Pediatrics

DEFINITION

Coeliac disease is a chronic, immune-mediated systemic disorder triggered by dietary gluten (present in wheat, barley and rye) in genetically susceptible individuals. It is characterised by a small-intestinal enteropathy (villous atrophy) leading to malabsorption, and it improves on a gluten-free diet.

ETIOLOGY & PATHOGENESIS

• Genetic susceptibility — strong association with HLA-DQ2 and HLA-DQ8.
• The trigger is gliadin (a gluten fraction); the enzyme tissue transglutaminase (tTG) modifies it, provoking a T-cell-mediated immune response.
• This causes villous atrophy, crypt hyperplasia and intraepithelial lymphocytosis → reduced absorptive surface → malabsorption.

CLINICAL FEATURES

• Classic (GI) form — appears months after gluten is introduced (6 months–2 years): chronic diarrhoea, steatorrhoea (bulky, pale, offensive stools), abdominal distension, failure to thrive, irritability and wasting of the buttocks and limbs.
• Non-classic / extra-intestinal — iron-deficiency anaemia unresponsive to iron, short stature, delayed puberty, rickets/osteopenia, dental enamel defects.
• Dermatitis herpetiformis — an itchy, blistering rash (the skin manifestation).
• Associations — type 1 diabetes, autoimmune thyroiditis, Down syndrome, selective IgA deficiency.

INVESTIGATIONS

• Serology (first-line) — IgA anti-tissue transglutaminase (anti-tTG) antibody with a total serum IgA (to exclude IgA deficiency); IgA anti-endomysial antibody (EMA) is highly specific.
• Duodenal biopsy — the confirmatory test; shows villous atrophy, crypt hyperplasia and raised intraepithelial lymphocytes (graded by the Marsh classification).
• HLA-DQ2/DQ8 typing — a negative result largely excludes the disease.
• Supportive — CBC (anaemia), iron/folate, calcium, vitamin D.

MANAGEMENT

• Lifelong strict gluten-free diet — avoid wheat, barley and rye; rice, maize, millets (ragi, jowar, bajra) and potato are safe.
• Correct deficiencies — iron, folate, calcium and vitamin D.
• Dietitian support and family education; monitor symptoms, growth and falling antibody titres as markers of adherence.
• Screen for associated autoimmune conditions.

COMPLICATIONS

• Persistent anaemia, osteoporosis, short stature and delayed puberty; infertility later.
• Refractory disease and (in long-standing untreated adults) small-bowel lymphoma.
• Coeliac crisis — a severe acute presentation with dehydration and electrolyte disturbance.

EPIDEMIOLOGY

• Prevalence ~1% and increasingly recognised; the majority remain undiagnosed (the 'coeliac iceberg').
• Higher in first-degree relatives and in certain autoimmune/genetic conditions.

CLINICAL SPECTRUM (the iceberg)

• Classic — the malabsorptive GI picture described above.
• Non-classic/atypical — extra-intestinal features (anaemia, short stature, arthralgia) with few GI symptoms.
• Silent — asymptomatic but positive serology and biopsy (found on screening).
• Potential — positive serology with a currently normal biopsy.

DIFFERENTIAL DIAGNOSIS

• Other causes of chronic diarrhoea & failure to thrive — cystic fibrosis, giardiasis, cow-milk protein enteropathy, tropical sprue, post-enteritis syndrome.
• Serology + biopsy distinguish coeliac disease from these.

WHO TO SCREEN (high-risk groups)

• First-degree relatives of coeliac patients.
• Type 1 diabetes, autoimmune thyroiditis, Down syndrome, Turner syndrome, selective IgA deficiency.

MONITORING & FOLLOW-UP

• Track symptom resolution, catch-up growth and a fall in anti-tTG titres as a marker of dietary adherence.
• Regular dietitian review; screen for and correct deficiencies (iron, calcium, vitamin D).

PROGNOSIS

With a strict, lifelong gluten-free diet the prognosis is excellent — symptoms resolve, the mucosa heals and growth normalises. Poor adherence causes ongoing mucosal damage, persistent deficiencies and the long-term risk of osteoporosis and malignancy.

THE GLUTEN-FREE DIET IN PRACTICE

Oats are usually tolerated but risk cross-contamination; careful label-reading is essential.

