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1.
Marcelo Chen Wing-Wai Wong Matthew G. Law Sasisopin Kiertiburanakul Evy Yunihastuti Tuti Parwati Merati Poh Lian Lim Romanee Chaiwarith Praphan Phanuphak Man Po Lee Nagalingeswaran Kumarasamy Vonthanak Saphonn Rossana Ditangco Benedict L. H. Sim Kinh Van Nguyen Sanjay Pujari Adeeba Kamarulzaman Fujie Zhang Thuy Thanh Pham Jun Yong Choi Shinichi Oka Pacharee Kantipong Mahiran Mustafa Winai Ratanasuwan Nicolas Durier Yi-Ming Arthur Chen 《PloS one》2016,11(3)
Background
We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region.Methods
Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.Results
A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.Conclusion
In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality. 相似文献2.
Ge Yu Xiumei Chi Ruihong Wu Xiaomei Wang Xiuzhu Gao Fei Kong Xiangwei Feng Yuanda Gao Xinxing Huang Jinglan Jin Yue Qi Zhengkun Tu Bing Sun Jin Zhong Yu Pan Junqi Niu 《PloS one》2015,10(9)
Background
Hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infections contributes to a substantial proportion of liver disease worldwide. The aim of this study was to assess the clinical and virological features of HBV-HCV co-infection.Methods
Demographic data were collected for 3238 high-risk people from an HCV-endemic region in China. Laboratory tests included HCV antibody and HBV serological markers, liver function tests, and routine blood analysis. Anti-HCV positive samples were analyzed for HCV RNA levels and subgenotypes. HBsAg-positive samples were tested for HBV DNA.Results
A total of 1468 patients had chronic HCV and/or HBV infections. Among them, 1200 individuals were classified as HCV mono-infected, 161 were classified as HBV mono-infected, and 107 were classified as co-infected. The HBV-HCV co-infected patients not only had a lower HBV DNA positive rate compared to HBV mono-infected patients (84.1% versus 94.4%, respectively; P<0.001). The median HCV RNA levels in HBV-HCV co-infected patients were significantly lower than those in the HCV mono-infected patients (1.18[Interquartile range (IQR) 0–5.57] versus 5.87[IQR, 3.54–6.71] Log10 IU/mL, respectively; P<0.001). Furthermore, co-infected patients were less likely to have detectable HCV RNA levels than HCV mono-infected patients (23.4% versus 56.5%, respectively; P<0.001). Those HBV-HCV co-infected patients had significantly lower median HBV DNA levels than those mono-infected with HBV (1.97[IQR, 1.3–3.43] versus 3.06[IQR, 2–4.28] Log10 IU/mL, respectively; P<0.001). The HBV-HCV co-infection group had higher ALT, AST, ALP, GGT, APRI and FIB-4 levels, but lower ALB and total platelet compared to the HBV mono-infection group, and similar to that of the HCV mono-infected group.Conclusion
These results suggest that co-infection with HCV and HBV inhibits the replication of both viruses. The serologic results of HBV-HCV co-infection in patients suggests more liver injury compared to HBV mono-infected patients, but is similar to HCV mono-infection. 相似文献3.
Background
Recent studies indicate that 27% of Dutch blood donors have evidence of past infection with HEV. However, the low number of diagnosed HEV infections indicates either an asymptomatic course or under diagnosis.Objectives
We investigated whether HEV is a cause of acute hepatitis in Dutch patients and which diagnostic modality (serology or PCR) should be used for optimal detection.Study design
Serum samples were retrospectively selected from non-severely immuno-compromised patients from a university hospital population, suspected of having an infectious hepatitis. Criteria were: elevated alanine aminotransferase (ALT> 34 U/l) and request for antibody testing for CMV, EBV or Hepatitis A (HAV).Results
All samples were tested for HEV using ELISA and PCR. Ninety patients/sera were tested, of which 22% were HEV IgG positive. Only one serum was IgM positive. HEV PCR was positive in two patients: one patient was both HEV IgM and IgG positive, the other patient was only IgG positive. Both HEV RNA positive samples belonged to genotype 3. Evidence of recent infection with CMV, EBV and HAV was found in 13%, 10% and 3% respectively.Conclusions
Although our study is limited by small numbers, we conclude that HEV is a cause of acute hepatitis in hospital associated patients in The Netherlands. Moreover, in our study population the prevalence of acute HAV (3%) was almost similar to acute HEV (2%). We propose to incorporate HEV testing in panels for acute infectious hepatitis. Negative results obtained for HEV IgM in a HEV PCR positive patient, indicates that antibody testing alone may not be sufficient and argues for PCR as a primary diagnostic tool in hospital associated patients. The high percentage of HEV IgG seropositivity confirms earlier epidemiological studies. 相似文献4.
