Chronic hepatitis

Chronic hepatitisChronic hepatitisin childrenin children

BYBYDr. Tai Al AkawyDr. Tai Al Akawy

Senior pediatrician at Alexandria Senior pediatrician at Alexandria University Children’s HospitalUniversity Children’s Hospital

الرحمن الله الرحمن بسم الله بسمالرحيمالرحيم

Chronic hepatitisChronic hepatitisBased on Nelson text book of pediatrics Based on Nelson text book of pediatrics

and many online articles that will be and many online articles that will be mentioned mentioned

on the slideson the slides

LiverLiver Diseases Diseases

DEFINITIONDEFINITION

The term chronic hepatitis means The term chronic hepatitis means ongoing inflammation of the liver ongoing inflammation of the liver

persisting for persisting for more than six more than six monthsmonths that is detectable by that is detectable by biochemical and histologic biochemical and histologic

means. means.

Clinical featuresClinical features

-Depend on pathology & aetiology -Depend on pathology & aetiology --Mild illness Mild illness with dyspepsia & with dyspepsia &

variablevariable increase in liver enzymes without increase in liver enzymes without

evidenceevidence of chronic liver disease of chronic liver disease --Florid progressive Florid progressive illness with illness with evidence of chronic liver disease.evidence of chronic liver disease.

DiagnosisDiagnosis

Elevated transaminasesElevated transaminases

Minimal elevation of alk. Phos.Minimal elevation of alk. Phos.

Hepatic dysfunctionHepatic dysfunction - serum bilirubin- serum bilirubin - serum albumin- serum albumin - P.T.- P.T. Liver biopsyLiver biopsy

Chronic hepatitisChronic hepatitis OLD CLASSIFICATIONOLD CLASSIFICATION

Chronic persistant hepatitisChronic persistant hepatitis

Chronic active hepatitisChronic active hepatitis

Based on histopathological Based on histopathological distinctiondistinction

1-Chronic persistent 1-Chronic persistent hepatitis (CPH)hepatitis (CPH)

-Chronic inflammatory infiltrate-Chronic inflammatory infiltrate confined to portal tractconfined to portal tract-Spotty necrosis-Spotty necrosis-Normal liver architecture -Normal liver architecture -Cirrhosis is rare -Cirrhosis is rare

2- Chronic active 2- Chronic active hepatitis (aggressive)hepatitis (aggressive)

-Inflammatory infiltrate in portal tract & -Inflammatory infiltrate in portal tract & parenchyma (piece meal necrosis)parenchyma (piece meal necrosis)-Distorted lobular architecture -Distorted lobular architecture -Septa linking portal tract -Septa linking portal tract & C.V& C.V-Subsequent Cirrhosis can -Subsequent Cirrhosis can follow.follow.

PRESENT PRESENT CLASSIFICATION of CLASSIFICATION of

chronic hepatirischronic hepatiris CAUSECAUSE

GRADEGRADE

SEVERITYSEVERITY

CAUSECAUSE Chronic viral hepatitisChronic viral hepatitis

Autoimmune hepatitisAutoimmune hepatitis

Drug induced hepatitisDrug induced hepatitis

Metabolic disorders associated Metabolic disorders associated with CLDwith CLD

GRADEGRADE -Histological -Histological assessment of assessment of

necroinflammatory activitynecroinflammatory activity Portal inflammationPortal inflammation

Periportal Periportal necrosis necrosis

Piecemeal Piecemeal necrosis or necrosis or interface interface hepatitishepatitis

Bridging necrosisBridging necrosis

SeveritySeverity

Level of progression of the Level of progression of the disease based on the degree of disease based on the degree of fibrosis orfibrosis or cirrhosiscirrhosis

CAUSESCAUSES Hepatitis B ,C , DHepatitis B ,C , D Autoimmune hepatitisAutoimmune hepatitis Drug-induced hepatitisDrug-induced hepatitis Metabolic :Wilson's disease ,A 1-Metabolic :Wilson's disease ,A 1-

antitrypsin antitrypsin deficiency ,haemochromatosis, deficiency ,haemochromatosis, glycogen storage disease type IVglycogen storage disease type IV

