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1.
J Clin Invest ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32163375

RESUMO

In patients with HBV and HCV coinfection, HBV reactivation leading to severe hepatitis has been reported with the use of direct-acting antivirals (DAAs) to treat HCV infection. Here we study the molecular mechanisms behind this viral interaction. In coinfected cell culture and humanized mice, HBV replication was suppressed by HCV coinfection. In vitro, HBV suppression was attenuated when interferon signaling was blocked. In vivo, HBV viremia, after initial suppression by HCV super-infection, rebounded following HCV clearance by DAA treatment that was accompanied by a reduced hepatic interferon response. Using blood samples of coinfected patients, interferon-stimulated gene products including C-X-C motif chemokine 10 (CXCL10) and C-C motif chemokine ligand 5 (CCL5), and alanine aminotransferase (ALT) were identified to have predictive value for HBV reactivation after HCV clearance. Taken together, our data suggest that HBV reactivation is a result of diminished hepatic interferon response following HCV clearance and identifies serologic markers that can predict HBV reactivation in DAA-treated HBV-HCV coinfected persons.

2.
Z Gastroenterol ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040979

RESUMO

BACKGROUND: Virologic failure to approved combinations of direct antiviral agents (DAA) in patients with chronic hepatitis C virus (HCV) infection is rare. Mostly it involves difficult to treat patients with advanced liver disease and prior interferon-experience. Before approval of VOX/VEL/SOF, a restricted number of patients received rescue treatment, and the choice of DAA combinations for re-treatment were selected on an individual basis. In the present analysis, patient characteristics and rescue-regimens after virologic failure mainly based on first generation DAAs are described. PATIENTS AND METHODS: Data were obtained from the German Hepatitis C-Registry (DHC-R), which is a national multicenter real-world cohort currently including about 16 500 patients recruited by more than 250 centers. The present analysis is based on 6683 patients who initiated a DAA therapy and for whom follow-up data (per-protocol analysis) were available. RESULTS: Among the patients, 188 (2.8 %) experienced a virologic relapse. Compared to SVR-patients, relapse patients were significantly more often male (77.7 % versus 56.9 %, respectively, p < 0.001), showed cirrhosis significantly more (48.4 % versus 28.1 %, respectively, p < 0.001) and a prior interferon-containing therapy (46.3 % versus 39.0 %, respectively, p = 0.049). The majority of patients who relapsed were infected with genotype 1 (47.4 %) followed by genotype 3 (29.8 %), and 95 relapse patients started DAA re-treatment. Characteristics of patients with rescue-treatment are similar to these of patients with relapse after initial DAA treatment. Thirty-one of 39 patients with complete follow-up data achieved SVR (79.5 %), and 8 patients had a relapse again (20.5 %). Patients who received rescue treatment including a new DAA class according to guidelines, except patients who received VOX/VEL/SOF, showed higher SVR rates than the entire group (21/25, 84 %). All patients who received VOX/VEL/SOF achieved SVR (n = 4, 100 %). CONCLUSIONS: Patients with failure with DAA combination therapies are a difficult but urgent to treat population with the frequent presence of cirrhosis and prior treatment failure with interferon-based therapies. Rescue therapy with inclusion of a new DAA class leads to high SVR rates, but multiple targeted therapy with VOX/VEL/SOF seems to be most effective.

3.
J Clin Med ; 8(12)2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810183

RESUMO

BACKGROUND: Accurate assessment of hepatic fibrosis in patients with chronic HBeAg-negative Hepatitis B is of crucial importance not only to predict the long-term clinical course, but also to evaluate antiviral therapy indication. The aim of this study was to prospectively assess the utility of point shear wave elastography (pSWE) for longitudinal non-invasive fibrosis assessment in a large cohort of untreated patients with chronic HBeAg-negative hepatitis B virus (HBV) infection. METHODS: 407 consecutive patients with HBeAg-negative HBV infection who underwent pSWE, transient elastography (TE) as well as laboratory fibrosis markers, including fibrosis index based on four factors (FIB-4), aspartate to platelet ratio index (APRI) and FibroTest, on the same day were prospectively followed up for six years. Patients were classified into one of the three groups: inactive carriers (IC; HBV-DNA <2000 IU/mL and ALT <40 U/L); grey zone group 1 (GZ-1; HBV DNA <2000 IU/mL and ALT >40 U/L); grey zone group 2 (GZ-2; HBV-DNA >2000 IU/mL and ALT <40 U/L). RESULTS: pSWE results were significantly correlated with TE (r = 0.29, p < 0.001) and APRI (r = 0.17; p = 0.005). Median pSWE values did not differ between IC, GZ-1 and GZ-2 patients (p = 0.82, p = 0.17, p = 0.34). During six years of follow-up, median pSWE and TE values did not differ significantly over time (TE: p = 0.27; pSWE: p = 0.05). CONCLUSION: Our data indicate that pSWE could be useful for non-invasive fibrosis assessment and follow-up in patients with HBeAg-negative chronic HBV infection.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31706062

