Z. Beketova

Out of all patients with NAFLD, around 20% develop non-alcoholic steatohepatitis, NASH. This condition is categorised by symptoms such as the progressive fibrosis of the liver, often followed with cirrhosis and liver failure.

In the general population, there are high prevalence rates of NAFLD, non-alcoholic fatty liver disease. Hence, it is vital to identify the advanced stages of liver fibrosis in these individuals accurately to allow for proper treatment. Non-invasive tests, such as FIB-4 and transient elastography, are valuable tools for identifying patients who require specialist care.

For the management of NASH, non-alcoholic steatohepatitis, stratifying disease severity is essential for implementing treatment and management strategies. Although liver biopsy is the standard for understanding fibrosis severity, there are also non-invasive tests such as FIB-4 and vibration-controlled transient elastography, VCTE.

For NASH and NAFLD, non-invasive tests are often used to measure liver fibrosis. These measurements can, in turn, be used to predict prognosis, meaning that non-invasive tests may function as prognostic markers for NAFLD. In this study, FIB4 and VCTE were used to stratify patients with NAFLD into groups which demonstrated significantly different prognoses, illustrating their effectiveness. Although liver biopsy is the current gold standard, VCTE demonstrated a similar level of accuracy for predicting liver-related events. The optimal thresholds for the diagnosis of advanced fibrosis in NAFLD are still being discussed. However, the benefits that these non-invasive methods bring to the management of NASH is that they can be easily prescribed and give almost immediate results. An idea for a sequential algorithm was also suggested, where blood tests such as the FIB4 is used first to determine prognosis; if results are not favourable, VCTE can be used to then identify advanced fibrosis.

Survival rates of patients who receive a liver transplant for NASH-related cirrhosis are generally good, being found to be similar to that of any other liver transplant cause. However, these patients face a high risk of waiting-list mortality, cardio-metabolic complications as well as recurrent or de novo NAFLD after the transplantation. Immunosuppressant drugs often exacerbate the possible cardio-metabolic issues after transplantation, so careful management of these as well as treatment of existing complications is necessary. The issues with recurrent NASH/NAFLD are a vital focus: up to 55% of cases of NASH post-transplantation were recurrent, and up to 20% were de novo. Currently, it is not known whether such patients may require a second transplant. Predictors of this recurrent/new development of NASH include weight gain, post-transplantation diabetes mellitus or immunosuppressant drugs. Donor-related risk factors such as PNPLA3 and TM6SF2 genetic variants can produce risk too. Effective interventions for this group are vital. One important factor is weight loss: for every 5kg of weight lost by an individual with NAFLD, around a 5% reduction in steatosis is found.

It is a general consensus that exercise training is an important part of the management of non-alcoholic fatty liver disease (NAFLD). Yet, it is not known what the exact effects are, and whether exercise training provides clinically meaningful improvements in liver fat. This information is vital, as due to the fact that there is no current effective cure for NAFLD, lifestyle modifications are the key point of management. This aims to prevent end-stage liver disease and liver cancer.

Fatty liver disease can be caused by many different autosomal recessive diseases. One includes Wilson’s disease, a condition which leads to abnormal copper accumulation in multiple organs. Cirrhosis is common in up to 30% of cases, as well as steatosis and steatohepatitis. Cystic fibrosis is another example, where steatosis is common and liver disease occurs in 0.1-3.6% of patients. Furthermore, alpha-1-antitrypsin deficiency and lysosomal acid lipase deficiency have been linked to steatosis accumulation, although have little research into their pathogenesis.

Non-alcoholic fatty liver disease (NAFLD) has a more progressive form, non-alcoholic steatohepatitis (NASH). In both conditions, inflammation is a key driver of the pathogenesis. There are various causes of metabolic injury in the conditions, leading to the activation of different immune cells such as hepatic Kupffer cells.

Non-alcoholic fatty liver disease (NAFLD) has a more progressive form, non-alcoholic steatohepatitis (NASH). In both conditions, inflammation is a key driver of the pathogenesis. Current treatments mostly focus on promoting weight loss (through encouraging lifestyle changes, or, if necessary, bariatric surgery) and improving comorbidities through pharmacotherapy, such as type 2 diabetes.