ABSTRACT
BACKGROUND: HIV and hepatitis C virus (HCV) are associated with increased risk of carotid artery atherosclerotic plaque and stroke. We examined associations of HIV- and HCV-related factors with echomorphologic features of carotid artery plaque. METHODS: This cross-sectional study included participants from the MACS (Multicenter AIDS Cohort Study)/WIHS (Women's Interagency HIV Study) Combined Cohort Study who underwent high-resolution B-mode carotid artery ultrasound. Plaques were characterized from 6 areas of the right carotid artery. Poisson regression controlling for demographic and cardiometabolic risk factors determined adjusted prevalence ratios (aPRs) and 95% CIs for associations of HIV- and HCV-related factors with echomorphologic features. RESULTS: Of 2655 participants (65% women, median age 44 [interquartile range, 37-50] years), 1845 (70%) were living with HIV, 600 (23%) were living with HCV, and 425 (16%) had carotid plaque. There were 191 plaques identified in 129 (11%) women with HIV, 51 plaques in 32 (7%) women without HIV, 248 plaques in 171 (28%) men with HIV, and 139 plaques in 93 (29%) men without HIV. Adjusted analyses showed that people with HIV and current CD4+ count <200 cells/µL had a significantly higher prevalence of predominantly echolucent plaque (aPR, 1.86 [95% CI, 1.08-3.21]) than those without HIV. HCV infection alone (aPR, 1.86 [95% CI, 1.08-3.19]) and HIV-HCV coinfection (aPR, 1.75 [95% CI, 1.10-2.78]) were each associated with higher prevalence of predominantly echogenic plaque. HIV-HCV coinfection was also associated with higher prevalence of smooth surface plaque (aPR, 2.75 [95% CI, 1.03-7.32]) compared with people without HIV and HCV. CONCLUSIONS: HIV with poor immunologic control, as well as HCV infection, either alone or in the presence of HIV, were associated with different echomorphologic phenotypes of carotid artery plaque.
Subject(s)
Carotid Artery Diseases , Carotid Stenosis , Coinfection , HIV Infections , Hepatitis C , Plaque, Atherosclerotic , Adult , Female , Humans , Male , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/epidemiology , Carotid Artery Diseases/complications , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/epidemiology , Carotid Stenosis/complications , Cohort Studies , Coinfection/diagnostic imaging , Coinfection/epidemiology , Coinfection/complications , Cross-Sectional Studies , Hepacivirus , Hepatitis C/complications , Hepatitis C/diagnostic imaging , Hepatitis C/epidemiology , HIV Infections/complications , HIV Infections/diagnostic imaging , HIV Infections/epidemiology , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/epidemiology , Plaque, Atherosclerotic/complications , Risk Factors , Middle Aged , Multicenter Studies as TopicABSTRACT
ABSTRACT: We assessed the performance characteristics of the Fibrosis-4 (FIB-4) score in a veteran population with chronic hepatitis C virus (HCV) infection and used vibration controlled transient elastography (VCTE) as the gold standard.All VCTE studies were performed by a single operator on United States veterans with HCV infection presenting for care at the Atlanta VA Medical Center (AVAMC) over a 2 year period. VCTE liver stiffness measurements (LSM) were categorized as cirrhotic if LSM was >12.5 kPa and non-cirrhotic if LSM was ≤12.5 kPa. FIB-4 scores ≤3.25 were considered non-cirrhotic and scores >3.25 were considered cirrhotic. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the FIB-4 score. A second analysis was done which identified and excluded indeterminate FIB-4 scores, defined as any value between 1.45 and 3.25.When FIB-4 was used to screen for liver cirrhosis using VCTE as the gold standard, sensitivity was 42%, specificity was 88%, PPV was 62%, and NPV was 76%. When indeterminate FIB-4 scores were excluded from the analysis, sensitivity was 95%, specificity was 61%, PPV was 62%, and NPV was 94.4%. In a veteran population with chronic HCV infection, we found the sensitivity of the FIB-4 score to be unacceptably low for ruling out liver cirrhosis when using a binary cutoff at 3.25. Using a second staging method like VCTE may be an effective way to screen for liver cirrhosis in persons with chronic HCV, especially when the FIB-4 score is in the indeterminate range.
