Association of IFNL3 and IFNL4 polymorphisms with liver-related mortality in a multiracial cohort of HIV/HCV-coinfected women.

African Americans coinfected with HIV and hepatitis C virus (HCV) have lower liver-related mortality than Caucasians and Hispanics. While genetic polymorphisms near the IFNL3 and IFNL4 genes explain a significant fraction of racial differences in several HCV-related outcomes, the impact of these variants on liver-related mortality has not been investigated. We conducted a cohort study of HIV/HCV-coinfected women followed in the multicentre, NIH-funded Women's Interagency HIV Study (WIHS) to investigate whether 10 polymorphisms spanning the IFN-λ region were associated with liver-related mortality by dominant, recessive or additive genetic models. We also considered whether these polymorphisms contributed to previously reported differences in liver-related death by race/ethnicity (ascertained by self-report and ancestry informative markers). Among 794 coinfected women, there were 471 deaths including 55 liver-related deaths during up to 18 years of follow-up. On adjusted analysis, rs12980275 GG genotype compared to AG+AA hazards ratios [(HR) 0.36, 95% CI 0.14-0.90, P = 0.029] and rs8109886 AA genotype compared to CC+AC (HR 0.67, 95% CI 0.45-0.99, P = 0.047) were most strongly associated with liver-related death although these associations were no longer significant after adjusting for race/ethnicity (HR 0.41, 95% CI 0.16-1.04, P = 0.060 and HR 0.78, 95% CI 0.51-1.19, P = 0.25, respectively). African American women had persistently lower liver-related death independent of IFN-λ variants (HRs ≤ 0.44, P values ≤ 0.04). The lower risk of death among African American HIV/HCV-coinfected women is not explained by genetic variation in the IFN-λ region suggesting, that other genetic, behavioural and/or environmental factors may contribute to racial/ethnic differences in liver-related mortality.

Differences in hepatitis C virus prevalence and clearance by mode of acquisition among men who have sex with men.

We examined the characteristics associated with hepatitis C virus (HCV) antibody (anti-HCV) prevalence and HCV clearance between injection drug using (IDU) and non-IDU men who have sex with men (MSM). Stored serum and plasma samples were tested for anti-HCV and HCV RNA to determine the HCV status of 6925 MSM at enrolment into the Multicentre AIDS Cohort Study (MACS). Prevalence and clearance ratios were calculated to determine the characteristics associated with HCV prevalence and clearance. Multivariable analyses were performed using Poisson regression methods with robust variance estimation. Anti-HCV prevalence was significantly higher among IDU than among non-IDU MSM (42.9% vs 4.0%), while clearance was significantly lower among IDU MSM (11.5% vs 34.5% among non-IDU MSM). HIV infection, Black race, and older age were independently associated with higher prevalence in both groups, while smoking, transfusion history, and syphilis were significantly associated with prevalence only among non-IDU MSM. The rs12979860-C/C genotype was the only characteristic independently associated with HCV clearance in both groups, but the effects of both rs12979860-C/C genotype [clearance ratio (CR) = 4.16 IDUs vs 1.71 non-IDUs; P = 0.03] and HBsAg positivity (CR = 5.06 IDUs vs 1.62 non-IDUs; P = 0.03) were significantly larger among IDU MSM. HIV infection was independently associated with lower HCV clearance only among non-IDU MSM (CR = 0.59, 95% CI = 0.40-0.87). IDU MSM have higher anti-HCV prevalence and lower HCV clearance than non-IDU MSM. Differences in the factors associated with HCV clearance suggest that the mechanisms driving the response to HCV may differ according to the mode of acquisition.

Incident hepatitis C virus in women with human immunodeficiency virus infection.

Individuals infected with human immunodeficiency virus type 1 (HIV-1) are frequently coinfected with hepatitis C virus (HCV). Acute HCV infection is often asymptomatic and poorly understood. We conducted a historical prospective study of HCV antibody and viremia in plasma samples obtained during 1994-1999 from a cohort of initially HIV-1-infected, HCV-uninfected women and from HIV-1-HCV-uninfected women. Twenty-two (1.5%) of 1517 experienced seroconversion. Of these, 14 (64%) truly acquired a new infection as assessed by enzyme immunoassay response and new-onset viremia. The incidence rate in HIV-1-infected women was 2.7 cases per 1000 person-years; it was 3.3 cases per 1000 person-years in HIV-1-seronegative women (relative risk, 1.21; P=.75). Acquisition of HCV was associated with any history of drug use (P<.01). Five of 12 viremic, seroconverting individuals cleared viremia. Incident HCV infection among HIV-1-infected and HIV-1-uninfected women was low. It was linked to drug use and commonly resolved.

