SKRIPSI

SULLY NUR AISYAH

STUDI PENGGUNAAN LAKTULOSA PADA

PASIEN SIROSIS HATI DENGAN HEPATIK

ENSEFALOPATI DI RSUD SIDOARJO

PROGRAM STUDI FARMASI

FAKULTAS ILMU KESEHATAN

UNIVERSITAS MUHAMMADIYAH MALANG

2020

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KATA PENGANTAR

Assalamu’alaikum Warahmatullahi Wabarakatuh

Alhamdulillahirabbil’alamiin, segala puji bagi Allah SWT yang telah

melimpahkan rahmat, hidayah, dan inayah-Nya. Rabb yang telah memberikan nikmat

sehat, waktu, kemudahan, dan kesabaran sehingga penulis dapat menyelesaikan

skripsi yang berjudul STUDI PENGGUNAAN LAKTULOSA PADA PASIEN

SIROSIS HATI DENGAN HEPATIK ENSEFALOPATI DI RSUD SIDOARJO

untuk mencapai gelar sarjana farmasi pada Program Studi Farmasi Fakultas Ilmu

Kesehatan Universitas Muhammadiyah Malang. Dalam penyusunan skripsi ini, tidak

terlepas dari peranan pembimbing dan bantuan dari seluruh pihak. Oleh karena itu,

dengan segala kerendahan hati, penulis ingin mengucapkan banyak terima kasih

kepada:

1. Bapak Faqih Ruhyanudin, M.Kep., Sp. Kep. MB. selaku Dekan Fakultas Ilmu

Kesehatan Universitas Muhammadiyah Malang

2. Ibu apt.Dian Ermawati, M.Farm. selaku Ketua Progam Studi Farmasi Universitas

Muhammadiyah Malang

3. Direktur dan staf Rumah Sakit Umum Daerah Sidoarjo yang telah membantu

kelancaran penelitian, terutama staf rekamedis Ibu Alia Chaerunisa, A.Md.Kes

dan Muhammad Wahyu Setiawan A.Md. Kes.

4. Ibu Dr.apt.Hidajah Rachmawati, S.Si.,Sp.FRS. dan Bapak Drs.apt.Didik

Hasmono, MS. selaku pembimbing I dan II yang selalu meluangkan waktu untuk

membimbing, memberikan ilmu, arahan, nasehat, serta dorongan, selama

menempuh pendidikan hingga terselesaikannya tugas akhir ini

5. Ibu Dr.apt.Lilik Yusetyani, Sp.FRS. dan Ibu apt.Aghnia Fuadatul Inayah,

M.Farm.Klin. selaku penguji I dan II yang telah memberikan masukan dan saran

untuk penyempurnaan tugas akhir ini

6. Ibu apt.Ika Ratna Hidayati, S.Farm., M.Sc. selaku dosen wali yang telah

memberikan nasehat dan bimbingan sejak awal semester

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7. Seluruh jajaran prodi, dosen dan staf tata usaha Farmasi yang telah memberikan

dedikasi yang besar kepada penulis

8. Kedua orang tua, Ibu Ciplis Sruhartati dan Ayah Gatot Sumijarlan tercinta yang

selalu mendoakan dan memberikan yang terbaik untuk anak-anaknya.

Terimakasih atas motivasi, kerja keras dan jerih pasyah ibu dan ayah selama ini

sehingga penulis bisa menyelesaikan tugas akhir ini

9. Seluruh teman-teman Farmasi 2016, khususnya Farmasi C terimakasih atas

kebersamaan dan kenangan indah selama ini. Tanpa kalian penulis tidak dapat

menikmati hari-hari perkuliahan dengan sukacita

10. Semua pihak yang tidak dapat disebutkan satu persatu, penulis mengucapkan

mohon maaf dan terimakasih yang sebesar-besarnya

Semoga Allah SWT membalas segala kebaikan dan bantuan yang telah diberikan.

