Cirrhosis

• Cirrhosis is the end result of chronic injury to the liver: broad bands of scar tissue divide the liver into nodules, distort its blood vessels and raise resistance to blood flowing through it.
• It begins as a compensated state (the patient feels well, liver tests may be near normal) and can progress to a decompensated state, marked by ascites, variceal bleeding or overt encephalopathy.
• Causes range from alcohol and viral hepatitis to fatty liver disease, autoimmune and metabolic conditions and vascular disorders; many patients have more than one.
• Portal hypertension is the central mechanism behind most of the trouble: it drives varices and bleeding, ascites, hypersplenism and the hyperdynamic circulation.
• Management means stopping the underlying injury (abstinence, antivirals, weight loss), protecting the liver (avoid alcohol excess and NSAIDs, vaccinate), preventing decline (beta blockers, nutrition, surveillance for liver cancer and varices) and referring early for transplantation.

By the end of this page you should be able to:

1. Define cirrhosis and distinguish compensated from decompensated disease.
2. Explain how scar and nodules raise portal pressure and how that leads to ascites, varices and hyperdynamic circulation.
3. Recognise cirrhosis from its full range of physical signs and typical laboratory changes.
4. Choose and interpret first-line investigations and non-invasive fibrosis tests, and know when biopsy is still needed.
5. Apply Child-Pugh and MELD-Na, and state when to refer for transplantation.
6. Outline management of the underlying cause, prevention of decompensation and long-term surveillance.
7. Explain the outline management of alcohol-associated hepatitis.
8. Describe the key points of AASLD 2024 guidance and Baveno VII practice.

Clinicians separate two clinical phases. In compensated cirrhosis there are no present or past complications: no ascites, no variceal bleeding and no overt hepatic encephalopathy. In decompensated cirrhosis at least one of these has occurred (and further decompensation means a second, different event or a recurrence). ^[1]

The transition matters more than the label: decompensation is associated with a large rise in mortality, and the whole goal of management in compensated disease is to delay it. ^[1]

Advanced fibrosis that has not yet become nodular cirrhosis is sometimes called compensated advanced chronic liver disease (cACLD); it behaves like cirrhosis for prognostic purposes. ^{[1] [2]}

Cirrhosis is a leading cause of liver-related death worldwide; the great majority of cases are due to alcohol, chronic viral hepatitis and fatty liver disease, with the proportions shifting by region and over time. In many countries chronic liver disease is now more common in younger adults and is strongly linked to alcohol use and to metabolic syndrome. The exact global prevalence varies by source and is not stated here beyond this broad pattern. ^[2]

Most patients have one dominant cause, but a second (for example alcohol on top of hepatitis C, or metabolic disease on top of an autoimmune condition) is common and accelerates fibrosis. A practical approach is to test for all the major causes in every patient rather than stopping after the first. ^[2]

Risk factors that speed progression include ongoing alcohol use, obesity and insulin resistance, older age, male sex for alcohol-related disease, co-infection with HIV, and the stage of fibrosis at first presentation. Aetiological treatment (stopping alcohol, treating hepatitis, losing weight) can reduce portal pressure and decompensation risk, particularly before cirrhosis is established. ^{[1] [2]}

Almost every insult injures hepatocytes and triggers an inflammatory response. Hepatic stellate cells (the vitamin-A-storing cells in the space of Disse) then activate into myofibroblast-like cells and lay down collagen; simultaneously, regenerative nodules form and the normal vascular architecture is lost. Hepatic stellate cell activation is the final common pathway of cirrhosis. ^[2]

Scar tissue plus active contraction of myofibroblasts shrinks sinusoidal channels, so intrahepatic resistance rises. Portal pressure is normal under 5 mmHg; when it exceeds 10 mmHg the condition is called clinically significant portal hypertension (CSPH), and that is the pressure at which complications begin. ^{[1] [2] [1] [2]}