RESUMO

Hepatitis C virus infection is causing chronic liver disease, cirrhosis, and hepatocellular carcinoma. By combining direct-acting antivirals (DAAs), high sustained virologic response rates (SVRs) can be achieved. Resistance-associated substitutions (RASs) are commonly observed after DAA failure, and especially nonstructural protein 5A (NS5A) RASs may impact retreatment options.1-3 Data on retreatment of DAA failure patients using first-generation DAAs are limited.4-7 Recently, a second-generation protease- and NS5A-inhibitor plus sofosbuvir (voxilaprevir/velpatasvir/sofosbuvir [VOX/VEL/SOF]) was approved for retreatment after DAA failure.8 However, this and other second-generation regimens are not available in many resource-limited countries or are not reimbursed by regular insurance, and recommendations regarding the selection of retreatment regimens using first-generation DAAs are very important. This study aimed to analyze patients who were re-treated with first-generation DAAs after failure of a DAA combination therapy.

5.
PLoS One ; 14(11): e0224751, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31738773

RESUMO

BACKGROUND: The COBAS AmpliPrep/COBAS TaqMan assay HCV (CAP/CTM) is widely used in clinical routine for HCV testing. Recently, the new cobas HCV test was established for high throughput testing with minimal operator intervention. As different assays may yield different quantitative/qualitative results that possibly impact treatment decisions, the aim of this study was to externally evaluate the cobas HCV test performance in comparison to CAP/CTM in a clinically relevant setting. METHODS: Serum samples were obtained from 270 patients who received direct acting antiviral therapy with different treatment regimens at two study sites (Hannover and Frankfurt) in 2016. Overall, 1545 samples (baseline, on-treatment and follow-up) were tested in parallel by both assays. RESULTS: The mean difference between cobas HCV and CAP/CTM for the quantification of HCV RNA was 0.008 log10 IU/ml HCV RNA (95% limits of agreement: -0.02-0.036) showing excellent agreement of both assays. With respect to clinical cut offs (HCV RNA detectable vs. target not detected and HCV RNA above the lower limit of quantification (LLOQ) vs.

6.
Clin Infect Dis ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513710

RESUMO

BACKGROUND: Treatment uptake for hepatitis C virus (HCV) infection in people who inject drugs (PWID) and patients on opioid substitution therapy (OST) is still low despite treatment guidelines that advocate the use of direct-acting antivirals (DAAs) in all patients. Our aim in this review was to investigate treatment outcomes among PWID and patients on OST in comparison to control cohorts. METHODS: A search of Embase, Medline, PubMed, and Web of Science (from October 2010 to March 2018) was conducted to assess sustained virologic response (SVR), discontinuation rates, adherence, and HCV reinfection in PWID and patients on OST. RESULTS: We identified 11 primary articles and 12 conference abstracts comprising 1702 patients on OST, 538 PWID, and 19 723 patients who served as controls. Among patients on OST, the pooled SVR was 90% (95% confidence interval [CI], 87% to 93%) and pooled treatment discontinuation rate was 7% (95% CI, 4% to 11%). Similarly, the pooled SVR was 88% (95% CI, 80% to 93%) in PWID and the pooled treatment discontinuation rate was 9% (95% CI, 5% to 15%). There was no significant difference regarding pooled rates of SVR, adherence, and discontinuation between patients on OST and controls as well as between PWID and controls. HCV reinfection rates among patients on OST ranged from 0.0 to 12.5 per 100 person-years. CONCLUSIONS: HCV treatment outcomes in PWID and patients on OST are similar to those in patients without a history of injecting drugs, supporting current guideline recommendations to treat HCV in these patient populations.