Subject(s)
Elasticity Imaging Techniques/standards , Hepatitis C/complications , Liver Cirrhosis/classification , Liver Cirrhosis/diagnostic imaging , Severity of Illness Index , Adult , Elasticity Imaging Techniques/methods , Elasticity Imaging Techniques/statistics & numerical data , Female , Georgia , Hepacivirus/pathogenicity , Hepatitis C/diagnostic imaging , Humans , Liver Cirrhosis/physiopathology , Male , Middle Aged , ROC Curve , VibrationABSTRACT
BACKGROUND AND AIMS: Risk stratification after cure from hepatitis C virus (HCV) infection remains a clinical challenge. We investigated the predictive value of noninvasive surrogates of portal hypertension (liver stiffness measurement [LSM] by vibration-controlled transient elastography and von Willebrand factor/platelet count ratio [VITRO]) for development of hepatic decompensation and hepatocellular carcinoma in patients with pretreatment advanced chronic liver disease (ACLD) who achieved HCV cure. APPROACH AND RESULTS: A total of 276 patients with pretreatment ACLD and information on pretreatment and posttreatment follow-up (FU)-LSM and FU-VITRO were followed for a median of 36.6 months after the end of interferon-free therapy. FU-LSM (area under the receiver operating characteristic curve [AUROC]: 0.875 [95% confidence interval [CI]: 0.796-0.954]) and FU-VITRO (AUROC: 0.925 [95% CI: 0.874-0.977]) showed an excellent predictive performance for hepatic decompensation. Both parameters provided incremental information and were significantly associated with hepatic decompensation in adjusted models. A previously proposed combined approach (FU-LSM < 12.4 kPa and/or FU-VITRO < 0.95) to rule out clinically significant portal hypertension (CSPH, hepatic venous pressure gradient ≥10 mm Hg) at FU assigned most (57.3%) of the patients to the low-risk group; none of these patients developed hepatic decompensation. In contrast, in patients in whom FU-CSPH was ruled in (FU-LSM > 25.3 kPa and/or FU-VITRO > 3.3; 25.0% of patients), the risk of hepatic decompensation at 3 years following treatment was high (17.4%). Patients within the diagnostic gray-zone for FU-CSPH (17.8% of patients) had a very low risk of hepatic decompensation during FU (2.6%). The prognostic value of this algorithm was validated in an internal (n = 86) and external (n = 162) cohort. CONCLUSION: FU-LSM/FU-VITRO are strongly and independently predictive of posttreatment hepatic decompensation in HCV-induced ACLD. An algorithm combining these noninvasive markers not only rules in or rules out FU-CSPH, but also identifies populations at negligible versus high risk for hepatic decompensation. FU-LSM/FU-VITRO are readily accessible and enable risk stratification after sustained virological response, and thus facilitate personalized management.
Subject(s)
Elasticity Imaging Techniques , Hepatitis C , Platelet Count , von Willebrand Factor , Adult , Aftercare , Aged , Chronic Disease , Disease Progression , Female , Hepacivirus , Hepatitis C/blood , Hepatitis C/complications , Hepatitis C/diagnostic imaging , Hepatitis C/drug therapy , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnostic imaging , Hepatitis C, Chronic/drug therapy , Humans , Liver Diseases/blood , Liver Diseases/diagnostic imaging , Liver Diseases/virology , Male , Middle Aged , Predictive Value of Tests , Prognosis , Risk Assessment , Sustained Virologic Response , von Willebrand Factor/analysisABSTRACT
BACKGROUND: We conducted a prospective study using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) to determine whether sustained virological response (SVR) by direct-acting anti-viral (DAA) drugs suppresses hepatocarcinogenesis in patients with hepatitis C virus (HCV) infection. AIM: To use serial Gd-EOB-MRI to assess the impact of DAAs on hepatocarcinogenesis. METHODS: Between February 2008 and December 2018, 1083 consecutive patients with HCV infection underwent Gd-EOB-MRI. Of these, 719 patients were enrolled, including 210 patients in the 'Non-DAA group', who did not receive DAAs before the introduction of DAAs, and 509 patients in the 'DAA group', who achieved SVR after the introduction of DDAs. Factors associated with hepatocarcinogenesis were analysed by a Cox proportional hazard model. In addition, hepatocarcinogenesis was classified into two types, 'multistep' and 'de novo', on the basis of Gd-EOB-MRI findings. Factors associated with each type were analysed by Fine and Gray proportional hazards models. RESULTS: Hepatocarcinogenesis was observed in 67 of 719 (9.3%) patients. Factors associated with hepatocarcinogenesis were male gender, albumin-bilirubin (ALBI) grade 2 or 3, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) ≥5%, the presence of nonhypervascular hypointense nodules (NHHNs) and Non-DAA group. Of 67 patients, multistep hepatocarcinogenesis occurred in 58 patients (86.6%) and de novo hepatocarcinogenesis occurred in nine patients (13.4%). Factors associated with multistep hepatocarcinogenesis were male gender and Non-DAA group. CONCLUSION: The eradication of HCV by DAA therapy reduces multistep hepatocarcinogenesis.
Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/etiology , Hepatitis C/complications , Hepatitis C/drug therapy , Liver Neoplasms/drug therapy , Liver Neoplasms/etiology , Aged , Bilirubin/blood , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/virology , Contrast Media , Female , Follow-Up Studies , Gadolinium DTPA , Hepatitis C/diagnostic imaging , Hepatitis C/virology , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/virology , Magnetic Resonance Imaging , Male , Middle Aged , Prospective Studies , Serum Albumin/analysis , Sex Characteristics , Sustained Virologic Response , alpha-Fetoproteins/analysisSubject(s)
Male , Female , Pregnancy , Infant, Newborn , Prenatal Care/methods , Prenatal Diagnosis/methods , Parasitic Diseases/diagnosis , Thyroid Diseases/diagnosis , Urinary Tract Infections/diagnosis , Syphilis/diagnosis , HIV Infections/diagnosis , Uterine Cervical Neoplasms/diagnosis , Toxoplasmosis/diet therapy , Clinical Protocols , Communicable Diseases/diagnosis , Hepatitis C/diagnosis , Hepatitis C/diagnostic imaging , Cytomegalovirus Infections/diagnosis , Infectious Disease Transmission, Vertical , Clinical Laboratory Techniques , Diabetes Mellitus/diagnosis , Medication Therapy Management , Neonatal Sepsis/diagnosis , Hemoglobinopathies/diagnosis , Hepatitis B/diagnosis , Hepatitis B/diagnostic imaging , Anemia/diagnosis , Measles/diagnosisSubject(s)
Benzimidazoles/administration & dosage , Fluorenes/administration & dosage , Hepacivirus , Hepatitis C , Positron Emission Tomography Computed Tomography , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Sofosbuvir/administration & dosage , Waldenstrom Macroglobulinemia , Hepatitis C/complications , Hepatitis C/diagnostic imaging , Hepatitis C/drug therapy , Humans , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnostic imaging , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Waldenstrom Macroglobulinemia/diagnostic imaging , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/etiologyABSTRACT
OBJECTIVE: The objective of this study is to compare the value of monoexponential and biexponential approach to the diffusion-weighted magnetic resonance imaging signal in the prediction of the liver fibrosis. METHODS: Forty patients with hepatitis C were included. Quantification of the apparent diffusion coefficient (ADC) and pure molecular diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) was performed using 9 b values (b = 0, 20, 50, 100, 200, 400, 600, 800, 1000 s/mm). RESULTS: Significant fibrosis was found in 14 subjects. Monoexponentally derived ADC parameters were significantly correlated. Apparent diffusion coefficient calculated from all b values and ADC based on high b values were significantly related to the fibrosis grade (P < 0.02), and none of intravoxel incoherent motion parameters presented such an association. Apparent diffusion coefficient based on high b values was the best predictor of significant fibrosis with area under the curve of 0.81, sensitivity of 0.57, and specificity of 0.92. CONCLUSION: Intravoxel incoherent motion parameters did not allow for prediction of the liver fibrosis. Apparent diffusion coefficient calculated based on high b values presents considerable specificity in predicting significant fibrosis.
Subject(s)
Hepatitis C/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Liver Cirrhosis/diagnostic imaging , Adult , Aged , Diffusion Magnetic Resonance Imaging , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Severity of Illness Index , Young AdultABSTRACT
Extrahepatic manifestations of hepatitis C virus (HCV) infection, in particular cognitive impairments, can be present in the absence of clinical liver dysfunction. Executive memory, attention, and concentration are cognitive domains that are most frequently affected. Microstructural and functional changes in cortical gray matter and basal ganglia associate these neuropsychiatric changes in early HCV infection. No study has covered the relationship between imaging features of HCV-related cognitive impairment and HCV pathology. Herein we summarize evidence suggesting a direct pathology of HCV in microglia, astrocytes, and microvascular endothelial cells, and a neuroinflammatory response in HCV-related cognitive decline. Lipoproteins and their receptors mediate HCV infectivity in the central nervous system and confer susceptibility to HCV-related cognitive decline. Magnetic resonance spectroscopy has revealed changes compatible with reactive gliosis and microglial activation in basal ganglia, frontal and occipital white matter, in the absence of cirrhosis or hepatic encephalopathy. Similarly, diffusion imaging shows evidence of structural disintegrity in the axonal fibers of white matter tracts associated with temporal and frontal cortices. We also discuss the cognitive benefits and side-effects of the two most popular therapeutic protocols interferon-based therapy and interferon-free therapy using direct acting anti-virals. Evidences support a network-based pattern of disruption in functional connectivity in HCV patients and a common neuronal substrate for HCV-related and interferon-therapy-associated cognitive decline. These evidences might help identify patients who benefit from either interferon-based or interferon-free treatment regimen.
