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Surveillance, treatment, and outcomes for African-American (AA) populations with hepatocellular carcinoma (HCC) remain under evaluated. This study evaluated demographics, surveillance, therapy, and outcomes for a predominately AA population.The electronic medical records of a large health-care provider were used to identify 274 patients with visits for HCC between 2010 and 2017. Tumor size at diagnosis was defined by imaging with ≤ 5 cm being defined as "small." Surveillance for HCC was defined based on ultrasound (US) assessments.Patients were primarily AA (78%) and male (76%) with an average age at diagnosis of 62 years. Hepatitis C virus (HCV) was more likely to be a risk factor for the development of HCC in AA as compared to non-AA (92% vs 67%; p0.005). Surveillance rates were low (16% for AA vs 7% for non-AA). An aspartate aminotransferase platelet ratio index (APRI) value0.7 within 2 years of tumor diagnosis was a strong predictor for the risk of the development of HCC (86% AA vs 79 % non-AA). In this study, race was not a factor in treatment or outcomes, and most patients received tumor ablative treatment.Given the low surveillance rates and the demonstrated increased survival for patients with small tumors, ways to increase surveillance must be initiated. The results of this study demonstrate the need for physician/patient education on the importance of surveillance US. Further, this study supports routine assessment of APRI in AA patients in an effort to identify patients in whom intensive surveillance will significantly improve earlier detection of tumors.

Introduction: Bowel preparation quality in colonoscopy is one of the most essential components of quality assessment. According to the latest guidelines, inadequate bowel preparation warrants repeat colonoscopy in less than a year. Our aim was to investigate the role of bowel preparation in adenoma detection rate (ADR), its relationship with patients' demographics, and compliance with subsequent surveillance recommendations with guidelines. Methods: This is a retrospective chart review study. Bowel preparation quality was divided into three categories: high, intermediate, and low. ADR and polyp detection rates (PDR) were calculated as the number of patients with adenoma or polyp divided by the total number of patients. Results: Among 1,062 patients (934 African American and 128 non-African American) 81%, 11%, and 8% had high, intermediate, and low-quality bowel preparations, respectively. Race, gender, age, type of endoscopist, and body mass index did not play any role in bowel preparation quality. ADR and PDR were significantly higher in African Americans as compared to non-African Americans. ADR was significantly lower in the low-quality as compared to the high- and intermediate-quality bowel preparations (OR=2.13; p=0.0032). Bowel preparation quality was not correlated with subsequent follow-up recommendations. Academic gastroenterologists and surgeons had the highest and lowest compliance with surveillance guidelines, respectively. Conclusions: Racial and gender disparity appears to have no meaningful effect on the quality of bowel preparation. Only two categories (adequate [high/intermediate] or inadequate [low-quality]) may be used for follow-up recommendations. Non-compliance with surveillance guidelines is concerning and may inadvertently increase the interval risk of colorectal cancer.

African Americans (AA) are 4 times as likely as Caucasians to have chronic Hepatitis B (CHB) and yet are under represented in the literature especially with respect to treatment response. The objective of this study was to compare demographics, treatment decisions and outcomes of AA to Non-AA patients seen in the same GI clinic. Of the 92 patients with CHB, 60% were AA. AA patients had similar ALT and viral load at early visits as compared to Non-AA but significantly less fibrosis as defined by AST Platelet Ratio Index. Treatment rates were lower but not statistically different for AA (38%) vs. Non-AA (46%) and the majority of patients (80%) were HBeAntigen (HBeAg) negative. The patients responded well to treatment, although HBeAg positive AA were less likely to have a decline in HBV DNA than HBeAg negative AA patients. The primary conclusions of this study are that AA as compared to Non-AA patients are less likely to have fibrosis and appear to have a dissimilar response to anti-viral therapy.