7.
Int J Clin Pract ; 73(11): e13405, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31408231

RESUMO

BACKGROUND: Patients with head and neck cancer (HNC) are at high risk for malnutrition because of tumour localisation and therapy. Prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement is common practice to prevent malnutrition. OBJECTIVE: To investigate the benefits of prophylactic PEG tube placement for HNC patients in terms of the influence on patients' nutritional status, utilisation rate, complications and to identify the predictors of PEG tube utilisation. METHODS: All consecutive HNC patients who underwent prophylactic PEG tube insertion between 1 January 2011 and 31 December 2012 prior to therapy were enrolled. The PEG tube utilisation rate, complications, the patients' nutritional status and tumour therapy were evaluated with the help of electronic patient charts and telephone interviews. RESULTS: A total of 181 patients (48 female, median 67.5 years) were included. The PEG utilisation rate in the entire cohort was 91.7%. One hundred and forty-nine patients (82.3%) used the PEG tube for total enteral nutrition, 17 patients (9.4%) for supplemental nutrition and 15 patients (8.3%) made no use of the PEG tube. Peristomal wound infections were the most common complications (40.3%) in this study. A high Nutritional Risk Screening (NRS) score prior to tube insertion was found to be independently associated with PEG utilisation. No significant weight changes were observed across the three patient subgroups. CONCLUSIONS: The overall PEG tube utilisation rate was high in this study. However, given the high rate of infections, diligent patient selection is crucial in order to determine which patients benefit most from prophylactic PEG tube insertion.


Assuntos
Nutrição Enteral/métodos , Gastrostomia/métodos , Neoplasias de Cabeça e Pescoço/terapia , Intubação Gastrointestinal/métodos , Desnutrição/prevenção & controle , Idoso , Nutrição Enteral/efeitos adversos , Feminino , Gastrostomia/efeitos adversos , Humanos , Intubação Gastrointestinal/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Estudos Retrospectivos
8.
Clin Infect Dis ; 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31228250

RESUMO

BACKGROUND: The efficacy of antibiotic prophylaxis to prevent spontaneous bacterial peritonitis (SBP) in patients colonized with multidrug-resistant organisms (MDRO) is unknown. We evaluated the effectiveness of fluoroquinolone-based SBP prophylaxis in an era and area of frequent antibiotic resistance. METHODS: This is a prospective observational study in patients with liver cirrhosis and an indication for fluoroquinolone-based prophylaxis of SBP. Patients were recruited and followed in a large German tertiary reference center with comprehensive microbiological and clinical monitoring performed at baseline and after 30, 60, 90 and 180 days of prophylaxis. RESULTS: Overall, 77 patients received antibiotic prophylaxis for an average of 93 days. Baseline prevalence of colonization with MDRO was high (N=39, 50.6%). At least one de novo MDRO was detected in 27 patients (35.1%) during antibiotic prophylaxis. 33 patients (42.9%) developed secondary infections, including 14 cases (17.9%) of infections with MDRO, and 13 cases (16.9%) of de novo/recurrent SBP. Thirty patients (39.0%) died during follow-up. Significantly higher risks of SBP development during antibiotic prophylaxis were observed for patients with versus without any apparent MDRO (P=0.009), vancomycin-resistant enterococci (P=0.008), multidrug-resistant Gram-negative bacteria (P=0.016), or quinolone-resistant Gram-negative bacteria (QR-GNB, P=0.015). In competing risk analysis, QR-GNBs were independently associated with prophylaxis failure (HR=3.39, P=0.045), and infections with QR-GNB were independently associated with death before SBP (SHR 6.47, P=0.034). CONCLUSION: Antibiotic prophylaxis of SBP appears to be less efficient in patients with known MDROs. Regular MDRO screening seems to be useful to tailor treatment of secondary infections and re-evaluate antibiotic prophylaxis in case of selection of quinolone-resistance.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31222832

