Cirrhosis

Epidemiology

Incidence

  • Cirrhosis and Schistosomiasis are the Two Most Common Etiologies of Portal Hypertension Worldwide
    • Cirrhosis Accounts for 90% of Portal Hypertension Cases in Western Countries
    • Non-Cirrhotic Causes Account for <10% of Portal Hypertension Cases in Western Countries

Etiology

XXXX


Physiology

Portal Hypertension (see Portal Hypertension, [[Portal Hypertension]])

  • xxxx

Diagnosis

Abdominal Ultrasound with Doppler Imaging (see Abdominal-Pelvic Ultrasound, [[Abdominal-Pelvic Ultrasound]])

  • May Be Used, But Hepatic Venous Pressure Measurement is Considered the Gold Standard Diagnostic Test
  • Findings Which May Occur with Portal Hypertension
    • Ascites (see Ascites, [[Ascites]])
    • Decreased or No Respiratory Variation in Splenic and Superior Mesenteric Vein Diameter
    • Inversion of Portal Vein Flow
    • Nodular Liver
    • Portal Flow Mean Velocity <12 cm/sec
    • Portal/Splenic/Superior Mesenteric Vein Thrombosis
    • Portal Vein Diameter >13 mm
    • Portosystemic Collaterals
      • Dilated Left and Short Gastric Veins
      • Patent Paraumbilical Vein
      • Splenorenal Collaterals
    • Splenomegaly (see Splenomegaly, [[Splenomegaly]])

Hepatic Elastography

  • xxxx

Abdominal CT (see Abdominal-Pelvic Computed Tomography, [[Abdominal-Pelvic Computed Tomography]])

  • xxx

Hepatic Venous Pressure Gradient (HVPG)

  • Definition: difference between the pressure in portal vein and the pressure in the inferior gene cava
    • Normal Hepatic Venous Pressure Gradient: 1-5 mm Hg
    • Portal Hypertension: ≥6 mm Hg
      • When Hepatic Venous Pressure Gradient is ≥10 mm Hg, Esophageal Varices Can Develop
      • When Hepatic Venous Pressure Gradient is ≥12 mm Hg, Variceal Bleeding and Ascites May Occur
  • Technique
    • Hepatic Vein Catheterization with Pressure Measurement
    • Portal Venous Pressure = Wedged Hepatic Venous Pressure (WHVP) – Free Hepatic Venous Pressure (FHVP)
      • Free Hepatic Venous Pressure (FHVP): reflects the intraabdominal pressure

Liver Biopsy (see Liver Biopsy, [[Liver Biopsy]])

  • Indications

BiLE Score

  • BiLE Score = TBili (umol/L)/100 + Lactate (mmol/L)
    • Add +4 for cryptogenic acute liver failure, Budd-Chiari syndrome, or phenprocoumon toxicity
    • Subtract -2 for acetaminophen toxicity
    • Add+0 for all other etiologies
    • BiLE >6.9: predictive of death or need for OLT
    • Sensitivity: 79% (sensitivity is 100% in cryptogenic acute liver failure cases)
    • Specificity: 84%
    • Superior to (Model for End-Stage Liver Disease) MELD and Simplified Acute Physiology Score (SAPS III)
      • MELD >32 had sensitivity of 65% and specificity of 69%

Clinical Manifestations

Cardiovascular Manifestations

Cirrhotic Cardiomyopathy (see xxxx, [[xxxx]])

  • Epidemiology: chronic cardiac dysfunction in the setting of cirrhosis (independent of alcohol exposure)
  • Physiology
    • Altered Diastolic Relaxation with Electrophysiologic Abnormalities
    • Decreased Myocardial Contractility in Response to Stress

Hypotension (see Hypotension, [[Hypotension]])

  • Physiology: due to vasodilation

Dermatologic Manifestations

  • Spider Angiomata
  • Palmar Erythema

Endocrinologic Manifestations

Gastrointestinal/Hepatic Manifestations

Abdominal Wall Collateral Vessels

  • xxx

Ascites (see Ascites, [[Ascites]])