Hepatitis B Virus

Hepatitis B (HBV) Hepadnaviridae (1970)

Hepatitis B Virus (HBV)Hepatitis B Virus (HBV)

1. Keeffe EB, et al. Clin Gastroenterol Hepatol. 2006;4:936–962.2. Lok AS, McMahon BJ. Hepatology. 2007;45:507–539.

19

HBVHBV : Structure: Structure

20

Hepatitis B VirusHepatitis B Virus

21

Replication of HBV

Epidemiology of Hepatitis BEpidemiology of Hepatitis B

Prevalent in Asia, Africa, Prevalent in Asia, Africa, Southern Europe and South Southern Europe and South America (2-20%)America (2-20%)

Age of infection Age of infection is important in is important in determining the outcome of the determining the outcome of the disease.disease.

Lok AS, et al. Hepatology. 2007;45:507-539.

Chronic Hepatitis B Chronic Hepatitis B InfectionInfection

Infections acquired perinatally and in early childhood usually becomes chronic

Symptomatic Infection

Chronic Infection

Age at Infection

Chronic Infection (%)

Symptom

atic Infection (%)

Birth 1-6 months 7-12 months 1-4 years Older Childrenand Adults

0

20

40

60

80

100100

80

60

40

20

0

Outcome of Hepatitis B Virus Infection

by Age at Infection

Chr

onic

Infe

ctio

n (%

)

Sexual - sex workers and homosexuals are particular at risk.

Parenteral - IVDA, Health Workers are at increased risk.

Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations.

Hepatitis B Virus Modes of Transmission

Keeffe EB, et al. Clin Gastroenterol Hepatol. 2006;4:936–962.

Diagnostic Interpretations of Diagnostic Interpretations of Hepatitis B markersHepatitis B markers

HBsAgHBsAg Non infectious component of viral coat

Indicator of disease. If > 6 months: chronic HBV

Anti-HBsAnti-HBs Antibody response to HBsAg

Indicates recovery and/or immunity

HBeAgHBeAg Antigen that correlates with replication and infectivity

High level of infectivity and replication

Anti-HBeAnti-HBe Antibody response to HBeAg

Decreasing level of replicationRemission/resolution

Anti-HBc Anti-HBc IgMIgM

Non protective antibody to the HBcAg

Recent HBV infection

Anti-HBc IgGAnti-HBc IgG As above Remote exposure to HBV

HBV DNAHBV DNA Replictative genetic material of HBV; infectious agent

Viral replication and continues infection

Diagnostic Interpretations of Diagnostic Interpretations of Hepatitis B markersHepatitis B markers

HBsAgHBsAg Non infectious component of viral coat

Indicator of disease. If > 6 months: chronic HBV

Anti-HBsAnti-HBs Antibody response to HBsAg

Indicates recovery and/or immunity

HBeAgHBeAg Antigen that correlates with replication and infectivity

High level of infectivity and replication

Anti-HBeAnti-HBe Antibody response to HBeAg

Decreasing level of replicationRemission/resolution

Anti-HBc Anti-HBc IgMIgM

Non protective antibody to the HBcAg

Recent HBV infection

Anti-HBc IgGAnti-HBc IgG As above Acute or remote exposure to HBV

HBV DNAHBV DNA Replictative genetic material of HBV; infectious agent

Viral replication and continues infection

Symptoms

HBeAg anti-HBe

Total anti-HBc

IgM anti-HBc anti-HBsHBsAg

0 4 8 12 16 20 24 28 32 36 52 100

Acute Hepatitis B Virus Infection with Recovery Typical

SerologicCourse

Weeks after Exposure

Titre

IgM anti-HBc

Total anti-HBc

HBsAg

Acute(6 months)

