Endoscopic Management of Pancreatic Fluid Collection in Acute Pancreatitis

Acute pancreatitis is an acute clinical condition where it can be manifested as mild disease or serious and life-threatening condition. There are several factors that may be responsible for this condition, such as genetic, gallstone disease, alcohol consumption, pancreatic trauma, medication, hypertriglyceridemia, autoimmune disease, and surgery. The most common manifestation of pancreatic parenchymal injury is pancreatic pseudocyst (PPC) formation, where peripancreatic fluid collection (PFCs) usually precedes this condition. Even though most of the pseudocyst can be managed conservatively, however in conditions such as infected pseudocyst or possible wall of necrosis (WON), there should be an early intervention management. Clinical evaluation and imaging studies have to be done in the beginning. Computed tomography (CT) scan or magnetic resonance imaging (MRI) are the main imaging techniques used to evaluate the characteristic of the cyst, the size, surrounding vascularity, and to assess the pancreatic duct itself with possible of fistula formation. Clinical conditions that are usually considered for early intervention management are symptomatic pseudocyst, large size of pseudocyst, presence of gastric outlet obstruction, or biliary obstruction. PFC should be evaluated as it has been classified based on type of pancreatitis, time frame, well-defined wall, and debris contained inside the cyst. Endoscopic management has replaced percutaneous and surgical approach in most of PFC cases. Nowadays, endoscopic ultrasound (EUS) has been widely used as the first-line tool for PFC drainage procedure. Pancreatic pseudocyst stenting is the most common procedure in most of the centers in the world. However, the cost, availability, and expertise are needed to be considered in clinical practice

The New Era of Immunotherapy in Bile Duct Cancer Management

Bile duct carcinoma or well known as cholangiocarcinoma (CCA) is the second most common of primary liver malignancy after hepatocellular carcinoma (HCC). Although cholangiocarcinoma is a rare cancer, it has an aggressive feature with very poor prognosis. The epidemiological profile of cholangiocarcinoma varies widely across the world, which is reflecting the exposure of different risk factors, such as chronic inflammatory disease of the biliary tract, specific infectious disease, and congenital malformation. Diagnosis of CCA is quite challenging. CCA is generally asymptomatic in the early stages. Therefore, the management of this malignancy is often delayed due to late diagnosed, where the metastasis has already present or even when it is causing bile duct obstruction. Treatment for CCA is often difficult and should be managed in the tertiary referral hospital with a multidisciplinary team approach. Surgical treatment with complete resection could be benefit only for patient with early stage of the disease. Other treatment modalities as adjuvant therapy are also have been developed to improve survival of the patient, such as chemotherapy, radiotherapy, molecular targeted therapy, targeting angiogenesis and EGFR, and immunotherapy. Recently, immunotherapy has also been developed as a new cancer treatment option and showed a promising result. Whether immunotherapy can be useful for treatment biliary malignancy is still controversial. Hence, a lot of studies is still required to confirm the preliminary findings

Clinical Profile of Cirrhotic Patient with Esophageal Varices Who Undergone Band Ligation in Cipto Mangunkusumo Hospital

Introduction. Liver cirrhosis (LC) is the end stage of chronic liver disease. One of the main complication caused by LC is esophageal varices (EV). Bleeding due to EV rupture is the main cause of mortality in patient with LC. EV band ligation can be used for primary or secondary prophylaxis to prevent bleeding. The purpose of this study was to know the clinical profile of LC patient with EV who underwent band ligation and who not underwent band ligation. Methods. A cross-sectional study was conducted in LC patients who underwent esophagogastroduodenoscopy (EGD) in Procedure Room Division of Hepatobiliary, Departement of Internal Medicine, Cipto Mangunkusumo Hospital from 2016 to 2017. Results. During January 2016-December 2017, a total of 313 patients underwent EGD. Most of them ( 73.2%) were male and predominantly > 60 years (34,2%). Most common LC etiology was hepatitis B (51.8%., There were 22% subjects with hepatocellular carcinoma (HCC). EV band ligations were done in 146 (46.7%) patients. In the ligation group, 56.2% patients were from outpatient clinic. The most common EGD indication (39%) was evaluation from previous ligation. Of 41.8% patients had Child-Turcotte-Pugh (CTP) class-A condition, 82.9% patients had MELD score < 15, 61.6% patients had large EV, 22.1% had red color sign (RCS) and 84,9% patients had portal hypertensive gastropathy. There were significant differences in CTP class, ascites, platelet, bilirubin, and albumin between ligation group compare to non-ligation group. Conclussion. Most of LC patients who underwent EV band ligation had CTP class-A, came from the outpatient clinic. The main finding in EGD was large EV with portal hypertensive gastropathy. There were significant differences in liver functions between patient in ligation group compared to patient in non-ligation group

APASL HCV guidelines of virus-eradicated patients by DAA on how to monitor HCC occurrence and HBV reactivation

