Gastroenterology & Hepatology
1. What this chapter covers, and how NEET PG actually tests it
Stems give a liver test panel, an endoscopic or histological description, or an acute abdominal presentation, and ask for the diagnosis or the next step.
The organising principle is to localise before diagnosing.
| Compartment | Marker of injury |
|---|---|
| Hepatocytes | Transaminases |
| Bile ducts | Alkaline phosphatase with gamma-glutamyl transferase |
| Synthetic function | Albumin and prothrombin time |
| Excretory function | Bilirubin |
The first three answer different questions, and the commonest error in the chapter is treating them as one measure of liver health.
Transaminases indicate injury, not function. A patient with advanced cirrhosis may have near-normal transaminases because there are too few hepatocytes left to leak them, while a patient with acute hepatitis may have values in the thousands and entirely preserved function.
2. Reading the liver panel
2.1 Two patterns
A hepatocellular pattern shows disproportionate transaminase elevation, and a cholestatic pattern shows disproportionate alkaline phosphatase elevation.
| Clue | Meaning |
|---|---|
| Aspartate to alanine ratio above 2 | Alcoholic liver disease |
| Alanine above aspartate | Viral hepatitis, fatty liver |
| Alkaline phosphatase raised with gamma-glutamyl transferase | Biliary origin |
| Alkaline phosphatase raised alone | Bone origin |
Gamma-glutamyl transferase is used to confirm that a raised alkaline phosphatase is hepatic rather than skeletal, which is its main clinical purpose.
Albumin has a half-life of about three weeks and therefore reflects chronic function, while prothrombin time responds within days and is the better acute marker.
2.2 Isolated hyperbilirubinaemia
| Disorder | Bilirubin | Feature |
|---|---|---|
| Gilbert syndrome | Unconjugated | Rises with fasting, illness or stress; entirely benign |
| Crigler-Najjar type 1 | Unconjugated | Absent enzyme, kernicterus, fatal untreated |
| Crigler-Najjar type 2 | Unconjugated | Partial deficiency, responds to phenobarbitone |
| Dubin-Johnson | Conjugated | Black pigmented liver |
| Rotor syndrome | Conjugated | No pigmentation |
Phenobarbitone works in type 2 but not type 1, because it induces residual enzyme, and there is no residual enzyme to induce in type 1. That response is therefore diagnostic as well as therapeutic.
3. Cirrhosis and portal hypertension
Complications follow directly from two consequences: portal pressure rises and hepatocyte mass falls.
| Complication | Mechanism |
|---|---|
| Varices | Portal pressure diverting blood into collaterals |
| Ascites | Portal hypertension with hypoalbuminaemia and sodium retention |
| Spontaneous bacterial peritonitis | Translocation into protein-poor ascitic fluid |
| Encephalopathy | Failure to clear nitrogenous products |
| Hepatorenal syndrome | Splanchnic vasodilatation causing renal vasoconstriction |
The serum-to-ascites albumin gradient separates the causes of ascites, and a value of 1.1 or above indicates portal hypertension while a lower value indicates peritoneal disease such as tuberculosis or malignancy.
Spontaneous bacterial peritonitis is diagnosed on an ascitic neutrophil count of 250 or more per cubic millimetre, regardless of whether the culture grows anything, because culture is negative in a large proportion of genuine cases.
Albumin is given alongside the antibiotic because it reduces the incidence of hepatorenal syndrome, which is the complication that kills these patients.
Encephalopathy is treated with lactulose, which acidifies the colon and traps ammonia, with rifaximin added for recurrence.
The serum ammonia level correlates poorly with the clinical grade and should not be used to guide treatment.
Non-selective beta blockade is used for primary prophylaxis of variceal bleeding, and an acute bleed is treated with terlipressin, antibiotics and endoscopic band ligation.
Antibiotics in acute variceal bleeding are not optional, because they independently reduce mortality by preventing the infections that precipitate rebleeding.
3.1 Grading severity
Two scores are used, and they answer different questions.
The Child-Pugh score combines bilirubin, albumin, prothrombin time, ascites and encephalopathy, and it predicts operative risk and general prognosis.
The model for end-stage liver disease uses bilirubin, creatinine and the international normalised ratio, and it is used to prioritise transplantation.
The transplant score deliberately excludes anything subjective, because ascites and encephalopathy are graded by clinical judgement and an allocation system based on judgement is open to manipulation.
