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Epstein RL, Munroe S, Taylor LE, Duryea PR, Buzzee B, Pramanick T, Feld JJ, Baptiste D, Carroll M, Castera L, Sterling RK, Thomas A, Chan PA, Linas BP. Clinical- and Cost-Effectiveness of Liver Disease Staging in Hepatitis C Virus Infection: A Microsimulation Study. Clin Infect Dis 2025; 80:300-313. [PMID: 39535186 PMCID: PMC11848265 DOI: 10.1093/cid/ciae485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Liver disease assessment is a key aspect of chronic hepatitis C virus (HCV) infection pre-treatment evaluation but guidelines differ on the optimal testing modality given trade-offs in availability and accuracy. We compared clinical outcomes and cost-effectiveness of common fibrosis staging strategies. METHODS We simulated adults with chronic HCV receiving care at US health centers through a lifetime microsimulation across five strategies: (1) no staging or treatment (comparator), (2) indirect serum biomarker testing (Fibrosis-4 index [FIB-4]) only, (3) transient elastography (TE) only, (4) staged approach: FIB-4 for all, TE only for intermediate FIB-4 scores (1.45-3.25), and (5) both tests for all. Outcomes included infections cured, cirrhosis cases, liver-related deaths, costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). We used literature-informed loss to follow-up (LTFU) rates and 2021 Medicaid perspective and costs. RESULTS FIB-4 alone generated the best clinical outcomes: 87.7% cured, 8.7% developed cirrhosis, and 4.6% had liver-related deaths. TE strategies cured 58.5%-76.6%, 16.8%-29.4% developed cirrhosis, and 11.6%-22.6% had liver-related deaths. All TE strategies yielded worse clinical outcomes at higher costs per QALY than FIB-4 only, which had an ICER of $12 869 per QALY gained compared with no staging or treatment. LTFU drove these findings: TE strategies were only cost-effective with no LTFU. In a point-of-care HCV test-and-treat scenario, treatment without any staging was most clinically and cost-effective. CONCLUSIONS FIB-4 staging alone resulted in optimal clinical outcomes and was cost-effective. Treatment for chronic HCV should not be delayed while awaiting fibrosis staging with TE.
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Affiliation(s)
- Rachel L Epstein
- Department of Medicine, Section of Infectious Diseases, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Pediatrics, Section of Infectious Diseases, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
- Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA
| | - Sarah Munroe
- Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA
| | - Lynn E Taylor
- Department of Pharmacy Practice and Clinical Research, University of Rhode Island, Kingston, Rhode Island, USA
- Department of Primary Care, HealthFirst Family Care Center Inc., Fall River, Massachusetts, USA
| | - Patrick R Duryea
- Department of Pharmacy Practice and Clinical Research, University of Rhode Island, Kingston, Rhode Island, USA
| | - Benjamin Buzzee
- Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA
| | - Tannishtha Pramanick
- Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Dimitri Baptiste
- Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA
| | - Matthew Carroll
- Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA
| | - Laurent Castera
- Department of Hepatology, Beaujon Hospital, Assistance Publique-Hopitaux de Paris, Université Paris Cité, Clichy, France
| | - Richard K Sterling
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Aurielle Thomas
- Department of Pharmacy Practice and Clinical Research, University of Rhode Island, Kingston, Rhode Island, USA
| | - Philip A Chan
- Rhode Island Department of Health, Providence, Rhode Island, USA
- Department of Medicine, Brown University, Providence, Rhode Island, USA
| | - Benjamin P Linas
- Department of Medicine, Section of Infectious Diseases, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
- Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA
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Duarte-Rojo A, Taouli B, Leung DH, Levine D, Nayfeh T, Hasan B, Alsawaf Y, Saadi S, Majzoub AM, Manolopoulos A, Haffar S, Dundar A, Murad MH, Rockey DC, Alsawas M, Sterling RK. Imaging-based noninvasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline. Hepatology 2025; 81:725-748. [PMID: 38489521 DOI: 10.1097/hep.0000000000000852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 01/19/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND AND AIMS Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). APPROACH AND RESULTS A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. CONCLUSIONS LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.