HBeAg

Chronic(Years)

anti-HBe

0 4 8 12 16 20 24 28 32 36 52 Years

Weeks after Exposure

Titre

Progression to Chronic Hepatitis B Virus Infection Typical Serologic

Course

HBV ScenariosHBV ScenariosHBsAgHBsAg anti-HBsanti-HBs anti-HBcanti-HBc

IgMIgManti-HBcanti-HBcIgGIgG

HBeAgHBeAg DXDX

++ -- ++ ++ ++

++ -- -- ++ ++

-- ++ -- -- --

-- ++ -- ++ --

-- -- ++ -- --

-- -- -- ++ --

Acute infection

Carrier

Vaccinated

ExposedImmune

AcuteWindow

ExposedAb lost

32

Possible Outcomes of HBV InfectionPossible Outcomes of HBV Infection

Acute hepatitis B infection

Chronic HBV infection

3-5% of adult-acquired infections

95% of infant-acquired infections

Cirrhosis

Chronic hepatitis

12-25% in 5 years

Liver failure Hepatocellular carcinoma

Liver transplant

6-15% in 5 years 20-23% in 5 years

DeathDeath

Chronic Hepatitis B Chronic Hepatitis B Infection in PediatricsInfection in Pediatrics

•Mostly asymptomaticMostly asymptomatic

•Normal growthNormal growth

•Liver damage is mild during childhoodLiver damage is mild during childhood

•Cirrhosis, hepatocellular carcinoma at any age Cirrhosis, hepatocellular carcinoma at any age (rare)(rare)

Zacharakis G. J Pediat Gastr Nutr; 44:84-91.2006

Natural History of Chronic HBV Natural History of Chronic HBV (in children)(in children)

•HBeAb seroconversion rate 55% HBeAb seroconversion rate 55% in 12 yearsin 12 years

•Lower seroconversion in vertical Lower seroconversion in vertical transmision (38.5%) Vs. transmision (38.5%) Vs. horizontal (74%)horizontal (74%)

•Loss of HBsAg seen in 5%Loss of HBsAg seen in 5%

Courtesy of Jerrold R. Turner, M.D., Ph.D.

Hepatitis B Liver BiopsyHepatitis B Liver Biopsy

This patient has cirrhosis due to hepatitis B virus (HBV)



The portal area is expanded, and the regenerative nodule is encircled by collagen



Ground-glass hepatocytes represent cells with cytoplasm swollen by viral particles.



Immunoreactive HBsAg(stained red) is deposited in the cytoplasm

Who to treat?Who to treat?

High ALTHigh ALT Inflammation in biopsyInflammation in biopsy Low HBV DNALow HBV DNA Late acquisition of Late acquisition of

infectioninfection

Better Better Response Response

to to treatmentreatmen

ttMei-Hwei Chang. Pediatric Gastroint Dis. 2004

Children with chronic HBV (HBsAg > 6 months)Children with chronic HBV (HBsAg > 6 months)

Goals of treatment in Pediatric Goals of treatment in Pediatric populationpopulation

Reducing the risk of HBV related Reducing the risk of HBV related cirrhosiscirrhosis and and HCCHCC

Elimination of Elimination of HBeAg HBeAg may may

considerably improve prognosisconsiderably improve prognosis

How to treat?How to treat?

PediatricsPediatrics

IFN-IFN-αα LamivudinLamivudinee

How to treat?How to treat?

PediatricsPediatrics

IFN-IFN-αα LamivudinLamivudinee

AdefovirAdefovirEntecavirEntecavir

Successful response to treatment will result in the disappearance of HBsAg,

HBV-DNA, and seroconversion of HBeAg.