Subject(s)
Cognitive Dysfunction/complications , Frontal Lobe/diagnostic imaging , Hepacivirus , Hepatitis C/complications , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/psychology , Gray Matter/diagnostic imaging , Hepatitis C/diagnostic imaging , Hepatitis C/psychology , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Memory/physiology , Neuroimaging , White Matter/diagnostic imagingABSTRACT
AIM: The aim of this study was to investigate the relationship between spleen stiffness value, splenic volume and the liver fibrosis stages. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board of our institute. We enrolled 109 patients that had undergone abdominal MR imaging and histopathological examination. The preoperative MR imaging, MR elastography and laboratory data were reviewed. Liver stiffness and spleen stiffness were determined with MR elastography, and splenic volume was calculated. Liver fibrosis stage was determined using surgical pathology. RESULTS: The correlation coefficient between the liver stiffness and the fibrosis stage was r = 0.72 and r = 0.62 when the passive driver was on right chest wall and the left chest wall, respectively. The correlation coefficient between the spleen stiffness and the fibrosis stage was r = 0.63 and r = 0.18 when the passive driver was on the left chest wall and the right chest wall, respectively. The correlation coefficient between the splenic volume and the fibrosis stage was r = 0.31. The diagnostic performance of spleen stiffness was similar to liver stiffness in prediction of advanced liver fibrosis. The combination of spleen stiffness and liver stiffness provided greater sensitivity in prediction of advanced fibrosis than spleen or liver stiffness alone, but no significant difference was found. CONCLUSION: According to our study, the spleen stiffness value was useful in staging liver fibrosis. The combination of spleen stiffness and liver stiffness could provide higher diagnostic sensitivity than liver stiffness alone in prediction of advanced fibrosis.
Subject(s)
Liver Cirrhosis/diagnosis , Liver/diagnostic imaging , Spleen/diagnostic imaging , Adult , Algorithms , Elasticity Imaging Techniques , Fatty Liver/diagnostic imaging , Fatty Liver/physiopathology , Female , Hepatitis B/diagnostic imaging , Hepatitis B/physiopathology , Hepatitis C/diagnostic imaging , Hepatitis C/physiopathology , Humans , Liver/physiopathology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Spleen/physiopathologyABSTRACT
OBJECTIVE: To determine the diagnostic accuracy of Doppler ultrasonography in predicting presence of esophageal varices in patients with hepatitis-C induced cirrhosis. STUDY DESIGN: Descriptive analytical study. PLACE AND DURATION OF STUDY: Department of Radiology, Jinnah Hospital, Lahore, from May 2016 to October 2016. METHODOLOGY: Patients aged 15-70 years, who presented with cirrhosis and proved to be cirrhosis caused by Hepatitis-C of any gender and duration of disease more than 6 months, were included. Patients with hepatocelullar carcinoma or portal vein thrombosis, having received treatment for esophageal varices, and unwilling to undergo endoscopy were excluded. All the patients then underwent Doppler ultrasonography to calculate splenoportal index and findings were correlated with endoscopy findings. RESULTS: Out of 200 patients, 137 (68.50%) were males and 63 (31.50%) were females. In Doppler ultrasonography positive patients, 113 were true positive and 8 were false positive. Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of Doppler ultrasonography in predicting presence of esophageal varices was 88.98%, 89.04%, 93.00%, 82.28% and 89.00%, respectively. CONCLUSION: Doppler ultrasonography is the non-invasive modality of choice with high diagnostic accuracy in predicting presence of esophageal varices in hepatitis-C induced cirrhosis.
