Personal Profile

Muhammad khayam Age 7 years s/o Mir Muhammad Resident of Gujar khan Admitted on 16-05-10

Presenting complaints
High grade fever 2 weeks Yellowish discoloration of sclera Black coloured stools 1 week Hematemesis - 4 days Progressive abdominal distension Generalised edema

Past history
No significant medical/surgical history Birth eventfull Product of consanginous marriage Developmentally normal vaccinated 3 rd among sibship of 5 family history of death of 1st cousin who had unexplained CLD

On examination
Febrile temp 103 F Deeply jaundiced Pallor Spider nevei Caput medusea Clubbing Liver 5 cm BCM

On examination
Spleen 3 cm BCM Ascites +ve [both shifting dullness and fluid thrill present] Palmer erythema Petechia and bruises over abdomen and lower limbs Pitting edema +ve

Lab work up
CBC Hb 7.2 gm/dl TLC 14.4 x109/l Plts 156 x 109/l LFTs Bilirubin 20 u mol/l ALT 59 ul ALK.PHOAPHATE 1051 ul

 Coagulation profile PT 48/13 APTT 38/36 S. Albumin 2.0 g/L RFTs Normal S. Electrolyte Normal

 S. cerruloplasmin 08 mg/dl Urinary copper 20 umol/24 hr KF ring negative

( 19- 57mg/dl ) ( 2.3-11.0 umol/24hr )

 Anti nuclear antibody ve Anti smooth antibody ve Liver Kidney Microsomal Antibodies ve

Final diagnosis
Wilsons disease

Family screening
Elder sister sabreena 11 years old Deteriorating school performance Dystonia 1 month Had KF Rings on slit lamp examination

One younger brother 5 years old Asymtomatic S. cerruloplasmin 12 mg/dl Also diagnosed as wilsons disease Treatment started

 2 more siblings 12 years old & 3 years old S.cerruloplasmin normal, no KF rings

CHRONIC LIVER DISEASE

CHRONIC LIVER DISEASE

Cirrhosis and its complications Progressive hepatic failure Chronicity is determined by
Duration of liver disease:
typically > 3-6 m

Evidence of physical stigmata of CLD:

Clubbing Spider telangiectasia Hepatosplenomegaly

ETIOLOGY
Wilson disease Galactosaemia Hereditary Fructose Intolerance Biliary Atresia Choledochal Cyst Total Parenteral Nutrition

ETIOLOGY
Viral: Hepatitis B & C Drugs: Isoniazid, Antimetabolites, Paracetamol Toxins: Indian childhood cirrhosis Metabolic: -1-antitrypsin deficiency, Tyrosinaemia, Haemochromatosis, Cystic Fibrosis Idiopatic: Autoimmune hepatitis, hepatocellular cholestasis, Alagille syndrome

Liver Disease
Arises from Congenital disorders Genetic disorders Medications/Drugs Toxins Infections

Inflammatory process

Cirrhosis

Wilson Disease
Reduced ceruloplasmin & defective excretion of copper Accumulation of copper in liver, brain, kidney & cornea May present with almost any form of liver disease (acute, fulminant, cirrhosis, portal hypertension) Neurological features Renal tubular defects Hemolytic anemia Copper accumulation in cornea (Kayser-Fleischer rings) Dx: serum ceruloplasmin, hepatic copper content, urinary copper Copper chelation therapy with D-penicillamine Liver transplantation

Galactosemia
Rare, 1 in 40000 Infant develop poor feeding, vomiting, jaundice & hepatomegaly when fed milk CLD, Cataract, developmental delay inevitable if untreated A rapid fatal course with shock, haemorrhage & DIC due to gram-Negative sepsis Screened by detecting galactose, a reducing substance, in urine Diagnosed by measuring galactose-1-phosphate-uridyl transferase in red cells Galactose-free diet prevents progression of liver disease

Biliary atresia
Progressive cholangiopathy 1 in 12000 15000 live births Presents as neonatal cholestasis (jaundice, pale stools, dark urine) Hepatomegaly Splenomegaly secondary to portal hypertension USG abdomen: absent or contracted gall bladder Radioisotope scan: uptake by liver but no excretion Chronic liver failure & death unless surgical intervention Hepatoportoenterostomy Liver Transplantation

Choledochal cyst
Cystic dilatation of extrahepatic biliary system ~ 25% present in infancy with cholestasis Older children present with abdominal pain, palpable mass, jaundice USG abdomen, radionuclide scan Surgical excision of the cyst

