Krzysztof Jurczyk

Original Protocol Using Computed Tomographic Angiography for Diagnosis of Brain Death: A Better Alternative to Standard Two-Phase Technique?

BACKGROUND The application of computed tomographic angiography (CTA) for the diagnosis of brain death (BD) is limited because of the low sensitivity of the commonly used two-phase method consisting of assessing arterial and venous opacification at the 60th second after contrast injection. The hypothesis was that a reduction in the scanning delay might increase the sensitivity of the test. Therefore, an original technique using CTA was introduced and compared with catheter angiography as a reference. MATERIAL AND METHODS In a prospective multicenter trial, 84 clinically brain-dead patients were examined using CTA and catheter angiography. The sensitivities of original CTA technique, involving an arterial assessment at the 25th second and a venous assessment at the 40th second, and the standard CTA, involving an arterial and venous assessment at the 60th second, were compared to catheter angiography. RESULTS Catheter angiography results were consistent with the clinical diagnosis of BD in all cases. In comparison to catheter angiography, the sensitivity of original CTA technique was 0.93 (95%CI, 0.85-0.97; p<0.001) and 0.57 (95%CI, 0.46-0.68; p<0.001) for the standard protocol. The differences were statistically significant (p=0.03 for original CTA and p<0.001 for standard CTA). Decompressive craniectomy predisposes to a false-negative CTA result with a relative risk of 3.29 (95% CI, 1.76-5.81; p<0.001). CONCLUSIONS Our original technique using CTA for the assessment of the cerebral arteries during the arterial phase and the deep cerebral veins with a delay of 15 seconds is a highly sensitive test for the diagnosis of BD. This method may be a better alternative to the commonly used technique.

Impact of Antiviral Treatment on Survival in HCV-Positive Liver Recipients

BACKGROUND Sequels of chronic HCV infection are currently one of the most common indications for liver transplantation (LTx). Because HCV reinfection and allograft injury are inevitable, it may influence survival. Earlier studies have not reported higher mortality among HCV-infected patients, but cumulative data seem to contradict these findings. The aim of the study was to analyze post-LTx survival in HCV-positive patients in comparison with non-HCV-positive recipients and impact of antiviral treatment on survival in patients with recurrent HCV hepatitis. MATERIAL AND METHODS Using data from the Polish national transplant registry, a retrospective cohort study of 327 patients who underwent LTx between 2000 and 2012 was performed. Cumulative 5-year mortality for HCV-positive patients vs. HCV-negative recipients and HCV-positive recipients treated with pegylated interferon/ribavirin vs. non-treated subjects was calculated using Kaplan-Meyer methodology. Mortality hazard rates were estimated using univariate proportional Cox models. RESULTS Liver transplantation in HCV-positive vs. HCV-negative recipients was associated with significantly lower survival rate (cumulative 5-year survival 89.8 vs. 80.26%, respectively, p=0.04276) with a 5-year mortality HR of 1.99. Antiviral treatment improved survival irrespective of virological response (84.06% treated vs. 51.22% non-treated, p=0.00003). Univariate Cox HR for HCV treated vs. untreated patients is 0.18. Further improvement of survival was significantly associated with sustained virological response (100% vs. 77.67%, p=0.042). CONCLUSIONS Our study confirms higher mortality risk among HCV-infected transplant recipients, improved survival related to the HCV treatment following graft reinfection, and positive association between the HCV treatment success and better survival.

Effect of Peginterferon or Ribavirin Dosing on Efficacy of Therapy With Telaprevir in Treatment-Experienced Patients With Chronic Hepatitis C and Advanced Liver Fibrosis: A Multicenter Cohort Study.

