Cirrhosis

A diffuse process characterized by fibrosis of the liver with conversion of normal architecture to structurally abnormal nodules

Etiology

Commonest causes is alcohol and HBV, BCV

Toxins & Drugs	Alcohol Methyldopa Methotrexate Isoniazid
Infections	HBV, HCV
Auto-immune	Chronic active hepatitis, Primary biliary cirrhosis
Metabolic	Wilsons disease Haemachromatosis Alpha1-antitrypsin deficiency Glycogen storage diseases
Vascular	Budd-chiari syndrome (hepatic venous outflow obstruction) Veno-occlusive disease Congestive cardiac failure

Clinical Features

Non-specific	Lethargy, weakness, anorexia, weight loss, abdominal pain, loss of libido, nausea & vomiting
Signs of Portal hypertension	Ascites Haematemesis and/or malena Splenomegaly Dilated abdominal veins
Signs of chronic liver disease	Spider naevi clubbing palmar erythema bruising fetor hepaticus gynecomastia testicular atrophy hepatosplenomegaly pedal oedema bruising jaundice
Signs of complications of liver failure	Hepatic encephalopathy – confusion, drowsy, →coma Renal failure Bleeding diathesis Infection Ascites

Complications of Cirrhosis

1. Portal hypertension
2. Ascites
3. Hepatic encephalopathy
4. Renal failure
5. Hepatocellular  carcinoma

ACUTE DECOMPENSATION

• Find cause:
  1. sepsis
  2. spontaneous bacterial peritonitis
  3. GI haemorrhage
  4. alcohol
  5. drugs (opiates, sedatives, diuretics)
  6. electrolyte imbalances
  7. hepatocellular carcinoma
  8. portal vein thrombosis
  9. dehydration

History

1. Symptoms Leading to Current Presentation

• Document the presenting symptoms that prompted the current evaluation (e.g., fatigue, abdominal swelling, jaundice).

2. Previous Decompensations or Complications of Liver Disease

• History of ascites, encephalopathy, variceal bleeding, etc.

3. Previous Endoscopies

• Presence or history of esophageal/gastric varices.

4. Infective Symptoms

• Fever.
• Dysuria.
• Shortness of breath.
• Cough.
• Painful/swollen joints.
• Skin rashes.

5. Gastrointestinal Symptoms

• Bowel habits, including constipation, melena, or hematemesis.

6. Recent Travel History

• Especially international travel that may raise concerns for infectious causes.

7. Abdominal Symptoms

• Pain, distension, or swelling.

8. Alcohol Consumption

• Quantify units/day of current and historical alcohol use.

9. Medications

• Compliance with prescribed medications.
• History of over-the-counter and recreational drug use.

10. Pruritus

• Presence and severity of itching.

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Examination

1. General Examination

• Abdominal distension.
• Jaundice.
• Cachexia (weight loss and muscle wasting).
• Bruising or evidence of coagulopathy.

2. Hands and Skin

• Palmar erythema.
• Bruising.
• Spider naevi (telangiectasias).
• Yellow sclerae (jaundice).
• Gynaecomastia (in men).

3. Abdominal Examination

• Masses or nodularity.
• Ascites.
• Hepatosplenomegaly (enlarged liver and spleen).
• Scars or bruising.

4. Grading of Hepatic Encephalopathy

• Grade 1: Trivial lack of awareness, euphoria, anxiety, shortened attention span, impaired simple calculations.
• Grade 2: Lethargy, minimal disorientation, subtle personality change, inappropriate behavior, presence of asterixis (flapping tremor).
• Grade 3: Somnolence to semi-stupor, responsive to verbal stimuli, confusion, gross disorientation.
• Grade 4: Coma.

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Investigations

1. Blood Tests

• Full Blood Count (FBC):
  • Anemia, leukopenia, thrombocytopenia (often pancytopenic due to hypersplenism or alcohol-induced marrow hypoplasia).
  • Leukocytosis (indicative of infection or acute alcoholic hepatitis).
• Electrolytes, Urea, Creatinine (EUC):
  • Assessment for renal impairment.
• Liver Function Tests (LFTs):
  • Elevated AST, ALT (suggestive of chronic active hepatitis).
  • Elevated ALP, GGT (suggestive of cholestatic causes, e.g., biliary cirrhosis).
• Coagulation Studies:
  • Prolonged prothrombin time (PT).
• Alpha-Fetoprotein (AFP):
  • Elevated levels if hepatocellular carcinoma is suspected.