High pressure in the portal system stresses the splanchnic vessels, which overproduce vasodilators such as nitric oxide. The systemic vessels then dilate, effective arterial blood volume falls and the heart compensates with a high cardiac output — the hyperdynamic circulation. The kidneys retain salt and water (renin-angiotensin-aldosterone system and antidiuretic hormone), which worsens ascites, and the low systemic vascular resistance predisposes to hyponatraemia. ^[2]

Grossly the cirrhotic liver is small, hard and nodular. Microscopy shows broad septa of fibrous tissue, regenerative nodules with hepatocytes that are abnormal in size and arrangement, and sometimes bile duct changes, iron or copper depending on the cause. Pathology is rarely needed to make the diagnosis today, but a biopsy can confirm cirrhosis and stage fibrosis when non-invasive tests are inconclusive. ^[4]

Many patients are asymptomatic and are found on routine blood tests or imaging. Early symptoms are non-specific: fatigue, anorexia, weight loss, pruritus, right upper quadrant discomfort or muscle cramps. Sexual dysfunction, loss of libido and altered menstrual periods can occur. Patients may report dark urine or pale stools. ^[2]

The decompensating events dominate the history once they occur: increasing abdominal girth and ankle swelling, breathlessness, vomiting blood, confusion or sleep inversion. ^[1]

A careful bedside examination covers the whole body. Spider naevi, palmar erythema, gynaecomastia and testicular atrophy reflect hyperestrogenism from reduced hepatic metabolism; muscle wasting, jaundice and leukonychia reflect synthetic failure and chronic disease; the abdominal and neurological signs reflect portal hypertension and ammonia detoxification.

How to elicit a few: hold the arms out straight and watch the wrists for asterixis; look for spider naevi over the upper trunk, face and arms; note nail changes and then record ascites with shifting dullness and a fluid thrill if present. Always record whether the liver edge is palpable and whether the spleen is enlarged. ^[2]

The differential depends on whether the patient arrives with complications (ascites, jaundice, bleeding) or with an isolated abnormality (a raised ALT, thrombocytopenia). Cirrhosis itself must be separated from acute hepatitis, from conditions that mimic portal hypertension without cirrhosis, and from other causes of nodular liver change.

A minimum panel assesses (a) severity of hepatocellular damage, (b) synthetic function, (c) cholestasis and (d) the complications of cirrhosis:

• Full blood count — anaemia, and thrombocytopenia from hypersplenism and reduced thrombopoietin. ^[5]
• Liver panel — bilirubin, AST, ALT, alkaline phosphatase and GGT; look for the pattern (hepatocellular versus cholestatic).
• Synthetic function — albumin (often low), INR / prothrombin time (often prolonged), bilirubin. ^[2]
• Urea and electrolytes — sodium often falls as cirrhosis decompensates; creatinine to stage kidney function. ^[6]
• Electrolytes and glucose — hypokalaemia with diuretics, diabetes in haemochromatosis and fatty liver.
• Urine dipstick and ascitic fluid analysis if ascites is present.
• Imaging: ultrasound of the liver and spleen, portal vein Doppler, elastography; CT or MRI when staging or searching for cancer.

Synthetic dysfunction. Falling albumin, a prolonged INR and a rising bilirubin are the classic triad; together they define severity. ^[2]

Thrombocytopenia. Platelets are low in roughly two-thirds to three-quarters of patients with cirrhosis (about 70%). The mechanisms are splenic sequestration from hypersplenism and reduced hepatic thrombopoietin production; immune destruction and alcohol or viral bone-marrow suppression also play a part. ^[5]

Hyponatraemia. Hypervolaemic (dilutional) hyponatraemia is common in decompensated cirrhosis and is defined as serum sodium under 130 mmol/L in this context; it reflects splanchnic vasodilation and non-osmotic antidiuretic hormone release. ^[6]

Macrocytosis. The mean cell volume is often raised in alcoholic and other chronic liver disease, chiefly through altered lipid metabolism in the red cell membrane and nutritional deficiency; it is a supportive, not specific, clue. ^[6]

Fibrosis can be estimated without biopsy, which makes early detection and staging much safer.

