ACUTE VIRAL HEPATITIS

DIAGNOSIS & MANAGEMENT

I DEWA NYOMAN WIBAWA DIV.GASTROENTERO-HEPATOLOGY DEPT. INTERNAL MED UDAYANA UNIV./ SANGLAH HOSPITAL, DENPASAR.

Curicullum Vitae
• Nama
• •

: Prof. DR.Dr I Dewa Nyoman Wibawa, SpPD-KGEH

Tempat/Tgl Lahir : Klungkung, 17 November 1952 Riwayat Pendidikan : – Pendidikan dokter : FK Unud Tahun 1979 – Spesialisasi : FK Undip Tahun 1986 – Konsultan : Tahun 1997 dari Organisasi PPHI, PGI, PEGI – Doktor : Tahun 2000 FK Unair – Guru Besar : Tahun 2002 FK Unud – Pendidikan tambahan : di Jepang Tahun 1995 sampai tahun 1996 Jabatan : – Kepala Divisi Gastroentero-Hepatologi FK Unud/RS Denpasar; – Ka LitBang FK Unud; – Ka Unit Epid Klinik FK Unud. – Ketua Organisasi PPHI, PGI, PEGI Cabang Denpasar

ACUTE HEPATITIS
Definition: • Any disease process characterized by a
– diffuse inflammatory infiltrate of liver tissue, – with or without a degree of hepatocellular necrosis and local fibrosis.

• Etiology
– Infectious, Chemical, Toxic and Autoimmune

Viral Hepatitis
• Viral infection of the Liver caused by
– viruses with specific Hepatotrophic replication

Or
– systemic viral infections involving hepatocytes

• The major biochemical marker is ALT

Viral Hepatitis - Historical Perspectives
“Infectious”

A
NANB

E

Enterically transmitted

Viral hepatitis

“Serum”

B D

C
F, G, TTV ? other

Parenteraly transmitted

exposure risk behavior immunization. modification risk behavior modification ensure safe drinking water .Type of Hepatitis A Source of virus feces B C D E feces blood/ blood/ blood/ blood-derived blood-derived blood-derived body fluids body fluids body fluids percutaneous percutaneous percutaneous permucosal permucosal permucosal Route of transmission fecal-oral fecal-oral Chronic infection Prevention no yes yes yes no pre/postexposure immunization pre/postexposure immunization blood donor pre/postscreening.

Acute Viral Hepatitis • Asymptomatic infection – Inappearance • Symptomatic infection – – – – – – Prodromal illness (Flu like) Vomiting Aversion to alcohol and cigarettes RUQ discomfort Pale faeces and dark urine Jaundice .

Hepatitis A Infection .

Hepatitis A Virus .

Hepatitis A • Symptomatic Illness – Symptomatic in 80% of adults but not children (<3%) – Malaise. Vomiting and jaundice prominent • Transmission patterns – Person to person contact – Common source outbreaks especially seafood • At risk groups – Family contacts – People in institutional settings – Partners of gay men and IVDUs .

Hepatitis A Virus (HAV) • Virion – – – – Non-enveloped 27-32nm virion Hepatovirus of Picornaviridae Linear ss+RNA genome of 7500 nm Single open reading frame with VPg at 5’end of RNA – Encodes 4 structural and several non-structural proteins .

. 14: 38-58.Possible enterohepatic cycling of HAV Cuthbert JA. Clin Microbiol Rev 2001..

HAV Pathogenesis • • • • • • Ingested orally Resistant to stomach acid Reaches the liver via the intestine Replicates in hepatocyte cytoplasm Secreted in the bile and excreted in faeces Cell mediated immune clearance and cyto-pathology • Symptoms last 2-3 weeks .

1 Preicteric 2 Icteric 3 Recovery .Clinical Manifestations • • • • Incubation period 2 – 6 weeks May be asymptomatic Overt illness in 5% Present as three stages.

Hepatitis A Infection Typical Serological Course Symptoms Total antiHAV Titer ALT Fecal HAV IgM anti-HAV 0 1 2 3 4 5 6 Months after exposure 1 2 2 4 .

Treatment • No specific antiviral drug is available • Treatment is symptomatic • Specific passive prophylaxis by pooled normal human immunoglobulin given before exposure or in early incubation period can prevent or attenuate clinical illness. .

and others at risk.Vaccination for HAV • Hepatitis A vaccination is recommended for all children starting at age 1 year. travellers to certain countries. • A safe and effective formalin inactivated alum conjugated vaccine containing HAV grown in human diploid cell culture is available • A full course containing two intramuscular injections of the vaccine • Protection starts after 4 weeks after injection and lasts for 10 – 20 years .

g.Prevention of Hepatitis A Infection • Pre-exposure – travelers to intermediate HAV-endemic regions and high • Post-exposure (within 14 days) Routine – household and other intimate contacts Selected situations – institutions (e.. day care centers) – common source exposure (e..g. food prepared by infected food handler) .

Hepatitis B Infection .

