NASKAH LENGKAP Liver Update and The Scientific Meeting of ...staff.ui.ac.id/system/files/users/rino.gani/publication/2018... · Wilson’s disease, primary biliary cirrhosis and family

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TIM EDITOR :Rino Alvani Gani

Irsan HasanC. Rinaldi A. Lesmana

PERHIMPUNAN PENELITI HATI INDONESIA

NASKAH LENGKAP The 11th Liver Update and

The Scientific Meeting of INA ASL/PPHIIn Conjunction with

The 7th China-Indonesia Joint Symposium onHepatobiliary Medicine and Surgery (CISHMS)

2018

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cover bk Liver Update.indd 2 11/7/2018 10:16:10 AM

NASKAH LENGKAP

The 11th Liver Update and

The Scientific Meeting of INA ASL/PPHI

In Conjunction with

The 7th China-Indonesia Joint Symposium on

Hepatobiliary Medicine and Surgery (CISHMS)

2018

Theme:

Future Treatment in Hepatopancreatobiliary Diseases

EDITORRino Alvani Gani

Irsan HasanC. Rinaldi A. Lesmana

Perhimpunan Peneliti Hati Indonesia

Hotel Raffles Jakarta, July 5th-7th 2018

Proceeding Book

The 11th Liver Update and The Scientific Meeting of INA ASL/PPHI

In Conjunction with

The 7th China-Indonesia Joint Symposium on Hepatobiliary Medicine and Surgery

(CISHMS) 2018

Theme: Future Treatment in Hepatopancreatobiliary Diseases

Susunan Panitia:Ketua Liver Update & CISHMS: Rino Alvani GaniBendahara: Andri SanityosoPublikasi: Indra Marki

Reviewer: Rino Alvani Gani

Tim Editor:Rino Alvani GaniIrsan HasanC. Rinaldi A. Lesmana

150 x 230 mm

ISBN 978-602-18991-9-9

Hak Cipta Dilindungi Undang-undang:Dilarang memperbanyak, mencetak dan menerbitkan sebagian atau seluruh isi buku ini dengan cara dan bentuk apapun tanpa seizin penulis dan penerbit

Diterbitkan oleh:Perhimpunan Peneliti Hati IndonesiaGedung Wisma Bhakti Mulya Lt. 6 Ruang 602Jl. Kramat Raya No. 160Jakarta 10430

Prohepa

Highlight

vThe 11th Liver Update and The Scientific Meeting of INA ASL/PPHI in Conjunction with The 7th CISHMS 2018

Aida LydiaDivisi Ginjal Hipertensi Departemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

David Handojo MuljonoLembaga Biologi Molekuler EijkmanJakarta

Alex ThompsonDirector, Department of GastroenterologySt Vincent’s HospitalThe University of MelbourneSVHM, Victoria, Australia

Fauzi YusufDivisi Gastroentero-hepatologi Bag/SMF Ilmu Penyakit DalamFK UNSYIAH/RSU Dr. Zainoel AbidinAceh

Anthony TeohDeputy Director of EndoscopyDepartment of Surgery The Chinese University of Hong KongHong Kong

Henry LY ChanThe Chinese University of Hong Kong, Hong Kong

Andri SanityosoDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

Hery Djagat PurnomoSubbag. Gastroentero-hepatologiBagian Ilmu Penyakit DalamFK UNDIP / RSUP Dr. KariadiSemarang

Chyntia Olivia Maurine JasirwanDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

Hui Ying RaoPeking University Hepatology InstitutePeking University People’s HospitalBeijing, China

Cleopas Martin RumendeDivisi Respirologi & Penyakit KritisDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

Irsan HasanDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

C. Rinaldi A. LesmanaDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

I Dewa Nyoman WibawaDivisi Gastroentero-Hepatologi Bag/SMF Ilmu Penyakit DalamFK UNUD/RSUP SanglahDenpasar, Bali

