CHRONIC HEPATITIS

DR LALITHA, AP ,Dept of Pediatrics

Definition Chronicity is determined- duration >3-6 months or-evidence of hepatic decompensation (hypoalbuminemia,encephalopathy,

coagulopathy)- Physical stigmata of chronic liver disease

Can lead to cirrhosis/ESLD/hepatocellular carcionoma

CAUSES

Chronic viral hepatitis Hepatitis B, C, D Autoimmune liver disease Autoimmune hepatitis Sclerosing cholangitis/primary biliary

cirrhosis Overlap syndrome with sclerosing

cholangitis and autoantibodies Systemic lupus erythematosus Coeliac disease

Drug-induced hepatitis Metabolic disorders associated with

chronic liver disease Wilson disease Nonalcoholic steatohepatitis α1-Antitrypsin deficiency Tyrosinemia Niemann-Pick disease type 2 Glycogen storage disease type iv Cystic fibrosis Galactosemia Bile acid biosynthetic abnormalities

Clinical presentation

Can present with acute decompensation Asymptomatic Signs of chronic liver disease/failure

MANAGEMENT DIAGNOSIS: to determine cause and

assess extent of liver dysfunction and complication

Investigations include: LFT, USG abdomen, liver biopsy

Specific to cause: viral markers,autoantibodies , metabolic workup

Hepatitis B

Chronic hepatitis : HBsAg positivity for >6 mo

Risk : >90% infected <1yr , 30% children & 2% of adults infected will become chronic carriers.

Three phases of this chronic infection include 1. Immunotolerant phase - active viral

replication and minimal liver damage.HBsAg & HBeAg are positive and anti Hbe is negative.

HBV DNA load is high. ALT normal

2. Immuno active phase- host tries to resolve infection HBsAg & HBeAg are positive and anti Hbe is negative.

HBV DNA load is low. ALT high & with flares3. Inactive carrier phase- HBsAg & anti Hbe are

positive and HBeAg is negative. HBV DNA load is very low. ALT normal. Sometimes may lead to resolution with

HBsAg being negative and Anti HBs positive.

Treatment Only useful for immunoactive phase as it will

reduce risk of hepatic cancer and cirrhosis Treatment for children is only by : Interferon(IF alpha 2b,peg IF) AND

lamivudine after thorough investigations and classification of stage of disease.

Adefovir ,entecavir and tenofovir are used in older children(>12 years)

Chronic hepatitis C Prevalence low in children Risk of perinatal transmission:5% Increases to 20% if mother coinfected

with HIV Poses 85 % risk of developing chronicity

but no good evidence in children

Mostly asymptomatic with fluctuating /normal transaminases levels

Slow progression to fibrosis/cirrhosis/CLD Associated with extrahepatic

manifestations

Diagnosis: HCV RNA and genotype , liver biopsy

Treatment: PEG INTERFERON ALPHA 2b and

RIBAVIRIN (in > 3yrs of age) for 2 year duration

Autoimmune liver disease

Autoimmune liver disease is a clinical constellation that suggests an immune-mediated process characterized by :

hypergammaglobulinemia, circulating autoimmune antibodies, necro inflammatory histology & responsive to immunosuppressive

therapy . They include autoimmune hepatitis,

autoimmune sclerosing cholangitis & de novo hepatitis.

Pathophysiology

Triggering factors : molecular mimicry,

infections, drugs, environment (toxins) in a genetically susceptible host

Inflammatory cells invades the surrounding parenchyma.

HLA DR3, DR4, and DR7 isoforms confer susceptibility to autoimmune hepatitis

Clinical manifestations Acute viral hepatitis like picture(40%)

can progress to ALF esp in Type 2 Insidious onset of liver disease with

fatigue, relapsing or prolonged jaundice. Chronic liver disease and its

complications Extrahepatic manifestations: arthritis,

vasculitis, nephritis, throiditis, anemia, rash

Management Diagnosis is done by: elevated transaminases, positive auto

antibodies , raised gammaglobulins and IgG levels, liver biopsy, absence of known etiology and response to immunosuppressive drugs.

Steroids, Azathioprine are first line drugs Cyclosporine and mycophenolate mofetil are

second line drugs Liver transplantation as and when required.

Drug induced liver disease Drugs commonly used in children that

can cause chronic liver injury include isoniazid, methyldopa, pemoline, nitrofurantoin, dantrolene, minocycline, pemoline, and the sulfonamides.

Anti tubercular and anticonvulsant drugs are major causes

Can be chemical hepatotoxicity/idiosyncratic heapatotoxicity

They can mimic any form of liver disease(acute &chronic hepatitis, ALF, portal hypertension)

Good history taking and high index of suspicion is required

Treatment is by withdrawal of drug and supportive care

Metabolic causes

Can account for 15-20% of liver diseases in India

Most common is Wilsons disease. Most symptoms are due o hepatocyte

injury or secondary to hypoglycemia or hyperammonemia

Treatment is cause specific.

Wilsons disease a/k/a hepatolenticular degeneration

Toxic accumulation of copper in liver,brain,cornea and other tissues

Due to abnormal gene, ATP 7B in chromosome 13

Clinical features Various forms of hepatic disease: Asymptomatic hepatomegaly subacute/chronic hepatitis Acute hepatic failure with/without hemolytic

anemia

Others: neuropsychiatric disease, KF Ring,sunflower cataract , coombs negative hemolytic anemia, arthritis, pancreatitis, nephrolithiasis, cardiomyopathy ,endocrinopathies

diagnosis Serum ceruloplasmin(<20mg/dl) 24 hr urinary copper

excretion(>100mcg/day) with penicillamine challenge test(>1600mcg/day)

KF ring(slit lamp) Liver biopsy: hepatic copper

(>250mcg/g) Family screening

Treatment Dietary restriction of copper Copper chelating

agents(penicillamine/triethylene tetramine hydrochloride, zinc, ammonium tetrathiomolybdenate)

Liver transplantation

Nonalcoholic steatohepatitis Usually associated with obesity and

insulin resistance Most children are asymptomatic May have vague abdominal pain. o/e: hepatomegaly , features of insulin

resistance like striae, acanthosis nigricans obesity and hepatomegaly.

It can progress to cirrhosis.

Diagnosis is usually clinicopathological correlation . Other causes to be excluded

Treatment is by weight reduction and dietary modifications.

Ursodeoxycholic acid and vitamin E have promising results

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