In the direct-acting antiviral (DAA) era for hepatitis C virus (HCV) infection, sustained virological response (SVR) is very high, but close attention must be paid to the possible occurrence of hepatocellular carcinoma (HCC) and reactivation of hepatitis B virus (HBV) in patients with co-infection who achieved SVR in short term. HCC occurrence was more often observed in patients with previous HCC history. We found occurrence of HCC in 178 (29.6%) of 602 patients with previous HCC history (15.4 months mean follow-up post-DAA initiation) but, in contrast, in only 604 (1.3%) of 45,870 patients without previous HCC history (18.2 months mean follow-up). Thus, in these guidelines, we recommend the following: in patients with previous HCC history, surveillance at 4-month intervals for HCC by ultrasonography (US) and tumor markers should be performed. In patients without previous HCC history, surveillance at 6- to 12-month intervals for HCC including US is recommended until the long-term DAA treatment effects, especially for the resolution of liver fibrosis, are confirmed. This guideline also includes recommendations on how to follow-up patients who have been infected with both HCV and HBV. When HCV was eradicated in these HBsAg-positive patients or patients with previous HBV infection (anti-HBc and/or anti-HBs-positive), it was shown that HBV reactivation or HBV DNA reappearance was observed in 67 (41.4%) of 162 or 12 (0.9%) of 1317, respectively. For these co-infected patients, careful attention should be paid to HBV reactivation for 24 weeks post-treatment

APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing

The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on “APASL consensus statements and recommendations for management of hepatitis C” in March 2015 to revise the “APASL consensus statements and management algorithms for hepatitis C virus infection” (Hepatol Int 6:409–435, 2012). The working party consisted of expert hepatologists from the Asian–Pacific region gathered at the Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed, and debated during the course of drafting a revision. Participants of the consensus meeting assessed the quality of the cited studies. The finalized recommendations for hepatitis C prevention, epidemiology, and laboratory testing are presented in this review

Technique innovation of endoscopic ultrasound portal pressure gradient measurement using standard manometer set for portal hypertension assessment

Abstract Portal hypertension (PH) is still a major challenge to be managed in clinical practice. However, hepatic vein pressure gradient (HVPG) measurement is not always reliable for portal hypertension (PH) diagnosis. This study showed the impact of endoscopic ultrasound (EUS) as a promising tool for diagnosis and management PH condition

Association between the severity of liver cirrhosis with quality of life and its impact on clinical practice

Abstract Introduction Liver cirrhosis (LC) has a significant impact in quality of life, and it is frequently linked to loss of a job, mood fluctuations, anxiety, low self-esteem, and despair. Recent LC treatment primarily focuses on clinical manifestations rather than the patient’s quality of life. By analyzing quality of life, one can learn about the disease’s emotional, physical, and lifestyle effects. Objectives To find the relationship between quality of life with the severity of liver cirrhosis. Methods The research was conducted as an observational study with cross-sectional data being collected. The study’s participants were recruited from Saiful Anwar Hospital’s outpatient and inpatient clinics. The individuals completed a chronic liver disease questionnaire to assess their quality of life, and the Child-Pugh score was used to determine the severity of their liver disease. The data was analyzed using Kruskal-Wallis and the rank Spearman test, with a significance level of 0.05. Result There were 54 individuals, with an average age of 53.71 years and a male-to-female ratio of 74%. The results showed that there was a significant difference between the Child-Pugh A, Child-Pugh B, and Child-Pugh C groups in all aspects of the chronic liver disease questionnaire (p = 0.000). The rank Spearman test revealed a substantial link between quality of life and liver cirrhosis severity (r: −0.817). Conclusion The severity of LC is associated with the quality of life of the patients

Endoscopic Management Using Novel Haemostatic Agents for Immediate Bleeding during Endoscopic Retrograde Cholangio-Pancreatography

Bleeding after endoscopic sphincterotomy (ES) remains as a major challenge during ERCP procedure. Standard endoscopic haemostatic procedures have demonstrated good performance for bleeding control. Novel endoscopic haemostatic agents have also been widely used in gastrointestinal bleeding management. Regardless, there is still a paucity of high-quality evidence evaluating the practicality of these agents in ERCP. This case series study was performed on the patients who underwent ERCP procedure in a tertiary referral private hospital within 2 years period. Post-ES immediate bleeding is defined as the onset of bleeding at the time of sphincterotomy. Treatment groups for post-ES bleeding are divided into (1) standard haemostatic methods and (2) novel haemostatic agents. There were 40 patients who received standard haemostatic treatment and 60 patients who received novel haemostatic agents. Initial haemostasis was achieved in all patients. Two patients who received standard haemostatic treatment had rebleeding. Meanwhile, no patients in novel haemostatic treatment group had rebleeding. In conclusion, novel haemostatic agent can be considered as an easy and practical method in daily practice, especially when an ERCP procedure is performed. Further studies with larger sample size which, if possible, can also include a cost-effectiveness analysis are still required to implement these agents as a standard procedure in clinical practice. (This abstract has been presented at the American College of Gastroenterology meeting October 2021)