AbstractWe investigated the safety, efficacy, and impact of ribavirin and peginterferon dose reduction on complete early virologic response and sustained virologic response (SVR) to triple therapy with telaprevir in treatment-experienced patients with advanced liver fibrosis.Treatment was initiated for 211 patients who failed treatment with peginterferon and ribavirin, with bridging fibrosis (F3, n = 68) or cirrhosis (F4, n = 143), including 103 (49%) null-responders (NR), 30 (14%) partial responders (PR), and 78 (37%) relapsers (REL). Impaired liver function (ILF) platelets <100,000/mm3 or albumin <35 g/L were present in 40 patients. The distribution of hepatitis C virus subtypes was: 1a, 1b, or 1, with undetermined subtype for 10 (5%), 187 (89%), and 14 (6%) patients, respectively. Treatment was started with peginterferon alpha-2a or alpha-2b, ribavirin, and telaprevir at standard doses.The overall SVR24 rate was 56% and was lower in cirrhotic patients (NR: 35%, PR: 40%, and REL: 63%, respectively) than in patients with bridging fibrosis (NR: 50%, PR: 75%, and REL: 75%, respectively). The lowest probability of SVR24 was in NRs with ILF (26%). The SVR24 rate significantly decreased in NRs receiving <60% vs >60% of the total ribavirin dose (23% vs 44%, respectively) or <80% vs >80% of the total ribavirin dose (33% vs 48%, respectively). A significant SVR24 decrease was noted subsequent to a total peginterferon dose reduction, both when comparing patients who received <60% vs >60% of the total dose (NR: 0% vs 44%; REL: 33% vs 68%) and patients who received <80% vs >80% of the total dose (NR: 17% vs 50%; REL: 46% vs 71%).Serious adverse events were observed in 31 patients (15%). Deaths occurred in 4 patients. All of the deceased subjects were cirrhotic members of the ILF (baseline serum albumin level <35 g/L and/or platelet count <100,000/mm3) group.Ribavirin dose reduction did not affect efficacy in REL but did in NR. Peginterferon dose reduction decreased the SVR24 rate for all groups, particularly in prior NR. ILF increased the risk of fatal complications with a low probability to achieve SVR24. One solution might be to provide wide and early access to novel, efficient, and safe interferon-free combinations to treatment-experienced patients, particularly those with liver cirrhosis.

