Chronic hepatitis

الرحمن ا الرحمن بسم ا بسمالرحيمالرحيم

LiverLiver Diseases Diseases

Chronic hepatitisChronic hepatitisin childrenin children

Dr Tai Al AkawyDr Tai Al Akawy

Alexandria university children hospitalAlexandria university children hospital

Based on Nelson text book of pediatrics and many online articles that will be mentioned on the slides

DEFINITIONDEFINITION

The term chronic hepatitis means ongoing The term chronic hepatitis means ongoing inflammation of the liver persisting for inflammation of the liver persisting for more more

than six monthsthan six months that is detectable by that is detectable by biochemical and histologic means. biochemical and histologic means.

Clinical featuresClinical features

-Depend on pathology & aetiology -Depend on pathology & aetiology

--Mild illness Mild illness with dyspepsia & variablewith dyspepsia & variable

increase in liver enzymes without evidenceincrease in liver enzymes without evidence

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 distinctionBased on histopathological distinction

1-Chronic persistent hepatitis 1-Chronic persistent hepatitis (CPH)(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 hepatitis 2- Chronic active hepatitis (aggressive)(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 CLASSIFICATION PRESENT CLASSIFICATION of chronic hepatirisof chronic hepatiris

CAUSECAUSE

GRADEGRADE

SEVERITYSEVERITY

CAUSECAUSE

Chronic viral hepatitisChronic viral hepatitis

Autoimmune hepatitisAutoimmune hepatitis

Drug induced hepatitisDrug induced hepatitis

Metabolic disorders associated with CLDMetabolic disorders associated with CLD

GRADEGRADE -Histological assessment of -Histological assessment of necroinflammatory activitynecroinflammatory activity

Portal inflammationPortal inflammation

Periportal necrosis Periportal necrosis

Piecemeal necrosis or Piecemeal necrosis or interface hepatitisinterface hepatitis

Bridging necrosisBridging necrosis

SeveritySeverity

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

CAUSESCAUSES

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

deficiency ,haemochromatosis, glycogen storage deficiency ,haemochromatosis, glycogen storage disease type IVdisease type IV

Hepatitis B Virus

Hepatitis B (HBV) Hepadnaviridae (1970)

Hepatit is B Virus (HBV)Hepatit is 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 Hepatit is BEpidemiology of Hepatit is B

Prevalent in Asia, Africa, Southern Prevalent in Asia, Africa, Southern Europe and South America (2-20%)Europe and South 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 Hepatit is B InfectionChronic Hepatit is B Infection

Infections acquired perinatally and in early childhood usually becomes chronic

Symptomatic Infection

Chronic Infection

Age at Infection

Chronic Infection (%)

Sym

pto

matic In

fection

(%)

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 Infectionby Age at Infection

Ch

ron

ic Infectio

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 Hepatit is B markersHepatit is B markers

HBsAgHBsAg Non infect ious 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 replicat ion and infectivity

High level of infect ivity and replicat ion

Anti-HBeAnti-HBe Antibody response to HBeAg

Decreasing level of replicat ionRemission/resolution

Anti-HBc IgMAnti-HBc IgM Non protective antibody to the HBcAg

Recent HBV infect ion

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

HBV DNAHBV DNA Replictative genetic material of HBV; infectious agent

Viral replicat ion and continues infection

Diagnostic Interpretations of Diagnostic Interpretations of Hepatit is B markersHepatit is B markers

HBsAgHBsAg Non infect ious 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 replicat ion and infectivity

High level of infect ivity and replicat ion

Anti-HBeAnti-HBe Antibody response to HBeAg

Decreasing level of replicat ionRemission/resolution

Anti-HBc IgMAnti-HBc IgM Non protective antibody to the HBcAg

Recent HBV infect ion

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

HBV DNAHBV DNA Replictative genetic material of HBV; infectious agent

Viral replicat ion 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-HBc

IgGIgGHBeAgHBeAg 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 Hepatit is B Chronic Hepatit is 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% in HBeAb seroconversion rate 55% in 12 years12 years

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

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

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

Hepatit is B Liver BiopsyHepatit is 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 acquisit ion of Late acquisit ion of

infectioninfection

Better Better Response Response

to to treatmenttreatment

Mei-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 LamivudineLamivudine

How to treat?How to treat?

PediatricsPediatrics

IFN-IFN- αα LamivudineLamivudine

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 administrat ionWeekly SC administrat ion Very expensiveVery expensive Adverse reactions:Adverse reactions: Flu-l ike symptoms, depression, Flu-l ike symptoms, depression,

anorexia, bone marrow suppressionanorexia, 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

Hepatit is C Virus Hepatit is C Virus (HCV)(HCV)

hypervariableregion

capsid envelopeprotein

protease/helicase

RNA-dependent

RNA polymerase

c22

5’

core E1 E2 NS2

NS3

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

50

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 Hepatit is Prevalence of Hepatit is CC

•1.8% prevalence in US 1.8% prevalence in US

•10,000-60,000 newborn wil l be infected 10,000-60,000 newborn wil l be infected worldwide yearlyworldwide yearly

Prevalence of Hepatit is Prevalence of Hepatit is CC

Genotype Distribution of Genotype Distribution of Hepatit is CHepatit is 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 Transmission Mode of Transmission of Hepatit is Cof Hepatit is 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 children) (most important among children)

