Liver fibrosis is a strong predictor of long-term mortality in patients with non-alcoholic fatty liver disease. “Many patients with advanced liver failure caused by obesity, diabetes and their comorbidities die from this liver disease,” warn researchers at Virginia Commonwealth University (VCU), revealing the true burden of this hidden epidemic that increases mechanistically with the spread of obesity. The study which was published in the New England Journal of Medicine (NEJM), provides guidance for the development of future treatments for non-alcoholic fatty liver disease, as there is currently no approved treatment.
A national (US) longitudinal study led by VCU researcher Arun Sanyal showed that the incidence of deaths from advanced liver fibrosis, a condition that develops silently goes mostly unreported. The study makes screening for liver disease a new urgency, particularly in populations with type 2 diabetes, but also clarifies the direction of therapeutic development. “This is the first snapshot of adverse outcomes in patients with non-alcoholic fatty liver disease,” he said.
Finally, the study is consistent with recent American Diabetes Association (ADA) guidelines, which recommend screening for liver disease in all patients with diabetes.
Liver fibrosis is not always a result of alcohol consumption
Liver fibrosis is still a poorly understood disease among the general public and is often associated with excessive alcohol consumption. The reality is quite different: a quarter of adults worldwide suffer from non-alcoholic fatty liver disease, a disease characterized by excessive liver fatty degeneration and usually associated with diabetes and obesity.
Non-alcoholic fatty liver disease (NAFLD) is not very well understood, although it is the most common liver disease in the world. It affects over 90% of obese people, 60% of diabetics, and up to 20% of normal-weight people. The liver can remain “fat” without interfering with its normal function, but the condition can also progress to non-alcoholic steatohepatitis, a more aggressive form of fatty liver, which is accompanied by inflammation and fibrosis, which in turn can lead to cirrhosis and then liver cancer and death. The first stage of non-alcoholic fatty liver disease is defined as asymptomatic, regardless of alcohol consumption. Therefore, the disease is called a “silent” disease.
If left untreated, the disease can progress to advanced fibrosis
Fibrosis is characterized by inflammation and scarring and/or cirrhosis of the liver, causing permanent damage to the liver. If the disease is at an advanced stage, transplantation becomes the only option.
The researchers followed more than 1,700 patients for an average of 4 years, some up to 10 years, to assess patient outcomes. The conclusions of the analysis are as follow:
- Patients with advanced fibrosis have a significantly higher risk of death.
- Fibrosis is associated with a higher risk of death.
- A progressive decline in brain function may be associated with liver disease.
- Increased scarring (fibrosis) is associated with an increased risk of death.
Implications for screening and treatment
The researchers noted that the treatment of diabetes is thus not sufficient to prevent worsening of liver fibrosis and the risk of death: “Among particularly obese diabetics, patients with advanced fibrosis are still likely to die of liver disease even when diabetes is treated.” In other words, a simple treatment of diabetes is not enough.
Drugs that can stop or halt the progression of fibrosis could save a significant number of lives. However, there are currently no drugs approved for the treatment of non-alcoholic fatty liver disease or its advanced variant, non-alcoholic steatohepatitis.
The study, therefore, highlights the need to better understand the processes underlying liver disease and to extend the development of new treatments to areas other than diabetes and endocrinology.