Does cyclosporine inhibit in vivo hepatitis C virus replication? – a pilot study

Hepatitis C virus (HCV)-related recurrent disease is one of the most important comorbidities after liver transplantation (LTx). Clinical analyses of outcome indicate a high rate of post-transplant progressive graft injury leading to fibrosis and cirrhosis, resulting in the graft loss. It is estimated that cirrhosis occurs in 25–33% of HCV-positive recipients within 5 years [1] and 1–5% of patients will develop rapidly progressive fibrosing cholestatic hepatitis [2]. This observation became especially evident since mid 1990s. Although factors influencing poor outcomes are not fully understood, more aggressive immunosuppression and older donor age, have been discussed as possible reasons for HCV-related disease acceleration [3,4,5]. Current aggressive and multidrug immunosuppressive regimens as well as treatment of acute cellular rejection episodes are associated with disease acceleration, with no single immunosuppressive agent considered superior with respect to influence on recurrent HCV disease [6]. An issue of calcineurin inhibitors role in HCV-related disease progression became valid again following publications of a few studies presenting evidence for in vitro inhibition of HCV replication by cyclosporine A (CsA) [7,8,9]. There was also data that CsA in combination with interferon improved chronic C hepatitis treatment results [10,11]. However, data on in vivo inhibition of HCV replication by CsA remain insufficient. We analysed HCV viral load and liver enzymes activity in patients who were initially on tacrolimus (TAC) based regimens and were subsequently converted to CsA. Among 84 patients who underwent LTx in years 2001– 2005, a total number of 32 subjects was transplanted due to the HCV-related end-stage liver disease (38,1%). Twenty-one patients initially received combination of TAC, mycophenolate mofetil (MMF) and steroids (withdrawn within 6 months), while in four patients CsA, MMF and steroids (withdrawn within 6 months) have been initiated. Pulse steroid therapy for rejection was used in one patient only. All patients were longitudinally followed-up by monthly biochemical evaluation in the first year after transplantation and by bi-monthly evaluation thereafter. Five TAC subjects were converted to CsA due to poor diabetes mellitus (DM) control after a median time of 17 months (range 3–59 months) post-transplant. Serum HCV load was measured by the quantitative PCR technique (RT PCR, HCV Test v. 2.0 Cobas Amplicor Monitor; Roche) at a time point of the first posttransplant aminotransferase increase at least two times the upper limit of normal, and compared to the retrospectively examined pre-transplant viraemia from the )80 C stored serum samples obtained prior to transplantation in each patient. In five cases, viral load was also measured 1 month after conversion from TAC to CsA. For the purpose of this report control examination of viraemia was performed after a median time of 12 months in all converted patients as well as in the six available TAC patients who were not treated with interferon and ribavirin. Results were analysed statistically by Mann–Whitney and Wilcoxon’s matched pairs test for comparisons of viraemia using licensed Statistica 6.0 PL (Statsoft, Krakow, Poland) program. Normal distribution was checked by Shapiro–Wilk test. Aminotransferases higher than 2· baseline (>80 U/l), confirmed by histological examination as an HCV-related hepatitis were observed in 21 patients (84%) after a median time of 15 months from LTx (range 3–59 months). Significant increase of the median viral load from pretransplant value of 1.27 · 10 (range 5.43 · 10–3.65 · 10 UI/ml) to 4.45 · 10 UI/ml (range 1.11 · 10–6.9 · 10 UI/ml, P < 0.03125) was noted. In four patients, aminotransferases remained normal. Three of them were HCV-RNA positive and HCV-RNA was repeatedly negative in one case (pretransplant value 1.11 · 10UI/ml, genotype 3a). In each of five patients with chronic recurrent C hepatitis, converted from TAC to CsA due to instable DM, a significant drop in Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activity was noted as well as reduction in HCV viraemia measured 1 month after conversion. Median viral load decreased from 4.37 · 10 to 1.69 · 10 UI/ml (Table 1). This difference, however, was not statistically significant probably due to a high dispersion of results.

Risk score based PEG Interferon alpha 2b and Ribavirin treatment response estimation model for genotype 1 chronic hepatitis C patients

PURPOSE Attempt to create simple practical algorithm for prospective assessment of PEG interferon/ribavirin related treatment response in individuals with chronic hepatitis C (CHC) basing on the risk factors defined prior to the treatment initiation. MATERIAL/METHODS Retrospective assessment of 45 female and 39 male previously untreated CHC patients aged 20 to 73 years, with genotype 1, undergoing standard treatment with PEG-IFNa2b+RBV was performed. For the final analysis 78 patients were included (38 effectively treated and 40 treatment failures). Thirty-six sustained virological response (SVR) related factors, which were routinely measured before treatment initiation were compared (including physical, biochemical, serologic and histopathologic). From this group the risk factors of the highest predictive value for treatment failure were selected. Cut-off values for statistical significance were defined for each parameter, with risk score (RS) calculated and compared in the group with and without SVR. RESULTS Seven factors related to treatment failure were identified: HCV>600000 IU/L, blood platelet count <150000/ul, GGTP>45 IU/ml, total serum protein<7.8 g/dl, glycaemia>105 mg/dl, detectable HBc IgG antibodies and cirrhosis. In the group with RS 1 the likelihood of SVR was 70% (p<0.028), while in patients with RS 3 the response was reduced to 23.8% (p<0.016), with no SVR achieved among patients with RS >3. CONCLUSIONS Low risk score (0-2) is associated with high probability of treatment success with scores >3 predictive for treatment failure. The presented model is a simple tool for prediction of treatment success for clinical use before PegIFN/RBV treatment initiation among genotype 1 CHC patients.