Decreased Hepatic Blood Flow Due to Left-Sided Heart Failure
Hepatic (Venous) Congestion Due to Right-Sided Heart Failure
Hepatic Artery Thrombosis Post-Orthotopic Liver Transplant or Associated with Concomitant Portal Vein Thrombosis (see Hepatic Artery Thrombosis, [[Hepatic Artery Thrombosis]])
Epidemiology: isolated hepatic artery thrombosis generally does not result in ischemic hepatitis without prior OLT or portal vein thrombosis
Physiology: focal interruption of hepatic blood supply
Hypotension/Shock (see Hypotension, [[Hypotension]])
Epidemiology
Approximately 50% of All Ischemic Hepatitis Cases are Due to Shock (Medicine (Baltimore), 2003) [MEDLINE]
Severity of Ischemic Hepatitis is Correlated with the Duration/Severity of Hepatic Ischemia (J Anesth, 2011) [MEDLINE]
Preexisting Portal Hypertension and Congestive Hepatopathy Increase the Risk of Shock-Associated Ischemic Hepatitis
Presence of Ischemic Hepatitis Increases the Mortality Rate in Intensive Care Unit Patients Requiring Vasopressor Therapy (Intensive Care Med, 2011) [MEDLINE]
Physiology: focal interruption of hepatic blood supply
Physiology
Background
Liver has Complex Vascular Supply and High Metabolic Rate: makes it vulnerable to circulatory dysfunction from a variety of etiologies
Congestive Hepatopathy (see Congestive Hepatopathy, [[Congestive Hepatopathy]]): passive hepatic congestion, usually attributable to right-sided congestive heart failure (with or without decreased cardiac output
Diffuse Hepatic Injury: this feature distinguishes it from the focal hepatic injury which occurs in hepatic infarction (see Hepatic Infarction, [[Hepatic Infarction]])
Necrosis of Hepatocytes Within Zone 3 of Hepatic Acinus: with severe and prolonged hepatic ischemia, necrosis may extend to the mid-zonal hepatocytes
Variable Architectural Collapse Around the Central Vein: depends on duration and extent of the hepatic ischemia
Few Inflammatory Cells
Coexistent Congestive Hepatopathy: may also be present (especially in patients with congestive heart failure/cardiogenic shock)
Cholestasis with Bile Thrombi Within Canaliculi
Degeneration/Hemorrhagic Necrosis in Zone 3
Fatty Change
Sinusoidal Enlargement
Diagnosis
Liver Function Tests (LFT’s) (see Liver Function Tests, [[Liver Function Tests]])
Findings
Elevation of Serum Aminotransferases (“Transaminitis”)
Aminotransferases Typically Increase to 25-250x the Upper Limit of Normal, Reaching Peak Levels Within 1-3 Days After a Hemodynamic Insult (Am J Gastroenterol, 1992) [MEDLINE]
Aminotransferases Descend to Normal Over the Subsequent 7-10 Days
Minimal Elevation of Serum Alkaline Phosphatase (see Serum Alkaline Phosphatase, [[Serum Alkaline Phosphatase]])
Serum Alkaline Phosphatase is Typically <2x the Upper Limit of Normal
Minimal Hyperbilirubinemia (see Serum Bilirubin, [[Serum Bilirubin]])
Increase in Total Bilirubin Usually Begins After the Start of Decline in the Aminotransferases
Bilirubin is Typically <4x the Upper Limit of Normal
Bilirubin Tends to Decline Slower than the Transaminases: if the bilirubin continues to rise, the diagnosis of acute liver failure should be considered
Ratio of Serum Aminotransferase/Serum LDH <1.5 Early in the Course of Acute Hepatitis Suggests Ischemic Hepatitis, Rather than Viral Hepatitis (J Clin Gastroenterol, 1994) [MEDLINE]
International Normalized Ratio (INR)Prothrombin Time (PT) (see Prothrombin Time, [[Prothrombin Time]])
May Be Minimally Elevated
Right Upper Quadrant Ultrasound with Doppler Ultrasound (see Abdominal-Pelvic Ultrasound, [[Abdominal-Pelvic Ultrasound]])
Rationale
