Hepatitis & Its 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
Dont 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 < 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), Dupuytrens 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