Cardiac Cirrhosis

Etiology

Cardiac cirrhosis is the consequence of the hemodynamic rearrangements caused by heart failure. Right-sided heart dysfunction can be due to left-sided heart failure, valvular diseases (tricuspid regurgitation, mitral stenosis), or decreases in relaxation or filling of the right-sided heart as in the setting of constrictive pericarditis. It produces an increase in the preload and back pressure to the hepatic system producing hepatic congestion. Prolonged hepatic congestion eventually leads to liver cirrhosis.[2] Congestive hepatopathy is common in patients with congenital heart disease and single ventricle physiology who have undergone the Fontan procedure.

Epidemiology

The prevalence of cardiac cirrhosis is hard to determine because this condition can be asymptomatic, or the diagnosis can be missed because of other causes of liver injury. Usually, in cardiac cirrhosis, mortality is related to the underlying cardiac disease rather than the hepatic congestion and injury. The age of presentation for cardiac cirrhosis is unclear as it depends on the onset of decompensated heart failure. As for cardiac diseases, the risk of cardiac cirrhosis increases with age. Similarly, it is more frequent in males as they also have an increased risk of developing heart failure and subsequently cardiac cirrhosis.[3][4]

Pathophysiology

There are several mechanisms that create unbalance in the circulatory system and will cause hepatic injury. The main mechanism causing hepatic dysfunction due to heart dysfunction is either an increase in cardiac filling pressures or low cardiac output and impaired perfusion. An increase in the preload or central venous pressure due to right ventricular dysfunction may cause direct liver damage due to increasing retrograde pressure to the venous and capillaries into the liver. This generates an elevation in liver enzymes. The elevated pressure is transmitted from the right heart chambers (right ventricle and atrium) to the hepatic veins and sinusoids, leading to intrahepatic edema, decreased perfusion and oxygen diffusion, as well as hemorrhagic injury and modification on the hepatocyte architecture and atrophy with associated collagen deposition, and fibrosis to the hepatic veins and sinusoids.

Another mechanism that can cause hepatic injury, especially when the left side of the heart is affected, is impaired perfusion and tissue hypoxia from decreased cardiac output. This may be associated with acute hepatocellular necrosis with marked elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and prolongation of coagulation studies as thrombin and prothrombin time.[5]

Histopathology

Gross Pathology

Congestive hepatopathy secondary to cardiac etiology causes nutmeg liver with reddish central areas, which represent sinusoidal congestion and bleeding in the atrophied regions, with contrasting yellowish discoloration, which represents either normal liver or fatty liver.  Hepatomegaly is very commonly seen with a purple hue.

Microscopic Examination  

Enlarged sinusoids, atrophied hepatocytes with variable degrees of hemorrhage, and necrosis in zone 3 of the hepatic acinus, fatty change is commonly seen under a microscope.  Mild thrombi are occasionally seen in patients with severe jaundice.  With chronic recurrent exacerbations of heart failure, collagen deposition occurs in zone 3, which eventually extends outwards, indicating portal tracts to the central veins causing cardiac sclerosis resembling micronodular cirrhosis.  With the progression of fibrosis, there may be the correction of rings of fibrosis around the stale portal region with bridging between adjacent hepatic and nodes which characterizes cardiac cirrhosis/cardiac fibrosis. Focal nodular hyperplasia is seen when there is a regeneration of periportal hepatocytes producing discrete nodules.  

History and Physical

Patients with cardiac cirrhosis are usually asymptomatic. This condition is usually suggested from abnormal liver function tests. Common symptoms are due to heart failure like shortness of breath, leg swelling, paroxysmal nocturnal dyspnea, and orthopnea. Patients who present with jaundice may be mistaken for biliary obstruction. When symptoms are present, these are gradual but may present abruptly in acute right ventricular decompensation, constrictive pericarditis, or acute decompensation of valve disease. Jugular venous distention is also present. Symptomatic patients due to liver dysfunction typically present with abdominal pain that can be localized in the right upper quadrant (secondary to hepatic capsule dilation), nausea and vomiting, jaundice, hepatomegaly, abdominal distention, and ascites. These findings are easily confused with biliary disease. Jaundice is not commonly reported. Liver injury can present in the setting of heart failure exacerbation with liver enzymes that are massively elevated after 24 to 72 hours after the cardiac decompensation. This can be as severe as hepatic encephalopathy and can clearly related to that. The term "acute cardiogenic liver injury" has been used when ischemic hepatitis occurs in the setting of congestive hepatopathy. 

Physical examination findings pertinent to congestive hepatopathy include an enlarged liver on abdominal palpation and enlarged liver span on ultrasound exam.  The liver edge is typically smooth, firm, and tender.  Splenomegaly is unusual.

