Wolfgang Vogel

A Randomized, Controlled Study to Assess the Conversion From Calcineurin-Inhibitors to Everolimus After Liver Transplantation—PROTECT

Posttransplant immunosuppression with calcineurin inhibitors (CNIs) is associated with impaired renal function, while mTor inhibitors such as everolimus may provide a renal‐sparing alternative. In this randomized 1‐year study in patients with liver transplantation (LTx), we sought to assess the effects of everolimus on glomerular filtration rate (GFR) after conversion from CNIs compared to continued CNI treatment. Eligible study patients received basiliximab induction, CNI with/without corticosteroids for 4 weeks post‐LTx, and were then randomized (if GFR > 50 mL/min) to continued CNIs (N = 102) or subsequent conversion to EVR (N = 101). Mean calculated GFR 11 months postrandomization (ITT population) revealed no significant difference between treatments using the Cockcroft‐Gault formula (−2.9 mL/min in favor of EVR, 95%‐CI: [−10.659; 4.814], p = 0.46), whereas use of the MDRD formula showed superiority for EVR (−7.8 mL/min, 95%‐CI: [−14.366; −1.191], p = 0.021). Rates of mortality (EVR: 4.2% vs. CNI: 4.1%), biopsy‐proven acute rejection (17.7% vs. 15.3%), and efficacy failure (20.8% vs. 20.4%) were similar. Infections, leukocytopenia, hyperlipidemia and treatment discontinuations occurred more frequently in the EVR group. No hepatic artery thrombosis and no excess of wound healing impairment were noted. Conversion from CNI‐based to EVR‐based immunosuppression proved to be a safe alternative post‐LTx that deserves further investigation in terms of nephroprotection.

Advanced-Stage Hepatocellular Carcinoma: Transarterial Chemoembolization versus Sorafenib

PURPOSEnTo compare the efficacies of transarterial chemoembolization (TACE) and sorafenib in patients with advanced-stage hepatocellular carcinoma (HCC).nnnMATERIALS AND METHODSnThe retrospective analysis of the data was approved by the institutional review board; the requirement to obtain informed consent was waived. Three hundred seventy-two patients with HCC were treated between January 1999 and December 2009. Patients with advanced HCC according to the Barcelona Clinic Liver Cancer (BCLC) staging classification (Child-Pugh class A or B, Eastern Cooperative Oncology Group performance status of 1-2, and/or macrovascular invasion or extrahepatic metastasis) were included in the study (n = 97). Thirty-four patients underwent conventional TACE with doxorubicin plus lipiodol or TACE with drug-eluting beads; 63 patients were treated with sorafenib.nnnRESULTSnThe median duration of sorafenib treatment was 4.6 months (95% confidence interval [CI]: 3.2, 6.0 months). The median number of TACE sessions per patient was 3 ± 2. Side effects of TACE and sorafenib were comparable to those reported in the literature. The median time to progression was similar between the two treatment groups (P = .737). The median overall survival was 9.2 months (95% CI: 6.1, 12.3 months) for patients treated with TACE and 7.4 months (95% CI: 5.6, 9.2 months) for those treated with sorafenib (P = .377). Only Child-Pugh class was associated with a better overall survival at uni- and multivariate analysis.nnnCONCLUSIONnTACE achieved a promising outcome in select patients with advanced HCC (BCLC stage C).

Early viral load and recipient interleukin‐28B rs12979860 genotype are predictors of the progression of hepatitis C after liver transplantation

