9
Abnormal Serum Liver Tests in Cardiac Disease

James Neuberger

Queen Elizabeth Hospital, Birmingham, UK

KEY POINTS

Abnormalities in serum liver tests are not uncommon in patients with heart disease.
Abnormal liver tests may arise as a consequence of heart disease, when heart disease is a consequence of liver disease, when there is a common cause for both heart and liver disease, or when the patient has unrelated heart and liver diseases.
Abnormalities of liver tests secondary to cardiac disease:
- Derangements in serum liver tests seen in atrial fibrillation and left‐ and right‐sided heart failure, and usually improve as the underlying cause is treated.
- Severe heart failure may result in ischemic hepatitis, which can be manifest as liver failure. Prolonged right‐sided heart failure can result in long‐term consequences with the development of “cardiac” cirrhosis. Standard tests for estimating the severity of the liver disease, including elastography, in this situation are unreliable.
- Cardiac abnormalities secondary to liver disease: cirrhosis may be associated with abnormalities of conduction and in cardiac function (hepatic cardiomyopathy).
There are many causes for both cardiac and liver damage, which include infectious, metabolic, and toxic disorders.
Drug‐induced liver disease should also be included in the differential diagnosis.
Patients with cardiac disease are also susceptible to liver disease unrelated to cardiac disease.

Introduction

Abnormal serum liver tests may be seen in many patients with cardiac disease. The abnormalities may reflect (Table 9.1):

liver disease causing heart disease
heart disease causing liver disease
heart and liver disease caused by one condition
liver disease unrelated to the heart disease

drug‐induced liver disease.

Table 9.1 Some causes of abnormal serum liver tests in patients with cardiac disease.

Classification	Examples
Liver diseases causing heart disorders	Hepatic cardiopathy
Heart disorders causing liver damage	Right‐sided heart failure
	Ischemic hepatitis
	Fontan surgery
Diseases causing both heart and liver disorders	Diabetes mellitus
	Metabolic syndrome
	Hyperlipidemia
	Amyloid
	Hemochromatosis
	Alcohol‐related disease
Drug‐induced liver disease	Statins
Drug‐induced liver disease	Amiodarone

When a patient with heart disease has abnormal liver tests, it is important to establish the cause of the liver abnormalities and to determine whether these abnormalities can be attributed to the cardiac problems or require additional treatment or alteration of the management of the patient. In practice, most patients under the cardiologist will have straightforward explanations for the liver abnormalities, which require little further investigation or change in management, but clinicians must be alert so as not to miss treatable disease.

Liver tests, especially transaminases in the upper end of the reference range, may be associated with reduced survival, especially in patients with cardiac disease. Furthermore, other studies have shown that increased levels of gamma‐glutamyl transferase (GGT) are associated with an increase in all‐cause mortality, as well as chronic heart disease events such as congestive heart failure and components of the metabolic syndrome (such as increased body mass index, diabetes, hyperlipidemia, and hypertension). GGT may be considered a biomarker for oxidative stress and a proatherogenic state, and so a marker for cardiovascular risk (hence one reason for its common use in life‐insurance medical evaluations). With rising rates of metabolic syndrome, associated non‐alcohol‐related fatty liver disease (NAFLD) will become commonly seen in a cardiology practice. Patients with cardiac disease who have coexistent NAFLD have higher risks for poor cardiac outcomes.

Liver Disease Causing Heart Disease

Abnormalities of cardiac function are becoming increasingly recognized in those with cirrhosis. In most cases, there is a common cause for both cardiac and hepatic disorder (see below) but some abnormalities do seem dependent on the presence of cirrhosis. On the electrocardiography, prolongation of the QT interval is related to an increased mortality rate in chronic liver disease and may revert after liver transplantation. Other interactions between the liver and thoracic organs include hepatopulmonary syndrome and emphysema are discussed elsewhere (Chapter 10).

Cirrhotic Cardiomyopathy

In recent years, there has been increasing recognition of a cardiomyopathy seen in patients with end‐stage liver disease; usually termed cirrhotic cardiomyopathy (CCM). This syndrome includes a combination of reduced cardiac contractility with systolic and diastolic dysfunction and electrophysiological abnormalities. CCM is characterized by an impaired contractile response to stress, so has become increasingly relevant to those being considered for liver transplantation. CCM is associated with the development of hepatic nephropathy and impaired survival. Liver tests are consistent with cirrhosis and, while the optimal approach to diagnosis is not yet fully established, imaging under circulatory stress testing, physiologically or pharmacologically induced, has been used to assess systolic dysfunction. Echocardiography with Doppler is probably the most preferred method to detect diastolic dysfunction, but increased use of magnetic resonance imaging is becoming established when additional investigations are needed.

Heart Disease Causing Liver Disease

The blood flow to and from the liver is affected by many factors. The blood supply to the liver is from the hepatic artery and the portal vein: since, in the normal situation, 70% of blood oxygen is supplied by the portal vein, reduced blood flow in the portal vein, as well as reduced hepatic artery flow, may result in ischemic changes in the liver. Conversely, reduced outflow (whether due to thrombosis or partial occlusion, raised pressure in the inferior vena cava) will have an impact on the liver which may in time lead to fibrosis and cirrhosis.

Liver tests may respond differently to raised right‐sided filling pressure and low cardiac output (Table 9.2).

Table 9.2 Liver tests in cardiac disease.