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Affiliation(s)
- Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Northwestern Medicine and Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Bachir Taouli
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Daniel H Leung
- Department of Pediatrics, Baylor College of Medicine and Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Deborah Levine
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Tarek Nayfeh
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Bashar Hasan
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Yahya Alsawaf
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Samer Saadi
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Samir Haffar
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Ayca Dundar
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - M Hassan Murad
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Don C Rockey
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Mouaz Alsawas
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Richard K Sterling
- Section of Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
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Patel K, Asrani SK, Fiel MI, Levine D, Leung DH, Duarte-Rojo A, Dranoff JA, Nayfeh T, Hasan B, Taddei TH, Alsawaf Y, Saadi S, Majzoub AM, Manolopoulos A, Alzuabi M, Ding J, Sofiyeva N, Murad MH, Alsawas M, Rockey DC, Sterling RK. Accuracy of blood-based biomarkers for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline. Hepatology 2025; 81:358-379. [PMID: 38489517 DOI: 10.1097/hep.0000000000000842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 02/19/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND AND AIMS Blood-based biomarkers have been proposed as an alternative to liver biopsy for noninvasive liver disease assessment in chronic liver disease. Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), as compared to biopsy in chronic liver disease. APPROACH AND RESULTS We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in HBV and HCV, HIV-HCV/HBV coinfection, and NAFLD. Positive (LR+) and negative (LR-) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86, respectively; LR+ and LR- for NAFLD F2-4, F3-4, and F4 were 2.65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15, respectively. Overall, the proportional odds ratio indicated FIB-4 <1.45 was better than aspartate aminotransferase-to-platelet ratio index <0.5 for F2-4. FIB-4 >3.25 was also better than aspartate aminotransferase-to-platelet ratio index >1.5 for F3-4 and F4. There was limited data for combined tests. CONCLUSIONS Blood-based biomarkers are associated with small-to-moderate change in pretest probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV coinfection, and NAFLD, with limited comparative or combination studies for other chronic liver diseases.
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Affiliation(s)
- Keyur Patel
- Department of Medcine, Division of Gastroenterology and Hepatology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Sumeet K Asrani
- Department of Medicine, Division of Hepatology, Baylor University Medical Center, Dallas, Texas, USA
| | - Maria Isabel Fiel
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Deborah Levine
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Daniel H Leung
- Department of Pediatrics, Baylor College of Medicine and Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Northwestern Medicine and Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Jonathan A Dranoff
- Yale School of Medicine, Department of Internal Medicine, Section of Digestive Diseases, New Haven, Connecticut, USA
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Tarek Nayfeh
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Bashar Hasan
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Tamar H Taddei
- Yale School of Medicine, Department of Internal Medicine, Section of Digestive Diseases, New Haven, Connecticut, USA
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Yahya Alsawaf
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Samer Saadi
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Muayad Alzuabi
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Jingyi Ding
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Nigar Sofiyeva
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Mohammad H Murad
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Mouaz Alsawas
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
- Department of Medicine, Section of Hepatology, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Don C Rockey
- Department of Medicine, Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Richard K Sterling
- Department of Medicine, Section of Hepatology, Virginia Commonwealth University, Richmond, Virginia, USA
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Xavier JB, Schmillevitch J, Emori C, Uehara S, Nunes EJ, Ferraz ML. EARLY NONINVASIVE EVALUATION OF LIVER FIBROSIS AFTER HEPATITIS C TREATMENT: THE IMPACT OF INFLAMMATION. ARQUIVOS DE GASTROENTEROLOGIA 2024; 61:e24043. [PMID: 39776122 DOI: 10.1590/s0004-2803.24612024-043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 10/29/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND Liver biopsy (LB) is still the gold standard method for assessing hepatic fibrosis (HF), associated diseases, and liver inflammation. Nowadays, noninvasive techniques such as Acoustic radiation force impulse (ARFI) elastography have been introduced instead of liver biopsy. However, there are controversies about the time it should be performed after treatment for hepatitis C virus (HCV). OBJECTIVE To evaluate hepatic fibrosis using ARFI technology before and after successive treatments for chronic HCV. METHODS We prospectively included 50 adult patients with chronic HCV (genotype 1). Patients were first submitted to triple therapy with first-generation protease inhibitors (boceprevir and telaprevir) at the hepatitis division of the Gastroenterology Department of the Federal University of São Paulo. The non-responders underwent re-treatment with interferon-free direct-acting antiviral agents (DDAs - sofosbuvir associated with daclatasvir or simeprevir). Assessment of hepatic stiffness by ARFI was performed before and after the first treatment and before and after the re-treatment with DDAs. RESULTS ARFI values decreased significantly after treatments. In patients on first-generation protease inhibitor therapy and achieving sustained virological response (SVR), ARFI decreased from 2.41±0.58 pre-treatment to 2.02+/-0.58 (P<0.042) post-treatment. In patients who did not reach SVR, that is, non-responders, a significant reduction was similarly observed (2.39±0.63 to 2.03±0.54; P<0.001 before and after treatment, respectively). Before starting the re-treatment, non-responders had elevated ARFI values again, dropping after SVR following re-treatment (from 2.46±0.57 to 1.45±0.68, P<0.004). Laboratory parameters such as AST and ALT were directly correlated to ARFI elastography. CONCLUSION The evaluation of hepatic elastography by the ARFI method before and after (6 - 9 months) successive treatment of hepatitis C in responders and non-responders led to the conclusion that the reduction of elastography parameters seems to be related to a decrease in hepatic inflammation rather than a reduction in fibrosis per se.
