Mutations in Hepatitis D Virus Allow It to Escape Detection by CD8 T Cells and Evolve at the Population Level.

Background & Aims: Hepatitis D virus (HDV) superinfection in patients with hepatitis B virus (HBV) is associated with rapid progression to liver cirrhosis and hepatocellular carcinoma. Treatment options are limited, and no vaccine is available. Although HDV-specific CD8 T cells are thought to control the virus, little is known about which HDV epitopes are targeted by virus-specific CD8 T cells or why these cells ultimately fail to control the infection.

Amino Acid Substitutions within HLA-B*27-Restricted T Cell Epitopes Prevent Recognition by Hepatitis Delta Virus-Specific CD8 T Cells.

Virus-specific CD8 T cell response seems to play a significant role in the outcome of hepatitis delta virus (HDV) infection. However, the HDV-specific T cell epitope repertoire and mechanisms of CD8 T cell failure in HDV infection have been poorly characterized. We therefore aimed to characterize HDV-specific CD8 T cell epitopes and the impacts of viral mutations on immune escape.

Structured reporting of CT examinations in acute pulmonary embolism.

Objectives: To evaluate the effect of structured reporting of CT pulmonary angiography (CTPA) studies on the content, clarity and clinical usefulness of radiology reports in acute pulmonary embolism (PE).

Methods: Conventional and structured reports were generated for 41 patients with a CTPA positive for acute PE. Conventional reports were dictated in a free-text form using speech recognition; structured reports contained a consistent ordering of observations with standardized subheadings.

Virus-Specific CD4+ T Cells Have Functional and Phenotypic Characteristics of Follicular T-Helper Cells in Patients With Acute and Chronic HCV Infections.

Background & Aims: Follicular T-helper (Tfh) cells contribute to pathogen-specific antibody responses by providing maturation signals to B cells. In mice with viral infections, virus-specific Tfh cells expand and are required to contain the infection. However, less is known about human virus-specific Tfh cells or their functions during infection.

Dysfunctional CD8+ T cells in hepatitis B and C are characterized by a lack of antigen-specific T-bet induction.

The transcription factor T-bet regulates the production of interferon-γ and cytotoxic molecules in effector CD8 T cells, and its expression correlates with improved control of chronic viral infections. However, the role of T-bet in infections with differential outcome remains poorly defined. Here, we report that high expression of T-bet in virus-specific CD8 T cells during acute hepatitis B virus (HBV) and hepatitis C virus (HCV) infection was associated with spontaneous resolution, whereas T-bet deficiency was more characteristic of chronic evolving infection.

Inhibitory phenotype of HBV-specific CD4+ T-cells is characterized by high PD-1 expression but absent coregulation of multiple inhibitory molecules.

Background: T-cell exhaustion seems to play a critical role in CD8+ T-cell dysfunction during chronic viral infections. However, up to now little is known about the mechanisms underlying CD4+ T-cell dysfunction during chronic hepatitis B virus (CHB) infection and the role of inhibitory molecules such as programmed death 1 (PD-1) for CD4+ T-cell failure.

Methods: The expression of multiple inhibitory molecules such as PD-1, CTLA-4, TIM-3, CD244, KLRG1 and markers defining the grade of T-cell differentiation as CCR7, CD45RA, CD57 and CD127 were analyzed on virus-specific CD4+ T-cells from peripheral blood using a newly established DRB1*01-restricted MHC class II Tetramer.

Lack of variant specific CD8+ T-cell response against mutant and pre-existing variants leads to outgrowth of particular clones in acute hepatitis C.

Background: CTL escape mutations have been described during acute hepatitis C in patients who developed chronic disease later on. Our aim was to investigate the mutual relationship between HCV specific CD8+ T cells and evolution of the viral sequence during early acute HCV infection.

Results: We sequenced multiple clones of NS3 1406 epitope in 4 HLA-A*02 patients with acute hepatitis C genotype 1b infection.

Influence of hepatitis C virus infection and high virus serum load on biliary complications in liver transplantation.

Background: Biliary complications (BCs) and recurrent hepatitis C virus (HCV) infection are among the major causes of morbidity and graft loss following liver transplantation. The influence of HCV on BCs has not been definitely clarified.