  • xxxx

Esophageal Varices (see Esophageal Varices, [[Esophageal Varices]])

  • Epidemiology
    • Esophageal Varices are Present in 40% of Cirrhotics {Expert Rev Gastroenterol Hepatol, 2013) [MEDLINE]
    • In Cirrhotics Who Do Not Have Esophageal Varices, They Develop at a Rate of Approximately 6% Per Year

Portal Hypertensive Gastropathy (PHG)

  • Physiology: congestive gastropathy

Spontaneous Bacterial Peritonitis (SBP) (see Spontaneous Bacterial Peritonitis, [[Spontaneous Bacterial Peritonitis]])

  • xxx

Increased Risk of Hepatocellular Carcinoma (see Hepatocellular Carcinoma, [[Hepatocellular Carcinoma]])

  • xxx

Portal Hypertension with Esophageal Varices/Gastric Varices/Portal Hypertensive Gastropathy

  • Physiology: xxx

Hematologic Manifestations

Anemia (see Anemia, [[Anemia]])

  • xxx

Hemolytic Anemia (see xxxx, [[xxxx]])

  • Physiologic Mechanisms Which Contribute to Hemolysis
    • Acquired Alterations of Red Blood Cell Membrane
      • Burr Cells (Echinocytes)
      • Spur Cells (Acanthocytes)
      • Stomatocytes: mouth-shaped area of central pallor
      • Target Cells (Bell-Shaped Codocytes, Mexican Hat Cells): due to decreased lecithin/cholesterol acyltransferase (LCAT) activity, resulting in increased cholesterol:phospholipid ratio -> absolute increase in surface area of the red blood cell membrane
    • Hypersplenism (see Splenomegaly, [[Splenomegaly]]): due to portal hypertension

Splenomegaly (see Splenomegaly, [[Splenomegaly]])

  • xxx

Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])

  • Physiology: due to hypersplenism

Coagulopathy (see Coagulopathy, [[Coagulopathy]])

  • Epidemiology: coagulopathy is common in hepatic failure
  • Physiology: abnormal synthesis of multiple clotting factors and platelet dysfunction
    • Factor VII has a relatively short half-life in the circulation: accounts for increased INR
    • Platelet Dysfunction (see Coagulopathy, [[Coagulopathy]]): due to platelet granule storage pool defect
      • Some patients manifest permanent platelet degranulation
  • Clinical
    • Bleeding in acute liver failure is often associated with procedures, such as a central line, nasogastric tube or liver biopsy
  • Treatment: increased INR alone is not an indication for correction of coagulopathy
    • FFP: first-line therapy to correct coagulopathy
      • However, in some patients, due to a consumptive coagulopathy combined with impaired synthetic function, even large amounts of FFP may fail to decrease the INR
      • FFP is a large volume infusion and volume-related complications may occur: pulmonary edema, cerebral edema
    • Recombinant Activated Factor VIIa: while expensive, may be used for bleeding unresponsive to FFP and other measures (especially in the setting of cerebral edema)
      • Produces a rapid (although temporary) correction of the INR in acute hepatic failure: however, controlled trials demonstrating long-term benefit are lacking
      • Commonly used prophylactically in acute liver failure with coagulopathy prior to the placement of an intracranial pressure monitor
    • Platelets: should be considered when the platelet count is less than 50k
    • Cryoprecipitate: should be considered if the plasma fibrinogen is less than 100 mg/dL
    • Anti-Fibrinolytic Agents (epsilon-aminocaproic acid, tranexamic acid): do not improve clotting ability and are not useful to stop active bleeding

Increased Risk of Venous Thromboembolism

  • Risk of Venous Thrombembolism is High in Hospitalized Patients with Liver Disease, Despite Abnormal Coagulation Parameters: risk of venous thromboembolism was 6.3% in this population [MEDLINE]

