Download - Chronic hepatits
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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