HEPATOBILIARY SYSTEM BLOCK

CASE 2

Ronald Chrisbianto Gani 405090223 Faculty of Medicine 2009 Tarumanagara University

LEARNING OBJECTIVES
Viral Hepatitis
HAV HBV HCV HDV HEV HGV HTT YF EBV

Toxic & Drug Induced Hepatitis Alcoholic Hepatitis Autoimmune Hepatitis

ACUTE VIRAL HEPATITIS

Harrisons Principle of Medicine 18th Ed

Harrisons Principle of Medicine 18th Ed

VIRUS HEPATITIS A
Masa inkubasi 2-6 mggu Paling sering menyerang umur 5-14 tahun Tidak menyebabkan hepatitis kronis Jarang menyebabkan hepatitis fulminan Angka mortalitas sangat rendah Endemik di negara sanitasi buruk Gejala klinis ringan atau asimtomatik Penularan fecal-oral, bisa melalui air Picornavirus, 27nm, ssRNA, unenveloped, tidak sitotoksik, kerusakan sel krn peran imunologis Profilaksis : ISG atau HAV vaccine

PENANDA SEROLOGIS HAV

Robbins Cotran Basic of Pathology 8ed

VIRUS HEPATITIS B
HBV menetap di darah selama pasien sakit Terdapat di semua cairan tubuh kec. Tinja Menyebar melalui kontak dg sekret/darah Terbukti ada penularan vertikal Infeksi perinatal HBV Kronis Hepadnaviridae, dsDNA Masa inkubasi 4-26mggu (~6-8mgg) Dua Fase infeksi HBV
Fase proliferatif - Fase Integratif

Strain yg tidak mengekspresikan HBeAg tapi membentuk HBcAg, berkaitan dg hepatitis fulminan, atau munculnya mutant virus

VIRUS HEPATITIS B

Robbins Cotran Basic of Pathology 8ed

STAGES OF HEPATITIS B

Sherlock & Dooley's Diseases of Liver and Biliary System 11th ed

PENANDA SEROLOGIS HBV

Robbins Cotran Basic of Pathology 8ed

HEPATITIS B MARKER

Sherlock & Dooley's Diseases of Liver and Biliary System 11th ed

SEROLOGIC PATTERNS

Harrisons Principle of Medicine 18th Ed

PROFILAKSIS

Sherlock & Dooley's Diseases of Liver and Biliary System 11th ed

NATURAL HISTORY

Sherlock & Dooley's Diseases of Liver and Biliary System 11th ed

VIRUS HEPATITIS C
Penyebaran terkait transfusi, pemakaian obat terlarang IV, pada petugas kesehatan Hepatitis sporadis sering tdk diketahui penyebabnya Penyebab utama penyakit hati kronis di negara Barat Flaviviridae, ssRNA Peningkatan IgG anti HCV tidak memberi imunitas selektif Masa inkubasi 2-26 mgg (~6-12mgg) Gejala HCV akut ringan, asimtomatik pd 75% org Peningkatan episodik kadar aminotransferase tanpa gejala klinis infeksi persisten

PENANDA SEROLOGIS HCV

Robbins Cotran Basic of Pathology 8ed

PERJALANAN PENYAKIT

VIRUS HEPATITIS DELTA

Bergantung scr mutlak pd koinfeksi HBV Tinggi di Afrika, jarang di Asia Tenggara dan Cina Indikator : IgM anti HDV Utk koinfeksi akut : IgM thd AgHDV dan HBcAg Pada superinfeksi : HBsAg ada di serum, antibodi anti HDV menetap dalam kadar rendah

KOINFEKSI DAN SUPERINFEKSI

Robbins Cotran Basic of Pathology 8ed

VIRUS HEPATITIS E
Transmisi melalui air, endemik di India dan negara sanitasi buruk lainnya Jarang terjadi infeksi sporadis Tidak menjadi kronis dan viremia Angka kematian tinggi pd wanita hamil (20%) Masa Inkubasi 2-8mgg (~6mgg) ssRNA, unenveloped, calcivirus Diagnosis : IgG dan IgM anti HEV, PCR HEV RNA

VIRUS HEPATITIS G
Flaviviridae, 25% homologi dg HCV Penularan melalui darah, seksual Tidak bersifat hepatotropik Tidak menyebabkan peningkatan aminotransferase serum Menimbulkan efek protektif pd pasien yg mengalami koinfeksi HIV

