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Abstrak :
HIV coinfection in HCV-infected patients accelerates the course of disease and affects the outcome of Peg-IFN/RBV combination treatment. HCV-HIV coinfected patients are suspected to have HCV mutation in NS5A-ISDR/PKR-BD region that had a role to the successfulness of Peg-IFN/RBV therapy. SNP IL-28B polymorphism is predicted to have an effect on the HCV quasi-species evolution. However, until now the effect of HCV NS5A mutation and SNP IL-28B of the host to the response of treatment is still unclear. This study aimed to determine the presence and role of HCV NS5A-ISDR/PKR-BD region mutation and host SNP IL-28B on the succes of Peg-IFN/RBV combination treatment in HCV-HIV coinfected patients. Prospective cohort study design was conducted in this study. Plasma sample was collected from 22 monoinfected and 134 HCV-HIV coinfected patients prior to therapy. All of them were treated with Peg-IFN/RBV for 48 weeks. The examination of HCV RNA was performed 24 weeks after the end of therapy. PCR nucleotide sequencing was performed after the RNA virus extraction and cDNA synthesis had been performed. Analysis of secondary structure and prediction of mutation function were assessed by PredictProtein (PP) program. Sixteen from thirthy HCV-HIV co-infection patients and none from eight HCV patients achieved SVR. Nonneutral mutation ≥ 1 was found in 23/30 subjects with HCV-HIV co-infection. The presence of nonneutral mutation ≥ 1 was observed more frequent in SVR group than non-SVR group. Nonneutral mutation ≥ 1 was associated with SVR achievement, regardless the monoinfection or coinfection status (p = 0.04). Interaction of CC gene and nonneutral mutation was not associated with SVR. Secondary structure transformation of VHC NS5A was not associated with SVR in coinfected subjects. NS5A binding site structure was different from consensus in SVR group, while the structure was similar to consensus in non-SVR group. Nonneutral mutation ≥ 1 has the most important role on the SVR achievement in patients treated with Peg-IFN/RBV. The interaction of CC-gene and nonneutral mutation was not associated with SVR. The change of secondary structure was also not associated with SVR achievement, however, the changes of NS5A binding site structure were found in HCV-HIV coinfected patients who achieved SVR.

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Koinfeksi HIV pada pasien dengan infeksi VHC dapat memperberat perjalanan penyakit dan memengaruhi keberhasilan terapi kombinasi Peg-IFN/RBV. Pasien koinfeksi VHC-HIV diduga mengalami mutasi VHC pada regio NS5A-ISDR/PKR-BD yang mempunyai peran terhadap keberhasilan terapi Peg-IFN/RBV. Polimorfisme SNP IL-28B diprediksi berpengaruh terhadap evolusi quasi-spesies VHC, namun hingga saat ini keberadaan dan peran mutasi VHC NS5A serta SNP IL-28B pejamu pada koinfeksi VHC-HIV terhadap keberhasilan terapi masih belum diketahui secara jelas. Penelitian ini bertujuan untuk mengetahui keberadaan dan peran mutasi VHC NS5A-ISDR/PKR-BD serta SNP IL-28B pejamu terhadap keberhasilan terapi dengan kombinasi Peg-IFN/RBV pada pasien koinfeksi VHC-HIV. Penelitian ini menggunakan desain studi kohort prospektif. Sampel plasma dikumpulkan dari 22 subjek monoinfeksi dan 134 subjek koinfeksi sebelum menjalani terapi. Seluruh pasien mendapatkan terapi Peg-IFN/RBV selama 48 minggu. Pemeriksaan VHC RNA setelah 24 minggu dari akhir terapi dilakukan untuk menilai respons terapi (sustained virological response/SVR 24). Sekuensing nukleotida menggunakan PCR dilakukan setelah ekstraksi RNA virus dan sintesis cDNA dari sampel plasma. Analisis struktur sekunder dan prediksi fungsi mutasi menggunakan program PredictProtein (PP). Sebanyak 16 pasien dari 30 pasien koinfeksi VHC-HIV yang mengalami SVR serta tidak ada dari 8 pasien monoinfeksi VHC yang mengalami SVR. Mutasi nonnetral ≥ 1 ditemukan pada 23/30 pasien koinfeksi VHC-HIV. Keberadaan mutasi nonnetral ≥ 1 didapatkan lebih tinggi pada kelompok SVR (14 pasien) dibandingkan dengan non-SVR (9 pasien). Mutasi nonnetral ≥1 berhubungan dengan kejadian SVR, tanpa memandang status monoinfeksi dan koinfeksi (p = 0,04). Interaksi antara gen CC dan mutasi nonnetral tidak berhubungan dengan SVR. Perubahan struktur sekunder NS5A tidak berhubungan dengan SVR pada pasien koinfeksi. Struktur binding site NS5A pada kelompok SVR didapatkan berbeda dengan konsensus, sedangkan pada kelompok non-SVR mirip dengan konsensus. Mutasi nonnetral ≥ 1 berperan terhadap kejadian SVR pada pasien yang mendapat terapi Peg-IFN/RBV. Interaksi mutasi nonnetral dan gen CC tidak berhubungan dengan pencapaian SVR. Perubahan struktur sekunder juga tidak berhubungan dengan pencapaian SVR, akan tetapi perubahan struktur binding site NS5A-ISDR/PKR-BD ditemukan pada pasien koinfeksi VHC-HIV yang mencapai SVR dengan terapi Peg-IFN/RBV.

