Cirrhosis

Meet the patient

A 58-year-old man with a long history of heavy alcohol use is brought in by his daughter. His abdomen has been swelling for two months, he slept most of yesterday, and this morning he could not draw a clock. On examination he has spider naevi, palmar erythema, a flapping tremor at the wrist, and shifting dullness in the abdomen.[1]

This is decompensated cirrhosis with hepatic encephalopathy, and three questions now run in parallel: what precipitated the decline?, is there an infection or a bleed hiding?, and how do I grade the severity and the transplant urgency? Hold those three and the rest of the topic slots in around them.[1]

Compensated versus decompensated — the line that decides survival

One clinical line divides the whole disease and predicts the prognosis more than any scan. Cirrhosis is compensated until one of the four decompensation events appears, and the drop in survival across that line is steep.[1]

• Compensated cirrhosis — the liver still performs its synthetic, detoxifying, and excretory functions despite architectural distortion. The patient is usually asymptomatic, detected by stigmata, abnormal liver tests, or incidental imaging. Median survival exceeds 10 to 12 years.
• Decompensated cirrhosis — defined by the development of one of four events: ascites, variceal haemorrhage, hepatic encephalopathy, or jaundice. Median survival without transplant falls to about 1.5 to 2 years.[1]

[1]

The number rule: 4 events, 1 line. Ascites, variceal bleed, encephalopathy, jaundice — any one moves the patient across the line. Ascites is the commonest first decompensation; name all four in a viva before you say anything else.[1]

Etymology for viva gold: cirrhosis is from Greek kirrhos, "tawny-yellow" — Laennec coined it from the nodular, yellow-green appearance of the chronically diseased liver at autopsy. The word survived because the gross pathology it describes is unchanged two centuries on.[1]

Baveno VII added a word that changes counselling: "recompensation". With sustained cause treatment — HCV cure, HBV suppression, alcohol abstinence — a decompensated patient who resolves ascites and encephalopathy off diuretics and off lactulose (or on stable low doses), with no further decompensation for at least 12 months, returns toward a compensated phenotype. The cirrhosis persists; the prognosis improves. This is not cure, but it is real.[2]

The stigmata — the viva shopping list

A cirrhotic announces the diagnosis on the hands, the skin, and the face before you scan the abdomen. Examiners expect ten signs, clustered so they stay:[1]

• Hands — palmar erythema (thenar and hypothenar, sparing the central palm), Dupuytren contracture, clubbing (especially in PBC), leuconychia (hypoalbuminaemia), asterixis if encephalopathic.
• Skin — spider naevi (a central arteriole with radiating vessels, confined to the drainage of the superior vena cava — above the nipple line), easy bruising.
• Face and head — parotid enlargement, fetor hepaticus (sweet faecal breath from mercaptans), xanthelasma in PBC, sallow complexion.
• Chest and endocrine — gynaecomastia (testosterone falls, oestrogen rises from reduced hepatic clearance), testicular atrophy, loss of secondary sexual hair.
• Abdomen — hepatosplenomegaly early, a small shrunken liver late, caput medusae (recanalised umbilical vein), ascites.
• General — sarcopaenia, especially temporal and proximal muscle wasting.[1]

Aetiology clues at the bedside narrow the cause faster than a panel: tattoos or IV drug use (HBV, HCV); a Kayser-Fleischer ring (Wilson); bronze diabetes and heart failure (haemochromatosis); parotid enlargement and Dupuytren (alcohol); xanthomata and pruritus (PBC); inflammatory bowel disease with recurrent cholangitis (PSC).[1]

Two master mechanisms — fibrogenesis and portal hypertension

The fibrogenesis cascade is the mechanism every candidate must recite as a chain. Each step earns its place because it explains a treatment.[1]

