Mitochondrial Roles and Cytoprotection in Chronic Liver Injury

The liver is one of the richest organs in terms of number and density of mitochondria. Most chronic liver diseases are associated with the accumulation of damaged mitochondria. Hepatic mitochondria have unique features compared to other organs' mitochondria, since they are the hub that integrates hepatic metabolism of carbohydrates, lipids and proteins. Mitochondria are also essential in hepatocyte survival as mediator of apoptosis and necrosis. Hepatocytes have developed different mechanisms to keep mitochondrial integrity or to prevent the effects of mitochondrial lesions, in particular regulating organelle biogenesis and degradation. In this paper, we will focus on the role of mitochondria in liver physiology, such as hepatic metabolism, reactive oxygen species homeostasis and cell survival. We will also focus on chronic liver pathologies, especially those linked to alcohol, virus, drugs or metabolic syndrome and we will discuss how mitochondria could provide a promising therapeutic target in these contexts

Autoimmune acute liver failure: Proposed clinical and histological criteria

Identifying autoimmune hepatitis as the etiology of acute liver failure (ALF) is potentially important, because administering corticosteroids might avoid the need for liver transplantation. However, clinical and histological criteria of autoimmune ALF (AI-ALF) have not been defined. Liver sections (biopsies and explants) from a 72-patient subset of the ALF Study Group Registry with indeterminate ALF were reviewed by a pathologist blinded to all clinical data and were diagnosed with probable AI-ALF based on four features suggestive of an autoi mmune pathogenesis: distinctive patterns of massive hepatic necrosis (present in 42% of sections), presence of lymphoid follicles (32%), a plasma cell–enriched inflammatory infiltrate (63%), and central perivenulitis (65%). Forty-two sections (58%) were considered probable for AI-ALF; this group demonstrated higher serum globulins (3.7 ± 0.2 g/dL versus 3.0 ± 0.2 g/dL; P = 0.037) and a higher prevalence of antinuclear and/or anti–smooth muscle antibodies (73% versus 48%; P = 0.034) compared to those without histology suggestive of probable AI-ALF. Thirty patients concordant for autoantibodies and probable AI-ALF upon histological analysis were more likely to have the classical autoimmune hepatitis phenotype (female predominance [72% versus 48%; P < 0.05], higher globulins [3.9 ± 0.2 g/dL versus 3.0 ± 0.2 g/dL; P < 0.005], and higher incidence of chronic hepatitis in long-term follow-up [67% versus 17%, P = 0.019]) compared to the population without concordant AI-ALF histology and autoantibodies. Conclusion: Patients with indeterminate ALF often have features of autoimmune disease by histological analysis, serological testing, and clinical recurrence during follow-up. In contrast to classical autoimmune hepatitis, histological features of AI-ALF predominate in the centrilobular zone. (H EPATOLOGY 2011;53:517-526)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79410/1/24080_ftp.pd

Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients in Korea

Purpose: We identified pediatric liver transplant recipients with successful withdrawal of immunosuppression who developed tolerance in Korea. Materials and Methods: Among 105 pediatric patients who received liver transplantation and were treated with tacrolimus-based immunosuppressive regimens, we selected five (4.8%) patients who had very low tacrolimus trough levels. Four of them were noncompliant with their medication and one was weaned off of immunosuppression due to life threatening posttransplant lymphoproliferative disorder. We reviewed the medical records with regard to the relationship of the donor-recipients, patient characteristics and prognosis, including liver histology, and compared our data with previous reports. Results: Four patients received the liver transplantation from a parent donor and one patient from a cadaver donor. A trial of withdrawal of the immunosuppressant was started a median of 45 months after transplantation (range, 14 months to 60 months), and the period of follow up after weaning from the immunosuppressant was a median of 32 months (range, 14 months to 82 months). None of the five patients had rejection episodes after withdrawal of the immunosuppression; they maintained normal graft function for longer than 3 years (median, 38 months; range, 4 to 53 months). The histological findings of two grafts 64 and 32 months after weaning-off of the medication showed no evidence of chronic rejection. Conclusion: The favorable markers for successful withdrawal of immunosuppression were 1) long-term (&gt; 3 years) stable graft function, 2) no rejection for longer than 1 year after withdrawal of immunosuppression

Banff 2022 liver group meeting report: monitoring long term allograft health.

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participantsincluded hepatologists, surgeons, pathologists, immunologists and histocompatibility specialists.Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimisation and long-term structural changes.Potential revision of the rejection classification scheme to better accommodate and communicate lateT cell-mediated rejection patterns and related structural changes, such as nodular regenerativehyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression tomatch the heterogeneity of patient settings will be central to improving long-term patient survival.Such personalised therapeutics are in turn contingent on better understanding and monitoring ofallograft status within a rational decision-making approach, likely to be facilitated in implementationwith emerging decision support tools. Proposed revisions to rejection classification emerging fromthe meeting include incorporation of interface hepatitis and fibrosis staging. These will be opened toonline testing, modified accordingly and subject to consensus discussion leading up to the next Banffconference

2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology: Introduction of Antibody-Mediated Rejection

The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included