Creatinine appears in the transplant score because renal function is among the strongest predictors of death in advanced liver disease, through hepatorenal physiology.
3.2 Acute liver failure
Acute liver failure is defined by coagulopathy and encephalopathy developing in a patient without pre-existing liver disease.
Paracetamol overdose is the commonest cause in many settings, and viral hepatitis, particularly hepatitis E in pregnancy, dominates in India.
Encephalopathy is what separates acute liver failure from acute hepatitis, and its appearance converts a self-limiting illness into a condition with high mortality that requires transplant assessment.
Cerebral oedema rather than bleeding is the usual cause of death, which is why the neurological state is monitored more closely than the coagulation profile.
Coagulopathy is not corrected prophylactically with fresh frozen plasma, because the prothrombin time is the main prognostic marker and correcting it removes the ability to monitor the patient's trajectory.
4. Specific liver diseases
| Disease | Diagnostic clue | Treatment |
|---|---|---|
| Wilson disease | Low ceruloplasmin, high urinary copper, Kayser-Fleischer rings | Chelation with penicillamine, or zinc |
| Hereditary haemochromatosis | High transferrin saturation and ferritin | Venesection |
| Autoimmune hepatitis | Antinuclear and smooth muscle antibodies, raised immunoglobulin G | Corticosteroids |
| Primary biliary cholangitis | Antimitochondrial antibody, middle-aged woman with itching | Ursodeoxycholic acid |
| Primary sclerosing cholangitis | Beaded ducts on cholangiography, associated with ulcerative colitis | No effective medical therapy |
Wilson disease should be considered in any young person with unexplained liver disease, particularly with neurological or psychiatric features, since it is treatable and fatal if missed.
Primary sclerosing cholangitis carries a substantial risk of cholangiocarcinoma, and its association with ulcerative colitis is strong enough that colonoscopy is indicated when it is diagnosed.
Non-alcoholic fatty liver disease is now the commonest chronic liver disease, and weight loss remains the only intervention with consistent benefit.
Simple steatosis carries little risk, while steatohepatitis with inflammation and fibrosis progresses to cirrhosis, and only biopsy or elastography distinguishes the two.
A loss of around ten per cent of body weight can reverse steatohepatitis histologically, which is a rare instance of an established liver disease being genuinely reversible without any drug.
5. Upper gastrointestinal disease
Helicobacter pylori causes most peptic ulceration not attributable to non-steroidal anti-inflammatory drugs, and it is detected by urea breath test or stool antigen, both of which require the patient to be off proton pump inhibitors.
Duodenal ulcer pain is classically relieved by food while gastric ulcer pain is worsened by it, which is why weight is often maintained in the first and lost in the second.
A gastric ulcer requires biopsy and repeat endoscopy to confirm healing, because it may be malignant, whereas a duodenal ulcer essentially never is.
Acute upper gastrointestinal bleeding is managed with resuscitation, a proton pump inhibitor and endoscopy within twenty-four hours, and a risk score determines who can be discharged without endoscopy.
Gastro-oesophageal reflux is treated with a proton pump inhibitor, and alarm features such as dysphagia, weight loss, anaemia or vomiting mandate endoscopy rather than empirical therapy.
Barrett oesophagus is intestinal metaplasia of the lower oesophagus and is a premalignant condition requiring surveillance, with adenocarcinoma the resulting malignancy.
5.1 Dysphagia
The first question is whether the difficulty is in initiating the swallow or in the passage afterwards.
Oropharyngeal dysphagia causes coughing, nasal regurgitation and choking at the moment of swallowing, and its causes are neurological or muscular rather than structural.
Oesophageal dysphagia causes food sticking some seconds after swallowing, and the next question separates mechanical from motility causes.
| Pattern | Interpretation |
|---|---|
| Solids only, progressive, with weight loss | Mechanical obstruction, suspect malignancy |
| Solids only, intermittent, long history | Benign stricture or ring |
| Solids and liquids from the outset | Motility disorder |
A dysphagia that involves liquids as much as solids from the beginning is a motility problem, because a narrowed lumen obstructs solids long before it obstructs fluid.
Achalasia shows failure of the lower sphincter to relax with absent peristalsis, a bird-beak appearance on barium and a dilated oesophagus, and it carries a small long-term risk of squamous carcinoma.
Progressive dysphagia for solids with weight loss in an older patient is carcinoma until proven otherwise and requires endoscopy rather than a trial of acid suppression.