Infectious Manifestations

  • Increased Risk of Vibrio Vulnificus Necrotizing Fasciitis (see Necrotizing Fasciitis, [[Necrotizing Fasciitis]])

Neurologic Manifestations

  • Cerebral Edema: leading cause of death in patients with early acute liver failure
    • Excessive volume resuscitation (especially with FFP) may worsen cerebral edema
  • Hepatic Encephalopathy (see Hepatic Encephalopathy, [[Hepatic Encephalopathy]])

Pulmonary Manifestations

Respiratory Alkalosis (see Respiratory Alkalosis, [[Respiratory Alkalosis]])

  • Physiology: likely due to sympathetic overactivity, elevated serum progesterone, and enhanced sensitivity to carbon dioxide (Int J Cardiol, 2012) [MEDLINE]

Hepatic Hydrothorax (see Hepatic Hydrothorax, [[Hepatic Hydrothorax]])

  • xxx

Hepatopulmonary Syndrome (see Hepatopulmonary Syndrome, [[Hepatopulmonary Syndrome]])

  • xxxx

Portopulmonary Hypertension (see Portopulmonary Hypertension, [[Portopulmonary Hypertension]])

  • xxxx

Renal Manifestations

Hepatorenal Syndrome (HRS) (see Hepatorenal Syndrome, [[Hepatorenal Syndrome]])

  • Epidemiology
    • xxxx

Type 1 Distal Renal Tubular Acidosis (RTA) (see Type 1 Distal Renal Tubular Acidosis, [[Type 1 Distal Renal Tubular Acidosis]])

  • Epidemiology
    • xxxx

Other Manifestations

  • xxx

Treatment

Treatment of Cirrhotic Ascites

  • Loop Diuretics
    • Bumetanide (Bumex) (see Bumetanide, [[Bumetanide]])
    • Furosemide (Lasix) (see Furosemide, [[Furosemide]])
  • Therapeutic Paracentesis (see Paracentesis, [[Paracentesis]])
  • Transjugular Intrahepatic Portosystemic Shunt (TIPS)
    • Indications: refractory ascites
    • Contraindications: encephalopathy (may worsen) and cardiac dysfunction (increases right-sided heart return and may precipitate CHF and worsen hepatopulmonary syndrome)
  • Peritoneovenous Denver Shunt
    • Indications
    • Contraindications

Treatment of Esophageal Varices

Treatment of Gastric Varices

Treatment of Hepatic Encephalopathy

Treatment of Hepatic Hydrothorax

Treatment of Hepatopulmonary Syndrome

Other Treatment

Orthotopic Liver Transplantation (OLT)

  • Indications
    • xxx
  • Contraindications
    • xxx

References

General

  • xxxx

Clinical

  • Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology. 2006;44:1039-1046.
  • Cirrhotic cardiomyopathy. Dig Liver Dis. 2007;39(6):507 [MEDLINE]
  • Cirrhotic cardiomyopathy. J Hepatol. 2010 Jul;53(1):179-90. Epub 2010 Mar 31 [MEDLINE]
  • Cirrhotic cardiomyopathy. J Am Coll Cardiol. 2010;56(7):539 [MEDLINE]
  • Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease. Chest. 2010;137(5):1145 [MEDLINE]
  • A perspective on cirrhotic cardiomyopathy. Transplant Proc. 2011 Jun;43(5):1649-53 [MEDLINE]
  • Abnormal hyperventilation in patients with hepatic cirrhosis: role of enhanced chemosensitivity to carbon dioxide. Int J Cardiol. 2012 Jan 12;154(1):22-6. doi: 10.1016/j.ijcard.2010.08.066. Epub 2010 Sep 20 [MEDLINE]

Treatment

  • Recombinant activated factor VII for coagulopathy in fulminant hepatic failure. Liver Transplant 2003; 9:438-443
  • Efficacy and safety of recombinant factor VII for treatment of severe bleeding: a systematic review. Crit Care Med. 2005;33:883-890