Subject(s)
Esophageal and Gastric Varices/diagnostic imaging , Esophageal and Gastric Varices/etiology , Hepatitis C/complications , Liver Cirrhosis/complications , Ultrasonography, Doppler , Adolescent , Adult , Aged , Cross-Sectional Studies , Female , Hepatitis C/diagnostic imaging , Humans , Liver Cirrhosis/diagnostic imaging , Male , Middle Aged , Predictive Value of Tests , Young AdultABSTRACT
RNA viruses represent a major global health threat, and the visualization of their RNA genome in infected cells is essential for virological research and clinical diagnosis. Due to the lack of chemical toolkits for the live-cell imaging of viral RNA genomes, especially native viral genomes without labeling and genetic modification, studies on native virus infection at the single-live-cell level are challenging. Herein, taking hepatitis C virus (HCV) as a representative RNA virus, we propose that the innate noncanonical G-quadruplex (G4) structure of viral RNA can serve as a specific imaging target and report a new benzothiazole-based G4-targeted fluorescence light-up probe, ThT-NE, for the direct visualization of the native RNA genome of HCV in living host cells. We demonstrate the use of the ThT-NE probe for several previously intractable applications, including the sensitive detection of individual virus-infected cells by small-molecule staining, real-time monitoring of the subcellular distribution of the viral RNA genome in live cells, and continuous live-cell tracking of the infection and propagation of clinically isolated native HCV. The fluorogenic-probe-based viral RNA light-up system opens up a promising chemical strategy for cutting-edge live-cell viral analysis, providing a potentially powerful tool for viral biology, medical diagnosis, and drug development.
Subject(s)
Fluorescent Dyes/analysis , Genome, Viral/genetics , Hepacivirus/genetics , Hepacivirus/isolation & purification , Hepatitis C/pathology , Hepatitis C/virology , Optical Imaging , RNA, Viral/analysis , Cell Line, Tumor , Cell Survival , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/chemistry , G-Quadruplexes , Hepatitis C/diagnostic imaging , Humans , Molecular Structure , RNA, Viral/geneticsABSTRACT
The study was performed to evaluate cerebral volume changes in HCV-infected subjects before and after interferon-free therapy with direct-acting antiviral agents (DAA). We aimed also to estimate the impact of successful DAA therapy on the neuropsychological state of patients. Eleven HCV genotype 1 (GT1) patients treated with ombitasvir/paritaprevir (boosted with ritonavir) and dasabuvir, with or without ribavirin underwent brain magnetic resonance (MR) before and 24â¯weeks after completion of therapy. All patients achieved sustained viral response. Precise automatic parcellation was made using the fully-available software FreeSurfer 6.0. Statistically significant volume deceleration six months after treatment was found in the subcallosal cingulate gyrus, transverse frontopolar gyri and sulci, anterior segment of the circular sulcus of the insula and horizontal ramus of the anterior segment of the lateral sulcus. After DAA therapy we found statistically significant improvement in the performance of all three tasks of the Rey Complex Figure Test that permits the evaluation of different functions (attention, planning, working,memory). Additionally, significant amelioration in Percentage Conceptual Level Responses in The Wisconsin Card Sorting Test (a neurocognitive test for assessing intellectual functioning) was also discovered. Successful interferon-free therapy may lead to transient cerebral atrophy, probably by reducing neuroinflammation and oedema. This is the first pilot study of the alterations in brain volume after successful interferon-free therapy in chronic HCV patients. Longitudinal follow-up study is needed to observe further effects of therapy on cerebral structures volume changes.
