Hepatitis & It’s Complication Fahmi Indrarti Sub Bagian Gastroenterohepatologi, Bagian Penyakit Dalam Fakultas Kedokteran Universitas Gadjah Mada/RSUP Dr. Sardjito Yogyakarta
A syndrome of diverse etiology Hepatic inflammation or injury with hepatic cell necrosis Characterized by elevation of aminotransferases ~How abrupt the liver damage acute & chronic - clinically unapparent
Causes of hepatitis Infection Viral Nonviral : bacterial Immune disorders Metabolic diseases Hepatic perfusion and oxygenation problems Toxic injury Medications Environmental or industrial toxins Use of chemical and herbs as complementary & alternative medicine (CAM) therapy Clues for etiology A careful history Use of medications, herbals, “natural therapies”, etc. … and physical exam does not give a clear and obvious cause for acute hepatitis * discontinue all possible hepatotoxins * investigate viral causes by ordering IgM anti-HAV, HBsAg, IgM anti-HBc, anti-HBs, anti- HCV, (HCV-RNA) sev. markers for * other common forms of viral hepatitis * forms of hepatitis that can have rapid and severe evolution but are treatable markers for uncommon forms Suggest chronic hepatitis The most common: chronic hepatitis C and B, alcoholic liver disease, autoimmune hepatitis, drug-induced (medication or CAM therapy), NAFLD
Other causes: metabolic disorders, immune disorders, exposure to industrial/environmental toxins
VIRAL HEPATITIS The most common cause of liver disease The major cause of persistent viremia Many hepatitis episodes : inkubation Pre-interic, icteric, or convalescense Historical Perspective
The Agents of Viral Hepatitis Classified into two groups I. Enterically transmitted • Hepatitis A Virus (HAV) • Hepatitis E Virus(HEV) II. Blood borne agents • Hepatitis B Virus (HBV) • Hepatitis D Virus (HDV) • Hepatitis C Virus (HCV) • Hepatitis G Virus (HGV) HAV, HEV, and etc are Non enveloped viruses Survive intact when exposed to bile Shed in feces Not linked to chronic liver disease Don’t result in a viremic or intestinal carrier state HBV, HCV, HDV and HGV are : Enveloped viruses Disrupted by exposure to bile / detergents Not shed in feces Linked to chronic liver diseases Associated with persistent viremia
Epidemiology & Risk Factors Hepatitis A Incubation period : 15-50 days Worldwide distribution : highly endemic in developing countries HAV is excreted in the stools Viremia is short lived Prolonged fecal excretion Enteric No evidence for maternal-neonatal transmission Prevalence correlates with sanitary standards & large household size Percutaneous transmission rare Hepatitis E Incubation period : 40 days Widely distributed : epidemic and endemic forms HEV RNA in serum and stool during acute phase The most common form of sporadic hepatitis A largely waterborne epidemic disease Intrafamilial, secondary cases are uncommon Maternal-neonatal transmission has been documented Prolonged viremia or fecal shedding unusual Hepatitis B Worldwide distribution : HBV carrier prevalence >15% in Asia Incubation period: 15 to 180 days (average 60-90 days) HBV present in blood, semen, cervicovaginal secretions, saliva, other body fluids HBV viremia lasts for weeks to months after acute infection Epidemiology & risk factors of Hepatitis B 1-5% of adults, 90% of infected neonates, and 50% of infants develop chronic infection and persistent viremia Persistent infection linked with chronic hepatitis, cirrhosis, hepatocellular carcinoma Hepatitis D Incubation period : 4-7 weeks Endemic in Mediterranean basin, European parts of former Soviet Union, parts of Africa, Middle East, and Amazon basin. Viremia short lived (acute infection) or prolonged (chronic infection). HDV infections occur solely in individuals at risk for HBV infection (coinfections or superinfections) Hepatitis C Incubation period :15 to 160 days (major peak at about 50 days) Prolonged viremia and persistent infection common : wide geographic distribution Persistent infection linked with chronic hepatitis, cirrhosis, hepatocellular carcinoma
Hepatitis G Incubation period uncertain Prolonged viremia and persistent infection common HGV RNA in 10 – 20% of patients with Chronic hepatitis Chronic hepatitis B Chronic hepatitis C Cryptogenic cirrhosis Clinical Features A. Self-limited disease Clinically a symtomatic in apparent infection fulminant, fatal disease Clinical syndromes: prodromal (non specific) Malaise, anorexia, nausea and vomiting Flu-like symptoms of pharyngitis, cough, coryza, photophobic, headache, and myalgias Fever uncommon except HAV infection Serum sickness syndrome < 10% of HBV infection Prodromal symptom disappear onset jaundice, dark urine, pruritus (mild, transient) Hepatomegaly Splenomegaly (10-20%) B. Fulminant disease Changes in mental status (encephalopaty) Lethargy, drowsiness, coma Reversal of sleep patterns Personality changes Cerebral edema Coagulopathy Multiple organ failure Development of ascites, anasarca Case fatality rate : 60% Serial physical examinations : shrinking liver Extraordinarily high rates, approaching 10-20%, in pregnant women with hepatitis E, particularly during the third trimester C. Cholestatic hepatitis Jaundice may be striking and persist for several months prior to complete resolution Pruritus may be prominent Persistent anorexia and diarrhea in a few patients Excellent prognosis for complete resolution Most commonly seen in HAV infection D. Relapsing Hepatitis
