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Serag D, Ragab E. Diffusion-weighted MRI in staging of post hepatitis C fibrosis: does ADC value challenge liver biopsy? THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2020. [DOI: 10.1186/s43055-020-00283-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
There is obvious interest in finding a non-invasive diagnostic tool to detect the development of hepatic fibrosis and distinguish between its various stages. Chronic inflammation of the liver secondary to viral hepatitis, autoimmune conditions, sclerosing cholangitis, drug toxicity, chronic alcohol intake, different metabolic disorders, and steatosis lead to fibrosis and maybe cirrhosis. The current study aimed to assess the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI) in diagnosis of post hepatitis C fibrosis and detection of its stage.
Results
A prospective study had included 232 participants; 120 patients had chronic hepatitis C with/without HCC and 112 subjects had normal liver. There was no significant difference between the two groups regarding age or gender (p 0.192 and 0.227 respectively). DW-MRI was performed using 1.5 T machine. The mean liver ADC values and normalized liver ADC (liver ADC/spleen ADC) were measured at b value 800 s/mm2; both were significantly lower among cases than controls. Cutoff values of liver ADC were 1.531 × 10−3 mm2/s, 1.409 × 10−3 mm2/s, 1.192 × 10−3 mm2/s, and 1.093 × 10−3 mm2/s for METAVIR stages ≥ F1, ≥ F2, ≥ F3, and F4, respectively. Normalized liver ADC showed larger area under the curve (AUC) than mean liver ADC in all differentiation categories except for differentiating between F0 and all other fibrosis stages.
Conclusion
In line with the literature, DW-MR imaging using b value of 800 s/mm2 has proved to be a valuable diagnostic technique for detection and staging of post hepatitis C fibrosis/cirrhosis being noninvasive procedure with acceptable accuracy. DWI using liver/spleen ADC values raised the diagnostic performance with AUC more than 90% in all fibrosis stages on METAVIR score.
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Gadoxetate-disodium-enhanced magnetic resonance imaging for liver fibrosis staging: a systematic review and meta-analysis. Clin Radiol 2019; 75:319.e11-319.e19. [PMID: 31831141 DOI: 10.1016/j.crad.2019.11.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 11/12/2019] [Indexed: 12/20/2022]
Abstract
AIM To identify and evaluate the efficiency of the most commonly used parameters applied to gadoxetate disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for liver fibrosis (LF) staging. MATERIALS AND METHODS Literature searches of PubMed, Web of Science, Embase, and MEDLINE databases from January 2004 to August 2018 were conducted. The applied parameters during imaging were noted and summarised. Studies using the most commonly used parameter were included. Extractive data were combined as pooled weighted mean difference (WMD) to determine the benefits in LF staging. The pooled sensitivity, specificity, and summary receiver operating characteristics (SROC) curve were calculated. RESULTS Among 57 relevant studies, the contrast enhancement index (CEI) was a relatively commonly used parameter. It was calculated as SIpost/SIpre, where SIpost and SIpre are the liver-to-muscle signal intensity ratios in the hepatocyte phase and pre-enhanced images, respectively. Six studies were included. F0 was regarded as normal liver, F1 as mild LF, F2 as moderate LF, and F3 and F4 as advanced LF. Comparisons of WMD revealed significant differences between F1-2 and F3-4. For stage ≥F1, the pooled sensitivity, specificity, and areas under SROC curve were 0.58, 0.84, and 0.85, respectively; the corresponding values for ≥F2 were 0.57, 0.68, and 0.76, while those for ≥F3 were 0.61, 0.75, and 0.72. CONCLUSION The methodology and parameters used for Gd-EOB-DTPA-enhanced MRI for LF staging are diverse, but the CEI was a relatively common parameter. Overall, there is evidence to support use of CEI, but more evidence from larger studies is needed.
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Smolders EJ, Thammajaruk N, de Kanter CTMM, Colbers A, Chaiyahong P, Cuprasitrut T, Chittmittraprap S, Apornpong T, Khemnark S, Tangkijvanich P, Burger DM, Avihingsanon A. Peg-interferon and ribavirin treatment in HIV/HCV co-infected patients in Thailand: efficacy, safety and pharmacokinetics. Trop Med Int Health 2018; 23:295-305. [PMID: 29247579 DOI: 10.1111/tmi.13027] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
OBJECTIVE In Thailand, 7.2% of HIV patients are co-infected with hepatitis C virus (HCV), and these patients are treated with peg-interferon + ribavirin (PR) for their HCV infection. This study evaluates efficacy and safety of PR treatment and pharmacokinetics of ribavirin in this population. METHODS HIV/HCV co-infected Thai patients were treated with PR for 24 or 48 weeks. Sustained virological response 24 weeks after the end of treatment (SVR24) was used to describe efficacy. (laboratory) safety parameters and ribavirin plasma concentrations were evaluated during study visits. Ribavirin concentrations were compared with t-tests for patients with and without anaemia (haemoglobin <10 g/dl) and SVR24. RESULTS A total of 101 HIV/HCV co-infected patients were included; 88% were male (n = 88), and 46% were infected with genotype 3. The median (IQR) start dose was 14.28 mg/kg/day. SVR24 rate was 56%. All patients reported at least one (serious) adverse event, of which 28% of patients developed anaemia. Seven patients discontinued treatment due to toxicity issues. Geometric mean (IQR) ribavirin concentration was 1.81 (1.42-2.32) mg/l at week 8 of treatment. At week 8, patients with and without anaemia and SVR had ribavirin concentrations of 2.29 and 1.63 mg/l and 1.91 and 1.74 mg/l, respectively. CONCLUSIONS PR treatment has comparable response rates and toxicity profile in Thai HIV/HCV co-infected patients as in Western HIV/HCV patients. However, ribavirin plasma concentrations were comparable with previously published studies in HIV/HCV co-infected patients, but both, just as SVR rate, were lower than in mono-infected patients.
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Affiliation(s)
- E J Smolders
- Department of Pharmacy & Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - N Thammajaruk
- HIV-Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
| | - C T M M de Kanter
- Department of Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands
| | - A Colbers
- Department of Pharmacy & Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - P Chaiyahong
- HIV-Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
| | - T Cuprasitrut
- HIV-Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
| | - S Chittmittraprap
- HIV-Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.,Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - T Apornpong
- HIV-Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
| | - S Khemnark
- Department of Medicine, Bamrasnaradura Institute, Nonthaburi, Thailand
| | - P Tangkijvanich
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - D M Burger
- Department of Pharmacy & Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - A Avihingsanon
- HIV-Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.,Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Shayesteh M, Shayesteh AA, Motamedfar A, Tahmasebi M, Bagheri S, Gharibvand MM. The clinical value of the apparent diffusion coefficient of liver magnetic resonance images in patients with liver fibrosis compared to healthy subjects. J Family Med Prim Care 2018; 7:1501-1505. [PMID: 30613549 PMCID: PMC6293959 DOI: 10.4103/jfmpc.jfmpc_299_18] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background: Fibrotic tissue forms following chronic inflammation in the liver, which may progress over time to cirrhosis. Liver biopsy is the gold standard for the diagnosis of liver fibrosis, and there has been a considerable interest in developing noninvasive methods. Objectives: In the present study, we evaluated the efficacy of the apparent diffusion coefficient (ADC) of the liver in the diagnosis and staging of liver fibrosis. Patients and Methods: This case–control study was conducted on 40 patients with chronic liver disease and 31 healthy controls who were subjected to diffusion-weighted magnetic resonance imaging (MRI). Diagnostic values for different stages of fibrosis were determined using receiver-operating characteristic (ROC) curves based on the sensitivity and specificity. Results: Of 37 patients in the case group, 12 were males (32.4%) and 25 (67.5%) were females, whereas in the control group of 31 patients, 11 were males (35.5%) and 20 (64.5%) were females. In the ROC analysis, area under the curve separating stage one or lower fibrosis from stage two or greater fibrosis groups with a b-value of 600 s/mm2 was 0.893 (98% confidence interval (CI): 0.795–0.955), and that with a b-value of 1000 s/mm2 was 0.946 (98% CI: 0.813–0.946). Conclusion: Our results are in line with the previous studies, which showed that liver ADC values could be considered as a method for the diagnosis and staging of liver fibrosis.
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Affiliation(s)
- Mehdi Shayesteh
- Department of Radiology, Golestan Hospital, Ahvaz Jundishapur University of Medicine, Ahvaz, Iran
| | - Ali Akbar Shayesteh
- Department of Internal Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Azim Motamedfar
- Department of Radiology, Golestan Hospital, Ahvaz Jundishapur University of Medicine, Ahvaz, Iran
| | - Morteza Tahmasebi
- Department of Radiology, Golestan Hospital, Ahvaz Jundishapur University of Medicine, Ahvaz, Iran
| | - Shahram Bagheri
- Department of Pathology, Shafa Hospital, Ahvaz Jundishapur University of Medicine, Ahvaz, Iran
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Jiang H, Chen J, Gao R, Huang Z, Wu M, Song B. Liver fibrosis staging with diffusion-weighted imaging: a systematic review and meta-analysis. Abdom Radiol (NY) 2017; 42:490-501. [PMID: 27678393 DOI: 10.1007/s00261-016-0913-6] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE A meta-analysis was performed to assess the diagnostic performance of diffusion-weighted imaging (DWI) in liver fibrosis (LF) staging. METHODS We conducted a comprehensive literature search to identify relevant articles. Diagnostic data were extracted for each METAVIR fibrosis stage (F0-F4). A bivariate binomial model was used to combine sensitivities and specificities. Summary receiver operating characteristics (SROC) curves were performed and areas under SROC curve (AUC) were calculated to indicate diagnostic accuracies. Subgroup analyses were performed between different study characteristics. RESULTS Twelve studies met the inclusion criteria for LF ≥F1, 16 for ≥F2, 18 for ≥F3, and 12 for F4. AUCs of DWI were 0.8554, 0.8770, 0.8836, and 0.8596 for ≥F1, ≥F2, ≥F3, and F4, respectively. Subgroup analyses showed that for LF ≥F2 and ≥F3, maximal b values (b max) ≥ 800 s/mm2 performed significantly better than b max < 800 s/mm2. The diagnostic accuracies of 3.0 T and intravoxel incoherent motion (IVIM)-DWI were significantly higher than those of 1.5 T and conventional DWI for diagnosing liver cirrhosis (F4). CONCLUSIONS DWI is a reliable noninvasive technique with good diagnostic accuracy for LF staging. Using b max ≥ 800 s/mm2, high-field strength (3.0 T) and IVIM-DWI can optimize the diagnostic performance of DWI.
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Affiliation(s)
- Hanyu Jiang
- Department of Radiology, Sichuan University West China Hospital, No. 37 Guoxue Alley, Chengdu, Sichuan, China
| | - Jie Chen
- Department of Radiology, Sichuan University West China Hospital, No. 37 Guoxue Alley, Chengdu, Sichuan, China
| | - Ronghui Gao
- Department of Radiology, Sichuan University West China Hospital, No. 37 Guoxue Alley, Chengdu, Sichuan, China
| | - Zixing Huang
- Department of Radiology, Sichuan University West China Hospital, No. 37 Guoxue Alley, Chengdu, Sichuan, China
| | - Mingpeng Wu
- Department of Radiology, Sichuan University West China Hospital, No. 37 Guoxue Alley, Chengdu, Sichuan, China
| | - Bin Song
- Department of Radiology, Sichuan University West China Hospital, No. 37 Guoxue Alley, Chengdu, Sichuan, China.