VIRUS HEPATITIS TT
Unenveloped ssDNA, Circoviridae 1% American Blood Donor Not causative agents for Hepatitis Sering ditemukan pd pasien akut atau kronik namun tidak menimbulkan gejala Carrier banyak trdpat pd org sehat, tidak menyebabkan kerusakan liver

YELLOW FEVER
Group B arbovirus Ditularkan oleh nyamuk yg terinfeksi Endemik di Amerika selatan dan Afrika Masa inkubasi 3-6 hari Gejala : demam, menggigil, sakit kepala, backache, lemah, muntah, BP turun, hemoragik, jaundice, albuminuria, bradikardia relatif. Namun pd kebnaykan kasus, gejala ringan, tidak ada ikterus Diagnosis : IgM thd Yellow Fever, serum transaminase meningkat relatif thd keparahan Tidak ada treatment spesifik. Kematian bisa disebabkan renal damage, lesi hepatik self-limited dan short-lived Pencegahan dg vaksinasi minimal 10 hari sebelum bepergian ke daerah endemik, dan kontrol thd nyamuk

 Human Herpes Virus IV (EBV) excites generalized reticuloendothelial reaction Pada anak : asimtomatik Pada remaja : mimic HAV, HBV, HCV Pada dewasa : demam, sakit di kuadran kanan atas, abdominal discomfort Pada usia lanjut : bisa menjadi fulminan Bisa menjadi pemicu hepatitis autoimun Pada pasien immunosupresi, bisa terjadi limphoproliferative disorders Dapat disertai dengan ikterus Penanda : Serum albumin sedikit menurun, serum globulin sedikit meningkat, hiperbilirubinemia (50%), serum transaminase meningkat 20x normal (80%), alkaline phospatase meningkat (30%), Monospot reaction (+), DIAGNOSIS : antibodi IgM terhadap kapsid EBV

INFECTIOUS MONONUCLEOSIS (Epstein-Barr Virus)

INFECTIOUS MONONUCLEOSIS

Sherlock & Dooley's Diseases of Liver and Biliary System 11th ed

CLINICAL SIGNS
Carrier State Asimptomatic Acute Hepatitis Chronic Hepatitis Fullminant Hepatitis

CLINICAL SIGNS
Carrier State Tanpa gejala Mampu menularkan Pada HBV : transmisi vertikal 90-95% kasus carrier, pd dewasa hanya 110% kasus carrier Gangguan imunitas resiko menjadi carrier HCV banyak (0,2-0,6% populasi USA) Asimptomatic Teridentifikasi scr tidak sengaja Peningkatan aminotransferase serum Ditemukan antibodi

CLINICAL SIGNS
Acute Viral Hepatitis

Masa Inkubasi Praikterik simtomatik

Gejala non spesifik : malaise, lelah, mual, nafsu makan hilang, weight loss, demam ringan, sakit kepala, nyeri sendi dan otot, muntah, diare, serum sickness, hepatomegali

Ikterus simtomatik
Ikterus muncul, gejala lain mereda Sering pd HAV dewasa, 50% HBV, jarang di HCV

Pemulihan

CLINICAL SIGNS

Chronic Hepatitis Bukti simtomatik, biokimiawi, serologis, penyakit hati yg berkelanjutan > 6bln. Paling sering krn virus, namun bisa krn etiologi lain (wilson disease, alpha1 antitripsin def, obat, etc) HCV paling sering Tanda : aminotransferase serum meningkat Gejala : malaise, spider angioma, eritema palmaris, hepatomegali ringan, nyeri tekan hati Lab : pemanjangan PT, kadang hipergamaglibulinemia, hiperbilirubinemia, fosfatase alkali meningkat, pada HBV dan HCV kompleks imun vaskulitis dan glomerulonefritis. Pd HCV 50% krioglobulinemia Penyebab kematian : sirosis, gagal hati, ensefalopati hepatika, hematemesis masif dari varises esofagus HBV kronis pd neonatus dan HCV karsinoma hepatoselular

DIAGNOSTIC APPROACH

Harrisons Principle of Medicine 18th Ed

TOXIC & DRUG-INDUCED HEPATITIS

TOXIC & DRUG INDUCED HEPATITIS

DIRECT TOXIC
Predictable regularity Dose dependent Latent period is short Clinical manifestation in under 48hr Special characteristic, ex: Carbon tetrachloride and tricholoroetylene centrilobular zone necrosis, tetracycline microvesicular fat deposits, etc

IDIOSYNCRATIC Infrequent, Inpredictable Not dose dependent Associated with extrahepatic manifestation, rash, arthralgia, fever, etc Immunologicaly mediated