Combination of Sofosbuvir-Ledipasvir and Sofosbuvir- Daclatasvir for Treatment HCV Patients in Indonesia

Introduction. Direct-acting antivirals (DAAs) has been developed for treatment hepatitis C virus (HCV). Therapy of HCV using DAA has shown high sustained virologic response (SVR) and shortening duration of therapy. Sofosbuvir-ledipasvir (SOF/LDV) is fixed dose combination tablet of DAAs which recommended for genotype 1, 4, 5, and 6 infected patients. In developing countries, SOF/LDV still can be used as cost-effective regimen in all genotype compared with sofosbuvir-daclatasvir (SOF/ DCV). This study aimed to evaluate the efficacy of combination sofosbuvir-ledipasvir in all genotypes of HCV patients compared with available DAA in Indonesia (sofosbuvir- daclatasvir). Methods. A retrospective study was conducted among patients who received HCV therapy in Klinik Hati and Cipto Mangunkusumo Hospital during January until December 2017. Demographic data, baseline characteristics virus, and baseline characteristics laboratory were collected from medical record. Quantitative polymerase chain reaction (PCR) for Jurnal Penyakit Dalam IndonesiaJurnal Penyakit Dalam Indonesia Volume 10 Issue 4 Article 3 12-31-2023 Kombinasi Sofosbuvir-Ledipasvir dan Sofosbuvir- DaclatasvirKombinasi Sofosbuvir-Ledipasvir dan Sofosbuvir- Daclatasvir pada Pengobatan Pasien Hepatitis C di Indonesiapada Pengobatan Pasien Hepatitis C di Indonesia Andri Sanityoso Sulaiman DrHepatobiliary Division, Medical Staff Group of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia., [email protected] Irsan Hasan DrHepatobiliary Division, Medical Staff Group of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia., [email protected] Cosmas Rinaldi Adithya Lesmana DrHepatobiliary Division, Medical Staff Group of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia., [email protected] Juferdy Kurniawan DrHepatobiliary Division, Medical Staff Group of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia., [email protected] Gita ApriliciaHepatobiliary Division, Medical Staff Group of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia., [email protected] See next page for additional authors Follow this and additional works at: https://scholarhub.ui.ac.id/jpdi Part of the Internal Medicine Commons, and the Virus Diseases Commons Recommended CitationRecommended Citation Sulaiman, Andri Sanityoso Dr; Hasan, Irsan Dr; Lesmana, Cosmas Rinaldi Adithya Dr; Kurniawan, Juferdy Dr; Aprilicia, Gita; Nugroho, Yayah Dr; Wahyuni, Nunuk Tri Dr; and Sulaiman, Budiman Sujatmika (2023) "Kombinasi Sofosbuvir-Ledipasvir dan Sofosbuvir- Daclatasvir pada Pengobatan Pasien Hepatitis C di Indonesia," Jurnal Penyakit Dalam Indonesia: Vol. 10: Iss. 4, Article 3. DOI: 10.7454/jpdi.v10i4.1501 Available at: https://scholarhub.ui.ac.id/jpdi/vol10/iss4/3 This Original Article is brought to you for free and open access by the Faculty of Medicine at UI Scholars Hub. It has been accepted for inclusion in Jurnal Penyakit Dalam Indonesia by an authorized editor of UI Scholars Hub. Kombinasi Sofosbuvir-Ledipasvir dan Sofosbuvir- Daclatasvir pada PengobatanKombinasi Sofosbuvir-Ledipasvir dan Sofosbuvir- Daclatasvir pada Pengobatan Pasien Hepatitis C di IndonesiaPasien Hepatitis C di Indonesia AuthorsAuthors Andri Sanityoso Sulaiman Dr, Irsan Hasan Dr, Cosmas Rinaldi Adithya Lesmana Dr, Juferdy Kurniawan Dr, Gita Aprilicia, Yayah Nugroho Dr, Nunuk Tri Wahyuni Dr, and Budiman Sujatmika Sulaiman This original article is available in Jurnal Penyakit Dalam Indonesia: https://scholarhub.ui.ac.id/jpdi/vol10/iss4/3 LAPORAN PENELITIAN183Jurnal Penyakit Dalam Indonesia | V o l . 