Analog Nukleosida/Nukleotida sebagai Terapi Hepatitis B Kronis: Studi Kohort 3 Tahun

Andri Sanityoso Sulaiman, Irsan Hasan, Cosmas Rinaldi A. Lesmana, Chyntia Olivia M. Jasirwan, Saut Horas H. Nababan, Kemal Fariz Kalista, Gita Aprilicia, Rino Alvani Gani

Abstract

Pendahuluan. Hepatitis B kronis merupakan penyakit endemis di Indonesia yang umumnya diobati menggunakan interferon pegilasi dan analog nukleosida/nukleotida. Tujuan dari penelitian ini ialah untuk menilai efikasi terapi hepatitis B kronis pada pasien Indonesia yang mendapatkan terapi analog nukleosida/nukleotida (lamivudin, telbivudin, and tenofovir) selama periode tiga tahun.

Metode. Penelitian ini meninjau catatan rekam medis secara retrospektif pada pasien dengan infeksi hepatitis B kronis yang mengunjungi Poliklinik Hepatobilier Rumah Sakit dr. Cipto Mangunkusumo periode 2010-2013. Kriteria inklusi ialah pasien dengan usia >18 tahun yang mendapatkan terapi analog nukleosida/nukleotida selama 3 tahun. Penilaian derajat kekakuan hati, kadar DNA virus hepatitis B (DNA-VHB), kadar alanine aminotransferase (ALT), dan antigen hepatitis B (HBeAg) dilakukan pemeriksaan sebelum dan sesudah terapi 3 tahun.

Hasil. Sebanyak 62 subjek terlibat dalam penelitian ini. Empat puluh delapan pasien (77%) mendapat terapi telbivudin, 9 (15%) tenofovir, dan 5 (8%) lamivudin. Pada saat sebelum terapi, 52 pasien (84%) memiliki HBeAg positif, 15 pasien (24%) memiliki derajat kekakuan hati F3 (fibrosis lanjut), dan 36 (58%) dinyatakan sirosis hati berdasarkan pemeriksaan elastografi. Pada tahun ke-3 akhir masa pengamatan, median derajat kekakuan hati menurun signifikan (14,5 (3,3–59,3) kPa vs. 6,7 (3,3 – 37,2) kPa, p=0,001), kadar DNA-VHB menurun signifikan (1,31 x 107 (2,0x106–1,0x108) kopi/mL vs. 0 (0–1,7 x 107) kopi/mL, p=0,001), kadar alanine aminotransferase (ALT) menurun signifikan (58 (11– 404) U/L vs. 27 (8-291) U/L, p = 0,001). Meskipun demikian, terdapat 5 pasien (8%) yang masih memiliki derajat kekakuan hati F3 dan 20 pasien (32,3%) memiliki derajat kekakuan hati F4, 21 (34%) tetap memiliki DNA-HBV yang terdeteksi, dan 17 (27%) tidak mencapai normalisasi ALT. Dari 52 pasien HBeAg positif pada awal studi, terdapat 20 pasien (39%) mengalami serokonversi menjadi HBeAg negatif setelah periode pengobatan 3 tahun.

Kesimpulan. Terapi analog nukleosida/nukleotida dapat mereduksi derajat fibrosis penyakit hati yang diinduksi oleh virus hepatitis B.

Kata Kunci: Analog nukleosida/nukleotida, hepatitis B kronis, studi kohort 3 tahun

 

Nucleoside/Nucleotide Analogues for the Treatment of Chronic Hepatitis B: A 3-Year Follow Up Study

Introduction. Chronic hepatitis B (CHB) is endemic in Indonesia, where it is usually treated with pegylated interferon and nucleoside/nucleotide analogs (NA). The aim of this study was to determine the efficacy of treating CHB infection among Indonesian patients with NA (lamivudine, telbivudine, and tenofovir) for a 3-year period.

Methods. We retrospectively reviewed the records of patients with CHB infection attending the Hepatology Clinic Cipto Mangunkusumo during 2010-2013 period. Subjects with inclusion criteria were all patients aged above 18 years treated with NA for at least three years. The degree of liver stiffness, hepatitis B virus deoxyribonucleic acid (HBV-DNA), alanine aminotransferase (ALT) levels, and hepatitis B antigen (HBeAg) were assessed before and after 3-years therapy.

Results. A total of 62 subjects were included in the study. Forty-eight patients (77%) were treated with telbivudine, 9 (15%) with tenofovir, and 5 (8%) with lamivudine. At baseline prior to the onset of therapy, 52 patients (84%) had a positive HBeAg test, 15 patients (24%) had F3 liver disease (advance fibrosis), and 36 (58%) had liver cirrhosis using transient elastography. At the end of the 3 year study period, median of liver stiffness significantly decline from baseline (14.5 (3.3 – 59.3) kPa to 6.7 (3.3 – 37.2) kPa, p = 0.001), HBV DNA load significantly decline (1.31 x 107 (2.0x106 – 1.0x108) copies/mL to 0 (0 – 1.7 x 107) copies/mL, p = 0.001), alanine aminotransferase (ALT) levels significantly decline (58 (11– 404) U/L to 27 (8-291) U/L, p = 0.001). Nevertheless, there were five patients (8%) who still had F3 liver disease, and 20 patients (32.3%) had F4 liver disease, 21 (34%) had detectable HBV-DNA, 17 (27%) had not achieved ALT normalization. From 52 patients with positive HBeAg baseline, there were 20 patients (39%) who had seroconversion to negative HBeAg after three year period.
Conclusion. NA therapy resulted in a reduction level of fibrosis in CHB induced liver disease.

Keywords

3-years follow up study, chronic hepatitis B, nucleoside/nucleotide analogue

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