Lay Summaries - Volume 69 Issue 4
Lay Summary: Limited access to the diagnostic tools used to assess treatment eligibility (liver biopsy/Fibroscan/hepatitis B virus DNA) has been an obstacle to the scale up of hepatitis B treatment programs in low- and middle-income countries. Using the data from African patients with chronic HBV infection, we developed and validated a new simple diagnostic score for treatment eligibility, which only consists of hepatitis B virus e antigen and alanine aminotransferase level. The diagnostic accuracy of the score for selecting patients for HBV treatment was high and could be useful in African settings.
Lay Summary: In the context of highly effective and well tolerated therapies for hepatitis C virus that are now recommended for all patients, a reassessment of hepatitis C screening strategies is needed. An effectiveness and cost-effectiveness study of different strategies targeting either the at-risk population, specific ages or all individuals was performed. In France, universal screening is the most effective strategy and is cost-effective when treatment is initiated regardless of fibrosis stage. From an individual and especially from a societal perspective of hepatitis C virus eradication, this strategy should be implemented.
Lay Summary: We investigated 21,182 patients with chronic hepatitis B receiving antiviral treatment. Alanine aminotransferase is a laboratory marker of liver function, with raised levels indicating liver dysfunction and in severe cases hepatitis. Normal on-treatment alanine aminotransferase during the first year of treatment in patients with CHB is associated with a lower risk of hepatic events.
Lay Summary: Liver function may abruptly deteriorate in patients with chronic liver disease with cirrhosis, often resulting in these patients being admitted to an intensive care unit (ICU) with organ failure. Previous studies have indicated that this sudden deterioration, called acute-on-chronic liver failure is associated with very high mortality rates, which often resulted in deferred ICU care because of a perception of futility. Our study now shows that the ICU course and outcome are not different when patients with acute-on-chronic liver failure are compared to other ICU patients matched for severity of illness. This demonstrates that patients with acute-on-chronic liver failure deserve the same ICU care given to other ICU populations.
Lay Summary: After the advent of direct-acting antivirals in 2014, a dramatic decline was observed in the number of liver transplants performed both in patients with decompensated cirrhosis due to hepatitis C virus (HCV), minus 60%, and in those with hepatocellular carcinoma associated with HCV, minus 41%. Furthermore, this is the first large-scale study demonstrating that the survival of liver transplant recipients with HCV-related liver disease has dramatically improved over the last three years and is now comparable to the survival of recipients with hepatitis B virus infection. The reduction in HCV-related indications for LT means that there is a greater availability of livers, at least 600 every year, which can be allocated to patients with indications other than HCV.
Lay Summary: The overall health of liver transplant recipients could be assessed by a simple clinical assessment tool called the Karnofsky performance status, which assesses an individual’s overall functional status on an 11-point scale, in increments of 10, where a score of 0 is considered dead and 100 is considered perfect health. In this study, using a large dataset, we show that the performance status before and after liver transplant is a predictor of survival. More importantly, those who have low performance status before transplant and do not show an improvement in performance status between 3–12?months after liver transplant have very poor survival.
Lay Summary: This study represents the most extensive pre-clinical characterization of anti-ANXA3 monoclonal antibodies for the treatment of hepatocellular carcinoma to date. These results support the clinical trial development of anti-ANXA3 antibodies in combination with sorafenib/regorafenib. Further studies will optimize patient target selection and identify the best treatment combinations.
Lay Summary: Mouse models are widely used to study the biology of cancer and to test potential therapies. Herein, we have described the mutational landscape of tumours arising in a carcinogen-induced mouse model of liver cancer. Since cancer is a disease caused by genomic alterations, information about the patterns and types of mutations in the tumours in this mouse model should facilitate its use to study human liver cancer.
Lay Summary: This study compared the gene expression and protein profiles of healthy liver cells and those affected by the inherited disease a1-antitrypsin deficiency. This approach identified specific factors primarily present in diseased samples which could provide new targets for drug development. This study also demonstrates the interest of using hepatic cells generated from human-induced pluripotent stem cells to model liver disease in vitro for uncovering new mechanisms with clinical relevance.
Lay Summary: Long noncoding RNAs play important roles in various biological processes. While long noncoding RNAs do not directly code proteins, they can regulate gene expression by diverse mechanisms. We identified the long noncoding RNA, termed lncHand2 because of its proximity to the gene Hand2, to be an important determinant of liver regeneration through c-Met signaling.
Lay Summary: Autoimmune hepatitis is a chronic liver disease caused by a dysfunctional immune system. It is widely believed that autoimmune hepatitis accumulates in families. We studied the family members of patients with autoimmune hepatitis from the entire Danish population. We found that autoimmune hepatitis does accumulate in families, but the risk of autoimmune hepatitis in the family members is very low.
Lay Summary: In non-alcoholic fatty liver disease-related compensated cirrhosis, the expanded Baveno VI criteria work better than the Baveno VI criteria for ruling out the presence of varices needing treatment, sparing unnecessary and invasive screening procedures. New diagnostic criteria for this patient group, based on liver stiffness measurement and platelet count, and optimized for the specific FibroScan® probe used, work better than both Baveno VI and expanded Baveno VI criteria. The accuracy of all non-invasive scoring criteria was lower in non-obese patients.
Lay Summary: Alcohol consumption alters gut microbiota and multiple intestinal barrier protecting factors that are regulated by intestinal hypoxia-inducible factor 1a (HIF-1a). Absence of intestinal HIF-1a exacerbates gut leakiness leading to an increased translocation of bacteria and bacterial products to the liver, consequently causing alcoholic liver disease. Intestinal specific upregulation of HIF-1a could be developed as a novel approach for the treatment of alcoholic liver disease.
Lay Summary: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years.
Lay Summary: In patients with fatty liver disease, the enzymes that convert nitrogen waste into urea may be affected, leading to the accumulation of ammonia, which is toxic. This accumulation of ammonia can lead to scar tissue development, increasing the risk of disease progression. In this study, we show that fat accumulation in the liver produces a reversible reduction in the function of the enzymes that are involved in detoxification of ammonia. These data provide potential new targets for the treatment of fatty liver disease.