• Suspect coeliac disease in any child with unexplained chronic diarrhoea, failure to thrive, or iron-deficiency anaemia not responding to iron.
• Always send a total IgA with the anti-tTG — a low IgA gives a false-negative result.
• Do the serology and biopsy BEFORE starting a gluten-free diet.
• A good clinical and serological response to gluten withdrawal supports the diagnosis.
• Emphasise lifelong adherence — even asymptomatic lapses cause ongoing mucosal damage.

• Immune-mediated gluten enteropathy in HLA-DQ2/DQ8 individuals.
• Classic: chronic diarrhoea, steatorrhoea, distension, failure to thrive after weaning.
• First-line test: IgA anti-tTG + total IgA; confirm with duodenal biopsy (Marsh).
• Test on a gluten-containing diet; treat with a lifelong gluten-free diet.
• Watch for anaemia, short stature, osteopenia and (late) lymphoma.

DEFINITION

Neonatal cholestasis is conjugated (direct) hyperbilirubinaemia in early infancy — defined as a direct bilirubin > 1 mg/dL (when total < 5) or > 20% of the total bilirubin. It always reflects hepatobiliary disease and, unlike physiological jaundice, is pathological and needs urgent evaluation.

CAUSES

• Obstructive/surgical — biliary atresia (the commonest surgical cause), choledochal cyst.
• Hepatocellular/'neonatal hepatitis' — idiopathic, infections (TORCH, hepatitis, sepsis, UTI).
• Metabolic — galactosaemia, tyrosinaemia, alpha-1-antitrypsin deficiency, hypothyroidism.
• Genetic/other — Alagille syndrome, progressive familial intrahepatic cholestasis, TPN-associated.

BILIARY ATRESIA

A progressive, inflammatory obliteration of the extrahepatic bile ducts of unknown cause, presenting in the first weeks of life; untreated, it leads to biliary cirrhosis and death.

• Clinical triad — persistent jaundice, pale/clay-coloured stools and dark urine, with hepatomegaly (later splenomegaly).
• The baby is often otherwise well and thriving initially, which can delay recognition.

CLINICAL EVALUATION

• Assess the stool colour (persistently pale stools strongly suggest biliary obstruction) and urine colour.
• Examine for hepatomegaly, splenomegaly, ascites and dysmorphism (Alagille); note the general condition (sick → sepsis/metabolic).
• Ask about consanguinity, family history and the antenatal/birth history.

INVESTIGATIONS

• Fractionated bilirubin (conjugated raised); liver function tests including GGT.
• Ultrasound abdomen — absent/contracted gallbladder and the 'triangular cord sign' suggest biliary atresia; detects a choledochal cyst.
• HIDA (hepatobiliary) scan — no excretion of tracer into the gut suggests biliary atresia.
• Liver biopsy — bile-duct proliferation and bile plugs favour biliary atresia.
• Metabolic & infection screen — galactosaemia (urine reducing substances), TORCH, thyroid, alpha-1-antitrypsin.

MANAGEMENT

• Biliary atresia — Kasai portoenterostomy, ideally performed before 8 weeks (60 days) of age; results are far better the earlier it is done.
• Liver transplantation — for failed Kasai or end-stage liver disease.
• Treat specific causes (galactose-free diet in galactosaemia, thyroxine in hypothyroidism, antibiotics for sepsis/UTI).
• Supportive — fat-soluble vitamins (A, D, E, K), MCT-based nutrition for catch-up growth, ursodeoxycholic acid.

STEP-WISE DIAGNOSTIC APPROACH

• Step 1 — confirm cholestasis by fractionating the bilirubin (raised conjugated fraction).
• Step 2 — decide 'sick' vs 'well': a sick baby suggests sepsis, galactosaemia or a metabolic crisis needing urgent treatment.
• Step 3 — assess stool colour and do targeted tests (USG, HIDA, biopsy) to identify/exclude biliary atresia (time-critical).
• Step 4 — pursue metabolic, infective and genetic causes in parallel.

BILIARY ATRESIA vs NEONATAL HEPATITIS

COMPLICATIONS

• Progressive biliary cirrhosis and portal hypertension if biliary atresia is untreated.
• Fat-soluble vitamin deficiency (A, D, E, K) — including vitamin-K-dependent bleeding.
• Failure to thrive, pruritus and (in the underlying cause) metabolic decompensation.

