MedInform

Journal of Medical and Dental Practice

www.medinform.bgISSN 2367-6795

Issue Two 2018

2018, Vol. 5 issue 2, (June)

Publisher: Medinform LTD
ISSN: 2367-6795
Pages: 790-831
Date of close: 2018/06/21

Original Article

Lamivudine today: Experience in a single Bulgarian center

Abstract:

Lamivudine (LAM) is not recommended in the treatment of chronic hepatitis B due to high-rate of resistance: 49% to 70% after 3rd and 5th treatment year. LAM-resistance is more frequent in cases with high viral load or lack of complete HBV-DNA suppression within 6 months. Antiviral effect of LAM is rapid and potent if HBV-DNA level is low. Subjects who are indicated for prophylactic NUC-therapy prior immunosuppression as well as cirrhotics are with relatively low viral load, but data on the LAM efficacy in such patient populations are limited.

 

We evaluated 97 patients (56 males) with chronic HBV-infection, mean age 56.5 (±13.1) years. Of them: 54 (56%) were with liver cirrhosis; 18 (18.5%) were with hematological malignancy or carcinoma and 16 (16.5%) with systemic autoimmune diseases. The rest 9 patients were of older age or started LAM after unsuccessful IFN-therapy. Initially 88 (91%) were HBeAg-negative. Co-infections with HCV and HDV were excluded. Patients received LAM 100mg/d for at least 36 months or until development of resistance. HBV-DNA was measured on 3-month interval by real-time PCR. Test for LAM-resistant mutations was performed in case of viral breakthrough.

 

At the treatment-month 6; 12; 24 and 36 a complete viral suppression was achieved in 73%; 89%; 95% and 96% of patients, respectively. During therapy 16/97(16.6%) developed LAM-resistance for median 18 (9-36) months.

 

Resistant patients were with higher median HBV-DNA: 28750000 (11751 – 7570000000) cp/mL vs. 949300 (380 – 4650000000) cp/mL; p<0.05. The complete viral suppression was induced more slowly in patients who developed drug resistance: median 9 (3-36) months vs. 3 (1 – 27); p<0.001. LAM-therapy was safe and very well tolerated. All patients with LAM-resistant mutations were switched to tenofovir and HBV-DNA rapidly decreased, to undetectable level within 6 months. Rescue therapy lead to durable and complete viral suppression. ALT-flare or hepatic decompensation was not observed.

 

In conclusion, LAM is effective, safe and cost-saving treatment option in selected patients with low baseline viral load. In this case LAM induces a rapid and durable viral suppression with risk of resistance far below previously reported levels. Patients should be carefully monitored during therapy. Tenofovir must be started immediately after viral breakthrough to avoid ALT flare and potential hepatic decompensation.

Authors:

Donika Krasteva; Clinic of Gastroenterology, St. Ivan Rilsky University Hospital, Sofia Medical University;;
Deian Jelev; Clinic of Gastroenterology, St. Ivan Rilsky University Hospital, Sofia Medical University;;
Krassimir Antonov; Clinic of Gastroenterology, St. Ivan Rilsky University Hospital, Sofia Medical University;;
Zoya Spassova; Clinic of Gastroenterology, St. Ivan Rilsky University Hospital, Sofia Medical University;;
Rossen Nikolov; Clinic of Gastroenterology, St. Ivan Rilsky University Hospital, Sofia Medical University;;
Georgi Mihailov; National Specialized Hospital for Active Therapy of Hematological Diseases, Sofia Medical University;;
Branimir Spassov; National Specialized Hospital for Active Therapy of Hematological Diseases, Sofia Medical University;;
Rasho Rashkov; Clinic of Rheumatology, St. Ivan Rilsky University Hospital, Sofia Medical University.;
Zlatimir Kolarov; Clinic of Rheumatology, St. Ivan Rilsky University Hospital, Sofia Medical University.;
Lyudmila Mateva; Clinic of Gastroenterology, St. Ivan Rilsky University Hospital, Sofia Medical University;;
Zahariy Krastev; Clinic of Gastroenterology, St. Ivan Rilsky University Hospital, Sofia Medical University;;

Corresponding Author:

Deian Jelev; Clinic of Gastroenterology, St. Ivan Rilsky University Hospital; Medical University, 15, Acad. Ivan Geshov blvd, 1431 Sofia, Bulgaria; Email this author