Predicting clinical and economic outcomes after liver transplantation using the Mayo primary sclerosing cholangitis model and Child-Pugh score. National Institutes of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database Group.

Issues in the selection and timing of liver transplantation for primary sclerosing cholangitis (PSC) remain controversial. Although the Child-Pugh classification (CP) score and Mayo PSC model have similar abilities to estimate pretransplantation survival, a comparison of these 2 scores in predicting survival after liver transplantation has not been conducted. The aim of this study is to compare the Mayo PSC model and CP score in predicting patient survival and related economic outcomes after liver transplantation. Data from 128 patients with PSC, identified from the NIDDK database, were used to calculate patient-specific Mayo PSC and CP scores before transplantation. Levels reflecting a poor outcome were defined a priori. Receiver operating characteristic (ROC) curves and regression methods (Cox proportional hazards and linear regression models) were used to assess the relationship between these 2 scores and 5 post liver transplantation outcome measures. CP score was found to be a significantly (P <.05) better predictor of death 4 months or less after liver transplantation than: (a) length of hospital stay >21 days (or death before discharge) and (b) resource utilization >200,000 units (measured by area under the ROC curve). The Cox model identified statistically significant (P <.05) associations between CP score and each outcome after adjusting for the Mayo PSC risk score. Similar results were not observed for the Mayo PSC model when adjusted for CP score. Among patients with PSC undergoing liver transplantation, CP score was a better overall predictor of both survival and economic resource utilization compared with the Mayo PSC model.

The economic impact of cytomegalovirus infection after liver transplantation.

BACKGROUND: We studied the economic impact of cytomegalovirus (CMV) disease and its effective reduction with antiviral prophylaxis in liver transplant recipients. METHOD: Analysis of institutional charge data accumulated during a prospective, randomized, controlled trial comparing oral acyclovir 800 mg four times daily for 120 days (ACV) and intravenous ganciclovir 5 mg/kg every 12 h for 14 days followed by ACV for 106 days (GCV) was performed. RESULTS: Liver transplant recipients who developed CMV disease had significantly higher charges (median: $148,300) than those who developed asymptomatic CMV infection ($119,600) or experienced no CMV infection ($114,100) (P<0.01). A multiple linear regression analysis indicated that CMV disease is associated with a 49% increase in charges, independent of other factors influencing increased hospitalization charges. In CMV-seronegative patients who received a CMV-seropositive donor organ, GCV prophylaxis was associated with a significant reduction in charges, as compared to ACV prophylaxis ($113,900 vs. $153,300, respectively; P=0.02). CONCLUSIONS: CMV disease is an independent risk factor for increased resource utilization associated with liver transplantation. The use of an effective prophylactic antiviral regimen provides savings in health care resources, particularly in patients at high risk for developing CMV disease.

A brief cognitive screening battery for dementia in the community.

Screening community samples for dementia often necessitates administering a cognitive test battery by trained personnel. Because diagnostic examinations are expensive, a useful screening battery must be highly specific in addition to having high sensitivity. The Monogahela Valley Independent Elders Survey (MoVIES) includes a random sample of community-dwelling participants at least 65 years of age who were screened using an extensive test battery of cognitive tests that required over 30 min to administer. Classification and Regression Trees (CART) was used to identify a subset of the battery that could be administered quickly and which maintained high levels of sensitivity and specificity for a diagnosis of dementia. The Short and Sweet Screening Instrument (SASSI) is a brief battery consisting of three standard cognitive tests that can be administered in approximately 10 min. Compared to the full battery, it was more sensitive (94% vs. 90%) and had comparable specificity (91% vs. 92%) for dementia in this sample.

Analysis of the reversibility of chronic liver allograft rejection implications for a staging schema.