PROGNOSIS

Outcome in biliary atresia depends heavily on the age at Kasai surgery — bile drainage is achieved in most when operated before 60 days, and in few when delayed. Even after a successful Kasai, many children eventually require liver transplantation.

SUPPORTIVE MANAGEMENT

• Nutrition — energy-dense feeds with medium-chain triglycerides (better absorbed in cholestasis).
• Fat-soluble vitamins — supplement A, D, E and K (K prevents bleeding).
• Pruritus — ursodeoxycholic acid, and agents such as rifampicin/cholestyramine for troublesome itch.
• Treat complications of portal hypertension as they arise.

• The single most important rule: fractionate bilirubin in any baby jaundiced beyond 2 weeks (3 weeks if breastfed and well).
• Pale stools + dark urine + conjugated jaundice = biliary atresia until proven otherwise.
• Kasai before 60 days gives the best chance of bile drainage — never delay referral.
• Always screen for galactosaemia and sepsis, which are treatable and rapidly fatal if missed.
• Give fat-soluble vitamins — cholestasis causes their malabsorption (vitamin K → bleeding).

• Fat-soluble vitamins: A, D, E, K; ursodeoxycholic acid 10–20 mg/kg/day.
• Kasai portoenterostomy before 60 days; treat sepsis (ampicillin + gentamicin).

• Neonatal cholestasis = conjugated hyperbilirubinaemia — always pathological.
• Fractionate bilirubin in any jaundice lasting > 2 weeks.
• Biliary atresia (commonest surgical cause): pale stools, dark urine, hepatomegaly.
• USG (triangular cord sign), HIDA scan and biopsy help diagnose it.
• Kasai portoenterostomy before 8 weeks; transplant later; give A,D,E,K vitamins.

DEFINITION

Acute viral hepatitis is an acute inflammation of the liver caused by the hepatotropic viruses (A, B, C, D and E). It is a common cause of jaundice in children; hepatitis A and E are the usual causes in India.

THE HEPATITIS VIRUSES

CLINICAL FEATURES (phases)

• Prodromal (pre-icteric) phase — fever, malaise, anorexia, nausea/vomiting, distaste for food (and cigarettes in adults), and right-upper-quadrant discomfort.
• Icteric phase — jaundice, dark urine and pale stools, with tender hepatomegaly; symptoms often improve as jaundice appears.
• Convalescent phase — gradual recovery over weeks.
• Many children (especially with hepatitis A) have an anicteric or subclinical illness.

INVESTIGATIONS

• Liver enzymes — markedly raised transaminases (ALT > AST); raised bilirubin (conjugated + unconjugated).
• Serology — IgM anti-HAV (acute A), HBsAg and IgM anti-HBc (acute B), anti-HCV/HCV-RNA, IgM anti-HEV.
• Prothrombin time / INR — the best marker of severity/prognosis (a prolonged PT warns of liver failure).
• Ultrasound to exclude obstruction if the picture is atypical.

MANAGEMENT

• Mostly supportive — rest, adequate nutrition and hydration; there is no need for a special 'liver diet' or forced fat restriction.
• Avoid hepatotoxic drugs (paracetamol in high doses, alcohol) and unnecessary medication.
• Monitor for fulminant hepatic failure — worsening jaundice, bleeding, altered sensorium (encephalopathy).
• Specific antiviral therapy for chronic hepatitis B or C (not for acute A/E).

COMPLICATIONS & PREVENTION

• Complications — fulminant hepatic failure (esp. E, B); chronic hepatitis, cirrhosis and hepatocellular carcinoma (B, C).
• Prevention — hepatitis A and B vaccines; safe water, sanitation and hand hygiene (A, E); safe blood/needles and birth-dose HBV + HBIG to prevent vertical B.

PATHOGENESIS

Most hepatocyte injury is immune-mediated (the host's cytotoxic T-cell response to virus-infected liver cells) rather than a direct cytopathic effect, causing hepatocyte necrosis, cholestasis and the rise in transaminases.