10, No. 4 | Desember 2 0 2 3 | Kombinasi Sofosbuvir-Ledipasvir dan Sofosbuvir- Daclatasvir pada Pengobatan Pasien Hepatitis C di Indonesia Combination of Sofosbuvir-Ledipasvir and Sofosbuvir- Daclatasvir for Treatment HCV Patients in Indonesia Andri Sanityoso Sulaiman1,2, Irsan Hasan1, Cosmas Rinaldi Adithya Lesmana1, Juferdy Kurniawan1, Gita Aprilicia1, Yayah Nugroho2, Nunuk Tri Wahyuni2, Budiman Sujatmika Sulaiman2 1Divisi Hepatobilier, Departemen Ilmu Penyakit Dalam, Fakultas Kedokteran Universitas Indonesia/RSUPN Dr. Cipto Mangunkusumo, Jakarta 2Klinik Hati Prof Ali Sulaiman, Jakarta Korespondensi: Andri Sanityoso Sulaiman. Divisi Hepatobilier, Departemen Ilmu Penyakit Dalam, Fakultas Kedokteran Universitas Indonesia/RSUPN Dr. Cipto Mangunkusumo, Jakarta, Indonesia. Email: [email protected] ABSTRAK Pendahuluan. Direct-acting antivirals (DAAs) telah dikembangkan untuk pengobatan virus hepatitis C (VHC). Terapi hepatitis C dengan menggunakan DAA telah menunjukkan respons virologis berkelanjutan yang tinggi (sustained virologic response/SVR) dan durasi terapi yang lebih singkat. Sofosbuvir-ledipasvir (SOF/LDV) adalah tablet kombinasi DAA dengan dosis tetap yang direkomendasikan untuk pasien yang terinfeksi genotipe 1, 4, 5, dan 6. Di negara berkembang, SOF/LDV masih dapat digunakan sebagai obat paduan dengan biaya yang lebih ekonomis untuk semua genotipe dibandingkan dengan sofosbuvir-daclatasvir (SOF/DCV). Tujuan dari penelitian ini adalah untuk mengevaluasi efikasi kombinasi sofosbuvir- ledipasvir pada semua genotipe pasien hepatitis C dibandingkan dengan DAA yang tersedia di Indonesia (sofosbuvir- daclatasvir). Metode. Penelitian ini merupakan penelitian retrospektif terhadap pasien yang mendapatkan terapi hepatitis C di Klinik Hati dan Rumah Sakit Cipto Mangunkusumo pada periode Januari hingga Desember 2017. Data demografi, karakteristik awal virus, dan karakteristik awal laboratorium dikumpulkan dari rekam medis. Polymerase chain reaction (PCR) kuantitatif untuk muatan virus hepatitis C dinilai pada titik akhir penelitian. Efikasi SOF/LDV dan SOF/DCV dilakukan dengan respons virologis yang berkelanjutan pada minggu ke-12 (SVR-12). Hasil. Sebanyak 214 pasien hepatitis C diikutsertakan dalam penelitian ini. Sebanyak 69 pasien diobati dengan SOF/LDV, sedangkan 145 pasien diobati dengan SOF/DCV. Pada kelompok SOF/LDV, sebanyak 20 (29%) pasien memiliki pengalaman terapi, 9 (13%) menerima terapi 24 minggu, dan 26 (37,7%) pasien memiliki sirosis. Pada kelompok SOF/DCV, 24 (16,6%) pasien memiliki pengalaman terapi, 38 (26,2%) menerima terapi 24 minggu, dan 41 (28,3%) pasien memiliki sirosis. Pasien hepatitis C didominasi oleh genotipe 1 pada kedua kelompok SOF/LDV dan SOF/DCV (63,7 vs. 67,6%). Virus hepatitis C tidak terdeteksi pada seluruh pasien setelah terapi kombinasi SOF/LDV, dengan angka SVR-12 adalah 69/69 (100%). Sementara itu, angka SVR-12 mencapai 142/145 (97,9%) pada kelompok SOF/DCV. Kesimpulan. SOF/LDV efektif pada semua genotipe pasien hepatitis C dan biaya kombinasi dosis tunggal SOF/LDV lebih terjangkau bagi pasien di negara berkembang dibandingkan dengan rejimen SOF/DCV. Kata Kunci: Direct-acting antivirals (DAAs), sofosbuvir-daclatasvir (SOF/DCV), sofosbuvir-ledipasvir (SOF/LDV), SVR-12, virus hepatitis C ABSTRACT Introduction. Direct-acting antivirals (DAAs) has been developed for treatment hepatitis C virus (HCV). Therapy of HCV using DAA has shown high sustained virologic response (SVR) and shortening duration of therapy. Sofosbuvir-ledipasvir (SOF/LDV) is fixed dose combination tablet of DAAs which recommended for genotype 1, 4, 5, and 6 infected patients. In developing countries, SOF/LDV still can be used as cost-effective regimen in all genotype compared with sofosbuvir-daclatasvir (SOF/ DCV). This study aimed to evaluate the efficacy of combination sofosbuvir-ledipasvir in all genotypes of HCV patients compared with available DAA in Indonesia (sofosbuvir- daclatasvir). Methods. A retrospective study was conducted among patients who received HCV therapy in Klinik Hati and Cipto Mangunkusumo Hospital during January until December 2017. Demographic data, baseline characteristics virus, and baseline characteristics laboratory were collected from medical record. Quantitative polymerase chain reaction (PCR) for 184| Jurnal Penyakit Dalam Indonesia | V o l . 