In contrast to all other vascularized organ allografts, chronic rejection (CR) of the liver is potentially reversible. We therefore studied demographic, perioperative, biochemical, and histologic features associated with reversibility or progression to graft failure. Using very stringent clinical and histological criteria, we identified a subgroup of 23 of 916 patients receiving primary liver allografts with CR from the Liver Transplantation Database. Of these, 13 experienced graft failure as a result of CR, and 10 patients recovered to normal histology or liver injury test results. Male-to-female sex mismatch (p = 0.07), younger recipient age (p = 0.09), younger donor age (p = 0.06), white-to-white race match (p = 0.09), primary diagnosis of biliary atresia (p = 0.02), and cold ischemia time of more than 12 hours (p = 0.02) were associated with graft failure. Patients who eventually recovered from CR were more likely to have acute rejection within the first 2 weeks (70% vs 23%; p = 0.04), had a higher number of acute rejection episodes (p = 0.08), and were more likely to have been treated with OKT3 (90% vs 46%, p = 0.07). Although overlap existed in the histopathologic findings between the patients whose grafts failed and those who recovered, those patients who developed bile duct loss in more than 50% of the portal tracts (p < 0.01), severe (bridging) perivenular fibrosis (p = 0.05), and the presence of foam cell clusters (p = 0.06) were more likely to require retransplantation. In contrast to other solid organ allografts, CR of the liver is not an irreversible process. These findings can be used to understand the evolution of CR and to design a biologically correct and clinically relevant staging system.

Impact of immunosuppression and acute rejection on recurrence of hepatitis C: results of the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.

Whereas the impact of early (first 6 postoperative weeks) acute cellular rejection on patient survival among liver transplant recipients as a whole has been reported to be favorable, we hypothesized treatment for acute cellular rejection may have differing impacts on patient and graft survival in hepatitis C virus (HCV)-infected and HCV-negative transplant recipients. We studied the impact of immunosuppression and rejection on patient and graft survival among the 166 HCV-infected and 602 HCV-negative transplant recipients enrolled onto the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database. All data were collected prospectively. The association of early acute cellular rejection with mortality was determined using a Cox proportional hazards model with a time-dependent covariate. Median follow-up was 5.0 years for HCV-infected and 5.2 years for HCV-negative transplant recipients. HCV-infected transplant recipients experienced similar frequencies of acute cellular and steroid-resistant rejection as patients undergoing liver transplantation for most other indications. The mortality risk was significantly increased (relative risk = 2.4; P =.03) for HCV-infected transplant recipients who developed early acute cellular rejection compared with HCV-negative transplant recipients. None of the HCV-infected transplant recipients developed allograft failure secondary to chronic rejection. The choice of calcineurin inhibitor did not affect posttransplantation outcomes. Early acute cellular rejection occurs at similar frequencies in HCV-infected and HCV-negative transplant recipients. Although an episode of early acute cellular rejection is associated with a lower cumulative mortality among HCV-negative transplant recipients, the opposite is true for HCV-infected transplant recipients, who experience an increased risk for mortality after an episode of early acute cellular rejection. The adverse impact of early acute cellular rejection on patient survival should be considered in developing primary immunosuppression and acute cellular rejection treatment protocols for HCV-infected transplant recipients.

Development of an activities of daily living scale to screen for dementia in an illiterate rural older population in India.

OBJECTIVE: to develop a measure of activities of daily living appropriate for use in assessing the presence of dementia in illiterate rural elderly people in India. DESIGN: identification of relevant items, pre-testing of items and refinement of administrative procedures and scoring in four successive groups of 30 subjects each, pilot testing in a group of 100 subjects comparable to those for whom the measure is intended, administration to a representative sample of 387 people aged 55 and older, and assessment of the reliability of the final measure. SETTING AND SUBJECTS: age-stratified random sample of older men and women in rural areas of Ballabgarh, Northern India. RESULTS: the original pool of 35 items covering mobility, instrumental and personal care activities was reduced to an 11-item unidimensional scale (to which an additional item on mobility was added) with internal consistency (Cronbach's alpha)=0.82, perfect inter- and intra-rater reliability, test-retest reliability (intraclass correlation)=0.82 (any disability) and 0.92 (unable to perform for 'mental' reasons). Women, older subjects, the totally illiterate and subjects with poorer cognitive function performed significantly more poorly (P < or = 0.02 for all). PRODUCT: a brief, reliable and valid activities of daily living measure, with norms, which is appropriate for use in assessing dementia in illiterate rural elderly people in India.

Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome.