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Haimerl M, Utpatel K, Verloh N, Zeman F, Fellner C, Nickel D, Teufel A, Fichtner-Feigl S, Evert M, Stroszczynski C, Wiggermann P. Gd-EOB-DTPA-enhanced MR relaxometry for the detection and staging of liver fibrosis. Sci Rep 2017; 7:41429. [PMID: 28128291 PMCID: PMC5269752 DOI: 10.1038/srep41429] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Accepted: 12/19/2016] [Indexed: 12/21/2022] Open
Abstract
Gd-EOB-DTPA, a liver-specific contrast agent with T1-shortening effects, is routinely used in clinical routine for detection and characterization of focal liver lesions and has recently received increasing attention as a tool for the quantitative analyses of liver function. We report the relationship between the extent of Gd-EOB-DTPA- induced T1 relaxation and the degree of liver fibrosis, which was assessed according to the METAVIR score. For the T1 relaxometry, a transverse 3D VIBE sequence with inline T1 calculation was acquired prior to and 20 minutes after Gd-EOB-DTPA administration. The reduction rates of the T1 relaxation time (rrT1) between the pre- and postcontrast images were calculated, and the optimal cutoff values for the fibrosis stages were determined with receiver operating characteristic (ROC) curve analyses. The rrT1 decreased with the severity of liver fibrosis and regression analysis revealed a significant correlation of the rrT1 with the stage of liver fibrosis (r = -0.906, p < 0.001). ROC analysis revealed sensitivities ≥78% and specificities ≥94% for the differentiation of different fibrosis stages. Gd-EOB-DTPA-enhanced T1 relaxometry is a reliable tool for both the detection of initial hepatic fibrosis and the staging of hepatic fibrosis.
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Affiliation(s)
- Michael Haimerl
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - Kirsten Utpatel
- Department of Pathology, University Regensburg, Regensburg, Germany
| | - Niklas Verloh
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - Florian Zeman
- Center for Clinical Trials, University Hospital Regensburg, Regensburg, Germany
| | - Claudia Fellner
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - Dominik Nickel
- MR Applications Predevelopment, Siemens AG, Healthcare GmbH, Erlangen, Germany
| | - Andreas Teufel
- Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | | | - Matthias Evert
- Department of Pathology, University Regensburg, Regensburg, Germany
| | | | - Philipp Wiggermann
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
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Deenen MJ, de Kanter CTMM, Dofferhoff ASM, Grintjes-Huisman KJT, van der Ven AJAM, Fleuren HWHA, Gisolf EH, Koopmans PP, Drenth JPH, Burger DM. Lower Ribavirin Plasma Concentrations in HCV/HIV-Coinfected Patients Than in HCV-Monoinfected Patients Despite Similar Dosage. Ther Drug Monit 2016; 37:751-5. [PMID: 26102531 DOI: 10.1097/ftd.0000000000000226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV)/HIV-coinfected patients respond worse to dual therapy with ribavirin (RBV)/peginterferon compared with HCV-monoinfected patients. Several trials found that lower RBV plasma concentrations are associated with impaired virological response rates. The aim of this study was to determine RBV plasma concentrations in a cohort of HCV-monoinfected and HCV/HIV-coinfected patients. Our hypothesis is that HCV/HIV-coinfected patients have lower RBV plasma concentrations, which may in part explain their inferior response to dual therapy. METHODS A retrospective cohort study was performed in chronic HCV-monoinfected and HCV/HIV-coinfected patients who received peginterferon and weight-based RBV. Plasma RBV concentrations were determined at weeks 4 and 12 by a validated high-performance liquid chromatography assay. RBV concentrations were compared between monoinfected and coinfected patients. We calculated the proportion of patients with a subtherapeutic RBV plasma concentration defined as <2.0 mg/L. RESULTS A total of 61 HCV-infected patients were included, of whom 21 (34%) were coinfected with HIV. Although there was no difference in the weight-based dose of RBV between monoinfected and coinfected patients, RBV exposure was significantly lower in HCV/HIV-coinfected patients than in HCV-monoinfected patients: the mean ± SD RBV plasma concentrations were 1.82 ± 0.63 mg/L versus 2.25 ± 0.80 mg/L (P = 0.04) at week 4 and 2.14 ± 0.65 mg/L versus 2.62 ± 0.81 mg/L (P = 0.05) at week 12, respectively. The percentage of patients with subtherapeutic plasma concentrations of RBV in coinfected patients versus monoinfected patients was 62% versus 46% (P = 0.240) at week 4 and 50% versus 16% (P = 0.01) at week 12 of treatment, respectively. CONCLUSIONS HIV/HCV-coinfected patients yield significantly lower plasma concentrations of RBV than HCV-monoinfected patients. This puts them at an increased risk of not achieving sustained virological response.
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Affiliation(s)
- Maarten J Deenen
- *Department of Pharmacy, Radboud University Medical Center, Nijmegen; †Department of Clinical Pharmacy, Rijnstate Hospital, Arnhem; ‡Nijmegen Institute for Health Sciences, Radboud University Medical Center, Nijmegen; §Department of General Internal Medicine, Radboud University Medical Center, Nijmegen; ¶Department of Internal Medicine, Canisius Wilhelmina Hospital, Nijmegen; ‖Department of Clinical Pharmacy, Canisius Wilhelmina Hospital, Nijmegen; **Department of Internal Medicine, Rijnstate Hospital, Arnhem; and ††Department of Internal Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
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Nam HC, Lee HL, Yang H, Song MJ. Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection. Clin Mol Hepatol 2016; 22:259-266. [PMID: 27377910 PMCID: PMC4946403 DOI: 10.3350/cmh.2016.0020] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2016] [Revised: 06/13/2016] [Accepted: 06/13/2016] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND/AIMS The treatment strategy for hepatitis C virus (HCV) has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV) and asunaprevir (ASV). We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. METHODS Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12) and safety. RESULTS This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN) and ribavirin (RBV) treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation) occurring in two patients. CONCLUSION In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.
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Affiliation(s)
- Hee Chul Nam
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hae Lim Lee
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyun Yang
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Myeong Jun Song
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Division of Hepatology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea
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Zhang B, Liang L, Dong Y, Lian Z, Chen W, Liang C, Zhang S. Intravoxel Incoherent Motion MR Imaging for Staging of Hepatic Fibrosis. PLoS One 2016; 11:e0147789. [PMID: 26820668 PMCID: PMC4731200 DOI: 10.1371/journal.pone.0147789] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Accepted: 01/09/2016] [Indexed: 12/14/2022] Open
Abstract
Objectives To determine the potential of intravoxel incoherent motion (IVIM) MR imaging for staging of hepatic fibrosis (HF). Methods We searched PubMed and EMBASE from their inception to 31 July 2015 to select studies reporting IVIM MR imaging and HF staging. We defined F1-2 as non-advanced HF, F3-4 as advanced HF, F0 as normal liver, F1 as very early HF, and F2-4 as significant HF. Then we compared stage F0 with F1, F0-1 with F2-3, and F1-2 with F3-4 using IVIM-derived parameters (pseudo-diffusion coefficient D*, perfusion fraction f, and pure molecular diffusion parameter D). The effect estimate was expressed as a pooled weighted mean difference (WMD) with 95% confidence interval (CI), using the fixed-effects model. Results Overall, we included six papers (406 patients) in this study. Significant differences in D* were observed between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 2.46, 95% CI 0.83–4.09, P = 0.006; WMD 13.10, 95% CI 9.53–16.67, P < 0.001; WMD 14.34, 95% CI 10.26–18.42, P < 0.001, respectively). Significant differences in f were also found between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 1.62, 95% CI 0.06–3.18, P = 0.027; WMD 5.63, 95% CI 2.74–8.52, P < 0.001; WMD 3.30, 95% CI 2.10–4.50, P < 0.001, respectively). However, D showed no differences between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 0.05, 95% CI -0.01─0.11, P = 0.105; WMD 0.04, 95% CI -0.01─0.10, P = 0.230; WMD 0.02, 95% CI -0.02─0.06, P = 0.378, respectively). Conclusions IVIM MR imaging provides an effective method of staging HF and can distinguish early HF from normal liver, significant HF from normal liver or very early HF, and advanced HF from non-advanced HF.
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Affiliation(s)
- Bin Zhang
- Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, Guangdong Province, China
- Graduate College, Southern Medical University, Guangzhou, China
| | - Long Liang
- Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, Guangdong Province, China
- Graduate College, Southern Medical University, Guangzhou, China
| | - Yuhao Dong
- Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, Guangdong Province, China
| | - Zhouyang Lian
- Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, Guangdong Province, China
- Graduate College, Southern Medical University, Guangzhou, China
| | - Wenbo Chen
- Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, Guangdong Province, China
| | - Changhong Liang
- Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, Guangdong Province, China
| | - Shuixing Zhang
- Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, Guangdong Province, China
- * E-mail:
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Mohamed AA, Elbedewy TA, El-Serafy M, El-Toukhy N, Ahmed W, Ali El Din Z. Hepatitis C virus: A global view. World J Hepatol 2015; 7:2676-2680. [PMID: 26609344 PMCID: PMC4651911 DOI: 10.4254/wjh.v7.i26.2676] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Revised: 07/29/2015] [Accepted: 11/04/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a global challenge; 130-175 million are chronically infected. Over 350000 die each year from HCV. Chronic HCV is the primary cause of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease. Management of chronic HCV is aimed at preventing cirrhosis, reducing the risk of HCC, and treating extra hepatic complications. New treatments for chronic HCV has been devoted based on direct-acting antivirals, as pegylated interferon (peginterferon) is responsible for many side effects and limits treatment access. Sofosbuvir is the first compound to enter the market with Peginterferon-free combination regimens.
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Latli B, Hrapchak M, Chevliakov M, Li G, Campbell S, Busacca CA, Senanayake CH. Synthesis of deleobuvir, a potent hepatitis C virus polymerase inhibitor, and its major metabolites labeled with carbon-13 and carbon-14. J Labelled Comp Radiopharm 2015; 58:250-60. [PMID: 25964148 DOI: 10.1002/jlcr.3294] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/10/2015] [Accepted: 04/01/2015] [Indexed: 01/09/2023]
Abstract
Deleobuvir, (2E)-3-(2-{1-[2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxamido]cyclobutyl}-1-methyl-1H-benzimidazol-6-yl)prop-2-enoic acid (1), is a non-nucleoside, potent, and selective inhibitor of hepatitis C virus NS5B polymerase. Herein, we describe the detailed synthesis of this compound labeled with carbon-13 and carbon-14. The synthesis of its three major metabolites, namely, the reduced double bond metabolite (2) and the acyl glucuronide derivatives of (1) and (2), is also reported. Aniline-(13) C6 was the starting material to prepare butyl (E)-3-(3-methylamino-4-nitrophenyl-(13) C6 )acrylate [(13) C6 ]-(11) in six steps. This intermediate was then used to obtain [(13) C6 ]-(1) and [(13) C6 ]-(2) in five and four more steps, respectively. For the radioactive synthesis, potassium cyanide-(14) C was used to prepare 1-cylobutylaminoacid [(14) C]-(23) via Buchrer-Bergs reaction. The carbonyl chloride of this acid was then used to access both [(14) C]-(1) and [(14) C]-(2) in four steps. The acyl glucuronide derivatives [(13) C6 ]-(3), [(13) C6 ]-(4) and [(14) C]-(3) were synthesized in three steps from the acids [(13) C6 ]-(1), [(13) C6 ]-(2) and [(14) C]-(1) using known procedures.
