Hepatitis C virus core antigen testing in liver and kidney transplant recipients.

HCV RNA levels correlate with the long-term outcome of hepatitis C in liver transplant recipients. Nucleic acid testing (NAT) is usually used to confirm HCV reinfection and to examine viral loads after liver transplantation. HCV core antigen (HCVcoreAg) testing could be an alternative to NAT with some potential advantages including very low intra- and interassay variabilities and lower costs. The performance of HCVcoreAg testing in organ transplant recipients is unknown. We prospectively studied 1011 sera for HCV RNA and HCVcoreAg in a routine real-world setting including 222 samples obtained from patients after liver or kidney transplantation. HCV RNA and HCVcoreAg test results showed a consistency of 98% with a very good correlation in transplanted patients (r > 0.85). The correlation between HCV RNA and HCVcoreAg was higher in sera with high viral loads and in samples from patients with low biochemical disease. Patients treated with tacrolimus showed a better correlation between both parameters than individuals receiving cyclosporine A. HCV RNA/HCVcoreAg ratios did not differ between transplanted and nontransplanted patients, and HCV RNA and HCVcoreAg kinetics were almost identical during the first days after liver transplantation. HCVcoreAg testing can be used to monitor HCV viral loads in patients after organ transplantation. However, the assay is not recommended to monitor antiviral therapies.

Liver fibrosis - mouse models and relevance in human liver diseases.

Liver fibrosis, the excessive accumulation of extracellular matrix (ECM) in the liver, develops as a long-term consequence of chronic liver injury, and significantly contributes to the mortal complications of chronic liver disease. Different cell types contribute to the hepatic wound healing response. Hepatic stellate cells (HSC) are the main fibrogenic cell in the liver. Upon liver injury, HSCs transdifferentiate into myofibroblasts and contribute to ECM deposition in the liver. Small animal models have provided insight into the activation process of HSCs and the complex interplay of the different cell types involved in liver fibrogenesis. Animal models not only allow one to identify relevant profibrogenic pathways, but also to test the contribution of these pathways to liver disease in preclinical settings. In this review, mouse models of toxic, cholestatic, apoptotic, acoholic, viral and metabolic liver fibrosis will be discussed, with a particular emphasis on the underlying pathophysiology, relevance to human liver disease and drug development.

Renal function during treatment with adefovir plus peginterferon alfa-2a vs either drug alone in hepatitis B/D co-infection.

Long-term safety of treatment with hepatitis B virus (HBV) polymerase inhibitors is a concern. Adefovir dipivoxil (ADV) therapy has previously been associated with impairment of renal function. Limited data are available on the safety of combination therapy with nucleos(t)ide analogues and interferon alfa (IFNα). The aim of this analysis was to assess the renal function during combination therapy with peginterferon alfa-2a (PegIFNα-2a) plus ADV vs either drug alone in patients with hepatitis B/D co-infection. We performed a retrospective analysis of renal function data of patients treated in the Hep-Net/International Delta Hepatitis Intervention Trial 1(HIDIT-1-trial), a European multicenter study to investigate the efficacy of 48 weeks of therapy with PegIFNα-2a+ADV vs either drug alone in 90 patients with chronic hepatitis B/D co-infection. Glomerular filtration rates (GFR) were calculated by Cockcroft-Gault (CG), abbreviated Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. After 48 weeks of therapy GFR values were significantly lower in patients receiving adefovir-containing treatment vs PegIFNα-2a alone [mean difference 16.1 mL/min (CG) and 10.2 mL/min (MDRD), respectively, P < 0.05] while no differences were observed between patients receiving adefovir alone vs combination treatment. Twenty-four weeks after treatment GFR values did not differ between treatment arms. A decrease in GFR ≥ 20% was observed more often in patients during adefovir-containing treatment vs PegIFNα-2a alone (P < 0.05) which was confirmed by Kaplan-Meier analysis. Adefovir-containing but not PegIFNα-2a treatment was associated with a decrease in GFR values in about one-fifth of patients. Combination treatment of PegIFNα-2a+ADV in chronic hepatitis B/D co-infection did not lead to any further impairment of kidney function.