Abstrak :
Latar Belakang: Saat ini hubungan antara kejadian SVR12 pasien hepatitis C, profil lipid, dan steatosis hati masih belum jelas. Hasil publikasi yang ada saat ini masih tidak konsisten mengenai perubahan nilai parameter tersebut pasca SVR12. Di Indonesia sendiri, belum ada penelitian yang mengevaluasi kejadian steatosis hati pasca SVR12, padahal karakteristik populasi di Indonesia berbeda dengan populasi negara lain. Penelitian ini bertujuan untuk meneliti perubahan derajat steatosis hati dan profil lipid pada pasien hepatitis C saat SVR12 dan mencari hubungannya. Metode: Penelitian dengan desain longitudinal, before and after study yang dilakukan di Rumah Sakit Cipto Mangunkusumo (RSCM). Penelitian dilakukan selama 1 tahun di Poliklinik Hepatobilier, Ruang Prosedur Terpadu (RPT) Divisi Hepatobilier. Pasien yang memenuhi kriteria inklusi akan diikutsertakan dan diperiksa profil lipid dan nilai controlled attenuated parameter sebelum dan sesudah terapi. Hasil: Rerata SD sampel penelitian adalah 45±8.78 tahun. Subjek sebagian besar (62%) berjenis kelamin laki-laki. Nilai rerata SD CAP meningkat, sebelum terapi 196±49.36 dB/m dan setelah terapi 227±47.11 dB/m. Nilai rerata SD kolesterol total meningkat, sebelum terapi 166±40.30 mg/dL dan setelah terapi 190±42.58 mg/dL. Nilai rerata SD trigliserida, sebelum terapi 94±45.39 mg/dL dan setelah terapi 109±49.83 mg/dL. Nilai rerata SD HDL meningkat, sebelum terapi 44.4±15.02 mg/dL dan setelah terapi 47.0±17.20 mg/dL. Nilai rerata SD LDL meningkat, sebelum terapi 109.48±39.57 mg/dL dan setelah terapi 130.88±34.32 mg/dL. Tidak ditemukan korelasi korelasi delta berbagai jenis kolesterol dengan delta CAP. Ditemukan adanya korelasi negatif antara nilai CAP pada pasien hepatitis C sebelum terapi dan perubahan nilai CAP sesudah terapi DAA. Terdapat penurunan nilai rerata SD kekakuan hati, sebelum terapi 6.90±2.34 kPa dan setelah terapi 5.35±1.79 kPa. Terdapat penurunan nilai median APRI, sebelum terapi 0.50 (0.3 – 0.7) dan setelah terapi 0.20 (0.20 – 0.30). Simpulan: 1) Terdapat perbedaan derajat steatosis hati sebelum terapi dan saat SVR12 pada pasien hepatitis C yang mendapat terapi DAA. 2) Terdapat perbedaan kadar kolesterol total, kolesterol HDL, kolesterol LDL, dan trigliserida sebelum terapi dan saat SVR12 pada pasien hepatitis C yang mendapat terapi DAA. 3) Tidak terdapat korelasi perubahan kadar kolesterol total, kolesterol HDL, kolesterol LDL, dan trigliserida terhadap derajat steatosis hati saat SVR12. ......Background: Currently, the relationship between hepatitis C patients' SVR12 events, lipid profiles and liver steatosis remains unclear. Current publications are inconsistent regarding the changes in these parameters after SVR12. In Indonesia alone, there are no studies evaluating the incidence of liver steatosis after SVR12, even though the characteristics of the population in Indonesia are different from those in other countries. This study aims to examine changes in the degree of hepatic steatosis and lipid profile in hepatitis C patients during SVR12 and find out the relationship. Method: Longitudinal design, before and after study conducted at Cipto Mangunkusumo Hospital (RSCM). The study was conducted for 1 year at the Hepatobiliary Polyclinic, Integrated Procedure Room of the Hepatobiliary Division. Patients who met the inclusion criteria were included and examined for lipid profile and controlled attenuated parameter values before and after therapy. Results: The mean age SD is 45±8.78 years. Subjects were mostly (62%) male. The mean SD value of CAP increased, before therapy 196±49.36 dB/m and after therapy 227±47.11 dB/m. The mean SD value of total cholesterol increased, before therapy 166±40.30 mg/dL and after therapy 190±42.58 mg/dL. The SD mean value of triglycerides, before therapy 94±45.39 mg/dL and after therapy 109±49.83 mg/dL. The mean SD value of HDL increased, before therapy 44.4±15.02 mg/dL and after therapy 47.0±17.20 mg/dL. The mean SD value of LDL increased, before therapy 109.48±39.57 mg/dL and after therapy 130.88±34.32 mg/dL. There was no correlation between the delta of various types of cholesterol and the delta of CAP. There was a negative correlation between CAP values in hepatitis C patients before therapy and changes in CAP values after DAA therapy. There was a decrease in the mean SD value of liver stiffness, before therapy 6.90±2.34 kPa and after therapy 5.35±1.79 kPa. There was a decrease in the median APRI value, before therapy 0.50 (0.3 - 0.7) and after therapy 0.20 (0.20 - 0.30). Conclusion: 1) There is a difference in the degree of liver steatosis before therapy and after SVR12 in hepatitis C patients who received DAA therapy. 2) There are differences in total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride levels before therapy and after SVR12 in hepatitis C patients who received DAA therapy. 3) There is no effect of changes in total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides before therapy and after SVR12 on the degree of liver steatosis after SVR12.