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Affiliation(s)
- Bachir Latli
- Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT, 06877-0368, USA
| | - Matt Hrapchak
- Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT, 06877-0368, USA
| | - Maxim Chevliakov
- Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT, 06877-0368, USA
| | - Guisheng Li
- Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT, 06877-0368, USA
| | - Scot Campbell
- Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT, 06877-0368, USA
| | - Carl A Busacca
- Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT, 06877-0368, USA
| | - Chris H Senanayake
- Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT, 06877-0368, USA
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Kocakoc E, Bakan AA, Poyrazoglu OK, Dagli AF, Gul Y, Cicekci M, Bahcecioglu IH. Assessment of Liver Fibrosis with Diffusion-Weighted Magnetic Resonance Imaging Using Different b-values in Chronic Viral Hepatitis. Med Princ Pract 2015; 24:522-6. [PMID: 26183515 PMCID: PMC5588272 DOI: 10.1159/000434682] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Accepted: 06/01/2015] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE To examine the effectiveness of apparent diffusion coefficient (ADC) values and to compare the reliability of different b-values in detecting and identifying significant liver fibrosis. SUBJECTS AND METHODS There were 44 patients with chronic viral hepatitis (CVH) in the study group and 30 healthy participants in the control group. Diffusion-weighted magnetic resonance imaging (DWI) was performed before the liver biopsy in patients with CVH. The values of ADC were measured with 3 different b-values (100, 600, 1,000 s/mm2). In addition, liver fibrosis was classified using the modified Ishak scoring system. Liver fibrosis stages and ADC values were compared using areas under the receiver-operating characteristic (ROC) curve. RESULTS The study group's mean ADC value was not statistically significantly different from the control group's mean ADC value at b = 100 s/mm2 (3.69 ± 0.5 × 10-3 vs. 3.7 ± 0.3 × 10-3 mm2/s) and b = 600 s/mm2 (2.40 ± 0.3 × 10-3 vs. 2.5 ± 0.5 × 10-3 mm2/s). However, the study group's mean ADC value (0.99 ± 0.3 × 10-3 mm2/s) was significantly lower than that of the control group (1.2 ± 0.1 × 10-3 mm2/s) at b = 1,000 s/mm2. With b = 1,000 s/mm2 and the cutoff ADC value of 0.0011 mm2/s for the diagnosis of liver fibrosis, the mean area under the ROC curve was 0.702 ± 0.07 (p = 0.0015). For b = 1,000 s/mm2 and the cutoff ADC value of 0.0011 mm2/s to diagnose significant liver fibrosis (Ishak score = 3), the mean area under the ROC curve was 0.759 ± 0.07 (p = 0.0001). CONCLUSION Measurement of ADC values by DWI was effective in detecting liver fibrosis and accurately identifying significant liver fibrosis when a b-value of 1,000 s/mm2 was used.
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Affiliation(s)
- Ercan Kocakoc
- Department of Radiology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Elazig, Turkey
| | - Ayse Ahsen Bakan
- Department of Radiology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Elazig, Turkey
- *Ayse Ahsen Bakan, Department of Radiology, Faculty of Medicine, Bezmialem Vakif University, TR-34093 Fatih, Istanbul (Turkey), E-Mail
| | | | - Adile Ferda Dagli
- Department of Pathology, Faculty of Medicine, Inonu University, Malatya, and Departments of, Elazig, Turkey
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Akhtar E, Manne V, Saab S. Cirrhosis regression in hepatitis C patients with sustained virological response after antiviral therapy: a meta-analysis. Liver Int 2015; 35:30-6. [PMID: 24766091 DOI: 10.1111/liv.12576] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Accepted: 04/19/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Chronic hepatitis C may be associated with cirrhosis, liver failure and hepatocellular carcinoma. Studies have demonstrated improved clinical outcome in patients who achieved a sustained viral response (SVR). METHODS A systematic literature search was performed to identify studies that assessed the association between SVR and cirrhosis regression. The main outcome studied was cirrhosis regression in patients with a SVR as compared with patients without a SVR. Six studies totalling 443 patients were included. Dichotomous outcomes were reported as risk ratios (RR) with 95% confidence intervals (CI). RESULTS Of the 443 patients with cirrhosis, 137 achieved a SVR. Of these 137 patients who achieved an SVR, 73 (53%) patients had regression of cirrhosis. The risk ratio of cirrhosis regression was 2.69 [Confidence Interval (CI) 1.45-4.97, P < 0.01] in patients who achieved a SVR. The risk of cirrhosis regression was consistently in favour of patients who achieved a SVR regardless of the length of the biopsy or whether the biopsy was reviewed by a single or multiple pathologists. The risk ratio of cirrhosis regression was related to the duration of follow-up between biopsies. The relative risk for regression of cirrhosis in studies in which the mean or median time for the follow-up liver biopsy was greater than 36-month was 4.33 (CI 1.1-17.0, P = 0.04) as compared to a relative risk of 1.79 (CI 1.26-2.29, P < 0.01) in studies with a mean or median time between the follow-up biopsy of less than 36-month. CONCLUSIONS Our results suggest that the majority of patients with cirrhosis who achieve a SVR develop cirrhosis regression. Time between biopsies appears to be an important determinant of the likelihood of cirrhosis regression.
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Affiliation(s)
- Ehsaan Akhtar
- Department of Medicine, Harbor UCLA Medical Center, Torrance, CA, USA
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14
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Tokgöz Ö, Unal I, Turgut GG, Yildiz S. The value of liver and spleen ADC measurements in the diagnosis and follow up of hepatic fibrosis in chronic liver disease. Acta Clin Belg 2014; 69:426-32. [PMID: 25103596 DOI: 10.1179/2295333714y.0000000062] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
AIMS To evaluate the value of spleen and liver apparent diffusion coefficients (ADC) in chronic liver disease patients, with and without hepatocellular carcinoma (HCC), and to investigate the use of diffusion-weighted imaging (DWI) in the diagnosis and follow-up of hepatic fibrosis. MATERIALS AND METHODS This study population comprised 68 chronic liver disease patients (Group 1) and 70 healthy volunteers as controls (Group 2). In Group 1, 40 patients had chronic hepatitis-B, 20 had chronic hepatitis-C, 5 had non-alcoholic steatohepatitis and 3 had alcoholic steatohepatitis. Diagnosis of chronic liver disease was made by percutaneous liver biopsy and the degree of fibrosis (stage) was determined using the METAVIR scoring system. HCC diagnosis was made with a lesion biopsy. The patient group was subdivided based on the degree of fibrosis (F1, F2, F3 and F4) and presence of HCC. After patient and control groups underwent b-value 600 s/mm(2) DWI examination, liver and spleen ADC values were mapped and measured. The ADC values of the patient groups (F1, F2, F3, F4; with HCC, without HCC) were compared with each other and with the control group. RESULTS Liver ADC values were lower in Group 1 compared to Group 2 (P<0·001). There was a statistically significant difference between the patient and control groups liver right lobe, left lobe and caudate lobe ADC values (P<0·001). Comparing the F1, F2, F3 and F4 groups, there was no statistically significant difference found in terms of ADC values (P>0·05). However, as degree of fibrosis increased there was a reduction in ADC values, though not statistically significant. Comparing the groups with HCC and without HCC, there was no statistically significant difference in ADC values (P>0·05). There was no statistical difference in average spleen ADC values between patient and control groups (P>0·05). CONCLUSIONS In chronic liver disease, ADC values were lower. As the degree of liver fibrosis increased, ADC levels decreased, though the relationship between ADC values and fibrosis degree was not statistically significant. Quantitative DWI may help in the diagnosis of fibrosis in chronic liver disease patients, however as it does not show the degree of fibrosis, its use in treatment planning and follow-up is controversial. Spleen DWI measurement is not a sufficient method to diagnose and determine the degree of fibrosis in chronic liver disease patients.
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Zaiton F, Dawoud H, El Fiki IM, Hadhoud KM. Diffusion weighted MRI and transient elastography assessment of liver fibrosis in hepatitis C patients: Validity of non invasive imaging techniques. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2014. [DOI: 10.1016/j.ejrnm.2014.02.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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Comparison of magnetic resonance elastography and gadoxetate disodium-enhanced magnetic resonance imaging for the evaluation of hepatic fibrosis. Invest Radiol 2014; 48:607-13. [PMID: 23538889 DOI: 10.1097/rli.0b013e318289ff8f] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVES The objective of this study was to compare the diagnostic performance of magnetic resonance elastography (MRE) and gadoxetate disodium-enhanced magnetic resonance imaging (MRI) in the staging of hepatic fibrosis (HF) in patients with liver diseases. MATERIALS AND METHODS This retrospective study was approved by our institutional review board, and the informed consent was waived. One hundred and sixty-eight patients with chronic liver disease or suspected focal hepatic lesions underwent MRE and gadoxetate disodium-enhanced MRI at 1.5 T. Liver stiffness values were measured on quantitative shear-stiffness maps. The contrast enhancement index (CEI) was calculated as SIpost / SIpre, where SIpost and SIpre are, respectively, the liver-to-muscle signal intensity (SI) ratio on hepatobiliary phase images and on unenhanced images. The diagnostic performance of MRE and CEI for staging HF was compared using the receiver operating characteristic curve analysis on the basis of the histopathologic analysis of HF. RESULTS The liver stiffness values measured on MRE (r = 0.802; P < 0.0001) were more strongly correlated with the HF stage than with the CEI (r = -0.378; P < 0.0001). The areas under the receiver operating characteristic curve values of the liver stiffness values were significantly larger than those of CEI were for discriminating all stages of HF (P < 0.001 for ≥ F1, ≥ F2, ≥ F3, and ≥ F4). Magnetic resonance elastography showed higher sensitivity and specificity for predicting HF ≥ F1 (91% and 87%), ≥ F2 (87% and 91%), ≥ F3 (80% and 89%), and F4 (81% and 85%) compared with CEI (46% and 85%, 46% and 82%, 63% and 68%, and 76% and 65%, respectively). CONCLUSIONS Magnetic resonance elastography was superior to the gadoxetate disodium-enhancement MRI for HF staging.
