Brain Integrity Changes Underlying Cognitive and Functional Recovery Postliver Transplant Continue to Evolve Over 1 Year.

BACKGROUND: There is evidence of brain recovery on brain magnetic resonance imaging (MRI) early postliver transplant (LT), but the longer-term impact is unclear. The aim of this study was to determine the change in brain MRI parameters, cognition, and health-related quality of life (HRQOL) between 6 and 12 months post-LT. METHODS: Listed cirrhotics underwent cognitive, HRQOL and brain MRI pre-LT, 6 months (post-LT1), and 1-year (post-LT2) post-LT. Assessment of MRI changes between visits was performed for ammonia-associated metabolite changes using magnetic resonance spectroscopy, white matter changes using tract-based spatial statistics analysis on diffusion tensor imaging data and grey matter changes using voxel-based morphometry analysis on 3D high resolution T1-weighted images. RESULTS: Forty-five patients were included, of which 23 were tested at all visits. Cognitive and HRQOL scores improved between all visits compared with pre-LT values. This trend continued on magnetic resonance spectroscopy with reduced glutamine + glutamate and higher myoinositol, choline between pre-LT/post-LT1 but lower degrees of improvement between post-LT1/post-LT2. On diffusion tensor imaging, mean diffusivity, linear diffusivity and mode of anisotropy continued to increase in the posterior internal capsule at both post-LT visits. On voxel-based morphometry, a continued increase was seen in basal ganglia grey matter between both post-LT visits was seen. CONCLUSIONS: HRQOL and cognition continue to improve compared with pre-LT values up to 1 year post-LT, although the rate of improvement slows down after 6 months. Grey matter increase is steady over time at 1 year although changes in ammonia-related metabolites and white matter integrity improve at a slower pace at 1 year post-LT.

Thromboelastography does not predict outcome in different etiologies of cirrhosis.

BACKGROUND: New laboratory tests that measure global hemostasis indicate generally preserved hemostatic function in patients with cirrhosis. It is not known whether normal hemostatic function is maintained across various subsets of patients. OBJECTIVES: In the present study, we investigated clot generation and clot lysis kinetics in a large group of patients with different etiologies of disease. PATIENTS/METHODS: Blood samples of 270 patients with cirrhosis were studied using thromboelastography (TEG), which measures the dynamic and physical properties of clot formation and lysis in whole blood. TEG parameters of different subsets of the patient population were compared. Correlations with routine laboratory tests as well as clinical outcomes were explored. RESULTS: Overall, TEG parameters were normal and similar between underlying disease etiologies. A proportion of subjects showed hypocoagulable features, with the exception of patients with cholestatic cirrhosis in whom TEG readings showed hypercoagulable features. In all groups, K-time, α-Angle, and MA correlated well with platelet counts and fibrinogen plasma levels. After a mean follow-up of 2 years and 11 months, 31 patients had experienced a bleeding event, 8 had developed thrombosis, and 173 patients (64%) had undergone liver transplantation and/or had died. TEG baseline parameters were similar between patients subdivided according to outcome. CONCLUSIONS: TEG parameters reflected generally preserved function of the hemostatic system in patients with cirrhosis, with hypo- and hypercoagulable features in subsets of patients with specific underlying disease etiologies. Abnormalities in TEG parameters did however not predict bleeding, thrombosis, or risk of liver transplantation and/or death.

Hepatitis C virus recurrence after liver transplantation: biomarkers of disease and fibrosis progression.

End-stage liver disease due to hepatitis C virus infection (HCV) is the principal indication for liver transplantation. In the USA, over a third of available liver allografts are transplanted into recipients with chronic HCV infection. Reinfection of the graft is universal, but the impact of reinfection on short- and long-term liver function is highly variable. HCV infection in liver transplantation recipients is characterized by an accelerated fibrogenesis, with approximately a third of patients developing cirrhosis within 5 years of follow-up. HCV is associated with decreased patient and graft survival when compared with other indications of orthotopic liver transplantation. The mechanisms responsible for the accelerated liver damage in HCV-infected orthotopic liver transplantation recipients remain largely unknown.

Adult living donor versus deceased donor liver transplantation: a 10-year prospective single center experience.

