Search

Objectives: Spleen stiffness (SS) correlates with liver stiffness (LS) and hepatic venous pressure gradient. The latter is currently the most accurate predictor of hepatic decompensation. Our study aims to check whether SS has a similar predictive capability, while being an easy-to-perform noninvasive test in a real-life patient cohort., Methods: Concomitantly, 210 successive patients were examined and received liver and SS measurements and a standard laboratory. Patients were observed for 1 year in terms of clinical signs of decompensation., Results: One hundred fifty-nine of the initial 210 patients had a valid LS and SS measurement and were evaluable for clinical follow-up. Twelve patients developed a hepatic decompensation; with a SS >39 kPa (P=0.0005). Especially in a group with elevated LS, patients with a high risk of decompensation could be identified using SS. Patients with comparable LS who suffered from acute liver damage had significantly lower SS than respective patients with chronic liver damage (30.97 vs. 46.03 kPa; P=0.04). Acute liver failure was associated with elevated LS (16.47 kPa) but not with elevated SS (30.97 kPa)., Conclusions: The risk of a hepatic decompensation can easily be assessed using SS measurement. Therefore SS measurement might be a powerful screening tool identifying patients who need closer monitoring. Moreover, SS is able to differentiate between acute and chronic or acute on chronic liver damage.

Unlabelled: Activation of hepatitis B virus (HBV)-specific CD8 T cells by therapeutic vaccination may promote sustained control of viral replication by clearance of covalently closed circular DNA from infected hepatocytes. However, little is known about the exact targets of the CD8 T-cell response and whether HBV reproducibly evades CD8 T-cell immune pressure by mutation. The aim of this study was to address if HBV reproducibly selects substitutions in CD8 T-cell epitopes that functionally act as immune escape mutations. The HBV core gene was amplified and sequenced from 148 patients with chronic HBV infection, and the human leukocyte antigen (HLA) class I genotype (A and B loci) was determined. Residues under selection pressure in the presence of particular HLA class I alleles were identified by a statistical approach utilizing the novel analysis package SeqFeatR. With this approach we identified nine residues in HBV core under selection pressure in the presence of 10 different HLA class I alleles. Additional immunological experiments confirmed that seven of the residues were located inside epitopes targeted by patients with chronic HBV infection carrying the relevant HLA class I allele. Consistent with viral escape, the selected substitutions reproducibly impaired recognition by HBV-specific CD8 T cells., Conclusion: Viral sequence analysis allows identification of HLA class I-restricted epitopes under reproducible selection pressure in HBV core; the possibility of viral escape from CD8 T-cell immune pressure needs attention in the context of therapeutic vaccination against HBV., (© 2015 by the American Association for the Study of Liver Diseases.)

Unlabelled: Acute liver failure (ALF) is associated with massive short-term cell death, whereas chronic liver injury is accompanied by continuous cell death. Hepatic stellate cells (HSCs) contribute to tissue repair and liver fibrosis in chronic liver injury, although their role in ALF remains unexplained. Twenty-nine patients (median age = 43 years, 17 females and 12 males) with ALF according to the Acute Liver Failure Study Group criteria were included. Upon the diagnosis of ALF and after 7 days, we determined liver stiffness (LS) with FibroScan, standard laboratory parameters, and serum levels of matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-9, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, hyaluronic acid, and markers of overall cell death (M65) and apoptosis (M30). Stellate cell activation and progenitor response were analyzed immunohistochemically in biopsy samples of 12 patients with alpha-smooth muscle actin (alpha-SMA), keratin-17, and keratin-19 staining, respectively. Cell death markers (M30 level = 2243 +/- 559.6 U/L, M65 level = 3732 +/- 839.9 U/L) and fibrosis markers (TIMP-1 level = 629.9 +/- 69.4 U/mL, MMP-2 level = 264 +/- 32.5 U/mL, hyaluronic acid level = 438.5 +/- 69.3 microg/mL) were significantly increased in patients versus healthy controls. This was paralleled by collagen deposition, elevated alpha-SMA expression, and higher LS (25.6 +/- 3.0 kPa). ALF was associated with ductular progenitor proliferation., Conclusion: Our results demonstrate HSC activation and a progenitor response in ALF. Positive correlations between LS, the degree of liver cell damage, and the intensity of HSC activation suggest that fibrosis is a response to ALF in an attempt to repair damaged tissue.

The unique ability of the liver to regenerate quickly after resection makes living donor liver transplantation (LDLT) possible. This technique uses the unique ability of the liver to regenerate to full size after partial resection. However, the quality and course of this regeneration process in humans are still widely unexplored. In the present study we investigated the quantitative liver function tests galactose elimination capacity (GEC), indocyanine green half-life (ICG), and lidocaine half-life as markers for the quality of the liver regeneration in the first 3 months after LDLT. In this study, 22 consecutive living liver donors and their corresponding recipients were analyzed at baseline and at 10 and 90 days after LDLT. Six recipients lost their grafts during the study period. We compared donors and recipients at the different time points. After LDLT, GEC decreased (-42.6%) and ICG increased (+50.6%) significantly in donors. ICG and GEC remained significantly altered over 3 months in donors with an improvement between days 10 and 90 (GEC, +59.3%; ICG, -9.1%). ICG and GEC improved significantly in recipients between days 10 and 90 (ICG, -63.7%; GEC, +16.3%). The lidocaine half-life showed no significant changes. The donors had better test results and recovered faster than the recipients. In conclusion, after LDLT the parameters for liver capacity and flow remain altered in donors and recipients despite rapid volume growth., (Copyright 2006 AASLD)

Our objective was to study the kinetics of recovery of the liver volume and liver function after right hepatectomy (RH) for living donation, comparing conventional and quantitative liver function tests, i.e., galactose elimination capacity (GEC). A total of 27 donors underwent RH averaging 61% of the whole liver volume. The conventional and quantitative liver function tests, as well as magnetic resonance imaging volumetric studies, were performed preoperatively at postoperative day (POD) 10, 90, 180, and 360. Mean residual volume increased by 88% within 10 days from RH and thereafter did not show any significant variation. After 1 year, only 83% of the original volume was reached. GEC per milliliter of liver volume expressed in percent of initial value (GEC/mL) showed a decrease of 25% at POD10, an increase up to 125% at POD 180, and returned to normal values at POD 360. Liver biochemistries, International Normalized Ratio (INR), and bilirubin returned to normal in 10 days. Cholinesterase showed a similar course like GEC. In conclusion, within 10 days of 61% loss of its initial volume, the liver is capable of regenerating a volume necessary to its function, although it corresponds to only 74% of the initial one. It takes only 10 days to normalize liver biochemistries, while cholinesterase and albumin recover over 90 days. However, a direct measure of the cytosolic liver function obtained by GEC shows that functional recovery occurs much more gradually than the recovery of volume and liver biochemistries.