• 1968 identified with association in serum hepatitis. names as Australia antigen. • Surface component of HBV called as surface antigen. .Hepatitis B Virus • Blumberg in 1965 discovers.

Acute Hepatitis B • Symptoms & signs – 70% sub-clinical and 30% icteric – Flu-like or serum sickness – Constitutional symptoms with Jaundice • Laboratory finding – AST / ALT increased and may rise 1000 IU/ml – High bilirubin – HBs Ag (+). HBc IgM (+) and HBV –DNA (+) .

• Infection – Immunodeficient person are likely to because asymptomatic carrier followed infection . N K cell and cytotoxic T cell attack In the absence of adequate immune response HBV infection may not cause hepatitis. • But lead to carrier state.Pathogenesis of HBV infection • • • • • Disease is Immune mediated Hepatocytes carry viral antigen Immune response subject to antibody dependent.

5%-1% <5 yrs. 2%-10% 15%-25%  Premature mortality from chronic liver disease: . 30%-50% 0.Clinical Features  Incubation period:  Clinical illness (jaundice):  Acute case-fatality rate:  Chronic infection: Average 60-90 days Range 45-180 days <5 yrs.Hepatitis B . <10% 5 yrs. 30%-90% 5 yrs.

What are the clinical symptoms of Hepatitis B ?? .

2003.The Clinical Outcomes of HBV Infection Recovery 10–70% Perinatal/childhood acute infection 30–90% Chronic infection Adult acute infection < 5% 95% < 1% Fulminant hepatitis Recovery  1* Mild. J. 39 (S1):S3–25 . Hepatol. moderate or severe chronic hepatitis Inactive carrier state 5–50 years  4* Decompensation  2–10* Cirrhosis  3* Transplant or Death 2–8* HCC * per 100 patient-years  0.1* Adapted from EASL Consensus Statement.

Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Symptoms HBeAg anti-HBe Total anti-HBc Titre HBsAg IgM anti-HBc anti-HBs 0 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure .

Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Acute (6 months) HBeAg HBsAg Total anti-HBc Chronic (Years) anti-HBe Titre IgM anti-HBc 0 4 8 12 16 20 24 28 32 36 52 Years Weeks after Exposure .

However.used as a general marker of infection. • anti-HBcIgG . more accurate than HBeAg especially in cases of escape mutants. • HBsAg . • HBsAb . • anti-HBc IgM .indicates active replication of virus and therefore infectiveness. • Anti-Hbe . Used mainly for monitoring response to therapy.past or chronic infection.used to document recovery and/or immunity to HBV infection. .Diagnosis • A battery of serological tests are used for the diagnosis of acute and chronic hepatitis B infection.marker of acute infection.indicates active replication of virus. the patient can still be positive for HBsAg which is made by integrated HBV.virus no longer replicating. • HBeAg . • HBV-DNA .

.Treatment • Patients with Hepatitis needs supportive treatment • Hepatotrophic agent is considerable treatment. • IN ACUTE EXCACERBATION CASES ORAL ANTI VIRAL IS IMPORTANT.

Hepatitis C Infection .

with high mutability .HCV Virology • The virus is not been grown in culture • The virus is 50.60 nm with linear single stranded RNA genome surrounded by an enveloped carrying glycoprotein spikes • Now classified as Hepacivirus in the family of Flaviviridae • Six genotypes are identified.

Hepatitis C .Clinical Features Incubation period: Clinical illness (jaundice): Average 6-7 wks Range 2-26 wks 30-40% (20-30%) 70% 85-100% No protective antibody response identified Chronic hepatitis: Persistent infection: Immunity: .

Hepatitis C Virus Infection Typical Serologic Course Symptoms antiHCV Titre ALT Normal 0 1 2 3 4 5 Months 6 1 2 3 4 Years Time after Exposure .

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.

Am J Gastroenterol.88:240. TX. Takahashi M et al.Disease Progression of Hepatitis C Virus (HCV) Acute HCV 60%-85% Chronic HCV 20%-50% Cirrhosis ~ 20% ~ 20% Liver Cancer Liver Transplant Candidates Hepatic Failure Adapted from Brown RS. 1993. NIH Consensus Development Conference Statement.36(suppl. Dallas. Gastroenterol Clin North Am. 1):S3. 1993. Koretz RL et al. . April 6. Hepatology. Epidemiology and Natural History of Hepatitis C.23:603. 1994. Presented at: ACG Clinical Implications meeting. Ann Intern Med. 2002. Davis GL et al. 2000.119:110.

Cohort Case Definition for Acute HCV Infection two of three: 1. marked elevation in ALT (> 10 x ULN) 3. wide fluctuations in HCV VL (> 1 log) characteristic of acute HCV infection . seroconversion (prefer < 1 year) 2.

Acute HCV Infection •first 6 months of infection •no specific diagnostic test •spontaneous clearance can occur •treatment highly effective Chronic HCV Infection •after 6 months of infection •less responsive to treatment •cause of almost all HCV-related liver damage .