• FIB-4 index (based on age, AST, ALT and platelets). Values under 1.3 (or under 1.45 in some series) make advanced fibrosis unlikely; higher values need a second, imaging-based assessment. ^[4]
• Transient elastography (liver stiffness measurement, LSM, in kPa). Rule of thumb from Baveno criteria: under 10 kPa makes cirrhosis / cACLD unlikely; 10 to 15 kPa suggests it; 15 kPa or more is highly suggestive; 25 kPa or more indicates clinically significant portal hypertension (CSPH) in viral or alcohol-related disease and in non-obese MASLD. ^[1]
• Enhanced liver fibrosis (ELF) test and other serum panels. An ELF below 9.8 helps exclude advanced fibrosis in NAFLD/ALD; 9.8 or more is in keeping with fibrosis. ^{[1] [4]}
• Baveno VI criteria: LSM under 20 kPa plus platelets above 150 x 10^9/L excludes high-risk varices in most patients, so screening endoscopy can be avoided. ^{[1] [4]}

Liver biopsy remains the reference test for diagnosis and staging when non-invasive results are discordant, when the aetiology is uncertain (e.g. autoimmune hepatitis), or when systemic disease is suspected; it is far more informative for inflammation than stiffness is, but it is invasive and samples only a tiny fraction of the liver. ^[4]

Do not stop after the first positive test. A reasonable first battery is:

• Hepatitis serology: HBsAg, anti-HCV, anti-HAV IgG, hepatitis D where endemic.
• Autoimmune markers: ANA, smooth muscle antibody, anti-mitochondrial antibody, anti-LKM, total IgG and IgM.
• Iron studies and HFE testing if iron studies are abnormal.
• Ceruloplasmin and 24-hour urinary copper if Wilson disease is possible (especially under 40 years).
• Alpha-1 antitrypsin level and phenotype.
• Metabolic assessment: fasting glucose/HbA1c, lipids, BMI and alcohol history.
• Imaging / biopsy of the liver if the diagnosis is unclear.

Cirrhosis is a clinical-pathological diagnosis: compatible history, physical signs, supporting labs and imaging showing a nodular liver with portal hypertension. Biopsy confirms it but is often not needed.

Two scores are used to grade severity:

Child-Pugh (Child-Turcotte-Pugh) — five items, 1 to 3 points each: bilirubin, albumin, INR (or prothrombin time), ascites and encephalopathy.

• Class A: 5 to 6 points (well-compensated).
• Class B: 7 to 9 points (significant functional compromise).
• Class C: 10 to 15 points (decompensated).

MELD and MELD-Na. The Model for End-Stage Liver Disease uses bilirubin, INR and creatinine to predict 3-month mortality:

MELD = 3.8 × log_e(bilirubin, mg/dL) + 11.2 × log_e(INR) + 9.6 × log_e(creatinine, mg/dL) + 6.4

MELD-Na adds serum sodium, because hyponatraemia carries a large independent mortality risk in advanced cirrhosis; the formula adjusts the MELD score for serum sodium. ^[9]

How to use them. Child-Pugh is simple, bedside and intuitive, and is still reported for every patient; MELD and MELD-Na predict short-term mortality more accurately and drive liver transplant allocation. Use MELD (or MELD-Na) to decide listing priority and to time referral, and Child-Pugh to describe overall clinical stage. MELD 15 and above is the point at which transplant survival benefit begins to outweigh risk; referral should also follow any new decompensating episode. ^{[2] [9]}

Treat the cause.