It has been 4 years since the first, long-term (> 3 years) prospective comparison of adult-to-adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) was reported. In this follow up, prospective, IRB approved, 10-year comparison of A2ALLTx to ADDLTx we expand on our initial observations. This data includes: age, gender, ethnicity, primary liver disease, waiting time, pretransplant CTP/MELD score, cold ischemia time (CIT), perioperative mortality, acute and chronic rejection, graft and patient survival, charges and post-transplant complications. In 10 years, 465 ADDLTx (81.3%) and 107 A2ALLTx (18.7%) were performed at VCUHS. Hepatitis C virus (HCV) was the most common reason for transplantation in both groups (54.5% vs. 48.2%). Data regarding overall patient and graft survival and retransplantation rates were similar. Comparison of patient/graft survivals, retransplantation rates in patients with and without HCV were not statistically different. A2ALLTx patients had less acute rejection (9.6% vs. 21.7%) and more biliary complications (27.1% vs. 17.6%). In conclusion, A2ALLTx is as durable a liver replacement technique as the ADDLTx. Patients with A2ALLTx were younger, had lower MELD scores, less acute rejection and similar histological HCV recurrence. Biliary complications were more common in A2ALLTx but were not associated with increased graft loss compared to ADDLTx.

Surveillance for hepatocellular carcinoma in patients with cirrhosis improves outcome.

OBJECTIVE: Liver transplantation has become an effective treatment for cirrhotic patients with early-stage hepatocellular carcinoma. We hypothesized that the quality of surveillance for hepatocellular carcinoma influences prognosis by affecting access to liver transplantation. METHODS: A total of 269 patients with cirrhosis and hepatocellular carcinoma were retrospectively categorized into 3 groups according to quality of surveillance: standard-of-care (n=172) (group 1); substandard surveillance (n=48) (group 2); and absence of surveillance in patients not recognized to be cirrhotic (n=59) (group 3). RESULTS: Three-year survival in the 60 patients who underwent liver transplantation was 81% versus 12% for patients who did not undergo transplantation (P<.001). The percentages of patients who underwent transplantation according to tumor stage at diagnosis (T1, T2, T3, and T4) were 58%, 35%, 10%, and 1%, respectively. Hepatocellular carcinoma was diagnosed at stages 1 and 2 in 70% of patients in group 1, 37% of patients in group 2, and only 18% of patients in group 3 (P <.001). Liver transplantation was performed in 32% of patients in group 1, 13% of patients in group 2, and 7% of patients in group 3 (P<.001). Three-year survival from cancer diagnosis in patients in group 3 (12%) was significantly worse than in patients in group 1 (39%) or group 2 (27%) (each P<.05). Eighty percent of patients in group 3 had subtle abnormalities of cirrhosis on routine laboratory tests. CONCLUSION: The quality of surveillance has a direct impact on hepatocellular carcinoma stage at diagnosis, access to liver transplantation, and survival.

Adult living donor versus deceased donor liver transplantation: a 6-year single center experience.

No long-term (>3 years) prospective comparison of adult-to-adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) has been reported. This is a prospective, IRB approved, 6-year comparison of A2ALLTx to ADDLTx. Data include: age, gender, ethnicity, primary liver disease, waiting time, pretransplant CTP/MELD score, cold ischemia time (CIT), perioperative mortality, acute and chronic rejection, graft and patient survival, charges and post-transplant complications. In 6 years, 202 ADDLTx (74.5%) and 69 A2ALLTx (25.5%) were performed at VCUHS. Hepatitis C virus (HCV) was the most common reason for transplantation in both groups (48.1% vs. 42%). Data regarding overall patient and graft survival, monetary charges and retransplantation rates were similar. Comparison of patient/graft survivals, retransplantation rates in patients with and without HCV were not statistically different. A2ALLTx patients had less acute rejection (11.5% vs. 23.9%) and more biliary complications (26.1% vs. 11.4%). Overall, A2ALLTx is as durable a liver replacement technique as the ADDLTx. Patients with A2ALLTx were younger, had lower MELD scores, less acute rejection and similar histological HCV recurrence. Biliary complications were more common in A2ALLTx but were not associated with increased graft loss compared to ADDLTx.