Sunil S. Solomon Aylur K. Srikrishnan Allison M. McFall M. Suresh Kumar Shanmugam Saravanan Pachamuthu Balakrishnan Suniti Solomon David L. Thomas Mark S. Sulkowski Shruti H. Mehta 《PloS one》2016,11(1)
Background and Objective
We characterize the burden of liver disease in a cohort of PWID in Chennai, India, with a high prevalence of HCV.Materials and Methods
1,042 PWID were sampled through community outreach in Chennai. Participants underwent fasting blood draw, questionnaire and an examination that included liver stiffness assessment using transient elastography (Fibroscan) and assessment of steatosis via ultrasound.Results
The median age was 39 years, all were male, 14.8% were HIV infected and 35.6% were HCV antibody positive, of whom 78.9% were chronically infected (HCV RNA positive). Median liver stiffness was 6.2 kPA; 72.9% had no evidence of or mild stiffness, 14.5% had moderate stiffness, and 12.6% had evidence of severe stiffness/cirrhosis. Prevalence of severe stiffness/cirrhosis was significantly higher among persons who were older, had a longer duration of injecting drugs, higher body mass index, higher prevalence of insulin resistance, higher prevalence of steatosis, higher HCV RNA levels and evidence of alcohol dependence. An estimated 42.1% of severe stiffness/cirrhosis in this sample was attributable to HCV. 529 (53.0%) had some evidence of steatosis. Prevalence of steatosis was higher among those who had larger waist circumference, insulin resistance, higher HDL cholesterol and a history of antiretroviral therapy.Conclusions
We observed a high burden of liver disease in this relatively young cohort that was primarily driven by chronic HCV infection, metabolic factors (insulin resistance and steatosis) and heavy alcohol use. Interventions to improve access to HCV treatment and reduce alcohol use are needed to prevent further progression of liver disease. 相似文献5.
Benjamin Maasoumy Bela Hunyady Vincenza Calvaruso Mihály Makara Johannes Vermehren Attila Haragh Simone Susser Birgit Bremer Gavin Cloherty Michael P. Manns Antonio Craxì Heiner Wedemeyer Christoph Sarrazin 《PloS one》2014,9(11)
Introduction
On-treatment HCV RNA measurements are crucial for the prediction of a sustained virological response (SVR) and to determine treatment futility during protease inhibitor-based triple therapies. In patients with advanced liver disease an accurate risk/benefit calculation based on reliable HCV RNA results can reduce the number of adverse events. However, the different available HCV RNA assays vary in their diagnostic performance.Aim
To investigate the clinical relevance of concordant and discordant results of two HCV RNA assays during triple therapy with boceprevir and telaprevir in patients with advanced liver fibrosis/cirrhosis.Methods
We collected on-treatment samples of 191 patients with advanced liver fibrosis/cirrhosis treated at four European centers for testing with the Abbott RealTime (ART) and COBAS AmpliPrep/COBAS TaqMan HCV v2.0 (CTM) assays.Results
Discordant test results for HCV RNA detectability were observed in 23% at week 4, 17% at week 8/12 and 9% at week 24 on-treatment. The ART detected HCV RNA in 41% of week 4 samples tested negative by the CTM. However, the positive predictive value of an undetectable week 4 result for SVR was similar for both assays (80% and 82%). Discordance was also found for application of stopping rules. In 27% of patients who met stopping rules by CTM the ART measured levels below the respective cut-offs of 100 and 1000 IU/ml, respectively, which would have resulted in treatment continuation. In contrast, in nine patients with negative HCV RNA by CTM at week 24 treatment would have been discontinued due to detectable residual HCV RNA by the ART assay. Importantly, only 4 of these patients failed to achieve SVR.Conclusion
Application of stopping rules determined in approval studies by one assay to other HCV RNA assays in clinical practice may lead to over and undertreatment in a significant number of patients undergoing protease inhibitor-based triple therapy. 相似文献6.