Kritik dan saran dari semua pihak sangat penulis harapkan agar dapat menjadi

intropeksi diri serta penyempurnaan karya penyusun selanjutnya. Semoga skripsi ini

dapat bermanfaat bagi siapapun yang membutukannya

Wassalamu’alaikum Warahmatullahi Wabarakatuh

Malang, 27 Juni 2020

Penulis

Sully Nur Aisyah

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DAFTAR ISI

HALAMAN JUDUL .................................................................................................... i

Lembar Pengesahan .................................................................................................... ii

Lembar Pengujian ...................................................................................................... iii

KATA PENGANTAR ................................................................................................ iv

RINGKASAN ............................................................................................................. vi

ABSTRAK ................................................................................................................ viii

ABSTRACT ................................................................................................................ ix

DAFTAR ISI.........................................................................................................................x

DAFTAR TABEL ..................................................................................................... xiii

DAFTAR GAMBAR ................................................................................................ xiv

DAFTAR LAMPIRAN ............................................................................................. xv

DAFTAR SINGKATAN .......................................................................................... xvi

BAB I PENDAHULUAN ............................................................................................ 1

1.1 Latar Belakang .................................................................................................... 1

1.2 Rumusan Masalah ............................................................................................... 4

1.3 Tujuan Penelitian ................................................................................................. 4

1.4 Manfaat Penelitian ............................................................................................... 4

BAB II TINJAUAN PUSTAKA ................................................................................. 6

2.1 Hati ...................................................................................................................... 6

2.1.1 Anatomi Hati ................................................................................................ 6

2.1.2 Fisiologi Hati ................................................................................................ 7

2.1.3 Fungsi Hati ................................................................................................... 8

2.2 Tinjauan Sirosis Hati ......................................................................................... 10

2.2.1 Definisi Sirosis Hati .................................................................................... 10

2.2.2 Epidemiologi Sirosis Hati ........................................................................... 11

2.2.3 Etiologi Sirosis Hati .................................................................................... 11

2.2.4 Patofisiologi Sirosis Hati ............................................................................ 12

2.2.5 Klasifikasi Sirosis Hati ............................................................................... 13

2.2.6 Komplikasi Sirosis Hati .............................................................................. 14

2.2.7 Penatalaksanaan Sirosis Hati ...................................................................... 16

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2.3 Tinjauan Hepatik Ensefalopati .......................................................................... 18

2.3.1 Definisi Hepatik Ensefalopati ..................................................................... 18

2.3.2 Epidemiologi Hepatik Ensefalopati ............................................................ 19

2.3.3 Etiologi Hepatik Ensefalopati ..................................................................... 19

2.3.4 Patofisiologi Hepatik Ensefalopati ............................................................. 20

2.3.5 Klasifikasi Hepatik Ensefalopati ................................................................ 22

2.3.6 Penatalaksanaan Hepatik Ensefalopati ....................................................... 23

2.4 Penggunaan Laktulosa pada Hepatik Ensefalopati ........................................... 26

2.4.1 Indikasi........................................................................................................ 26

2.4.2 Mekanisme Kerja ........................................................................................ 27

2.4.3 Farmakokinetika ......................................................................................... 27

2.4.4 Dosis dan Rute Pemberian .......................................................................... 28

2.4.5 Sediaan yang Beredar di Indonesia ............................................................. 28

BAB III KERANGKA KONSEPTUAL DAN OPERASIONAL .......................... 30

3.1 Kerangka Konseptual ........................................................................................ 30

3.2 Kerangka Operasional ....................................................................................... 32

BAB IV METODE PENELITIAN .......................................................................... 33

4.1 Rancangan Penelitian ........................................................................................ 33

4.2 Populasi dan Sampel ......................................................................................... 33

4.2.1 Populasi ....................................................................................................... 33

4.2.2 Sampel ........................................................................................................ 33

4.2.3 Kriteria Data Inklusi ................................................................................... 33

4.2.4 Kriteria Data Eksklusi ................................................................................. 33

4.3 Instrumen Penelitian .......................................................................................... 33

4.4 Tempat dan Waktu Penelitian ........................................................................... 34

4.5 Definisi Operasional .......................................................................................... 34

4.6 Metode Pengumpulan Data ............................................................................... 35

4.7 Analisis Data ..................................................................................................... 35