1. Chronic hepatocellular injury — virus, alcohol, fat, cholestasis, autoimmune, metabolic — produces apoptotic hepatocytes and reactive oxygen species.
2. Injured hepatocytes, sinusoidal endothelium, and Kupffer cells release profibrogenic cytokines — TGF-beta1, PDGF, CTGF.
3. These activate quiescent hepatic stellate cells (the vitamin-A storing Ito cells of Disse space), which transdifferentiate into proliferating, contractile myofibroblasts.
4. Activated stellate cells secrete type I and III collagen into the space of Disse, express TIMPs that block matrix breakdown, and contract around sinusoids to raise intrahepatic resistance.
5. Sinusoidal endothelium loses its fenestrations (capillarisation), impeding oxygen and metabolite exchange; fibrous septa bridge portal tracts to central veins; regenerative nodules form.[1]

The regression half of the story is why cause-treatment works. Remove the injurious stimulus — HCV cure, alcohol abstinence, HBV suppression — and activated stellate cells undergo apoptosis or senescence, collagenases (MMP-1) break down matrix, and fibrosis can regress. This is the biological basis of Baveno VII's "recompensation".[2]

Portal hypertension has two components, and the split is therapeutically loaded. The structural component — fibrosis, nodules, distortion — is fixed. The dynamic component — stellate cell contraction driven by endothelin, thromboxane, and angiotensin-II against deficient intrahepatic nitric oxide — is reversible, and it is the rationale for NSBB (lowering portal inflow) and terlipressin (splanchnic vasoconstriction). Meanwhile excess splanchnic nitric oxide and glucagon dilate the splanchnic arteriolar bed, increasing portal inflow and worsening the pressure.[1]

The HVPG thresholds are the single most reproduced numbers in hepatology exams.[1]

[1]

The hyperdynamic circulation explains ascites, hyponatraemia, and hepatorenal syndrome in one chain. Splanchnic vasodilation drops systemic vascular resistance and the effective arterial blood volume, which fires the RAAS, the sympathetic nervous system, and non-osmotic vasopressin. The consequences are avid sodium retention (ascites), free-water retention (dilutional hyponatraemia), and renal vasoconstriction (hepatorenal syndrome). Ascites itself needs three things together — sinusoidal portal hypertension (HVPG over 12), splanchnic vasodilation, and hypoalbuminaemia lowering oncotic pressure.[1]

Hepatic encephalopathy — ammonia, inflammation, and the precipitants

Hepatic encephalopathy is reversible, and the single most important step is finding and treating the precipitant. The dominant hypothesis is ammonia modified by systemic inflammation: gut-derived nitrogenous toxins (chiefly ammonia) bypass hepatic clearance through portosystemic collaterals or the failing liver, cross the blood-brain barrier, and astrocytes metabolise ammonia to glutamine — which is osmotically active, swelling the astrocyte. Increased GABAergic tone and cytokine-driven blood-brain barrier permeability synergise with ammonia to depress neuronal function.[1]

The precipitants are the list you hunt when a cirrhotic deteriorates — and they explain the management:[1]

[1]

The West Haven grades are reproduced verbatim, and the bedside test for grade I to II is the clock.[1]

[1]

The bedside exam for encephalopathy is asterixis and construction. Ask the patient to hold the hands dorsiflexed with fingers spread for 30 seconds — a liver flap (rapid flexion-extension at the wrist and MCP) appears bilaterally; it is also seen in uraemia and hypercapnia. Then ask them to draw a clock — failure indicates grade I to II. Overt HE is grades II to IV; covert and minimal HE predict overt HE and impair driving.[1]

A deteriorating cirrhotic is not automatically encephalopathic — run the differential. Hyponatraemia (sodium under 125), sepsis or septic encephalopathy, an intracranial lesion (subdural haematoma from a fall and coagulopathy — CT head if any focal sign or unexplained deterioration), Wernicke encephalopathy (give IV thiamine before glucose), and drug or sedative accumulation all mimic HE.[1]

Ascites and the SAAG — the single most testable ascites concept

Tap the ascites, then read the serum-ascites albumin gradient. The SAAG (serum albumin minus ascitic albumin, on the same day) classifies ascites by mechanism and is a viva staple:[1]

[1]

