ABSTRACT
Portal vein thromboses (PVTs) are associated with hepatic decompensation, worse survival, and worse liver transplant outcomes. We evaluated the impact of anticoagulation (AC) and transjugular intrahepatic portosystemic shunting (TIPS) on recanalization and mortality in patients with cirrhosis and PVT. Systematic search of electronic databases was performed. Clinical trials and observational studies that evaluated primary outcomes of recanalization and survival in patients with cirrhosis having PVT treated with AC or TIPS were included. Risk of bias was assessed. Summary odds ratios (ORs) for pooled data from the included studies were generated using a random effects model. A total of 505 studies were screened for inclusion. After review, 7 studies were ultimately included. Data from 327 patients in total were evaluated. Overall, treatment with either AC or TIPS resulted in partial or complete recanalization (OR: 4.56 [95% confidence interval, CI: 2.46-8.47]) but did not significantly impact mortality (OR: 0.57 [95% CI: 0.21-1.57]). The summary OR of AC for recanalization was 6.00 (95% CI: 2.38-15.07). The summary OR of TIPS for recanalization was 3.80 (95% CI: 1.47-9.83). The summary OR of mortality in patients treated with AC for PVT was 0.28 (95% CI: 0.08-0.95). The mortality summary OR was 1.10 (95% CI 0.23-5.16) in patients who underwent TIPS. There was insufficient data to assess complications such as hepatic encephalopathy or bleeding. Both AC and TIPS have a significant effect on recanalization. Anticoagulation appears to have a protective effect on mortality that is not seen with TIPS. More studies with control groups are need.
ABSTRACT
UNLABELLED: The liver changes with age, leading to an impaired ability to respond to hepatic insults and increased incidence of liver disease in the elderly. Therefore, there is critical need for rapid model systems to study aging-related liver changes. One potential opportunity is murine models of human progerias or diseases of accelerated aging. Ercc1(-/Δ) mice model a rare human progeroid syndrome caused by inherited defects in DNA repair. To determine whether hepatic changes that occur with normal aging occur prematurely in Ercc1(-/Δ) mice, we systematically compared liver from 5-month-old progeroid Ercc1(-/Δ) mice to old (24-36-month-old) wild-type (WT) mice. Both displayed areas of necrosis, foci of hepatocellular degeneration, and acute inflammation. Loss of hepatic architecture, fibrosis, steatosis, pseudocapillarization, and anisokaryosis were more dramatic in Ercc1(-/Δ) mice than in old WT mice. Liver enzymes were significantly elevated in serum of Ercc1(-/Δ) mice and old WT mice, whereas albumin was reduced, demonstrating liver damage and dysfunction. The regenerative capacity of Ercc1(-/Δ) liver after partial hepatectomy was significantly reduced. There was evidence of increased oxidative damage in Ercc1(-/Δ) and old WT liver, including lipofuscin, lipid hydroperoxides and acrolein, as well as increased hepatocellular senescence. There was a highly significant correlation in genome-wide transcriptional changes between old WT and 16-week-old, but not 5-week-old, Ercc1(-/Δ) mice, emphasizing that the Ercc1(-/Δ) mice acquire an aging profile in early adulthood. CONCLUSION: There are strong functional, regulatory, and histopathological parallels between accelerated aging driven by a DNA repair defect and normal aging. This supports a role for DNA damage in driving aging and validates a murine model for rapidly testing hypotheses about causes and treatment for aging-related hepatic changes.