RESUMO

BACKGROUND AND AIM: A number of studies were able to show a reduction of hypoxemia episodes during procedural sedation through the use of capnography (CA). The present study investigates the number of episodes of hypoxemia during percutaneous endoscopic gastrostomy (PEG) placement with propofol sedation comparing standard monitoring (SM) versus SM with additional CA surveillance. METHODS: In this single center randomized controlled trial, 150 patients were prospectively randomized 1:1 in either the SM group or the CA group after stratification for ASA class, PEG method (push or pull method), presence of head and neck tumor, and tracheostomy. CA analysis was performed for all patients but was blinded for the endoscopic team in the SM group. RESULTS: In the SM group, 57% episodes of hypoxemia (SpO2  < 90% for > 15 s) and 41% episodes of severe hypoxemia (SpO2  < 85% for > 15 s) were observed in comparison with 28% and 20% in the CA group, respectively. Odds ratios for hypoxemia and severe hypoxemia were 0.29 (confidence interval 0.15-0.57; P = 0.0005) and 0.35 (confidence interval 0.17-0.73; P = 0.008) in favor of the CA group. On average, CA was able to detect imminent mild and severe hypoxemia 83 and 99 s before standard monitoring. Standard monitoring represented an independent risk factor for hypoxemia and severe hypoxemia. CONCLUSIONS: Respiratory complications of sedation during PEG placement are frequent events. CA is able to detect imminent hypoxemia at an early time point. This allows an early intervention and consecutively the avoidance of mild and severe hypoxemia. Therefore, CA monitoring can be recommended particularly during PEG insertion procedures.

10.
Antivir Ther ; 24(6): 437-442, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31180334

RESUMO

BACKGROUND: Patients with chronic HCV infection are at increased risk of developing B-cell non-Hodgkin lymphoma (B-NHL). Regression of HCV-associated B-NHL (HCV-NHL) can be achieved through HCV eradication using interferon (IFN). However, only about two-thirds of patients with sustained virological response (SVR) also had a consecutive lymphoma response. miRNA-26b is associated with HCV-NHL response to antiviral therapy. Recent data suggest that IFN-free direct-acting antiviral (DAA) regimens also have anti-lymphoma activity in this patient population. METHODS: We report four patients with HCV-NHL who were treated with different IFN-free DAA regimens as oncological monotherapy in our centre between 2015 and 2016. We analysed the virological and lymphoproliferative disease response. Moreover, we analysed miRNA-26b expression in peripheral blood mononuclear cells at different time points during antiviral therapy for all included patients as well as for a total of 10 controls with (n=5) and without (n=5) chronic HCV infection. RESULTS: All patients had marginal zone lymphoma subtype and received different DAA regimens for 12-24 weeks. All four patients achieved SVR, but only three patients also had lymphoma response (one complete response, two partial responses). One patient showed progression to a high-grade lymphoma subtype after SVR. miRNA-26b expression was generally decreased in patients with HCV-NHL. Moreover, miRNA-26b expression was restored in those HCV-NHL patients with lymphoma response after 6 months (P=0.009). CONCLUSIONS: We have demonstrated that IFN-free DAA treatment of HCV can improve or even cure NHL. miRNA-26b-levels could be a potentially useful biomarker to predict lymphoma response in HCV-NHL patients.

11.
Liver Int ; 39(11): 2174-2183, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31207039

RESUMO

BACKGROUND & AIMS: Curing hepatitis C virus (HCV) infection reduces the risk of hepatocellular carcinoma (HCC) development, yet HCC occurs despite sustained virologic response (SVR) in 2%-8% of cirrhotic patients. Sphingolipids (SLs) have been identified as new biomarkers of chronic liver disease and HCC. The aim of this study was to evaluate serum SLs as diagnostic HCC biomarkers in patients with HCV-associated cirrhosis at SVR12. METHODS: From 2014 to 2016, 166 patients with HCV-cirrhosis and SVR were recruited and SL profiles were measured at baseline and 12 weeks after completion of direct-acting antiviral (DAA) therapy. All patients received HCC surveillance in line with current guideline recommendations. Minimum follow-up period comprised 6 months. RESULTS: Our study included 130 (78%) patients without history of HCC, 25 (15%) with history of HCC prior DAA therapy and 11 (7%) patients with de novo HCC after FU12. In those with upcoming de novo HCC serum C24DHC (P = 0.006), C24:1DHC (P = 0.048) and C16Cer (P = 0.011) were significantly upregulated at FU12, but not AFP (P = 0.138). Contemporaneous ultrasound did not visualize HCC, at this time. C16Cer stayed sole independent predictor with high diagnostic accuracy of AFP-positive (AUC = 0.741) and -negative (AUC = 0.766) HCC development. Serum SL parameters decreased from baseline to SVR12. CONCLUSIONS: C24DHC, C24:1DHC and especially C16Cer were superior to AFP in early detection of AFP-positive and -negative de novo HCC development. We observed significant SL profile changes upon SVR. SLs may play a role in non-invasive HCC surveillance and hepatocarcinogenesis.