Hepatic allograft rejection remains an important problem following liver transplantation, and, indeed, complications related to the administration of immunosuppressive therapy remain a predominant cause of posttransplantation morbidity and mortality. The Liver Transplantation Database (LTD) was used to study a cohort of 762 consecutive adult liver transplantation recipients and determined the incidence, timing, and risk factors for acute rejection. We also evaluated the impact of histological severity of rejection on the need for additional immunosuppressive therapy and on patient and graft survival. Four hundred ninety (64%) of the 762 adult liver transplantation recipients developed at least one episode of rejection during a median follow-up period of 1,042 days (range, 336-1,896 days), most of which occurred during the first 6 weeks after transplantation. Multivariate analysis revealed that recipient age, serum creatinine, aspartate transaminase (AST) level, presence of edema, donor/recipient HLA-DR mismatch, cold ischemic time, and donor age were independently associated with the time to acute rejection. An interesting observation was that the histological severity of rejection was an important prognosticator: the use of antilymphocyte preparations was higher, and the time to death or retransplantation was shorter, for patients with severe rejection. Findings from this study will assist in decision-making for the use of immunosuppressive regimens and call into question whether complete elimination of all rejection or alloreactivity is a desirable goal in liver transplantation.

Predictors of patient and graft survival following liver transplantation for hepatitis C.

End-stage liver disease secondary to hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the United States. Recurrence of HCV infection is nearly universal. We studied the patients enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database to determine whether pretransplantation patient or donor variables could identify a subset of HCV-infected recipients with poor patient survival. Between April 15, 1990, and June 30, 1994, 166 HCV-infected and 509 HCV-negative patients underwent liver transplantation at the participating institutions. Median follow-up was 5.0 years for HCV-infected and 5.2 years for HCV-negative recipients. Pretransplantation donor and recipient characteristics, and patient and graft survival, were prospectively collected and compared. Cumulative patient survival for HCV-infected recipients was similar to that of recipients transplanted for chronic non-B-C hepatitis, or alcoholic and metabolic liver disease, better than that of patients transplanted for malignancy or hepatitis B (P = .02 and P = .003, respectively), and significantly worse than that of patients transplanted for cholestatic liver disease (P = .001). Recipients who had a pretransplantation HCV-RNA titer of > or = 1 x 10(6) vEq/mL had a cumulative 5-year survival of 57% versus 84% for those with HCV-RNA titers of < 1 x 10(6) vEq/mL (P = .0001). Patient and graft survival did not vary with recipient gender, HCV genotype, or induction immunosuppression regimen among the HCV-infected recipients. While long-term patient and graft survival following liver transplantation for end-stage liver disease secondary to HCV are generally comparable with that of most other indications, higher pretransplantation HCV-RNA titers are strongly associated with poor survival among HCV-infected recipients.

Effects of literacy and education on measures of word fluency.

As part of a cross-national study of dementia epidemiology, two types of verbal fluency tasks were administered to three groups of subjects, varying in level of literacy and education, recruited from the rural district of Ballabgarh in northern India. Subjects were asked to list items in a given semantic category (animals; fruits) or words beginning with a given sound (the phonemes /p/ and /s/) the latter being a minor modification of the more familiar initial letter fluency task in view of the high prevalence of illiteracy in Ballabgarh. Analysis of variance revealed main effects of education and task with a task by education interaction such that education had a greater effect on initial sound fluency than on category fluency. The results are discussed in terms of their implication for the design of cross-cultural studies and the evidence that the ability to segment speech into phonemic units is dependent on literacy.

Chronic liver allograft rejection: a National Institute of Diabetes and Digestive and Kidney Diseases interinstitutional study analyzing the reliability of current criteria and proposal of an expanded definition. National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.