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Ozkurt H, Keskiner F, Karatag O, Alkim C, Erturk SM, Basak M. Diffusion Weighted MRI for Hepatic Fibrosis: Impact of b-Value. IRANIAN JOURNAL OF RADIOLOGY 2014; 11:e3555. [PMID: 24693297 PMCID: PMC3955853 DOI: 10.5812/iranjradiol.3555] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2012] [Revised: 04/28/2013] [Accepted: 07/17/2013] [Indexed: 12/13/2022]
Abstract
Background Hepatic fibrosis is a typical complication of chronic liver diseases resulting in cirrhosis that remains a major public health problem worldwide. Liver biopsy is currently the gold standard for diagnosing and staging hepatic fibrosis. Percutaneous liver biopsy; however, is an invasive procedure with risks of complications. Therefore, there is need for alternative non-invasive techniques to assess liver fibrosis and chronic liver diseases. In recent years, MRI techniques, including diffusion weighted imaging (DWI), have been developed for in vivo quantification of liver fibrosis. Objectives The purpose of this study is to evaluate the utility of diffusion weighted MRI in the diagnosis and quantification of the degree of hepatic fibrosis and to investigate the influence of b-value. Patients and Methods Twenty-four patients (13 males, 11 females), with a mean age of 46 years (36-73 years) diagnosed as chronic hepatitis and histopathologically proven liver fibrosis and 22 other patients (8 males, 14 females) with no clinical or biochemical findings of liver disease, with a mean age of 51.2 years (32-75 years) were included in the study. All patients with chronic hepatitis underwent percutaneous liver biopsy by an experienced hepatologist without sonographic guidance. The Knodell histology activity index (HAI) for grading of necroinflammatory changes and Metavir scoring system for staging of the liver fibrosis were used to record the severity of the disease. All patients were examined with a 1.5 Tesla MRI system and the patients underwent diffusion weighted imaging (DWI) with a routine hepatic MRI protocol. Different b-values including 250, 500, 750, and 1000 sec/mm 2 were used to calculate apparent diffusion coefficients. Results We detected decreased apparent diffusion coefficient values in patients with hepatic fibrosis compared to patients without chronic hepatitis and there was a trend toward decrease in hepatic apparent diffusion coefficient values with an increasing degree of fibrosis. Conclusions Our findings suggest that hepatic apparent diffusion coefficient measurement with a b-value of 750 sec/mm 2 or greater is useful in accurate quantification of liver fibrosis and necroinflammation.
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Affiliation(s)
- Huseyin Ozkurt
- Department of Radiology, Sisli Etfal Education and Research Hospital, Istanbul, Turkey
- Corresponding author: Huseyin Ozkurt, Department of Radiology, Sisli Etfal Education and Research Hospital, Istanbul, Turkey. Tel: +90-5325958625, Fax: +90-2122965467, E-mail:
| | - Firat Keskiner
- Department of Radiology, Sisli Etfal Education and Research Hospital, Istanbul, Turkey
| | - Ozan Karatag
- Department of Radiology, Canakkale Onsekiz Mart University, Faculty of Medicine, Canakkale, Turkey
| | - Canan Alkim
- Department of Gastroenterology, Sisli Etfal Education and Research Hospital, Istanbul, Turkey
| | - Sukru Mehmet Erturk
- Department of Radiology, Sisli Etfal Education and Research Hospital, Istanbul, Turkey
| | - Muzaffer Basak
- Department of Radiology, Sisli Etfal Education and Research Hospital, Istanbul, Turkey
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Haimerl M, Verloh N, Zeman F, Fellner C, Müller-Wille R, Schreyer AG, Stroszczynski C, Wiggermann P. Assessment of clinical signs of liver cirrhosis using T1 mapping on Gd-EOB-DTPA-enhanced 3T MRI. PLoS One 2013; 8:e85658. [PMID: 24392025 PMCID: PMC3877368 DOI: 10.1371/journal.pone.0085658] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Accepted: 11/29/2013] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES To assess the differences between normal and cirrhotic livers by means of T1 mapping of liver parenchyma on gadoxetic acid (Gd-EOB-DTPA)-enhanced 3 Tesla (3T) MR imaging (MRI). METHODS 162 patients with normal (n = 96) and cirrhotic livers (n = 66; Child-Pugh class A, n = 30; B, n = 28; C, n = 8) underwent Gd-EOB-DTPA-enhanced 3T MRI. To obtain T1 maps, two TurboFLASH sequences (TI = 400 ms and 1000 ms) before and 20 min after Gd-EOB-DTPA administration were acquired. T1 relaxation times of the liver and the reduction rate between pre- and post-contrast enhancement images were measured. RESULTS The T1 relaxation times for Gd-EOB-DTPA-enhanced MRI showed significant differences between patients with normal liver function and patients with Child-Pugh class A, B, and C (p < 0.001). The T1 relaxation times showed a constant significant increase from Child-Pugh class A up to class C (Child-Pugh class A, 335 ms ± 80 ms; B, 431 ms ± 75 ms; C, 557 ms ± 99 ms; Child-Pugh A to B, p < 0.001; Child-Pugh A to C, p < 0.001; Child-Pugh B to C, p < 0.001) and a constant decrease of the reduction rate of T1 relaxation times (Child-Pugh class A, 57.1% ± 8.8%; B, 44.3% ± 10.2%, C, 29.9% ± 6.9%; Child-Pugh A to B, p < 0.001; Child-Pugh A to C,p < 0.001; Child-Pugh B to C, p < 0.001). CONCLUSION Gd-EOB-DTPA-enhanced T1 mapping of the liver parenchyma may present a useful method for determining severity of liver cirrhosis.
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Affiliation(s)
- Michael Haimerl
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
- * E-mail:
| | - Niklas Verloh
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - Florian Zeman
- Center for Clinical Trials, University Hospital Regensburg, Regensburg, Germany
| | - Claudia Fellner
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - René Müller-Wille
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - Andreas G. Schreyer
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | | | - Philipp Wiggermann
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
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Li H, Chen TW, Zhang XM, Li ZL, Zhang JL, Wang D, Li T, Wu JL, Guo X, Chen XL, Li L, Xie XY, Zhang ZS. Liver lobe volumes and the ratios of liver lobe volumes to spleen volume on magnetic resonance imaging for staging liver fibrosis in a minipig model. PLoS One 2013; 8:e79681. [PMID: 24223184 PMCID: PMC3819276 DOI: 10.1371/journal.pone.0079681] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Accepted: 09/23/2013] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE To investigate liver lobe volumes and the ratios of liver lobe volumes to spleen volume measured with magnetic resonance imaging (MRI) for quantitatively monitoring and staging liver fibrosis. METHODS Animal study was approved by Institutional Animal Care and Use Committee. Sixteen minipigs were prospectively used to model liver fibrosis, and underwent abdominal gadolinium-enhanced MRI on 0, 5(th), 9(th), 16(th) and 21(st) weekend after modeling this disease staged by biopsy according to METAVIR classification system. On MRI, volume parameters including left lateral liver lobe volume (LLV), left medial liver lobe volume (LMV), right liver lobe volume (RV), caudate lobe volume (CV), and spleen volume (SV) were measured; and LLV/SV, LMV/SV, RV/SV and CV/SV were calculated. Statistical analyses were performed for staging this fibrosis. RESULTS LLV and CV increased with increasing stage of fibrosis (r = 0.711, 0.526, respectively; all P < 0.05). RV and LMV increased from stage 0 to 2 and decreased from 2 to 4; and RV/SV decreased from 0 to 1, increased from 1 to 2, and decreased from 3 to 4 (all P > 0.05). LLV/SV, LMV/SV and CV/SV decreased from stage 0 to 4 (r = -0.566, -0.748 and -0.620, respectively; all P < 0.05). LLV, CV, LLV/SV, LMV/SV, RV/SV, and CV/SV could distinguish stage 0-1 from 2-4 and 0-2 from 3-4 (all P < 0.05). Among these parameters, LLV and LMV/SV could best classify stage ≥2 and ≥3, respectively (area under receiver operating characteristic curve = 0.893 and 0.946, respectively). CONCLUSION LLV and LMV/SV complement each other in staging liver fibrosis, and both parameters should be used to stage this disease.
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Affiliation(s)
- Hang Li
- Sichuan Key Laboratory of Medical Imaging, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
- Department of Radiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China
| | - Tian-wu Chen
- Sichuan Key Laboratory of Medical Imaging, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Xiao-ming Zhang
- Sichuan Key Laboratory of Medical Imaging, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Zhen-lin Li
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Jin-ling Zhang
- Department of Radiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Dan Wang
- Sichuan Key Laboratory of Medical Imaging, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Ting Li
- Sichuan Key Laboratory of Medical Imaging, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Jian-lin Wu
- Department of Radiology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
| | - Xing Guo
- Department of Ultrasonography, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Xiao-li Chen
- Sichuan Key Laboratory of Medical Imaging, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Li Li
- Department of Pathology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Xian-yong Xie
- Department of Pathology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Zi-shu Zhang
- Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, United States of America
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Amblard F, Zhang H, Zhou L, Shi J, Bobeck DR, Nettles JH, Chavre S, McBrayer TR, Tharnish P, Whitaker T, Coats SJ, Schinazi RF. Synthesis and evaluation of non-dimeric HCV NS5A inhibitors. Bioorg Med Chem Lett 2013; 23:2031-4. [PMID: 23466233 DOI: 10.1016/j.bmcl.2013.02.023] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2012] [Revised: 01/22/2013] [Accepted: 02/01/2013] [Indexed: 12/01/2022]
Abstract
Based on the symmetrical bidentate structure of the NS5A inhibitor BMS-790052, a series of new monodentate molecules were designed. The synthesis of 36 new non-dimeric NS5A inhibitors is reported along with their ability to block HCV replication in an HCV 1b replicon system. Among them compound 5a showed picomolar range activity along with an excellent selectivity index (SI > 90,000).
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Affiliation(s)
- Franck Amblard
- Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA
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Karoney MJ, Siika AM. Hepatitis C virus (HCV) infection in Africa: a review. Pan Afr Med J 2013; 14:44. [PMID: 23560127 PMCID: PMC3612901 DOI: 10.11604/pamj.2013.14.44.2199] [Citation(s) in RCA: 79] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Accepted: 12/29/2012] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a viral pandemic and a leading cause of chronic liver disease. This review highlights the epidemiology and management of Hepatitis C in Africa. We searched for articles on medline using the terms, "Hepatitis C", "Prevalence", "Epidemiology", "Africa" and "Treatment". The bibliographies of the articles found were used to find other references. We included articles published after 1995 only. The data was summarized and presented in tables and figures. Africa has the highest WHO estimated regional HCV prevalence (5.3%). Egypt has the highest prevalence (17.5%) of HCV in the world. Genotypes commonly found in Africa are 1, 4 and 5. Genotype 3 is found in Egypt and parts of Central Africa. Blood transfusion is a major means of acquisition of HCV infection. While treatment with peginterferon and ribavirin is recommended for patients with chronic HCV, no data were found on their use in Africa. Neither were there any data on definitive management (liver transplantation) for those with end stage disease. Data on HCV infection in Africa are scarce. This suggests that hepatitis C is still a neglected disease in many countries. Limited data exist in literature on HCV in Africa.
