Physiology

• Liver has Complex Vascular Supply and High Metabolic Rate: makes it vulnerable to circulatory dysfunction from a variety of etiologies
  • Congestive Hepatopathy: passive hepatic congestion, usually attributable to right-sided congestive heart failure (with or without decreased cardiac output
  • Hepatic Infarction (see Hepatic Infarction, Hepatic Infarction)
  • Hepatic Sinusoidal Obstruction Syndrome
  • Hepatic Vein Thrombosis (Budd-Chiari Syndrome) (see Hepatic Vein Thrombosis, Hepatic Vein Thrombosis)
  • Ischemic Hepatitis (Hypoxic Hepatitis, Shock Liver) (see Ischemic Hepatitis, Ischemic Hepatitis)
• Mechanism of Hyperbilirubinemia: unknown
  • Possible Contributors
    • Canalicular Obstruction Due to Distended Hepatic Veins
    • Hemolysis
    • Hepatocellular Dysfunction
    • Medications
    • Pulmonary Infarction
    • Co-Existing Sepsis
• “Nutmeg Liver”: classical pathologic term used to describe the gross appearance of a congested liver
  • Reddish central areas: sinusoidal congestion and bleeding into atrophic regions surrounding enlarged hepatic veins
  • Contrasting yellowish areas: represent either normal liver tissue or fatty liver
  • Hepatomegaly with a purple hue and prominent hepatic veins

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Etiology

Right-Sided Congestive Heart Failure (CHF) (see Congestive Heart Failure, Congestive Heart Failure)

• Ischemic Cardiomyopathy (approximately 31% of cases)
• Pericardial Disease (approximately 8% of cases)
  • Constrictive Pericarditis (see Constrictive Pericarditis, Constrictive Pericarditis): hepatic vein pressures are typically higher in constrictive pericarditis than those in other etiologies of right-sided congestive heart failure -> increasing probablity of developing hepatic necrosis (and ultimately “cardiac cirrhosis”)
• Valvular Heart Disease (approximately 23% of cases)
  • Aortic Stenosis (AS) (see Aortic Stenosis, Aortic Stenosis)
  • Mitral Stenosis (MS) (see Mitral Stenosis, Mitral Stenosis)
  • Tricuspid Regurgitation (TR) (see Tricuspid Regurgitation, Tricuspid Regurgitation): results in direct transmission of right ventricular pressure into the hepatic veins
• Pulmonary Disease/Cor Pulmonale (approximately 15% of cases)
  • Chronic Thromboembolic Pulmonary Hypertension (CTEPH) (see Chronic Thromboembolic Pulmonary Hypertension, Chronic Thromboembolic Pulmonary Hypertension)
  • Idiopathic Pulmonary Arterial Hypertension (IPAH) (see Idiopathic Pulmonary Arterial Hypertension, Idiopathic Pulmonary Arterial Hypertension)
• Other
  • Atrial Septal Defect (ASD) (see Atrial Septal Defect, Atrial Septal Defect)

Other

• Fontan Procedure (see Fontan Procedure, Fontan Procedure): directs systemic venous return to the pulmonary artery with bypass of the right ventricle

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Diagnosis

Serum/Urine Testing

• Testing for Viral Hepatitis: to rule out viral hepatitis
• Ferritin: to rule out hemochromatosis
• Ceruloplasmin: to rule out Wilson’s disease
• Serum Copper: to rule out Wilson’s disease
• Urinary Copper: to rule out Wilson’s disease
• Alpha-1 Antitrypsin Level: to rule out alpha-1 antitrypsin deficiency
• Testing for Celiac Disease: to rule out celiac disease
• Thyroid Function Tests (TFT’s): to rule out thyroid disease

Radiographic Imaging

• Cardiac MRI: useful to define pericardial disease
• Chest CT: useful to define pericardial disease
• Echocardiogram: to evaluate for congestive heart failure with/without vavlular heart disease
• RUQ U/S with Dopplers: to evaluate for possible hepatic disease