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

Perinatal Transmission Perinatal Transmission of Hepatit is Cof Hepatit is 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 posit ive mothers, 25%Infection rate in HIV posit ive mothers, 25%

Breast feeding and Breast feeding and transmission of Hepatit is Ctransmission of Hepatit is C

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

• Rate of transmission is identical to bott le-fed Rate of transmission is identical to bott le-fed infantsinfants

• 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 Hepatit is CTransmission of Hepatit is C

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


Risk Factors for Vertical Risk Factors for Vertical Transmission of Hepatit is CTransmission of Hepatit is 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 (>6 Prolonged rupture of membranes (>6

h)h) HIV co-infectionHIV co-infection


Natural History of Hepatit is CNatural History of Hepatit is C

ExposureExposure

No No infectioninfection

AcuteAcuteChronicChronic

SpontaneouSpontaneous clearance s clearance

(early)(early)•Cirrhosis Cirrhosis (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 Hepatit is C in Hepatit is C in

PediatricsPediatrics•Normal growthNormal growth

•Mostly are asymptomaticMostly are asymptomatic

•HepatomegalyHepatomegaly

•Elevated l iver enzymesElevated l iver enzymes

Diagnosis of Hepatit is Diagnosis of Hepatit is CC

HCV HCV antibodies antibodies (IgG)(IgG)

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

Init ial screeningInit ial screening

DiagnosisDiagnosis

Confirmation of DiagnosisConfirmation of Diagnosis (qualitative)(qualitative)

Pretreatment Pretreatment evaluationevaluationPost treatment monitorPost treatment monitor

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. 2001

Wirth 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 Hepatit is Antiviral Therapy for Hepatit is CC

•Combined PEGCombined PEG Interferon and RibavarinInterferon and Ribavarin•45-62% sustained virological response45-62% sustained virological response

•Better responseBetter response

•Ribavir in Side effectsRibavir in Side effects

•Anemia/ThrombocytopeniaAnemia/Thrombocytopenia

•Fetal malformationsFetal malformations

(teratogenic)(teratogenic)

Genotype 2, 3Genotype 2, 3

Low pretreatment viral loadLow pretreatment viral load

Younger 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.

64

Symptoms

anti-HCV

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4

Hepatitis C Virus InfectionTypical Serologic Course

Titre

Months Years

Time after Exposure

Hepatitis C Virus InfectionHepatitis C Virus InfectionNatural 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

73

HBsAg

RNA

δ antigen

Hepatitis D (Delta) Virus

Hepatitis D (HDV) ? (1977)

Hepatitis DHepatitis D

Requires coexistent Hep BRequires coexistent Hep B CoinfectionCoinfection: does not worsen acute Hep B or : does not worsen acute Hep B or ⇑⇑

risk for chronic staterisk for chronic state SuperinfectionSuperinfection::

– usually develop chronic HDV infection.usually develop chronic HDV infection.– high risk of severe chronic liver disease.high risk of severe chronic liver disease.

Diagnosis: Anti-HDV IgMDiagnosis: Anti-HDV IgM

75

Jaundice

Symptoms

ALTTotal anti-HDV

IgM anti-HDV

HDV RNA

HBsAg

HBV – HDV SuperinfectionTypical Serologic Course

Time after Exposure

Titre

76

HBV-HDV Coinfection

Pre or post exposure prophylaxis to prevent HBV infection.

HBV-HDV Superinfection

Education to reduce risk behaviors among persons with chronic HBV infection.

Hepatitis D - Prevention

Immune disordersImmune disorders

Autoimmune disease can affect the hepatocyte Autoimmune disease can affect the hepatocyte or bile duct 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, toxins, :Infections, medications, toxins,

molecular mimicry?molecular mimicry?

AutoantigensAutoantigens Genetic predisposition:Genetic predisposition:Antigen presentation/immunocyte Antigen presentation/immunocyte

activation, DRB1,activation, DRB1, TNF*2A, TNF*2A, HLA B14, HLA DR3,DR4 HLA B14, HLA DR3,DR4

Immunoregulatory mechanismsImmunoregulatory mechanisms

Krawitt. 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 Over 70% are

female and over female and over 40%40% younger age younger age groupgroup..


Type 2 AIHType 2 AIH More common in More common in

Europe and south Europe and south America.America.

Associated with Associated with anti-LKManti-LKM

Described in Described in paediatrics patient paediatrics patient but in Europe 20% but in Europe 20% are adultsare adults

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 AIHVariant type 1 AIH

(soluble liver antigen/ liver-pancreas antigen)

Diagnostic criteriaDiagnostic criteria

Diagnosis require presence of Diagnosis require presence of characteristics features characteristics features & & exclusion of other exclusion of other condition that resemble AIHcondition that resemble AIH

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

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

to < 2 x ULNto < 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 CHRONIC IBD AS A CAUSE OF CHRONIC LIVER DISEASESLIVER DISEASES

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. hepatitisDrug induced Chr. hepatitis

(Medication-induced liver diseases)(Medication-induced liver diseases) History of medicines , herbals and alternate History of medicines , herbals and alternate

medicinesmedicines

Mild to very severe hepatic dysfunctionMild to very severe hepatic dysfunction

Drug induced chr. Liver DiseaseDrug induced chr. Liver Disease

Idiosyncratic reactionsIdiosyncratic reactions- - Isoniazid, sodium Isoniazid, 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

Transcript of Chronic hepatitis