Within high-SAAG ascites, the ascitic total protein splits cirrhosis from cardiac. In cirrhotic ascites the protein is under 2.5 g/dL; in cardiac ascites it is over 2.5 g/dL (with JVP distension, hepatomegaly, and no splenomegaly). Budd-Chiari adds painful hepatomegaly, sudden-onset ascites, and caudate lobe hypertrophy.[1]

The diagnostic paracentesis is mandatory in every cirrhotic with new or worsening ascites, and in every cirrhotic admitted to hospital with ascites — the commonest pitfall is failing to tap. Insert the needle in the left lower quadrant, 2 cm medial and 2 cm superior to the anterior superior iliac spine (avoiding the inferior epigastric vessels). Send fluid for cell count (PMN), albumin (for SAAG), culture in blood-culture bottles at the bedside (yield rises to 80 percent), total protein, and — if indicated — cytology, ADA or TB-PCR, amylase, and triglycerides.[1]

Severity — Child-Pugh and MELD-Na

Two scores divide the labour, and reproducing their components verbatim is a viva staple. The Child-Pugh mixes labs with clinical findings and stratifies prognosis; the MELD-Na is a pure lab score that predicts 3-month mortality and drives transplant priority.[1]

Child-Pugh — five components, each 1 to 3 points:[1]

[1]

Grades: A is 5 to 6 (1-year survival around 100 percent); B is 7 to 9 (1-year around 80 percent); C is 10 to 15 (1-year around 45 percent). Class C carries the highest mortality without transplant.[1]

MELD predicts 3-month mortality from bilirubin, INR, and creatinine; MELD-Na adds sodium because hyponatraemia independently predicts death in cirrhosis.[1]

MELD = 3.78 x ln(bilirubin mg/dL) + 11.2 x ln(INR) + 9.57 x ln(creatinine mg/dL) + 6.43[1]

MELD-Na = MELD + 1.32 x (137 minus Na) minus [0.033 x MELD x (137 minus Na)][1]

Approximate 3-month mortality by MELD: 10 is around 6 percent, 20 around 20 percent, 30 around 53 percent, 40 around 71 percent. A MELD of 15 or more is the threshold to refer for transplant assessment.[1]

Treat the cause — the most powerful long-term modifier

Before any complication bundle, the single intervention that transforms prognosis is treating the underlying cause. Name the cause, then the cause-specific therapy.[1]

[1]

The four complications and their bundles

Ascites — the stepwise ladder

Four rungs, in order, and the diuretic ratio is the dose every candidate must reproduce.[1]

1. Dietary sodium restriction to under 2 g (88 mmol) per day — the cornerstone.
2. Fluid restriction only if hyponatraemia (sodium under 120 to 125 mmol/L).
3. Diuretics — spironolactone plus furosemide in a 100:40 ratio (e.g. spironolactone 100 mg plus furosemide 40 mg orally in the morning), titrated up to a maximum of 400 mg plus 160 mg daily. The ratio maintains normokalaemia; spironolactone beats a loop alone because of secondary hyperaldosteronism. Target weight loss 0.5 kg/day (1 kg/day if peripheral oedema); watch for gynaecomastia, hyperkalaemia, dehydration.
4. Refractory ascites — large-volume paracentesis (drain over 5 L per session with intravenous albumin 8 g per litre drained over 5 L to prevent post-paracentesis circulatory dysfunction), TIPS in selected patients, or liver transplantation.[1]

[1]

Spontaneous bacterial peritonitis — cefotaxime plus albumin, do not wait for culture

The diagnostic threshold is a PMN count of 250 cells/mm^3 or more, and the antibiotic starts the moment it is met.[1]

• Treatment — cefotaxime 2 g IV every 12 hours for 5 to 7 days (or ceftriaxone 1 g IV daily), plus intravenous albumin 1.5 g/kg on day 1 and 1 g/kg on day 3 — albumin halves hepatorenal syndrome and mortality.
• Secondary prophylaxis (after one episode — high recurrence) — norfloxacin 400 mg orally daily or ciprofloxacin 500 mg daily indefinitely, or until transplant.
• Primary prophylaxis — for ascitic protein under 1.5 g/dL with impaired renal or hepatic function (creatinine over 1.2, BUN over 25, Child-Pugh over 9, sodium under 130).[1]