INCUBATION & COURSE

• Hepatitis A — incubation ~2–6 weeks; almost always self-limiting in children.
• Hepatitis E — ~2–9 weeks; self-limiting but severe in pregnancy.
• Hepatitis B — ~1–6 months; risk of chronicity (highest when acquired young).

DIFFERENTIAL DIAGNOSIS OF JAUNDICE

• Pre-hepatic — haemolysis (unconjugated, normal enzymes).
• Hepatic — other causes: drug-induced, autoimmune hepatitis, Wilson disease, leptospirosis, enteric fever.
• Post-hepatic — obstruction (choledochal cyst, stones) — pale stools, high GGT/ALP.

WARNING SIGNS OF FULMINANT FAILURE

• Deepening jaundice with altered behaviour/drowsiness (encephalopathy).
• Bleeding, a prolonging PT/INR, and a shrinking liver — refer urgently.

PROGNOSIS

Hepatitis A and E in children usually recover completely without sequelae. The main risks are fulminant failure (a small minority) and, with hepatitis B/C, progression to chronic liver disease, cirrhosis and hepatocellular carcinoma.

SUPPORTIVE CARE IN DETAIL

• Rest as needed; maintain hydration and a normal balanced diet (no forced fat restriction).
• Antiemetics for troublesome vomiting; avoid sedatives and hepatotoxic drugs.
• Daily assessment for jaundice, bleeding and mental status in significant cases.

POST-EXPOSURE PROPHYLAXIS & PUBLIC HEALTH

• Hepatitis A — vaccine (± immunoglobulin) for susceptible close contacts; ensure safe water and hand hygiene.
• Hepatitis B — vaccine + HBIG after significant exposure; birth-dose vaccine for newborns of carrier mothers.
• Hepatitis A/E — enteric precautions; both are notifiable in outbreaks.

• ALT rises higher than AST in viral hepatitis (the reverse of alcoholic liver disease).
• PT/INR — not the bilirubin level — is the key prognostic marker; a rising INR signals impending failure.
• Symptoms often ease once jaundice appears in hepatitis A.
• Hepatitis E is particularly dangerous in pregnancy (high mortality).
• Prevent vertical hepatitis B with the birth-dose vaccine (± HBIG) within 24 hours.

• Caused by hepatotropic viruses A–E; A & E faeco-oral (no chronicity), B/C/D parenteral (chronic).
• Phases: prodromal → icteric (jaundice, dark urine, pale stools) → convalescent.
• ALT > AST; confirm by serology; PT/INR indicates severity.
• Supportive care; avoid hepatotoxins; watch for fulminant failure.
• Prevent with hepatitis A & B vaccines, hygiene and safe blood.

DEFINITION

Portal hypertension is a sustained increase in the pressure within the portal venous system (portal pressure > 10–12 mmHg, or a hepatic venous pressure gradient > 5 mmHg). It leads to the opening of porto-systemic collaterals, splenomegaly and the risk of variceal bleeding.

CLASSIFICATION BY SITE OF OBSTRUCTION

CLINICAL FEATURES

• Splenomegaly (often massive) — a common presenting sign; may cause hypersplenism (anaemia, leucopenia, thrombocytopenia).
• Upper GI bleeding from oesophageal/gastric varices — haematemesis and/or melena (often the first and dramatic presentation).
• Ascites and dilated abdominal wall veins — more with intrahepatic (cirrhotic) causes.
• Features of the underlying liver disease (jaundice, growth failure) in intrahepatic causes.

INVESTIGATIONS

• Ultrasound with Doppler — assesses the portal vein (thrombosis/cavernoma in EHPVO), liver echotexture, spleen size and collaterals.
• Upper GI endoscopy — detects and grades oesophageal/gastric varices.
• Liver function tests, CBC (hypersplenism), coagulation profile; liver biopsy if intrinsic liver disease is suspected.

MANAGEMENT — Acute variceal bleed

• Resuscitation first — airway, breathing, IV access, restore circulation (cautious transfusion), correct coagulopathy.
• Vasoactive drugs — octreotide/somatostatin (or terlipressin) to reduce portal pressure.
• Endoscopic therapy — variceal band ligation (preferred) or sclerotherapy.
• Balloon tamponade as a temporary bridge; prophylactic antibiotics.