BAB V HASIL PENELITIAN ................................................................................. 36

5.1 Data Demografi Pasien ...................................................................................... 36

5.1.1 Distribusi Berdasarkan Jenis Kelamin ........................................................ 36

5.1.2 Distribusi Berdasarkan Usia ....................................................................... 37

5.1.3 Distribusi Berdasarkan Status Pasien.......................................................... 37

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5.2 Pola Penggunaan Laktulosa pada Pasien Sirosis Hati dengan Hepatik

Ensefalopati (HE) .................................................................................................... 37

5.2.1 Pola Penggunaan Terapi Laktulosa pada Pasien Hepatik Ensefalopati ...... 37

5.2.2 Pola Penggunaan Laktulosa Tunggal .......................................................... 38

5.2.3 Pola Penggunaan Laktulosa Kombinasi ...................................................... 38

5.2.4 Pola Penggunaan Switch Kombinasi Dua ................................................... 39

5.2.5 Lama Penggunaan Terapi Laktulosa ........................................................... 39

5.3 Diagnosis Penyerta ............................................................................................ 39

5.4 Profil Terapi Lainnya ............................................................................................... 40

5.5 Lama Rawat Inap Pasien Sirosis Hati dengan Hepatik Ensefalopati ................. 41

5.6 Kondisi Keluar Rumah Sakit (KRS) Pasien Sirosis Hati dengan Hepatik

Ensefalopati ............................................................................................................. 42

BAB VI PEMBAHASAN .......................................................................................... 43

BAB VII KESIMPULAN DAN SARAN ................................................................. 52

DAFTAR PUSTAKA ................................................................................................ 53

LAMPIRAN ............................................................................................................... 60

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DAFTAR TABEL

Tabel II.1 Stadium Hepatik Ensefalopati Kriteria West Haven ................................... 23

Tabel II.2 Sediaan Laktulosa di Indonesia .................................................................. 28

Tabel V.1 Distribusi Berdasarkan Jenis Kelamin........................................................ 36

Tabel V.2 Distribusi Berdasarkan Usia ....................................................................... 37

Tabel V.3 Distribusi Berdasrkan Status Pasien ........................................................... 37

Tabel V.4 Pola Penggunaan Terapi Laktulosa pada Pasien Hepatik Ensefalopati ...... 38

Tabel V.5 Pola Penggunaan Terapi Laktulosa Tunggal pada Pasien Hepatik

Ensefalopati ..................................................................................................... 38

Tabel V.6 Pola Penggunaan Laktulosa Kombinasi pada Pasien Hepatik Ensefalopati

..................................................................................................................................... 38

Tabel V.7 Penggunaan Switch Kombinasi Dua ........................................................... 39

Tabel V.8 Lama Penggunaan Terapi Laktulosa pada Pasien Hepatik Ensefalopati .... 39

Tabel V.9 Diagnosis Penyerta pada Pasien Sirosis Hati dengan Hepatik Ensefalopati

..................................................................................................................................... 40

Tabel V.10 Terapi Lainnya selain Laktulosa pada Pasien Sirosis Hati dengan Hepatik

Ensefalopati ..................................................................................................... 40

Tabel V.11 Lama Perawatan pada Pasien Hepatik Ensefalopati ................................. 41

Tabel V.12 Kondisi KRS Pasien Hepatik Ensefalopati ............................................... 42

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DAFTAR GAMBAR

Gambar 2.1 Anatomi Hati ............................................................................................. 6

Gambar 2.2 Struktur Dasar Hati .................................................................................... 7

Gambar 2.3 Sirosis Mikronoduler dan Makronoduler ................................................ 10

Gambar 2.4 Patogenesis Komplikasi Sirosis ............................................................... 12

Gambar 2.5 Komplikasi Sirosis Hati ........................................................................... 13

Gambar 2.6 Patofisiologi Hepatik Ensefalopati .......................................................... 21

Gambar 2.7 Mekanisme Kerja Laktulosa .................................................................... 27

Gambar 3.1 Skema Kerangka Konseptual .................................................................. 30