KONTRIBUTOR

vi The 11th Liver Update and The Scientific Meeting of INA ASL/PPHI in Conjunction with The 7th CISHMS 2018

Ji Dong JiaDirector, Liver Research CenterBeijing Friendship HospitalCapital Medical UniversityBeijing, China

Li Ying SunVice Director, Department of Critical Care MedicineBeijing Friendship HospitalCapital Medical University, Beijing, China

Juferdy KurniawanDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

Lim Seng GeeDivision of Gastroenterology and HepatologyUniversity Medicine ClusterNational University HospitalSingapore

Jun Qi NiuDirector, Department of HepatologyThe First Hospital of Jilin UniversityChangcun, China

Manoj Kumar SharmaInstitute of Liver and Biliary ScienceNew Delhi, India

Kemal Fariz KalistaDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

Masashi MizokamiDirector, Genome Medical Sciences ProjectNational Center for Global Health and MedicineJapan

Lai WeiDirector of Peking University Hepatology InstituteChief Department of HepatologyPeking University People’s HospitalBeijing, China

Meta Dewi ThedjaLembaga Biologi Molekuler EijkmanJakarta

Laurentius A. LesmanaDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

M. Begawan BestariDivisi Gastroentero-hepatologi Departemen Ilmu Penyakit DalamFKU UNPAD/RSUP Dr. Hasan SadikinBandung

Lawrence Ho Khek YuDivision of Gastroenterology and HepatologyNational University Hospital Singapore

Poernomo Boedi SetiawanSubbag. Gastroentero-hepatologiBagian Ilmu Penyakit DalamFK UNAIR / RSUP Dr. SoetomoSurabaya

Lianda SiregarSMF Gastroentero-HepatologiRS Kanker DharmaisJakarta

Rino Alvani GaniDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

viiThe 11th Liver Update and The Scientific Meeting of INA ASL/PPHI in Conjunction with The 7th CISHMS 2018

Sang Hoon AhnInstitute of GastroenterologyDepartment of Internal MedicineYonsei University College of MedicineSeoul, Korea

Stephen KY ChangMedical Director, GLAD ClinicMount Elizabeth HospitalSingapore

Shuichiro ShiinaDepartment of Gastroenterological Imaging and Interventional OncologyJuntendo UniversityJapan

Toar JM LalisangDepartemen Bedah Digestif FKUI/RSCM Dr. Cipto MangunkusumoJakarta

xiThe 11th Liver Update and The Scientific Meeting of INA ASL/PPHI in Conjunction with The 7th CISHMS 2018

Complications Management in Liver TransplantationRino Alvani Gani, Steven Zulkifly ............................................................................................... 77

Symposium 5

The Role of Image-Guided Ablation Therapy in HCC: an UpdateShuichiro SHIINA .............................................................................................................................. 85

HCC When to Refer to SurgeonStephen Chang .................................................................................................................................... 87

Symposium 6

Hepatitis B and C Co-Infection Management in The Era of Direct-Acting AntiviralAndri Sanityoso Sulaiman, M. Yusuf Hanif ............................................................................. 88

HIV Co-infection Hepatitis Virus: DAA & ARVJuferdy Kurniawan, Putra Nur Hidayat ................................................................................... 93

Screening in Population for HBV Infection: The Role of InternistPoernomo Boedi Setiawan ............................................................................................................ 99

Symposium 7

Peg-Interferon (Peg-IFN) Therapy: Sound a Death Knell?Huiying RAO ........................................................................................................................................ 100

Meet the Expert 1

RFA for Liver Metastasis: New Dawn for a Better Future?Shuichiro SHIINA .............................................................................................................................. 101

Symposium 8

Critical Care Concept in Liver Patients: What Internist Should Know?Manoj Kumar Sharma ..................................................................................................................... 104

Management of Severe Pneumonia in Liver CirrhosisC. Martin Rumende ........................................................................................................................... 105