A study was conducted to assess the inter and intrarater agreement for the histopathologic features and diagnosis of chronic rejection (CR) and several other important causes of late liver allograft dysfunction. On two occasions, five pathologists, experienced with liver transplantation, reviewed a set of 49 slides representing a range of diagnoses, without knowledge of the clinical history or liver injury test results. The readings were correlated with the original histopathologic diagnosis, liver injury tests, and clinicopathologic follow-up. Assessment of biopsy adequacy (kappa = 0.69) and portal tract counts (kappa = 0.79) showed good to excellent intrarater agreement, whereas interrater agreement for these variables was moderate to good, respectively (kappa = 0.44 and 0.65). Likewise, the intrarater agreement for the diagnosis of CR (kappa = 0.68), hepatitis (kappa = 0.77), and obstructive cholangiopathy (kappa = 0.55) showed good to excellent agreement, whereas the interrater agreement for these same diagnoses ranged from fair to good (kappa = 0.58, 0.46, and 0.25, respectively). In 18 specimens, there was a near unanimous diagnosis of CR across both readings. These biopsies were obtained at a median of 7.1 months (range, 42 days to 4.9 years) after transplantation, and the average number of portal tracts was 8.4 (range, 4-15). Interestingly, only 13 of these 18 specimens showed bile duct loss in >50% of the portal triads; the remaining cases showed atrophy/pyknosis of the biliary epithelium in a majority of small bile ducts. Clinicopathologic correlation showed that these 18 biopsies were obtained from 16 grafts from 15 patients, 14 of whom ultimately required retransplantation or died of or with CR, whereas two of the grafts/patients recovered. A high rate of sensitivity (92%) and a somewhat lower, but acceptable, rate of specificity (71% to 80%) was found for the diagnosis of CR. Chronic rejection and other causes of late liver allograft dysfunction can be diagnosed reliably by a group of pathologists experienced with liver transplantation, and the diagnosis of CR correlates with clinical course and liver function abnormalities. Expanded criteria for the diagnosis of CR are presented, and potential problem areas for practicing pathologists are discussed.

Liver transplantation in the United States from 1987-1998: updated results from the Pitt-UNOS Liver Transplant Registry.

CENTERS: Between 1988-1997, the total number of liver transplantations performed in the US more than doubled from 1,713-4,158, and the number of centers performing liver transplantations increased from 59-107. In recent years, the yearly net gain in the number of operating centers has slowed, and the differences in LT volume across centers has remained stable. OUTCOMES: During the first year following transplantation, patient survival was approximately the same for adults and children, while retransplantation-free survival was poorest among children. Thereafter, survival declined more rapidly among adults than among children. SURVIVAL AMONG PEDIATRIC RECIPIENTS: The estimated cumulative probability of a pediatric recipient surviving for 10 years following transplantation was .80, and surviving for 10 years without retransplantation was .59. In general, few deaths or retransplantations were observed more than 4 years after the initial transplantation. Factors independently associated with patient and retransplantation-free survival among children were year of transplantation, recipient age, being on life support while awaiting transplantation, primary liver disease, serum creatinine, total bilirubin, donor age, donor race, and warm ischemic time. Recipient race, a multi-organ transplant procedure, and serum albumin level were significantly associated with patient survival only. The use of a reduced-size or split liver for transplantation in children was independently associated with retransplantation-free survival, but not with patient survival. SURVIVAL AMONG ADULT RECIPIENTS: The estimated cumulative probability of an adult recipient surviving for 10 years following transplantation was .61, and surviving for 10 years without retransplantation was .46 with the median retransplantation-free survival time estimated at 9.2 years. Factors independently associated with patient and retransplantation-free survival among adults were year of transplantation, recipient age, recipient race, recipient location awaiting transplantation, primary liver disease, serum creatinine and albumin levels, hepatitis B surface antigen status, donor age, donor anti-CMV status, warm ischemic time, sex match, pretransplant ventilator or inotrope use, and recipient anti-HCV status. Pre-transplant bilirubin level, a multi-organ transplant procedure, and the finding of an incidental tumor were significantly associated with patient survival; and donor race, ABO match, and uncontrolled variceal bleeding were associated with retransplantation-free survival.

Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.

BACKGROUND & AIMS: Organ donors are a potential source of transmissible disease after transplantation. The aim of this study was to evaluate the risk of acquiring hepatitis B among transplantation recipients of livers from donors without serum hepatitis B surface antigen (HBsAg) but with antibody to hepatitis B core antigen (anti-HBc). METHODS: The transplantation experience of four centers between 1989 and 1994 was reviewed. Recipients of livers from 674 donors were considered informative for hepatitis B virus transmission. RESULTS: Hepatitis B developed in 18 of 23 recipients of livers from anti-HBc-positive donors (78%) compared with only 3 of 651 recipients of anti-HBc-negative donor livers (0.5%) (P < 0.0001). HBsAg persisted in all recipients with donor-related hepatitis B. Liver histology showed chronic hepatitis of moderate severity in 2 of 13 recipients at 1 year and 5 of 8 recipients between 1.6 and 4.5 years from transplantation. Liver transplantation from an anti-HBc-positive donor was associated with decreased 4-year survival (adjusted mortality hazard ratio of 2.4; 95% confidence interval, 1.4-4.0). CONCLUSIONS: De novo posttransplantation hepatitis B infection occurs at a high rate in recipients of donors with anti-HBc. Transmission of hepatitis B through transplantation suggests that the virus may persist in the liver despite serological resolution of infection.