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Gonçalves CBT, Amaral KM, Sander GB, Martins NLC, Pereira L, Picon PD. Effectiveness of alpha interferon (+ ribavirin) in the treatment of chronic viral hepatitis C genotypes 2 and 3 in a Brazilian sample. ARQUIVOS DE GASTROENTEROLOGIA 2012; 49:150-6. [PMID: 22767003 DOI: 10.1590/s0004-28032012000200010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2011] [Accepted: 12/28/2011] [Indexed: 11/22/2022]
Abstract
CONTEXT Pharmacovigilance studies aim to detect, assess, understand and prevent risks of adverse effects of medications or any other possible drug related problem. Alpha interferon is being produced by Bio-Manguinhos/Fiocruz, Rio de Janeiro, RJ, Brazil and used in the treatment of chronic hepatitis C at Brazilian National Health System. OBJECTIVE To study the safety profile and effectiveness of alpha interferon in a sample of Brazilian patients with chronic hepatitis C genotypes 2 and 3, in Porto Alegre, RS, Brazil. METHOD We followed a cohort of chronic hepatitis C genotypes 2 and 3 patients treated with alpha interferon plus ribavirin in a specialized outpatient clinic in southern Brazil. Adverse events were collected and classified according to severity in monthly structured interviews. To measure effectiveness, hepatitis C viral load was evaluated before, at the end and 24 weeks after the treatment. RESULTS We followed 141 patients during the study period, of which 52.5% were female with mean age of 52 years. The most frequent adverse events were fatigue (84%), headache (79%) and myalgia (75%). There were 13 treatment interruptions due to adverse events, 9 of those considered serious adverse events. Virological response at end of treatment was 54.6% and after 24 weeks 39.7%, considering all patients who started treatment. CONCLUSION The product produced by Bio-Manguinhos has similar efficacy and adverse event and sustained virological response profiles comparable to those found in the literature. This is the first study of pharmacovigilance performed with the Brazilian product. These data will be useful for planning and management of this disease in Brazil.
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Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir (BMS-650032). Antimicrob Agents Chemother 2012; 56:5387-96. [PMID: 22869577 DOI: 10.1128/aac.01186-12] [Citation(s) in RCA: 163] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Asunaprevir (ASV; BMS-650032) is a hepatitis C virus (HCV) NS3 protease inhibitor that has demonstrated efficacy in patients chronically infected with HCV genotype 1 when combined with alfa interferon and/or the NS5A replication complex inhibitor daclatasvir. ASV competitively binds to the NS3/4A protease complex, with K(i) values of 0.4 and 0.24 nM against recombinant enzymes representing genotypes 1a (H77) and 1b (J4L6S), respectively. Selectivity was demonstrated by the absence of any significant activity against the closely related GB virus-B NS3 protease and a panel of human serine or cysteine proteases. In cell culture, ASV inhibited replication of HCV replicons representing genotypes 1 and 4, with 50% effective concentrations (EC(50)s) ranging from 1 to 4 nM, and had weaker activity against genotypes 2 and 3 (EC(50), 67 to 1,162 nM). Selectivity was again demonstrated by the absence of activity (EC(50), >12 μM) against a panel of other RNA viruses. ASV exhibited additive or synergistic activity in combination studies with alfa interferon, ribavirin, and/or inhibitors specifically targeting NS5A or NS5B. Plasma and tissue exposures in vivo in several animal species indicated that ASV displayed a hepatotropic disposition (liver-to-plasma ratios ranging from 40- to 359-fold across species). Twenty-four hours postdose, liver exposures across all species tested were ≥110-fold above the inhibitor EC(50)s observed with HCV genotype-1 replicons. Based on these virologic and exposure properties, ASV holds promise for future utility in a combination with other anti-HCV agents in the treatment of HCV-infected patients.
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Nishie A, Asayama Y, Ishigami K, Tajima T, Kakihara D, Nakayama T, Takayama Y, Okamoto D, Taketomi A, Shirabe K, Fujita N, Obara M, Yoshimitsu K, Honda H. MR prediction of liver fibrosis using a liver-specific contrast agent: Superparamagnetic iron oxide versus Gd-EOB-DTPA. J Magn Reson Imaging 2012; 36:664-71. [PMID: 22532503 DOI: 10.1002/jmri.23691] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2011] [Accepted: 04/02/2011] [Indexed: 12/30/2022] Open
Abstract
PURPOSE To examine whether the uptake of a liver-specific contrast agent in the liver parenchyma was correlated with the degree of liver fibrosis. MATERIALS AND METHODS This retrospective study included 54 and 63 patients who underwent superparamagnetic iron oxide (SPIO)- and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI before liver surgery, respectively. For each patient, we calculated ΔR2* and ΔR2, which represent differences in R2* and R2 values of the liver parenchyma before and after administration of SPIO; and the increase rate of liver-to-spleen signal intensity ratio (LSR) on the hepatobiliary phase compared with the precontrast image. The correlation of each MR parameter with the degree of liver fibrosis (F0 to F4) was assessed using Spearman's rank correlation test. RESULTS The increase rate of LSR was best correlated with the degree of liver fibrosis and significantly decreased as the liver fibrosis progressed (rho = -0.641; P < 0.0001). It showed sensitivity of 76.9% and specificity of 83.3% in differentiating F3 or greater fibrosis when 1.126 or less was set up as a cut-off value. No significant correlation was obtained between ΔR2* or ΔR2 and the degree of liver fibrosis. CONCLUSION The uptake of Gd-EOB-DTPA in the liver parenchyma decreased as the liver fibrosis progressed. J. Magn. Reson. Imaging 2012;36:664-671. © 2012 Wiley Periodicals, Inc.
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Affiliation(s)
- Akihiro Nishie
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan.
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Kim BH, Lee JM, Lee YJ, Lee KB, Suh KS, Han JK, Choi BI. MR elastography for noninvasive assessment of hepatic fibrosis: experience from a tertiary center in Asia. J Magn Reson Imaging 2011; 34:1110-6. [PMID: 21932355 DOI: 10.1002/jmri.22723] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2011] [Accepted: 06/23/2011] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To determine the sensitivity and specificity of MR elastography (MRE) in the staging of hepatic fibrosis (HF) using histopathology as the reference standard in an Asian population. MATERIALS AND METHODS MRE was performed on 55 patients with chronic liver diseases or biliary diseases and on 5 living related liver donors (48 men and 12 women; mean age, 55.7 years). MRE was performed with modified, phase-contrast, gradient-echo sequences, and the mean stiffness values were measured on the elastograms in kilopascals(kPa). Receiver operating characteristic curve analysis was performed to determine the cutoff value and accuracy of MRE for staging HF. Histopathologic staging of HF according to the METAVIR scoring system served as the reference. RESULTS Liver stiffness increased systematically along with the fibrosis stage. With a shear stiffness cutoff value of 3.05 kPa, the predicted sensitivity and specificity for differentiating significant liver fibrosis (≥ F2) from mild fibrosis (F1) were 89.7% and 87.1%, respectively. In addition, MRE was able to discriminate between patients with severe fibrosis (F3) and those with liver cirrhosis (sensitivity, 100%; specificity, 92.2%), with a shear stiffness cutoff value of 5.32 kPa. CONCLUSION MRE could be a promising, noninvasive technique with excellent diagnostic accuracy for detecting significant HF and liver cirrhosis.
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Affiliation(s)
- Bo Hee Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
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McCombs JS, Yuan Y, Shin J, Saab S. Economic Burden Associated With Patients Diagnosed With Hepatitis C. Clin Ther 2011; 33:1268-80. [DOI: 10.1016/j.clinthera.2011.07.008] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/11/2011] [Indexed: 12/19/2022]
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Ibrahim HR, EL-Hamid AA, Tohamy A, Habba MR. Diagnostic value of apparent diffusion coefficient calculated with diffusion-weighted MRI for quantification of liver fibrosis. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2011. [DOI: 10.1016/j.ejrnm.2011.05.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Zhao S, Liu E, Wei K, Wang Y, Li Y, Huang B, Chen Y, Yang P. Treatment with peginterferon versus interferon in Chinese patients with chronic hepatitis C. Eur J Clin Microbiol Infect Dis 2010; 30:51-7. [PMID: 20827497 DOI: 10.1007/s10096-010-1051-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2010] [Accepted: 08/20/2010] [Indexed: 12/09/2022]
Abstract
Higher sustained virological response (SVR) rates after treating with peginterferon than after treating with interferon have been obtained in some randomized clinical trials (RCTs) in Chinese patients with chronic hepatitis C (CHC). However, the numbers of patients included in these clinical trials were too small to draw a clear conclusion. Therefore, a new meta-analysis including a large number of patients was needed to compare peginterferon with interferon in the treatment of Chinese CHC patients. A search of Medline, the China National Knowledge Infrastructure, the Wanfang Database, and the China Biomedical Database for relevant articles published between 1966 and 2009 was performed. RCTs comparing the use of peginterferon and interferon for the treatment of Chinese patients with CHC were assessed. Of the 236 studies screened, 18 RCTs including 1,148 patients (659 treated with peginterferon therapy and 489 treated with interferon therapy) were analyzed. The total SVR rates obtained in patients treated with peginterferon were significantly higher than those obtained in patients treated with interferon (64% vs. 40%; relative risk, 1.56; 95% confidence interval: 1.28-1.91; p < 0.01), but the difference between the peginterferon α-2b and interferon α-2b treatments was not significant. Withdrawal rates were similar between patients treated with peginterferon and interferon. Chinese patients with CHC have a greater likelihood of achieving an SVR with peginterferon α-2a.
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Affiliation(s)
- S Zhao
- Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University School of Medicine, Shaanxi, China.
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Do RKG, Chandarana H, Felker E, Hajdu CH, Babb JS, Kim D, Taouli B. Diagnosis of liver fibrosis and cirrhosis with diffusion-weighted imaging: value of normalized apparent diffusion coefficient using the spleen as reference organ. AJR Am J Roentgenol 2010; 195:671-6. [PMID: 20729445 DOI: 10.2214/ajr.09.3448] [Citation(s) in RCA: 105] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The purpose of this study is to compare the diagnostic accuracy of liver apparent diffusion coefficient (ADC) versus normalized liver ADC using the spleen as a reference organ for the diagnosis of liver fibrosis and cirrhosis. MATERIALS AND METHODS Fifty-six patients, 34 with liver disease and 22 control subjects, were assessed with breath-hold single-shot echo-planar diffusion-weighted imaging using b values of 0, 50, and 500 s/mm(2). Liver ADC and normalized liver ADC (defined as the ratio of liver ADC to spleen ADC) were compared between patients stratified by fibrosis stage. Receiver operating characteristic (ROC) analysis was used to determine the performance of ADC and normalized liver ADC for prediction of liver fibrosis and cirrhosis. Reproducibility was assessed by measuring coefficient of variation (n = 7). RESULTS Liver ADC failed to distinguish individual stages of fibrosis, except between stages 0 and 4. There were significant differences in normalized liver ADC between control livers and intermediate stages of fibrosis (stages 2-3) and cirrhosis (stage 4) and between stages 1 and 4, and there was a trend toward significance between stages 0 and 1 (p = 0.051) and stages 1 and 3 (p = 0.06). ROC analysis showed that normalized liver ADC was superior to liver ADC for detection of stage > or = 2 (area under the ROC curve, 0.864 vs 0.655; p = 0.013) and stage > or =3 (0.805 vs 0.689; p = 0.015), without a difference for diagnosing cirrhosis (0.935 vs 0.720; p = 0.185). Normalized liver ADC had higher reproducibility than ADC (mean coefficient of variation, 3.5% vs 12.6%). CONCLUSION Our results suggest that normalizing liver ADC with spleen ADC improves diagnostic accuracy for detection of liver fibrosis and cirrhosis when using breath-hold diffusion-weighted imaging, with better reproducibility.