Gambar 3.2 Skema Kerangka Operasional ................................................................. 32

Gambar 5.1 Skema sampel yang memenuhi kriteria inklusi penelitian pada pasien

sirosis hati dengan hepatik ensefalopati di RSUD Sidoarjo ........................................ 36

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DAFTAR LAMPIRAN

Lampiran 1. Daftar Riwayat Hidup ............................................................................. 60

Lampiran 2. Surat Pernyataan...................................................................................... 61

Lampiran 3. Surat Laik Etik ........................................................................................ 62

Lampiran 4. Lembar Pengumpul Data......................................................................... 63

Lampiran 5. Tabel Data Induk ................................................................................... 120

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DAFTAR SINGKATAN

AAT : Aspartate Aminotransferase

ASDR : Age Spesific Death Rate

BBB : Blood Brain Barrier

BCAA : Branched Chain Amino Acids

BUN : Blood Urea Nitrogen

CSDR : Cause Spesific Death Rate

EASL : European Association for the Liver Dissease

EBL : Endoscopic Band Ligand

ECM : Extracelullar Matrix

FDA : Food and Drug Association

GABA : Γ-aminobutyric acid

GI : Gastrointestinal

HB : Hemoglobin

HCT : Hematocrit

HE : Hepatik Ensefalopati

ISO : Informasi Spesialite Obat

LED : Laju Endap Darah

LOLA : L-ornithine L-aspartate

MELD : Model for End-Stage Liver Disease

NAD : Non-absorbable Disaccharides

NIDDK: National Institute of Diabetes and Digestive and Kidney Disease

NSBB : Non-Selective β-blocker

OAT : Ornithine Aminotrasnferase

PLT : Platelet

RAAS : Renin Angiotensin Aldosterone System

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RBC : Red Blood Cell

RSUD : Rumah Sakit Umum Daerah

SBP : Spontaneous Bacterial Peritonitis

SGOT : Serum Glutamic Oxaloacetic Transaminase

SGPT : Serum Glutamic Pyruvic Transaminase

SSP : Sistem Syaraf Pusat

TIPS : Transjugular Intrahepatic Portosystemic

VEH : Variceal Esophageal Hemorrhage

WHO : World Health Organization

WBC : White Blood Cell

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DAFTAR PUSTAKA

Ahmad, Raja Shoaib., Muhammad Adnan., Hira Jabeen. 2018. Original Article

Efficacy of Lactulose vs Lactulose with Rifaximin in Patients with Hepatic

Encephalopathy : A Randomized Control Trial. 9(April): 39 – 41.

Aires, F. T., Ramos, P. T., & Bernardo, W. M. 2016. Efficacy of lactulose in the

prophylaxis of hepatic encephalopathy in cirrhotic patients presenting

gastrointestinal bleeding. Revista Da Associação Médica Brasileira, 62(3),

243–247

Amalina, Hilyati Ajrina, and Rina Kriswiastiny. 2015. Perdarahan Saluran Cerna

Bagian Atas Karena Sirosis Hepatis. Jurnal Unila 4(2): 74–79.

Boregowda Umesha, C.U. 2019. Update on The Management of Gastrointestinal

Varices. World Journal of Gastrointestinal Pharmacology and

Therapeutics: 2019 January 21; 10(1): 1-21.

Cai, G., Chen, Y., Zhou, B., Hu, C., Yu, Y., XuM., Yao, J. 2018. Meta-Analysis of

Risk Factors for Development of Liver Cirrhosis in Chronic Hepatitis B Patients.

(R. Chalik, Ed.) Global Journal Of Infectious Diseases and Clinical

Research, 4(2), 004-006. Retrieved from

https://www.peertechz.com/articles/GJIDCR-4-118

Chapin, C. A., & Bass, L. M. 2018. Cirrhosis and Portal Hypertension in the Pediatric

Population. Clinics in Liver Disease, 22(4), 735–752.

https://doi.org/10.1016/j.cld.2018.06.007

Chaudhry, Saira B., Michael P. veve, and Jamie L. Wagner. 2019. Cephalosporin : A

focus on Side Chains and B-lactam Cross-Reactivity. Pharmacy, 1-16.