ARFI elastography of the spleen is inferior to liver elastography for the detection of portal hypertension.

PURPOSE: To date, the use of transient elastography has been limited to the liver. Acoustic radiation force impulse imaging (ARFI) is a new technology offering elastography of different tissues. Here, we present initial spleen elastography data and evaluate its influencing factors, especially portal hypertension. MATERIALS AND METHODS: Elastography of the spleen and liver using the ARFI method was performed in 30 patients with portal hypertension, 70 patients with chronic liver disease without portal hypertension and 25 healthy controls. RESULTS: ARFI elastography of the spleen was feasible in 99% of patients and valid in 78%. The mean propagation velocity inside the spleen was 2.95 ± 0.60 m/sec, thus much higher than in the normal liver (< 1.10 m/sec). Spleen stiffness was higher in the patients with portal hypertension (p < 0.008) but did not correlate to spleen size. Spleen stiffness increased with patient age and liver stiffness (both p < 0.0001) as confirmed by multivariate analysis (R2 = 0.19, p < 0.01). In ROC analysis, spleen elastography was inferior to liver elastography for the detection of portal hypertension (area under the curve 0.68 vs. 0.90). CONCLUSION: The new ARFI method allows accurate elastography of the spleen. The stiffness of the normal spleen is much higher than that of the normal liver and increases with age. However, spleen elastography is inferior to liver elastography for the detection of portal hypertension.

Simultaneous mitral valve replacement and liver transplantation.

We report the case of a 57-year-old man who underwent successful simultaneous surgery involving mitral valve replacement for acute endocarditis and orthotopic liver transplantation for end-stage liver disease.

[Interferon-alfa induced reactivation of sarcoidosis in a patient with chronic hepatitis C]. / Interferon-alpha-induzierte Reaktivierung einer Sarkoidose bei einer Patientin mit chronischer Hepatitis C.

The data on reactivation of sarcoidosis during treatment with interferon-alfa is unsatisfactory. We here report the case of a female patient with a history of sarcoidosis more than 20 years ago. Due to chronic hepatitis C the patient was treated with pegylated interferon-alfa and ribavirin. Beginning in the 32(nd) week, the patient developed a reactivation of sarcoidosis. The antiviral therapy was continued until week 48 without administration of systemic steroids. Six month after the end of antiviral treatment the sarcoidosis was in remission and the hepatitis C was cured.

Peripheral blood dendritic cells are phenotypically and functionally intact in chronic hepatitis B virus (HBV) infection.

Persistence of hepatitis B virus (HBV) infection is associated with reduced anti-viral T cell responses. Impaired dendritic cell (DC) function was suggested as the cause of reduced T cell stimulation in chronic HBV carriers. Thus, we compared myeloid (mDC) and plasmacytoid DC (pDC) from chronic HBV carriers and controls. Frequency and phenotype of isolated DC were analysed by fluorescence activated cell sorter staining, DC function by mixed lymphocyte reaction, cytokine bead array, intracellular cytokine staining, enzyme-linked immunosorbent assay and enzyme-linked immunospot. Expression of HBV DNA and mRNA was studied by polymerase chain reaction (PCR). Circulating total DC, mDC or pDC were not reduced in chronic HBV carriers. Isolated mDC and pDC from chronic HBV carriers exhibited similar expression of co-stimulatory molecules and alloreactive T helper cell stimulation as control DC, whether tested directly ex vivo or after in vitro maturation. Secretion of pro- and anti-inflammatory cytokines by CD40 or Toll-like receptor ligand-stimulated patient DC was intact, as was human leucocyte antigen A2-restricted HBV-specific cytotoxic lymphocyte stimulation. Although both DC populations contained viral DNA, viral mRNA was undetectable by reverse transcription-PCR, arguing against viral replication in DC. We found no quantitative, phenotypic or functional impairment of mDC or pDC in chronic hepatitis B, whether studied ex vivo or after in vitro maturation.