• Alcohol: long-term abstinence is central; it produces meaningful reductions in portal pressure and decompensation risk. ^[1]
• Viral hepatitis: suppress hepatitis B and cure hepatitis C; these changes are associated with falling HVPG and lower decompensation. ^[1]
• MASLD/MASH: weight reduction, glycaemic control and treatment of dyslipidaemia. Weight loss of at least 10% in overweight patients is associated with larger falls in HVPG. ^[2]

Non-selective beta-blockers (NSBBs). In compensated cirrhosis with CSPH (liver stiffness 25 kPa or more, or the combination of 20 to 24.9 kPa with platelets under 150 x 10^9/L, or 15 to 19.9 kPa with platelets under 110 x 10^9/L) NSBBs (propranolol, nadolol or carvedilol) should be considered to prevent decompensation. Carvedilol is the preferred agent — more effective at lowering HVPG and better tolerated — and is usually titrated to an optimal dose of 12.5 mg per day. ^{[1] [2]}

Carvedilol dosing in practice: start low and uptitrate to the highest tolerated dose; contraindications include asthma, advanced heart block and bradyarrhythmias, and caution is needed in refractory ascites. ^{[1] [2]}

Endoscopic prophylaxis is used when NSBBs are contraindicated or not tolerated, with beta-blocker-intolerant patients undergoing endoscopic band ligation for high-risk varices and surveillance as described below. ^[1]

• Avoid alcohol excess entirely; even modest intake promotes progression, especially in MASLD and after hepatitis cure. ^[1]
• Avoid NSAIDs and limit other hepatotoxins (including many herbal and dietary supplements): NSAIDs risk renal dysfunction, GI bleeding and worsened ascites. ^[2]
• Avoid unnecessary procedures that carry bleeding risk when platelets are very low. ^[5]

• Vaccination: offer hepatitis A and hepatitis B vaccination to non-immune patients and keep influenza, pneumococcal and COVID-19 vaccination up to date. ^[2]
• Infection control: bacterial infections are major triggers of decompensation, so search and treat them promptly. ^[1]

Patients with cirrhosis are catabolic and frequently under-nourished. Aim for about 35 kcal/kg/day and protein 1.2 to 1.5 g/kg/day. An early breakfast and a late evening snack reduce nocturnal fasting and limit muscle protein breakdown. Protein should not be restricted in hepatic encephalopathy. Vitamin and micronutrient repletion (including thiamine where alcohol is involved) is given as needed. ^[2]

HCC occurs in cirrhosis of almost any cause. Surveillance with ultrasound, with or without AFP, every 6 months detects tumours at a treatable stage. ^[3]

Every patient with cirrhosis should be assessed for portal hypertension and varices.

• If NSBBs are being used for decompensation prevention, endoscopic screening is not needed because it will not change management. ^[1]
• If NSBBs are contraindicated or not tolerated, screen endoscopically if liver stiffness by TE is at least 20 kPa or the platelet count is at most 150 x 10^9/L. ^[1]
• Baveno VII non-invasive rule-in of CSPH when appropriate: liver stiffness at least 25 kPa, or 20 to 24.9 kPa with platelets under 150 x 10^9/L, or 15 to 19.9 kPa with platelets under 110 x 10^9/L. Ruling out (stiffness at most 15 kPa plus platelets at least 150 x 10^9/L) safely excludes CSPH. ^[1]
• Repeat elastography and platelets yearly if endoscopy was avoided; image or scope sooner if stiffness rises to 20 kPa or more or platelets fall to 150 x 10^9/L or less. ^[1]

• Ascites: sodium restriction 2 g/day, diuretics (spironolactone with or without furosemide), large-volume paracentesis for tense ascites with 6 to 8 g of albumin per litre removed, keeping each session under 8 L. ^[2]
• Hepatic encephalopathy: identify triggers (infection, bleeding, constipation, drugs); treat with lactulose, and rifaximin after recurrent episodes. ^[2]
• Variceal bleeding: urgent vasoactive drugs, antibiotic prophylaxis, transfusion to haemoglobin 7 to 8 g/dL, band ligation or tissue adhesive, with pre-emptive TIPS in high-risk patients. ^{[1] [2]}
• Transplant referral: MELD 15 or above, or after any new decompensating event. ^[2]

Severe alcoholic hepatitis is usually considered Maddrey discriminant function of 32 or more, or a MELD score above 20. The discriminant function is:

4.6 × (patient's prothrombin time in seconds − control prothrombin time in seconds) + serum bilirubin (mg/dL)

Prednisolone 40 mg daily for 28 days improves 28-day survival when infection has been excluded and contraindications (such as severe infection or GI bleeding) are absent; response is reassessed at day 7 with a validated score, continuing steroids only in responders. Evidence for longer-term survival benefit is much weaker. ^[7]

Paediatric cirrhosis is relatively uncommon and usually stems from biliary disease (especially biliary atresia), metabolic disorders, autoimmune hepatitis or genetic conditions rather than alcohol. Presentation ranges from poor growth and jaundice to portal hypertension; management is largely by paediatric hepatology teams, with attention to growth, nutrition and early transplant assessment when indicated. ^[2]

• Ascites and spontaneous bacterial peritonitis.
• Variceal haemorrhage (acute variceal bleeding carries 10 to 15% mortality at 6 weeks). ^[2]
• Hepatic encephalopathy.
• Hepatorenal syndrome.
• Hyponatraemia, sarcopenia and frailty.
• Hepatocellular carcinoma.
• Hypogonadism, osteoporosis and infection susceptibility.

Prognosis depends heavily on stage and aetiology. Compensated patients can remain stable for years with good aetiological control; decompensation reduces survival sharply and marks the need for transplant assessment. Treated early, before cirrhosis and diabetes, even severe iron-storage or alcoholic disease can normalise life expectancy; once cancer or decompensation occurs, survival falls. ^{[1] [2]}

• Older adults: more likely to have MASLD, to be malnourished and to have reduced drug tolerance. Doses of diuretics and beta-blockers need care.
• Pregnancy: cirrhosis in pregnancy is high risk; management needs a joint liver-obstetric team.
• Immunocompromised patients: lower threshold for infection and more aggressive surveillance.

• Baveno VII (de Franchis 2022) sets the modern non-invasive roadmap: cACLD and CSPH thresholds, variceal screening rules, NSBBs (preferably carvedilol) to prevent the first decompensation, and management of bleeding and further decompensation. ^[1]
• AASLD 2024 practice guidance on portal hypertension and varices aligns on early, carvedilol-based prevention of decompensation, conservative transfusion and prompt vasoactive therapy for acute bleeding, and TIPS for refractory ascites and high-risk bleeding. ^[2]
• EASL guidance underpins the non-invasive tests used for fibrosis and staging. ^[4]
• Points where guidance still differs: the exact thresholds for ruling in CSPH in NASH with BMI above 30 kg/m^2, the role of spleen stiffness outside viral disease, and how often endoscopic surveillance should be repeated (still incompletely defined). ^{[1] [2]}

• Where resources are very limited, simple clinical signs, cheap LFTs and a basic ultrasound go a long way.
• Ultrasound elastography and platelet counts may be unavailable: rely on palpable splenomegaly, ascites, thrombocytopenia, spider naevi and a nodular liver on basic ultrasound. ^[2]
• NSBBs and diuretics are cheap and effective; carvedilol may not be available, so propranolol is a reasonable alternative. ^{[1] [2]}
• Band ligation needs an endoscopist; where none exists, make early referral to a centre that does.
• HCC surveillance with ultrasound is often limited; use 6-monthly ultrasound where possible and consider AFP where imaging is sporadic. ^[3]
• Nutrition is the cheapest intervention: high-energy, adequate protein with a late-evening snack. ^[2]
• Vaccination programmes (hepatitis B) are the most cost-effective prevention of cirrhosis at population level. ^[2]

Liver fibrosis and staging; portal hypertension, ascites and spontaneous bacterial peritonitis; alcohol-related liver disease and alcohol-associated hepatitis; hepatitis B, hepatitis C; NAFLD/MASLD and steatohepatitis; haemochromatosis and Wilson disease; alpha-1 antitrypsin deficiency; autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis; hepatocellular carcinoma; liver transplantation; nutrition in chronic liver disease.