INF-INF-αα Approx 58% of patient show Approx 58% of patient show

responseresponse Advantage:Advantage:

More durable responseMore durable response Lack of resistant mutantsLack of resistant mutants

Disadvantage:Disadvantage: Weekly SC administrationWeekly SC administration Very expensiveVery expensive Adverse reactions:Adverse reactions: Flu-like symptoms, Flu-like symptoms,

depression, anorexia, bone marrow suppressiondepression, anorexia, bone marrow suppression

LamivudineLamivudine

Virologic response in children, 23% Virologic response in children, 23% compared to 13% in placebocompared to 13% in placebo

Ad:Ad: OralOral Well toleratedWell tolerated CheapCheap

Dis:Dis: Less durability of responseLess durability of response Increased risk of drug resistant , 70% by 5 yearsIncreased risk of drug resistant , 70% by 5 years

HEPATITISHEPATITIS - C - C

Courtesy of the C. Everett Koop Institute at Dartmouth

Hepatitis C Virus Hepatitis C Virus (HCV)(HCV)

hypervariableregion

capsid envelopeprotein

protease/helicase

RNA-dependent

RNA polymerase

c22

5’core E1 E2 NS

2NS3

33c

NS4

c-100

NS5

3’

Hepatitis C Virus

Hepatitis C (HCV) Flaviviridae (1988)Structural genes at the 5' end, the non-structural genes at the 3' end

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HCV replicates exclusively in the cytoplasmvia an RNA intermediate

Nucleus

Viral entry & uncoating

Translation & processing(+)

(+)

(-)

(+)

HCV RNAreplicationVirus particle

assembly Replicativeintermediate

El-Kamary SS. J Pediatr. 143:54-9, 2003.Jonas MM. J Pediatr. 131:314-6, 1997.

Yeung LT. Hepatology. 34:223-9, 2001.

Aletr MJ. N Engl J Med. 341; 556-62. 1999

Prevalence of Hepatitis Prevalence of Hepatitis CC

•1.8% prevalence in US 1.8% prevalence in US

•10,000-60,000 newborn will be 10,000-60,000 newborn will be infected worldwide yearlyinfected worldwide yearly

Prevalence of Hepatitis Prevalence of Hepatitis CC

Genotype Distribution Genotype Distribution of Hepatitis Cof Hepatitis C

Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014.

Mode of Mode of Transmission of Transmission of

Hepatitis CHepatitis C•Transfusion of blood or contaminated Transfusion of blood or contaminated products (prior to 1992)products (prior to 1992)

•Use of intravenous drugsUse of intravenous drugs

•SexualSexual

•VerticalVertical (most important among (most important among children)children)

Mast EE. J Infect Dis. 192:1880-1889, 2005

Perinatal Perinatal Transmission of Transmission of

Hepatitis CHepatitis C•3.7% of the infants(born to HCV infected 3.7% of the infants(born to HCV infected mothers) acquired HCV.mothers) acquired HCV.

•Infection rate in HIV positive mothers, Infection rate in HIV positive mothers, 25%25%

Breast feeding and Breast feeding and transmission of Hepatitis transmission of Hepatitis

CC• HCV detected in breast milk and colostrumHCV detected in breast milk and colostrum

• Rate of transmission is identical to bottle-Rate of transmission is identical to bottle-fed infantsfed infants

• Safety based on the absence of traumatized, Safety based on the absence of traumatized, cracked or bleeding nipplescracked or bleeding nipples

Yeung LT. Hepatology.34:223-9, 2001.

Risk Factors for Vertical Risk Factors for Vertical Transmission of Hepatitis CTransmission of Hepatitis C

Breast feedingBreast feeding Vaginal deliveryVaginal deliverydoes not increasedoes not increase vertical vertical

transmissiontransmission


Risk Factors for Vertical Risk Factors for Vertical Transmission of Hepatitis CTransmission of Hepatitis C

Does increaseDoes increase vertical transmission: vertical transmission: Use of internal fetal monitoring Use of internal fetal monitoring

devicesdevices High viral loadsHigh viral loads Prolonged rupture of membranes Prolonged rupture of membranes

(>6 h)(>6 h) HIV co-infectionHIV co-infection


Natural History of Natural History of Hepatitis CHepatitis C

ExposureExposure

No No infectioninfection

AcuteAcuteChronicChronic

SpontaneoSpontaneous us

clearance clearance (early)(early)

•CirrhosiCirrhosis s (20-40%)(20-40%)

•HCC HCC (1-4%/year)(1-4%/year)

<75%<75%

>20%>20%

England K. J Pediatr. 147:227-32, 2005.