The relationship between self-rated health and depressive symptoms in an epidemiological sample of community-dwelling older adults.

OBJECTIVE: To confirm the association between depression and self-rated general health, independent of demographics, functional disability, physical illness burden, and health services utilization. DESIGN: Logistic regression analyses of data obtained in a cross-sectional epidemiological survey. SETTING: The mid-Monongahela Valley, a rural, nonfarm, low SES community. PARTICIPANTS: Random sample of 880 subjects aged 65 and older. MEASUREMENTS: The dependent variable was self-rated overall health, categorized as excellent, good, fair, or poor. The independent variables were demographics (age, gender, education), number of depressive symptoms, number of impaired instrumental activities of daily living (IADLs), measures of physical illness burden (individual medical conditions, number of affected organ systems or disease processes, and number of prescription medications), and measures of health services utilization (number of visits to physicians, and acute hospitalization). RESULTS: Univariate analyses indicated that poorer self-rated health was associated with lesser education, higher numbers of depressive symptoms, impaired IADLs, prescription medications, physician visits, hospitalizations, and affected organ systems, and with the presence of several specific conditions. However, multiple logistic regression analyses revealed that only the following variables were associated independently with poorer self-rated health: age less than 75 years, education less than high school graduation, greater numbers of depressive symptoms, impaired IADLs, prescription medications, and physician visits. CONCLUSIONS: Even when controlling for physical illness and functional disability, subjective rating of overall health remains strongly and independently associated with depressive symptoms.

Prophylaxis of cytomegalovirus infection in liver transplantation: a randomized trial comparing a combination of ganciclovir and acyclovir to acyclovir. NIDDK Liver Transplantation Database.

BACKGROUND: The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients remains to be established. We tested whether a combination of intravenous ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone. METHODS: One hundred sixty-seven liver-transplant recipients were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective laboratory and clinical surveillance was performed to determine primary endpoints (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal and bacterial infection, allograft rejection, and survival after transplantation). One-year event rates are presented as cumulative percentages. RESULTS: During the first year after transplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11% of patients treated with GCV + ACV (P=0.03). In seronegative recipients of allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated with GCV + ACV developed infection with Candida albicans (P=0.05). CONCLUSIONS: Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high-dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R- CMV serological group.

Adult heart transplantation under tacrolimus (FK506) immunosuppression: histopathologic observations and comparison to a cyclosporine-based regimen with lympholytic (ATG) induction.

BACKGROUND: Tacrolimus (FK506) is an effective immunosuppressant for human heart transplantation, but information about its effects on cardiac allograft and nonallograft kidney and liver histopathologic study is limited. METHODS: We therefore reviewed 1145 endomyocardial biopsy specimens and eight autopsy results from 80 heart transplant recipients who received tacrolimus as baseline immunosuppression. These were compared with 619 endomyocardial biopsy specimens and four autopsy results from 51 patients treated with cyclosporine-based immunosuppression with lympholytic induction (CLI) by use of rabbit anti-thymocyte globulin. Twenty-one histologic features including the International Society for Heart and Lung Transplantation histopathologic grade were retrospectively assessed without knowledge of the treatment regimen. The lymphocyte growth index on biopsy specimens obtained from these patients was also compared. RESULTS: In general, there were no qualitative differences in the histopathologic appearance of various allograft syndromes between tacrolimus- and CLI-treated patients. Thus histopathologic criteria used to diagnose various graft syndromes are applicable under tacrolimus immunosuppression. However, early (between 10 and 30 days) after transplantation, biopsy specimens from patients treated with tacrolimus showed a significantly higher percentage of inflamed fragments (p = 0.02), the inflammation tended to be more severe (p = 0.09), and the rejection grade tended to be slightly higher (p = 0.08). In contrast, during the late transplantation period (275 to 548 days), biopsy specimens from patients treated with CLI showed a significantly higher percentage of inflamed fragments (p = 0.03), more severe inflammation (p = 0.03), higher rejection grades (p = 0.01), and a higher frequency of Quilty lesions (p = 0.05). Although overall freedom from any grade 3A or higher rejection was greater in the CLI-treated arm, tacrolimus was successfully used to treat refractory rejection in three patients from the CLI-treated arm. Concern has been raised in the literature about the possibility of tacrolimus being a direct hepatotoxin and an accelerant of allograft obliterative arteriopathy. However, no evidence to support either of these contentions was detected in this patient population. In contrast, tacrolimus is clearly nephrotoxic, although similar to cyclosporine in this regard. CONCLUSIONS: Tacrolimus is an effective immunosuppressive drug for heart transplantation. The cardiac allograft histopathologic study of patients treated with tacrolimus immunosuppression does not significantly differ from those given conventional, cyclosporine-based triple therapy with lympholytic induction.

