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LIVER DISEASE


almost daily basis, and potential temporary cessation of transplantation in areas where the virus is prevalent. A key message was that although those who have undergone liver transplantation are at increased risk of COVID-19, disease severity appears to be in line with that in the general population. Guidelines also broadly advise against reduction of immunosuppressive therapy as this has not been demonstrated to increase risk.


Liver fibrosis and diabetic patients Delegates also learned how liver fibrosis assessment in routine care for diabetic 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 the need for 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 leads to inflammation and fibrosis. This more advanced condition is known as non-alcoholic steatohepatitis (NASH). Type 2 diabetes (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 the age of 35 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 three years. However, 24 patients had an LSM of >8 kPa, indicating significant fibrosis, and were referred to secondary care. Patients thought to have advanced


Non-alcoholic fatty liver disease. This condition is considered to be the liver manifestation of metabolic syndrome and affects up to 25% of adults worldwide (trichrome stain).


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 that 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. “To our knowledge, this is the first pathway incorporating two-tier liver fibrosis assessment into routine diabetic reviews in primary care,” she stated. “Non-alcoholic fatty liver disease 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, 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


WWW.PATHOLOGYINPRACTICE.COM DECEMBER 2020


diabetic clinics. This study provides the proof of concept that such pathways are feasible and highly effective.”


Intestinal microflora


Other key insights included the findings of studies on the significance of intestinal microflora in alcohol-related liver disease and hepatocarcinogenesis. The key role of microbial biodiversity in the intestine was highlighted in a study of faecal 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 the intestinal microbiota with the action of key signalling molecules, mediating the risk of hepatocarcinogenesis. In recent years, imbalances in the intestinal 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 permeability and alter microbiota composition. This includes expansion of inflammation-associated bacteria such as Proteobacteria, and reduction of protective species such as those of Faecalibacterium. Increased intestinal permeability is believed to lead to translocation of 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 intestinal microbiota raises the possibility of exploiting its manipulation to improve patient outcomes.


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