Negative Regulation of Hepatitis C Virus Specific Immunity Is Highly Heterogeneous and Modulated by Pegylated Interferon-Alpha/Ribavirin Therapy

Specific inhibitory mechanisms suppress the T-cell response against the hepatitis C virus (HCV) in chronically infected patients. However, the relative importance of suppression by IL-10, TGF-beta and regulatory T-cells and the impact of pegylated interferon-alpha and ribavirin (PegIFN-alpha/ribavirin) therapy on these inhibitory mechanisms are still unclear. We revealed that coregulation of the HCV-specific T-cell responses in blood of 43 chronic HCV patients showed a highly heterogeneous pattern before, during and after PegIFN-alpha/ribavirin. Prior to treatment, IL-10 mediated suppression of HCV-specific IFN-gamma production in therapy-naive chronic HCV patients was associated with higher HCV-RNA loads, which suggests that protective antiviral immunity is controlled by IL-10. In addition, as a consequence of PegIFN-alpha/ribavirin therapy, negative regulation of especially HCV-specific IFN-gamma production by TGF-beta and IL-10 changed dramatically. Our findings emphasize the importance of negative regulation for the dysfunctional HCV-specific immunity, which should be considered in the design of future immunomodulatory therapies. Citation: Claassen MAA, de Knegt RJ, Turgut D, Groothuismink ZMA, Janssen HLA, et al. (2012) Negative Regulation of Hepatitis C Virus Specific Immunity Is Highly Heterogeneous and Modulated by Pegylated Interferon-Alpha/Ribavirin Therapy. PLoS ONE 7(11): e49389. doi:10.1371/journal.pone.004938

Evaluation of IL-28B Polymorphisms and Serum IP-10 in Hepatitis C Infected Chimpanzees

In humans, clearance of hepatitis C virus (HCV) infection is associated with genetic variation near the IL-28B gene and the induction of interferon-stimulated genes, like IP-10. Also in chimpanzees spontaneous clearance of HCV is observed. To study whether similar correlations exist in these animals, a direct comparison of IP-10 and IL-28B polymorphism between chimpanzees and patients was performed. All chimpanzees studied were monomorphic for the human IL-28B SNPs which are associated with spontaneous and treatment induced HCV clearance in humans. As a result, these particular SNPs cannot be used for clinical association studies in chimpanzees. Although these human SNPs were absent in chimpanzees, gene variation in this region was present however, no correlation was observed between different SNP-genotypes and HCV outcome. Strikingly, IP-10 levels in chimpanzees correlated with HCV-RNA load and gamma GT, while such correlations were not observed in humans. The correlation between IP-10, cGT and virus load in chimpanzees was not found in patients and may be due to the lack of lifestyle-related confounding factors in chimpanzees. Direct comparison of IP-10 and IL-28B polymorphism between chimpanzees and patients in relation to HCV infection, illustrates that the IFN-pathways are important during HCV infection in both species. The Genbank EMBL accession numbers assigned to chimpanzees specific sequences near the IL-28B gene are HE599784 and HE599785

Prevalence and predictors of complementary and alternative medicine modalities in patients with chronic hepatitis B

Background & Aims The use of complementary and alternative medicine (CAM) in patients with chronic hepatitis B (CHB) can interact with antiviral treatment or influence health‐seeking behaviour. We aimed to study the use of individual CAM modalities in CHB and explore determinants of use, particularly migration‐related, socio‐economic and clinical factors. Methods A total of 436 CHB outpatients who attended the Toronto Centre for Liver Disease in 2015‐2016 were included in this cross‐sectional study. Using the comprehensive I‐CAM questionnaire and health records, data were collected on socio‐demographic and clinical variables and on usage of 16 CAM modalities in the last year. Results Sixty percent of patients were male, 74% were Asian and 46% were using antiviral treatment. Three‐hundred and nine (71%) patients used CAM. Vitamin/mineral preparations (45% of patients) were most commonly used. Overall CAM use and the specific use of potentially injurious CAM, such as green tea extract (9.2%) and St. John's wort (0.2%), were not associated with liver disease severity. Female sex, family history of CHB, lower serum HBV DNA, and higher socio‐economic status were independently associated with bio‐holistic CAM use, the clinically most‐relevant CAM group (P < 0.05); ethnicity, antiviral therapy use and liver disease severity were not. Conclusions CAM use among CHB patients was extensive, especially use of vitamin and mineral preparations, but without direct influence on liver disease severity. Bio‐holistic CAM use appeared to be associated with socio‐economic status rather than with ethnicity or liver disease severity. Despite the rare use of hepatotoxins, physicians should actively inquire about it

Etiology, Management, and Outcome of the Budd-Chiari Syndrome

Background: The Budd-Chiari syndrome (BCS) is hepatic venous outflow obstruction. What is known about the syndrome is based on small studies of prevalent cases. Objective: To characterize the causes and treatment of incident BCS. Design: Consecutive case series of patients with incident BCS, enrolled from October 2003 to October 2005 and followed until May 2006. Setting: Academic and nonacademic hospitals in France, Spain, Italy, Great Britain, Germany, Belgium, the Netherlands, Portugal, and Switzerland. Patients: Persons older than 16 years with definite hepatic outflow obstruction diagnosed by imaging. Persons with hepatic outflow obstruction due to heart failure, sinusoidal obstruction syndrome, cancer, or liver transplantation were excluded. Measurements: Signs and symptoms; laboratory and imaging findings; diagnosis; treatment; and overall, transplantation-free, and intervention-free survival. Results: 163 incident cases of BCS were identified. Median follow-up was 17 months (range, 0.1 to 31 months). Most patients (84%) had at least 1 thrombotic risk factor, and many (46%) had more than 1; the most common was myeloproliferative disorders (49% of 103 tested patients). Patients were mainly treated with anticoagulation (140 patients [86%]), transjugular intrahepatic porto-systemic shunting (56 patients [34%]), or liver transplantation (20 patients [12%]), and 80 patients (49%) were managed noninvasively. Only 3 patients underwent surgical shunting. The survival rate was 87% (95% CI, 82% to 93%) at 1 year and 82% (CI, 75% to 88%) at 2 years. Limitation: Treatment was not standardized across all centers, and data on important clinical variables were missing for some patients. Conclusion: Most patients with BCS have at least 1 thrombotic risk factor, and many have more than 1; myeloproliferative disorders are most common. One- and 2-year survival rates are good with contemporary management, which includes noninvasive therapies (anticoagulation and diuretics) and invasive techniques. Transjugular intrahepatic portosystemic shunting seems to have replaced surgical shunting as the most common invasive therapeutic procedure. Primary Funding Source: Fifth Framework Programme of the European Commission