Antibiotic Treatment for Pneumonia in Cirrhotic PatientsC. Martin Rumende ........................................................................................................................... 112

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77The 11th Liver Update and The Scientific Meeting of INA ASL/PPHI in Conjunction with The 7th CISHMS 2018

LUNCH

SYMPOSIUM 01

Complications Management

in Liver Transplantation

Rino Alvani Gani1, Steven Zulkifly2

1 Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia/ Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia2 Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

Introduction

The indications of liver transplantation (LT) aresevere acute liver failure, end-stage liver disease and hepatocellular carcinoma (HCC).1,2 Cirrhosis is the leadingcause for transplantation procedure in adults in Europe.The prognosis of LT has improved for acute liver failure, causing survival rate to increase from 10-20% (all causes combined) to 75-80% at 1 year and 70% at 5 years.2 The outcome after LT varies greatly depending on the preoperative state, quality of the donated organ and the surgery.3

The LT complications are divided into immediate complications and long-term complications. The immediate complications are associated with graft dysfunction and rejection, the surgical technique, infections and systemic abnormality (pulmonary, renal or neurological). However, long-term complications are related to diabetes mellitus, hypertension, de novo neoplasia, organ toxicities and the consequences of the prolonged immunosuppressive therapy.3

Immediate Complications of LT

Immediate complications after transplantation procedures are categorized into medical complications, technical complications, liver graft dysfunction and infections (Table 1).

Rino Alvani Gani, Steven Zulkifly

78 The 11th Liver Update and The Scientific Meeting of INA ASL/PPHI in Conjunction with The 7th CISHMS 2018

Table 1. Immediate Complications of Liver Transplantation

Medical Complications

Hemodynamic complications

Respiratory changes

Renal dysfunction

Neurological complications

Techincal Complications

Postoperative hemorrhage

Vascular complications

Biliary tract complications

Liver Graft Dysfunction

Primary poor function

Acute cellular rejection

Recurrent viral hepatitis

Infections

Bacterial

Viral

Fungal

Medical Complications

The most common hemodynamic complication during early post-transplant period is arterial hypertension. The intense pain after the procedure, hypervolemia due to excessive hydrous replacement and effect of immunosuppressive agents (calcineurin inhibitors and corticosteroids) are the cause of arterial hypertension.3 The use of antihypertensive drugs (calcium channel blocker and diuretics) can control the blood pressure.4

Pleural effusion, atelectasis, pulmonary edema, acute respiratory distress syndrome (ARDS) and pneumonia are the major pulmonary complications after the procedure. Pleural effusion is mainly involved the right side and usually transudate. The effusion expands during the first operative week and frequently disappear in the following week. Thoracentesis or chest tube placement if the effusion is persistent or massive.5

Pulmonary edema is rare after transplantation procedure, unless the patient had acute onset of severe left ventricular dysfunction and acute fluid overload in renal dysfunction. Acute respiratory distress syndrome (ARDS) is developed within 24 hours or the first day after transplantation. Crystalloid infusion overload, massive blood transfusion, severe ischemic-reperfusion syndrome are the cause of ARDS. Treatment of ARDS is supportive, including fluid restriction, mechanical ventilation, mild hypercapnia and optimal PEEP.5

Complications Management in Liver Transplantation


Risk factors for developing pneumonia after transplantation procedure are prolonged orotracheal intubation (massive intraoperative bleeding, the persistence of severe encephalopathy, diffuse pleural exudates, postoperative ARDS and severe renal dysfunction), greater exposure to nosocomial agents and reduction in immune function.5

Renal dysfunction or acute kidney injury (AKI) after LT procedure is found in 12 – 70% patients. In multivariate analysis, preoperative increased creatinine, vasopressor use, and postoperative anemia are independent predictors of early post transplantation renal dysfunction. Euvolemia with adequate renal perfusion pressures should be maintained by colloid based hydrous replacement. Early renal replacement therapy can be considered.6