Chen, Gina, Ryan Cheung, and James W. Tom. 2017. Hepatitis: Sedation and

Anesthesia Implications. Anesthesia Progress 64(2): 106–18.

Cordoba, Juan. 2014. Hepatic Encephalopathy: From the Pathogenesis to the New

Treatments. ISRN Hepatology 2014: 1–16.

Dam, G., Aamann, L., Vistrup, H., & Gluud, L. L. 2018. The role of Branched Chain

Amino Acids in the treatment of hepatic Encephalopathy. Journal of Clinical

and Experimental Hepatology, 8(4), 448–451.

https://doi.org/10.1016/j.jceh.2018.06.004

DiPiro J.T., Wells B.G., Schwinghammer T.L. and DiPiro C. V., 2015,

Pharmacotherapy Handbook, Ninth Edit., McGraw-Hill Education

Companies, Inggris.

xvi

DiPiro J.T., Wells B.G., Schwinghammer T.L. and DiPiro C. V., 2017,

Pharmacotherapy Handbook, Tenth Edit. McGraw-Hill Education

Companies, Inggris.

Elwir, Saleh and Robert S. Rahimi. 2017. Hepatic Encephalopathy: An Update on the

Pathophysiology and Therapeutic Options. Journal of Clinical and

Translational Hepatology 2017 vol. 5 | 142–151.

European Association for the Liver Dissease (EASL). 2014. Hepatic Encephalopathy

in Chronic Liver Disease: 2014 Practice Guideline by the European Association

for the Study of the Liver and the American Association for the Study of Liver

Diseases. J Hepatology; 61, 642–659.

European Association for the Liver Dissease (EASL). 2018. Clinical Practice

Guidelines For The Management Of Patients With Decompensated Cirrhosis. J

Hepatology.

Farida, Yeni. T.M. 2014. Analisis Penggunaan Obat Pada Komplikasi Sirosis

Hati. Yogyakarta.

Ferenci, Peter. 2017.Hepatic Encephalopathy. British Medical Journal 3(5874):

279–81.

Friedman, Lawrence S. 2016. Liver, Biliary Tract & Pancreas Disorders. In Current

Medical Diagnosis & Treatment, by Stephen J. MacPhee, Michael W. Rabow,

Maxine A. Papadakis. 663-720.

Gluud, Lise Lotte., G, Dam., I, Les.,G, Marchesini., M., Borre., NK, Aagaard., H,

Vilstrup. 2017. Branched-Chain Amino Acids for People with Hepatic

Encephalopathy. Cochrane Database of Systematic Reviews 2017(5).

Goh, E. T., Stokes, C. S., Sidhu, S. S., Vilstrup, H., Gluud, L. L., & Morgan, M. Y.

2018. L-ornithine L-aspartate for prevention and treatment of hepatic

encephalopathy in people with cirrhosis. Cochrane Database of Systematic

Reviews, 2018(5). https://doi.org/10.1002/14651858.CD012410.pub2

Guyton, A. C., Hall, J. E., 2014. Buku Ajar Fisiologi Kedokteran. Edisi 12. Jakarta

: EGC, 1022.

Hadjihambi, Anna., De Chiara, F., Hosfurd, P.S., Habtetion, A., Karagiannis, A.,

Davies, N., Gourine, A.V., Jalah, R. 2017. Ammonia Mediates Cortical

Hemichannel Dysfunction in Rodent Models of Chronic Liver Disease

Hepatolgy. vol 65 no 4.

Hasan, Irsan., Araminta, Abirianti P. 2014. Ensefalopati Hepatik: Apa, Mengapa, dan

Bagaimana. Medisinus.

xvii

HD, Zacharias., AP, Zacharias., LL, Gluud., MY, Morgan. 2019. Pharmacotherapies

that specifically target ammonia for theprevention and treatment of hepatic

encephalopathy in adultsprevention and treatment of hepatic encephalopathy

in adults with cirrhosis (Review). Cochrane Database of Systematic

Reviews, Issue 6. Art. No.: CD012334.