10, No. 4 | Desember 2 0 2 3 Andri S. Sulaiman, Irsan Hasan, C.R.A Lesmana, Juferdy Kurniawan, Gita Aprilicia,Yayah Nugroho, Nunuk Tri Wahyuni, Budiman S. Sulaiman HCV RNA were assessed at the end point of study. The efficacy of SOF/LDV and SOF/DCV were carried out by sustained virological response at 12 weeks (SVR-12). Results. A total of 214 HCV patients were include in this study. Sixty-nine patients treated with SOF/LDV, whereas 145 patients treated with SOF/DCV. In group of SOF/LDV, 20 (29%) patients had an experience therapy, 9 (13%) received 24-week therapy, 26 (37.7%) patients observed with cirrhosis. In group of SOF/DCV, 24 (16.6%) patients had an experience therapy, 38 (26.2%) received 24-week therapy, 41 (28.3%) patients observed with cirrhosis. The patients were dominated by HCV genotype 1 in both of group SOF/LDV and SOF/DCV (63.7% vs. 67.6%). All patients had undetected HCV RNA virus after the combination therapy of SOF/LDV, with the SVR-12 rate was 69 (100%) patients. Meanwhile, SVR-12 rate was achieved in 142 (97.9%) patients in group SOF/DCV. Conclusion. SOF/LDV is effective in all genotype of HCV patients and the cost fix dose combination of SOF/LDV more affordable to patients in developing countries compared with SOF/DCV regimen. Keywords: Direct acting antiviral agents (DAAs), HCV, sofosbuvir-daclatasvir (SOF/DCV), sofosbuvir-ledipasvir (SOF/LDV), SVR-12 PENDAHULUAN Infeksi hepatitis C telah menjadi epidemi global. Pada tahun 2015, World Health International (WHO) memperkirakan bahwa 71 juta penduduk dunia terinfeksi hepatitis C kronis.1 Total kematian terkait hepatitis C mencapai 399.000 penduduk pada tahun 2018, yang sebagian besar disebabkan oleh karsinoma hepatoseluler dan sirosis akibat infeksi virus hepatitis C.2 Virus hepatitis C (VHC) ditandai dengan variabilitas genetik yang beragam. Terdapat 7 genotipe dan lebih dari 67 subtipe VHC yang telah teridentifikasi di seluruh dunia.3 Genotipe yang paling banyak ditemukan di Indonesia adalah genotipe 1, dengan prevalensi diperkirakan 62,7%, diikuti oleh genotipe 2 (16,4%), genotipe 3 (13,0%), dan sebagian kecil genotipe 4 (2,7%), genotipe 5 (0,9%), dan genotipe 6 (1,3%).4 Genotipe 1 adalah genotipe yang paling sulit diobati dengan obat paduan pegylated interferon/ ribavirin (Peg-IFN/RBV). Sebuah studi oleh Juniastuti5 di Indonesia melaporkan bahwa hanya 73,5% pasien mencapai early virological response (EVR) dan sustained virological response (SVR) setelah pengobatan dengan Peg-IFN/RB. Sejak tahun 2016, direct acting antiviral agent (DAA) diusulkan menjadi pengobatan standar baru untuk pasien hepatitis C di Indonesia. Penemuan DAA telah mengubah pengobatan hepatitis C dengan meningkatkan sustained virologic response (SVR) dan memperpendek durasi pengobatan.6 Pencapaian SVR setelah pengobatan dengan DAA dikaitkan dengan berkurangnya risiko penyakit hati dan komplikasinya, termasuk dekompensasi sirosis, karsinoma hepatoseluler, dan kematian.7 Beberapa obat paduan kombinasi sofosbuvir (SOF) telah menunjukkan efektivitas dan keamanan yang unggul untuk mengobati infeksi VHC kronis. Secara khusus, kombinasi SOF dengan inhibitor protein nonstruktural 5A (NS5A), misalnya ledipasvir (LDV), daclatasvir (DCV), atau velpatasvir (VEL) telah menunjukkan efektivitas