Robert Strassl Karoline Rutter Albert Friedrich St?ttermayer Sandra Beinhardt Michael Kammer Harald Hofer Peter Ferenci Theresia Popow-Kraupp 《PloS one》2015,10(8)
Background and Aims
Monitoring of chronic Hepatitis C (CHC) treatment relies on HCV RNA quantification by means of real-time PCR methods. Assay specific analytical sensitivities may impact therapy management.Methods
Comparative analysis between three commercial assays (Roche COBAS AmpliPrep/COBAS TaqMan Version 1 (CAP/CTM Ver. 1), Version 2 (CAP/CTM Ver. 2) and the Abbott RealTime HCV (ART) assay) was performed on 247 available samples taken at key decision time points during antiviral therapy of 105 genotype 1 patients (triple therapy: n = 70; dual therapy: n = 35).Results
Overall concordance of HCV RNA measurements was high between the two Roche systems (89%; n = 220/247) but lower between the Roche assays and the ART (CAP/CTM Ver. 1 vs ART: 77.3%; n = 191/247 and CAP/CTM v.2 vs ART: 80.1%; n = 198/247). Most discrepancies were noted in week 4/8 samples with residual viremia (<LLOQ) detected by ART (<LLOQ: n = 45, 44.1%) but undetectable HCV RNA by CAP/CTM Ver. 1 (<LLOQ: n = 18, 17.6%) or CAP/CTM Ver. 2 (<LLOQ: n = 26, 25.5%). Based on results by CAP/CTM Ver. 1, 13 eligible patients underwent an abbreviated course of therapy (24 weeks). Only 1 patient experienced virologic breakthrough. If tested by ART, only 6/13 patients (46.2%) would have been eligible for shortened treatment. Consequently, RGT guidelines were adapted and shortening of therapy was allowed if residual viremia was detected by ART at week 4/8.Conclusion
An abbreviated course of treatment can safely be applied in patients with residual viremia (<LLOQ) detected by ART in samples collected at week 4/8 of treatment. 相似文献7.
8.
Kathleen C. Rollet-Kurhajec Erica E. M. Moodie Sharon Walmsley Curtis Cooper Neora Pick Marina B. Klein Canadian Co-infection Cohort Study 《PloS one》2015,10(6)
Background
In Hepatitis C virus (HCV) mono-infection, male sex is associated with faster liver fibrosis progression but the effects of sex have not been well studied in HIV-HCV co-infected patients. We examined the influence of sex on progression to significant liver fibrosis in HIV-HCV co-infected adults receiving antiretroviral therapy (ART) using the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate biomarker of liver fibrosis.Methods
We evaluated 308 HIV infected, HCV RNA positive participants of a Canadian multicentre prospective cohort receiving antiretrovirals and without significant liver fibrosis or end-stage liver disease at baseline. We used multivariate discrete-time proportional hazards models to assess the effect of sex on time to significant fibrosis (APRI≥1.5) adjusting for baseline age, alcohol use, cigarette smoking, HCV duration, and APRI and time-updated CD4 count and HIV RNA.Results
Overall, 55 (18%) participants developed an APRI ≥ 1.5 over 544 person-years of at-risk follow-up time; 18 (21%) women (incidence rate (IR)=14.0/100 PY; 7.5-20.4) and 37 (17%) men (IR=8.9/100 PY; 6.0-11.8). Women had more favourable profiles with respect to traditional risk factors for liver disease progression (younger, shorter duration of HCV infection and less alcohol use). Despite this, female sex was associated with a greater than two-fold increased risk of fibrosis progression (adjusted hazard rate (HR) =2.23; 1.22-4.08).Conclusions
HIV-HCV co-infected women receiving antiretroviral therapy were at significantly greater risk of progressing to liver fibrosis as measured by APRI compared with men. Enhanced efforts to engage and treat co-infected women for HCV are needed. 相似文献9.
