Cirrhosis 

 Definition

Cirrhosis is a diffuse, progressive, and irreversible liver disease characterized by:

• 🔹 Bridging fibrosis
• 🔹 Regenerative nodules
• 🔹 Distortion of normal hepatic architecture
• 🔹 Development of portal hypertension and hepatic insufficiency

It represents the end stage of chronic liver injury, regardless of etiology.

 Normal Liver vs Cirrhotic Liver

Normal Liver

• Smooth surface
• Uniform parenchyma
• Intact lobular architecture

Cirrhotic Liver

• Irregular, nodular surface
• Fibrous septa
• Regenerative nodules
• Distorted vascular channels

 Etiology of Cirrhosis

1️⃣ Alcohol-Related Liver Disease

• Chronic ethanol toxicity
• Most common in many regions
• Associated with:
• Steatosis → alcoholic hepatitis → cirrhosis

2️⃣ Chronic Viral Hepatitis

• Hepatitis B
• Hepatitis C

3️⃣ Metabolic & Genetic

• Non-alcoholic fatty liver disease (NAFLD/NASH)
• Wilson disease
• Hemochromatosis
• Alpha-1 antitrypsin deficiency

4️⃣ Autoimmune

• Autoimmune hepatitis
• Primary biliary cholangitis
• Primary sclerosing cholangitis

5️⃣ Vascular Causes

• Budd–Chiari syndrome
• Chronic right heart failure

6️⃣ Drugs & Toxins

• Methotrexate
• Amiodarone
• Aflatoxins

 Pathophysiology — Step-by-Step

1️⃣ Chronic Injury

Persistent inflammation → hepatocyte necrosis.

2️⃣ Stellate Cell Activation

• Hepatic stellate cells (Ito cells)
• Transform into myofibroblasts
• Produce collagen types I & III

3️⃣ Fibrosis

• Portal–portal and portal–central bridging fibrosis
• Sinusoidal capillarization

4️⃣ Architectural Distortion

• Regenerative nodules form
• Intrahepatic resistance increases

5️⃣ Portal Hypertension Develops

Due to:

• Increased intrahepatic resistance
• Splanchnic vasodilation
• Hyperdynamic circulation

 Portal Hypertension — Core Concept

Portal pressure = Flow × Resistance

Cirrhosis increases:

• 🔺 Resistance (fibrosis, nodules)
• 🔺 Flow (NO-mediated vasodilation)

Consequences

• Varices
• Ascites
• Splenomegaly
• Hepatorenal syndrome
• Portosystemic shunts

 Compensated vs Decompensated Cirrhosis

Transition to decompensation dramatically worsens prognosis.

Causes of Decompensated Cirrhosis

Decompensation occurs when portal hypertension or hepatic insufficiency crosses a threshold.

Common Triggers

 ACLF vs Decompensated Cirrhosis

Cirrhosis is not a static disease. Once a patient develops ascites, variceal bleed, or encephalopathy, they enter decompensated cirrhosis.

However, a subset of these patients deteriorate rapidly, develop organ failures, and have very high short-term mortality — this is Acute-on-Chronic Liver Failure (ACLF).

 1️⃣ Definitions

🔹 Decompensated Cirrhosis

Cirrhosis with one or more of:

• Ascites
• Variceal bleeding
• Hepatic encephalopathy
• Jaundice

Progression is usually gradual.

 Acute-on-Chronic Liver Failure (ACLF)

Two major definitions exist:

 EASL-CLIF Definition

From the European Association for the Study of the Liver

Acute decompensation of cirrhosis associated with organ failure(s) and high 28-day mortality

Organ failures are defined by the CLIF-SOFA score.

 APASL Definition

From the Asian Pacific Association for the Study of the Liver

Acute hepatic insult manifesting as jaundice (bilirubin ≥5 mg/dL) and coagulopathy (INR ≥1.5), complicated within 4 weeks by ascites and/or encephalopathy.

 APASL focuses more on acute hepatic insult, while EASL emphasizes multi-organ failure.