Subject(s)
Antiviral Agents/pharmacology , Attention/drug effects , Brain/drug effects , Hepatitis C/diagnostic imaging , Memory, Short-Term/drug effects , Adult , Aged , Anilides/pharmacology , Anilides/therapeutic use , Antiviral Agents/therapeutic use , Brain/diagnostic imaging , Carbamates/pharmacology , Carbamates/therapeutic use , Cyclopropanes , Drug Therapy, Combination , Female , Hepatitis C/drug therapy , Hepatitis C/psychology , Humans , Lactams, Macrocyclic , Macrocyclic Compounds/pharmacology , Macrocyclic Compounds/therapeutic use , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Organ Size/drug effects , Pilot Projects , Proline/analogs & derivatives , Ritonavir/pharmacology , Ritonavir/therapeutic use , Sulfonamides , ValineSubject(s)
Coinfection , Elasticity Imaging Techniques , HIV Infections/epidemiology , Hepatitis C/diagnostic imaging , Liver/diagnostic imaging , Marijuana Abuse/epidemiology , Marijuana Smoking/epidemiology , Adult , Female , HIV Infections/diagnosis , HIV Infections/virology , Hepatitis C/epidemiology , Hepatitis C/virology , Humans , Liver/virology , Male , Marijuana Smoking/adverse effects , Middle Aged , Paris/epidemiology , Predictive Value of Tests , Risk FactorsABSTRACT
Interferon-alpha (IFN-α) is an important mediator of antiviral immune responses. It is also used clinically in the treatment of hepatitis-C infection. Though effective, IFN-α-based therapies can often impair mood, motivation and cognition, which when severe can appear indistinguishable from major depression. In susceptible patients, fatigue and motivational impairment emerge early and have been linked to changes in basal ganglia (striatal) metabolism, neurochemistry and microstructural integrity. Here we use neurite orientation dispersion and density imaging (NODDI) modeling of multi-shell diffusion MRI to investigate whether changes in orientation-dispersion index (ODI) or neurite density index (NDI) can predict the later emergence of IFN-α-induced fatigue. Eighteen patients initiating IFN-α-based treatment for hepatitis-C underwent diffusion MRI and blood sampling at baseline and 4â¯h after their first IFN-α injection. They were then followed up with regular psychological assessments for 12â¯weeks of treatment. IFN-α injection stimulated an acute inflammatory cytokine response and evoked acute fatigue that peaked between 4 and 12â¯weeks of treatment. Within the brain, IFN-α induced an acute increase in NDI in patients that experienced a simultaneous increase in IFN-α-induced fatigue but not in patients that did not. Acute changes in striatal microstructure additionally predicted the continued development of fatigue but not mood symptoms 4 and 8â¯weeks later into treatment. Our findings highlight the value of NODDI as a potential in vivo biomarker of the central effects of peripheral inflammation. We highlight the exquisite sensitivity of the striatum to IFN-α and further implicate striatal perturbation in IFN-α-induced fatigue.
Subject(s)
Brain/diagnostic imaging , Diffusion Magnetic Resonance Imaging/methods , Fatigue/diagnostic imaging , Fatigue/etiology , Immunologic Factors/therapeutic use , Interferon-alpha/therapeutic use , Cytokines/blood , Depression/blood , Depression/diagnostic imaging , Depression/immunology , Fatigue/blood , Fatigue/immunology , Female , Hepatitis C/blood , Hepatitis C/diagnostic imaging , Hepatitis C/immunology , Hepatitis C/therapy , Humans , Immunologic Factors/adverse effects , Inflammation/blood , Inflammation/diagnostic imaging , Inflammation/immunology , Inflammation/therapy , Interferon-alpha/adverse effects , Male , Middle Aged , Neurites , Prospective Studies , Treatment OutcomeABSTRACT
Accumulated evidence has suggested associations between glucose abnormalities and insulin resistance with hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. However, few studies have reported the effect of hepatitis virus infections on body composition. Our aim was to explore the association of hepatitis virus infections with percent body fat (PBF) in a cross-sectional analysis. A total of 69226 subjects obtained from the health examinations at Tri-Service General Hospital (TSGH) from 2010 to 2016 were enrolled in the study. Participants were divided into subgroups based on the presence of hepatitis B surface antigen (HBsAg) and anti-HCV. PBF was measured by bioelectrical impedance analysis (BIA). A multivariable linear regression model was applied to test the association of hepatitis virus infections with PBF and glycemic status. In male participants, hepatitis virus infections were closely associated with increased PBF, especially in those subjects with HCV/HBV coinfection. HCV/HBV coinfection was positively correlated with fasting plasma glucose and postprandial glucose while HCV and HBV mono-infection were not. The impact of hepatitis virus infection on increased PBF was observed in general population with gender difference. A further study on the treatment of hepatitis virus infection might help prevent the development of obesity-related diseases.