12.
J Clin Microbiol ; 57(7)2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31043467

RESUMO

Besides seven major hepatitis C virus (HCV) genotypes (GT), a number of intergenotypic recombinant strains have been described. These so-called chimeras combine genetic characteristics of different HCV genotypes. However, correct genotype classification is important, as choice and duration of direct-acting antiviral (DAA) treatment is mainly based on the viral genotype. Therefore, misclassification of chimeras might lead to suboptimal treatment of patients infected with these strains. For example, 2k/1b chimeras are typically described as HCV genotype 2 strains by commercially available hybridization assays, but real-time PCR-based tests recognizing another HCV region might be more suitable for correct chimera detection. In this study, the analytic capacity of the hybridization-assay Versant HCV Genotype 2.0 (LiPA 2.0) and the real-time PCR-based-assays cobas HCV GT and Abbott RealTime HCV Genotype II were tested in a selected cohort of 230 patients infected with HCV genotype 1 (n = 53) and 2 (n = 177) and 48 patients infected with HCV 2/1 chimeric strains. While the Versant HCV Genotype 2.0 (LiPA 2.0) assay failed to identify chimeras in all of the patients (48/48, 100%), cobas HCV GT and Abbott HCV Genotype II assays identified chimeras correctly in 90% (43/48) and 65% (31/48) of the cases, respectively. In conclusion, while the hybridization-based Versant HCV Genotype 2.0 (LiPA 2.0) assay seems to be unsuitable for detection of HCV 2/1 chimeras, use of the real-time PCR-based assays cobas HCV GT and Abbott RealTime HCV Genotype II led to a higher rate of chimera detection.

13.
Liver Int ; 39(9): 1652-1660, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31033122

RESUMO

BACKGROUND&AIMS: Since the introduction of direct-acting antivirals (DAAs) several studies have reported high efficacy and safety in Hepatitis C infected patients, even in those earlier considered difficult-to-treat. We aimed to assess the efficacy and safety of DAA therapy in elderly patients. METHODS: The PubMed MEDLINE, Embase and Cochrane databases were searched through July 2018. Two independent researchers extracted data and assessed the quality and risk of bias. Risk ratios (RRs) were pooled using random effects models. The primary outcome was efficacy of DAA therapy assessed by the RR for non-sustained virologic response (SVR) among patients aged <65 vs ≥65 years. RESULTS: Overall, we identified 63 studies including 34 082 patients treated with different DAAs. Risk for non-SVR was comparable in patients <65 and ≥65 years of age (RR 1.00, 95% CI 0.86-1.15; P = 0.979) and even lower in a subgroup analysis of cirrhotic patients ≥65 years of age (RR 0.59, 95% CI 0.35-0.99, P = 0.044). Risk for non-SVR was similar between age groups in all other subgroup analyses. Elderly patients had a significantly increased risk of adverse events (AEs) (RR 1.30, 95% CI 1.11-1.52, P = 0.001), but not for serious adverse events (P = 0.43) or treatment discontinuation (P = 0.15). Risk for anaemia if treated with additional ribavirin was 2.84 (95% CI 1.73-4.66, P < 0.001) in elderly patients compared to patients <65 years. CONCLUSION: Our results show that DAAs are highly effective and safe in elderly patients. Ribavirin should be avoided in the elderly as more AEs and particularly anaemia is observed. Further cost-effectiveness analyses are needed to evaluate the socio-economic benefit of treating elderly people without advanced liver disease.

