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