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Affiliation(s)
| | - Joel Schmillevitch
- Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP, Brasil
| | - Christini Emori
- Instituto de Infectologia Emílio Ribas, São Paulo, SP, Brasil
| | - Silvia Uehara
- Universidade Federal de Mato Grosso do Sul, Hospital Universitário Maria Aparecida Pedrossian, Campo Grande, MS, Brasil
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Epstein RL, Buzzee B, White LF, Feld JJ, Castera L, Sterling RK, Linas BP, Taylor LE. Test characteristics for combining non-invasive liver fibrosis staging modalities in individuals with Hepatitis C virus. J Viral Hepat 2024; 31:277-292. [PMID: 38326950 PMCID: PMC11102317 DOI: 10.1111/jvh.13925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 12/27/2023] [Accepted: 01/17/2024] [Indexed: 02/09/2024]
Abstract
Non-invasive methods have largely replaced biopsy to identify advanced fibrosis in hepatitis C virus (HCV). Guidelines vary regarding testing strategy to balance accuracy, costs and loss to follow-up. Although individual test characteristics are well-described, data comparing the accuracy of using two tests together are limited. We calculated combined test characteristics to determine the utility of combined strategies. This study synthesizes empirical data from fibrosis staging trials and the literature to estimate test characteristics for Fibrosis-4 (FIB4), APRI or a commercial serum panel (FibroSure®), followed by transient elastography (TE) or FibroSure®. We simulated two testing strategies: (1) second test only for those with intermediate first test results (staged approach), and (2) second test for all. We summarized empiric data with multinomial distributions and used this to estimate test characteristics of each strategy on a simulated population of 10,000 individuals with 4.2% cirrhosis prevalence. Negative predictive value (NPV) for cirrhosis from a single test ranged from 98.2% (95% CB 97.6-98.8%) for FIB-4 to 99.4% (95% CB 99.0-99.8%) for TE. Using a staged approach with TE second, sensitivity for cirrhosis rose to 93.3-96.9%, NPV to 99.7-99.8%, while PPV dropped to <32%. Using TE as a second test for all minimally changed estimated test characteristics compared with the staged approach. Combining two non-invasive fibrosis tests barely improves NPV and decreases or does not change PPV compared with a single test, challenging the utility of serial testing modalities. These calculated combined test characteristics can inform best methods to identify advanced fibrosis in various populations.
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Affiliation(s)
- Rachel L. Epstein
- Department of Medicine, Section of Infectious Diseases, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Pediatrics, Section of Infectious Diseases, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
| | - Benjamin Buzzee
- Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA
| | - Laura F. White
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
| | - Jordan J. Feld
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Laurent Castera
- Department of Hepatology, Beaujon Hospital, Assistance Publique-Hopitaux de Paris, Université Paris Cité, Clichy, France
| | - Richard K. Sterling
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Benjamin P. Linas
- Department of Medicine, Section of Infectious Diseases, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA
| | - Lynn E. Taylor
- College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA
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Kang YW, Baek YH, Lee JH, Roh YH, Kwon HJ, Moon SY, Son MK, Jeong JS. Assessing the Utility of Acoustic Radiation Force Impulse in the Evaluation of Non-Alcoholic Fatty Liver Disease with Severe Obesity or Steatosis. Diagnostics (Basel) 2024; 14:1083. [PMID: 38893610 PMCID: PMC11171891 DOI: 10.3390/diagnostics14111083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/16/2024] [Accepted: 05/20/2024] [Indexed: 06/21/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) encompasses a heterogeneous spectrum ranging from simple steatosis to fibrosis and cirrhosis. Fibrosis, associated with long-term overall mortality and liver-related events, requires evaluation. Traditionally, liver biopsy has been the gold standard for diagnosing fibrosis. However, its invasive nature, potential complications, and sampling variability limit widespread use. Consequently, various non-invasive tests have been developed as alternatives for diagnosing fibrosis in NAFLD patients. AIM This study aimed to compare the accuracy of non-invasive tests (NITs) and evaluate the diagnostic accuracy of acoustic radiation force impulse (ARFI), one of the point shear wave techniques, compared to conventional methods, assessing its effective role in diagnosis. METHODS This is a retrospective study; a total of 136 patients diagnosed with fatty liver disease through ultrasonography were enrolled. The anthropometric data of the patients were collected on the day of admission and blood tests, measurements of ARFI, and a point shear test were conducted using abdominal ultrasound; a biopsy was performed the following day. In addition, we calculated the aspartate aminotransferase-to-platelet ratio index (APRI) index based on four factors (FIB-4) and the NAFLD fibrosis score (NFS). Subsequently, we assessed the diagnostic accuracy of NITs within various subgroups based on the extent of obesity, steatosis, or NAFLD activity score. RESULTS ARFI has been shown to have the highest diagnostic value among various NITs, with AUROC values of 0.832, 0.794, 0.767, and 0.696 for ARFI, APRI, FIB-4, and NFS, respectively. In the morbidly obese subgroup, the AUROC values of ARFI, APRI, FIB-4, and NFS were 0.805, 0.769, 0.736, and 0.674. In the group with severe steatosis or non-alcoholic steatohepatitis (NASH), the AUROC values were 0.679, 0.596, 0.661, and 0.612, respectively, for severe steatosis and 0.789, 0.696, 0.751, and 0.691, respectively, for NASH. CONCLUSIONS In conclusion, ARFI is not affected by various factors and maintains diagnostic accuracy compared to serum NITs. Therefore, we can recommend ARFI as a valuable diagnostic test to screen for advanced fibrosis in patients with NAFLD.