Clinical Features of Clinical Features of Hepatitis C in Hepatitis C in

PediatricsPediatrics•Normal growthNormal growth

•Mostly are asymptomaticMostly are asymptomatic

•HepatomegalyHepatomegaly

•Elevated liver enzymesElevated liver enzymes

Diagnosis of Diagnosis of Hepatitis CHepatitis C

HCV HCV antibodies antibodies (IgG)(IgG)

HCV RNA PCR HCV RNA PCR (quantitative/qualitativ(quantitative/qualitative)e)

Initial Initial screeningscreeningDiagnosisDiagnosis

Confirmation of DiagnosisConfirmation of Diagnosis (qualitative)(qualitative)

Pretreatment Pretreatment evaluationevaluationPost treatment Post treatment monitormonitor

Fried MW, et al. N Eng J Med. 2002;347:975-982.

Manns MP, et al. Lancet 2001;358:958-965.

Kelly DA. Hepatology; 34:680A. 2001Wirth S. Hepatology; 36:1280-4. 2002

Davis GL. N Engl J Med; 339:1493-9.1998

McHutchinson JG. N Engl J Med; 339:1485-92.1998

Antiviral Therapy for Antiviral Therapy for Hepatitis CHepatitis C

•Combined PEGCombined PEG Interferon and Interferon and RibavarinRibavarin

•45-62% sustained virological response45-62% sustained virological response•Better responseBetter response

•Ribavirin Side effectsRibavirin Side effects•Anemia/ThrombocytopeniaAnemia/Thrombocytopenia•Fetal malformationsFetal malformations(teratogenic)(teratogenic)

Genotype 2, Genotype 2, 33Low pretreatment viral Low pretreatment viral loadloadYounger ageYounger ageAbsence of cirrhosisAbsence of cirrhosis

Hepatitis C VirusHepatitis C VirusFate of Acute InfectionFate of Acute Infection

15%

Chronic

85%

Spontaneousresolution

Alter MJ, et al. N Eng J Med. 1999;341:556-562.

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Symptoms

anti-HCV

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4

Hepatitis C Virus InfectionTypical Serologic Course

Titre

Months YearsTime after Exposure

Hepatitis C Virus Hepatitis C Virus InfectionInfection

Natural HistoryNatural History

Stable80% (68%)

HCCLiver failure25% (4%)

Slowlyprogressive75% (13%)

Resolved15% (15%)

Acute HCV

Cirrhosis20% (17%)

Chronic HCV85% (85%)

Liver cancer and liver failure occur in 4% of patients who are exposed to HCV over a 20- to 25-year period.

Chronic Viral Hepatitis in Chronic Viral Hepatitis in PediatricsPediatrics

PreventionPrevention

The Good News: Hepatitis BThe Good News: Hepatitis B

(HBV)(HBV)VaccineVaccineHBsAg recombinant DNA technology HBsAg recombinant DNA technology

90%-95% efficacy (anti-HBs titers 90%-95% efficacy (anti-HBs titers >> 10mIU/ml) 10mIU/ml)Long-term protection Long-term protection

Post Exposure Prophylaxis(PEP)Post Exposure Prophylaxis(PEP)Hep B Immunoglobulin(HBIG),passively acquired anti-HBs Hep B Immunoglobulin(HBIG),passively acquired anti-HBs

Infants born to HBsAg+ mothers Infants born to HBsAg+ mothers (HBIG & vaccine, efficacy 95% )(HBIG & vaccine, efficacy 95% )

HBV: ACIP 2005 RecommendationsHBV: ACIP 2005 Recommendations Birth Dose Birth Dose

““For all medically stable infants weighing ≥2,000 grams For all medically stable infants weighing ≥2,000 grams at birth and born to HBsAg at birth and born to HBsAg negative negative mothers, the first mothers, the first dose of HB vaccine should be administered before dose of HB vaccine should be administered before hospital discharge.” hospital discharge.”