MECHANISM OF LIVER INJURY

Harrisons Principle of Medicine 18th Ed

DRUG-INDUCED HEPATITIS

Harrisons Principle of Medicine 18th Ed

Harrisons Principle of Medicine 18th Ed

Harrisons Principle of Medicine 18th Ed

Harrisons Principle of Medicine 18th Ed

ACETAMINOPHEN OVERDOSAGE
Acetaminophen metabolized by Phase 2 Metabolite : N-acetyl-benzoquinone-imine (NAPQI) detoxified by binding to gluthatione High NAPQI or low gluthathione cause NAPQI to bind to nucleophilic hepatocytes macromolecules hepatocyte necrosis Alcohol supress hepatic gluthathione production alcoholics has lower maximum dose of acetaminophen Cause severe centrilobular hepatic necrosis Fatal fullminant in ingestion >25g 4-12hr after ingestion : nausea, vomiting, diarrhea, abdominal pain, shock 24-48 hr : hepatic injury 4-6 days : hepatic failure, Aminotransferase levels reach 10.000, renal failure, myocardial injury

ACETAMINOPHEN OVERDOSAGE
Treatment : gastric lavage, supportive measures, oral administration High acetaminophen blood level sulfhydryl compounds (ex: Nacetylsisteine) Therapy starts 8hr after ingestion and effective until 24-36hrs after ingestion Hepatic Failure liver transplant
Harrisons Principle of Medicine 18th Ed

AUTOIMMUNE HEPATITIS

HEPATITIS AUTOIMUN
Sindrom hepatitis kronis pada pasien dengan beragam kelainan imunologis Mortalitas dalam 6 bulan tanpa treatment : 40% Survival rate 10tahun dengan treatment : 80-90% Gambaran utama
Predominasi wanita (70%) Tidak ada penanda serologis u/ etiologi virus Peningkatan IgG serum (>2,5 g/dL) Titer antibodi tinggi pd 80% kasus Peningkatan frekuensi HLA-B8 atau HLA-DRw3 Adanya penyakit autoimun lain, mis : artritis rematoid, tiroiditis, sindrom Sjorgen, kolitis ulserativa

HEPATITIS AUTOIMUN
3 Tipe Hepatitis autoimun
Tipe I : antibodi antinukleus dan atau antiotot polos dalam darah (80-85%) Tipe II : antibodi mikrosom hati/ginjal (5%), biasanya pd pasien muda Tipe III : antibodi thd antigen hati / pankreas

Pasien simtomatik cenderung kerusakan hati parah, jarang mengalami remisi sempurna. Resiko sirosis adalah 5%. Kematian disebabkan karena sirosis Treatment : Prednisone / Prednisolone monotherapy, or half-dose Prednisone + Azathioprine. If refracter, give high dose. If still refracter, give cyclosporin, tacrolismus, mycophenolate mofetil, then liver transplant

ALCOHOLIC LIVER DISEASE

ALCOHOLIC LIVER DISEASE

Caused by chronic excessive alcohol ingestion Three major lesion
Fatty liver (most common) Alcoholic Hepatitis Cirrhosis

Only 10-20% alcoholics will develop alcoholic hepatitis

Harrisons Principle of Medicine 18th Ed

PATHOGENESIS OF LIVER INJURY TO CHRONIC ETHANOL INGESTION

Harrisons Principle of Medicine 18th Ed

ALCOHOLIC LIVER DISEASE

Chronic HCV infection is an important comorbidity of alcoholic hepatitis to cirrhosis Alcohol is a direct hepatotoxin. But also initiates a variety of metabolic responses which cause hepatotoxic response Natural History
Fatty Liver (reversible) Alcoholic Hepatitis Cirrhosis

Character of Alcohol hepatitis : ballooning degeneration, spotty necrosis, PMN infiltrate, fibrosis in perivenular and perisinusoidal space

ALCOHOLIC LIVER DISEASE

Clininal Features : right upper quadrant discomfort, tender hepatomegaly, nausea, jaundice. Accurate drinking history is important for diagnosis Some patient may be asimptomatic Critically ill patients have short term mortality rates >50% Severe : coagulopathy, anemia, albumin serum <25g/L, bilirubin serum >8mg/dL, renal failure, ascites Treatment : Complete abstinence of alcohol and administration of glucocorticoid or alternatives Discriminant Function : 4.6 x [PT-control (seconds)] + serum bilirubin (mg/dL) . IF >32 poor prognosis

TREATMENT ALGORITHM

Harrisons Principle of Medicine 18th Ed