[1]

Acute variceal bleed — the time-critical bundle

The variceal bleed bundle starts at first suspicion, before endoscopy confirms varices — every component is examinable.[1]

• Vasoactive drug — terlipressin 2 mg IV every 4 hours for 2 to 5 days (a vasopressin V1 agonist causing splanchnic vasoconstriction; the only vasoactive shown to reduce mortality). Alternative: octreotide 50 microgram IV bolus then 50 microgram/hour infusion.
• Antibiotic — ceftriaxone 1 g IV daily for up to 7 days, to all cirrhotics with any GI bleed (reduces SBP, bacteraemia, rebleeding, and death).
• Endoscopy — endoscopic band ligation within 12 hours for oesophageal varices; cyanoacrylate glue for gastric varices (banding a gastric varix risks catastrophic bleeding).
• Restrictive transfusion — target Hb 7 to 8 g/dL; over-transfusion raises portal pressure and worsens bleeding.
• Rescue — balloon tamponade (Sengstaken-Blakemore or Minnesota tube) or a self-expanding metal oesophageal stent as a temporary bridge (maximum 24 hours), then TIPS for failure to control or early rebleeding. Pre-emptive TIPS within 72 hours for high-risk cirrhotics (Child-Pugh C under 14, or Child-Pugh B with active bleeding).[1]

Hepatic encephalopathy — fix the precipitant, lactulose, then rifaximin

• Identify and treat the precipitant — the most important single intervention.
• Lactulose 15 to 30 mL orally two to four times daily, titrated to 2 to 3 soft stools per day — acidifies the colon (converting ammonia to non-absorbable ammonium) and is an osmotic laxative.
• Rifaximin 550 mg orally twice daily — added for secondary prevention of overt HE (reduces recurrence and hospitalisation).
• Nutrition — do NOT restrict protein. Daily protein 1.2 to 1.5 g/kg; treat sarcopaenia. Vegetable and dairy proteins may be better tolerated.[1]

Hepatorenal syndrome — stop the nephrotoxins, albumin challenge, then terlipressin

Diagnostic criteria (ICA): a rise in serum creatinine (AKI criteria), no response to an albumin challenge of 1 g/kg/day for 2 days, absence of shock, no current nephrotoxins, and no structural kidney disease.[1]

• Stop all diuretics and nephrotoxins — NSAIDs, ACE-inhibitors, aminoglycosides, iodinated contrast.
• Albumin challenge 1 g/kg/day for 2 consecutive days (max 100 g/day) after withdrawing diuretics.
• If creatinine fails to improve, the diagnosis is HRS-AKI — escalate to terlipressin 1 to 2 mg IV every 4 to 6 hours with albumin (the CONFIRM trial confirmed terlipressin efficacy; monitor for ischaemia and fluid overload). Where terlipressin is unavailable, a noradrenaline infusion in ICU.
• Renal replacement therapy as a bridge; liver transplant, or simultaneous liver-kidney transplant, is definitive.[1]

Prevent decompensation — NSBB, HCC surveillance, and the Baveno rule-out

In compensated cirrhosis the goal is to prevent the first decompensation, and two interventions do the heavy lifting.[2]

Primary prophylaxis of first variceal bleed in those with high-risk varices (medium or large, or small with red wale signs or Child-Pugh B or C): a non-selective beta-blocker — propranolol 20 to 80 mg BD, nadolol 20 to 40 mg daily, or carvedilol 6.25 to 12.5 mg daily — titrated to a resting heart rate of 55 to 60. Carvedilol is preferred for clinically significant portal hypertension because its additional alpha-1 blockade lowers intrahepatic resistance (Baveno VII); avoid it in severe asthma, decompensated heart block, or hypotension (SBP under 90). The alternative is serial endoscopic band ligation. Secondary prophylaxis after a bleed is NSBB plus EVL combined — the lowest rebleeding rate.[2]