 Clinical Features

Early (Compensated)

• Fatigue
• Anorexia
• Weight loss

Late (Decompensated)

1️⃣ Portal Hypertension Signs

• Ascites
• Caput medusae
• Splenomegaly
• Variceal bleed

2️⃣ Hepatic Failure Signs

• Jaundice
• Encephalopathy
• Coagulopathy
• Hypoalbuminemia

3️⃣ Stigmata of Chronic Liver Disease

• Spider angiomas
• Palmar erythema
• Gynecomastia
• Testicular atrophy
• Dupuytren contracture

 Laboratory Findings

 Imaging

Ultrasound

• Nodular liver
• Coarse echotexture
• Splenomegaly
• Ascites

CT / MRI

• Irregular liver margin
• Caudate lobe hypertrophy
• Portosystemic collaterals

🧮 Severity Scoring

1️⃣ Child–Pugh Score

Class A, B, C

2️⃣ MELD Score

• Based on bilirubin, INR, creatinine
• Used for transplant allocation

 Major Complications

1️⃣ Variceal Hemorrhage

• Due to portal hypertension
• Life-threatening

2️⃣ Ascites

• Most common complication
• Due to RAAS activation + hypoalbuminemia

3️⃣ Hepatic Encephalopathy

• Ammonia accumulation
• Astrocyte swelling

4️⃣ Hepatorenal Syndrome

• Functional renal failure
• Intense renal vasoconstriction

5️⃣ Spontaneous Bacterial Peritonitis (SBP)

6️⃣ Hepatocellular Carcinoma (HCC)

 Management — Etiology + Complication Based

 Step 1: Confirm “Compensated” Status

Compensated =

• No ascites
• No variceal bleed
• No encephalopathy
• No jaundice

Normal daily functioning.

 Step 2: Treat the Underlying Etiology (Most Important)

Cirrhosis progression depends heavily on cause control.

 Viral Hepatitis

• Hepatitis B → Tenofovir / Entecavir
• Hepatitis C → Direct-acting antivirals

👉 Viral suppression reduces decompensation and HCC risk.

 Alcohol-Related

• Strict alcohol abstinence
• Addiction counseling
• Nutritional optimization

Even advanced fibrosis may partially regress with abstinence.

 Metabolic (NASH)

• Weight reduction (7–10%)
• Diabetes control
• Lipid control

Related to Non-alcoholic fatty liver disease.

 Autoimmune

• Autoimmune hepatitis → Steroids ± Azathioprine

 Iron / Copper Disorders

• Hemochromatosis → Phlebotomy
• Wilson disease → Chelation

 Step 3: Prevent First Decompensation

1️⃣ Screen for Varices

All compensated cirrhosis patients need baseline endoscopy.

If varices present:

• Non-selective beta blockers (NSBB)
• Propranolol
• Carvedilol

If no varices:

• Repeat every 2–3 years

2️⃣ Vaccination

Mandatory:

• Hepatitis A
• Hepatitis B
• Influenza
• Pneumococcal vaccine

3️⃣ Avoid Hepatotoxic Drugs

Avoid:

• NSAIDs
• Unnecessary sedatives
• High-dose acetaminophen (>2 g/day)

4️⃣ Nutritional Advice

• Protein: 1.2–1.5 g/kg/day
• Avoid prolonged fasting
• Late evening snack (reduces sarcopenia)

Malnutrition accelerates decompensation.

 Step 4: HCC Surveillance (Critical)

All cirrhotics require screening for hepatocellular carcinoma.

Every 6 Months:

• Ultrasound abdomen
• ± AFP

Because cirrhosis is the strongest risk factor for HCC.

 Step 5: Monitoring

Every 3–6 months:

• LFT
• INR
• Albumin
• Creatinine
• Sodium
• Platelets

Calculate:

• MELD score periodically

 Clinically Significant Portal Hypertension (CSPH)

If HVPG ≥10 mmHg → high risk of decompensation.

Carvedilol may reduce portal pressure.

📈 Prognosis

Compensated cirrhosis:

• Median survival >12 years
• Annual decompensation risk: 5–7%

Once decompensation occurs → mortality rises sharply.