• Ascites with shifting dullness or fluid thrill.
• Hepatojugular reflux is usually present and can help in differentiating hepatic congestion from Budd-Chiari syndrome.
• A pulsatile liver can be seen with severe tricuspid regurgitation or pericardial disease-causing congestive hepatopathy.
• Loss of pulsatility suggests longstanding liver disease or progression to cardiac cirrhosis.

In constrictive pericarditis causing congestive hepatopathy, hepatomegaly with a pulsatile liver and are seen Kussmaul's sign (a rise in the jugular venous pressure on inspiration), a pericardial knock, and pericardial calcification on the chest are seen. Scleral icterus might be absent in these patients.

Evaluation

At the time of presentation, the cause of liver injury and cardiac decompensation needs to be evaluated. A careful history and physical examination should be done to evaluate possible causes of liver injury like hepatitis, medications, gallbladder disease, and others. An initial evaluation of liver function should also be done. The most common finding is the elevation of the total bilirubin due to increasing indirect bilirubin. This finding has been found in 70% of patients with cardiac cirrhosis, and the bilirubin levels are rarely greater than 3 mg/dl. Alteration of the synthetic function of the liver presents with prolongation of the coagulation times. Despite this, increases in the international normalized ratio are not that common but can be elevated in severe cases of ischemic injury. Serum albumin levels can be decreased in 40% of patients. Hypoalbuminemia is rarely less than 2.5 g/dL.  This factor is an independent predictor of death in patients with acute on chronic heart failure.  The degree of reduction in serum albumin does not correlate with the degree of liver damage.  This is because the loss of albumin is more likely secondary to bowel edema from heart failure causing protein-losing enteropathy and malnutrition. Severe elevation in LDH and ALT/LDH ratio of less than 1.5 helps to differentiate perfusion injury from other causes of acute hepatitis.[6][7][8][9]

Evaluation of causes that can explain exacerbation of heart failure is important. Cardiac enzymes and brain peptide natriuretic peptide (BNP) may be elevated. An electrocardiogram can demonstrate arrhythmias and ischemic changes as well as suggest right ventricular hypertrophy. An echocardiogram is an important test to evaluate the underlying cause of congestive hepatopathy. The echo evaluates for valvular disease, wall motion abnormalities, pulmonary artery systolic pressure, mitral inflow, atrial and ventricular size, and evaluation for pericardial effusion or constrictive pericarditis. Inferior vena cava (IVC) evaluation would help to define volume status and pressure between the right atrium and the hepatic circulation. IVC respiratory variation (normally greater than or equal to 50% narrowing during inspiration) or IVC diameter greater than or equal to 2.3 cm suggests right-sided cardiac disease with increased right atrial filling pressures. CT and MRI evaluations of cardiac and hepatic conditions also can be used to determine the etiology of the clinical presentation. Due to common signs and symptoms of biliary disease, imaging evaluation should be considered. Abdominal ultrasound for evaluation of the biliary tract and gallbladder can rule out acute obstructive disease or hepatic vein thrombosis. In the presence of ascites, paracentesis should be performed. This fluid typically reveals a high protein content, commonly more than 2.5 g/dl. This increase in protein can be related to hepatic lymphatic ruptured with leakage of protein-rich fluid. Serum to ascites albumin gradient (SAAG) greater than 1.1 reflects portal hypertension.

Treatment / Management

The treatment of cardiac cirrhosis is based on the management of the underlying cardiac condition causing a hemodynamic imbalance. Determination of the volume status and adequate management of fluids for these patients is important. Clinical features of cardiac cirrhosis may improve dramatically with adequate diuresis.  Close monitoring of cardiac output is important to prevent ischemic hepatitis. Usual management of liver cirrhosis as indicated in the setting of liver dysfunction irrespective of the etiology, such as beta-blockers to reduce portal hypertension, diuretics for recurrent ascites, spontaneous bacterial peritonitis prophylaxis in the setting of GI bleed, etc.[10][11] In patients who are on chronic warfarin anticoagulation, dosage adjustment needs to be considered. 

Differential Diagnosis

• Alcoholic liver cirrhosis
• Primary biliary cirrhosis
• Chronic viral hepatitis
• Wilson disease
• Veno-occlusive disease
• Nonalcoholic steatohepatitis (NASH)
• Autoimmune hepatitis
• Ischemic hepatitis

Prognosis

The prognosis of cardiac cirrhosis depends on the prognosis of the underlying cardiac abnormality. Increasing liver enzymes and decreasing serum albumin during the early part of hospital admission for acute exacerbation of heart failure is associated with adverse outcomes at 6-month follow-up.[12] A higher score of liver stiffness on noninvasive measures reflecting liver fibrosis is associated with increased all-cause mortality in patients with heart failure.

Complications

The complications of cardiac cirrhosis depend on the complications of the underlying cardiac abnormality and liver dysfunction. It can lead to portal hypertension, hepatic encephalopathy, variceal bleeding, recurrent ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, and hepatopulmonary syndrome. In advanced cases, it causes coma and death.