5.2 Localising gastrointestinal bleeding
Upper bleeding arises proximal to the ligament of Treitz and lower bleeding distal to it, and the presentation usually separates them.
Haematemesis is always upper, melaena is usually upper, and fresh red rectal bleeding is usually lower.
The exceptions matter: a brisk upper bleed can present as fresh rectal blood because the transit time is too short for degradation, and a slow right-sided colonic bleed can present as melaena.
A raised urea with a normal creatinine supports an upper source, because digested blood in the small bowel is absorbed as a protein load.
6. Lower gastrointestinal disease
6.1 Inflammatory bowel disease
| Feature | Ulcerative colitis | Crohn disease |
|---|---|---|
| Distribution | Continuous from the rectum | Skip lesions, mouth to anus |
| Depth | Mucosal | Transmural |
| Histology | Crypt abscesses | Non-caseating granulomas |
| Typical stool | Bloody diarrhoea | Diarrhoea, often without blood |
| Fistulae | Rare | Characteristic |
| Surgery | Colectomy is curative | Recurrence after resection |
Smoking worsens Crohn disease but is protective in ulcerative colitis, which is one of the few instances where a harmful exposure protects against a disease, and it is examined regularly.
Toxic megacolon is a complication of both and is worsened by antimotility agents, which are therefore contraindicated in acute severe colitis.
Colonic dilatation on plain film in a patient with severe colitis is an emergency, and a plain abdominal radiograph is the one imaging study that must not be omitted in acute severe presentations.
The extraintestinal manifestations separate into those tracking disease activity, such as peripheral arthritis and erythema nodosum, and those running independently, such as sclerosing cholangitis and ankylosing spondylitis.
That distinction is practical rather than academic, because treating the bowel disease will settle the first group but will not touch the second.
6.2 Other conditions
Coeliac disease is screened with tissue transglutaminase antibody, confirmed by duodenal biopsy showing villous atrophy with crypt hyperplasia, and the antibody is immunoglobulin A, so coexisting deficiency must be excluded.
Dermatitis herpetiformis is the skin manifestation and responds to gluten withdrawal in the same way as the enteropathy.
Irritable bowel syndrome is diagnosed on symptom criteria in the absence of alarm features, and it is a positive diagnosis rather than a diagnosis of exclusion.
Colorectal cancer screening is recommended from the fifth decade in average-risk populations, and colonoscopy is both the most sensitive test and the only one that removes the lesion it finds.
6.3 Approaching malabsorption
Steatorrhoea points to fat malabsorption, and the next question is whether the defect is in digestion or in absorption.
Pancreatic insufficiency impairs digestion, so the mucosa is normal and the deficiency pattern is dominated by fat and the fat-soluble vitamins.
Mucosal disease such as coeliac impairs absorption, so iron, folate and calcium are affected as well, and the biopsy is abnormal.
Bile salt deficiency is the third mechanism, arising in cholestasis or after terminal ileal resection, and it produces fat malabsorption with a normal pancreas and a normal proximal mucosa.
Terminal ileal disease is distinctive because that segment alone absorbs vitamin B12 and bile salts, so Crohn disease or resection there produces a deficiency pattern no other site reproduces.
Tropical sprue is relevant in India, presenting with malabsorption and megaloblastic anaemia after a diarrhoeal illness, and it responds to tetracycline with folate.
7. Pancreas
Gallstones and alcohol account for most acute pancreatitis, with hypertriglyceridaemia, hypercalcaemia, drugs, trauma and endoscopic retrograde cholangiopancreatography making up much of the remainder.
Lipase is preferred over amylase because it remains elevated longer and is more specific, since amylase also rises in salivary disease, bowel perforation and renal failure.
The degree of enzyme elevation does not indicate severity, which is judged by organ failure and its persistence rather than by any laboratory value.
Management is aggressive early fluid resuscitation, analgesia and early enteral nutrition, with prophylactic antibiotics specifically not indicated in sterile necrosis.
Enteral feeding is preferred over parenteral because it maintains gut mucosal integrity and reduces bacterial translocation, reversing the older practice of resting the gut completely.
Chronic pancreatitis produces steatorrhoea and diabetes only after most of the gland is destroyed, because the pancreas has a very large functional reserve.
Roughly ninety per cent of exocrine function must be lost before steatorrhoea appears, which is why chronic pancreatitis presents with pain for years before any malabsorption is detectable.
Tropical calcific pancreatitis is a distinct Indian entity affecting young non-alcoholic patients, with large intraductal calculi and early diabetes.