Introduction Quality metrics of colonoscopy should be routinely monitored with a focus on optimizing the patient’s subsequent risk of colorectal cancer development. Documentation of bowel preparation, adenoma detection rate (ADR), and post-colonoscopy follow-up recommendations are three of the most important quality indicators for colonoscopy, but significant improvement has been challenging to achieve. The goal of this study is to determine whether the publication of colonoscopy quality indicator guidelines in 2015 resulted in an improvement in quality measures of physicians in our endoscopy suite as compared to before. Methods We reviewed the electronic medical records of patients who underwent a screening or surveillance colonoscopy in 2014 and 2017. Colonoscopies were performed in an open-access medical center endoscopy suite, staffed by three groups of physicians (academic gastroenterologists (AGs), non-academic gastroenterologists (non-AGs), and surgeons). We gathered demographic data, bowel preparation reports, follow-up recommendations, and notice to patient’s primary care physician, and calculated ADR for patients. Age- and gender-matched patients in both years were analyzed for ADR. These data were further subcategorized for each group of physicians. Results There were 553 patients in 2014 and 1,095 in 2017. Overall, male gender and African American race constituted the majority of patients in both years. Among age- and gender-matched patients in 2014 and 2017 (412 and 243 patients, respectively), ADR within each group of endoscopists was not significantly different between these two years (AGs 44% vs. 50%; non-AGs 32% vs. 27%; surgeons 25% vs. 21%; p>0.05 for all). However, in 2014 and 2017, ADR was significantly higher in the AG group as compared to the non-AG group and surgeons (p

Hepatitis B virus (HBV) causes both acute and chronic hepatitis and infects large numbers of individuals worldwide. Unfortunately, prediction of typical clinical outcome is problematic and there is considerable variability in the frequency, duration and severity of disease progression. The mainstay of HBV treatment is directed towards the suppression of HBV replication by nucleos(t)ide analogs (NUCs). The use of immunomodulators such as α-Interferon and thymosin α1 can, in select patients, results in elimination of both HBsAg and HBeAg. Given the observation that viral clearance is most effective in the presence of a strong immune response, this review summarizes data suggesting that the use of a combination of an immune modulator such as Tα1 with a highly effective NUC may result in a more successful therapeutic approach in patients with chronic hepatitis B (CHB). Results from small studies using combination Tα1 and NUCs are encouraging, and ongoing clinical trials combining entecavir with Tα1 are anticipated to provide important data assessing the use of a combination of Tα1 with a NUC to achieve resolution of CHB.

African Americans (AA) in the US are twice as likely to be infected with hepatitis C virus (HCV) compared to the non-Hispanic-white US population (Cau). They are also more likely to be infected with HCV genotype 1, more likely to develop hepatocellular carcinoma, and, in addition, have a lower response rate to interferon-based therapies. With the increase in response rates reported for combinations of direct-acting antivirals, the possibility that racial disparity would be eliminated by agents that directly inhibit virus replication has become a reality. The objective of this review is to evaluate the literature from clinical studies and retrospective analysis with respect to the response of AA to the most prescribed antiviral combination sofosbuvir plus ledipasvir. While few studies have focused on AA patients, sufficient information is availed from the literature and studies in our predominately AA clinic population to confirm that ledipasvir-sofosbuvir has a similar effectiveness in AA as compared to Cau.