tinggi dengan tingkat SVR pada 12 minggu pasca pengobatan mencapai 80-90%.8 Sebagian besar data tentang efektivitas DAA pada pasien hepatitis C berasal dari negara barat, hanya sedikit data yang diperoleh dari negara di Asia, khususnya Indonesia. Penelitian ini bertujuan untuk mengetahui efektivitas kombinasi Sofosbuvir-Ledipasvir pada semua genotipe pasien hepatitis C dibandingkan dengan DAA yang tersedia di Indonesia (sofosbuvir- daclatasvir). METODE Semua pasien dewasa dengan hepatitis C positif berusia di atas 18 tahun yang diobati dengan sofosbuvir di Klinik Hati Prof Ali Sulaiman dan Rumah Sakit Cipto Mangunkusumo pada periode Januari hingga Desember 2017 diikutsertakan dalam penelitian ini secara retrospektif. Kriteria eksklusi adalah pasien dalam masa kehamilan, pasien dengan keganasan, dan pasien dengan adanya gangguan ginjal. Sumber data serial kasus SOF/ LDV hanya diperoleh dari Klinik Hati Prof Ali Sulaiman, sedangkan data serial kasus SOF/DCV diperoleh dari Klinik Hati Prof Ali Sulaiman dan Rumah Sakit Cipto Mangunkusumo. Pada kelompok pertama, pasien menerima kombinasi SOF/LDV dengan dosis tetap tunggal secara oral (90 mg ledipasvir dan 400 mg sofosbuvir). Pada kelompok lain, pasien menerima SOF/DCV (60 mg daclatasvir dan 400 mg sofosbuvir). Jika pasien memiliki koinfeksi dengan human immunodeficiency virus (HIV), pasien menerima penyesuaian dosis daclatasvir 90 mg. Durasi pemberian DAA pada regimen SOF/DCV diberikan selama 12 minggu atau 24 minggu tergantung pada adanya sirosis hati. Sementara pada regimen SOF/LDV, sebagian besar pasien diberikan terapi selama 12 minggu dan ditambahkan menjadi 24 minggu pengobatan sesuai dengan kesanggupan pembiayaan pasien. Sebelum terapi, beberapa pemeriksaan klinis dan laboratorium dilakukan. Viral load HCV RNA, genotipe, riwayat terapi sebelumnya, ada tidaknya sirosis, riwayat diabetes melitus, dan kekakuan hati dikumpulkan 185Jurnal Penyakit Dalam Indonesia | V o l . 10, No. 4 | Desember 2 0 2 3| Kombinasi Sofosbuvir-Ledipasvir dan Sofosbuvir-Daclatasvir pada Pengobatan Pasien Hepatitis C di Indonesia sebelum terapi. Efikasi utama SOF/LDV dan SOF/DCV dilakukan dengan SVR-12 (tingkat SVR pada 12-minggu paska pengobatan). SVR didefinisikan sebagai virus yang tidak terdeteksi setelah dinilai dengan polymerase chain reaction (PCR) kuantitatif untuk RNA HCV. Analisis statistik dilakukan dengan menggunakan SPSS versi 25. Data dinyatakan sebagai rerata [simpang baku (SB)] atau median (rentang) untuk data kontinu dan dinyatakan sebagai proporsi n (%) untuk data kategorikal. Perbandingan antarkelompok dinilai dengan uji t-test independent atau uji Man-Whitney untuk data kontinu dan uji chi square untuk data kategorik. Nilai p<0,05 dianggap signifikan secara statistik. Penelitian ini telah disetujui oleh Komite Etik Fakultas Kedokteran Universitas Indonesia (no: 0068/ UN2.F1/ETIK/2018, nomor protokol: 17-12-1208) HASIL Sebanyak 214 pasien hepatitis C yang mendapat terapi sofosbuvir diikutsertakan dalam penelitian ini. Sebanyak 69 pasien menerima SOF/LDV dan 145 pasien menerima SOF/DCV (Tabel 1). Pada kelompok SOF/LDV, sebagian besar pasien dalam penelitian ini menerima terapi selama 12 minggu (87%), sementara sisanya menerima terapi kombinasi selama 24 minggu. Lebih dari 1/3 dari total pasien (37,7%) didiagnosis sirosis, sedangkan median kekakuan hati pada subjek penelitian ini adalah 11,80 kPa (3,60 - 49,70 kPa). Sebagian besar subjek tidak memiliki riwayat diabetes melitus (DM), hanya 6 pasien (8,7%) yang memiliki riwayat DM. Koinfeksi HIV tercatat pada 1 pasien (1,4%). Pada kelompok SOF/ DCV, pasien yang menerima terapi selama 12 minggu lebih rendah dibandingkan kelompok SOF/LDV (masing- masing 73,8% vs. 87%) dan pada sirosis hati lebih rendah