There have been few detailed studies of viral kinetics after liver transplantation (LT), and conflicting data have been reported on viral loads and the severity of recurrent hepatitis C virus (HCV) disease. This long‐term study aimed to examine (1) the impact of HCV RNA levels at specific points in time within the first year and (2) the influence of interleukin‐28B (IL‐28B) genotypes on patient outcomes and the severity of recurrent HCV disease. The viral loads were measured 2, 4, 12, 24, and 48 weeks after LT, and the recipient/donor IL‐28B genotypes of 164 patients were determined. A Cox regression analysis showed that the viral load at week 2 was an independent negative predictor of recipient outcomes. A week 2 viral load ≥ 6.0 log10 IU/mL was significantly associated with reduced patient survival. After a mean follow‐up of 6.5 years, 21 of 164 patients (12.8%) developed a cholestatic type of HCV recurrence and/or rapidly progressed to cirrhosis within 1 year. A multivariate binary regression analysis showed that HCV viremia at week 2 and a non‐C/C recipient IL‐28B genotype were independent risk factors for cholestatic recurrent HCV. No predictive factors could be found for the occurrence of recurrent liver cirrhosis 5 and 10 years after LT. Our study shows that the HCV RNA level at week 2 and the recipient IL‐28B genotype are independent, statistically significant risk factors for post‐LT cholestatic HCV, and it emphasizes the importance of viral load monitoring and IL‐28B genotyping for identifying HCV recipients at risk for severe HCV recurrence. Liver Transpl 18:671–679, 2012.

Pulmonary radiographic abnormalities in shock. Roentgen-clinical-pathological correlation.

Pulmonary insufficiency is one of the most frequent causes of death in patients subjected to shock. The continuous radiographic series, clinical data and autopsy findings in 46 patients are described. The changes in the chest radiograph can be related to the histological findings and are clearly related to changes found by arterial blood analysis. Given the appropriate history, the radiographic picture can provide a clue for the diagnosis of a shock syndrome.

Hepcidin is correlated to soluble hemojuvelin but not to increased GDF15 during pregnancy.

Increased maternal and foetal iron requirements during pregnancy are compensated by an increase of intestinal iron absorption. Animal studies have shown that the expression of the main iron regulator hepcidin is significantly suppressed during pregnancy, but the factors associated with hepcidin suppression remain unknown. To investigate possible suppressors of hepcidin expression during pregnancy we determined serum concentrations of growth-differentiation factor-15 (GDF15), erythropoietin (EPO), soluble hemojuvelin (HJV) and hepcidin in 42 pregnant women at different time points of gestation and correlated them with serum iron and haematological parameters. Serum iron parameters and serum hepcidin concentration significantly decreased during pregnancy, whereas serum concentrations of GDF15, EPO and soluble HJV significantly increased. A negative correlation of hepcidin with EPO and soluble HJV but no correlation between hepcidin and GDF15 was found. Hepcidin and ferritin were positively correlated throughout the pregnancy. Our findings suggest that hepcidin expression is controlled by body iron stores where soluble HJV and EPO may act as suppressors of hepcidin.

Coronary computer tomographic angiography for preoperative risk stratification in patients undergoing liver transplantation

The assessment of the cardiovascular risk profile in patients with end-stage liver disease is essential prior to liver transplantation (LT) as cardiovascular diseases are major causes of morbidity and mortality in the posttransplant course. The aim of this study was to evaluate the accuracy of a 64-slice coronary computed tomographic angiography (CTA) and coronary calcium scoring (CCS) to predict the postoperative cardiovascular risk of patients assessed for LT. In this single center, observational study we included 54 consecutive patients who were assessed for LT and consequently transplanted. Twenty-four patients (44%) presented with a high CCS above 300 and/or a significant stenosis (>50% percent narrowing due to stenotic plaques) and were further referred to coronary angiography. Three of these patients had a more than 70% LAD stenosis with subsequent angioplasty (n=1) or conservative therapy (n=2). The other patients showed only diffuse CAD without significant stenosis. The remaining 30 patients with normal CTA findings were listed for LT without further tests. None of the 54 patients developed cardiovascular events peri- and postoperatively. This study indicated that CTA combined with CCS is a useful non-invasive imaging technique for pre-LT assessment of coronary artery disease and safe tool in the risk assessment of peri- and postoperative cardiovascular events in patients undergoing LT.