Subject(s)
Adipose Tissue/pathology , Coinfection/pathology , Hepatitis B/pathology , Hepatitis C/pathology , Adipose Tissue/diagnostic imaging , Adult , Blood Glucose , Body Composition , Coinfection/blood , Coinfection/diagnostic imaging , Coinfection/epidemiology , Cross-Sectional Studies , F Factor , Female , Hepatitis B/blood , Hepatitis B/diagnostic imaging , Hepatitis B/epidemiology , Hepatitis B Surface Antigens/blood , Hepatitis C/blood , Hepatitis C/diagnostic imaging , Hepatitis C Antibodies/blood , Humans , Male , Middle AgedABSTRACT
BACKGROUND: To analyze ultrasound findings of liver damage in alcohol use disorder (AUD) patients. METHODS: A cross-sectional analysis of detoxification patients. Clinical and laboratory parameters were obtained at admission. Analytical liver injury (ALI) was defined as at least two of the following: aspartate aminotransferase (AST) levels ≥74â¯<â¯300 U/L, AST/alanine aminotransferase (ALT) ratio >2, and total bilirubin >1.2â¯mg/dL. Advanced liver fibrosis (ALF) was defined as a FIB-4 score ≥3.25. Abdominal ultrasound was used to identify steatosis, hepatomegaly, heterogeneous liver, and portal hypertension. Predictors of these findings were determined by logistic regression. RESULTS: We included 301 patients (80% male) with a median age of 46 years (IQR: 39-51 years) and alcohol consumption of 180â¯g/day (IQR: 120-201â¯g). The prevalence of Hepatitis C virus (HCV) was 21.2%; AST and ALT serum levels were 42 U/L (IQR: 23-78 U/L) and 35 U/L (IQR: 19-60 U/L), respectively; 16% of patients had ALI and 24% ALF. Ultrasound findings were: 57.2% steatosis, 49.5% hepatomegaly, 17% heterogeneous liver, and 16% portal hypertension; 77% had at least one ultrasound abnormality, and 45% had ≥2. HCV infection was associated with heterogeneous liver (pâ¯=â¯0.046) and portal hypertension (pâ¯<â¯0.01). ALI and ALF were associated with steatosis (both pâ¯<â¯0.01) and hepatomegaly (both pâ¯<â¯0.01), ALI with portal hypertension (pâ¯=â¯0.08), and ALF with heterogeneous liver (pâ¯<â¯0.01). In logistic regression, ALI and ALF were associated with ≥2 abnormalities [OR (95%CI): 5.2 (2.1-12.8), pâ¯<â¯0.01 and 4.7 (2.2-9.7), pâ¯<â¯0.01; respectively]. CONCLUSIONS: Ultrasound findings of liver damage may facilitate clinical decisions and alcohol cessation in AUD patients.
Subject(s)
Alcoholism/diagnostic imaging , Alcoholism/therapy , Liver Diseases/diagnostic imaging , Liver Diseases/therapy , Patient Admission/trends , Adult , Alanine Transaminase/blood , Alcohol Drinking/blood , Alcohol Drinking/therapy , Alcoholism/blood , Aspartate Aminotransferases/blood , Cross-Sectional Studies , Fatty Liver/blood , Fatty Liver/diagnostic imaging , Fatty Liver/epidemiology , Female , Hepatitis C/blood , Hepatitis C/diagnostic imaging , Hepatitis C/epidemiology , Humans , Liver Diseases/blood , Male , Middle Aged , Prevalence , Treatment OutcomeABSTRACT
BACKGROUND: Paritaprevir inhibits organic anion-transporting polypeptide (OATP)1B1 and OATP1B3, which transport bilirubin. Hyperbilirubinemia is an adverse event reported during hepatitis C treatment. Gadoxetic acid is also transported by OATP1B1/1B3. We evaluated whether the enhancement effect in gadoxetic acid-enhanced magnetic resonance (MR) imaging could predict the plasma concentration of paritaprevir and might anticipate the development of hyperbilirubinemia. METHODS: This prospective study evaluated 27 patients with hepatitis C who underwent gadoxetic acid-enhanced MR imaging prior to treatment with ombitasvir, paritaprevir, and ritonavir. The contrast enhancement index (CEI), a measure of liver enhancement during the hepatobiliary phase, was assessed. Plasma trough concentrations, and concentrations at 2, 4, and 6 h after dosing were determined 7 d after the start of treatment. RESULTS: Seven patients (26%) developed hyperbilirubinemia (≥ 1.6 mg/dl). Paritaprevir trough concentration (Ctrough) was significantly higher in patients with hyperbilirubinemia than in those without (p = 0.022). We found an inverse relationship between CEI and Ctrough (r = 0.612, p = 0.001), while there was not a significantly weak inverse relationship between AUC0-6 h and CEI (r = -0.338, p = 0.085). The partial correlation coefficient between CEI and Ctrough was -0.425 (p = 0.034), while excluding the effects of albumin and the FIB-4 index. Receiver operating characteristic (ROC) curve analysis showed that the CEI was relatively accurate in predicting hyperbilirubinemia, with area under the ROC of 0.882. Multivariate analysis showed that the CEI < 1.61 was the only independent predictor related to the development of hyperbilirubinemia, with an odds ratio of 9.08 (95% confidence interval 1.05-78.86, p = 0.046). CONCLUSIONS: Hepatic enhancement with gadoxetic acid was independently related to paritaprevir concentration and was an independent pretreatment factor in predicting hyperbilirubinemia. Gadoxetic acid-enhanced MR imaging can therefore be useful in determining the risk of paritaprevir-induced hyperbilirubinemia.