14.
Eur J Gastroenterol Hepatol ; 31(8): 1049-1056, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30807443

RESUMO

BACKGROUND: Even with highly effective direct-acting antivirals (DAAs) treatment of patients with decompensated hepatitis C (HCV) cirrhosis remains challenging. Clinical deterioration and the need for liver transplantation (LT) may arise despite previous antiviral treatment. It is unclear whether in patients with high Model for End-Stage Liver Disease (MELD) antiviral treatment is too risky and should thus be deferred until after LT. Treatment choices that are currently made in the real-world setting are unclear. METHODS: We performed a retrospective multicenter data analysis of patients with decompensated HCV cirrhosis (MELD ≥15) that presented to liver transplant centers that are part of the German Center for Infection Research when highly active DAA therapy was available. Choice of treatment strategy (DAA first vs. transplantation first) was analyzed and correlated with baseline and outcome parameters. RESULTS: Thirty-five patients fulfilled the inclusion criteria and their mean MELD score was 18.5±3.78 (median: 17, interquartile range=16-19). In the majority of patients (85.7%) DAA therapy was initiated before LT; survival rates and change in MELD were numerically better in this group compared with those where DAA therapy was withheld (82.1 vs. 40%, P=0.078; ΔMELD: -2.68±6.2 vs. 5.8±14.4, P=0.157). However, DAA treatment was more often initiated in patients with better liver function (MELD: 18±3.54 vs. 21.8±3.9, P=0.008). Three patients discontinued DAA treatment because of clinical deterioration; these patients all had a MELD score above 20 at the start of therapy. CONCLUSION: At liver transplant centers in Germany DAA before LT is attempted in the majority of cases. It appears to be associated with an improved outcome and seems safe at least in individuals with MELD below or equal to 20.

15.
Open Forum Infect Dis ; 6(1): ofy340, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30648130

RESUMO

Background: Patients with chronic hepatitis C virus (HCV) infection and active or previous hepatitis B virus (HBV) are at risk of HBV reactivation (HBV-R) during direct-acting antiviral (DAA) therapy. Recent reports suggest that HBV-R may even occur several months after completion of DAA therapy. The aim of this study was to assess the risk of HBV-R in patients with resolved HBV after successful DAA therapy during long-term follow-up (FU). Methods: Among 848 patients treated for chronic HCV, all patients with resolved HBV and long-term FU data were eligible for inclusion. Patients were HBV DNA/hepatitis B surface antigen (HBsAg)-negative at the end of therapy (EOT) and were followed for up to 52 weeks thereafter. Patients underwent regular alanine transaminase (ALT) testing, and additional HBV DNA/HBsAg testing was performed at FU week 12, end of FU, and in case of an ALT increase above the upper limit of normal (>ULN). Results: A total of 108 patients were followed up for a mean (range) of 41.5 (24-52) weeks after EOT. None of the patients experienced reverse HBsAg seroconversion or reappearance of HBV DNA. One patient received a liver transplantation; 1 patient was diagnosed with de novo hepatocellular carcinoma, and 2 patients died. Eighteen patients (16.7%) had increased ALT levels (grade 0/1). Of those, the majority were male (72.2%) and significantly more patients had cirrhosis (66.7% vs 36.2%, P = .015) or received ribavirin as part of their treatment regimen (86.7% vs 46.8%, P = .041). None of these were associated with HBV-R. Conclusions: Our results indicate that the risk of HBV-R in patients with resolved HBV treated with DAAs for HCV is low during long-term follow-up.

16.
J Cancer Res Clin Oncol ; 145(1): 253-259, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30374657

RESUMO

INTRODUCTION: Nivolumab is the first checkpoint-inhibitor approved for the treatment of advanced HCC patients. Real-life experience data of nivolumab treatment in HCC patients, especially those with advanced liver disease, is scarce. MATERIALS AND METHODS: All patients with confirmed advanced HCC and nivolumab treatment from three large German centers were retrospectively analyzed. Clinical parameters and outcome were assessed. RESULTS: A total of 34 patients were included. At the time of treatment initiation 5 patients (14.7%) were classified as stage BCLC B and 29 (85.3%) BCLC C, respectively. 25 (73.5) patients had received prior sorafenib treatment. All patients presented with cirrhosis, namely Child-Pugh stages A (56%) or B (41%), respectively. At time of patient's assessment, 20 out of 34 (58.8%) patients had died. Grade 3 toxicities occurred in two patients (5.9%). Best overall responses were partial response in four patients (11.8%) and stable disease in eight patients (23.5%). The median overall survival of the whole cohort was 7.5 weeks (range 0-46). Child-Pugh B stage disease at treatment start was significantly associated with poor outcome. DISCUSSION: Nivolumab treatment seems safe and clinical efficacious. Patients with advanced liver disease require further prospective evaluation due to probable limited efficacy of nivolumab.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Adulto , Idoso , Estudos de Viabilidade , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
18.
Infect Drug Resist ; 11: 2047-2061, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464547

