Highly multiplexed 2-dimensional imaging mass cytometry analysis of HBV-infected liver.

Studies of human hepatitis B virus (HBV) immune pathogenesis are hampered by limited access to liver tissues and technologies for detailed analyses. Here, utilizing imaging mass cytometry (IMC) to simultaneously detect 30 immune, viral, and structural markers in liver biopsies from patients with hepatitis B e antigen+ (HBeAg+) chronic hepatitis B, we provide potentially novel comprehensive visualization, quantitation, and phenotypic characterizations of hepatic adaptive and innate immune subsets that correlated with hepatocellular injury, histological fibrosis, and age. We further show marked correlations between adaptive and innate immune cell frequencies and phenotype, highlighting complex immune interactions within the hepatic microenvironment with relevance to HBV pathogenesis.

Optimizing hepatitis C therapy in HIV/hepatitis C virus (HCV) coinfected patients: Analysis of HCV viral kinetics on treatment.

INTRODUCTION: Hepatitis C virus (HCV) infection is potentially curable, but the sustained virological response (SVR) has been shown to be lower in patients coinfected HIV. A single-centre experience treating individuals with HCV and HIV coinfection is reported. METHODS: Twenty-one patients who received standard doses of pegylated interferon with weight-based dosing of ribavirin (mean 14.3 mg/kg) were retrospectively reviewed. Qualitative HCV polymerase chain reaction (PCR) was performed prospectively every four weeks if the patient remained HCV PCR positive. All patients with HCV genotype 1 were treated for 48 weeks. Patients with genotype 2 or 3 were treated for 24 weeks and 32 weeks to 36 weeks if their HCV RNA level was undetectable after four weeks (RVR4) or eight weeks (RVR8) of therapy, respectively. If RVR8 was not achieved, the treatment was continued for 48 weeks. RESULTS: There were no dropouts or dose reductions within the first 12 weeks of treatment. SVR status was available for 20 patients and adequate serum for viral kinetics analyses was available for 17 patients. Eighty per cent of the patients achieved SVR (50% genotype 1; 100% genotypes 2 and 3). The week 8 viral load remained elevated for all genotype 1 nonresponders. DISCUSSION: High effectiveness rates were seen, particularly in patients with HCV genotype 2 and 3 who were treated for shorter durations. HCV viral loads after eight weeks of therapy helped distinguish patients with HCV genotype 1 who would respond to therapy. INTRODUCTION: Hepatitis C virus (HCV) infection is potentially curable, but the sustained virological response (SVR) has been shown to be lower in patients coinfected HIV. A single-centre experience treating individuals with HCV and HIV coinfection is reported. METHODS: Twenty-one patients who received standard doses of pegylated interferon with weight-based dosing of ribavirin (mean 14.3 mg/kg) were retrospectively reviewed. Qualitative HCV polymerase chain reaction (PCR) was performed prospectively every four weeks if the patient remained HCV PCR positive. All patients with HCV genotype 1 were treated for 48 weeks. Patients with genotype 2 or 3 were treated for 24 weeks and 32 weeks to 36 weeks if their HCV RNA level was undetectable after four weeks (RVR4) or eight weeks (RVR8) of therapy, respectively. If RVR8 was not achieved, the treatment was continued for 48 weeks. RESULTS: There were no dropouts or dose reductions within the first 12 weeks of treatment. SVR status was available for 20 patients and adequate serum for viral kinetics analyses was available for 17 patients. Eighty per cent of the patients achieved SVR (50% genotype 1; 100% genotypes 2 and 3). The week 8 viral load remained elevated for all genotype 1 nonresponders. DISCUSSION: High effectiveness rates were seen, particularly in patients with HCV genotype 2 and 3 who were treated for shorter durations. HCV viral loads after eight weeks of therapy helped distinguish patients with HCV genotype 1 who would respond to therapy.

INTRODUCTION: L'infection par le virus de l'hépatite C (VHC) se soigne, mais on a observé que la réponse virologique soutenue (RVS) est plus faible chez les patients co-infectés par le VIH. Les chercheurs rendent compte de l'expérience monocentrique du traitement de personnes co-infectées par le VHC et le VIH. MÉTHODOLOGIE: Les chercheurs ont procédé à l'analyse rétrospective de 21 patients qui avaient reçu des doses standard d'interféron pégylé associées à une dose de ribavirine fondée sur le poids (moyenne de 14,3 mg/kg). La réaction en chaîne de la polymérase (PCR) qualitative du VHC était exécutée de manière prospective toutes les quatre semaines si celle-ci révélait que le patient demeurait positif au VHC. Tous les patients ayant un VHC de génotype 1 ont été traités pendant 48 semaines. Les patients ayant le génotype 2 ou 3 ont été traités pendant 24 semaines et 32 à 36 semaines si leur taux de VHC dans l'ARN n'était plus décelable au bout de quatre semaines (RVR4) ou de huit semaines (RVR8) de traitement, respectivement. Si on ne parvenait pas à une RVR8, le traitement était maintenu pendant 48 semaines. RÉSULTATS: Il n'y a pas eu d'abandon ou de réduction des doses dans les 12 premières semaines du traitement. Les chercheurs connaissaient la RVS de 20 patients et les analyses sériques pertinentes de la cinétique virale de 17 patients. Quatre-vingts pour cent des patients ont obtenu une RVS (50 % des cas de génotype 1; 100 % des cas de génotypes 2 et 3). La huitième semaine, la charge virale demeurait élevée pour tous les non-répondants de génotype 1. EXPOSÉ: Les chercheurs ont observé un taux d'efficacité élevé, particulièrement chez les patients ayant un VHC de génotype 2 ou 3 qui avaient été traités moins longtemps. La charge virale du VHC au bout de huit semaines de traitement contribuait à faire ressortir les patients ayant un VHC de génotype 1 qui répondaient au traitement.

Hepatitis B learning needs assessment of family medicine trainees in Canada: results of a nationwide survey.

BACKGROUND: An estimated 350 million people worldwide have chronic hepatitis B (CHB), which is a major cause of cirrhosis and hepatocellular carcinoma. OBJECTIVE: To assess the level of knowledge among family medicine trainees regarding the identification and management of CHB. METHODS: questionnaire to assess knowledge regarding screening and management of patients with CHB and cirrhosis was developed. The questionnaire was pilot tested among primary care physicians, subsequently revised and distributed to family medicine trainees across Canada through an online survey program (QuestionPro). RESULTS: A total of 158 trainees completed the questionnaire. Of these, 54% to 56% routinely offered vaccination against hepatitis A or hepatitis B virus (HBV), and 42% regularly screened patients for HBV risk factors. The percentage who recognized the need to screen highrisk populations for CHB, ie, individuals from an HBV-endemic country, men who have sex with men, or intravenous drug users was 73%, 66% and 74%, respectively. While less than 50% of respondents used the appropriate HBV screening tests, 86% to 91% correctly interpreted various HBV serological patterns. Only 3% recognized cirrhosis in our case scenario. Almost 80% of respondents inappropriately preferred prescribing a narcotic or nonsteroidal anti-inflammatory drug over acetaminophen (4%) for pain control in a patient with cirrhosis. While less than 60% recognized HBeAg negative CHB as an indication for referral and treatment, 90% would have referred a patient in the immune-tolerant phase, even though treatment is not indicated. CONCLUSIONS: Knowledge gaps regarding CHB among family medicine trainees in the areas of primary prevention, disease recognition and management of cirrhosis were identified. Results suggest that opportunities to prevent potentially life-threatening complications are being missed.