Hicks, Angel Mier., Joanne Chou, Marinela Capanu, Maever A. Lowery, Kenneth H.

Yu, and Eileen M. O’Reilly. 2016. Pancreas Adenocarcinoma: Ascites, Clinical

Manifestations, and Management Implications. Clin Colorectal Cancer 15(4):

360–68.

Higuera-De-La-Tijera, Fátima, Alfredo I., Servin-Caamano, Francisco Salas-Gordilo,

Jose L. Perez. 2018. Primary Prophylaxis to Prevent the Development of Hepatic

Encephalopathy in Cirrhotic Patients with Acute Variceal Bleeding. Canadian

Journal of Gastroenterology and Hepatology

Holeček, M. (2018). Branched-chain amino acids in health and disease: metabolism,

alterations in blood plasma, and as supplements. Nutrition and Metabolism,

15:33. https://doi.org/10.1186/s12986-018-0271-1

Hudson, Mark and Marcus Schuchmann. 2019. Long-term Management of Hepatic

Encephalopathy with Lactulose and/or Rifaximin: A review of the Evidence.

European Journal of Gastroenterology & Hepatology 2019, 31:434–450.

Jang, J. Y., Kim, S. G., Seo, Y. S., Kim, M. Y., Kim, B. K., Kim, B. S., Jun, D. W.

2020. KASL clinical practice guidelines for liver cirrhosis: Varices, hepatic

encephalopathy, and related complications. Clinical and Molecular Hepatology,

26(2), 83–127. https://doi.org/10.3350/cmh.2019.0010n

Jawaro, T., Yang, A., Dixit, D., & Bridgeman, M. B. 2016.Management of Hepatic

Encephalopathy. Annals of Pharmacotherapy, 50(7), 569–577

Jeyaraj, Rebecca, Marsha Y Morgan, and Lise Lotte Gluud. 2017. Aminoglycosides

and Metronidazole for People with Cirrhosis and Hepatic Encephalopathy.

Cochrane Database of Systematic Reviews (7).

KASL Clinical Practice Guidelines for Liver Cirrhosis: Ascites and Related

Complications. 2018. Clinical and Molecular Hepatology 24(3): 23-77.

Khalili, M., & Burman, B. 2014. Liver Disease. In : Hammer, G.D., McPhee, SJ.

Pathophysiology of Disease : An Introduction to Clinical Medicine, Ed 7th,

USA: The McGraw-Hill Companies, Inc. 385-425.

Kim, J. 2015. Management and Prevention of Upper GI Bleeding. Gastroenterology

and Nutrition, 7-26

xviii

La Mura, Vincenzio, Nicolini, A., Tosetti, G., Primignani, M. 2015. Chirrosis and

Portal Hypertension: The Importalnce of Risk Stratification, The Role of

Hepatic Venous Pressure Gradient Measurement. Italy.

Lee, Yeong Yeh, Hoi Poh Tee, and Sanjiv Mahadeva. 2014. Role of Prophylactic

Antibiotics in Cirrhotic Patients with Variceal Bleeding. World Journal of

Gastroenterology 20(7): 1790–96.

Leise, M.D., John J. Poterucha, Patrick S. Kamath, Ray Kim. 2014. Management of

Hepatic Encephalopathy in the Hospital. Mayo Clinic Proceedings 89(2): 241–

53.

Liu, A., Perumpail, R. B., Kumari, R., Younossi, Z. M., Wong, R. J., & Ahmed, A.

2015. Advances in cirrhosis: Optimizing the management of hepatic

encephalopathy. World Journal of Hepatology, 7(29), 2871–2879.

https://doi.org/10.4254/wjh.v7.i29.2871

Lo, E. A. G., Wilby, K. J. 2015. Use of Proton Pump Inhibitors in the

Management of Gastroesophageal Varices : A Systematic Review. Annals of

Pharmacotherapy, 207-219.

Lovena A, Miro S, Efrida. Karakteristik Pasien Sirosis Hepatis Di RSUP Dr. M.

Djamil Padang. Padang: Universitas Andalas; 2015.

