HE PATOLOGY
patients could uncover a hidden population of people living with advanced liver disease. A pilot study, conducted in two primary care practices in North East England, tested a two-tier liver fibrosis assessment as part of routine diabetic reviews and discovered that 4.8% of their patients with diabetes also had advanced fibrosis or cirrhosis of the liver, putting them at elevated risk of liver cancer or liver transplant.
Non-alcoholic fatty liver disease (NAFLD) is considered to be the liver manifestation of metabolic syndrome and affects up to 25% of adults worldwide. It is a progressive condition characterised by deposition of fat in the liver that, eventually, leads to inflammation and scarring (known as fibrosis). This more advanced condition is known as non-alcoholic steatohepatitis (NASH). T2DM is an important risk factor for NAFLD, with prevalence as high as 50% in this population, and may also accelerate progression to NASH and liver cirrhosis. Despite some guidelines recommending screening for NASH or advanced fibrosis in at-risk populations, it is not universally implemented and remains controversial. In this pilot study, a two-tier fibrosis assessment was incorporated into routine diabetic review for 477 successive patients with T2DM (between April 2018 and September 2019). All patients over 35 years of age had their FIB-4 score (a measure of potential liver fibrosis based on blood biomarkers and age) calculated. A total of 84 patients had a FIB-4 score above the age- related cut-off, of whom 56 were suitable for assessment of their fibrosis by transient elastography (FibroScan). Patients with a liver stiffness measurement (LSM) of ≤8 kPa remained in primary care and were advised to repeat staging in 3 years. However, 24 patients had an LSM of
>8 kPa, indicating significant fibrosis, and were referred to secondary care. Patients
Recent results from studies of several novel agents designed to achieve a functional cure for this chronic liver disease were presented at the congress. While many of these early trials focused on safety and tolerability, they also showed some promising signs of progress in combating HBV infection.
thought to have advanced fibrosis/cirrhosis on specialist assessment were enrolled into surveillance programmes. The overall rate of advanced fibrosis/cirrhosis was 4.8%, representing a seven-fold increase in the diagnosis of advanced liver disease/cirrhosis over what had been previously experienced in patients with diabetes at this centre. In addition, the study found that over 50% of patients who were diagnosed with significant fibrosis or advanced liver disease presented with normal alanine aminotransferase (ALT) levels. Two asymptomatic patients were also diagnosed with hepatocellular carcinoma. “We identified a significant number of patients with advanced liver disease, over half of whom had normal ALT, who would have been missed if only national guidelines had been followed,” said Dr. Dina Mansour, consultant gastroenterologist at the Queen Elizabeth Hospital in Gateshead, UK. “To our knowledge, this is the first pathway incorporating two-tier liver fibrosis assessment into routine diabetic reviews in primary care.” “NAFLD is very prevalent and is rapidly becoming the main indication for liver transplantation. It is therefore important to diagnose severe liver disease when patients are still in the asymptomatic phase
so that further disease progression can be prevented,” said Professor Emmanuel Tsochatzis of the Royal Free Hospital and University College London, UK, and an EASL Governing Board member. “We cannot rely on clinical judgment or abnormal liver tests for this and we do need staging pathways with non-invasive fibrosis assessment in primary care or diabetic clinics. This study provides the proof of concept that such pathways are feasible and highly effective.”
Gut microflora
Other key insights included the findings of studies on the significance of gut microflora in alcohol-related liver disease and hepatocarcinogenesis. The key role of microbial biodiversity in the gut was highlighted in a study of fecal microbial transplant, with the technique showing promise as an intervention to improve some aspects of alcohol-related liver disease. A second study used a mouse model to associate changes in gut microbiota with the action of key signalling molecules, mediating the risk of hepatocarcinogenesis. In recent years, imbalances in gut microbiota, or dysbiosis, have been implicated as contributing to alcoholic liver disease. In cases of chronic alcohol use, reactive oxygen species produced by alcohol metabolism can lead to chronic intestinal inflammation, which in turn can increase gut permeability and alter microbiota composition. This includes expansion of inflammation-associated bacteria such as Proteobacteria, and reduction of protective species such as Faecalibacterium. Increased gut permeability is believed to lead to translocation of gut bacterial DNA and endotoxins to the liver. The latter, in particular, are thought to induce pro- inflammatory toll-like receptor 4 (TLR4) signalling pathways that are associated with hepatocarcinogenesis. The importance of gut microbiota raises the possibility of exploiting its manipulation to improve patient outcomes.
The first study tested whether fecal microbial transplant (FMT) – the transfer of fecal bacteria from a healthy individual to a
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