Liver Biopsy

• Indications: may be helpful in establishing the diagnosis in equivocal cases (especially in the setting of cirrhosis)
• Contraindications : avoid in the setting of ascites
• Pathology in Passive Hepatic Congestion
  • Sinusoidal engorgement, degeneration, and variable hemorrhagic necrosis in zone 3 of the hepatic acinus
  • Fatty change
  • Variable degrees of cholestasis with occasional bile thrombi in the canaliculi (bile thrombi are more commonly seen in patients with severe jaundice)
• Pathology in Cardiac Cirrhosis
  • Reticulin and collagen accumulate in zone 3 -> fibrous bands extend outward from the central veins, occasionally linking with portal tracts to produce called cardiac sclerosis that resembles micronodular cirrhosis
  • Progressive fibrosis may lead to bridging between adjacent hepatic venules, producing rings of fibrosis around the spared portal regions that characterizes “cardiac cirrhosis” (or, more accurately, cardiac fibrosis)
  • Histologic pattern is distinct from other forms of cirrhosis where fibrous bands tend to link adjacent portal areas
  • Fibrosis can also involve terminal hepatic venules, causing phlebosclerosis
  • Regeneration of periportal hepatocytes may result in focal nodular hyperplasia pattern

Endomyocardial Biopsy

• Indication: suspicion of myocarditis or infiltrative cardiac disease (hemochromatosis, sarcoidosis)

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Clinical

General Comments

• Asymptomatic: in many cases (abnormal LFT’s may be the only finding in these cases)

Gastrointestinal Manifestations

Abnormal Liver Function Tests (LFT’s)

• Hyperbilirubinemia with Jaundice (see Hyperbilirubinemia, Hyperbilirubinemia): hyperbilirubinemia is the most common isolated abnormality in congestive hepatopathy (occurs in 70% of cases)
  • Mechanism: unknown
  • Usually <3 mg/dL (and mostly unconjugated = indirect)
  • However, marked elevation may be seen in the setting of acute right-sided congestive heart failure
  • Serum bilirubin correlates with right atrial pressures, but not with cardiac output
  • Serum bilirubin may predict morbidity/mortality
  • Jaundice/hyperbiliruinemia is often absent in cases due to constrictive pericarditis (for unclear reasons)
• Transaminitis: present in 33% of cases
  • Usually <2-3x upper limit of normal
  • However, may be more significantly elevated in cases with associated hypoxic/ischemic hepatitis due to decreased cardiac output (in such cases, the degree of transaminitis correlates with the amount of zone 3 necrosis on liver biopsy): in these cases, diagnostic confusion with acute viral hepatitis may occur
• Alkaline Phosphatase: usually normal-slightly elevated, even in the presence of jaundice -> aids in distinguishing jaundice due to congestive hepatopathy from biliary obstruction
• Hypoalbuminemia (see Hypoalbuminemia, Hypoalbuminemia): present in 30-50% of cases
  • Mechanism: likely caused by malnutrition and protein-losing gastroenteropathy due to increased intestinal lymphatic pressure
  • Rarely <2.5 g/dL
  • Degree of hypoalbuminemia does not correlate with the degree of histologic liver damage

Ascites (see Ascites, Ascites)

• Diagnostic
  • High Total Protein: usually greater than 2.5 g/dL, reflecting the preserved serum albumin levels and the contribution of “hepatic lymph” to the ascites (presumably due to rupture of hepatic lymphatics, which are rich in protein)
  • Serum/Ascites Albumin Gradient (SAAG): >1.1 (suggetsing portal hypertension)

“Cardiac Cirrhosis” (see End-Stage Liver Disease, End-Stage Liver Disease)

• Epidemiology: may occur in cases with chronic passive congestion that is long-standing over months-years
  • Cirrhosis due to chronic passive congestion may particularly occur in constrictive pericarditis, mitral valve disease, and pulmonary hypertension (due to pulmonary vascular disease
• Clinical: cirrhosis due to chronic passive congestion uncommonly results in complications such as esophageal variceal bleeding [MEDLINE]

Fulminant Hepatic Failure (FHF) (see Fulminant Hepatic Failure, Fulminant Hepatic Failure)

• Epidemiology: cases reported have been typically in the setting of superimposed shock and hepatic ischemia rather than passive congestion alone

Hepatic Encephalopathy (see Hepatic Encephalopathy, Hepatic Encephalopathy)

• Epidemiology: congestive hepatopathy rarely causes hepatic encephalopathy

Hepatic Pulsatility

• Epidemiology: may be seen in cases associated with tricuspid regurgitation (presystolic pulsations corresponding to prominent “v waves” on a right atrial pressure tracing)
• Clinical: loss of hepatic pulsatility in a patient with long-standing congestive hepatopathy suggests progression to cardiac cirrhosis

Hepatojugular Reflux (see Hepatojugular Reflux, Hepatojugular Reflux)

• Epidemiology: usually present
• Clinical: useful to differentiate passive hepatic congestion from Budd-Chiari Syndrome and primary liver disease

Hepatomegaly (see Hepatomegaly, Hepatomegaly)

• Clinical
  • May be massive in some cases
  • Liver edge is usually firm, smooth, and may be tender
  • Splenomegaly is uncommon (but if it occurs, it is due to transmitted elevated central venous pressure)

