Faculty Bibliography

Several studies have shown a direct role of liver atrophy in the pathogenesis of thrombocytopenia of cirrhosis via reduced production of thrombopoeitin. About 181 patients listed for liver transplantation at a single transplant center were evaluated at the time of listing with laboratory tests and volumetric liver measurements using computed tomography. Expected normal liver volume was calculated using the Heinemann formula. Liver volume ratio (LVR) was calculated as actual liver volume over expected liver volume. Patients were predominantly male (70.7%), with viral hepatitis (60.2%), had a mean age of 51.8 years (SD 8.7), model for end stage liver disease (MELD) of 14 (SD 6.4), LVR of 0.95 (SD 0.3), and platelet count of 105,000/mcL (SD 66,000). Platelet count (P < 0.0001) correlated more strongly with LVR than MELD, MELD components (P = 0.27) or serum albumin (P = 0.003). Platelet count (HR 0.987, 95% CI 0.979-0.994, P = 0.001) was a strong independent predictor of mortality. Patients with platelet count < 100,000/mcL had a shorter survival (935 vs. 1396 days, P = 0.002) and higher death rate (42.2% vs. 23.6%, P = 0.01), but no different transplantation rate (36.7% vs. 33.3%, P = 0.64) compared to those with platelet count ≥ 100,000/mcL. Low platelet count corresponds to higher waiting list mortality and is a sign of advanced liver atrophy.

Until recently, it was widely accepted that patients with cirrhosis have a bleeding tendency related to the changes in the hemostatic system that occur as a consequence of the disease. However, it has now been well established that patients with cirrhosis are at risk for both bleeding and thrombotic complications. These thrombotic complications include portal vein thrombosis, deep vein thrombosis and pulmonary embolism, and coronary or cerebrovascular infarctions. Antithrombotic drugs to prevent or treat thrombotic complications in patients with cirrhosis have been used only minimally in the past due to the perceived bleeding risk. As the thrombotic complications and the necessity of antithrombotic treatment in these patients are increasingly recognized, the use of antithrombotic drugs in this population is likely increasing. Moreover, given the rising incidence of fatty liver disease and generally longer survival times of patients with chronic liver diseases, it would be reasonable to presume that some of these thrombotic complications may be increasing in incidence over time. In this review, we will outline the indications for antithrombotic treatment in patients with cirrhosis. Furthermore, we will discuss the available antithrombotic drugs and indicate possible applications, advantages, and caveats. Since for many of these drugs very little experience in patients with cirrhosis exists, these data are essential in the design of future clinical and laboratory studies on mechanisms, efficacy, and safety of the various antithrombotic strategies in these patients.

Non-selective beta-blockers have been a cornerstone of therapy for prevention of esophageal variceal bleeding in cirrhosis patients for more than two decades. When lowering the hepatic vein portal pressure gradient (HVPG) below 12 mm Hg or decreasing the pressure by 20% from baseline, these drugs are of proven benefit in reducing variceal bleeding and improving survival in this patient population. The recent work by Hendández-Gea et al., suggests that initiation of the beta-blocker nadolol in cirrhosis patients with high-risk varices can delay or prevent the first occurrence of clinically evident ascites. This finding comes with some caveats, however. The beneficial effect was only seen in patients who had an improvement by 10% or more from baseline HVPG pressure (only 51% of the treated patients in this study). This class of medications has some risk and tolerance issues, and many patients do not respond, even when the heart rate is optimally decreased. Despite this, the use of beta-blockers may be beneficial in the primary prevention of the formation of ascites and further decompensation of cirrhosis.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of disorders with a high prevalence in the industrialized world. Despite the high prevalence, the etiology and fundamental pathophysiology for the disease process is poorly understood. There is now a growing fund of knowledge suggesting that the ongoing inflammatory state associated with NAFLD leads to a low-level activation of the coagulation system. Although the data supporting this activation of the coagulation system are significant, the link with end-organ disease, mainly cardiovascular disease, is less firm and mostly epidemiological. In this review, we will explore the evidence for and against a hypercoagulable or thrombophilic state in NAFLD. We will examine possible pathophysiologic explanations and mechanisms, human epidemiologic and population-based data, and the possible therapeutic and preventative implications for treatment of thrombophilia in patients with this disease process.

BACKGROUND:Transcatheter arterial chemoembolization (TACE) improves survival in patients with unresectable hepatocellular carcinoma (HCC). Partial liver radiotherapy with modern techniques has been shown to be safe. The purpose of this study was to evaluate the survival value of external beam radiation therapy (EBRT) with concurrent chemotherapy combined with TACE. METHODS:A University of Virginia Interventional Radiology patient log was used to identify patients treated with TACE ± another modality from 1999 through 2005. During this time, 44 patients received TACE for unresectable HCC, and 7 of these received adjuvant EBRT. Univariate analysis and multivariable proportional hazards survival modeling were used to identify factors impacting survival. RESULTS:We compared 37 patients receiving TACE alone to 7 receiving TACE and EBRT (5 with concurrent capecitabine). Unadjusted mean transplant-free survival times were TACE only = 376 days (standard error [SE] = 63 days), TACE + EBRT = 879 days (SE = 100 days). EBRT, TNM stage, and MELD score were important predictors for survival on univariate analysis (p < .10). The adjusted hazard ratio for transplant or death in the TACE + EBRT group was 0.15 (0.02-0.95, p = .026). CONCLUSION/CONCLUSIONS:EBRT with concurrent chemotherapy following TACE is feasible and well tolerated with modern treatment techniques. Further research should be directed toward determining the potential overall survival benefit of adjuvant EBRT with chemotherapy following TACE for hepatocellular carcinoma.

BACKGROUND:The relative incidence of bleeding and thrombotic events and the use of blood products in hospitalized cirrhosis patients have not been widely reported. We aimed to estimate the magnitude of bleeding events and venous thrombosis in consecutive hospitalized cirrhotic patients over a finite time period and to examine the amount and indications for blood product use in cirrhosis patients admitted to a tertiary care center. RESULTS:Among patients admitted with decompensated liver disease, 34 (40%) suffered bleeding events (about one-half non-variceal) and 6 patients (7%) suffered deep venous thrombosis. In the blood product survey, 168 patients were transfused with plasma or platelets during the survey inter- vals. Liver disease patients accounted for 7.7% of the total but disproportionately consumed 32.4% (46 of 142) of the units of plasma mostly administered as prophylaxis. In contrast, cirrhosis patients received only 7 of the 53 units of platelets transfused (13.2%) during the survey intervals. CONCLUSIONS:Coagulation issues constitute a common problem in patients with liver disease. Recent advances in laboratory testing have shown that stable cirrhosis patients are relatively hypercoagulable. The result of this prospective survey among decompensated (unstable) cirrhosis patients shows that, while DVT is not uncommon, bleeding (non-variceal in one half) remains the dominant clinical problem. This situation likely sustains the common practice of plasma infusion in these patients although its use is of unproven and questionable benefit. Better clinical tools are needed to refine clinical practice in this setting.