INTRODUCTION: There is considerable uncertainty with respect to predicting the liver disease status of African American (AA) patients with Hepatitis C seen in the current era of highly effective direct acting anti-virals (DAA). This uncertainty is due to the complex interplay between the identification of patients early in their disease progression by screening, the fact that many AA patients failed earlier interferon based therapy, duration of the HCV viremia in AA patients, the possible variation In disease course in AA as compared to other races, and potential early mortality of AA patients due to liver disease. Understanding the evolution of HCV infection as defined by comparing previous and current patient populations provides information relevant to both therapeutic and health costs decisions. METHODS: We selected patients from a 24 month period between 2002 and 2003 (Epoch 1; n = 414) to compare with patients seen in the same GI clinic between 2012 and 2013 (Epoch 2; n=405). Epoch 1 was the beginning of the peg-interferon and ribavirin treatment era and Epoch 2 reflects the patient population seen when DAA therapy was first available. RESULTS: Epoch 2 patients were older (59.7 vs 50.3 years) with a similar gender distribution (55% vs 59% male). Consistent with the change in clinic demographics, more AA patients were seen in Epoch 2 (89%) as compared to Epoch 1 (77%). There was no significant difference between hepatic fibrosis as assessed by APRI (1.1 vs 0.9) or FIB-4 (2.4 vs 2.6) but there was an increase in intermediate degree of fibrosis as defined by liver biopsy. The majority of Epoch 2 patients were still naive to treatment (96% Epoch 1 vs 61% Epoch 2) and a similar proportion had cirrhosis (15% Epoch 1 vs 17% Epoch 2) at the time of first visit in the different time periods. CONCLUSIONS: The patients in Epoch 2 from this urban GI referral clinic are older and the majority of them had not been treated or had not responded to treatment. This age demographic continues to reflect patients who were likely infected during the 1960’s-1980’s which is when HCV infection became widespread. Epoch 2 patients also do not have more advanced liver disease as defined either by significant fibrosis or cirrhosis as compared to Epoch 1. Possible explanations include that Epoch 2 patients’ disease was detected earlier by surveillance, progressed very slowly to advanced liver disease, or had a high mortality that resulted in a decline in patients with advanced disease. The role of access to therapy in patients not treated remains to be determined and the increased effectiveness of DAA are predicted to increase the number of AA patients seeking and accepting treatment.

Background: Screening colonoscopy aims to interrupt the adenoma-carcinoma sequence by removing all precancerous adenomatous polyps. Adenomatous polyp detection rate (ADR) can vary between endoscopists as well as between race, age, and risk of colorectal cancer (CRC). The purpose of this study was to compare ADR among academic gastroenterologists (A-GI), non-A-GI, and surgeons for endoscopies performed in the same endoscopic suite of a large medical center with a predominately African American (AA) population. Methods: All screening colonoscopies performed in 2014 for patients aged 62-76 years were identified using the electronic medical records data. Patients with average risk and high risk of CRC defined as having a 'personal history of polyps' or 'family history of CRC', and history of ulcerative colitis and Fecal Occult Blood Test/Fecal Immunochemical Test (FOBT/FIT) positivity were included. Patients with incomplete colonoscopy (defined as failing to achieve cecal intubation or poor preparation) and unrecovered tissue biopsy were excluded. ADR was calculated for three groups of endoscopists: A-GIs, non-A-GIs, and surgeons. Results: A total of 573 screening colonoscopies was analyzed. The endoscopists comprised five A-GIs, eight non-A-GIs, and six surgeons. The majority of patients were of AA decent (71%), female (54%) with an average age of 66 years. Patients classified as average risk comprised 79% of the population. Most of the colonoscopies were performed by A-GI (n=339), followed by non-A-GI (n=144), and surgeons (n=90). The ADR for A-GI was 50% as compared to 32% for non-A-GI (p

Background: Evaluation of advanced fibrosis in patients with hepatitis C virus (HCV) infection is used to facilitate decisions on treatment strategy and to initiate additional screening measures. Unfortunately, most studies have predominately Caucasian (Cau) patients and may not be as relevant for African Americans (AA). Aims: This study specifically addresses the issue of defining minimal vs. significant fibrosis in African Americans (AA) with chronic hepatitis C (CHC) using noninvasive assays. Methods: All patients (n = 319) seen between 1 January 2008 and 30 June 2013 for whom a FibroSpect II® (FSII) assay was performed and had data for calculation of aspartate aminotransferase (AST) platelet ratio index (APRI) and Fibrosis-4 (FIB-4) were identified using the medical records. Results: When liver biopsy score and FSII assay results for the AA patients with CHC were compared, 31% of AA had advanced FSII fibrosis scores (F2-F4) despite a biopsy score of F0-F1. In contrast, 10% of Cau over-scored. The AA false positive rate was 14% for APRI and 34% for FIB-4. Combining FSII with either APRI (7% false positive) or FIB-4 (10% false positive) improved the false positive rate in AA to 7% (FSII + APRI) and 10% (FSII + FIB-4) but reduced the sensitivity for significant fibrosis. Conclusions: The FSII assay overestimates fibrosis in AA and should be used with caution since these patients may not have significant fibrosis. If the APRI or FIB-4 assay is combined with the FSII assay, minimal fibrosis in AA can be defined without subjecting the patients to a subsequent biopsy.