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Affiliation(s)
- Richard K G Do
- Department of Radiology, New York University Langone Medical Center, New York, NY 10029, USA
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Zhao S, Liu E, Chen P, Cheng D, Lu S, Yu Q, Wang Y, Wei K, Yang P. A comparison of peginterferon α-2a and α-2b for treatment-naive patients with chronic hepatitis C virus: A meta-analysis of randomized trials. Clin Ther 2010; 32:1565-77. [PMID: 20974315 DOI: 10.1016/j.clinthera.2010.08.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/22/2010] [Indexed: 01/12/2023]
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Chen YC, Su WC, Huang JY, Chao TC, Jeng KS, Machida K, Lai MMC. Polo-like kinase 1 is involved in hepatitis C virus replication by hyperphosphorylating NS5A. J Virol 2010; 84:7983-93. [PMID: 20534861 PMCID: PMC2916529 DOI: 10.1128/jvi.00068-10] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2010] [Accepted: 05/28/2010] [Indexed: 01/08/2023] Open
Abstract
Hepatitis C virus (HCV) replication involves many viral and host factors. Here, we employed a lentivirus-based RNA interference (RNAi) screening approach to search for possible cellular factors. By using a kinase-phosphatase RNAi library and an HCV replicon reporter system, we identified a serine-threonine kinase, Polo-like kinase 1 (Plk1), as a potential host factor regulating HCV replication. Knockdown of Plk1 reduced both HCV RNA replication and nonstructural (NS) protein production in both HCV replicon cells and HCV-infected cells while it did not significantly affect host cellular growth or cell cycle. Overexpression of Plk1 in the knockdown cells rescued HCV replication. Interestingly, the ratio between the hyperphosphorylated form (p58) and the basal phosphorylated form (p56) of NS5A was lower in the Plk1 knockdown cells and Plk1 kinase inhibitor-treated cells than in the control groups. Further studies showed that Plk1 could be immunoprecipitated together with NS5A. Both proteins partially colocalized in the perinuclear region. Furthermore, Plk1 could phosphorylate NS5A to both the p58 and p56 forms in an in vitro assay system; the phosphorylation efficiency was comparable to that of the reported casein kinase. Taken together, this study shows that Plk1 is an NS5A phosphokinase and thereby indirectly regulates HCV RNA replication. Because of the differential effects of Plk1 on HCV replication and host cell growth, Plk1 could potentially serve as a target for anti-HCV therapy.
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Affiliation(s)
- Yung-Chia Chen
- Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan, Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, Institute of Biotechnology, National Tsing Hua University, Hsinchu 300, Taiwan, Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2001 Zonal Avenue, Los Angeles, California 90033, National Cheng Kung University, Tainan 701, Taiwan
| | - Wen-Chi Su
- Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan, Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, Institute of Biotechnology, National Tsing Hua University, Hsinchu 300, Taiwan, Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2001 Zonal Avenue, Los Angeles, California 90033, National Cheng Kung University, Tainan 701, Taiwan
| | - Jing-Ying Huang
- Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan, Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, Institute of Biotechnology, National Tsing Hua University, Hsinchu 300, Taiwan, Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2001 Zonal Avenue, Los Angeles, California 90033, National Cheng Kung University, Tainan 701, Taiwan
| | - Ti-Chun Chao
- Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan, Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, Institute of Biotechnology, National Tsing Hua University, Hsinchu 300, Taiwan, Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2001 Zonal Avenue, Los Angeles, California 90033, National Cheng Kung University, Tainan 701, Taiwan
| | - King-Song Jeng
- Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan, Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, Institute of Biotechnology, National Tsing Hua University, Hsinchu 300, Taiwan, Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2001 Zonal Avenue, Los Angeles, California 90033, National Cheng Kung University, Tainan 701, Taiwan
| | - Keigo Machida
- Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan, Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, Institute of Biotechnology, National Tsing Hua University, Hsinchu 300, Taiwan, Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2001 Zonal Avenue, Los Angeles, California 90033, National Cheng Kung University, Tainan 701, Taiwan
| | - Michael M. C. Lai
- Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan, Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, Institute of Biotechnology, National Tsing Hua University, Hsinchu 300, Taiwan, Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2001 Zonal Avenue, Los Angeles, California 90033, National Cheng Kung University, Tainan 701, Taiwan
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Patel J, Sigmund EE, Rusinek H, Oei M, Babb JS, Taouli B. Diagnosis of cirrhosis with intravoxel incoherent motion diffusion MRI and dynamic contrast-enhanced MRI alone and in combination: preliminary experience. J Magn Reson Imaging 2010; 31:589-600. [PMID: 20187201 DOI: 10.1002/jmri.22081] [Citation(s) in RCA: 304] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
PURPOSE To report our preliminary experience with the use of intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (DW-MRI) and dynamic contrast-enhanced (DCE)-MRI alone and in combination for the diagnosis of liver cirrhosis. MATERIALS AND METHODS Thirty subjects (16 with noncirrhotic liver, 14 with cirrhosis) were prospectively assessed with IVIM DW-MRI (n = 27) and DCE-MRI (n = 20). IVIM parameters included perfusion fraction (PF), pseudodiffusion coefficient (D*), true diffusion coefficient (D), and apparent diffusion coefficient (ADC). Model-free DCE-MR parameters included time to peak (TTP), upslope, and initial area under the curve at 60 seconds (IAUC60). A dual input single compartmental perfusion model yielded arterial flow (Fa), portal venous flow (Fp), arterial fraction (ART), mean transit time (MTT), and distribution volume (DV). The diagnostic performances for diagnosis of cirrhosis were evaluated for each modality alone and in combination using logistic regression and receiver operating characteristic analyses. IVIM and DCE-MR parameters were compared using a generalized estimating equations model. RESULTS PF, D*, D, and ADC values were significantly lower in cirrhosis (P = 0.0056-0.0377), whereas TTP, DV, and MTT were significantly increased in cirrhosis (P = 0.0006-0.0154). There was no correlation between IVIM- and DCE-MRI parameters. The highest Az (areas under the curves) values were observed for ADC (0.808) and TTP-DV (0.952 for each). The combination of ADC with DV and TTP provided 84.6% sensitivity and 100% specificity for diagnosis of cirrhosis. CONCLUSION The combination of DW-MRI and DCE-MRI provides an accurate diagnosis of cirrhosis.
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Affiliation(s)
- Jignesh Patel
- NYU Langone Medical Center, Department of Radiology, New York, New York, USA
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Abstract
Hepatitis C virus (HCV) causes significant morbidity and mortality worldwide with nearly 3% of the world population infected by this virus. Fortunately, this virus does not establish latency, and hence it may be possible to eradicate it. HCV is strongly associated with liver cirrhosis and hepatocellular carcinoma and is currently treated with pegylated interferon-alpha (peg-IFN-alpha) and ribavirin. Unfortunately, these limited treatment options often produce significant side effects, and currently, complete eradication of virus with combined drug modalities has not yet been achieved for the majority of chronically HCV-infected individuals. Restricted treatment options, lack of a universal cure for HCV and the link between chronic infection, liver cirrhosis and hepatocellular carcinoma necessitate design of novel drugs and treatment options. Understanding the relationship between the immune response, viral clearance and inhibition of viral replication with pharmacology-based design can ultimately allow for complete eradication of HCV. This review focuses upon significant novel preclinical and clinical specifically targeted antiviral therapy (STAT-C) drugs under development, highlights their mechanism of action, and discusses their impact on systemic viral loads and permanent clearance of infection.
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Affiliation(s)
- R F Schinazi
- Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Veterans Affairs Medical Center/Emory University School of Medicine, Atlanta, GA, USA.
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Value of diffusion-weighted MRI for assessing liver fibrosis and cirrhosis. AJR Am J Roentgenol 2010; 193:1556-60. [PMID: 19933647 DOI: 10.2214/ajr.09.2436] [Citation(s) in RCA: 151] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The objective of our study was to determine the usefulness of the apparent diffusion coefficient (ADC) of liver parenchyma for determining the severity of liver fibrosis. MATERIALS AND METHODS This study investigated 78 patients who underwent diffusion-weighted imaging (DWI) with 1.5-T MRI and pathologic staging of liver fibrosis based on biopsy. DWI was performed with b values of 50 and 400 s/mm(2). ADCs of liver were measured using 2.0- to 3.0-cm(2) regions of interest in the right and left lobes of the liver; the mean ADC value was used for analysis. Pathologic METAVIR scores for liver fibrosis stage were used as a reference standard. RESULTS The mean ADC values for fibrosis pathologically staged using the METAVIR classification system as F0 (n = 11), F1 (n = 16), F2 (n = 10), F3 (n = 14), and F4 (n = 27) were 125.9, 105.0, 104.5, 103.2, and 99.1 x 10(-5) s/mm(2), respectively. The correlation between the ADC values and the degree of liver fibrosis was moderate (Spearman's test, rho = -0.36). There was a significant difference in ADC values between patients with nonfibrotic liver (F0) and those with cirrhotic liver (F4) (p = 0.008). The best cutoff ADC value to distinguish between these groups was 118 x 10(-5) s/mm(2). However, ADC values were not useful for differentiating viral hepatitis patients with F2 fibrosis or higher from those with a lower degree of fibrosis (area under the receiver operating characteristic curve [AUC] = 0.66) or for differentiating low-stage fibrosis in all patients from high-stage fibrosis in all patients (AUC = 0.54). CONCLUSION The ADCs in cirrhotic livers are significantly lower than those in nonfibrotic livers. However, ADC values measured using the current generation of scanners are not reliable enough to replace liver biopsy for staging hepatic fibrosis.
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Gidding HF, Topp L, Middleton M, Robinson K, Hellard M, McCaughan G, Maher L, Kaldor JM, Dore GJ, Law MG. The epidemiology of hepatitis C in Australia: notifications, treatment uptake and liver transplantations, 1997-2006. J Gastroenterol Hepatol 2009; 24:1648-54. [PMID: 19798783 DOI: 10.1111/j.1440-1746.2009.05910.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND AND AIM Regular monitoring of hepatitis C (HCV)-related surveillance data is essential to inform and evaluate strategies to reduce the expanding HCV burden. The aim of this study was to examine trends in the epidemiology and treatment of HCV in Australia. METHODS We reviewed data about HCV notifications, treatment of HCV infection through the Highly Specialised Drugs (s100) Program, and liver transplants (Australia and New Zealand Liver Transplant Registry) for the period 1997-2006. RESULTS HCV case notification rates declined by almost 50% between 1999 and 2006, with the greatest reductions between 2001 and 2002 and amongst young adults. For newly acquired HCV cases, 89% were Australian-born and 90% reported injecting drug use as a risk factor for infection. Overall, 30% of liver transplant recipients had HCV-related cirrhosis, but the number and proportion of HCV diagnoses increased between 1997 and 2006. HCV treatment also increased over the review period. However, only 1.4% of the 202,400 people estimated to be living with chronic HCV at the end of 2006 received treatment that year. CONCLUSION The decline in HCV notifications is consistent with a decline in HCV incidence in Australia. However, the burden of advanced HCV disease continues to expand. To reduce this burden, treatment uptake needs to increase. Consistent and sensitive surveillance mechanisms are required to detect newly acquired cases together with an expansion of surveillance for chronic HCV infections.
