Liver biopsy findings from healthy potential living liver donors: Reasons for disqualification, silent diseases and correlation with liver injury tests

Minervini, Marta Ida; Ruppert, Kristine; Fontes, Paulo; Volpes, Riccardo; Vizzini, Giovanni; Vera, Michael E. de; Gruttadauria, Salvatore; Miraglia, Roberto; Pipitone, Loredana; Marsh, J. Wallis; Marcos, Amadeo; Gridelli, Bruno; Demetris, Anthony J.

doi:10.1016/j.jhep.2008.10.030

Cited by 88 publications

(55 citation statements)

References 24 publications

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“…A similar prevalence (15–25%) had been reported in the past by autoptic studies [20,21]. A surprisingly high prevalence of histologically diagnosed NAFLD has been reported in apparently healthy liver donors (12–18% in Europe [22,23] and 27–38% in the USA [24,25]). With sensitive imaging techniques such as magnetic resonance spectroscopy (MRS), 34% of US adults appear to have NAFLD [26].…”

Section: Definition Epidemiology and Natural Historysupporting

confidence: 80%

ASH and NASH

Scaglioni

Ciccia

Marino

et al. 2011

Dig Dis

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Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) have a similar pathogenesis and histopathology but a different etiology and epidemiology. NASH and ASH are advanced stages of non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD). NAFLD is characterized by excessive fat accumulation in the liver (steatosis), without any other evident causes of chronic liver diseases (viral, autoimmune, genetic, etc.), and with an alcohol consumption ≤20–30 g/day. On the contrary, AFLD is defined as the presence of steatosis and alcohol consumption >20–30 g/day. The most common phenotypic manifestations of primary NAFLD/NASH are overweight/obesity, visceral adiposity, type 2 diabetes, hypertriglyceridemia and hypertension. The prevalence of NAFLD in the general population in Western countries is estimated to be 25–30%. The prevalence and incidence of NASH and ASH are not known because of the impossibility of performing liver biopsy in the general population. Up to 90% of alcoholics have fatty liver, and 5–15% of these subjects will develop cirrhosis over 20 years. The risk of cirrhosis increases to 30–40% in those who continue to drink alcohol. About 10–35% of alcoholics exhibit changes on liver biopsy consistent with alcoholic hepatitis. Natural histories of NASH and ASH are not completely defined, even if patients with NASH have a reduced life expectancy due to liver-related death and cardiovascular diseases. The best treatment of AFLD/ASH is to stop drinking, and the most effective first-line therapeutic option for NAFLD/NASH is non-pharmacologic lifestyle interventions through a multidisciplinary approach including weight loss, dietary changes, physical exercise, and cognitive-behavior therapy.

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Section: Definition Epidemiology and Natural Historysupporting

confidence: 80%

ASH and NASH

Scaglioni

Ciccia

Marino

et al. 2011

Dig Dis

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“…These differences were exclusively due to hepatocyte, rather than mesenchymal (endothelial and Kupffer cell), iron accumulation ( Figure 4A). The periportal hepatocellular distribution of iron deposits noted in operationally tolerant recipients resembled findings previously reported in a minority of male healthy individuals with normal liver function (18). We then explored the relationship between iron stores and the differentially expressed gene set by deriving gene influence plots ( Figure 4B).…”

Section: Before the Initiation Of Drug Minimization Liver Grafts Frosupporting

confidence: 60%

Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation

Bohne

Martínez‐Llordella²,

Lozano³

et al. 2012

J. Clin. Invest.

189

209

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Following organ transplantation, lifelong immunosuppressive therapy is required to prevent the host immune system from destroying the allograft. This can cause severe side effects and increased recipient morbidity and mortality. Complete cessation of immunosuppressive drugs has been successfully accomplished in selected transplant recipients, providing proof of principle that operational allograft tolerance is attainable in clinical transplantation. The intra-graft molecular pathways associated with successful drug withdrawal, however, are not well defined. In this study, we analyzed sequential blood and liver tissue samples collected from liver transplant recipients enrolled in a prospective multicenter immunosuppressive drug withdrawal clinical trial. Before initiation of drug withdrawal, operationally tolerant and non-tolerant recipients differed in the intragraft expression of genes involved in the regulation of iron homeostasis. Furthermore, as compared with nontolerant recipients, operationally tolerant patients exhibited higher serum levels of hepcidin and ferritin and increased hepatocyte iron deposition. Finally, liver tissue gene expression measurements accurately predicted the outcome of immunosuppressive withdrawal in an independent set of patients. These results point to a critical role for iron metabolism in the regulation of intra-graft alloimmune responses in humans and provide a set of biomarkers to conduct drug-weaning trials in liver transplantation.

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“…Similar rates of NAFLD are reported in healthy people evalu ated in transplantation units as potential living liver donors. In a single retrospective study performed in a mixed US and Italian cohort in this setting, the histological prevalence of steatosis and steatohepatitis was 48.5% and 15.5%, resepctively 41 . However, both NAFLD and NASH were more frequently found in Americans compared with Italians (54% versus 34% for NAFLD and 17.6% versus 16.2% for NASH, respectively).…”

Section: Nafld In Europementioning

confidence: 95%