Martindale. 2009. The Complete Drug Reference Thirty-sixth Edition. United

Kingdom: Pharmaceutical Press.

Martinez-Esparza, Maria. Manzano, M.T., Ruiz-Alcaraz, A.J., García-Peñarrubia, P.

2015. "World Journal of Gastroenterology". World J Gastroenterol 2015

November 7; 21(41): 11522-11541 ISSN 1007-9327 (print) ISSN 2219-2840

(online).

Matherly,S.C., & Bajaj, J.S. 2016. In : Podolsky, D. K., Camilleri, M., Fitz, J.G.,

Kalloo, A. N., Shanahan. F., Wang, T. C. Yamada’s Textbook of

gastroenterology, sixth edition. West Sussex : John Willey & Sons Ltd., pp

2107-2128.

Marciano, S., F. Morando, and P. Angeli. 2019. Spontaneous Bacterial Peritonitis in

Patients with Cirrhosis and Ascites. Hepatic Medicine : Evidence and

Research. 2019:11. 13-22.

Maulina, Meutia. 2018. Zat-Zat Yang Mempengaruhi Histopatologi Hepar.

Lhokseumawe : Unimal Press.

McCormick, P. Aiden. 2011. Hepatic Cirrhosis. In : Sherlock’s Diseases of the

Liver and Biliary System 12th Ed, by James Dooley, Andrew Burroughs,

xix

Anna Lok, Jenny Heathcote, Publication. 103–120.

MD, C. 2013. Ensefalopati Hepatikum Pada Pasien Sirosis Hepatis. Medula, Volume

1, Nomor 4,Oktober 2013. Lampung : FK Universitas Lampung.

Metwally, K., Fouad, T., Assem, M., & Yousery, M. 2018. Predictors of

Spontaneous Bacterial Peritonitis in Patients with Cirrhotic Ascites.

Journal of Clinical and Translational Hepatology, 6(4), 372–376.

doi:10.14218/JCTH.2018.0000

Montagnese, S., Russo, F. P., Amodio, P., Burra, P., Gasbarrini A., Loguercio, C.,

Scarpignato, C. 2018. Hepatic Encephalopathy: A clinical Practice Guideline

by the Italian Association for the Study of the Liver (AISF). vol. 51, issue 2,

pages 190 - 205.

National Institute of Diabetes and Digestive and Kidney Disease. 2014. "Liver

Disease, Chirrosis. Diakses dari https://www.niddk.nih.gov/health-

information/liver-disease pada 29 Agustus 2019.

Ninan J and Feldman L. 2017. Ammonia Levels and Hepatic Encephalopathy in

Patients with Known Chronic Liver Disease. USA.

Nurdjanah S. Sirosis Hati. Dalam: Sudoyo AW, Setiyohadi B, Alwi I, Simadibrata

KM, Setiati S. Buku ajar ilmu penyakit dalam. Edisi ke 6 Jakarta: Internal

Publishing; 2014. 1978-1983.

Nursalam. 2015. Manajemen Keperawatan: Aplikasi dalam Praktik

Keperawatan Profesional. Jakarta: Salemba Medika

Pantham, Ganesh, and Kevin D. Mullen. 2017. Practical Issues in the Management of

Overt Hepatic Encephalopathy. Gastroenterology and Hepatology 13(11):

659–65.

Patidar, K. R., & Bajaj, J. S. 2013. Antibiotics for the treatment of hepatic

encephalopathy. Metabolic Brain Disease, 28(2), 307–312

Pedersen, Julie Steen., Bendtsen, Flemming., Moller, Soren. 2015. Management of

Cirrhotic Ascites: DOI 10.1177/2040622315580069.

Poudyal, Nandu S., Chaudhary, Sitaram, Sudhamshu KC, Bidhan N., Paudel,

Buphendra K. 2019. Precipitating Factors and Treatment Outcomes of Hepatic

Encephalopathy in Liver Cirrhosis. Cureus 11(4): e4363

Prio, P., & Wibowo, A. 2017. Ensefalopati Hepatik pada Pasien Sirosis Hepatik. J

Medula Unila vol 7 nomor 2, 90-94.

xx

Sauerbruch, Tilman, Robert Schierwagen, and Jonel Trebicka. 2018. Managing Portal

Hypertension in Patients with Liver Cirrhosis [Version 1; Referees: 2

Approved]. F1000Research 7: 1–17.

