HIV Preexposure Prophylaxis-The Role of Primary Care Clinicians in Ending the HIV Epidemic.

A global human immunodeficiency virus (HIV) epidemic persists despite data to support multiple effective and safe tools that prevent HIV transmission and acquisition. Human immunodeficiency virus preexposure prophylaxis (PrEP) for HIV-uninfected at-risk populations using tenofovir disoproxil fumarate emtricitabine is highly effective, safe, and recently endorsed by the US Preventive Services Task Force (USPSTF) as a grade A recommendation. In this Special Communication, we summarize current guidelines and expert recommendations in a call for wider adoption of PrEP prescribing activities by frontline primary care clinicians. Key components include the ideal contexts in which PrEP may be prescribed, eligibility criteria, clinical considerations and pitfalls, laboratory monitoring, prescription practices, situations that may warrant expert consultation, and future directions. Given the broad scope, access, and point-of-entry status of primary clinicians in health systems, generalists will need to be at the center of any successful effort to leverage the power of, and destigmatize PrEP to end the HIV epidemic.

Evaluation of absolute serum α-fetoprotein levels in liver transplant for hepatocellular cancer.

HYPOTHESIS: An elevated serum α-fetoprotein (AFP) level before orthotopic liver transplant (OLT) is predictive of mortality after OLT for hepatocellular carcinoma (HCC). DESIGN: Retrospective analysis of a population-based cohort. SETTING: United Network for Organ Sharing registry (2003-2008). PATIENTS: We identified 2253 patients who underwent OLT for HCC with available pre-OLT serum AFP values. METHODS: Patients were stratified by AFP levels into low (<20 ng/mL), medium (20-399 ng/mL), or high (≥400 ng/mL) groups. Clinical and pathological characteristics were compared among groups. Survival curves were constructed by the Kaplan-Meier method, and univariate and multivariate Cox-regression analysis was performed. RESULTS: Of the 2253 patients, 1210 (53.7%), 805 (35.7%), and 238 (10.6%) were in the low, medium, and high AFP groups, respectively. On univariate analysis, the low AFP group demonstrated the best 4-year survival (76%) compared with the medium (65%; P = .001) and high (57%; P < .001) AFP groups. When AFP levels in patients with only stage II HCC underwent assessment, improved survival in the low AFP group was still observed (P < .001). On multivariate analysis, the medium and high AFP groups were associated with higher mortality (hazard ratios, 1.50 [95% confidence interval, 1.19-1.89; P = .001] and 2.11 [1.55-2.88; P < .001], respectively). CONCLUSIONS: Serum AFP level is an independent prognostic predictor of outcome after OLT for HCC. The association between serum AFP value and post-OLT survival warrants further investigation to potentially better allocate donor allografts for HCC.

Race, ethnicity, and socioeconomic status influence the survival of patients with hepatocellular carcinoma in the United States.

BACKGROUND: Racial, ethnic, and socioeconomic disparities in the survival of patients with hepatocellular carcinoma (HCC) continue to exist. The authors of this report hypothesized that these differences result from inequities in access to care and in response to therapy. METHODS: Patients with HCC (n = 20,920) were identified from the Surveillance, Epidemiology, and End Results (SEER) database, and patients who underwent liver transplantation for HCC (n = 4735) were identified from the United Network for Organ Sharing (UNOS) database. Clinical and pathologic factors were compared after patients were stratified by race and ethnicity. RESULTS: The survival of patients with HCC improved over time for all racial, ethnic, and income groups (P < .001). Black and low income individuals had the poorest long-term survival (P < .001). On multivariate analysis, black race was predictive of the poorest survival (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.09-1.22; P < .001), whereas Asian race was associated with the best survival (HR, 0.87; 95% CI, 0.83-0.91; P < .001). After liver transplantation, black patients had the worst graft survival and overall survival (median survival [MS], 30.5 months and 39.7 months, respectively; P < .001), whereas Hispanics had the best survival (MS, 83.4 months and 86.6 months, respectively; P < .001). In a multivariate analysis of transplantation patients, race and ethnicity were associated significantly with outcome. CONCLUSIONS: Significant racial and ethnic disparities in the outcome of patients with HCC persist despite the receipt of comparable treatment. The authors concluded that further investigations are warranted to identify the reasons for the stark disparity in outcomes between black patients and Hispanic patients after liver transplantation for HCC.

A disease-based comparison of liver transplantation outcomes.

An increasing demand for transplant donor organs has made optimal allocation of resources a priority. Our objective was to evaluate outcomes for orthotopic liver transplantation (OLT) performed in the United States. A query of the United Network for Organ Sharing registry between 1988 and 2007 was performed for patients who underwent OLT for all etiologies. Patients were stratified by pathology necessitating OLT and clinical and pathologic factors were compared. Multivariate Cox-regression analysis was used to assess the association of pathology with survival. Of 61,823 patients, 33 per cent (n = 20,305) of OLTs were secondary to hepatitis C virus, 21 per cent autoimmune disease, 17 per cent alcohol-induced injury, 11 per cent cryptogenic cirrhosis, 8 per cent hepatocellular carcinoma (HCC), 6 per cent hepatitis B virus, and 4 per cent metabolic disease. Patients with autoimmune disease and HCC demonstrated the best and worst survival, respectively, after OLT (median survival 16.0 vs 6.4 yrs, respectively, P < 0.001). By multivariate analysis, OLT for HCC was significantly associated with poorer overall survival (hazard ratio [HR] 2.19, 95% confidence interval [CI]: 2.02-2.37, P < 0.001). Our results indicate that outcomes for liver transplantation vary by primary hepatic pathology with HCC patients having the poorest overall survival. To optimize organ allocation for all patients with end-stage liver disease, a better understanding of poor survival for HCC is necessary.

Surgical resection of primary and metastatic hepatic malignancies following portal vein embolization.

BACKGROUND: Portal vein embolization (PVE) has been used to induce hypertrophy in future liver remnants (FLRs) in preparation for major hepatic resection. We report our initial experience with PVE and identify potential predictors of unresectability following PVE. METHODS: Patients with primary and metastatic hepatic malignancies (n = 20) who underwent PVE between 2004 and 2008 were categorized by surgical resection status and clinicopathologic factors were compared. RESULTS: The cohort had the following histologies: colorectal adenocarcinoma (45%, n = 9), hepatocellular carcinoma (20%), cholangiocarcinoma (20%), and other (15%). Seven patients (35%) had previous liver-directed or regional therapy; 55% subsequently underwent successful liver resection, whereas 45% were deemed unresectable. Patients who underwent successful resection had tumor shrinkage after PVE compared to unresectable patients (% change in maximal tumor diameter, -6% vs. +45%, respectively; P = 0.027) and had a lower rate of baseline liver function test abnormality (0% vs. 56%, respectively; P = 0.004). Resected patients had an 83% 5-year overall survival. CONCLUSIONS: Baseline liver dysfunction may predict subsequent unresectable hepatic disease following PVE and tumor progression after PVE appears to increase the likelihood for finding unresectable hepatic disease. Select patients should be considered for PVE with careful surveillance during the period of FLR hypertrophy.