2. Ascitic Fluid Analysis (if applicable)

3. Disease-Specific Tests

• Viral Hepatitis: HbsAg, anti-HCV.
• Autoimmune Diseases: SMA (Smooth Muscle Antibody), ANA (Antinuclear Antibody), AMA (Anti-Mitochondrial Antibody), Anti-liver kidney microsomal antibodies.
• Hemochromatosis: Iron studies.
• Wilson’s Disease: Ceruloplasmin and serum copper

4. Imaging

• Ultrasound (U/S): Initial imaging modality.
• CT Scan: Consider if there is a suspicion of hepatocellular carcinoma.
• Liver Biopsy:
  • Confirms the diagnosis of cirrhosis.
  • Helps determine the underlying cause (e.g., chronic active hepatitis (CAH), primary biliary cholangitis (PBC)).

• Child-Pugh Classification

	A	B	C
Mortality	< 5%	5-50%	50%
Bilirubin (mmol/L)	<25	25-40	40
Albumin (g/L)	>35	30-35	<30
Ascites	none	moderate	marked
Nutrition	excellent	good	poor
INR	<1.7	1.7-2.3	>2.3
Encephalopathy	grade 0	grade 1-2	grade 3-4

Management Principle for Cirrhotic Patients

1. Withdrawal of Causative Agent (if possible)

• Example: Alcohol cessation.

2. Treatment of the Underlying Cause

• Address specific etiologies:
  • Spontaneous Bacterial Peritonitis (SBP): Administer third-generation cephalosporins or piperacillin/tazobactam (tazocin) alongside spironolactone.
  • Alcoholic Hepatitis: Use corticosteroids.

3. Management of Coagulopathy

• Vitamin K: Administer intramuscular Vitamin K if prothrombin time (PT) is prolonged.
• Fresh Frozen Plasma (FFP): Use in cases of active bleeding.
• Note: Persistent elevation of PT despite Vitamin K indicates hepatic failure, not cholestasis.

4. Management of Bacterial Infections

• Recognize bacterial infections as a frequent cause of deterioration in cirrhotic patients.
• SBP in Ascites: Treat with cefotaxime.

5. Management of Renal Failure

• Hepatorenal Syndrome: Be vigilant for rapidly progressive renal impairment.
• Abdominal Compartment Syndrome: Consider as a differential diagnosis.
• Investigations: Use ultrasound (U/S) for renal and hepatic assessment.
• Treatment:
  • Volume expansion with colloid (albumin).
  • Vasoconstriction using noradrenaline or glypressin.
  • Ascitic drainage with albumin loading.
  • Consider Transjugular Intrahepatic Portosystemic Shunt (TIPS) for specific cases such as Budd-Chiari syndrome.
  • Consider liver transplantation.

6. Management of Malnutrition

• Dietitian Consultation: Essential for personalized dietary management.
• Dietary Recommendations:
  • High-calorie intake, including as much protein as tolerated without precipitating hepatic encephalopathy.
  • Consider nasogastric (NG) or parenteral feeding if required.

7. Upper Gastrointestinal (GI) Bleeding

• Ammonia Reduction: Administer lactulose to reduce ammonia levels.

8. Management of Ascites

• Restrict fluid and sodium intake.
• Administer diuretics.

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Pharmacological Management

1. Coagulopathy:
   • Vitamin K (intramuscular) for prolonged PT.
   • Fresh Frozen Plasma (FFP) for active bleeding.
2. Spontaneous Bacterial Peritonitis (SBP):
   • Third-generation cephalosporins or piperacillin/tazobactam (tazocin).
3. Hepatorenal Syndrome:
   • Volume expansion (albumin).
   • Vasoconstriction (noradrenaline or glypressin).
   • Ascitic drainage with albumin loading.
4. Upper GI Bleeding:
   • Lactulose for ammonia reduction.
5. Ascites:
   • Diuretics.
6. Alcoholic Hepatitis:
   • Corticosteroids.

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Non-Pharmacological Management

Lifestyle Modifications

• Alcohol Abstinence: Critical for alcoholic cirrhosis or alcohol-related liver disease.
• Smoking Cessation: Reduces the risk of liver cancer and other complications.

Dietary Management

• Low Sodium Diet: Target less than 2 grams per day to control ascites and edema.
• Protein Intake: Recommend 1-1.5 grams/kg body weight with necessary adjustments to prevent muscle wasting and minimize hepatic encephalopathy.
• Balanced Diet: Emphasize fruits, vegetables, lean proteins, and whole grains.
• Small Frequent Meals: Helps with anorexia and early satiety.

Monitoring and Follow-Up

• Regular Monitoring: Blood tests to track liver and renal function, as well as electrolytes.
• Ultrasound and Surveillance: Regular ultrasound and AFP testing every 6 months for hepatocellular carcinoma (HCC) surveillance in high-risk patients.
• Ascites Monitoring: Routine evaluation for new or worsening ascites; paracentesis if necessary.