HCC surveillance is for life, in every cirrhotic, regardless of cause or viral control. 6-monthly ultrasound plus or minus serum alpha-fetoprotein; a nodule with arterial hypervascularity and washout on multiphase CT or MRI is hepatocellular carcinoma by imaging criteria (LI-RADS) without biopsy.[1]

The Baveno VI rule-out avoids unnecessary endoscopy. A liver stiffness under 25 kPa and platelets over 110 x 10^9/L makes high-risk varices unlikely, and screening endoscopy can be safely skipped.[2]

Liver transplantation and HCC

Liver transplantation is the definitive therapy for decompensated cirrhosis. Indications: decompensation with MELD 15 or more, a first episode of SBP, a first episode of overt HE, refractory ascites, or HCC within Milan criteria (a single tumour under 5 cm, or up to 3 nodules each under 3 cm, no vascular invasion, no extrahepatic spread). Absolute contraindications: active alcohol or substance misuse, uncontrolled extrahepatic sepsis, severe cardiopulmonary disease, uncontrolled extrahepatic malignancy. Survival is around 85 to 90 percent at 1 year and 70 to 75 percent at 5 years.[1]

HCC is staged and treated by the BCLC framework. Very early or early disease (single tumour, preserved function): resection, thermal ablation, or transplant within Milan criteria. Intermediate (multinodular, preserved function): transarterial chemoembolisation. Advanced (portal invasion, metastases): systemic therapy — atezolizumab plus bevacizumab first-line, or sorafenib or lenvatinib. Terminal: best supportive care.[1]

How cirrhosis patients come to harm — the preventable list

• Failing to perform a diagnostic tap in a cirrhotic with new or worsening ascites — SBP missed.[1]
• Over-transfusing a variceal bleed to a haemoglobin of 9 or 10 — portal pressure rises and bleeding worsens.[1]
• Giving NSAIDs, ACE-inhibitors, aminoglycosides, or iodinated contrast — precipitating hepatorenal syndrome.[1]
• Protein-restricting an encephalopathic patient — worsening malnutrition and mortality.[1]
• Missing HCC surveillance in a stable compensated cirrhotic.[1]
• Rapidly correcting hyponatraemia — osmotic demyelination.[1]
• Forgetting the antibiotic and vasoactive drug in the acute variceal bleed bundle.[1]
• Forgetting thiamine before glucose in the alcoholic hypoglycaemic patient — Wernicke encephalopathy.[1]

Acute-on-chronic liver failure — the precipitant-driven emergency

When organ failure accompanies acute decompensation, the syndrome is acute-on-chronic liver failure (ACLF), and 28-day mortality is 20 to 60 percent. It is graded ACLF-1, -2, or -3 by the number of organ failures on the CLIF-C organ-failure score — liver (bilirubin), kidney (creatinine), brain (West Haven), coagulation (INR), circulation (vasopressors), lung (PaO2 over FiO2). Management is treat the precipitant (infection, bleed, alcohol binge), organ support in ICU, terlipressin and albumin if HRS, and early transplant in selected patients.[1]

The trials and scores that set the standard

[1] [2]

Special populations — what changes

Alcohol-related cirrhosis. The classical micronodular pattern with AST over ALT (ratio over 2), raised gamma-GT and MCV. Abstinence is disease-modifying at every stage. Give thiamine 100 mg IV or IM daily for 3 to 5 days before any glucose; manage withdrawal with a long-acting benzodiazepine (chlordiazepoxide) by a CIWA regimen. Malnutrition and sarcopaenia are near-universal — aggressive nutrition (35 to 40 kcal/kg/day, 1.2 to 1.5 g/kg protein) improves survival. Consider corticosteroids in severe alcoholic hepatitis (Maddrey discriminant function 32 or more) after excluding infection.[1]