Neurological complications are found in 15%-27% after liver transplantation. Encephalopathy, seizure, brain hemorrhage, CNS infections, and stroke are the common neurological complications. Hepatic failure, Wilson’s disease, primary biliary cirrhosis and family amyloidosis are the risk factor associated with liver disease. Other underlying diseases are chronic hyponatremia, high level of immunosuppression, sepsis, history of alcohol abuse, etc.7

Technical Complications

Abdominal bleeding within 1 month was found in 94 patients (9%) who undergone LT procedure. The control of active bleeding was completely achieved by endovascular interventional techniques (39%), surgical ligation or vascular reconstruction (46%) and sequential combinations of endovascular intervention and surgery (15%). In multivariate analysis, intraoperative blood loss was the only independent factor for bleeding.8

Arterial complications after liver transplantation are hepatic artery thrombosis (HAT), hepatic artery stenosis (HAS), hepatic artery pseudoaneurysm (HAP) and hepatic artery rupture (HAP). The clinical manifestation of early HAS is abnormal transaminase, fever, biliary complications, graft failure, and coagulopathy. Late HAS is asymptomatic in few patients, while others develop fever, abnormal transaminase, bile leak, hepatic abscess, and cholangitis. The treatment for HAT is emergent revascularization by endovascular intervention or surgical revascularization or re-LT.9



The clinical presentation of HAS is graft failure and biliary complications. In late HAS, some patients are asymptomatic, and few patients develop fever and abnormal liver function. The diagnosis is made by doppler ultrasound (DUS), contrast-enhanced multi detector computed tomography (ce-MDCT) and angiography. HAS is treated by endovascular intervention or surgical revascularization.9

In HAP, abdominal pain is found in several patients, while others are asymptomatic. DUS and ce-MDCT help the confirmation of diagnosis. Endovascular intervention or surgical resection and revascularization are the treatment options for HAP. Fever, gastrointestinal bleeding, massive bleeding through abdominal drains and hemorrhagic shock are the clinical manifestation of HAR. Emergent surgical hemostasis and surgical repair is the emergency procedure for rupture.9

Portal vein thrombosis (PVT) and portal vein stenosis (PVS) are venous complications after LT. Early PVT is manifested by an abnormal transaminase, graft dysfunction, multi-organ failure and variceal bleeding. Confirmation of diagnosis is using DUS, ce-MDCT (portal phase) and portography. Therapy for PVT is including rLT or surgical repair or endovascular interventions. Ascites, portal vein hypertension, splenomegaly and variceal bleeding are the manifestation of late PVT. DUS, ce-MDCT (portal phase) and portography help the confirmation of diagnosis. Curative anticoagulant therapy is the treatment for late PVT.9

Early PVS is asymptomatic, while others develop portal vein hypertension and abnormal transaminase level. Late PVS is also asymptomatic, and others have ascites and abnormal liver function test. The diagnosis is confirmed by DUS, ce-MDCT (portal phase) and portography. The treatment of early PVS is endovascular interventions, while late PVS is anticoagulant therapy and/or endovascular intervention.9

Biliary complicationsafter LT are biliary leakage, biliary strictures, sphincter of Oddi dysfunction (SOD), biloma and hemobilia. Biliary leakage is one of the most common biliary complications, accounting for 2-25%. The etiologies of bile leakage are T-tube removal, ischemia and relative downstream obstruction. Abdominal pain, fever and any sign of peritonitis, especially after T-tube removal are the clinical manifestations of bile leakage.



