Lay Summaries - Volume 3 Issue 2
Lay Summary: Hepatocellular carcinoma is the third leading cause of cancer-related death worldwide. Prognosis is affected by many clinical factors including liver function both before and during anticancer treatment. Here we have used a validated approach to assess liver function using 2 laboratory parameters, serum albumin and bilirubin (ALBI), both before and during treatment with ramucirumab in 2 phase III placebo-controlled studies. We confirm the practicality of using this more simplistic approach in assessing liver function prior to and during anticancer therapy, and demonstrate ramucirumab did not impair liver function when compared with placebo.
Lay Summary: In the largest case-control study ever conducted in patients with LPAC syndrome, a rare genetic form of intrahepatic cholelithiasis in young adults, LPAC syndrome was found in approximately 1% of all patients admitted to the hospital for symptomatic gallstones and, in addition to the pre-established characteristics of the syndrome (age at first symptoms <40 years, recurrence of symptoms after cholecystectomy, and/or imaging evidence of intrahepatic microlithiasis), was associated with lower BMI, higher prevalence of common bile duct stones, and lower incidence of acute cholecystitis. ABCB4 gene variants, which were detected in about half of cases, were associated with common bile duct stones and a personal or family history of hepato-biliary cancer.
Lay Summary: Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.
Lay Summary: Through multiple in vivo experimental approaches in mice, together with a patient study, this work brings some new light on the relationships between biliary homeostasis, gallbladder function, and liver protection. We showed that hepatic bile acid composition is crucial for optimal liver repair, not only in mice, but also in human patients undergoing major hepatectomy.
Lay Summary: Excessive chronic alcohol intake can induce liver disease. Bile acids are molecules produced by the liver and can modulate disease severity. We addressed the specific role of TGR5, a bile-acid receptor. We found that TGR5 deficiency worsened alcohol-induced liver injury and induced both intestinal microbiota dysbiosis and bile-acid pool remodelling. Our data suggest that both the intestinal microbiota and TGR5 may be targeted in the context of human alcohol-induced liver injury.
Lay Summary: Inflammatory processes contribute to the increased risk of death in patients with cirrhosis and ascites. We show that patients with high serum levels of the inflammatory cytokine macrophage migration inhibitory factor (MIF) alongside low levels of its binding receptor sCD74 in blood indicate an increased mortality risk in patients with ascites. The cirrhotic liver is a relevant source of elevated circulating MIF levels.
Lay Summary: Circulating miRNAs are small molecules in the blood that can be used to identify or predict a clinical condition. Our study aimed to identify miRNAs for use as biomarkers in patients with cirrhosis or acute-on-chronic liver failure. Several miRNAs were found to be dysregulated during the progression of disease, and some were also related to organ failure and disease-related outcomes.
Lay Summary: Patients with low platelet counts caused by chronic liver disease may not receive planned invasive procedures or surgeries because of an increased risk of bleeding. Lusutrombopag has previously demonstrated efficacy in raising platelet counts and is approved to treat chronic liver disease patients with low platelet counts in advance of a planned surgery. Physicians need to understand more clearly what to expect in terms of platelet count change when using lusutrombopag; this integrated analysis provides data to help guide its clinical application.
Lay Summary: We have used a mouse model, human cells, and liver tissue to test how exposure to fructose can cause the liver to store excess fat and become damaged and scarred. We have then inhibited a key enzyme within the liver that is responsible for fructose metabolism. Our findings show that inhibition of fructose metabolism reduces liver injury and fibrosis in mouse and human livers and thus this may represent a potential route for treating patients with fatty liver disease in the future.
Lay Summary: Non-alcoholic steatohepatitis (NASH) is a progressive liver disease that frequently occurs in patients with obesity and type 2 diabetes. Reliable markers for the diagnosis of NASH are needed. Plasma bile acids have been proposed as NASH biomarkers. Herein, we found that plasma bile acids are only elevated in patients with NASH when significant insulin resistance is present, limiting their utility as NASH markers.
Lay Summary: Both non-alcoholic fatty liver disease (NAFLD) and dementia are increasing in prevalence because of a more sedentary lifestyle, increased prevalence of obesity and population ageing. However, the link between these 2 diseases is not well studied. We investigated the association between NAFLD and the risk of dementia and found no association. However, liver histology parameters, especially fibrosis, could significantly improve the prediction of dementia risk.
Lay Summary: Non-alcoholic fatty liver disease (NAFLD), which is closely associated with obesity, metabolic syndrome, and diabetes, is a highly prevalent condition that can be optimally managed through a multidisciplinary patient-centred approach. National preparedness to address NAFLD is essential to allow for effective public health measures aimed at preventing disease while also ensuring that health systems can deliver effective care to affected populations. This study defined preparedness as having adequate policies and civil society engagement, guidelines, epidemiology, and care management. NAFLD preparedness was found to be deficient in all 29 countries studied, with great variation among the countries and the 4 categories studied.
Lay Summary: Hepatocellular carcinoma (HCC) is the most common type of liver cancer, increasingly arising in patients with liver disease caused by metabolic syndrome, termed non-alcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD). We assessed all patients with HCC between 1990 and 2014 in the canton of Geneva (western Switzerland) and found an increase in all HCC cases in this timeframe, particularly in women. In addition, we found that HCC caused by NAFLD or MAFLD significantly increased over the years, particularly in women, possibly driving the increase in overall HCC cases.
Lay Summary: ZBTB20 has been implicated as a potential oncogene in liver cancer. Herein, we uncover its important role in liver cancer development. We show that it interacts with PPARG to upregulate the WNT/CTNNB1 signalling pathway, leading to tumourigenesis.
Lay Summary: Many more people are getting liver cancer, particularly the subtype hepatocellular carcinoma, than 20 years ago. Men in Scotland are most likely to get liver cancer and to die from it. Survival after liver cancer diagnosis is getting longer but still less than half are alive after 1 year.
Lay Summary: The purpose of hospice care is to provide comfort and lessen suffering at the end of life. Hospice care allows one to die outside the hospital environment which is the wish of most people. However, we found that among persons aged 65 years and older who were diagnosed with liver cancer (which has a poor prognosis), only 25% were enrolled in hospice care and the majority used a hospice only in the last weeks of life. This is a disheartening finding as liver cancer patients with longer hospice enrolment had lower costs and improved survival. We suggest that healthcare practitioners consider discussion of palliative and hospice care routinely with patients suffering from liver cancer.
Lay Summary: Hepatitis B virus (HBV) can only naturally infect humans and chimpanzees. Mouse models have been developed with the HBV genome integrated into mouse chromosomes, but this prevents mice from being cured. We developed a new transgenic mouse model that allows for HBV to be excised from mouse chromosomes to form a recombinant circular DNA molecule resembling the natural circular HBV genome. HBV expression could be reduced in these mice, enabling curative therapies to be tested in this new mouse model.
Lay Summary: To date, the predominant focus of the global response towards elimination of hepatitis C has been on the testing and treatment of adults. Much less attention has been paid to testing and treatment among children and adolescents, although in 2018 an estimated 3.26 million were infected with HCV. Our review shows that many countries have no national guidance on HCV testing and treatment in children and adolescents. It highlights the urgent need for advocacy and updated policies and guidelines specific for children and adolescents.
Lay Summary: Our findings suggest that some chemotherapies may impair the anti-tumor efficacy of immunotherapy. Further studies are required to uncover the specific effects of different chemotherapies on the immunological profile of tumors. This data will be critical for the rational design of combination immunotherapy strategies for patients with hepatocellular carcinoma.