MANAGEMENT — Long-term

• Non-selective beta-blockers (propranolol) and endoscopic obliteration to prevent re-bleeding.
• Shunt surgery / Meso-Rex bypass (especially in EHPVO) for uncontrolled bleeding.
• Treat the underlying cause; manage hypersplenism and ascites; liver transplant for end-stage cirrhosis.

PATHOPHYSIOLOGY

Obstruction to portal flow (pre-/intra-/post-hepatic) → Rise in portal venous pressure → Opening of porto-systemic collaterals + splenomegaly → Varices (oesophageal/gastric) → GI bleeding; ascites (intrahepatic)

SITES OF PORTO-SYSTEMIC COLLATERALS

• Oesophageal & gastric varices (the ones that bleed dangerously).
• Rectal (haemorrhoids), umbilical (caput medusae), and retroperitoneal collaterals.

EXTRAHEPATIC PORTAL VEIN OBSTRUCTION (EHPVO)

• The commonest cause in Indian children; the obstructed portal vein is replaced by a network of collaterals (a 'portal cavernoma').
• Risk factors — neonatal umbilical sepsis or umbilical vein catheterisation, dehydration, prothrombotic states.
• Liver function is preserved, so ascites and encephalopathy are uncommon; growth retardation can occur.

COMPLICATIONS

• Recurrent variceal bleeding; hypersplenism (cytopenias); ascites (intrahepatic causes).
• Hepatic encephalopathy and portal biliopathy (in EHPVO); growth failure.

PROGNOSIS

EHPVO has a good long-term prognosis because liver function is preserved — the main challenge is controlling variceal bleeding, which can often be managed endoscopically or by a shunt (Meso-Rex). Prognosis in intrahepatic causes depends on the underlying liver disease.

PRIMARY PROPHYLAXIS OF BLEEDING

• Screening endoscopy detects varices at risk of bleeding.
• Non-selective beta-blockers (propranolol) and/or prophylactic band ligation reduce the risk of a first bleed.

MANAGEMENT OF OTHER FEATURES

• Hypersplenism — usually needs no specific treatment unless severe cytopenias occur.
• Ascites (intrahepatic causes) — salt restriction and diuretics.
• Nutritional support and growth monitoring, especially in EHPVO.

• A well child with massive splenomegaly and/or a sudden GI bleed = EHPVO until proven otherwise.
• In EHPVO the liver function is normal — the problem is mechanical, not hepatocellular.
• Resuscitate before endoscopy in a variceal bleed — restore the circulation first.
• Band ligation is preferred over sclerotherapy; add octreotide and antibiotics.
• Ascites points more to an intrahepatic (cirrhotic) cause than to EHPVO.

• Portal pressure > 10–12 mmHg → collaterals, splenomegaly, variceal bleeding.
• Sites: pre-hepatic (EHPVO — commonest in Indian children), intrahepatic (cirrhosis), post-hepatic.
• EHPVO: preserved liver function, massive splenomegaly, variceal bleed.
• USG Doppler + endoscopy are key investigations.
• Bleed: resuscitate → octreotide → band ligation; propranolol prevents re-bleeding.

DEFINITION

Cirrhosis is the end-stage of chronic liver disease, defined pathologically by diffuse fibrosis with nodular regeneration that distorts the normal hepatic architecture. It results in impaired liver function and portal hypertension.

CAUSES (differ from adults)

• Biliary — biliary atresia (the commonest cause of childhood cirrhosis), choledochal cyst.
• Metabolic — Wilson disease, galactosaemia, tyrosinaemia, alpha-1-antitrypsin deficiency, glycogen storage disease.
• Infective — chronic hepatitis B and C.
• Autoimmune hepatitis; non-alcoholic fatty liver disease (with rising childhood obesity); cryptogenic.

CLINICAL FEATURES

• Jaundice, growth failure and malnutrition; fatigue and anorexia.
• Hepatosplenomegaly (the liver may be small and hard in advanced disease) and features of portal hypertension (splenomegaly, varices, ascites).
• Stigmata of chronic liver disease — spider naevi, palmar erythema, clubbing, dilated abdominal veins.
• Decompensation — ascites, variceal bleeding, hepatic encephalopathy, coagulopathy (easy bruising/bleeding).

