Faculty Bibliography

Patients with chronic or acute liver failure frequently show profound abnormalities in their hemostatic system. Whereas routine laboratory tests of hemostasis suggest these hemostatic alterations result in a bleeding diathesis, accumulating evidence from both clinical and laboratory studies suggest that the situation is more complex. The average patient with liver failure may be in hemostatic balance despite prolonged routine coagulation tests, since both pro- and antihemostatic factors are affected, the latter of which are not well reflected in routine coagulation testing. However, this balance may easily tip towards a hypo- or hypercoagulable situation. Indeed, patients with liver disease may encounter both hemostasis-related bleeding episodes as well as thrombotic events. During the 3rd International Symposium on Coagulopathy and Liver disease, held in Groningen, The Netherlands (18-19 September 2009), a multidisciplinary panel of experts critically reviewed the current data concerning pathophysiology and clinical consequences of hemostatic disorders in patients with liver disease. Highlights of this symposium are summarized in this review.

The Model for End-Stage Liver Disease system has given priority on the liver transplant waiting list to candidates with renal failure. This study determined the predictors of spontaneous recovery of renal function after transplantation in 1041 liver transplant recipients on renal replacement therapy (RRT) at the time of transplant (from February 2002 to January 2007). Data from these patients were obtained from the US Organ Procurement and Transplantation Network and US Renal Data System databases. Univariate and multivariate survival models were constructed along with multivariate logistic regression models to find independent predictors of spontaneous renal recovery. Seven hundred seven recipients (67.9%) had spontaneous recovery of renal function after liver transplantation. Those recovering spontaneously had a significantly shorter course of RRT in the pretransplant time period (15.6 versus 36.6 days, P < 0.001). Recovery of renal function was observed in 70.8% and 11.5% of recipients on RRT for less than 30 days and more than 90 days, respectively. Other statistically significant pretransplant variables independently associated with recovery of renal function included recipient age, recipient pretransplant diabetes, and donor age. In conclusion, the duration of pretransplant RRT is highly predictive of spontaneous renal recovery post-transplant. Liver transplant candidates requiring less than 30 days of pretransplant RRT are likely to spontaneously recover renal function after liver transplantation, whereas those on RRT for more than 90 days are not.

INTRODUCTION/BACKGROUND:Epidemiological studies indicate that nonalcoholic steatohepatitis (NASH) is a common cause of cirrhosis described as 'cryptogenic'. To address this from a histological perspective and to examine the significance of residual histological findings as an indication of prior NASH, we looked back at biopsies in patients who presented with cirrhosis without sufficient histological features to diagnose NASH but who had prior histologically confirmed non-cirrhotic NASH. METHODS:Seven patients were identified with biopsy pairs showing non-specific (cryptogenic) cirrhosis in the latest specimen and a prior biopsy showing non-cirrhotic NASH. Using an expanded NASH-CRN system scored blindly by light microscopy, we compared the early and late biopsies to each other and to a cohort of 13 patients with cirrhosis due to hepatitis C without co-existing metabolic syndrome. RESULTS:Macrosteatosis, although uniformly present in the non-cirrhotic NASH specimens, declined in the late stage cirrhotic NASH specimens and was not useful in the distinction of late cirrhotic NASH from cirrhotic viral hepatitis. However, the presence of ballooned cells, Mallory-Denk bodies, and megamitochondria and the absence of apoptotic bodies were significantly different in late stage cirrhotic NASH compared to cirrhosis due to hepatitis C. CONCLUSIONS:Histologically advanced NASH presenting as non-specific or cryptogenic cirrhosis has residual changes which are consistent with prior steatohepatitis but which differ from cirrhosis due to hepatitis C. These results provide histological support for the more established epidemiological associations of NASH with cryptogenic cirrhosis and for criteria used in several proposed classifications of cryptogenic cirrhosis.