V. Treatment of hepatitis B. Clin Cornerstone. 2001;3(6):24-36.
  • 15. Chen CF, Lee WC, Yang HI, Chang HC, Jen CL, Iloeje UH, et al. Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma. Gastroenterology. 2011 Oct;141(4):1240- 1248.
There are 15 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Article
Authors

Hasan Karsen

Azize Sezin Seyhanoğlu

Emine Ayca Güler This is me

Publication Date August 31, 2017
Submission Date April 18, 2017
Acceptance Date August 4, 2017
Published in Issue Year 2017 Volume: 14 Issue: 2

Cite

Vancouver Karsen H, Seyhanoğlu AS, Güler EA. Persistent ALT Elevation in Chronic Hepatitis B Patients Entering to Remission with Treatment. Harran Üniversitesi Tıp Fakültesi Dergisi. 2017;14(2):87-94.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty