Cases of chronic or prolonged hepatitis E virus (HEV) infections have been described in solid organ transplant recipients, HIV infected patients and in patients with malignancies or idiopathic CD4+ T ...lymphopenia. It is unknown if HEV infection also takes chronic courses in patients with common variable immunodeficiency (CVID). We studied a cohort of 73 CVID patients recruited in a low endemic Central European country. None of the subjects tested positive for HEV RNA or anti-HEV IgG. Immunoglobulin transfusions (n=10) tested negative for HEV RNA but all were anti-HEV positive. To verify that such pooled blood products contain anti-HEV protective antibodies we measured the anti-HEV IgG optical density (OD) values in patients before and after transfusion. Anti-HEV OD values increased after infusion but did not reach the cut-off considered as positive. Thus, chronic HEV infections seem to be rare events in CVID patients in Germany. Commercially available immuno globulin infusions contain anti HEV antibodies and may contribute to protection from HEV infection
Background & Aims
While hepatitis E virus infections are a relevant topic in Europe, knowledge about epidemiology of hepatitis E virus infections in the USA and Latin America is still limited. Aim of ...this study was to estimate anti‐hepatitis E virus IgG seroprevalence in the Americas and to assess whether low socioeconomic status is associated with hepatitis E virus exposure.
Methods
We performed a systematic review and meta‐analysis. Literature search was performed in PubMed for articles published 01/1994‐12/2016. Prevalence was estimated using a mixed‐effects model and reported in line with PRISMA reporting guidelines.
Results
Seroprevalence was significantly higher in the USA than in Latin America, independently of assay, patient cohort, methodological quality or study year (OR: 1.82 (1.06‐3.08), P = .03). Patients in the USA had a more than doubled estimated seroprevalence (up to 9%, confidence interval 5%‐15.6%) than those in Brazil (up to 4.2%, confidence interval 2.4%‐7.1%; OR: 2.27 (1.25‐4.13); P = .007) and Mixed Caribbean (up to 1%, OR: 8.33 (1.15‐81.61); P = .04). A comparison with published data from Europe demonstrated that anti‐hepatitis E virus seroprevalence in the USA and Europe did not differ significantly (OR: 1.33 (0.81‐2.19), P = .25), while rate in South America was significantly lower than that in Europe (OR: 0.67 (0.45‐0.98), P = .04).
Conclusions
Hepatitis E virus is common in the USA. Surprisingly, the risk of hepatitis E virus exposure was low in many South American countries. Seroprevalence did not differ significantly between Europe and the USA. Hence, hepatitis E virus is not limited to countries with low sanitary standards, and a higher socioeconomic status does not protect populations from hepatitis E virus exposure.
Stopping long-term nucleos(t)ide analogue therapy increases hepatitis B virus (HBV) surface antigen (HBsAg) loss rates in HBV e antigen (HBeAg)-negative patients. Viral rebound may induce immune ...responses facilitating functional cure. We analyzed which factors are associated with timing of virological relapse in 220 Asian HBeAg-negative patients from the prospective ABX203 vaccine study. Unexpectedly, only the type of antiviral therapy was significantly associated with early virological relapse, defined as an HBV DNA load of >2000 IU/mL until week 12, and relapse occurred earlier in patients treated with tenofovir versus those treated with entecavir (median time, 6 vs 24 weeks; P < .0001). This should be considered for future trials and monitoring of patients after treatment discontinuation.
Patients who discontinue nucleo(s)tide analogue therapy are at risk of viral rebound and severe hepatitis flares, necessitating intensive off-treatment follow-up.
We studied the association between ...hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels at off-treatment follow-up week 24 (FU W24), with subsequent clinical relapse, and HBsAg loss in a multicenter cohort of hepatitis B e antigen (HBeAg)–negative patients with chronic hepatitis B who discontinued nucleo(s)tide analogue therapy.
We studied 475 patients, 82% Asian, and 55% treated with entecavir. Patients with higher HBV DNA levels at FU W24 had a higher risk of clinical relapse (hazard ratio HR, 1.576; P < .001) and a lower chance of HBsAg loss (HR, 0.454; P < .001). Similarly, patients with higher HBsAg levels at FU W24 had a higher risk of clinical relapse (HR, 1.579; P < .001) and a lower chance of HBsAg loss (HR, 0.263; P < .001). A combination of both HBsAg <100 IU/mL and HBV DNA <100 IU/mL at FU W24 identified patients with excellent outcomes (9.9% clinical relapse and 58% HBsAg loss at 216 weeks of follow-up). Conversely, relapse rates were high and HBsAg loss rates negligible among patients with both HBsAg >100 IU/mL and HBV DNA >100 IU/mL (P < .001).
Among HBeAg-negative patients with chronic hepatitis B who discontinued antiviral therapy and who did not experience clinical relapse before FU W24, serum levels of HBV DNA and HBsAg at FU W24 can be used to predict subsequent clinical relapse and HBsAg clearance. A combination of HBsAg <100 IU/mL with HBV DNA <100 IU/mL identifies patients with a low risk of relapse and excellent chances of HBsAg loss and could potentially be used as an early surrogate end point for studies aiming at finite therapy in HBV.
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The current multicenter study shows that blood levels of hepatitis B virus DNA and hepatitis B surface antigen at 24 weeks after withdrawal of antiviral treatment can predict subsequent outcomes. These findings can be used to identify patients who may or may not require retreatment.
Background. Hepatitis D virus (HDV) infection affects 15–20 million individuals worldwide and causes severely progressive hepatitis. It is unknown to what extent cellular immune responses contribute ...to liver disease and control of viral replication in HDV infection. Methods. Immune cell frequencies and phenotypes were determined in 49 HDV-infected patients, 25 individuals with hepatitis B virus monoinfection and 18 healthy controls. T-cell proliferative and cytokine-producing capacities were analyzed by stimulation with overlapping peptides spanning the large HDV antigen. To restore T-cell responses, blocking antibodies (anti-cytotoxic T-lymphocyte antigen 4, anti-programmed death ligand 1) or proinflammatory cytokines (interleukin IL 12) were used. Results. Immune cell frequencies and phenotypes did not vary between the groups. Exclusively, the senescence marker CD57 was significantly up-regulated in CD8⁺ T cells from patients with hepatitis delta. HDV-specific T-cell proliferation and cytokine production were weak and could only partly be rescued by blockade of the programmed death 1 pathway. However, a more robust and consistent increase in HDV-specific CD4⁺ and CD8⁺ T-cell responses was evident when the third signal cytokine IL-12 was added, which also affected cytomegalovirus- and Epstein-Barr virus-specific T cells. Conclusions. This investigation of virus-specific T-cell immunity in patients with HDV infection, the largest to date, revealed premature aging of immune cells and impaired T-cell functionality. This could be restored by blocking inhibitory pathways and, in particular, by supplementing with IL-12.
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