A gallstone cause is sought in every case of acute pancreatitis with an ultrasound, because cholecystectomy during the same admission prevents recurrence and no other cause is as readily removable.
Fluid collections that persist beyond four weeks and acquire a wall become pseudocysts, and they are drained only if symptomatic, infected or enlarging, since most resolve spontaneously.
8. Worked examples
Example 1. A patient with cirrhosis has ascites with 400 neutrophils per cubic millimetre and a negative culture. What is the diagnosis and treatment?
Spontaneous bacterial peritonitis. The count alone is diagnostic, since culture is negative in many genuine cases. Treatment is a third-generation cephalosporin with intravenous albumin to reduce the risk of hepatorenal syndrome.
Example 2. Aspartate transaminase is 180 and alanine transaminase is 70. What does the pattern suggest?
A ratio above two suggests alcoholic liver disease. In viral hepatitis and fatty liver the alanine transaminase is usually the higher of the two.
Example 3. A young man has cirrhosis, a tremor and psychiatric symptoms. What must be excluded?
Wilson disease. Measure ceruloplasmin and twenty-four hour urinary copper and examine for Kayser-Fleischer rings, because the condition is treatable and fatal if missed.
Summary
Localise before diagnosing: hepatocytes, ducts, synthetic function and excretion are answered by different tests.
Transaminases indicate injury, not function, and may be near-normal in advanced cirrhosis.
A ratio of aspartate to alanine above two suggests alcohol; the reverse suggests viral or fatty liver disease.
Gamma-glutamyl transferase confirms that a raised alkaline phosphatase is hepatic rather than skeletal.
Albumin reflects chronic function while prothrombin time reflects acute function.
Gilbert syndrome is benign unconjugated hyperbilirubinaemia worsened by fasting and illness.
Phenobarbitone works in Crigler-Najjar type 2 because there is residual enzyme to induce.
Dubin-Johnson gives conjugated hyperbilirubinaemia with a black liver; Rotor has no pigmentation.
A serum-to-ascites albumin gradient of 1.1 or above indicates portal hypertension.
Spontaneous bacterial peritonitis is diagnosed at 250 neutrophils per cubic millimetre whatever the culture shows.
Albumin is given with the antibiotic because it prevents hepatorenal syndrome.
Lactulose is first-line for encephalopathy, and ammonia levels should not guide treatment.
Antibiotics in acute variceal bleeding independently reduce mortality.
Wilson disease must be excluded in any young person with unexplained liver disease.
Primary biliary cholangitis has antimitochondrial antibodies; primary sclerosing cholangitis has beaded ducts and colitis.
Non-alcoholic fatty liver disease is now the commonest chronic liver disease, and weight loss is the only proven treatment.
Duodenal ulcer pain is relieved by food; gastric ulcer pain is worsened by it.
A gastric ulcer needs biopsy and repeat endoscopy; a duodenal ulcer essentially never is malignant.
Alarm features in reflux mandate endoscopy rather than empirical acid suppression.
Ulcerative colitis is continuous and mucosal; Crohn disease is patchy and transmural with granulomas.
Smoking worsens Crohn disease and protects against ulcerative colitis.
Antimotility agents are contraindicated in acute severe colitis because of toxic megacolon.
Coeliac serology is an immunoglobulin A antibody, so deficiency must be excluded.
Lipase is preferred to amylase in pancreatitis for specificity and duration.
Enzyme levels do not indicate severity, which is judged by organ failure.
Early enteral feeding is preferred to resting the gut, and prophylactic antibiotics are not indicated.
Child-Pugh predicts operative risk; the transplant score uses only objective values so allocation cannot be manipulated.
Encephalopathy is what converts acute hepatitis into acute liver failure, and cerebral oedema is the usual cause of death.
Coagulopathy in acute liver failure is not corrected prophylactically, because the prothrombin time is the prognostic marker.
Dysphagia for liquids as well as solids from the outset indicates a motility disorder, not obstruction.
A raised urea with a normal creatinine supports an upper gastrointestinal source.
Terminal ileal disease uniquely impairs vitamin B12 and bile salt absorption.
Around ninety per cent of exocrine pancreatic function is lost before steatorrhoea appears.
A pseudocyst is drained only if symptomatic, infected or enlarging, since most resolve spontaneously.
Extraintestinal manifestations that track disease activity settle with bowel treatment; those that run independently do not.
