16060 Background: Prolonged ADT for men with PC increases risk of osteoporosis and fracture. Z is a potent IV bisphosphonate that can improve the bone mineral density (BMD) in patients on ADT. There are no established treatment guidelines for such patients. We propose treatment recommendations based on two recent VA studies - our main study evaluating Z for prevention of osteoporosis due to ADT, and its companion study evaluating Z for treatment of patients with pre-existing osteoporosis. Methods: The main double blind, placebo (P) controlled trial randomized 93 patients to receive Z or P q3 mos. Preplanned strata (St) included 50 patients on ADT < 1 year (St 1) and 43 patients on ADT > 1 year (St 2). Baseline BMD T score was ≥ -2.0. The companion trial enrolled 27 patients with pre-existing osteoporosis (baseline BMD score < -2.0) on an open label, single arm trial to receive Z q3 mos. for 1 year. All patients in both trials received calcium, vitamin D, & counseling on lifestyle modification. BMD was measured by DEXA scan at enrollment, 6 and 12 mos. The primary endpoint was the % change in BMD at the lumbar spine at 12 mos. Results: In the main trial, patients were matched within the St across the treatment arms with respect to age, race, BMI, and osteoporosis risk factors. In St 1, spine BMD increased 5.95% in the Z arm and decreased 3.23% in the P arm (p=0.0044). In St 2, spine BMD increased 6.08% in the Z arm and increased only 1.57% in the P arm (p=0.0005). In the companion trial, lumbar spine BMD increased an average of 5.11% (p<0.0001) compared to baseline. In both trials, Z infusion was well tolerated with few side effects. Conclusions: Zoledronic acid improves BMD in men with PC on ADT. Benefit can be seen even in patients on prolonged ADT or those with pre-existing osteoporosis. We propose the following: patients initiating ADT should be evaluated for osteoporosis risk factors and counseled on preventive lifestyle modifications. DEXA scans should be obtained at baseline and repeated annually if normal. Treatment with Z should be considered for prevention and/or treatment of osteopenia/osteoporosis in men with PC who are on ADT. Supported by a grant from Novartis Pharmaceuticals Corporation Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis

From 8 Department of Veterans Affairs Medical Centers, 296 patients with varying degrees of alcoholic liver disease were tested for hepatitis C (HCV) infection using an EIA and RIBA 2. A high frequency of positive response was observed with 13.9% reactive to both and an additional 4.4% positive only to RIBA 2 (total 18.3%). An evaluation of known risk factors (injection drug use and prior blood transfusions) failed to account for the mode of transmission in 42.6% of the HCV+ patients. The clinical severity of the liver disease and degree of liver pathology were nearly identical in HCV+ vs. HCV- patients. However, the process was accelerated in the HCV+ patients occurring at a 12.8% younger age (p< 0.0001) with a 43% increase in ALT (p=0.05). The most striking differences were observed in immune parameters. In peripheral blood, total lymphocyte counts were increased 20% (p=0.01) accompanied by a 56% increase in B cells (p=0.01) and a 35% elevation of IgG levels (p=0.0001) in HCV+ patients. T cell changes consisted of a 50% increase in CD8 cells (p=0.047). However, lymphocyte infiltration into liver was not significantly different (HCV+ vs. HCV−) for any of the subsets studied (CD4, CD8, B cells, NK cells). The combined presence of HCV and alcohol injury did not significantly increase mortality but did significantly increase the number of hospitalizations from 2.4 to 4.0 per year (p= 0.0005).

Of 288 patients with alcoholism and various stages of alcoholic hepatitis, 18.4% (53 of 288) reacted serologically for hepatitis C (HCV). An evaluation of the risk factors associated with HCV indicated that parenteral drug use, even in the distant past, increased the risk for infection 10.1-fold (p = 0.0001). Ethnicity was also a significant, independent risk factor. Minorities (i.e., African-Americans or Hispanic-Americans) had a 2.4-fold increase (p = 0.038). Prior blood transfusions, even if multiple, showed only a tendency toward increased infections (p = 0.088) in this population. An interaction between age and contact with parenteral drug users was demonstrated such that the risk of HCV infection was increased by contact with drug users. This was further increased with increasing age (p = 0.006). There was no relationship between HCV reactivity and the severity of the liver disease; however, the liver injury appeared to be accelerated since it occurred at a younger age (p = 0.0001) and was associated with more frequent hospitalizations (p = 0.0005).

Of 288 patients with alcoholism and various stages of alcoholic hepatitis, 18.4% (53 of 288) reacted serologically for hepatitis C (HCV). An evaluation of the risk factors associated with HCV indicated that parenteral drug use, even in the distant past, increased the risk for infection 10.1-fold (p = 0.0001). Ethnicity was also a significant, independent risk factor. Minorities (i.e., African-Americans or Hispanic-Americans) had a 2.4-fold increase (p = 0.038). Prior blood transfusions, even if multiple, showed only a tendency toward increased infections(p = 0.088) in this population. An interaction between age and contact with parenteral drug users was demonstrated such that the risk of HCV infection was increased by contact with drug users. This was further increased with increasing age (p = 0.006). There was no relationship between HCV reactivity and the severity of the liver disease; however, the liver injury appeared to be accelerated since it occurred at a younger age (p = 0.0001) and was associated with more frequent hospitalizations (p = 0.0005).