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Affiliation(s)
- Heather F Gidding
- National Centre in HIV Epidemiology and Clinical Research, Darlinghurst, NSW 2010, Australia.
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Abstract
OBJECTIVE With recent advances in technology, advanced MRI methods such as diffusion-weighted and perfusion-weighted MRI, MR elastography, chemical shift-based fat-water separation, and MR spectroscopy can now be applied to liver imaging. We will review the respective roles of these techniques for assessment of chronic liver disease. CONCLUSION MRI plays an increasingly important role in assessment of patients with chronic liver disease because of the lack of ionizing radiation and the possibility of performing multiparametric imaging.
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Affiliation(s)
- Bachir Taouli
- Department of Radiology New York University Medical Center 560 First Avenue New York, NY, 10016
| | - Richard L. Ehman
- Department of Radiology Mayo Clinic 200 First St. SW Rochester, MN, 55905
| | - Scott B. Reeder
- Department of Radiology, Medical Physics and Biomedical Engineering University of Wisconsin 600 Highland Ave, CSC E1/374 Madison, WI 53792-3252
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Zule WA, Costenbader EC, Coomes CM, Wechsberg WM. Effects of a hepatitis C virus educational intervention or a motivational intervention on alcohol use, injection drug use, and sexual risk behaviors among injection drug users. Am J Public Health 2009; 99 Suppl 1:S180-6. [PMID: 19218179 PMCID: PMC2724936 DOI: 10.2105/ajph.2007.126854] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/10/2008] [Indexed: 01/23/2023]
Abstract
OBJECTIVES We compared the effects of 2 interventions on alcohol use, use of a new syringe at last injection, and condom use at last sexual encounter in a community sample of injection drug users. METHODS Between 2003 and 2006, 851 out-of-treatment injection drug users were recruited in Raleigh, NC, and Durham, NC, through street outreach and were randomly assigned to either a 6-session educational intervention or a 6-session motivational intervention. Intervention effects were examined at 6 and 12 months after enrollment. RESULTS In multiple logistic regression analyses adjusted for baseline alcohol use and HCV status, participants assigned to the motivational intervention were significantly less likely than were participants in the educational intervention to be drinking at the 6-month follow-up (odds ratio = 0.67; 95% confidence interval = 0.46, 0.97). There were no significant between-group differences in use of a new syringe at last injection or condom use at last sexual encounter at either follow-up. CONCLUSIONS Reducing alcohol use among persons with HCV may slow disease progression and provide important health benefits. Additional strategies are needed for slowing HCV disease progression until more effective HCV treatments are available.
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Affiliation(s)
- William A Zule
- Behavioral Health Criminal Justice Research Division, RTI International, P.O. Box 12194, Research Triangle Park, NC 27709-2194, USA.
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Kleppinger EL, Ragan AP. Elevated hepatic transaminases associated with the use of interferon alfacon-1 and ribavirin. Am J Health Syst Pharm 2009; 66:465-8. [PMID: 19233994 DOI: 10.2146/ajhp080243] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
PURPOSE The case of a patient with hepatitis C who developed elevated hepatic transaminase levels associated with the use of interferon alfacon-1 and ribavirin is described. SUMMARY A 55-year-old Caucasian man arrived at a hepatitis C clinic to discuss alternative treatment options for his hepatitis C virus (genotype 1a) infection, which did not respond to a 48-week course of peginterferon and ribavirin therapy. He was subsequently treated with interferon alfacon-1 9 microg subcutaneously daily plus ribavirin 200 mg orally twice daily. During treatment with interferon alfacon-1, he developed elevated hepatic transaminase levels despite a decrease in viral load. His hepatic transaminase levels returned to baseline when interferon alfacon-1 was discontinued and rose again upon rechallenge. Ribavirin was not the likely cause of the increase in transaminases since the patient previously tolerated it in combination with peginterferon. While activation of autoimmune hepatitis is a potential cause of acute decompensation in patients treated with interferons, it was not believed to be the case in this patient. Interferon alfacon-1 was determined to be the probable cause of the rise in hepatic transaminase levels in this patient, since his levels declined when therapy was discontinued and rose dramatically once it was restarted. This case illustrates the importance of monitoring both viral loads and hepatic transaminase levels in patients with hepatitis C being treated with interferon therapy. CONCLUSION A patient with hepatitis C developed elevated hepatic transaminase levels despite showing an improvement in viral load after receiving interferon alfacon-1 and ribavirin.
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Affiliation(s)
- Erika L Kleppinger
- Department of Pharmacy Practice, Harrison School of Pharmacy, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.
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DENHOLM JT, WRIGHT EJ, STREET A, SASADEUSZ JJ. HCV treatment with pegylated interferon and ribavirin in patients with haemophilia and HIV/HCV co-infection. Haemophilia 2009; 15:538-43. [DOI: 10.1111/j.1365-2516.2009.01972.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Abstract
UNLABELLED The prevalence of chronic hepatitis C infection in U.S. prisons is 12% to 31%. Treatment of this substantial portion of the population has been subject to much controversy, both medically and legally. Studies have demonstrated that treatment of chronic hepatitis C with pegylated interferon (PEG IFN) and ribavirin is a cost-effective measure in the general population; however, no study has addressed whether the same is true of the prison population. The aim of this study was to determine the cost-effectiveness of hepatitis C treatment with PEG IFN and ribavirin in the U.S. prison population. Cost-effectiveness was determined via a decision analysis model employing Markov simulation. The cohort of prisoners had a distribution of genotypes and stages of fibrosis in accordance with prior studies evaluating inmate populations. The probability of transitioning from one health state to another, reinfection rates, in-prison and out-of-prison mortality rates, sustained viral response rates, costs, and quality of life weights were also obtained from the literature. Sensitivity analysis was performed. In a strategy without a pretreatment liver biopsy, treatment was cost-effective for all ages and genotypes. This model was robust to rates of disease progression, mortality rates, reinfection rates, sustained viral response rates, and costs. In a strategy employing a pretreatment liver biopsy, treatment was also cost-saving for prisoners of all ages and genotypes with portal fibrosis, bridging fibrosis, or compensated cirrhosis. Treatment was not cost-effective in patients between the ages of 40 and 49 with no fibrosis and genotype 1. CONCLUSION Treatment of chronic hepatitis C with PEG IFN and ribavirin in U.S. prisons results in both improved quality of life and savings in cost for almost all segments of the inmate population. If the decision to treat hepatitis C is based on pharmaco-economic measures, this significant proportion of infected individuals should not be denied access to therapy.
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Affiliation(s)
- Jennifer A Tan
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA
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Publicly funded pegylated interferon-alpha treatment in British Columbia: disparities in treatment patterns for people with hepatitis C. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2008; 22:359-64. [PMID: 18414709 DOI: 10.1155/2008/243607] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND An estimated 60,000 British Columbians are chronically infected with the hepatitis C virus (HCV); 10% to 20% will develop cirrhosis after 20 years and 5% to 10% of these will develop hepatocellular carcinoma. Although treatment may prevent cirrhosis and liver cancer, and improve quality of life, availability is limited. METHODS Individuals with HCV genotypes 1, 4, 5 and 6 who underwent baseline HCV-RNA tests between January 1, 2003 and December 31, 2005, and were eligible for publicly funded treatment through PharmaCare were linked to British Columbia's reportable disease database. Patterns in treatment were examined, including age at treatment, sex, location, time to treatment from HCV diagnosis and seasonality of treatment. RESULTS When corrected for HCV prevalence, men were more likely to receive treatment than women (RR 1.16, 95% CI 1.02 to 1.31). Patients aged 35 to 54 years and 55 years or older were 3.45 times (95% CI 2.80 to 4.26 times) and 4.49 times (95% CI 3.55 to 5.69 times), respectively, more likely to initiate treatment than 15- to 34-year-olds. Differences were noted between health authorities. Patients in rural health service delivery areas (HSDAs) were 1.25 times (95% CI 1.10 to 1.42 times) more likely to receive treatment than those in urban HSDAs. Patients had an average lapse of four years between HCV diagnosis and receiving treatment. The highest proportion of patients initiated therapy between January and March (36.5%), with the lowest between October and December (less than 14%). CONCLUSIONS This data linkage enabled us to identify populations less likely to receive publicly funded treatment. Rural HSDAs have higher rates of therapy initiation; this pattern merits further research but may be a result of integrated prevention and care projects in rural areas. Policy changes to the current PharmaCare funding co-payment schedules could reduce seasonal variability of treatment initiations throughout the year.
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Molino C, Fabbian F, Cozzolino M, Longhini C. The management of viral hepatitis in CKD patients: an unresolved problem. Int J Artif Organs 2008; 31:683-696. [PMID: 18825641 DOI: 10.1177/039139880803100802] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Abstract
Chronic kidney disease (CKD) patients in dialysis (HD) show peculiar, atypical features of clinical presentation and diseases (cardiovascular, metabolic, hematologic). This is also true for viral hepatitis infections, for which CKD patients represent an important risk group. In the past, hepatitis B virus (HBV) was the major cause of viral hepatitis in end-stage renal disease (ESRD). However, the introduction of a rigorous infection-control strategy, routine screening of patients and staff for hepatitis B serologic markers, vaccination of susceptible patients and staff, use of separate rooms and dedicated machines for HD of HbsAg-positive patients have all led to a decline in the spread of HBV infection in dialysis. Despite the prevalence of the antibody-hepatitis C virus (HCV), there has been a marked decrease in HD patients; after the introduction of routine screening for HCV and the use of erythropoietin, its occurrence ranges from 5% to 25% in the United States, with a prevalence of 6.8% in Europe. In CKD and in HD patients, the presence of HBV and HCV is an independent and significant risk factor for death and this risk may be at least partially attributed to chronic liver disease with its attendant complications. Liver disease can progress with modest hepatic inflammation and prominent fibrosis; the natural history of viral hepatitis in these patients is dependent on the immune dysfunction typical of kidney disease. Despite recent advances in antiviral therapy, there are still many uncertainties in regards to the efficacy and long-term outcomes of treatment with antiviral agents.
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Affiliation(s)
- C Molino
- Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy.