Hereditary fructose intolerance

Tissue accumulation of fructose-1-phosphate on fructose ingestion Hypoglycemia, FTT, vomiting, jaundice, hepatomegaly, proteinuria, generalized aminoaciduria Death from liver failure in untreated Suggested by finding fructosuria Hypoglycemia & hypophosphatemia after i.v., fructose loading (200 mg/kg) test Confirmed by reduced fructose-1-phosphate aldolase in liver Treatment: strict dietary avoidance of fructose

HEPATITIS B
Hepatitis B S Ag > 6 months Variable biochemical tests Congenital ( 85% rate) or acquired Other Markers: DNA PCR, HBe Ag, Anti-HB c , Anti- HB e 1-5% of acute attacks become chronic 70 % cirrhosis HCC carcinoma ( monitor alpha fetoprotein)

HEPATITIS C
Congenital 1-10% or acquired Anti HCV: maternal persist up to 18 months, takes 6 weeks to show. HCV RNA: I U 6 genotypes 1-6- geographically variable and determines the response to therapy Peg-Interferon and Ribavirin ( duration depends on genotype)

HEPATITIS D
Co-infection with B Outcome similar to B

Autoimmune
2 Types serologically ASMA, LKM Hypergammaglobuliniemia Elevated LFT Treatment: Prednisone and Azathioprine. High relapse rate

CIRRHOSIS
Many definitions but common theme is injury, repair, regeneration and scarring NOT a localized process; involves entire liver Primary histologic features:
1. 2. 3. 4. Marked fibrosis Destruction of vascular & biliary elements Regeneration Nodule formation

DIAGNOSIS
Can be asymptomatic for decades History Physical findings: Hepatomegaly, jaundice, ascites, spider angioma, splenomegaly, palmar erythema, fetor hepaticus, purpura etc. Elevated LFTs, thrombocytopenia,

DIAGNOSIS
Definitive diagnosis is by biopsy or gross inspection of liver Noninvasive methods include US, CT scan, MRI Indirect evidence - esophageal varices seen during endoscopy

Portal Hypertension (PH)

Portal vein pressure above the normal range of 5 to 8 mm Hg Portal vein - Hepatic vein pressure gradient greater than 5 mm Hg (>12 clinically significant) Represents an increase of the hydrostatic pressure within the portal vein or its tributaries

Sequelae of cirrhosis
Hepatic encephalopathy Esophageal varices Portal hypertension Ascites Thrombosis of portal vein Infection (peritonitis) Carcinoma (hepatocellular)

Investigations
Non-specific: Liver function tests Serum billirubin aminotransferases alkaline phosphatases Serum albumin level Coagulation profile USG abdomen Endoscopy

Specific investigations
HIDA scan Viral serology for hepatitis B & C ANA, anti LKM, anti smooth muscle antibodies IgG levels Serum ceruloplasmin levels and 24 hours urinary excretion of copper Alpha 1 anti trypsin levels

Delta 508 mutation analysis Enzyme levels for various storage disorders Cholangiography Liver biopsy

Treatment
General measures

Treatment of cholestasis
Malnutrition Vitamin A Vitamin D Vitamin E Vitamin K Water soluble vitamins xanthomas End stage liver disease Medium chain triglycerides 10,000- 15,000 IU / day 5000-8000 IU/day 50-400 IU/day 2.5-5 mg/day Twice the recommended dose Ursodeoxycholic acid 1520mg/kg/day Liver transplant

Management of ascites
Salt restriction Prevention of spontaneous bacterial peritonitis (pneumococcal vacccine) Albumin Diuretics

Variceal bleeding

Management Acute Management Long term management

Acute management

Plasma expanders

Blood transfusion

Endoscopy. Sclerotheraby & band ligation

Treatment of encephalopathy:
Treat the precipitating cause Restriction of protein intake Laxatives for constipation Treat the infection

Specific treatment
Wilsons disease Hepatitis B Pencillamine 20 mg/kg/day Interferon(5-10 MU/meter square S/C 3times/week for 4-6 months alpha & lamivudine Interferon alpha 3MU/mter sq. S/C 3 times/ week+ ribavarin 15mg/kg in two divided doses or pegylated interferon

Hepatitis C

Autoimmune Hepatitis

Prednisolone 2mg/kg/day Azathioprine 2mg/kg/day Extrahepatic biliary atresia Kasai procedure (hepatoportoenterostomy)

Liver transplantation:
Ultimate and curative treatment > 85% success rate Limitations due to donor availability, cost and expertise available

THANKS