Behzad Hajarizadeh Bart Grady Kimberly Page Arthur Y. Kim Barbara H. McGovern Andrea L. Cox Thomas M. Rice Rachel Sacks-Davis Julie Bruneau Meghan Morris Janaki Amin Janke Schinkel Tanya Applegate Lisa Maher Margaret Hellard Andrew R. Lloyd Maria Prins Gregory J. Dore Jason Grebely InC Study Group 《PloS one》2015,10(4)
Background
Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV) infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection.Methods
Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study). Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels≤120 days) were categorised by a priori-defined patterns of HCV RNA levels: i) spontaneous clearance, ii) partial viral control with persistence (≥1 log IU/mL decline in HCV RNA levels following peak) and iii) viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak). Factors associated with HCV RNA patterns were assessed using multinomial logistic regression.Results
Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%), partial viral control with persistence (27%), and viral plateau with persistence (41%). HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P=0.018). In the two groups with persistence, Interferon lambda 3 (IFNL3) CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02). In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83).Conclusions
Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex is associated with ultimate spontaneous clearance. 相似文献10.
11.
Resistance-Associated NS5A Variants of Hepatitis C Virus Are Susceptible to Interferon-Based Therapy
Jun Itakura Masayuki Kurosaki Mayu Higuchi Hitomi Takada Natsuko Nakakuki Yoshie Itakura Nobuharu Tamaki Yutaka Yasui Shoko Suzuki Kaoru Tsuchiya Hiroyuki Nakanishi Yuka Takahashi Shinya Maekawa Nobuyuki Enomoto Namiki Izumi 《PloS one》2015,10(9)
Background & Aims
The presence of resistance-associated variants (RAVs) of hepatitis C virus (HCV) attenuates the efficacy of direct acting antivirals (DAAs). The objective of this study was to characterize the susceptibility of RAVs to interferon-based therapy.Methods
Direct and deep sequencing were performed to detect Y93H RAV in the NS5A region. Twenty nine genotype 1b patients with detectable RAV at baseline were treated by a combination of simeprevir, pegylated interferon and ribavirin. The longitudinal changes in the proportion of Y93H RAV during therapy and at breakthrough or relapse were determined.Results
By direct sequencing, Y93H RAV became undetectable or decreased in proportion at an early time point during therapy (within 7 days) in 57% of patients with both the Y93H variant and wild type virus at baseline when HCV RNA was still detectable. By deep sequencing, the proportion of Y93H RAV against Y93 wild type was 52.7% (5.8%– 97.4%) at baseline which significantly decreased to 29.7% (0.16%- 98.3%) within 7 days of initiation of treatment (p = 0.023). The proportion of Y93H RAV was reduced in 21 of 29 cases (72.4%) and a marked reduction of more than 10% was observed in 14 cases (48.7%). HCV RNA reduction was significantly greater for Y93H RAV (-3.65±1.3 logIU/mL/day) than the Y93 wild type (-3.35±1.0 logIU/mL/day) (p<0.001).Conclusion
Y93H RAV is more susceptible to interferon-based therapy than the Y93 wild type. 相似文献12.
Aiko Fukuma Shuetsu Fukushi Tomoki Yoshikawa Hideki Tani Satoshi Taniguchi Takeshi Kurosu Kazutaka Egawa Yuto Suda Harpal Singh Taro Nomachi Mutsuyo Gokuden Katsuyuki Ando Kouji Kida Miki Kan Nobuyuki Kato Akira Yoshikawa Hiroaki Kitamoto Yuko Sato Tadaki Suzuki Hideki Hasegawa Shigeru Morikawa Masayuki Shimojima Masayuki Saijo 《PLoS neglected tropical diseases》2016,10(4)
Background
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease with a high case fatality rate, and is caused by the SFTS virus (SFTSV). SFTS is endemic to China, South Korea, and Japan. The viral RNA level in sera of patients with SFTS is known to be strongly associated with outcomes. Virological SFTS diagnosis with high sensitivity and specificity are required in disease endemic areas.Methodology/Principal Findings
We generated novel monoclonal antibodies (MAbs) against the SFTSV nucleocapsid (N) protein and developed a sandwich antigen (Ag)-capture enzyme-linked immunosorbent assay (ELISA) for the detection of N protein of SFTSV using MAb and polyclonal antibody as capture and detection antibodies, respectively. The Ag-capture system was capable of detecting at least 350–1220 TCID50/100 μl/well from the culture supernatants of various SFTSV strains. The efficacy of the Ag-capture ELISA in SFTS diagnosis was evaluated using serum samples collected from patients suspected of having SFTS in Japan. All 24 serum samples (100%) containing high copy numbers of viral RNA (>105 copies/ml) showed a positive reaction in the Ag-capture ELISA, whereas 12 out of 15 serum samples (80%) containing low copy numbers of viral RNA (<105 copies/ml) showed a negative reaction in the Ag-capture ELISA. Among these Ag-capture ELISA-negative 12 samples, 9 (75%) were positive for IgG antibodies against SFTSV.Conclusions
The newly developed Ag-capture ELISA is useful for SFTS diagnosis in acute phase patients with high levels of viremia. 相似文献13.