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Beckwith AR. The Precipitation of Mania by Citalopram in a Patient With Interferon-Induced Depression. PSYCHOSOMATICS 2008; 49:362-3. [DOI: 10.1176/appi.psy.49.4.362-a] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Peginterferon vs. interferon in the treatment of different HCV genotype infections in HIV patients. Eur J Clin Microbiol Infect Dis 2008; 27:1183-92. [PMID: 18560911 DOI: 10.1007/s10096-008-0557-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2008] [Accepted: 05/13/2008] [Indexed: 12/22/2022]
Abstract
It remains difficult to achieve high sustained response rates (SVRs) in chronic hepatitis patients coinfected with human immunodeficiency virus (HIV). The aim of this study was to perform a meta-analysis of randomized controlled trials (RCTs) comparing peginterferon with interferon in the treatment of patients carrying different genotypes of hepatitis C virus (HCV) and coinfected with HIV. A Medline literature search was conducted to identify RCTs evaluating SVRs to peginterferon and interferon in HCV/HIV-coinfected patients. Six studies matched the selection criteria, and the HCV genotype of 1,717 coinfected patients was reported. For genotypes 1 or 4 HCV and HIV-coinfected patients, both types of peginterferon, alpha-2a and alpha-2b, achieved higher SVRs compared with the respective types of interferon. The SVRs achieved in patients infected with HCV genotypes 1 or 4 treated with peginterferon and ribavirin was not satisfactory in comparison with those of patients infected with HCV genotypes 2 or 3 (26% vs. 55%). The probability of achieving higher SVRs in patients when treated with peginterferon plus ribavirin increased compared with other therapies, especially for patients coinfected with HCV genotypes 1 or 4 and HIV. The likelihoods of serious adverse effects and withdrawal rates were similar.
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Kresina TF, Sylvestre D, Seeff L, Litwin AH, Hoffman K, Lubran R, Clark HW. Hepatitis infection in the treatment of opioid dependence and abuse. Subst Abuse 2008; 1:15-61. [PMID: 25977607 PMCID: PMC4395041 DOI: 10.4137/sart.s580] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Many new and existing cases of viral hepatitis infections are related to injection drug use. Transmission of these infections can result directly from the use of injection equipment that is contaminated with blood containing the hepatitis B or C virus or through sexual contact with an infected individual. In the latter case, drug use can indirectly contribute to hepatitis transmission through the dis-inhibited at-risk behavior, that is, unprotected sex with an infected partner. Individuals who inject drugs are at-risk for infection from different hepatitis viruses, hepatitis A, B, or C. Those with chronic hepatitis B virus infection also face additional risk should they become co-infected with hepatitis D virus. Protection from the transmission of hepatitis viruses A and B is best achieved by vaccination. For those with a history of or who currently inject drugs, the medical management of viral hepatitis infection comprising screening, testing, counseling and providing care and treatment is evolving. Components of the medical management of hepatitis infection, for persons considering, initiating, or receiving pharmacologic therapy for opioid addiction include: testing for hepatitis B and C infections; education and counseling regarding at-risk behavior and hepatitis transmission, acute and chronic hepatitis infection, liver disease and its care and treatment; vaccination against hepatitis A and B infection; and integrative primary care as part of the comprehensive treatment approach for recovery from opioid abuse and dependence. In addition, participation in a peer support group as part of integrated medical care enhances treatment outcomes. Liver disease is highly prevalent in patient populations seeking recovery from opioid addiction or who are currently receiving pharmacotherapy for opioid addiction. Pharmacotherapy for opioid addiction is not a contraindication to evaluation, care, or treatment of liver disease due to hepatitis virus infection. Successful pharmacotherapy for opioid addiction stabilizes patients and improves patient compliance to care and treatment regimens as well as promotes good patient outcomes. Implementation and integration of effective hepatitis prevention programs, care programs, and treatment regimens in concert with the pharmacological therapy of opioid addiction can reduce the public health burdens of hepatitis and injection drug use.
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Affiliation(s)
- Thomas F Kresina
- Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, Rockville, MD
| | - Diana Sylvestre
- Department of Medicine, University of California, San Francisco and Organization to Achieve Solutions In Substance Abuse (O.A.S.I.S.) Oakland, CA
| | - Leonard Seeff
- Division of Digestive Diseases and Nutrition, National Institute on Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD
| | - Alain H Litwin
- Division of Substance Abuse, Albert Einstein College of Medicine, Montefiore Medical Center Bronx, NY
| | - Kenneth Hoffman
- Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, Rockville, MD
| | - Robert Lubran
- Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, Rockville, MD
| | - H Westley Clark
- Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, Rockville, MD
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Abstract
A disease whose reputation is often worse than its reality, hepatitis C is usually benign. Most infected individuals do not experience symptoms requiring treatment, and roughly half of those treated will become free of detectable virus for an extended, perhaps permanent, period. Moreover, a growing body of data suggests that drug users can attain successful treatment outcomes, even when not completely abstinent. Addiction professionals belong in the forefront of prevention and management of this disease. We can assist our patients by helping them stabilize their lifestyles, correcting misperceptions about the disease, teaching prevention and health maintenance, promoting access to diagnosis and treatment, monitoring for treatment side effects, and providing encouragement to remain in treatment.
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Hagiwara M, Rusinek H, Lee VS, Losada M, Bannan MA, Krinsky GA, Taouli B. Advanced liver fibrosis: diagnosis with 3D whole-liver perfusion MR imaging--initial experience. Radiology 2008; 246:926-34. [PMID: 18195377 DOI: 10.1148/radiol.2463070077] [Citation(s) in RCA: 182] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. The purpose of this study was to prospectively evaluate sensitivity and specificity of various estimated perfusion parameters at three-dimensional (3D) perfusion magnetic resonance (MR) imaging of the liver in the diagnosis of advanced liver fibrosis (stage >or= 3), with histologic analysis, liver function tests, or MR imaging as the reference standard. Whole-liver 3D perfusion MR imaging was performed in 27 patients (17 men, 10 women; mean age, 55 years) after dynamic injection of 8-10 mL of gadopentetate dimeglumine. The following estimated perfusion parameters were measured with a dual-input single-compartment model: absolute arterial blood flow (F(a)), absolute portal venous blood flow (F(p)), absolute total liver blood flow (F(t)) (F(t) = F(a) + F(p)), arterial fraction (ART), portal venous fraction (PV), distribution volume (DV), and mean transit time (MTT) of gadopentetate dimeglumine. Patients were assigned to two groups (those with fibrosis stage <or= 2 and those with fibrosis stage >or= 3), and the nonparametric Mann-Whitney test was used to compare F(a), F(p), F(t), ART, PV, DV, and MTT between groups. Receiver operating characteristic curve analysis was used to assess the utility of perfusion estimates as predictors of advanced liver fibrosis. There were significant differences for all perfusion MR imaging-estimated parameters except F(p) and F(t). There was an increase in F(a), ART, DV, and MTT and a decrease in PV in patients with advanced fibrosis compared with those without advanced fibrosis. DV had the best performance, with an area under the receiver operating characteristic curve of 0.824, a sensitivity of 76.9% (95% confidence interval: 46.2%, 94.7%), and a specificity of 78.5% (95% confidence interval: 49.2%, 95.1%) in the prediction of advanced fibrosis.
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Affiliation(s)
- Mari Hagiwara
- Department of Radiology, New York University Medical Center, 560 First Ave, New York, NY 10016, USA
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Taouli B, Tolia AJ, Losada M, Babb JS, Chan ES, Bannan MA, Tobias H. Diffusion-weighted MRI for quantification of liver fibrosis: preliminary experience. AJR Am J Roentgenol 2007; 189:799-806. [PMID: 17885048 DOI: 10.2214/ajr.07.2086] [Citation(s) in RCA: 275] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The purpose of this study was to evaluate our preliminary experience using diffusion-weighted MRI for quantification of liver fibrosis. SUBJECTS AND METHODS Diffusion-weighted MRI with single-shot echo-planar technique at b values of 50, 300, 500, 700, and 1,000 s/mm2 was prospectively performed on 23 patients with chronic hepatitis and on seven healthy volunteers. The apparent diffusion coefficient (ADC) was measured in four locations in the liver. Liver biopsy results (n = 19) were retrospectively reviewed by two hepatopathologists in consensus to determine stage of fibrosis and grade of inflammation. A Mann-Whitney test was used to compare the ADCs between patients classified with respect to having stage 2 or greater versus stage 1 or less fibrosis and stage 3 or greater versus stage or less 2 fibrosis. Receiver operating characteristics analysis was used to assess the performance of ADC in prediction of the presence of stage 2 or greater and stage 3 or greater fibrosis. RESULTS Using a b value of 500 s/mm2 and all combined b values, we found significantly lower hepatic ADCs in stage 2 or greater versus stage 1 or less fibrosis and stage 3 or greater versus stage 2 or less fibrosis. The mean ADCs (x 10(-3) mm2/s) with all b values were 1.47 +/- 0.11 (SD) versus 1.65 +/- 0.10 for stage 2 or greater versus stage 1 or less fibrosis (p < 0.001) and 1.44 +/- 0.07 versus 1.66 +/- 0.10 for stage 3 or greater versus stage 2 or less fibrosis (p <0.001). Hepatic ADC was a significant predictor of stage 2 or greater and stage 3 or greater fibrosis, with areas under the curve of 0.896 and 0.896, sensitivity of 83.3% and 88.9%, and specificity of 83.3% and 80.0% (ADC with all b values, 1.54-1.53 x 10(-3) mm2/s or less). CONCLUSION Diffusion-weighted MRI can be used for prediction of the presence of moderate and advanced liver fibrosis.
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Affiliation(s)
- Bachir Taouli
- New York University Medical Center, MRI, 530 First Ave., New York, NY 10016, USA.
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Abstract
OBJECTIVE To review the epidemiology, pathophysiology, and therapeutics of chronic hepatitis C virus (HCV) infection, focusing on patient counseling and adverse effects, to serve as a resource for pharmacists in multiple patient care settings. DATA SOURCES Published articles identified through Medline using search terms such as hepatitis C virus, hepacivirus, ribavirin, interferon alfa-2a, or interferon alfa-2b. Therapeutic guidelines retrieved from www.guidelines.gov and the Centers for Disease Control and Prevention (CDC). Additional resources identified from personal bibliographies collected by the author and bibliographies from gathered articles. STUDY SELECTION By the author. DATA EXTRACTION By the author. DATA SYNTHESIS HCV is a blood-borne pathogen affecting an estimated 4 million Americans and 170 million people worldwide. An estimated two-thirds to three-fourths of those infected with HCV have not been diagnosed, and in the next 10 to 20 years, the number of patients diagnosed with HCV is likely to increase. Thus, the health care community, including pharmacists, needs to be educated about the disease, how it is spread, and the details related to treatment of HCV. The standard therapy for HCV is combination therapy with pegylated interferon and ribavirin. This therapy has a varied rate of response that improves with medication adherence. Adherence is often reduced as a result of adverse effects of therapy. In this article, a basic review of HCV is provided, as well as a thorough discussion of strategies to reduce the incidence and severity of adverse effects related to therapy. CONCLUSION Pharmacists have an important role in educating other health care practitioners and the community about HCV, providing injection training and medication and adverse effect counseling for patients initiating therapy, and engaging in follow-up and monitoring of patients to encourage therapeutic success by improving medication adherence and patient tolerance of adverse effects.
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Affiliation(s)
- Jennifer Rodis
- Division of Pharmacy Practice and Administration, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
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