Gastroenterology.Outcome of Acute HCV Infection 54 cases observed for 3 months without treatment 46 symptomatic 24 cleared (52%).125:80. all within 16 wks 9 asymptomatic None cleared Gerlach JT et al. 2003. .

125:80.141:W-91. 2001. polymerase chain reaction Gerlach JT et al. 2003. Gastroenterology. 50% chance of spontaneous viral clearance by 12 weeks • If no symptoms in first 12 weeks. little chance of spontaneous clearance • If PCR still positive at 5-6 weeks. 2004. . N Engl J Med.First 12 Weeks Are Important • If symptoms develop. Pimstone NR et al. Ann Int Med. little chance of spontaneous clearance • Transition from acute to chronic infection probably occurs between 12 and 16 weeks • Nearly 100% cure rate if antiviral treatment started by 12 weeks PCR.345:1452. Jaeckel E et al.

Hepatology. Hepatology. Gerlach JT et al. 2.Acute HCV: Treatment Studies N 1. treatment 1. Nomura H et al.39:1213.39:1721. N Engl J Med. Jaeckel E et al. Kamal SM et al. 2004. . 20 20 Time to Rx (wk) Treatment 12 12 PEG (180 or 1.5/kg) PEG + Ribavirin SVR (%) 80 85 2. 2003. 2004. 15 15 26 44 8 52 12-24 4-16 IFN 6MU/d x 4 wks 6MU TIW x 20 wks IFN or PEG x 24-52 wks IFN 5MU TIW 100 53 80 98 3. 4.125:80. Rx. 3. Gastroenterology. 2001. 4.345:1452.

anti-HCV negative PCR weekly x 2 Negative Positive (Get viral load) Flu sx/Jaundice Repeat at 12 weeks Asymptomatic (-) Done sx.Acute HCV: Management Summary ALT normal. symptoms (+) PCR at 6 weeks (+) (-) PCR at 12 weeks (+) (-) PEG-IFN x 24 weeks Done .

gov/ncidod/diseases/hepatitis/slideset/. . Accessed 10/1/04.Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection Anti-HCV Symptoms +/- HCV RNA Titer ALT Normal 0 1 4 6 1 2 3 2 3 5 [Months] [Years] Time After Exposure 4 Adapted from CDC Hepatitis Slide Kit. http://www.cdc.

Symptomatic patients may clear HCV 2.Acute HCV Infection: Summary 1. Standard dose of PEG-IFN weekly x 24 weeks will achieve SVR in 85%-100% . almost always by 12 weeks 3. Start treatment for asymptomatic infections at 6 weeks 4. Start treatment for symptomatic infections if still positive at 12 weeks 5. Spontaneous clearance usually occurs by 6 weeks.

Hepatitis D Infection .

Acute hepatitis D .

 Superinfection – usually develop chronic HDV infection.Hepatitis D . – may present as an acute hepatitis. . – high risk of severe chronic liver disease. – low risk of chronic infection.Clinical Features  Coinfection – severe acute disease.

Hepatitis D Virus Modes of Transmission  Percutanous exposures  injecting drug use  Permucosal exposures  sex contact .

HDV Coinfection Typical Serologic Course Symptoms ALT Elevated Titre IgM anti-HDV anti-HBs HDV RNA HBsAg Total anti-HDV Time after Exposure .HBV .

HDV Superinfection Typical Serologic Course Jaundice Symptoms ALT Total anti-HDV Titre HDV RNA HBsAg IgM anti-HDV Time after Exposure .HBV .

Hepatitis E Infection .

6 kb in size.Hepatitis E Virus • • • • • Calicivirus-like viruses unenveloped RNA virus. 32-34 nm in diameter +ve stranded RNA genome. very labile and sensitive Can only be cultured recently . 7.

15%-25% Increased with age None identified . 1%-3% Pregnant women.Hepatitis E .Clinical Features  Incubation period: Case-fatality rate:    Illness severity: Chronic sequelae: Average 40 days Range 15-60 days Overall.

Hepatitis E Virus Infection Typical Serologic Course Symptoms ALT IgG anti-HEV Titer Virus in stool IgM anti-HEV 0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 Weeks after Exposure .

MANAGEMENT • No specific therapy. high calory & protein diet. . • Bed rest. • Special treatment for fulminant hepatitis and cases with encephalopathy hepatic.

LIVER FUNCTION TEST ABNORMALITIES. 1/21/2014 56 .SUMMARY • DIAGNOSIS OF ACUTE HEPATITIS BASED ON CLINICAL APPEARANCE. AND SEROLOGIC DIAGNOSIS FOR ACUTE VIRAL HEPATITIS. • MANAGEMENT IN GENERAL CONSIST OF SUPPORTIVE AND SYMPTOMATIC TREATMENTS. EXCEPT FOR ACUTE HEPATITIS C EARLY INTERFERON TREATMENT IS IMPORTANT FOR PREVENTION OF CHRONICITY . HEPATOTROPHIC DRUGS.

MATUR SUKSMA 1/21/2014 57 .