Viral hepatitis B or C. Treat HCV with DAAs when feasible (curative); suppress HBV lifelong with tenofovir or entecavir to reduce decompensation and HCC risk. HCC surveillance continues regardless of viral control — antiviral cure does not eliminate HCC risk. Vaccinate for HAV and HBV if non-immune.[2]

MASLD or cryptogenic cirrhosis. Look for the metabolic syndrome; many present as cryptogenic (burnt-out MASLD). Cardiovascular disease is the leading cause of death — manage aggressively with statins (safe and beneficial in cirrhosis), antihypertensives (avoid ACE-inhibitors and NSAIDs), tight glycaemic control, and weight loss of 7 to 10 percent.[1]

Pregnancy with cirrhosis. High risk of variceal bleed in the second trimester and at delivery (increased blood volume and intra-abdominal pressure); screen and band varices before conception if known, prefer regional anaesthesia, and plan delivery in a tertiary centre.[1]

The mantra

The mantra: treat the cause, prevent the first decompensation with a beta-blocker, tap every new ascites, give the antibiotic to every cirrhotic who bleeds — and watch for the cancer for life.[1][2]

Ward-round test — three stems, thirty seconds each

Stem 1 — the man from the top of the topic (answer)

The 58-year-old with alcohol use, abdominal swelling, sleepiness, and an inability to draw a clock, with spider naevi, palmar erythema, asterixis, and shifting dullness. What is your first move? Model: This is decompensated cirrhosis with hepatic encephalopathy. The first move is to find and treat the precipitant — send cultures, check the sodium, do a diagnostic paracentesis (any cirrhotic with ascites who deteriorates gets a tap — SBP is the commonest hidden precipitant), a rectal exam for melaena, and review the drug chart. Start lactulose 15 to 30 mL two to four times daily titrated to 2 to 3 soft stools. Grade the encephalopathy by West Haven and the severity by Child-Pugh and MELD-Na. Do not restrict protein; treat the sarcopaenia. If the PMN count is 250 or more, treat SBP with cefotaxime plus albumin.[1]

Stem 2 — the cirrhotic who bleeds (answer)

A known cirrhotic presents with massive haematemesis. What do you start before the endoscopy? Model: Start the variceal bleed bundle at first suspicion — do not wait for endoscopy to confirm varices. Terlipressin 2 mg IV every 4 hours, ceftriaxone 1 g IV daily to all cirrhotics, protect the airway (intubate early if encephalopathic), resuscitate with a restrictive transfusion to Hb 7 to 8 g/dL (over-transfusion raises portal pressure and worsens bleeding), and correct coagulopathy judiciously. Book endoscopic band ligation within 12 hours (cyanoacrylate glue for gastric varices). If bleeding is uncontrolled or recurs early, balloon tamponade or a self-expanding metal stent as a bridge to TIPS; consider pre-emptive TIPS within 72 hours for Child-Pugh B with active bleeding or Child-Pugh C under 14.[1]

Stem 3 — the rising creatinine in tense ascites (answer)

A decompensated cirrhotic with tense ascites on spironolactone and furosemide has a rising creatinine. What is the pathway? Model: First exclude the reversible causes — check for SBP (diagnostic tap), hypovolaemia from over-diuresis, and nephrotoxins. Stop all diuretics and nephrotoxins (NSAIDs, ACE-inhibitors, aminoglycosides, contrast). Give an albumin challenge of 1 g/kg/day for 2 consecutive days. If the creatinine does not improve, the diagnosis is hepatorenal syndrome-AKI — escalate to terlipressin 1 to 2 mg IV every 4 to 6 hours with albumin (monitor for ischaemia and fluid overload), renal replacement therapy as a bridge, and liver transplant as definitive therapy. The recurring error is reaching for more diuretics or a fluid bolus without excluding SBP first.[1]

References

1. [1]Kaplan DE, Ripoll C, Thiele M, et al. AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis Hepatology, 2024.PMID 37870298
2. [2]de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII - Renewing consensus in portal hypertension J Hepatol, 2022.PMID 35120736