Hyperammonemia

• Epidemiology: may occur occasionally
• Mechanism: probably related to congestive heart failure itself, rather than being due to liver disease

RUQ Abdominal Pain (see Abdominal Pain, Abdominal Pain)

• Mechanism: due to distention of hepatic capsule

Other Manifestations

• Coagulopathy/Elevated INR: usually mildly elevated
  • Mechanism: probably due (in part) to impaired hepatic synthesis of coagulation factors II, V, VII, IX, and X
    • However, INR may not correct completely with administration of vitamin K, suggesting that other coagulation defects (such as disseminated intravascular coagulation) may contribute
• Elevated Serum N-Terminal Pro-BNP (NT Pro-BNP) Level (see Brain Natriuretic Peptide, Brain Natriuretic Peptide): may help distinguish ascites due to congestive heart failure from ascites due to cirrhosis

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Treatment

• Treatment of Underlying Congestive Heart Failure (see Congestive Heart Failure, Congestive Heart Failure): aim to optimize cardiac output
  • Diuretics: may significantly improve jaundice and ascites
    • However, over-diuresis may precipitate hepatic necrosis [MEDLINE]
  • Improvement in LFT’s with treatment of congestive heart failure -> supports diagnosis
• Cautious Use of Coumadin (see Coumadin, Coumadin): hepatic congestion may increase sensitivity to coumadin
• Cautious Use of Medications with Hepatic Metabolism: hepatic congestion may impair their clearance
• Cautious Use of Transjugular intrahepatic Portosystemic Shunt (TIPSS): usually contraindicated, due to risk of worsening right-sided congestive heart failure

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References

• The liver in heart failure; relation of anatomical, functional, and circulatory changes. Br Heart J 1951; 13:273
• The blood ammonia in congestive heart failure. Am Heart J 1955; 50:715
• Case Records of the Massachusetts General Hospital; case 44212. N Engl J Med 1958; 258:1058
• Alterations in indices of liver function in congestive heart failure with particular reference to serum enzymes. Am J Med 1961; 30:211
• Cardiac failure simulating viral hepatitis. Three cases with serum transaminase levels above 1,000. Ann Intern Med 1962; 56:784
• The liver in congestive heart failure: a review. Am J Med Sci 1973; 265:174
• Fulminant hepatic failure secondary to congestive heart failure. Am J Dig Dis 1976; 21:895 [MEDLINE]
• Left-sided heart failure presenting as hepatitis. Gastroenterology 1978; 74:583
• Ischemic hepatitis. Dig Dis Sci 1979; 24:129
• Fulminant hepatic failure due to transient circulatory failure in patients with chronic heart disease. Dig Dis Sci 1980; 25:49
• Severe hyperbilirubinemia and coma in chronic congestive heart failure. Dig Dis Sci 1982; 27:175
• Constrictive pericarditis mimicking Budd-Chiari syndrome. Am J Med 1986; 80:113
• Liver function abnormalities in chronic heart failure. Influence of systemic hemodynamics. Arch Intern Med. Jul 1987;147(7):1227-30
• Cardiac ascites: a characterization. J Clin Gastroenterol 1988; 10:410
• Constrictive pericarditis masquerading as Budd-Chiari syndrome. J Clin Gastroenterol 1991; 13:178
• Hypercoagulability in heart failure. Semin Thromb Hemost 1997; 23:543
• Heart diseases affecting the liver and liver diseases affecting the heart. Am Heart J 2000; 140:111 [MEDLINE]
• The liver in heart failure. Clin Liver Dis 2002; 6:947
• Acute hypoxic hepatitis (‘liver shock’): still a frequently overlooked cardiological diagnosis. Eur J Heart Fail 2004; 6:561
• Cardiac hepatopathy before and after heart transplantation. Transpl Int. Jun 2005;18(6):697-702
• Liver function abnormalities and outcome in patients with chronic heart failure: data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program. Eur J Heart Fail 2009; 11:170
• Cardiac cirrhosis: a rare manifestation of an uncorrected primum atrial septal defect. J Cardiovasc Med (Hagerstown). Dec 3 2009
• The value of hepatic diffusion-weighted MR imaging in demonstrating hepatic congestion secondary to pulmonary hypertension. Cardiovasc Ultrasound 2010; 8:28
• Usefulness of serum N-terminal-ProBNP in distinguishing ascites due to cirrhosis from ascites due to heart failure. J Clin Gastroenterol 2010; 44:e23
• Congenital heart disease and the liver. Hepatology 2012; 56:1160