Abstrak :
Latar belakang: Insidensi dan faktor risiko karsinoma hepatoseluler (KSH) pada pasien hepatitis C virus (HCV) yang sudah mencapai sustained virological response (SVR) pasca terapi direct acting antiviral (DAA) belum banyak diketahui. Mengingat terdapat perbedaan jenis DAA, genotype virus, dan profil pasien di Indonesia, dilakukan studi untuk menilai insidensi dan faktor-faktor yang memengaruhi KSH pada pasien HCV pasca SVR post terapi DAA. Tujuan: Mengetahui insidensi dan faktor-faktor yang memengaruhi kejadian KSH pada pasien HCV yang mencapai SVR pasca pengobatan DAA. Metode: Desain penelitian kohort retrospektif di RSUPN Cipto Mangunkusumo, sampel pasien HCV yang SVR pasca DAA tahun 2017 – 2019, diikuti hingga 2024. Pasien dilakukan skrining USG abdomen, alpha-fetoprotein (AFP) dan CT Scan abdomen 3 fase apabila terdapat indikasi. Dilakukan analisis deskriptif, bivariat dengan Fisher’s exact, dan multivariat dengan regresi logistik bila terdapat faktor risiko di analisis bivariat (p <0,25). Hasil: Dari 180 subjek penelitian, insidensi dan rasio insidensi KSH pada seluruh populasi mencapai 4,4% (rasio insidens 0,91/100PY). Terdapat hubungan signifikan dari analisis bivariat variabel sirosis hepatis (RR 10,5; IK 95% (1,32 – 83,5); p =0,0073) dan DM tipe 2 (RR 8,47; IK 95% (2,3 – 31,1) p = 0,0048). Terdapat hubungan signifikan dari analisis multivariat variabel DM tipe 2 (aRR 3,1; IK 95% (0,86 – 3,83); p=0,002). Kesimpulan: Insidensi KSH mencapai 4,4% dari total populasi. DM tipe 2 memiliki hubungan yang signifikan terhadap kejadian KSH pada pasien HCV yang mencapai SVR pasca pengobatan DAA. ......Background: The incidence and risk factors for hepatocellular carcinoma (HCC) in hepatitis C (HCV) patients who have achieved sustained virological response (SVR) after direct-acting antiviral (DAA) therapy are not well established. Considering there are differences in DAA types, virus genotypes, and patient profiles in Indonesia, this study was conducted to assess the incidence and factors influencing HCC in HCV patients after SVR post DAA therapy. Objective: To determine the incidence and factors influencing HCC in HCV patients achieving SVR after DAA treatment. Method: Retrospective cohort study conducted at Cipto Mangunkusumo National General Hospital, sample of HCV patients had SVR after DAA therapy in 2017 – 2019, followed until 2024. Patients were screened for abdominal ultrasound, alpha-fetoprotein (AFP) and 3-phase abdominal CT scan, if indicated. Descriptive, bivariate analysis with Fisher's exact, and multivariate analysis with logistic regression were conducted. Results: Among 180 subjects, the incidence and incidence ratio of HCC is 4.4% (0.91/100PY). Significant correlation in bivariate analysis from the variables liver cirrhosis (RR 10.5; CI 95% (1. 32 – 83.5); p = 0.0073) and type 2 DM (RR 8.47; CI 95% (2, 3 – 31.1) p = 0.0048). In multivariate analysis, there was significant correlation from type 2 DM variable (aRR 3.1; CI 95% (0.86 – 3.83); p=0.002). Conclusion: The incidence of HCC reaches 4.4% of the total population. Type 2 DM has significant correlation with the incidence of HCC in HCV patients who achieve SVR after DAA treatment.