ACIP= Advisory committee of immunization practice

HepatitisHepatitis C C Prevention Prevention The Less Good News:The Less Good News:

There is NO effective vaccineThere is NO effective vaccineBUT;BUT;

Spontaneous clearance of HCV can occur in Spontaneous clearance of HCV can occur in 20-30% of acute infections20-30% of acute infections

Immunity against persistent HCV can be acquiredImmunity against persistent HCV can be acquired

England K. J Pediatr. 147:227-32, 2005.

Prevention HCVPrevention HCVImmune Correlates of Viral ClearanceImmune Correlates of Viral Clearance

Humoral Immunity Humoral Immunity Neutralizing antibodies, in vitro, are not necessary for Neutralizing antibodies, in vitro, are not necessary for

resolution of HCV infection.resolution of HCV infection.

Cellular ImmunityCellular Immunity Vigorous polyclonal CD4+ and CD8+ T-cell responses Vigorous polyclonal CD4+ and CD8+ T-cell responses Weak and narrow in chronically infectedWeak and narrow in chronically infected

HCVHCV Cellular Immune Response in Acute Cellular Immune Response in Acute

InfectionInfection

Bowen and Walker, Nature 2005

HCV Prevention StrategyHCV Prevention Strategy

Increased screening and knowledge of HCV status Increased screening and knowledge of HCV status reduces HCV transmissionreduces HCV transmission

2/3 of people with chronic HCV are not 2/3 of people with chronic HCV are not diagnoseddiagnosed

10% of people with HCV infection have 10% of people with HCV infection have no recognized source for their infection no recognized source for their infection

Hagan 2001 Am J Pub HealthHagan 2001 Am J Pub Health

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HBsAg

RNA

antigenHepatitis D (Delta) Virus

Hepatitis D (HDV) ? (1977)

Hepatitis DHepatitis D Requires coexistent Hep BRequires coexistent Hep B CoinfectionCoinfection: does not worsen acute : does not worsen acute

Hep B or Hep B or risk for chronic state risk for chronic state SuperinfectionSuperinfection::

– usually develop chronic HDV usually develop chronic HDV infection.infection.

– high risk of severe chronic liver high risk of severe chronic liver disease.disease.

Diagnosis: Anti-HDV IgMDiagnosis: Anti-HDV IgM

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JaundiceSymptoms

ALT Total anti-HDV

IgM anti-HDV

HDV RNAHBsAg

HBV – HDV SuperinfectionTypical Serologic

Course

Time after Exposure

Titre

76

HBV-HDV CoinfectionPre or post exposure prophylaxis to prevent HBV infection.

HBV-HDV SuperinfectionEducation to reduce risk behaviors among persons with chronic HBV infection.

Hepatitis D - Prevention

Immune disordersImmune disordersAutoimmune disease can affect the Autoimmune disease can affect the hepatocyte or bile duct hepatocyte or bile duct And, is characterized by And, is characterized by The presence of The presence of autoantibodies autoantibodies Increased Increased Ig Ig levels.levels.

DefinitionDefinitionAutoimmune HepatitisAutoimmune Hepatitis

Unresolving inflammation of the liver of unknown Unresolving inflammation of the liver of unknown cause.cause.