Sven Pischke Anett Gisa Pothakamuri Venkata Suneetha Steffen Bj?rn Wiegand Richard Taubert Jerome Schlue Karsten Wursthorn Heike Bantel Regina Raupach Birgit Bremer Behrend Johann Zacher Reinhold Ernst Schmidt Michael Peter Manns Kinan Rifai Torsten Witte Heiner Wedemeyer 《PloS one》2014,9(1)
Background
Hepatitis E virus (HEV) infection takes a clinically silent, self-limited course in the far majority of cases. Chronic hepatitis E has been reported in some cohorts of immunocompromised individuals. The role of HEV infections in patients with autoimmune hepatitis (AIH) is unknown.Methods
969 individuals were tested for anti-HEV antibodies (MP-diagnostics) including 208 patients with AIH, 537 healthy controls, 114 patients with another autoimmune disease, rheumatoid arthritis (RA), and 109 patients with chronic HCV- or HBV-infection (HBV/HCV). Patients with AIH, RA and HBV/HCV were tested for HEV RNA. HEV-specific proliferative T cell responses were investigated using CFSE staining and in vitro stimulation of PBMC with overlapping HEV peptides.Results
HEV-antibodies tested more frequently positive in patients with AIH (n = 16; 7.7%) than in healthy controls (n = 11; 2.0%; p = 0.0002), patients with RA (n = 4; 3.5%; p = 0.13) or patients with HBV/HCV infection (n = 2; 2.8%; p = 0.03). HEV-specific T cell responses could be detected in all anti-HEV-positive AIH patients. One AIH patient receiving immunosuppression with cyclosporin and prednisolone and elevated ALT levels had acute hepatitis E but HEV viremia resolved after reducing immunosuppressive medication. None of the RA or HBV/HCV patients tested HEV RNA positive.Conclusions
Patients with autoimmune hepatitis but not RA or HBV/HCV patients are more likely to test anti-HEV positive. HEV infection should been ruled out before the diagnosis of AIH is made. Testing for HEV RNA is also recommended in AIH patients not responding to immunosuppressive therapy. 相似文献14.
Joseph Humphrey Kofi Bonney Mubarak Osei-Kwasi Theophilus Korku Adiku Jacob Samson Barnor Robert Amesiya Chrysantus Kubio Lawson Ahadzie Stephan ?lschl?ger Michaela Lelke Beate Becker-Ziaja Meike Pahlmann Stephan Günther 《PLoS neglected tropical diseases》2013,7(9)
Background
Viral hemorrhagic fevers (VHF) are acute diseases associated with bleeding, organ failure, and shock. VHF may hardly be distinguished clinically from other diseases in the African hospital, including viral hepatitis. This study was conducted to determine if VHF and viral hepatitis contribute to hospital morbidity in the Central and Northern parts of Ghana.Methodology/Principal Findings
From 2009 to 2011, blood samples of 258 patients with VHF symptoms were collected at 18 hospitals in Ashanti, Brong-Ahafo, Northern, Upper West, and Upper East regions. Patients were tested by PCR for Lassa, Rift Valley, Crimean-Congo, Ebola/Marburg, and yellow fever viruses; hepatitis A (HAV), B (HBV), C (HCV), and E (HEV) viruses; and by ELISA for serological hepatitis markers. None of the patients tested positive for VHF. However, 21 (8.1%) showed anti-HBc IgM plus HBV DNA and/or HBsAg; 37 (14%) showed HBsAg and HBV DNA without anti-HBc IgM; 26 (10%) showed anti-HAV IgM and/or HAV RNA; and 20 (7.8%) were HCV RNA-positive. None was positive for HEV RNA or anti-HEV IgM plus IgG. Viral genotypes were determined as HAV-IB, HBV-A and E, and HCV-1, 2, and 4.Conclusions/Significance
VHFs do not cause significant hospital morbidity in the study area. However, the incidence of acute hepatitis A and B, and hepatitis B and C with active virus replication is high. These infections may mimic VHF and need to be considered if VHF is suspected. The data may help decision makers to allocate resources and focus surveillance systems on the diseases of relevance in Ghana. 相似文献15.