Antiviral therapy and fibrosis progression in patients with mild-moderate hepatitis C recurrence after liver transplantation. A randomized controlled study.

BACKGROUNDS/AIMSnWe evaluated the effect of antiviral therapy on fibrosis progression in patients with histological features of mild/moderate HCV disease recurrence defined by a Grading score≥4 and Staging score up to 3 (Ishak) at 1 year after liver transplantation.nnnMETHODSnSeventy-three consecutive patients with mild/moderate recurrence were randomized either to no treatment or to receive Pegilated-Interferon-alfa-2b and ribavirin for 52 weeks. Liver biopsies obtained at baseline (1 year after transplantation) and 2 years afterwards were evaluated for assessment of disease progression, defined as worsening of at least 2 staging points or progression to stage 4 or higher.nnnRESULTSnAs for these two major histological end points there were no statistically significant differences between the 2 groups (36.1% vs. 50%, p=0.34 and 36.1% vs. 38.9%, p=1). Fifteen treated patients (41%) achieved a sustained virological response which was associated with a reduced risk of fibrosis worsening for both endpoints when compared to viremic patients (p=0.04).nnnCONCLUSIONSnAlthough antiviral-therapy was beneficial in preventing fibrosis progression in patients achieving a sustained virological response, the majority of the overall population of our patients with mild-moderate disease recurrence could not benefit from antiviral therapy either because they either could not be treated or did not respond to treatment (EudraCT number: 2005-005760).

Cystatin C is a strong predictor of survival in patients with cirrhosis: is a cystatin C‐based MELD better?

The model of end stage liver disease (MELD) includes serum creatinine, which is a poor surrogate marker of renal function in patients with cirrhosis. Especially in women and patients with advanced disease creatinine underestimates true renal function. Our objective was to assess whether or not the substitution of creatinine by cystatin C improves the prognostic performance of the model.

Identification of a novel Wilson disease gene mutation frequent in Upper Austria: a genetic and clinical study

Wilson disease (WD), a disorder of copper metabolism is caused by mutations in the ATP7B gene, a copper transporting ATPase. In the present study we describe a novel mutation in exon 9 of the ATP7B gene. The ATP7B gene was analyzed for mutations by denaturing HPLC and direct sequencing. DNA from 100 healthy blood donors from the same geographic area was examined as control. Sixteen (7.4%) out of the 216 patients diagnosed with WD in Austria carried the newly identified R816S(c.2448G>T) point mutation in exon 9 (4 male, age: 19 (6–30) years, median (range)). One patient was homozygous for R816S(c.2448G>T). Thirteen patients were compound heterozygotes (p.H1069Q(c.3207C>A)/R816S(c.2448G>T) (N=6), P539L/R816S(c.2448G>T) (N=3), each one G710S/R816S(c.2448G>T), P767P(2299insC)/R816S(c.2448G>T), W779G/R816S(c.2448G>T), T1220M/R816S(c.2448G>T)). In two patients no second mutation was identified. Interestingly, all but three of the patients originated within a distinct geographical area in Austria. Eleven patients presented with hepatic disease, 3 patients with neurological disease and 2 were asymptomatic sisters of an index case. A liver biopsy was available in 14 patients. Three patients showed advanced liver disease with liver transplantation for acute hepatic failure in two. The remaining patients had only mild histological changes, most commonly steatosis. Chronic hepatitis was described in five patients. Kayser–Fleischer ring was present in five patients. None of the 100 healthy controls carried the mutation. We describe a novel mutation in the ATP7B gene, occurring in patients originated from a distinct geographical area in Austria associated with a variable course of the disease.

Hepatitis C and autoimmunity: a therapeutic challenge

Abstract.u2002 Böckle BC, Baltaci M, Ratzinger G, Graziadei I, Vogel W, Sepp NT (Innsbruck Medical University, Anichstrasse, Innsbruck, Austria). Hepatitis C and autoimmunity: a therapeutic challenge (Case Report). J Intern Med 2012; 271: 104–106.