Could a Routine Blood Test Help Diagnose NASH Cirrhosis?

A routine blood draw includes the levels of aspartate transaminase (AST) and alanine transaminase (ALT) in the bloodstream, both of which are reflective of liver health. Just as important as the absolute levels of AST and ALT is the ratio between the two, known as the De Ritis ratio. This ratio is an important prognostic tool in chronic liver diseases. New research by Galectin Therapeutics indicates that, in patients who have developed a cirrhosis of the liver due to NASH, the De Ritis ratio is also a useful marker of the degree of portal hypertension, a phenomenon that is associated with the severity of the disease.

First described by Fernando De Ritis in 1957, the De Ritis ratio (AST/ALT) should normally be below 1.0. Anything above this could indicate a problem with your liver.

The De Ritis Ratio and Nonalcoholic Fatty Liver Disease (NAFLD)

Nonalcoholic Fatty Liver Disease (NAFLD) has been called a “hidden epidemic,” tied closely to the growing number of people who are obese and/or diabetic. Researchers estimate that around 25% of adults in the U.S. suffer from NAFLD. Contrary to fat cells (adipocytes), liver cells (hepatocytes) do not normally store fat. When too much fat becomes available, hepatocytes also start to store fat.

The problem is that the presence of fat in the liver can cause inflammation and fibrosis, a phenomenon called Nonalcoholic Steatohepatitis (NASH), and if the phenomenon persists long enough, NASH can lead to liver cirrhosis. The name ‘cirrhosis’ comes from the Greek work kirrhos, which means that the liver takes a yellowish color. Cirrhosis indicates that the liver has become fibrotic and cannot function normally anymore.

One of the trickier aspects of NAFLD and NASH is that they are largely asymptomatic until relatively late in their progression. Doctors also have few simple tools at their disposal to monitor the progression of the disease. Until recently, a liver biopsy — a somewhat risky procedure — was the only way to achieve a definitive diagnosis of NASH. The advent of non-invasive tools such as Transient Elastography, which uses ultrasound to measure liver stiffness, has made it somewhat easier to monitor patients without biopsy. Unfortunately, such tools are not yet widely available.

In this context, the De Ritis ratio — which is available through a routine blood test — may help to suspect the progression of NAFLD/NASH to liver cirrhosis.

With this new research, the De Ritis ratio appears closely tied to the pressure in the portal vein. This vein is very important as it brings the nutrient-rich blood from the digestive tract to the liver where it will be processed into essential components. High portal pressure is an early sign of the potentially deadly complications of cirrhosis.

The research involved 161 patients, all confirmed to have liver cirrhosis due to NASH with a liver biopsy. All were also considered to have “compensated” cirrhosis, meaning they hadn’t yet progressed to the more serious complications. Researchers evaluated the patients’ portal pressure by measuring the gradient between wedge pressure and free hepatic vein pressure (HVPG). When HVPG is above 6 mm Hg, the diagnosis of portal hypertension is made. Patients are then further classified as having clinically significant portal hypertension (HVPG ≥ 10) or moderate portal hypertension (HVPG 6 to <10).

108 patients had clinically significant portal hypertension with an average De Ritis ratio of 1.21, while 53 patients with moderate portal hypertension had a ratio of 1.09. The coefficient of correlation (R2) between the De Ritis ratio and the measured HVPG was 0.84, meaning the numbers were highly correlated and not likely due to chance.

This is very informative news. An AST/ALT (De Ritis) ratio above 1 is frequently seen in patients with compensated NASH cirrhosis and portal hypertension, and the De Ritis ratio is strongly correlated with portal vein pressure as measured by HVPG.

This new use of the AST/ALT ratio could help physicians to identify cirrhosis in a patient with NAFLD/NASH. When cirrhosis is present, the De Ritis ratio also provides a simple, non-invasive way to estimate the degree of portal hypertension. As treatments for NASH cirrhosis become available, it will become increasingly important for physicians to be able to diagnose and monitor NASH cirrhosis quickly and easily.