1.
The role of the gut microbiome in graft fibrosis after pediatric liver transplantation.
Qin, T, Fu, J, Verkade, HJ
Human genetics. 2021;(5):709-724
-
-
Free full text
-
Abstract
Liver transplantation (LT) is a life-saving option for children with end-stage liver disease. However, about 50% of patients develop graft fibrosis in 1 year after LT, with normal liver function. Graft fibrosis may progress to cirrhosis, resulting in graft dysfunction and ultimately the need for re-transplantation. Previous studies have identified various risk factors for the post-LT fibrogenesis, however, to date, neither of the factors seems to fully explain the cause of graft fibrosis. Recently, evidence has accumulated on the important role of the gut microbiome in outcomes after solid organ transplantation. As an altered microbiome is present in pediatric patients with end-stage liver diseases, we hypothesize that the persisting alterations in microbial composition or function contribute to the development of graft fibrosis, for example by bacteria translocation due to increased intestinal permeability, imbalanced bile acids metabolism, and/or decreased production of short-chain fatty acids (SCFAs). Subsequently, an immune response can be activated in the graft, together with the stimulation of fibrogenesis. Here we review current knowledge about the potential mechanisms by which alterations in microbial composition or function may lead to graft fibrosis in pediatric LT and we provide prospective views on the efficacy of gut microbiome manipulation as a therapeutic target to alleviate the graft fibrosis and to improve long-term survival after LT.
2.
Liver fibrosis in the context of nonalcoholic steatohepatitis: the role of adipokines.
DI Maira, G, Pastore, M, Marra, F
Minerva gastroenterologica e dietologica. 2018;(1):39-50
Abstract
Liver fibrosis is a multifaceted process that occurs as a consequence of chronic liver injury. This process is characterized by inflammation, activation of matrix-producing cells, matrix deposition and remodeling, and epithelial cell regeneration. In subjects with chronic liver damage, fibrogenesis is favored by the presence of obesity and insulin resistance, which are also relevant risk factors for the development and progression of nonalcoholic steatohepatitis (NASH). It is now well-known that adipose tissue is not only involved in energy storage but also functions as an endocrine organ that secretes various bioactive substances known as adipokines. This term identifies a group of polypeptide molecules, which exert local, peripheral and/or central actions. Additionally to their well-established role in controlling adipose tissue physiology, energy homeostasis, inflammation and immune function, adipokines have been shown to be involved in different obesity-related diseases, such as hypertension, atherosclerosis and type 2 diabetes. In liver diseases, the biologic actions of these factors may contribute to the mechanisms leading to NASH. In this review, we focus on the role of adipokines in liver fibrogenesis and discuss their potential as regulators of this pathological condition and as targets for future pharmacological treatment strategies of chronic liver diseases.
3.
Risk factors for hepatic decompensation in patients with HIV/HCV coinfection and liver cirrhosis during interferon-based therapy.
Mauss, S, Valenti, W, DePamphilis, J, Duff, F, Cupelli, L, Passe, S, Solsky, J, Torriani, FJ, Dieterich, D, Larrey, D
AIDS (London, England). 2004;(13):F21-5
Abstract
OBJECTIVE Hepatic decompensation was reported from two recent trials (APRICOT and RIBAVIC) assessing interferon (IFN)-based treatment of hepatitis C virus (HCV) in HIV/HCV-coinfected patients. This paper identifies risk factors associated with hepatic decompensation in APRICOT. METHODS APRICOT is a randomized, partially-blinded, controlled trial comparing treatment with peg-IFN alpha-2a 180 microg once weekly plus ribavirin/placebo 400 mg twice daily with IFN alpha-2a 3 million units three times weekly plus ribavirin 400 mg twice daily for 48 weeks in a total of 859 patients. Multiple logistic regression analysis was performed comparing the baseline characteristics of those cirrhotic patients who experienced decompensation with those of the other cirrhotic patients enrolled. RESULTS Fourteen patients, all cirrhotic, experienced hepatic decompensation during the study. The incidence in the cirrhotic subgroup of the study was 10.4% (14/134). Six of the 14 patients died as a result of hepatic decompensation. The risk factors associated with hepatic decompensation were increased bilirubin, decreased haemoglobin, increased alkaline phosphatase or decreased platelets, and treatment with didanosine. Markers of viral replication, histological activity, cellular immune status or HCV-therapy, treatment with ribavirin and pegylated versus non-pegylated IFN were not associated with hepatic decompensation. CONCLUSIONS The results from APRICOT indicate that the overall risk of hepatic decompensation in HIV/HCV-coinfected patients without cirrhosis receiving IFN-based treatment is low. In contrast, patients with markers of advanced cirrhosis, despite the absence of a history of hepatic decompensation, should be monitored closely during IFN-based therapy, because they are at risk of hepatic decompensation. Treatment with antiretrovirals such as didanosine may increase the risk further.
4.
Does hepatitis C virus cause severe liver disease only in people who drink alcohol?
Vento, S, Cainelli, F
The Lancet. Infectious diseases. 2002;(5):303-9
Abstract
Hepatitis C virus (HCV) infects about 170 million people worldwide, and has been portrayed in the media as a silent killer, incorrectly implying that cirrhosis and hepatocellular carcinoma are the certain final outcomes of infection. Results of numerous population-based surveys indicate that chronic HCV infection is highly prevalent in elderly people who, in most instances, do not develop end-stage liver disease. In individuals who do progress to cirrhosis and hepatocellular carcinoma alcohol plays a fundamental part, via mechanisms that result in increased viral replication, enhanced HCV quasispecies complexity, increased liver-cell death, suppression of immune responses, and iron overload. Although overlaps are present in the histological appearance of the liver in patients with hepatitis C who do and do not drink alcohol, histology could be of some help in revealing the role of alcohol in HCV disease progression even in people who deny drinking. Interventions and high-impact, continuous public-health campaigns are needed to persuade doctors and patients infected with HCV of the importance of abstaining from alcohol if risk of progression towards cirrhosis and hepatocellular carcinoma is to be reduced.