Setiati S, Alwi I, Sudoyo AW, Stiyohadi B, Syam AF. 2014. Buku Ajar Ilmu

Penyakit Dalam jilid I. VI. Jakarta: Interna Publishing.

Shayto, Rani H., Rachel Abou Mrad, and Ala I. Sharara. 2016. Use of Rifaximin in

Gastrointestinal and Liver Diseases. World Journal of Gastroenterology

22(29): 6638–51.

Suraweera, D., Sundaram, V., & Saab, S. 2016. Evaluation and management of

hepatic encephalopathy: Current status and future directions. Gut and Liver,

10(4), 509–519. https://doi.org/10.5009/gnl15419

Suyoso, Mustika. S, and Achmad. H. 2015. Ensefalopati Hepatik Pada Sirosis Hati:

Faktor Presipitasi Dan Luaran Perawatan Di RSUD Dr. Saiful Anwar Malang.

Jurnal Kedokteran Brawijaya 28(4): 340–44.

Swaminathan, Mirashini, Mark Ellul, and Tim Cross. 2018. Hepatic Encephalopathy:

Current Challenges and Future Prospects. Hepatic Medicine: Evidence and

Research Volume 10: 1–11.

Tapper, E. B., Parikh, N. D., Sengupta, N., Mellinger, J., Ratz, D., Lok, A. S.-F., &

Su, G. L. 2018. A risk score to predict the development of hepatic

encephalopathy in a population-based cohort of patients with cirrhosis.

Hepatology 68(4).

Tjokroprawiro, Askandar. 2015. Ilmu Penyakit Dalam. Surabaya : Airlangga

University Press.

Tripathi, Diraj, Stanley, Adrian, J., Hayes, Peter C., Patch, David, Millson, Charles.

2015. UK Guidelines on the Management of Variceal Haermorrhage in Cirrhotic

Patients. Gut;64:1680-1704.

Tsochatzis EA, Bosch J, Burroughs AK. 2014. Liver Cirrhosis. Lancet. 2014; 383

(9930): 1749-1761.

Wang, Zhida, Pei Chu, and Wenjin Wang. 2019. Combination of Rifaximin and

Lactulose Improves Clinical Efficacy and Mortality in Patients with Hepatic

Encephalopathy. Drug Design, Development and Therapy 13: 1–11.

WHO. 2016. The Global Burden of Disease. www.who.int, diakses pada 19

September 2019.

Wiranata, I. M., Hasmono, D., & Surdijati, S. 2017. Studi Penggunaan Omeprazole

xxi

pada Pasien Sirosis Hati dengan Hemetamesis Melena Rawat Inap di RSUD

Kabupaten Sidoarjo. J Pharm Sci & Pract, 4(1): 36-43.

Wolf, D.C. 2012. Cirrhosis. http://emedicine.medscape.com/article/ 185856-

overview#showall, diakses pada 19 September 2019.

Xu, X.-Y., Ding, H.-G., Li, W.-G., Jia, J.-D., Wei, L., Duan, Z.-P. 2019. Chinese

guidelines on management of hepatic encephalopathy in cirrhosis. World

Journal of Gastroenterology, 25(36), 5403–5422.

https://doi.org/10.3748/wjg.v25.i36.5403

Zanetto, Alberto dan Guadalupe Garcia-Tsao. 2019. Management of Acute

Variceal Haemorrhage. F1000Research 2019, 8(F1000 Faculty Rev):966

Last updated: 25 Juni 2019 .

Zubir, N. 2009. Koma Hepatik. Dalam Buku Ajar Ilmu Penyakit Dalam Jilid 2,

edisi 5. Jakarta : Pusat Penerbitan Ilmu Penyakit Dalam Fakultas Kedokteran

Universitas Indonesia. 677-680.

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