Patients And Methods: We performed a retrospective cohort study to analyze risk factors and outcome of post orthotopic liver transplantation (OLT) BCs in 352 liver transplant recipients over 12 years in Munich, Germany (n = 84 with HCV; living donor and re-OLT were excluded).

Inhibitory molecules that regulate expansion and restoration of HCV-specific CD4+ T cells in patients with chronic infection.

Background & Aims: Inhibitory receptors such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen (CTLA)-4 mediate CD8+ T-cell exhaustion during chronic viral infection, but little is known about roles in dysfunction of CD4+ T cells.

Methods: We investigated the functions of inhibitory molecules on hepatitis C virus (HCV)-, influenza-, and Epstein-Barr virus (EBV)-specific CD4+ T cells in patients with chronic infections compared with patients with resolved HCV infection and healthy donors. Expression of PD-1, CTLA-4, CD305, and CD200R were analyzed on HCV-specific CD4+ T cells, isolated from peripheral blood using major histocompatibility complex class II tetramers.

The immunoregulatory role of CD244 in chronic hepatitis B infection and its inhibitory potential on virus-specific CD8+ T-cell function.

Unlabelled: Multiple inhibitory receptors may play a role in the weak or absent CD8+ T-cell response in chronic hepatitis B virus (HBV) infection. Yet few receptors have been characterized in detail and little is known about their complex regulation. In the present study, we investigated the role of the signaling lymphocyte activation molecule (SLAM)-related receptor CD244 and of programmed death 1 (PD-1) in HBV infection in 15 acutely and 66 chronically infected patients as well as 9 resolvers and 21 healthy controls.

Intra-hepatic splenosis as an unexpected cause of a focal liver lesion in a patient with hepatitis C and liver cirrhosis: a case report.

Introduction: Splenosis is the heterotopic autotransplantation of splenic tissue, mostly found after splenic trauma or surgery in the abdominal, pelvic or thoracic cavity. Here we report a patient with a history of splenectomy after polytrauma with chronic hepatitis C and liver cirrhosis presenting with an hepatic mass of unknown origin.

Case Presentation: The lesion could not be exactly classified by ultrasound, computed tomography, angiography and biopsy, classical features of malignancy were not fulfilled, and on the other hand a neoplastic process could neither be excluded.

FOXP3 expression in hepatitis C virus-specific CD4+ T cells during acute hepatitis C.

Background & Aims: Down-regulation of hepatitis C virus (HCV)-specific CD4(+) T-cell responses is a hallmark of chronic viral persistence in acute hepatitis C. FOXP3(+)CD25(+)CD4(+) regulatory T cells can modulate HCV-specific immune responses in vitro, but the role of virus-specific regulatory T cells in the pathogenesis of chronic viral persistence is unknown.

Methods: Two novel HLA-DR15 tetramers were synthesized to study the kinetics and phenotype of FOXP3(+)-expressing HCV-specific CD4(+) T cells from 10 patients with acute hepatitis C and 15 patients with chronic hepatitis C.

Antiviral therapy for recurrent hepatitis C after liver transplantation: sustained virologic response is related to genotype 2/3 and response at week 12.

Objectives: Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) is a major cause of transplant failure in HCV-positive patients. We retrospectively assessed the efficacy and safety of antiviral therapy and determined the factors influencing sustained virologic response (SVR) in LT recipients.

Methods: Between 1998 and 2007, we treated 36 LT recipients for hepatitis C cirrhosis and subsequent HCV recurrence (27 genotype 1 and 9 genotypes 2/3) with pegylated interferon alpha-2a (180 microg/week), pegylated interferon alpha-2b (1.

Recurrence of hepatitis C virus during leucocytopenia and spontaneous clearance after recovery from cytopenia: a case report.

Introduction: There is little information about the risk of HCV recurrence in immunosuppressed patients. Although the presence of antibodies to HCV and the absence of HCV-RNA is usually considered to indicate viral elimination, the virus may not be completely eliminated but may be under control of an effective immune response.

Case Presentation: A 69 year old man presented with jaundice, elevated ALT, AST, lipase and concomitant abdominal pain.

[Orellanus syndrome: a rare cause of acute renal failure].

History And Clinical Findings: A 26-year-old woman with no contributory medical history became anuric after several days of nausea and vomiting. She was admitted to our hospital with suspected acute renal failure.

Investigations: Laboratory tests revealed greatly elevated BUN and creatinine.