dibandingkan kelompok SOF/LDV (masing-masing 28,3% vs. 37,7%). Median kekakuan hati pada SOF/DCV adalah 12,30 kPa (5,2 - 37,4 kPa). Pada kelompok pasien dengan SOF/DCV, sebanyak 10 (6,9%) pasien memiliki riwayat DM dan sebanyak 14 (9,7%) memiliki koinfeksi HIV. Pasien didominasi oleh HCV genotipe 1, baik pada kelompok SOF/LDV maupun SOF/DCV [44 (63,7%) pasien vs. 98 (67,6%)]. Rerata tingkat RNA HCV yang terdeteksi pada subjek sebelum pemberian terapi SOF/LDV dan SOF/ DCV memiliki viral load yang sama [1,14 x 106 (1,43 x 102 - 4,39 x 107) vs. 3,67 x 105 (1,29 x 103 - 1,49 x 108); p=0,639]. Semua pasien tidak terdeteksi virus RNA HCV setelah terapi kombinasi SOF/LDV, dengan proporsi SVR-12 adalah 69 (100%) pasien. Hanya sebagian kecil dari total subjek pengobatan kelompok SOF/LDV yang membutuhkan durasi terapi yang lama untuk mencapai SVR (24 minggu), yaitu 9 dari 69 pasien SOF/LDV. Proporsi SVR-12 pada kelompok SOF/DCV adalah 142 (97,9%) pasien. Dari 3 pasien non- SVR-12 pada kelompok SOF/DCV adalah genotipe 3 dan menerima terapi selama 12 minggu. Salah satu dari pasien yang gagal terapi memiliki koinfeksi. Analisis angka SVR-12 berdasarkan genotipe HCV dilakukan dalam penelitian ini (Gambar 1). DISKUSI Penemuan DAA sebagai modalitas terapi merupakan salah satu pondasi penting dalam penatalaksanaan hepatitis C. Terapi dengan DAA menunjukkan hasil SVR yang lebih baik, durasi pengobatan yang lebih singkat secara signifikan, dan menunjukkan profil toksisitas yang cukup rendah. Terapi DAA juga terbukti berhasil pada pasien hepatitis C yang tidak dapat menerima pengobatan interferon (misalnya intoleransi interferon, sirosis lanjut, dan adanya komorbiditas).9 Genotipe yang paling sering ditemui pada penelitian ini adalah genotipe 1. Distribusi genotipe ini serupa dengan penelitian lain yang dilakukan di Indonesia, dengan prevalensi genotipe 1 berkisar antara 46,7-64,4%.10-12 Genotipe 1 adalah genotipe yang paling sulit diobati dengan obat paduan interferon.13 Pada penelitian ini, meskipun mayoritas infeksi adalah genotipe 1, pemberian SOF/LDV dan SOF/DCV menunjukkan hasil yang baik (angka SVR-12: 100% vs. 97,9%). Hasil ini didukung oleh penelitian yang dilakukan di Thailand, dengan tingkat SVR- 12 secara keseluruhan yang dicapai adalah 98,0% (IK95%: 96,7-98,8%) dan SVR-12 pada obat paduan kombinasi SOF/LDV ialah 97,9% (IK95%: 94,8-99,2%).8 Pada penelitian ini, 100% SVR-12 tercapai pada 69 pasien dengan variasi genotipe HCV yang diobati dengan SOF/LDV, sedangkan terdapat tiga pasien yang gagal mencapai SVR-12 pada pengobatan kelompok SOF/DCV. Meskipun tidak terdapat perbedaan yang signifikan dalam hasil SVR-12 antara kelompok SOF/DCV dan kelompok SOF/ LDV, perlu diketahui bahwa kelompok SOF/DCV memiliki jumlah sampel yang lebih besar (n=145) dibandingkan dengan kelompok sofosbuvir-ledipasvir (n=69). Dalam analisis statistik, peningkatan jumlah sampel dapat memengaruhi hasil dan meningkatkan kemungkinan deteksi perbedaan yang kecil antarkelompok. Tiga pasien yang gagal mencapai SVR-12 memiliki HCV genotipe 3. Hepatitis C Virus Therapeutic Registry and Research Network (HCV-TARGET) melaporkan bahwa HCV genotipe 3 masih menjadi tantangan untuk diobati, terutama pada pasien dengan sirosis.14 Genotipe 3 merupakan genotipe yang unik di antara genotipe-genotipe virus hepatitis C karena memiliki angka steatosis yang lebih tinggi, perkembangan fibrosis yang lebih cepat, dan 186| Jurnal Penyakit Dalam Indonesia | V o l . 