Subject(s)
Gadolinium DTPA/chemistry , Hepatitis C/diagnostic imaging , Hepatitis C/drug therapy , Hyperbilirubinemia/chemically induced , Macrocyclic Compounds/adverse effects , Magnetic Resonance Imaging , Adult , Aged , Aged, 80 and over , Contrast Media , Cyclopropanes , Female , Hepatitis C/complications , Humans , Lactams, Macrocyclic , Male , Middle Aged , Proline/analogs & derivatives , Prospective Studies , Sulfonamides , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Little is known about the utility of transient elastography (TE) for assessing the prognosis of patients with decompensated cirrhosis (DC). METHODS: We analyzed HIV/HCV-coinfected patients with DC who underwent TE as part of their routine follow-up between 2006 and 2015. We also calculated the liver stiffness spleen diameter-to-platelet score (LSPS), FIB-4 index, albumin, MELD score, and Child-Pugh score. The primary outcome was death. RESULTS: The study population comprised 65 patients. After a median follow-up of 32 months after the first TE, 17 patients had received anti-HCV therapy and 31 patients had died. The highest area under the receiver operating characteristic curve (AUROC) value for prediction of death was observed with albumin (0.695), followed by Child-Pugh score (0.648), both with P values < .05. Lower AUROC values were observed with MELD score (0.633), TE (0.618), LSPS score (0.595), and FIB-4 (0.569), all with P values > .05. In the univariate Cox regression analysis, albumin, FIB-4, Child-Pugh score, and MELD score, but not TE, were associated with death. In the multivariate analysis, albumin and Child-Pugh score were the only baseline variables associated with death. CONCLUSIONS: Our results suggest that TE is not useful for assessing the prognosis of HIV-infected patients with decompensated HCV-related cirrhosis. Albumin concentration and Child-Pugh scores were the most consistent predictors of death in this population group.
Subject(s)
AIDS-Related Opportunistic Infections/diagnostic imaging , Elasticity Imaging Techniques/methods , HIV Infections/diagnostic imaging , Hepatitis C/diagnostic imaging , Liver/diagnostic imaging , AIDS-Related Opportunistic Infections/complications , AIDS-Related Opportunistic Infections/mortality , Adult , Area Under Curve , Female , HIV Infections/complications , HIV Infections/mortality , Hepatitis C/complications , Hepatitis C/mortality , Humans , Liver/pathology , Liver/virology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/virology , Male , Middle Aged , Prognosis , Proportional Hazards Models , ROC CurveABSTRACT
OBJECTIVE: To determine the accuracy of shear-wave elastography (SWE) to differentiate low from advanced degrees of liver fibrosis in hepatitis C patients. MATERIAL & METHOD: Consented native/transplant hepatitis C patients underwent SWE using a C1-6 MHz transducer before ultrasound (US)-guided liver biopsy. Five interpretable SWE samples were obtained from the right lobe of the liver immediately before US-guided random biopsy of the right lobe. Average kilopascal (kPa) values were compared to the meta-analysis of histological data in viral hepatitis (METAVIR) fibrosis grading. SWE values were correlated with the degree of inflammation and fatty infiltration. RESULTS: Study population consisted of 115 patients (63 with transplant, and 52 with native liver) including 29 women and 86 men, with a mean ± SD age of 56 ± 8.7 years. Mean ± SD SWE values were 7.9 ± 3 kPa in 83 patients with METAVIR scores of 0-2 and 13.2 ± 5.9 kPa in 32 patients with METAVIR scores of 3 or 4 (P < .001). Area under curve (AUC) of a Receiver Operating Characteristics curve for advanced degrees of fibrosis was 0.81 (95% CI: 0.71, 0.90) (P < .001). AUCs of transplant versus native livers (0.78 [CI:0.62, 0.94] versus 0.85 [CI: 0.73, 0.96]), degree of inflammation (0.81 [CI: 0.65, 0.97] versus 0.72 [0.56, 0.88]), or degree of fat deposition (0.81 [CI:0.70, 0.92] versus 0.80 [CI:0.61, 1]) were not statistically different (P > .05). for kPa threshold of SWE value of 10.67 kPa to differentiate advanced from low degree of fibrosis had a sensitivity of 59% (CI: 41%-76%) and specificity of 90% (CI: 82%-96%). CONCLUSION: Liver stiffness evaluated by SWE can differentiate low from advanced liver fibrosis.