Lay Summaries - Volume 71 Issue 5

Lay Summary: Chronicity is a serious threat to infants infected with hepatitis B. However, no treatment measure has been recommended for infantile-onset hepatitis B in current guidelines. In order to evaluate the benefit and safety of antiviral therapy in infantile-onset hepatitis B, a real-world cohort study was conducted. Long-term follow-up results showed that early initiation of antiviral therapy with lamivudine safely led to a rapid and significant loss of serum hepatitis B surface antigen in the present subset of infants with alanine aminotransferase ≥2× upper limit of normal. Further trials with larger cohorts are needed.
Lay Summary: Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations.
Lay Summary: Direct-acting antiviral therapy results in cure of hepatitis C virus (HCV) in almost all treated patients. However, the impacts of HCV cure on immune responses remain controversial. Whether immune responses to HCV recover is important in cases of re-exposure, or for the resolution of extrahepatic manifestations. The main finding of our study was that HCV-specific T cells remain functionally impaired despite HCV clearance. This finding could explain the fact that HCV cure does not lead to protective immunity and that re-infections have frequently been observed.
Lay Summary: Chronic hepatitis B virus infection (CHB) is characterized by a dysfunctional immune response. In patients with CHB, inhibitory receptors, such as programmed death receptor 1 (PD-1) are overexpressed on T cells, leading to an ineffective immune response in the liver. Herein, we show that the PD-1 inhibitor, nivolumab, is safe and effective for the treatment of virally suppressed patients with CHB.
Lay Summary: B cells are best known for their capacity to produce antibodies, which often play a deleterious role in the development of autoimmune diseases. During chronic hepatitis C, self-reactive B cells proliferate and can be responsible for autoimmune symptoms (arthritis, purpura, neuropathy, renal disease) and/or lymphoma. Direct-acting antiviral therapy clears the hepatitis C virus and eliminates deleterious B cells.
Lay Summary: In patients with liver cirrhosis, the risk of a hepatectomy is difficult to appreciate. We propose a statistical tool to estimate this risk, preoperatively and immediately after surgery, using readily available parameters and on online calculator. This model could help to improve the selection of patients with the best risk-benefit profiles for hepatectomy.
Lay Summary: Patients with liver cirrhosis frequently exhibit hyperammonemia and suffer from cognitive and motoric dysfunctions, which at least in part involve premature ageing of the astrocytes in the brain. This study identifies glucosamine and an O-GlcNAcylation-dependent disruption of iron homeostasis as novel triggers of oxidative stress, thereby mediating ammonia toxicity in the brain.
Lay Summary: The hepatic venous pressure gradient is associated with outcomes in patients with cirrhosis undergoing elective extrahepatic surgery. It enables a better stratification of risk in these patients and provides the foundations for potential interventions to improve post-surgical outcomes.
Lay Summary: We report a unique experience with 50 living donors who volunteered to donate to a recipient with whom they had no biological connection or prior relationship (anonymous living donors). This report is the first to discuss motivations, strategies and facilitators that may mitigate physical, social and ethical risk factors in this patient population. With rigorous protocols, anonymous liver donation and recipient outcomes are excellent; with appropriate clinical expertise and system facilitators in place, our experience suggests that other centers may consider the procedure for its significant potential to reduce the gap between transplant organ demand and availability.
Lay Summary: The liver, the primary organ for ethanol metabolism, can be damaged by the byproducts of ethanol metabolism, including reactive oxygen species. In this study, we have identified a key epigenetic regulator SIRT6 that plays a critical role in protecting the liver from oxidative stress-induced liver injury. Thus, our data suggest that SIRT6 may be a potential therapeutic target for alcohol-related liver disease.
Lay Summary: A functionally mature, human cell-based liver model exhibiting human responses in toxicity prediction and drug evaluation is urgently needed for pre-clinical drug development. Here, we develop a novel human pluripotent stem cell-derived hepatocyte-like liver organoid that is critically advanced in terms of its generation method, functional performance, and application technologies. Our organoids can contribute to the better understanding of liver development and regeneration, and provide insights for metabolic studies and disease modeling, as well as toxicity assessments and drug screening for personalized medicine.
Lay Summary: Obeticholic acid increased human gallbladder cholesterol saturation and bile acid hydrophobicity, both decreasing cholesterol solubility in bile. Together with increased hepatobiliary levels of fibroblast growth factor 19, our findings suggest that pharmacological activation of the farnesoid X receptor increases the risk of gallstone formation.
Lay Summary: In our study we assessed whether the Amsterdam-Oxford model (AOM) is able to correctly estimate the risk of liver transplantation or death in patients with primary sclerosing cholangitis (PSC). This model uses 7 objective and readily available variables to estimate prognosis for individual patients at the time of PSC diagnosis. The AOM may aid in patient counselling and timing of diagnostic procedures or therapeutic interventions for complications of liver disease. We confirm that the model works well at PSC diagnosis, but also when the AOM is recalculated at different timepoints during follow-up, greatly improving the applicability of the model in clinical practice and for individual patients.
Lay Summary: Alcoholics with an ALDH2 polymorphism have an increased risk of digestive tract cancer development, however, the link between ALDH2 deficiency and hepatocellular carcinoma (HCC) development has not been well established. In this study, we show that ALDH2 deficiency exacerbates alcohol-associated HCC development both in patients and mouse models. Mechanistic studies revealed that after chronic alcohol exposure, Aldh2-deficient hepatocytes produce a large amount of harmful oxidized mitochondrial DNA via extracellular vesicles, which can be delivered into neighboring HCC cells and subsequently activate multiple oncogenic pathways, promoting HCC.
Lay Summary: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is likely due to the interaction between a deranged metabolic milieu and local mediators of hepatic inflammation and fibrosis in the insulin resistant state. This study provides in vivo support for a possible link between deranged metabolism in the adipose tissue and activation of hepatic macrophages in patients with NAFLD, most likely in response to free fatty acid overflow and independent of obesity and diabetes.