Over-the-counter medication use in an older rural community: the MoVIES Project.

OBJECTIVE: To examine the self-reported use of over-the-counter (OTC) medications and the factors associated with OTC use in a rural older population. DESIGN: A cross-sectional study of an age-stratified random community sample. SETTING: The mid-Monongahela Valley, a rural area of Southwestern Pennsylvania. PARTICIPANTS: A total of 1059 older individuals with a mean age of 74.5 (+/- 5.5) years, 96.9% of whom were white and 57.3% of whom were women. MEASUREMENTS: Self-reported over-the-counter drug use and demographic information, and information about prescription drug use and recent use of health services. RESULTS: The majority (87.0%) of the sample were taking at least one OTC medication; 5.7% reported taking five or more OTCs. Women took significantly more OTCs than did men (P < .001). Individuals with more education took significantly more OTCs than those who had less (P = .018). The OTC category used most commonly was analgesics (66.3% overall), followed by vitamin and mineral supplements (38.1%), antacids (27.9%), and laxatives (9.7%). The use of analgesics decreased significantly (P = .018) with increasing age, whereas the use of laxatives increased significantly (P < .001). Women were more likely than men to be using each of these four major OTC groups. Unlike the associations with prescription drug use we reported previously in the same population, there were no significant associations for overall OTC use with age or with the use of health services. However, although vitamin use (as an example of an OTC drug taken for "preventive" purposes) was not associated with health services use, the use of laxatives (as an example of a "curative" OTC) was significantly associated (P < or = .002) with a greater number of physician visits, emergency room visits, hospitalizations during the past 6 months, home health care service utilization, and number of prescription medications. CONCLUSIONS: A substantial proportion of our older sample reported using a variety of over-the-counter drugs. Analgesics and vitamin/mineral supplements were the most frequently used categories. Women and those with more education were taking more OTC drugs. OTC use was not related to age, but the use of analgesics decreased with age while laxative use increased with age. Unlike prescription drug use, overall OTC drug use was not associated with health services utilization.

Long-term patient and retransplantation-free survival by selected recipient and donor characteristics: an update from the Pitt-UNOS Liver Transplant Registry.

CENTERS: Between 1988 and 1996, the total number of liver transplantations performed in the United States more than doubled, and the number of centers performing liver transplantations increased from 58 to 106. The yearly net gain in number of centers has slowed substantially in recent years, and the reduced differences in volume per center reported previously has continued through 1996. SURVIVAL AMONG PEDIATRIC RECIPIENTS: The estimated cumulative probability of a pediatric recipient surviving for 9 years following transplantation was .71, and surviving for 9 years without retransplantation was .58. In general, few deaths or retransplantations were observed more than 5 years following the initial transplantation. Factors independently associated with patient and retransplantation-free survival among children were year of transplantation, recipient age, location awaiting transplantation, primary liver disease, pre-LT serum creatinine, pre-LT bilirubin, and donor age. Recipient race and multiorgan transplantation were significantly associated with patient survival. Interestingly, of the 23 multi-organ recipients who survived at least 3 years, none died or required retransplantation. SURVIVAL AMONG ADULT RECIPIENTS: The estimated cumulative probability of an adult recipient surviving for 9 years following transplantation was .55, and surviving for 9 years without retransplantation was .48. Though the one-year survival rate among adults was slightly better than among children, long-term survival was substantially worse. Factors independently associated with patient and retransplantation-free survival among adults were year of transplantation, recipient age, race, location awaiting transplantation, primary liver disease, pre-LT creatinine, pre-LT albumin, recipient HBsAg status, donor age, donor anti-CMV status, ABO match, and sex match. Pre-LT bilirubin was significantly associated with patient survival, and pre-LT prothrombin time was associated with retransplantation-free survival.