Cirrhosis diagnosis and prognosis

Chronic Liver Disease, Cirrhosis Complications & Acute Hepatitis

Chronic liver disease (CLD) and cirrhosis represent significant contributors to morbidity and mortality in Australia. Cirrhosis is the histopathological end-stage of chronic necroinflammatory liver injury, characterized by diffuse replacement of normal hepatic architecture with fibrotic regenerative nodules and altered intrahepatic vascular resistance. Decompensation marks the transition from a stable asymptomatic state to high-mortality clinical failure.

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Cirrhosis Aetiologies & Pathophysiology

Primary Aetiologies in Australia

• Alcohol-related disease: Ask about quantities in Australian standard drinks, duration and dependence without treating a grams-per-day cut-off as a safe level. Liver risk depends on multiple factors. Abstinence is recommended with established alcohol-related liver disease, with withdrawal risk addressed safely.

1. Metabolic Dysfunction-Associated Steatohepatitis (MASH): Formerly termed non-alcoholic steatohepatitis (NASH). Driven by metabolic syndrome, insulin resistance, type 2 diabetes mellitus, dyslipidaemia, and obesity. Histology shows ballooned hepatocytes, Mallory-Denk bodies, and pericellular 'chicken-wire' fibrosis.
2. Chronic Viral Hepatitis (HBV & HCV): Non-cytopathic viral persistence causing immune-mediated hepatocyte destruction and progressive fibrogenesis.
3. Autoimmune & Cholestatic Liver Diseases:
   • Autoimmune Hepatitis (AIH): Interface hepatitis with prominent plasma cell infiltration, elevated serum IgG, and autoantibodies (anti-nuclear antibody [ANA], anti-smooth muscle antibody [ASMA], anti-liver kidney microsomal-1 [anti-LKM1]).
   • Primary Biliary Cholangitis (PBC): T-cell mediated autoimmune destruction of small intrahepatic interlobular bile ducts occurring primarily in middle-aged women. Characterised by raised alkaline phosphatase (ALP), antimitochondrial antibody (AMA) positivity in $> 95\%$, and elevated serum IgM.
   • Primary Sclerosing Cholangitis (PSC): Fibro-obliterative destruction of medium and large intra- and extrahepatic bile ducts strongly linked to inflammatory bowel disease ($70-80\%$ have ulcerative colitis). Leads to multifocal strictures ('beading') on MRCP.
4. Genetic & Metabolic Infiltration:
   • Hereditary Haemochromatosis: Autosomal recessive HFE gene mutation (C282Y homozygosity), causing unregulated intestinal iron absorption and parenchymal iron deposition. Screened via transferrin saturation ($> 45-50\%$) and serum ferritin.
   • Wilson Disease: Autosomal recessive ATP7B mutation causing impaired biliary copper excretion. Presents in adolescents or young adults with acute hepatitis, cirrhosis, Kayser-Fleischer rings, and basal ganglia neuropsychiatric symptoms. Low serum caeruloplasmin and elevated 24-hour urinary copper.
   • Alpha-1 Antitrypsin Deficiency: SERPINA1 gene mutation (PiZZ phenotype); misfolded glycoprotein aggregates within hepatocyte endoplasmic reticulum (PAS-positive, diastase-resistant globules), predisposing to cirrhosis and panacinar emphysema.

Pathophysiological Cascade of Portal Hypertension

Normal hepatic venous pressure gradient (HVPG) is $1-5\text{ mmHg}$. Clinically significant portal hypertension (CSPH) develops when $HVPG \ge 10\text{ mmHg}$:

1. Increased Intrahepatic Resistance: Structural distortion from collagen deposition in the space of Disse plus functional vasoconstriction driven by decreased endothelial nitric oxide (NO) synthase activity.
2. Splanchnic Arterial Vasodilation: Splanchnic endothelial release of endogenous vasodilators (predominantly nitric oxide) leads to massive splanchnic arterial vasodilation.
3. Hyperdynamic Circulation & Neurohormonal Activation: Pooling of blood in the splanchnic bed causes a decrease in effective arterial blood volume (EABV). Baroreceptors sense arterial underfilling, triggering intense activation of the renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system (SNS), and non-osmotic release of arginine vasopressin (ADH).
4. Fluid Retention: Sustained renal sodium and water retention causes plasma volume expansion, elevating portal inflow and perpetuating ascites, variceal enlargement, and circulatory collapse.

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Clinical Prognostic Scoring Systems

Risk stratification directs transplant assessment and monitors disease progression.

The Child-Turcotte-Pugh (CTP) Score

The Child-Pugh score evaluates five clinical and laboratory parameters, each assigned 1, 2, or 3 points:

• Total Bilirubin: 1 Point: $< 34\ \mu\text{mol/L}$; 2 Points: $34-50\ \mu\text{mol/L}$; 3 Points: $> 50\ \mu\text{mol/L}$

• Serum Albumin: 1 Point: $> 35\text{ g/L}$; 2 Points: $28-35\text{ g/L}$; 3 Points: $< 28\text{ g/L}$

• INR: 1 Point: $< 1.7$; 2 Points: $1.7-2.3$; 3 Points: $> 2.3$

• Ascites: 1 Point: Absent; 2 Points: Mild / Controlled by diuretics; 3 Points: Moderate to severe / Refractory

• Grade 1: Subtle attention, personality or sleep changes; clear asterixis is more typical of grade 2. Exclude infection, medicines, glucose/electrolyte disturbance and intracranial disease.

• Child-Pugh Class A (5 to 6 points): Well-compensated disease. 1-year survival approximately $100\%$.

• Child-Pugh Class B (7 to 9 points): Significant functional compromise. 1-year survival approximately $80\%$.

• Child-Pugh Class C (10 to 15 points): Decompensated cirrhosis. 1-year survival approximately $45\%$; urgent referral for liver transplantation evaluation required.

The Model for End-Stage Liver Disease (MELD) Score

MELD is a validated mathematical model predicting 90-day mortality based on objective objective variables:

• Serum Bilirubin
• Serum Creatinine
• INR
• Serum Sodium (MELD-Na)

Used across Australian liver transplant centers to prioritize deceased donor organ allocation based on medical urgency rather than waiting time.

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Prognosis is not a fixed prediction

A person with ascites, low albumin and a raised INR needs assessment of decompensation, reversible triggers and suitability for transplant referral. Calculate the score from the actual components and check whether anticoagulants or other factors confound them. A prognostic category describes risk in populations; it does not give an exact remaining lifespan or establish that treatment is futile. Reassess nutrition, alcohol dependence, infection risk and follow-up access. A patient who improves after treating the cause can still need surveillance for complications.

Primary references (checked 7 October 2026): ADQI–ICA cirrhosis/AKI consensus.