Defining mortality for Caucasians and African American patients with chronic hepatitis C with respect to racial diversity is critical for counselling patients on therapy options. The objective of this study was to define racial diversity influence on mortality and morbidity of 3724 consecutive hepatitis C virus (HCV)-infected patients seen in an urban clinic between 1995 and 2008. Mortality, as of 2011, was defined using the SSA National Death Index and correlated with early visit medical information. The HCV chronically infected patient population consisted of 2879 African Americans (AA), 758 Caucasians and 87 other, and the majority were not treated for their infection prior to 2011. The average time to death from first visit was 5 years, the average age at death was 55 years, and despite racial diversity, AA were just as likely to be reported dead as Caucasians (23% AA vs 22% Caucasians). Cirrhosis and fibrosis (liver biopsy, AST Platelet Ratio Index or Fibrosis-4) at first visit as well as low albumin, diabetes, renal impairment and cardiac symptoms were associated with increased mortality. Treated patients who cleared the virus (sustained viral response (SVR); AA = 59; Caucasians = 40) had lower mortality than patients who were not treated (AA: 5% vs 27%; Caucasians 5% vs 26%). Hence, we find that race is not a factor in the early mortality of patients with chronic HCV infection and achieving a SVR reduced mortality. Unexpectedly, nonresponding AA also benefited by a lower mortality. African American patients with kidney disease and low albumin were at highest risk and should be treated as soon as identified.

With the recent approvals of immune therapies such as checkpoint inhibitors and chimeric antigen receptor cell therapy, the development of immune modulators for cancer therapy has been given new li...

Background and Aims: African Americans (AA) historically have a low response rate to hepatitis C therapies, and there is limited information available for this patient population regarding the development and treatment of chronic hepatitis C (CHC). The aim of this study was to evaluate liver disease progression and hepatocellular carcinoma (HCC) development in AA with CHC. Methods: Between 1995 and 2008, 246 AA patients with CHC were identified from a database of patients and followed until 2012-2013 (average 8 years) or the development of HCC after 2008. Results: Viral clearance (intent to treat; sustained virus response (SVR)) was achieved in 15% of patients with interferon based therapies with or without ribavirin. AA patients who achieved an SVR (n=22) did not develop HCC or new onset cirrhosis, whereas the HCC incidence in untreated AA patients was 23% (51/203). Patients who achieved an SVR also had improved fibrosis, as defined by the AST Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) score, relative to nonresponders and untreated patients. Conclusions: The severity of liver disease at the first visit (except for cirrhosis) correlated with the development of HCC, but because of the overlap in values between patients, these measurements were not useful for predicting individual risk. Since cirrhosis at the first visit was not a predictive factor, treatment with newer antiviral therapies is the best option for reducing the incidence of advanced liver disease and its harmful outcomes in the AA population.

Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets. In this study, we investigated primary human LC activation after exposure to HPV16, followed by treatment with IRX-2 in vitro, and evaluated their subsequent ability to induce HPV16-specific T cells. In contrast to its activity on dendritic cells, HPV16 alone is not sufficient to induce phenotypic and functional activation of LCs. However, IRX-2 induces a significant upregulation of antigen presentation and costimulatory molecules, T helper 1 (Th1)-associated cytokine release, and chemokine-directed migration of LCs pre-exposed to HPV16. Furthermore, LCs treated with IRX-2 after HPV16 exposure induced CD8(+) T-cell responses against specific HLA-A*0201-binding HPV16 T-cell epitopes. The present study suggests that IRX-2 is an attractive immunomodulator for assisting the immune response in eradication of HPV-infected cells, thereby potentially preventing HPV-induced cancers.

Twenty-seven subjects with squamous cell cancer of the head and neck received the neoadjuvant IRX-2 immunotherapy regimen prior to surgery in a Phase 2 trial. Pretreatment tumor biopsies were compared with the primary tumor surgical specimens for lymphocyte infiltration, necrosis and fibrosis, using hematoxylin and eosin stain and immunohistochemistry in 25 subjects. Sections were examined by three pathologists. Relative to pretreatment biopsies, increases in lymphocyte infiltration (LI) were seen using H and E or immunohistochemistry. CD3+ CD4+ T cells and CD20+ B cells were primarily found in the peritumoral stroma and CD3+ CD8+ T cells and CD68+ macrophages were mainly intratumoral. LI in the surgical specimens were associated with reductions in the primary tumor size. Improved survival at 5 years was correlated with high overall LI in the tumor specimens. Neoadjuvant IRX-2 immunotherapy regimen may restore immune responsiveness presumably by mobilizing tumor infiltrating effector lymphocytes and macrophages into the tumor.

Thymosin alpha1 (Talpha1) is a 28 amino acid biologically active protein with pleiotropic immune enhancing activity. IRX-2 is a primary cell-derived biologic containing multiple cytokines that enhance dendritic cell maturation, promote T-cell growth and differentiation, and inhibit tumor-mediated apoptosis of T cells. IRX-2 is being developed as an immunotherapeutic agent as a novel T-cell adjuvant platform for vaccines as well. Based on their biological activities, thymosin alpha1 and IRX-2 were predicted to exhibit synergistic effects when evaluated in animal and human studies. In animal studies, the combination of IRX-2 and Talpha1 (IRX-3) increased T-cell numbers compared to either alone during recovery from hydrocortisone mediated reduction. IRX-3 further enhanced reduction in tumor burden following chemotherapy compared to IRX-2. Based on these studies, IRX-3 is predicted to be especially important in a setting where reversal of immune suppression due to the presence of tumor, irradiation, and/or chemotherapy is likely to be an important factor in cytokine activity.

Thymosin alpha1 (Talpha1) is a 28 amino acid biologically active protein cleaved from positions 2-29 of a precursor protein, prothymosin alpha. Since its discovery, Talpha1 has been administered to animals and humans in a wide variety of settings and its pharmacologic effects are to enhance cellular immunity. Talpha1 administration is highly effective in settings where irradiation, chemotherapy, tumor burden, or immune senescence have caused a reduction of T cell number and/or function. Recent in vitro studies, including the one reported here, suggest that Talpha1 may act via pathways commonly used by various cytokines. This raises the possibility that Talpha1 and cytokines may have synergistic activity through potentiation of cytokine activity by Talpha1. Improved control of tumor growth when tumor-bearing mice were treated with Talpha1 and high doses of IL-2 has been previously reported. We extended those studies with the Lewis lung carcinoma mouse model using IRX-2, a natural well-defined biologic containing multiple cytokines, in combination with Talpha1 (IRX-3). Although IRX-2 was effective alone (using doses that contain significantly less IL-2 than in most typical studies), adding Talpha1 led to significant improvement in survival of the tumor-bearing mice. Based on these observations, the immunopharmacology of Talpha1 predicts an important clinical role for Talpha1 in the restoration of cellular immune activity when used in combination with cytokines. Patients who experience immune suppression due to the presence of tumor, irradiation, and/or chemotherapy or aging of the host would most benefit from this treatment combination.