The liver is a large highly vascularized organ with a central function in metabolic homeostasis, detoxification, and immunity. Due to its roles, the liver is frequently exposed to various insults which can cause cell death and hepatic dysfunction. Alternatively, the liver has a remarkable ability to self-repair and regenerate after injury. Liver injury and regeneration have both been linked to complex extracellular matrix (ECM) related pathways. While normal degradation of ECM components is an important feature of tissue repair and remodeling, irregular ECM turnover contributes to a variety of liver diseases. Matrix metalloproteinases (MMPs) are the main enzymes implicated in ECM degradation. MMPs not only remodel the ECM, but also regulate immune responses. In this review, we highlight some of the MMP-attributed roles in acute and chronic liver injury and emphasize the need for further experimentation to better understand their functions during hepatic physiological conditions and disease progression.

The Model for End-Stage Liver Disease (MELD) system has dramatically increased the number of recipients requiring pretransplant renal replacement therapy (RRT) prior to liver transplantation (LT). Factors affecting post-LT outcomes and the need for intraoperative RRT (IORRT) were analyzed in 500 consecutive recipients receiving pretransplant RRT, including comparisons among recipients not receiving IORRT (No-IORRT, n ¼ 401), receiving planned IORRT (Pl-IORRT, n ¼ 70), and receiving emergent, unplanned RRT after LT initiation (Em-IORRT, n ¼ 29). Despite a median MELD of 39, overall 30-day, 1-, 3-and 5-year survivals were 93%, 75%, 68% and 65%, respectively. Em-IORRT recipients had significantly more intraoperative complications (arrhythmias, postreperfusion syndrome, coagulopathy) compared with both No-IORRT and Pl-IORRT and greater 30-day graft loss (28% vs. 10%, p ¼ 0.004) and need for retransplantation (24% vs. 10%, p ¼ 0.099) compared with No-IORRT. A risk score based on multivariate predictors of IORRT accurately identified recipients with chronic (sensitivity 84%, specificity 72%, concordancestatistic [c-statistic] 0.829) and acute (sensitivity 93%, specificity 61%, c-statistic 0.776) liver failure requiring IORRT. In this largest experience of LT in recipients receiving RRT, we report excellent survival and propose a practical model that accurately identifies recipients who may benefit from IORRT. For this select group, timely initiation of IORRT reduces intraoperative complications and improves posttransplant outcomes.

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In patients with PRA levels >80%, a higher HLA MM is associated with higher incidence of acute rejection. Acute rejection was the only significant variable affecting graft loss. We found a trend toward more CMV infections and worse graft outcomes with higher MM. Closer HLA matching and immunologic monitoring needs to be considered to improve graft outcomes among sensitized recipients.

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