Symptoms and liver test abnormalities recur weeks to months after improvement or apparent recovery Most commontly seen in HAV infection – IgM anti-HAV may remain positive, and HAV may once again be shed in stool. Arthritis, vasculitis, and cryoglobulinemia may be seen. Prognosis is excellent for complete recovery even after multiple relapses (particularly common in children)
Diagnosis Differential diagnosis Drug and toxin induced liver disease Ischemic hepatitis Autoimmune hepatitis Alcoholic hepatitis Acute biliary tract obstruction Diagnosis-Hepatitis A
Diagnosis-Hepatitis E
Diagnosis-Hepatitis B
Diagnosis-Hepatitis D
Diagnosis-Hepatitis C
Serologic diagnosis
Treatment A. Self-limited infection Outpatient care unless persistent vomiting or severe anorexia leads to dehydration Maintenance of adequate caloric and fluid intake No specific dietary recommendations A large breakfast may be best-tolerated meal Prohibitation of alcohol during acute phase Vigorous or prolonged physical activity should be avoided Limitation of daily activities and rest periods determined by the severity of fatigue and malaise No specific drug treatment; corticosteroids of no value All nonessential drugs: discontinued B. Fulminant hepatitis Hospitalization required As soon as diagnosis made Management best undertaken in a center with a liver transplantation program No specific therapy available Goals Continous monitoring and supportive measures while awaiting spontaneous resolution of infection and restoration of hepatic function Early recognition and treatment of life-threatening complications Maintenance of vital functions Preparation for liver transplantation if recovery appears unlikely Survival rates of about 65% or greater achieved by early referral for liver transplantation
C. Cholestatic hepatitis Course may be shortened by short-term treatment with prednisone or ursodeoxycholic acid, but no clinical trials available Pruritus may be controlled with cholestyramine D. Relapsing hepatitis Management identical to that of self-limited infection CHRONIC COMPLICATIONS OF HEPATITIS Cirrhosis Characteristics - Diffuse process - Fibrosis and the conversion of normal liver architecture into structurally abnormal nodules which lack normal lobular organization (WHO) - Regeneration of hepatic cell necrosis Failure function of hepatic cells & interference blood flow in the liver Jaundice, portal hypertension & varices, ascites, hepatic encephalopathy, ultimately hepatic failure Classification Morphologic less useful, considerable overlap Micronodular: uniform nodules Ø < 3 mm, in alcoholic,hemochromatosis, billiary obstr., hepatic vein obstr. Macronodular: nodular variation > 3 mm, in HBV/HCV, Fe+Cu deposit, 1-antitrypsin def., PBC Mixed Etiologic Most usefull clinically Excessive alcohol use & viral hepatitis Clinical features
General features: fatigue, anorexia, malaise, weight loss, muscle wasting, fever
Dermatologic: spider telangiectasis, palmar erythema, nail changes (clubbing, white nails, azure lunules), Dupuytren’s contractures, jaundice
Neurologic: hepatic encephalopathy, peripheral neuropathy
Musculoskeletal: reduction in lean muscle mass, hypertrophic osteoarthropathy (synovitis, clubbing, and periostitis), hepatic osteodystrophy, muscle cramps, umbilical herniation
Potential complications of cirrhosis
Ascites permagna
Spontaneous bacterial peritonitis Variceal hemorrhage Hepatic encephalopathy Hepatorenal syndrome Hepatopulmonary syndrome Hepatocellular carcinoma
Diagnosis Physical examination Laboratory evaluation Imaging modalities Management Most cases: focuses on treatment of complication Specific treatment Phlebotomy for hemochromatosis Alcohol avoidance for alcohol induced cirrhosis Antiviral drug Liver transpantation Screening for HCC (every 6 months) Serial USG Serum alpha feto protein Karsinoma Hepatoselulare (KHS) Merupakan 40% dari tumor ganas hati 70-80% berkaitan dengan sirosis hati Insiden + 250.000 kasus pertahun meski sangat berbeda di beberapa negara Negara maju : Insiden rendah Sering pada usia tua Berkaitan dg sirosis o.k. alkohol Negara berkembang : Insiden tinggi Usia lebih muda berkaitan dg hepatitis B, C Prognosis buruk,rata2 kelangsunagn hidup 3-4 bl Etiologi Hepatitis virus B, C Aflatoksin yg dikaitkan oleh jamur apergilus florus Sirosis hati terutama makronoduler Diagnosis Anamnesis Pemeriksaan fisik Biokimia darah : Alfa fetoprotein meningkat pada 60-80% kasus PIVKA II (Protein Induced by Vit. K Absence Antagonist II) Bilirubin Alkali fosfatase Transaminase Radiologi : pada hampir 30% terjadi peninggian USG : mendeteksi nodul ca gambaran tidak khas
Angiography : sangat vaskuler. Dd tumor metastase = sedikit vaskularitas CT Scan dan MRI Canggih Informasi perluasan tumor & hubungannya dg vasa2 Laparoskopi : melihat perluasan tumor ekstrahepatik dan biopsi hati, kel. Limfe, perifonem dg tepat Patologi anatomi : diambil sel hati dg jalan biopsi aspirasi dg jarum halus (AJH) membuka/bimbingan USG Terapi Keberhasilan terapi tergantung : Besar/kecil/perluasan tumor Ada/tidak latar belakang sirosis Transplantasi Operasi berhasil baik bila : tumor kecil, satu lobus, belum metastase, tidak ada sirosis Dengan skining yg baik kelangsungan hidup 50-60% Radioterapi : Jarang Hanya untuk mengurangi nyeri pd metastase tulang Kemoterapi : Keberhasilan diragukan Embolisasi (TAE) dengan alkohol Suportif : mengurangi penderitaan Upaya pencegahan : mencegah penularan virus hepatitis B & C