10, No. 4 | Desember 2 0 2 3 Andri S. Sulaiman, Irsan Hasan, C.R.A Lesmana, Juferdy Kurniawan, Gita Aprilicia,Yayah Nugroho, Nunuk Tri Wahyuni, Budiman S. Sulaiman Tabel 1. Parameter demografis dan klinis awal pasien hepatitis C Variabel Sofosbuvir-ledipasvir (n=69) Sofosbuvir-daclatasvir (n=145) Nilai p Usia (tahun), rerata (SB) 51,1 (15,66) 51,9 (14,82) 0,696 Pria, n (%) 40 (58,0) 94 (64,8) 0,413 Terapi, n (%) Pengobatan terdahulu 20 (29) 24 (16,6) 0,055 Naif 49 (71) 121 (83,4) Durasi pengobatan, n (%) 24 minggu 9 (13) 38 (26,2) 0,046 12 minggu 60 (87) 107 (73,8) Sirosis, n (%) 26 (37,7) 41 (28,3) 0,219 Kekakuan hati (kPa), median (RIK) 11,80 (3,60 – 49,70) 12,30 (5,2 – 37,4) 0,149 Diabetes melitus, n (%) 6 (8,7) 10 (6,9) 0,850 Koinfeksi HIV, n (%) 1 (1,4) 14 (9,7) 0,056 Karakteristik dasar virus hepatitis C HCV RNA awal, median (RIK) 1,14 x 106 (1,43 x 102 – 4,39 x 107) 3,67 x 105 (1,29 x 103 – 1,49 x 108) 0,639 GenotIpe, n (%) 1/1a/1b/1c 11 (15,9)/ 12 (17,4)/ 20 (29)/ 1 (1,4) 28 (19,3)/ 32 (22,1)/ 33 (22,8)/ 5 (3,4) 0,062 2/ 2a/ 2c 4 (5,8%) / - / - 4 (2,8)/ 3 (2,1)/ 1 (0,7) 3 / 3a / 3f / 3k 5 (7,2)/ 1 (1,4)/ - / - 9 (6,2)/ 6 (4,1)/ 1 (0,7)/ 5 (3,4) 4/4a/4c/4h 4 (5,8)/ 2 (2,9)/ 1 (1,4) 1 (0,7)/ - / - / 3 (2,1) Indeterminan 8 (11,6) 8 (5,5) Tidak diketahui - 6 (4,1) Karakteristik dasar laboratorium Trombosit, rerata (SB) 200 (66,53) 103/μL 171 (94,14) 103/μL 0,145 Bilirubin, median (RIK) 0,70 (0,10 – 4,05) mg/dL 0,82 (0,16 – 4,41) mg/dL 0,583 SGOT, median (RIK) 68 (12 – 336) U/L 53 (20 – 245) U/L 0,097 SGPT, median (RIK) 69 (7 – 327) U/L 47 (3 – 204) U/L 0,173 Kreatinin, rerata (SB) 0,92 (0,24) mL/min 0,92 (0,27) mL/min 0,269 Albumin, median (RIK) 4,20 (2,6 – 4,9) g/dL 4,23 (2,5 – 5,0) g/dL 0,880 Luaran terapi SVR-12, n (%) Ya 69 (100) 142 (97,9) 0,561 Tidak 0 (0) 3 (2,1) SB= simpang baku; RIK= rentang interkuartil Gambar 1. Tingkat SVR-12 berdasarkan genotipe virus hepatitis C Rerata SVR-12 (%) 187Jurnal Penyakit Dalam Indonesia | V o l . 10, No. 4 | Desember 2 0 2 3| Kombinasi Sofosbuvir-Ledipasvir dan Sofosbuvir-Daclatasvir pada Pengobatan Pasien Hepatitis C di Indonesia angka kesembuhan yang lebih rendah.15 Dalam penelitian ini, efektivitas SOF/DCV pada pasien hepatitis C genotipe 3 lebih rendah dibandingkan dengan obat paduan SOF/ LDV (3/21 pasien genotipe-3 yang diobati dengan SOF/ DCV tidak dapat mencapai SVR-12). Salah satu dari pasien yang mengalami kegagalan terapi pada pasien dengan genotipe 3 adalah pasien dengan koinfeksi HIV. Koinfeksi HIV dapat menjadi salah satu faktor yang memengaruhi respons pengobatan. Pasien dengan koinfeksi HIV memiliki karakteristik klinis yang berbeda akibat adanya kondisi imunosupresif yang dapat memengaruhi respons pen

National Consensus on Portal Hypertension Management in Indonesia

Portal hypertension is a clinical syndrome that consists of hypersplenism, ascites, gastroesophageal varices, and encephalopathy. This condition is marked by increased portal pressure gradient and may occur with or without liver cirrhosis. To date, portal hypertension remains as the leading cause of severe complications and death of a patient with chronic liver disease, especially liver cirrhosis. Therefore, thorough understanding about management of portal hypertension is strongly required, especially considering that many complications of portal hypertension require early diagnosis and treatment to improve the prognosis of the patients. Additionally, although hepatic venous pressure gradient (HVPG) measurement has become a gold standard procedure for measuring portal pressure in the last twenty years, utilization of this method in Indonesia has been hindered by reluctance of the patients due to its invasiveness, high cost, and limited availability. This consensus is developed with evidence-based medicine principles to provide a guideline for portal hypertension management for general practitioners, specialists, and consultants, to achieve better clinical outcomes of portal hypertension in Indonesia.  Keywords: portal hypertension, liver cirrhosis, chronic liver diseas