Reflect a complex interaction between Reflect a complex interaction between Triggering factorsTriggering factors :Infections, medications, :Infections, medications,

toxins,toxins, molecular mimicry? molecular mimicry? AutoantigensAutoantigens Genetic predisposition:Genetic predisposition:Antigen Antigen

presentation/immunocyte activation, DRB1,presentation/immunocyte activation, DRB1, TNF*2A,TNF*2A, HLA B14, HLA DR3,DR4 HLA B14, HLA DR3,DR4

Immunoregulatory mechanismsImmunoregulatory mechanismsKrawitt. N Engl J Med 2006;354:54

Autoimmune HepatitisAutoimmune Hepatitis Characterized by the presence of interface Characterized by the presence of interface

hepatitis & portal plasma cell infiltration in hepatitis & portal plasma cell infiltration in histological examinationhistological examination

hypergammaglobulinaemia hypergammaglobulinaemia auto antibodiesauto antibodies

Manns et al. Hepatology 2006;43:S132

epidemiologyepidemiology In northern EuropeansIn northern Europeans Annual incidence 1.9/100,000Annual incidence 1.9/100,000 Prevalence 16.9/100,000Prevalence 16.9/100,000 2.6% of liver transplant2.6% of liver transplant Female affected more than males Female affected more than males gender ratio 3.6:1gender ratio 3.6:1

classificationclassification 3 main subtypes3 main subtypes

Based on difference in their Based on difference in their immunological immunological markersmarkers

Czaja et al. Hepatology 2002;36:479

Type 1 AIHType 1 AIH The most common The most common

form of the disease form of the disease worldwideworldwide

Associated with Associated with ANAANA and/or and/or SMASMA

HLA DR3 & DR4HLA DR3 & DR4 Over 70% are female Over 70% are female

and over 40%and over 40% younger age groupyounger age group..


Type 2 AIHType 2 AIH More common in More common in

Europe and south Europe and south America.America.

Associated with Associated with anti-anti-LKMLKM

Described in Described in paediatrics patient paediatrics patient but but in Europe 20% are in Europe 20% are adultsadults

Krawitt. N Engl J Med 2006;354:54Czaja et al. Am J Gastroenterol 1995;90:1206

Type 3 AIHType 3 AIH

Is the least Is the least established form of established form of the disease.the disease.

Associated with Associated with anti-SLA/LPanti-SLA/LP

ReclassificationReclassification: Variant type 1 : Variant type 1 AIHAIH

(soluble liver antigen/ liver-pancreas antigen)

Diagnostic criteriaDiagnostic criteria Diagnosis require presence of Diagnosis require presence of characteristics characteristics

features features & & exclusion of other condition that exclusion of other condition that resemble AIHresemble AIH

All patients must be evaluated for All patients must be evaluated for hereditaryhereditary, , infectiousinfectious and and drugdrug induced liver injury. induced liver injury.

Interface hepatitis Interface hepatitis is the histologic hall mark is the histologic hall mark of the syndrome & of the syndrome & portal plasma portal plasma infiltration infiltration typifies the disorder, but typifies the disorder, but neither are specific.neither are specific.

Autoimmune HepatitisClinical Manifestations

Fatigue Fever Jaundice(+/-) RUQ pain Myalgia/arthralgia Anorexia Hepatosplenomegaly Spider angiomata Cushingoid features

Hirsuitism Acne Portal hypertension

– Ascites– Varices– Encephalopathy

FHF HCC Asymptomatic

Desmet et al. Hepatology 1994;19:1513

Autoimmune HepatitisExtrahepatic Autoimmune Diseases

Autoimmune thyroiditis

Grave’s disease Connective tissue

diseases Inflammatory bowel

disease Celiac disease Adrenal insufficiency

Autoimmune hematologic disorders

Type 1 DM Sjogren’s syndrome Fibrosing alveolitis Vitiligo Vasculitis Nephritis

Krawitt. N Engl J Med 2006;354:54Czaja et al. Hepatology 2002;36:479

Interface hepatitis and bridging necrosis in severe type 1 autoimmune hepatitisInterface hepatitis and bridging necrosis in severe type 1 autoimmune hepatitis

Autoimmune HepatitisHistology

Lymphoplasmacytic infiltrate

Interface hepatitis

Portal inflammation and invasion of limiting plate

Plasma cell infiltration of the portal tracts in type 1 autoimmune hepatitisPlasma cell infiltration of the portal tracts in type 1 autoimmune hepatitis