Doppler Ultrasound is Useful to Exclude the Diagnosis of Portal Vein Thrombosis, Hepatic Artery Thrombosis, and/or Hepatic Vein Thrombosis
Clinical Manifestations
General Comments
Association with Other Organ Injury
Concomitant Elevation in Serum Creatinine (Indicative of Acute Kidney Injury, Due to Hypoperfusion) Suggests a Diagnosis of Ischemic Hepatitis (Am J Med, 2000) [MEDLINE]
Statin Therapy Prior to Intensive Care Unit Admission Has Been Demonstrated to Decrease the Risk of Ischemic Hepatitis in Critically Ill Patients (J Hepatol, 2014) [MEDLINE]
Treatment
Hemodynamic Optimization
Treatment of Choice: since ischemic hepatitis is usually self-limited
Avoid Overdiuresis: which may worsen hepatic ischemia
Dopamine (see Dopamine, [[Dopamine]]): while dopamine has been suggested to preserve or augment hepatic blood flow, its efficacy is unproven (J Cardiovasc Pharmacol, 1980) [MEDLINE]
Prognostic Factors
Presence of Underlying Disease
Prognosis of Ischemic Hepatitis is Most Closely Correlated with the Severity of the Underlying Disease (Aust N Z J Med, 1984) [MEDLINE]
Presence of Critical Illness
Risk Factors for Increased Mortality Rate of Ischemic Hepatitis in the Setting of Critical Illness (Intensive Care Med, 2011) [MEDLINE]
Coagulopathy
Renal Failure
Septic Shock
Presence of Hyperbilirubinemia
Presence of Jaundice Increases the Risks of Requiring Vasopressors, Hemodialysis, Mechanical Ventilation, Mortality Rate at One Year, and Complications During Follow-Up in Ischemic Hepatitis (Hepatology, 2012) [MEDLINE]
Presence of Cirrhosis
Mortality Rate for Ischemic Hepatitis in the Setting of Cirrhosis is 60-100% (J Clin Gastroenterol, 1993) [MEDLINE]
References
Left-sided heart failure presenting as hepatitis. Gastroenterology. 1978;74(3):583 [MEDLINE]
Fulminant hepatic failure due to transient circulatory failure in patients with chronic heart disease. Dig Dis Sci. 1980;25(1):49 [MEDLINE]
Effect of dopamine on hepatosplanchnic blood flow. J Cardiovasc Pharmacol. 1980;2(3):257 [MEDLINE]
Fulminant hepatic failure due to transient circulatory failure in patients with chronic heart disease. Dig Dis Sci. 1980;25(1):49 [MEDLINE]
Ischemic hepatitis: clinical features, diagnosis and prognosis. Aust N Z J Med. 1984;14(6):822 [MEDLINE]
Ischemic hepatitis: widening horizons. Am J Gastroenterol. 1992;87(7):831 [MEDLINE]
Ischemic hepatitis in cirrhosis. Rare but lethal. J Clin Gastroenterol. 1993;16(1):35 [MEDLINE]
Serum lactic dehydrogenase in the differential diagnosis of acute hepatocellular injury. J Clin Gastroenterol. 1994;19(2):118 [MEDLINE]
Ischemic hepatitis: clinical presentation and pathogenesis. Am J Med. 2000;109(2):109 [MEDLINE]
Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases. Medicine (Baltimore). 2003;82(6):392 [MEDLINE]
Hepatopulmonary syndrome in patients with hypoxic hepatitis. Gastroenterology. 2006;131(1):69 [MEDLINE]
Acute lower limb ischemia as a triggering condition in hypoxic hepatitis: a study of five cases. J Clin Gastroenterol. 2011 Mar;45(3):274-7 [MEDLINE]
Hypoxic hepatitis in critically ill patients: incidence, etiology and risk factors for mortality. J Anesth. 2011 Feb;25(1):50-6. Epub 2010 Dec 9 [MEDLINE]
Impact of hypoxic hepatitis on mortality in the intensive care unit. Intensive Care Med. 2011 Aug;37(8):1302-10. Epub 2011 Jun 7 [MEDLINE]
Jaundice increases the rate of complications and one-year mortality in patients with hypoxic hepatitis. Hepatology. 2012 Dec;56(6):2297-304. Epub 2012 Sep 24 [MEDLINE]
Statin therapy is associated with reduced incidence of hypoxic hepatitis in critically ill patients. J Hepatol. 2014 Jun;60(6):1187-93. Epub 2014 Feb 5 [MEDLINE]