Cristina Mussini Patrizia Lorenzini Massimo Puoti Miriam Lichtner Giuseppe Lapadula Simona Di Giambenedetto Andrea Antinori Giordano Madeddu Alessandro Cozzi-Lepri Antonella d’Arminio Monforte Andrea De Luca ICONA Foundation study group 《PloS one》2015,10(12)
Objective
To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART).Design
Retrospective analysis of a prospective cohort study.Setting
Italian HIV care centers participating to the ICONA Foundation cohort.Participants
Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up.Methods
Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD.Results
Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/mL, 65.9% had a FIB-4 <1.45, 26.4% 1.45–3.25 and 7.7% >3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6–3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45–3.25: HR 3.55, 95% CI 1.09–11.58; FIB-4>3.25: HR 4.25, 1.21–14.92) and time-updated FIB-4 (FIB-4 1.45–3.25: HR 3.40, 1.02–11.40; FIB-4>3.25: HR 21.24, 6.75–66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART.Conclusions
The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART. 相似文献16.
Tarik Asselah Alex J. Thompson Robert Flisiak Manuel Romero-Gomez Diethelm Messinger Georgios Bakalos Mitchell L. Shiffman 《PloS one》2016,11(3)
Background
Access to direct-acting antiviral agents (DAAs) is restricted in some settings; thus, the European Association for the Study of the Liver recommends dual peginterferon/ribavirin (PegIFN/RBV) therapy wherever DAAs are unavailable. HCV genotype (GT) 3 infection is now the most difficult genotype to eradicate and PegIFN/RBV remains an effective option. The goal of this study was to devise a simple predictive score to identify GT3 patients with a high probability of achieving a sustained virologic response (SVR) with PegIFN alfa-2a/RBV therapy.Methods
Relationships between baseline characteristics and SVR were explored by multiple logistic regression models and used to develop a simple scoring system to predict SVR using data from 1239 treatment-naive GT3 patients who received PegIFN alfa-2a/RBV for 24 weeks in two large observational cohort studies.Results
The score was validated using a database of 473 patients. Scores were assigned for six factors as follows: age (years) (≤40: 2 points; >40 but ≤55: 1); bodyweight (kg) (<70: 2; ≥70 but <90: 1); no cirrhosis/transition to cirrhosis (2); ALT ≤2.5 x ULN (1); platelets (109/L) (>200: 2; ≥100 but <200: 1); HCV RNA (<400,000 IU/mL: 1). The points are summed to arrive at a score ranging from 0‒10 where higher scores indicate higher chances of SVR; 141, 123, 203, 249, 232, and 218 patients had total scores of 0‒4, 5, 6, 7, 8, and 9–10, respectively, among whom SVR rates were 45%, 62%, 72%, 76%, 84%, and 89%. Among 622 patients who had scores of 6‒10 and HCV RNA <50 IU/mL by treatment week 4 the SVR rate was 86% (532/622).Conclusions
A simple baseline scoring system involving age, bodyweight, cirrhosis status, ALT level, platelet count and HCV RNA level can be used to identify treatment-naive Caucasian patients with HCV GT3 infection with a high probability of SVR with PegIFN alfa-2a/RBV therapy. 相似文献17.
Background
Hepatitis C virus genotype 4 (HCV-4) infection is common in the Middle East and Africa, with an extraordinarily high prevalence in Egypt. MicroRNAs (miRNAs) play an important role in various diseases, including HCV infection. The aim of the present study was to assess serum miR-122, miR-221 and miR-21 expression profiles in HCV-4 patients prior to treatment with HCV-4 combination therapy (pegylated alpha interferon and ribavirin) and to determine whether the miRNAs were associated with the drug response.Methods
RNA was extracted from pretreatment serum samples, and miR-122, miR-221 and miR-21 levels were measured by quantitative PCR. The results were compared among patients with sustained virological responses (SVR) and non-responders (NR).Results
The expression levels of miR-21 and miR-122 were significantly different between the SVR and NR groups. Receiver operator characteristic (ROC) analysis revealed that the sensitivity, specificity and positive predictive values of miR-21 were 82.2%, 77.3% and 88.1%, respectively, with a cut-off value of 1.7. The sensitivity, specificity and positive predictive values of miR-122 were 68.9%, 59.1% and 77.5%, respectively, with a cut-off value of 3.5.Conclusion and Significance
miR-21 and miR-122 might be useful predictors for SVR in HCV-4 patients prior to the administration of combination therapy. A higher predictive response power was obtained for miR-21 than for miR-122. These results should reduce ineffective treatments. 相似文献18.