INVESTIGATIONS

• Liver function — bilirubin, transaminases, albumin (low), PT/INR (prolonged); ammonia (encephalopathy).
• Imaging — ultrasound (coarse echotexture, nodularity, splenomegaly, ascites, portal flow); elastography for fibrosis.
• Aetiological workup — serum ceruloplasmin & urinary copper (Wilson), viral serology, autoimmune markers, alpha-1-antitrypsin, metabolic screen.
• Liver biopsy — confirms cirrhosis and may indicate the cause.

MANAGEMENT

• Treat the specific cause where possible (chelation for Wilson, galactose-free diet, antivirals, immunosuppression for autoimmune hepatitis).
• Nutrition — high-calorie diet, MCT, and fat-soluble vitamins (A, D, E, K).
• Manage complications — ascites (salt restriction, diuretics), varices (band ligation, propranolol), encephalopathy (lactulose, protein moderation), coagulopathy (vitamin K).
• Liver transplantation — the definitive treatment for end-stage disease.

COMPLICATIONS

• Portal hypertension with variceal bleeding; ascites and spontaneous bacterial peritonitis.
• Hepatic encephalopathy; hepatorenal and hepatopulmonary syndromes.
• Coagulopathy; growth failure; and hepatocellular carcinoma.

PATHOPHYSIOLOGY

Chronic liver injury (any cause) → Progressive fibrosis + regenerative nodules → Distorted architecture → portal hypertension → Loss of hepatocyte mass → synthetic failure (albumin, clotting factors)

COMPENSATED vs DECOMPENSATED

• Compensated — the liver still maintains function; few or no symptoms (may be found on examination/tests).
• Decompensated — the onset of jaundice, ascites, variceal bleeding or encephalopathy marks a major fall in reserve and a worse prognosis.

ASSESSING SEVERITY

• Synthetic function — serum albumin and PT/INR — reflects liver reserve better than transaminases.
• Scoring systems (e.g. Child-Pugh — bilirubin, albumin, INR, ascites, encephalopathy) grade severity and guide transplant timing.
• Growth failure is an important marker of chronic liver disease in children.

HEPATIC ENCEPHALOPATHY (a key decompensation)

• Altered consciousness/behaviour from the accumulation of ammonia and other toxins.
• Precipitated by GI bleeding, infection, constipation, electrolyte disturbance or excess protein.
• Treated with lactulose, treatment of the precipitant, and protein moderation.

PROGNOSIS

Prognosis depends on the cause and the degree of decompensation. Some causes (Wilson disease, autoimmune hepatitis, treatable metabolic disease) can stabilise or improve with specific therapy; decompensated cirrhosis ultimately needs liver transplantation, which offers good long-term survival.

MANAGEMENT OF ASCITES

• Salt restriction and diuretics (spironolactone ± furosemide); fluid restriction if hyponatraemic.
• Therapeutic paracentesis (with albumin) for tense ascites.

SPONTANEOUS BACTERIAL PERITONITIS (SBP)

Infection of ascitic fluid presenting with fever, abdominal pain and worsening ascites/encephalopathy — diagnosed by an ascitic neutrophil count and treated promptly with antibiotics; a common and serious decompensating event.

NUTRITION

Malnutrition worsens outcome — provide a high-calorie diet, MCT-based feeds, and fat-soluble vitamins, avoiding unnecessary protein restriction.

• Cirrhosis in a child is not alcoholic — always search for a treatable cause (especially Wilson disease).
• Screen every child with unexplained chronic liver disease over ~3 years of age for Wilson disease.
• Albumin and PT/INR reflect the liver's synthetic function and prognosis better than transaminases.
• New confusion/altered behaviour = hepatic encephalopathy — look for and treat a precipitant (bleed, infection, constipation).
• Refer early for transplant assessment in decompensated disease.

• Cirrhosis = diffuse fibrosis + nodular regeneration → impaired function + portal hypertension.
• Childhood causes: biliary atresia, Wilson & other metabolic disease, chronic hepatitis, autoimmune.
• Features: jaundice, growth failure, hepatosplenomegaly, portal hypertension, decompensation.
• Albumin & PT/INR reflect synthetic function; always look for a treatable cause (Wilson).
• Treat the cause + nutrition + complications; transplant for end-stage disease.