The diagnosis of AIH requires The diagnosis of AIH requires Determination of Determination of elevated aminotransferase elevated aminotransferase

and and gamma globulins gamma globulins Detection of Detection of ANAANA and/or and/or SMASMA or in their or in their

absence, absence, anti-LKManti-LKM liver tissue examinationliver tissue examination

Indications for treatmentIndications for treatment


Treatment regimensTreatment regimens

Two regimens comparable with each other Two regimens comparable with each other Prednisone alone orPrednisone alone orlower dose of prednisone in conjunction with lower dose of prednisone in conjunction with azathioprineazathioprineAll patients should be monitored for the All patients should be monitored for the development of drug side effectdevelopment of drug side effect

Czaja et al. Hepatology 2002;36:479Krawitt. N Engl J Med 2006;354:54

Autoimmune HepatitisAutoimmune HepatitisDisease RemissionDisease Remission

Disappearance of symptomsDisappearance of symptoms Normalization or near Normalization or near

normalization of AST to < 2 x ULNnormalization of AST to < 2 x ULN GG and bilirubin: normalGG and bilirubin: normal Minimal or no hepatic inflammationMinimal or no hepatic inflammation

10 year survival: 90%10 year survival: 90%Czaja et al. Hepatology 2002;36:479Krawitt. N Engl J Med 2006;354:54

relapserelapse

Relapse is common after drug withdrawalRelapse is common after drug withdrawal Patients Patients should be monitored should be monitored by serum by serum

aminotransferase ,bilirubin and gamma aminotransferase ,bilirubin and gamma globulin levelglobulin level

IBD AS A CAUSE OF IBD AS A CAUSE OF CHRONIC LIVER CHRONIC LIVER

DISEASESDISEASES

Primary sclerosing cholangitis

• PSC is an idiopathic inflammatory disease resulting in intra and extra hepatic biliary strictures and cholestasis

cirrhosis;often assoc.with ulcerative cholitis

• It can occur in infancy and childhood

•This is a cholestatic disease whose etiology is unknown

• This disease differs from primary biliary cirrhosis in that the large bile ducts, the extra hepatic biliary tree ,are affected

Symptoms:FatiguePruritisJaundiceFeverWeight loss

Diagnosis: Liver function tests CT scan Ultrasound ERCP is the diagnostic tool of choice. (Endoscopic retrograde cholangiopancreatography) Liver biopsy

Immunosuppressants and steroids

Ursodeoxycholic acid Endoscopic dilation of dominant strictures, with or without stenting

Treatment

Drug induced Chr. Drug induced Chr. hepatitishepatitis

(Medication-induced liver (Medication-induced liver diseases)diseases)

History of medicines , herbals History of medicines , herbals and alternate medicinesand alternate medicines

Mild to very severe hepatic Mild to very severe hepatic dysfunctiondysfunction

Drug induced chr. Liver DiseaseDrug induced chr. Liver Disease

Idiosyncratic reactionsIdiosyncratic reactions- - Isoniazid, Isoniazid, sodium sodium

valproate, phenytoinvalproate, phenytoin

Cholestatic reactionsCholestatic reactions- - Erythromycin, Erythromycin, phenothiazinesphenothiazines

Acute and chronic hepatitisAcute and chronic hepatitis – – Amiodarone, HIV drugs, Amiodarone, HIV drugs, àà methyl dopa methyl dopa

Discontinuation of the offending drug is the main line of therapy

Metabolic and genetic disorders:Metabolic and genetic disorders: (a) Haemochromatosis(a) Haemochromatosis (b) Wilson’s disease(b) Wilson’s disease (c) (c) αα- antitrypsin deficiency- antitrypsin deficiency (d) Glycogen storage disease type IV(d) Glycogen storage disease type IV

Thank youThank you

Chronic hepatitis

Health & Medicine

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