RESUMO

Background and aims: Spontaneous bacterial peritonitis (SBP) is a severe complication of decompensated cirrhosis. The prevalence of multidrug-resistant organisms (MDROs) in patients with cirrhosis is increasing. Identification of patients at risk for SBP due to MDROs (ie, SBP with the evidence of MDROs or Stenotrophomonas maltophilia in ascitic culture, MDRO-SBP) is crucial to the early adaptation of antibiotic treatment in such patients. We therefore investigated whether MDROs found in ascitic cultures can also be found in specimens determined by noninvasive screening procedures. Patients and methods: This retrospective study was conducted at the liver center of the University Hospital Frankfurt, Germany. Between 2011 and 2016, patients with cirrhosis were included upon diagnosis of SBP and sample collection of aerobic/anaerobic ascitic cultures. Furthermore, the performance of at least one complete MDRO screening was mandatory for study inclusion. Results: Of 133 patients diagnosed with SBP, 75 (56.4%) had culture-positive SBP and 22 (16.5%) had MDRO-SBP. Multidrug-resistant Escherichia coli (10/22; 45.5%) and vancomycin-resistant enterococci (7/22; 36.4%) resembled the major causatives of MDRO-SBP. Rectal swabs identified MDROs in 17 of 22 patients (77.3%) who developed MDRO-SBP with a time-dependent sensitivity of 77% and 87% after 30 and 90 days upon testing, while negative predictive value was 83% and 76%, respectively. The majority of patients were included from intensive care unit or intermediate care unit. Conclusion: MDRO screening may serve as a noninvasive diagnostic tool to identify patients at risk for MDRO-SBP. Patients with decompensated cirrhosis should be screened for MDROs from the first day of inpatient treatment onward.

19.
Lancet Gastroenterol Hepatol ; 3(12): 856-864, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30274834

RESUMO

BACKGROUND: Direct-acting antivirals for chronic hepatitis C (HCV) infection have reduced the need for on-treatment HCV RNA monitoring. We assessed the accuracy and cost implications of using HCV core antigen testing to replace HCV RNA testing for confirmation of diagnosis, on-treatment monitoring, and determination of sustained virological response (SVR). METHODS: In a retrospective screening cohort study, de-identified residual serum from unselected samples were obtained from commercial laboratories in Ontario, Canada. Samples from each 5-year age-sex band from birth years 1945-74 collected from Aug 1, 2014, to Feb 28, 2015, were included. All samples that tested positive for HCV antibodies, and 10% of samples that tested negative for HCV antibodies, were tested for HCV core antigen and HCV RNA. A retrospective clinical cohort study was also done using blood samples from patients with confirmed HCV infection collected at four tertiary academic centres: one in Canada, two in Germany, and one in the USA. For assessment of SVR, we included samples from patients who started direct-acting antiviral-based treatment (excluding telaprevir and boceprevir) with or without peginterferon, ribavirin, or both, from Jan 1, 2014, to March 31, 2015. To ensure inclusion of adequate numbers for analysis, patients who relapsed after any treatment regimen were included. Serum samples included in the study were from baseline, week 4 on-treatment (only for patients treated with direct-acting antivirals), end of treatment, and week 12 or 24 of follow-up. The sensitivity and specificity of core antigen testing as a diagnostic tool was assessed in the screening cohort, using HCV RNA as a reference. The sensitivity and specificity of core antigen testing as well as its concordance with HCV RNA testing in the clinical cohort was assessed at baseline, week 4 on-treatment, and at weeks 12 or 24 after the end of treatment in patients undergoing therapy with direct-acting antivirals. The cost-effectiveness of core antigen testing with and without confirmatory HCV RNA testing for negative samples was also assessed. FINDINGS: From 10 006 samples in the screening cohort, 75 of 80 viraemic (HCV RNA-positive) samples tested positive for HCV core antigen (sensitivity 94%, 95% CI 86-98), and none of the 993 HCV RNA-negative samples tested positive for HCV core antigen (specificity 100%, 95% CI 94-100). The five viraemic samples that tested negative for HCV core antigen had low corresponding HCV RNA concentrations. In the clinical cohort, two (1%) of 202 baseline samples tested negative for HCV core antigen; one had a low HCV RNA concentration (468 IU/mL), the other had a high HCV RNA concentration (>2 000 000 IU/mL). By week 4 of treatment, HCV core antigen concentrations decreased in all patients but were not predictive of SVR. Although there was good concordance between HCV RNA and HCV core antigen results at 12 weeks after the end of treatment (r=0·97; p<0·0001), three of the 148 patients who achieved SVR at 12 weeks tested HCV core antigen positive. 12 weeks after the end of treatment, HCV core antigen was undetectable in one (1%) of 71 samples from patients who were identified as having relapsed according to HCV RNA detection. On-treatment and end-of-treatment testing of core antigen or HCV RNA provided little clinical value. The use of HCV core antigen testing as a confirmatory diagnostic strategy was cost saving relative to HCV RNA testing, with a reduction of CAD$0·29-3·70 per patient screened depending on whether HCV RNA testing was used to confirm HCV core antigen-negative results. INTERPRETATION: These data support the use of HCV core antigen testing to document HCV viraemia in a cost-saving diagnostic algorithm. In a treatment setting, HCV core antigen testing can be used instead of HCV RNA testing for diagnosis and documentation of treatment adherence, but it might not be adequate to determine SVR. This approach might improve access to care, particularly in low-income and middle-income countries. FUNDING: Abbott Diagnostics and Toronto Centre for Liver Disease.


