Toll‐like receptors (TLRs) play a key role in transplantation biology. The effect of immunosuppression on TLR function after liver transplantation is unknown. Peripheral blood mononuclear cells (PBMCs) from 113 post–liver transplant patients and 13 healthy controls were stimulated with TLR‐specific ligands [lipopolysaccharide (TLR4), pan‐3‐cys (P3C) (TLR2), Poly (I:C) (PIC) (TLR3), R848 (TLR7/8), and CpG (TLR9)] for 24 hours. PBMCs from 5 healthy controls were also cultured with therapeutic concentrations of cyclosporine A (CYA) and tacrolimus (TAC). Cytokine production was measured with enzyme‐linked immunosorbent assays and flow cytometry. PBMCs from patients on calcineurin inhibitors after liver transplantation produced less interleukin‐6 (IL‐6) and tumor necrosis factor α (TNFα) in response to TLR2 stimulation (IL‐6: P=0.02; TNFα: P=0.01), TLR4 stimulation (IL‐6: P=0.02; TNFα: P=0.01), and TLR7/8 stimulation (IL‐6: P=0.02; TNFα: P=0.02), compared with healthy controls. Both CD56bright and CD56dim natural killer (NK) cells from patients on calcineurin inhibitors also produced less interferon‐γ (IFNγ) with TLR7/8 stimulation compared with healthy controls (CD56bright: P=0.002; CD56dim: P=0.004). Similar findings were demonstrated in healthy PBMCs cultured with CYA (PBMCs: TLR2, IL‐6: P=0.005; TLR4, IL‐6: P=0.03, TNFα: P=0.03; TLR7/8, IL‐6: P=0.02, TNFα: P=0.01; CD56dim NK cells: TLR7/8, IFNγ: P=0.03). TAC impaired TLR4‐mediated IL‐6 and TNFα production by PBMCs (IL‐6; P = 0.02; TNFα P = 0.009). In conclusion, patients on calcineurin inhibitors had impaired inflammatory cytokine production in response to TLR2, TLR4, and TLR7/8 stimulation compared comparison with healthy controls. Importantly, TAC and CYA appear to have different effects on TLR signaling. Impaired TLR function has important repercussions for risk of infection, graft rejection, and disease recurrence after transplantation, and the different immunosuppressive profiles of CYA and TAC may guide the choice of therapy to improve disease outcomes. Liver Transpl 19:1099‐1107, 2013. © 2013 AASLD.

SUMMARYThe diagnosis of acute pancreatitis requires the presence of at least two of the three diagnostic criteria -characteristic abdominal pain, elevated serum amylase or lipase, and radiological evidence of pancreatitis.Serum concentrations of amylase and lipase rise within hours of the pancreatic injury. A threshold concentration 2-4 times the upper limit of normal is recommended for diagnosis.

Background and Aims: Current guidelines recommend long-term nucleot(s)ide analogue (NA) therapy for patients with HBeAg-negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss. Methods:We performed a prospective multi-centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg-negative CHB, the absence of cirrhosis and HBVDNA

No abstract

Acute and chronic infection with hepatitis B virus (HBV) is associated with an increased risk of developing liver disease including cirrhosis, decompensated liver disease, and hepatocellular carcinoma. The clinical presentation and natural history of HBV infection is mediated through complex interactions between the virus and the host immune response. HBV is not directly cytopathic to heptocytes; however, the interaction between the virus and the host immune response plays a central role in the pathogenesis of necroinflammation and liver fibrosis. Emerging data from immunopathogenesis studies in animal models and in vitro studies of liver biopsies from patients with chronic hepatitis B demonstrate a potentially important interaction between hepatitis B e antigen, HBV, and components of the innate immune response including Toll-like receptors, Kupffer cells, natural killer T-cells, and dendritic cells. These findings suggest that the innate immune response has an important role in influencing the outcome of acute and chronic HBV infection. The current knowledge regarding the interaction between HBV and components of the innate immune response during acute and chronic HBV infection is reviewed.

In the context of a small possible effect size and high frequency in Asian populations, IL28B genotyping is likely to have, at best, limited clinical utility for predicting peg-IFN treatment outcome for CHB patients in the Asia-Pacific region.

Recurrence of hepatitis C (HCV

In everyday clinical practice PEG-IFN therapy in CHB is well tolerated and can achieve a similar efficacy to that seen in large controlled trials.