Stephanie Hametner Arnulf Ferlitsch Monika Ferlitsch Alexandra Etschmaier Rainer Sch?fl Alexander Ziachehabi Andreas Maieron 《PloS one》2016,11(2)
Background
Clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) ≥10 mmHg, causes major complications. HVPG is not always available, so a non-invasive tool to diagnose CSPH would be useful. VWF-Ag can be used to diagnose. Using the VITRO score (the VWF-Ag/platelet ratio) instead of VWF-Ag itself improves the diagnostic accuracy of detecting cirrhosis/ fibrosis in HCV patients.Aim
This study tested the diagnostic accuracy of VITRO score detecting CSPH compared to HVPG measurement.Methods
All patients underwent HVPG testing and were categorised as CSPH or no CSPH. The following patient data were determined: CPS, D’Amico stage, VITRO score, APRI and transient elastography (TE).Results
The analysis included 236 patients; 170 (72%) were male, and the median age was 57.9 (35.2–76.3; 95% CI). Disease aetiology included ALD (39.4%), HCV (23.4%), NASH (12.3%), other (8.1%) and unknown (11.9%). The CPS showed 140 patients (59.3%) with CPS A; 56 (23.7%) with CPS B; and 18 (7.6%) with CPS C. 136 patients (57.6%) had compensated and 100 (42.4%) had decompensated cirrhosis; 83.9% had HVPG ≥10 mmHg. The VWF-Ag and the VITRO score increased significantly with worsening HVPG categories (P<0.0001). ROC analysis was performed for the detection of CSPH and showed AUC values of 0.92 for TE, 0.86 for VITRO score, 0.79 for VWF-Ag, 0.68 for ELF and 0.62 for APRI.Conclusion
The VITRO score is an easy way to diagnose CSPH independently of CPS in routine clinical work and may improve the management of patients with cirrhosis. 相似文献19.
Janneke A. Cox Robert L. Lukande Sam Kalungi Eric Van Marck Koen Van de Vijver Andrew Kambugu Ann M. Nelson Robert Colebunders Yukari C. Manabe 《PloS one》2015,10(4)
Objective
The detection of urinary lipoarabinomannan (LAM), a mycobacterial cell wall component, is used to diagnose tuberculosis (TB). How LAM enters the urine is not known. To investigate if urinary LAM-positivity is the result of renal TB infection we correlated the outcomes of urinary LAM-antigen testing to renal histology in an autopsy cohort of hospitalized, Ugandan, HIV-infected adults.Methods
We performed a complete autopsy, including renal sampling, in HIV-infected adults that died during hospitalization after written informed consent was obtained from the next of kin. Urine was collected postmortem through post-mortem catheterisation or by bladder puncture and tested for LAM with both a lateral flow assay (LFA) and an ELISA assay. Two pathologists assessed the kidney histology. We correlated the LAM-assay results and the histology findings.Results
Of the 13/36 (36%) patients with a positive urinary LAM ELISA and/or LFA, 8/13 (62%) had renal TB. The remaining 5 LAM-positive patients had disseminated TB without renal involvement. Of the 23 LAM-negative patients, 3 had disseminated TB without renal involvement. The remaining LAM-negative patients had no TB infection and died mostly of fungal and bacterial infections. LAM LFA had a sensitivity of 81% and specificity of 100% to diagnose TB at any location, and the LAM ELISA a sensitivity of 63% and a specificity of 100%. 54% (7/13) LAM LFA-positive patients were not on anti-TB treatment at the time of death.Conclusion
Renal TB infection explained LAM-positivity in the majority of patients. Patients with disseminated TB without renal involvement can also be diagnosed with LAM. This suggests that other mechanisms that lead to urinary LAM-positivity exist in a minority of patients. 相似文献20.
Patrick Ndase Connie Celum Lara Kidoguchi Allan Ronald Kenneth H. Fife Elizabeth Bukusi Deborah Donnell Jared M. Baeten for the Partners PrEP Study Team 《PloS one》2015,10(4)