Complication Management

• Fluid Restriction: For severe hyponatremia.
• Infection Prevention: Administer hepatitis A and B vaccines, pneumococcal vaccine, and influenza vaccine.
• Hepatic Encephalopathy Prevention: Educate patients on early signs and avoid triggers like constipation, infections, GI bleeding, and certain medications.

Patient Education and Support

• Comprehensive Education: Cover disease processes, management, and complications.
• Psychosocial Support: Referral to support groups, counseling, or social services.
• Exercise: Encourage regular physical activity within tolerance to maintain muscle mass and overall health.

Coordination of Care

• Multidisciplinary Approach: Collaboration with hepatologists, dietitians, social workers, and other healthcare providers.
• Specialist Referral: Timely referral for advanced therapies, liver transplantation evaluation, or complex complication management.

Avoidance of Hepatotoxic Substances

• NSAIDs: Avoid due to risk of renal impairment and GI bleeding.
• Medication Review: Evaluate all prescribed, over-the-counter, and herbal medications for hepatotoxicity.

Portal Hypertension

1. Pre-hepatic – blockage of the portal vein before the liver
2. Intra-hepatic – due to distortion of the liver architechture.  Can be presinusoidal (schistosomiasis) or post-sinusoidal (cirrhosis)
3. Post-hepatic – due to venous blockage outside the liver (rare)

The portal vein is formed by the union of the superior mesenteric and splenic veing  Pressure is normally 5-8mmHg.  As portal pressure rises to 10-20mmHg →opening of the porto-systemic anastomoses.

Collaterals occur at the 

• Gastro-oesophageal junction
• The rectum
• The left renal vein
• The diaphragm
• The retroperitoneum
• Anterior abdominal wall

Etiology- Commonest cause is cirrhosis

Prehepatic	Intra-hepatic	Post-hepatic
Portal vein thrombosis Portal vein compression	Cirrhosis Alcoholic hepatitis Idiopathic Infiltrative – sarcoid, lymphoma, leukemia Congenital hepatic fibrosis Granulomata Extra-medullary heamatopoesis	Budd-chiari syndrome Veno-occlusive disease Right heart failure Constrictive pericarditis

Clinical Signs of portal hypertension

• Splenomegaly
• Collateral veins (umbilical veins –caput medusa pattern away from umbilicus
• Ascites

Ascites

Pathogenesis

• Sodium and water retention – peripheral arterial dilatation → retention via activation of neurohumoral mechanisms (RAAA, ANP etc)
• Portal hypertension – exerts a local hydrostatic pressure and lead to increased hepatic and splanchnic production of lymph and transudation of fuid into the peritoneal cavity
• Hypoalbuminemia – ↓ plasma oncotic pressure

Causes of Ascites

Infective	Tuberculosis SBP in cirrhotics	Bacterial Peritonitis
Malignancy	Peritoneal metastases	Meigs syndrome (ovarian tumour)
Cirrhosis
Inflammatory	Pancreatitis
Post-hepatic obstruction	Budd-chiari syndrome Right heart failure	Constrictive pericarditis
Hypoproteinemia	Nephrotic syndrome Malabsorption	Liver failure
Traumatic	Trauma	Ruptured ectopic

Investigations

1. Aspiration of ascitic fluid

• Cell count: neutrophil count >250 is indicatvie on underlying bacterial peritonitis
• Gram Stain and Culture 
• Protein: differentiate between transudates and exudates (<11g/L>). Lower levels of protein (<10) are at an increased risk of SBP (↓Ig and complement).  

Note: cirrhotic ascites should be a transudate, if exudative consider SBP or hepatocellular carcinoma

• Cytology:  for malignant cells
• Amylase: to exclude pancreatic ascites

Management

Aim to reduce sodium intake and increase sodium excretion.  

Maximum rate at which ascites should be mobilized is 500-700mL/day

• Check EUC, weight and urinary output daily
• Fluid restriction to 1000-12000 mL daily
• Diuretics 

• spironolactone 100mg/day increasing to 600 mg/day as necessary
• response is evaluated by weight and urine output
• add frusemide if insufficient diuresis
• Discontinue diuretics if hypokalemic or if creatinine rises (indicating overdiuresis and hypovolemia)

Paracentesis

• Coming back into vogue but still controversial
• May be indicated for tense ascites, but beware hypovolemia as fluid re-accumulates in peritoneum
• Give with albumin to prevent hypovolemia
• Definitely contra-indicated in end-stage cirrhosis or renal failure

Interventions

• Peritoneo-venous shunt (not often done as it frequently blocks
• Transjugular Intrahepatic portocaval shunt (TIPS)

Spontaneous Bacterial Peritonitis

• Common complication of ascites in cirrhosis
• Common pathogens are E.coli, Klebsiella and enterococci
• Suspect in any patient with ascites with clinical evidence of deterioration
• 50% mortality rate

Give: Cefotaxime (preferable if renal impairment)