Assuntos
Antivirais/uso terapêutico , Monitoramento de Medicamentos/economia , Monitoramento de Medicamentos/métodos , Antígenos da Hepatite C/sangue , Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , RNA Viral/sangue , Proteínas do Core Viral/sangue , Adulto , Idoso , Redução de Custos , Feminino , Hepatite C/genética , Hepatite C/imunologia , Hepatite C Crônica/diagnóstico , Humanos , Masculino , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Adesão à Medicação , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Viremia/sangue , Viremia/diagnóstico , Viremia/tratamento farmacológico
20.
PLoS One ; 13(7): e0200855, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30011326

RESUMO

BACKGROUND AND AIMS: Expression of carbonic anhydrase IX (CA9), an enzyme expressed in response to hypoxia, acidosis and oncogenic alterations, is reported to be a prognostic factor in HCC patients. Here we evaluated serum CA9 levels in HCC and cirrhosis patients. METHODS: HCC and cirrhosis patients were prospectively recruited and CA9 levels were determined. CA9 levels were compared to stages of cirrhosis and HCC stages. The association of the CA9 levels and overall survival (OS) was assessed. Furthermore, immunohistochemical CA9 expression in HCC and cirrhosis was evaluated. RESULTS: 215 patients with HCC were included. The median serum CA9 concentration in patients with HCC was 370 pg/ml and significantly higher than in a healthy cohort. Patients with advanced cancer stages (BCLC and ALBI score) had hid significant higher levels of CA9 in the serum. HCC patients with high serum CA9 concentrations (>400 pg/ml) had an increased mortality risk (hazard ratio (HR) 1.690, 95% confidence interval (CI) 1.017-2.809, P = 0.043). Serum CA9 concentration in cirrhotic patients did not differ significantly from HCC patients. Higher CA9 levels in cirrhotic patients correlated with portal hypertension and esophageal varices. Patients with ethanol induced cirrhosis had the highest CA9 levels in both cohorts. Levels of CA9 did not correlate with immunohistochemical expression. CONCLUSIONS: We conclude that a high CA9 level is a possible prognostic indicator for a poor outcome in HCC patients. The high CA9 levels are probably mainly associated with portal hypertension. Ductular reactions might be a possible source of serum CA9.


Assuntos
Antígenos de Neoplasias/sangue , Anidrase Carbônica IX/sangue , Carcinoma Hepatocelular/sangue , Hipóxia , Cirrose Hepática/sangue , Neoplasias Hepáticas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Resultado do Tratamento
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