The initial managements are administration of analgesics, intravenous fluid, and supportive care. The definitive therapy is endoscopic sphincterectomy with/without endoscopic stenting.10

Biliary strictures are classified as anastomotic and non-anastomotic strictures. Biliary anastomotic strictures occur in both choledochocholedochostomy (CC) and choledochojejunostomy (CJ) type reconstruction. Inadequate mucosa to mucosae anastomosis, surgical technique, and local ischemia are the pathogenesis of biliary anastomotic stricture. Patients should undergo ERCP and stenting of the stricture.10

Biliary non-anastomotic stricture or ischemic type stricture is caused by the remaining blood supply to the supraduodenal bile duct is highly susceptible to ischemic injury, leading to stricture. If hepatic artery thrombosis (HAT) exists, aggressive therapy such as revascularization or early re-transplantation is recommended. Endoscopic or percutaneous therapy and repeated dilatation with stenting is performed in patients without HAT.10

Denervation of sphincter during transplantation procedure increases basal pressure, therefore increased pressure in choledochal duct and continued with chronic inflammation and fibrosis. These two features made stenosis or dysfunction of sphincter of Oddi/SOD. Endoscopic therapy with sphincterotomy with/without stenting is the therapy for patients with SOD.10

Biloma is formed by the bile rupture and spill within the liver and abdominal cavity. Small biloma may resolve spontaneously. The treatment of biloma includes antibiotics and percutaneous/surgical drainage. Hemobilia is a rare complication and associated with percutaneous liver biopsy. Treatment of hemobilia is hemostasis (supportive therapy, correction of coagulopathy and embolization of the bleeding vessel).10

Liver Graft Dysfunction

Primary graft dysfunction (PGD) is one of most serious complications after LT. PGD is categorized into initial poor function (IPF) and primary non-function (PNF). Until now, there is no consensus of the definitions of PGD, IPF and PNF. However, the definition of PGD should include one or more



alanine aminotransferase or aspartate aminotransferase >2000 IU/L within postoperative day 7.11

The incidence of IPF and PNF were reported 5.2% to 36.3% and 0.9% to 7.2%, respectively, from several studies. Several factors have been analyzed that associated with PGD, including donor-and graft-related factors, procurement- and transplant-related factors and recipient-related factors. Retransplantation is the only treatment of choice for PNF. Patients with IPF can recover spontaneously without specific therapy. The normalization of graft function, serum bilirubin, and albumin needs 28 days after LT.11

Rejection after LT was classified into 3 categories, such as hyperacute, acute and chronic liver rejection. The most common rejection is acute cellular rejection (15%-80%) with time peak 5-30 days after the procedure. Liver biopsy plays a major role in the diagnosis of acute cellular rejection. The classic triad (Snover’s triad) of acute rejection includes portal inflammation, portal bile duct injury and inflammatory vascular lesions.12 Therapy for acute rejection is the administration of immunosuppression agents (corticosteroids, calcineurin inhibitors, mTOR inhibitor, antimetabolite and IL-2 receptor monoclonal antibodies).13

The antiviral therapy in HCV recurrent patients is initiated early in

longer recommended. EASL 2016 recommended sofosbuvir/ledipasvir plus ribavirin and sofosbuvir plus simeprevir (with or without ribavirin) as the treatment of choice in this setting. More data is required about pharmacokinetics and drug-drug interaction in LT recipients.14

More than 75% of liver grafts became infected before the use of the hepatitis B immunoglobulin (HBIG). The effective strategy to prevent HBV recurrence is combination of HBIG and NUCs. The controlling infection recurrence is used by monotherapy with entecavir or tenofovir, but not enough to prevent HBV graft infection. Recurrence is defined by the reappearance of serum HBsAg and quantifiable HBV DNA. Entecavir or tenofovir is the first line therapy for HBV recurrence.14

Infections

Infections after transplantation procedure are divided into three different timelines: 1) first months after the procedure (nosocomial infection); 2) 2-6 months after transplantation (opportunistic infections and



reactivation of latent infections); and 3) later than 6 months (community acquired infections).14

The most common pathogens for bacterial infections after LT is gram-negative bacteria, including Escherichia colli, Enterobacter, and Pseudomonas. The source of infections mainly in the surgical site, abdominal cavity, urinary tract, and bloodstream. Antibiotics should be administered based on the specific pathogens and its resistance profile.15

