BACKGROUND:The C-C chemokine receptor Type 5 (CCR5) is a key receptor for human immunodeficiency virus type 1 (HIV-1) entry into T-cells and a variant allele, CCR5 delta-32, is associated with decreased viral replication and disease progression. Active HIV-1 replication is highly associated with accelerated rates of hepatic fibrosis. We postulated that CCR5 plays a role in the development of hepatic fibrosis and evaluated the longitudinal effect of natural or drug-induced CCR5 mutation and blockade on biomarkers of liver fibrosis in HIV-1 patients.METHODS:To accomplish this goal, we examined 2 distinct cohorts. First, we evaluated fibrosis markers in the Multicenter Hemophilia Cohort Studies (MHCS), which included subjects with HIV and hepatitis C virus (HCV) coinfection with the CCR5 delta-32 allele. We also evaluated an HIV-1 infected cohort that was treated with a dual CCR5/CCR2 antagonist, cenicriviroc. The enhanced liver fibrosis (ELF) index was validated against liver histology obtained from HCV/HIV and HCV patients and demonstrated strong correlation with fibrosis stage.RESULTS:In both the MHCS patients and patients treated with cenicriviroc, CCR5 mutation or blockade was associated with a significant decrease in the ELF index. Among the patients with the delta-32 allele, the ELF index rate significantly decreased in sequential samples as compared to CCR5 wild-type patients (P = .043). This was not observed in control subjects treated with efavirenz nor with a lower dose of 100 mg cenicriviroc.CONCLUSION:These findings suggest that hepatic fibrosis in HIV-1 infected patients can be modulated by the mutation of CCR5 and/or use of CCR5/CCR2 blockade agents.CLINICAL TRIALS REGISTRATION:NCT01338883.

Hepatitis D virus (HDV) infection may accompany acute or chronic hepatitis B virus infection. While HDV infection in the United States is thought to be uncommon, there are limited data regarding frequency of testing, and prevalence of HDV antibody and HDV RNA. We evaluated the use of HDV antibody testing using electronic medical record (EMR) data. Among 1007 HBsAg positive patients, only 121 had been tested for HDV antibody. Testing was performed primarily by gastroenterologists/hepatologists and limited testing was performed in identifiable high risk groups including those with HBV/HIV coinfection. Overall, HDV antibody was detected in 3.3% (95% C.I. = 0.9%-8.2%) An HDV RNA assay was developed and validated and 138 HBV or HBV/HIV coinfected patients were tested. The prevalence of HDV among the HBV/HIV coinfected subjects was 2.2% (95% C.I. = 0-5.3%). In a U.S. Midwestern population of HBV infected patients, HDV testing is under-employed. Overall prevalence exceeds 2% whether testing by antibody or HDV RNA and more comprehensive HDV surveillance may be indicated.

Background: Cancer patients receiving chemotherapy face an increased risk of reactivation of chronic hepatitis B virus infection (HBVr), which may be associated with serious and/or fatal reactivation.Aim: To determine the HBV screening rate and characterize the HBV infection status in cancer patients receiving chemotherapy at a major US cancer center.Method: We included all adult patients (age ≥ 18 years) with newly diagnosed cancer starting chemotherapy between 2012 and 2015 within a major US hospital network, including a large university teaching hospital, a community teaching hospital, and affiliate outpatient oncology clinics.We excluded patients who received investigational chemotherapy within clinical trials, or chemotherapy administered by non-parental route.Demographic information, clinical setting, chemotherapy regimen and HBV serology data were collected.Result: Among 11,243 patients receiving chemotherapy, 1,016 patients (9.0%) were tested for either HBV surface antigen (HBsAg) or HBV core antibody (anti-HBc) before initiation of chemotherapy, 825 patients (7.3%) had both HBsAg and anti-HBc tested before chemotherapy, and 1,906 patients (9.8%) were tested for HBsAg or anti-HBc after starting chemotherapy.A total of 201 patients (9.5%) were exposed to HBV (positive for either HBsAg, anti-HBc or HBV DNA), and 21 patients (1.0%) had chronic HBV infection (both positive for HBsAg and anti-HBc).Older patients over age 50 years were screened less for HBV (8.1 vs 15.9%, p<0.001) despite higher prevalence of HBV exposure (10.7 vs 5.0%, p<0.001).Asian patients were less screened for HBV compared to other ethnicities (8.5 vs 13.5 vs 16.1 vs 7.9%, p<0.001,Asian, Black, Hispanic, and White respectively) despite higher prevalence of HBV infection (34.4 vs 18.8 vs 11.8 vs 6.4%, p<0.001,Asian, Black, Hispanic, and White respectively).Patients receiving chemotherapy in local oncology clinics were less likely to be screened for HBV (3.47 vs 11.8 vs 10.7, p<0.001, local clinic, university medical center, and community hospital, respectively), despite no difference in HBV infection rate (p= 0.249).Patients receiving chemotherapy known to have moderate to high risk of HBVr had higher screening rate (27.3 vs 14.8 vs 11.1 vs 15.6 vs 57.14 vs 50.0 vs 10.0%, p<0.001,B cell-depleting agent, Anthracycline derivatives, high dose corticosteroid, immunotherapy, anti-TNF alpha inhibitors, cytokine/integrin inhibitors, and other conventional chemotherapy, respectively).Conclusion: HBV screening rate among patients undergoing cancer chemotherapy was very low.Older and Asian patients were less screened for HBV despite higher prevalence of HBV infection.HBV screening was underperformed in communitybased oncology clinics compared to teaching hospitals.

AIM To study the intrahepatic expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in chronic hepatitis B patients with and without hepatocellular carcinoma. METHODS A total of 33 chronic hepatitis B patients (mean age of 40.3 ± 2.5 years), comprising of 14 HBeAg positive and 19 HBeAg negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma (mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBcAg and HBsAg was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBcAg and HBsAg staining distributions and patterns were described according to a modified classification system. RESULTS Compared to the HBeAg negative patients, the HBeAg positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBeAg positive patients had intrahepatic HBcAg staining; predominantly with "diffuse" distribution (79%) and "mixed cytoplasmic/nuclear" pattern (79%). In comparison, only 5% of the HBeAg-negative patients had intrahepatic HBcAg staining. However, the intrahepatic HBsAg staining has wider distribution among the HBeAg negative patients, namely; majority of the HBeAg negative cases had "patchy" HBsAg distribution compared to "rare" distribution among the HBeAg positive cases. All but one patient with HCC were HBeAg negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBcAg and HBsAg were seen in 13 (100%) and 10 (77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBcAg and HBsAg were detected in tumor tissues but not the adjacent liver in 4 (44%) and 1 (11%) patient respectively. CONCLUSION Isolated intrahepatic HBcAg and HBsAg can be present in tumors of patients with suppressed HBV DNA on antiviral therapy; that may predispose them to cancer development.

Background:Patients with inflammatory bowel disease have higher proportions of immunoglobulin G (IgG) antibodies lacking N-galactose, also called agalactosyl IgG, in their serum. Such agalactosyl IgGs have been associated with disease activity and the immunogenicity of biologics. The aim was to describe the relationship between circulating levels of a subset of agalactosyl IgGs (anti--Gal) and Crohn's disease (CD) phenotypes.Methods:Prospectively collected serum samples of a well-characterized cohort of patients with inflammatory bowel disease and controls were used. Serum anti--Gal levels were measured by a high-affinity enzyme-linked immunosorbent assay and referenced to a standard control.Results:Serum samples from 167 subjects were tested; 62 with CD, 76 with ulcerative colitis, and 29 controls. Agalactosyl anti--Gal levels were significantly higher in active CD than in active ulcerative colitis (P = 0.0043) or healthy controls (P < 0.0001). Among patients with CD, agalactosyl anti--Gal levels were significantly higher in those with a history of arthritis, than those without (P = 0.0002), but lower in those taking immunomodulators (P = 0.03). There was no correlation between agalactosyl anti--Gal levels and indices of Crohn's severity, including C-reactive protein levels or Harvey-Bradshaw index. Patients who were primary or secondary nonresponders to infliximab had similar agalactosyl anti--Gal levels to clinical responders.Conclusions:Patients with CD have greater amounts of agalactosylated anti--Gal antibodies in their serum, particularly in those with associated joint disease. This increase seems to be independent of indices of disease activity, but is influenced by immunomodulator use.

BACKGROUND:Patients with inflammatory bowel disease have higher proportions of immunoglobulin G (IgG) antibodies lacking N-galactose, also called agalactosyl IgG, in their serum. Such agalactosyl IgGs have been associated with disease activity and the immunogenicity of biologics. The aim was to describe the relationship between circulating levels of a subset of agalactosyl IgGs (anti-α-Gal) and Crohn's disease (CD) phenotypes.METHODS:Prospectively collected serum samples of a well-characterized cohort of patients with inflammatory bowel disease and controls were used. Serum anti-α-Gal levels were measured by a high-affinity enzyme-linked immunosorbent assay and referenced to a standard control.RESULTS:Serum samples from 167 subjects were tested; 62 with CD, 76 with ulcerative colitis, and 29 controls. Agalactosyl anti-α-Gal levels were significantly higher in active CD than in active ulcerative colitis (P = 0.0043) or healthy controls (P < 0.0001). Among patients with CD, agalactosyl anti-α-Gal levels were significantly higher in those with a history of arthritis, than those without (P = 0.0002), but lower in those taking immunomodulators (P = 0.03). There was no correlation between agalactosyl anti-α-Gal levels and indices of Crohn's severity, including C-reactive protein levels or Harvey-Bradshaw index. Patients who were primary or secondary nonresponders to infliximab had similar agalactosyl anti-α-Gal levels to clinical responders.CONCLUSIONS:Patients with CD have greater amounts of agalactosylated anti-α-Gal antibodies in their serum, particularly in those with associated joint disease. This increase seems to be independent of indices of disease activity, but is influenced by immunomodulator use.

histology, endoscopy, partial and full Mayo scores.Addition of endoscopy subscore adds little to the assessment based on the partial Mayo domains which can be used to predict the total Mayo score.However, endoscopy score could not be accurately predicted from clinical domains.During follow-up in trials, sigmoidoscopy may be avoided without significant loss of information.However, at the first and final visit sigmoidoscopy should be retained as the mucosal appearance cannot be predicted from the partial Mayo score.References 1