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LIVER DISEASE The first study tested whether faecal


microbial transplant (FMT) – the transfer of faecal bacteria from a healthy individual to a patient – could reduce cravings for alcohol as the first step for use in subsequent larger trials. In a pilot, double-blind, placebo-controlled, randomised clinical trial, 20 patients with alcohol use disorder (AUD) and liver cirrhosis, who had tried several options to quit alcohol unsuccessfully, were given FMT or placebo, with FMT shown to reduce alcohol cravings as well as total and psychosocial sickness impact profile at Day 15 post-treatment. A corresponding significant increase in


microbiota diversity was seen in FMT patients compared with baseline (P=0.02), including a higher relative abundance of Odoribacter, Alistipes and Roseburia in patients given FMT compared with placebo at Day 15. “Faecal microbial transplant was safe and shown to have an impact on reducing short-term alcohol cravings and improving psychosocial quality of life in patients with cirrhosis and AUD,” added study presenter Dr Jasmohan S Bajaj, of McGuire VA Medical Center in the USA. “The relative abundance of short-chain fatty acid-producing bacteria identified in patients with higher diversity after FMT demonstrates that altering the intestine– brain axis is a potential avenue to alleviating AUD in those with cirrhosis.” A second study explored how intestinal microbiota may affect the process of developing hepatocellular carcinoma, using mice that have been genetically engineered to develop steatohepatitis. By crossing these mice with others that have had other genes involved in the inflammatory response to bacteria inactivated, and then altering the intestinal microbial balance with broad-spectrum antibiotics, the research team showed that knocking out the NLRP6 receptor (a key mediator of colonic homeostasis that can cause intestinal dysbiosis if deficient) leads to more severe steatohepatitis and a higher tumour burden. The degree of intestinal barrier


permeability correlated with tumour burden as well as several indicators of inflammation in the liver. Crucially, this immune phenotype could be transferred to other mice by FMT, provided they had functional TLR4 signalling, and it could be reversed if the transplanted microbiota were depleted with broad-spectrum antibiotics. “Strikingly, we also found that


replacing depleted Akkermansia muciniphila bacteria in the intestine of these mice helped ameliorate their inflammation and steatohepatitis,” said


46


Fibrolamellar hepatocellular carcinoma. A rare variant of HCC that tends to afflict younger individuals who have none of the classical risk factors associated with the disease (haematoxylin and eosin [H&E] stain).


Dr Kai Markus Schneider of University Hospital RWTH Aachen, Germany. “This knowledge of how short-term changes to microbiota reshape the hepatic tumour microenvironment has the potential to reveal new therapeutic options for cancer prevention and therapy.”


Reducing mortality The conference also provided important insights into reducing liver transplant waiting-list mortality. Prioritising patients for liver transplantation using the Model for End-stage Liver Disease Sodium (MELD-Na) score, instead of the more commonly used MELD score, could increase the chances of high-risk patients receiving a transplant, and reduce the risk of dying while on the waiting list, according the results of a large study using data from the Eurotransplant network. Researchers from Leiden University Medical Center in the Netherlands evaluated more than 5000 patients with chronic liver disease who had been allocated to the Eurotransplant liver waiting list using the MELD score, and found that more than one-quarter of those who died within three months of


Non-alcoholic fatty liver disease is a progressive condition characterised by deposition of fat in the liver that, eventually, leads to inflammation and fibrosis


being listed might have received a transplant if the MELD-Na score had been used instead.


The MELD score, which estimates mortality risk for patients with end-stage liver disease using laboratory variables, has been used to prioritise patients on liver transplant lists for almost 20 years. Although MELD has been very successful in prioritising patients, it does not reflect accurately the risk of death in patients with hyponatraemia, which is an important predictor of mortality in patients on liver transplant lists. The MELD-Na score, which includes serum sodium in the risk calculation, was adopted in the USA in 2016 for liver transplant prioritisation, but is not yet used routinely across Europe. To test whether the use of the MELD-Na score in the Eurotransplant region (which includes Austria, Belgium, Croatia, Germany, Hungary, Luxembourg, the Netherlands and Slovenia) could improve outcomes, the Leiden team evaluated 5223 patients who were allocated onto the Eurotransplant liver transplant waiting list between 2007 and 2018 using their MELD scores.


These patients were followed from their first listing to the time of delisting or until 90 days after listing. As part of the study, each patient was reclassified retrospectively based on their MELD-Na score, allowing an estimation of the number of lives saved if MELD-Na allocation had been used. According to Dr Ben Goudsmit from Leiden University Medical Center, who presented the study results, a large proportion (40%) of patients on the transplant waiting list had hyponatraemia, and these patients had a three-fold increased risk of dying within 90 days of being listed.


DECEMBER 2020 WWW.PATHOLOGYINPRACTICE.COM


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