Cytomegalovirus (CMV) is the most common opportunistic infections after LT procedure. The clinical manifestations of CMV infection are viremia, bone marrow suppression, colitis, and hepatitis. In patient with mild disease, intravenous ganciclovir or oral valganciclovir is the treatment of choice. However, only intravenous ganciclovir should be used in severe CMV infection. Patients with Epstein Barr Virus (EBV) seropositive have a higher risk to develop post-transplant lymphoproliferative disorders (PTLD), particularly in patients who received immunosuppressive regimens. Reducing immunosuppressive therapy dose is the initial step of treating patients with PTLD. Rituximab, chemotherapy, radiation, and surgery are indicated if no response after immunosuppressive reduction.15

Candida infections are the leading causes of early invasive infection after the procedure. EASL recommended oral prophylaxis during the first months. Fluconazole is the treatment of choice in Candida infections. The primary sites of Aspergillus infection are lung and cerebral. Inhaled amphotericin B and micafungin are the treatment in this setting. The rate of Pneumocystis jirovecci infections has been reduced after the administration of TMP-SMX prophylaxis. Corticosteroid can be used to reduce the pulmonary inflammation and post-infection fibrosis.15

References

1. Burra P, Burroughs A, Graziadei I, Pirenne J, Valdecasas JC, Muiesan P, et al. EASL Clinical Practice Guidelines: Liver transplantation. J Hepatol. 2015.

2. Martin P, DiMartini A, Feng S, Brown Jr R, Fallon M. Evaluation for Liver Transplantation in Adults: 2013 Practice Guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology. 2014;59(3).



3. Moreno R, Berenguer M. Post-liver transplantation medical complications. Annals of Hepatology. 2006;5(2):77-85.

4. Aparicio LS, Alfie J, Barochiner J, Cuffaro PE, Rada M, et al. Hypertension: the neglected complication of transplantation. ISRN Hypertension. 2013.

5. Feltracco P, Carollo C, Barbieri S, Pettenuzzo T, Ori C. Early respiratory complications after liver transplantation. World J Gastroenterol. 2013;19(48):9271-81.

6. Wiesen P, Massion PB, Joris J, Detry O, Damas P. Incidence and risk factors for early renal dysfunction after liver transplantation. World J Transplant. 2016;6(1):220-32.

7. Zivkovic SA. Neurologic complications after liver transplantation. World J Hepatol. 2013;5(8):409-16.

8. Jung JW, Hwang S, Namgoong JM, Yoon SY, Park CS, Park YH, et al. Incidence and management of postoperative abdominal bleeding after liver transplantation. Transplant Proc. 2012;44(3):765-8.

9. Piardi T, Lhuaire M, Bruno O, Memeo R, Pessaux P, Kianmanesh R, et al. Vascular complications following liver transplantation: a literature review of advances in 2015. World J Hepatol. 2016;8(1):36-57.

10. Kochhar G, Parungao JM, Hanouneh IA, Parsi MA. Biliary complications following liver transplantation. World J Gastroenterol. 2013;19(19):2841-46.

11. Chen XB, Xu MQ. Primary graft dysfunction after liver transplantation. Hepatobiliary Pancreat Dis Int. 2014;13:125-137.

12. Panqueva RPL. Liver biopsies in transplant pathology: histopathological diagnosis and clinicopathological correlation in the early post-transplant period. Rev Col Gastroenterol. 2016;31(2)

13. Charlton MR. How important is acute cellular rejection ? Liver Transplant. 2013;19:S9-S13.

14. European Association for The Study of the Liver. EASL Clinical Practice Guidelines: Liver transplantation. J Hepatol. 2016;64:433-85.

15. Kim SI. Bacterial infection after liver transplantation. World J Gastroenterol. 2014;20(20):6211-20.

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NASKAH LENGKAP Liver Update and The Scientific Meeting of ...staff.ui.ac.id/system/files/users/rino.gani/publication/2018... · Wilson’s disease, primary biliary cirrhosis and family