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Affiliation(s)
- Yeo Wool Kang
- Department of Internal Medicine, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea; (Y.W.K.); (J.H.L.); (S.Y.M.)
| | - Yang Hyun Baek
- Department of Internal Medicine, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea; (Y.W.K.); (J.H.L.); (S.Y.M.)
| | - Jong Hoon Lee
- Department of Internal Medicine, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea; (Y.W.K.); (J.H.L.); (S.Y.M.)
| | - Young Hoon Roh
- Department of General Surgery, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea;
| | - Hee Jin Kwon
- Department of Radiology, Dong-A University College of Medicine, 1,3-ga Dongdaesindong, Seo-gu, Busan 49201, Republic of Korea;
| | - Sang Yi Moon
- Department of Internal Medicine, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea; (Y.W.K.); (J.H.L.); (S.Y.M.)
| | - Min Kook Son
- Department of Physiology, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea;
| | - Jin Sook Jeong
- Department of Pathology, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea;
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Loarec A, Gutierrez AG, Muvale G, Couto A, Nguyen A, Yerly S, Pinto Y, Madeira N, Gonzales A, Molfino L, Ciglenecki I, Antabak NT. Hepatitis C treatment program in Maputo, Mozambique, the challenge of genotypes and key populations: A 5-year retrospective analysis of routine programmatic data. Health Sci Rep 2023; 6:e1165. [PMID: 37008813 PMCID: PMC10061494 DOI: 10.1002/hsr2.1165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 03/10/2023] [Accepted: 03/13/2023] [Indexed: 04/04/2023] Open
Abstract
Background and Aims Hepatitis C (HCV) programs face challenges, especially linked to key populations to achieve World Health Organization (WHO) goals of eliminating hepatitis. Médecins Sans Frontières and Mozambique's Ministry of Health first implemented HCV treatment in Maputo, in 2016 and harm reduction activities in 2017. Methods We retrospectively analyzed routine data of patients enrolled between December 2016 and July 2021. Genotyping was systematically requested up to 2018 and subsequently in cases of treatment failure. Sustainable virological response was assessed 12 weeks after the end of treatment by sofosbuvir-daclatasvir or sofosbuvir-velpatasvir. Results Two hundred and two patients were enrolled, with 159 (78.71%) males (median age: 41 years [interquartile range (IQR): 37.10, 47.00]). Risk factors included drug use (142/202; 70.29%). One hundred and eleven genotyping results indicated genotype 1 predominant (87/111; 78.37%). Sixteen patients presented genotype 4, with various subtypes. The people who used drugs and HIV coinfected patients were found more likely to present a genotype 1. Intention-to-treat analysis showed 68.99% (89/129) cure rate among the patients initiated and per-protocol analysis, 88.12% (89/101) cure rate. Nineteen patients received treatment integrated with opioid substitution therapy, with a 100% cure rate versus 59.37% (38/64) for initiated ones without substitution therapy (p < 0.001). Among the resistance testing performed, NS5A resistance-associated substitutions were found in seven patients among the nine tested patients and NS5B ones in one patient. Conclusion We found varied genotypes, including some identified as difficult-to-treat subtypes. People who used drugs were more likely to present genotype 1. In addition, opioid substitution therapy was key for these patients to achieve cure. Access to second-generation direct-acting antivirals (DAAs) and integration of HCV care with harm reduction are crucial to program effectiveness.
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Affiliation(s)
- Anne Loarec
- Médecins Sans Frontières (MSF)MaputoMozambique
| | | | | | | | - Aude Nguyen
- Service des Maladies InfectieusesHôpitaux Universitaires de GenèveGenèveSwitzerland
| | - Sabine Yerly
- Laboratory of VirologyHôpitaux Universitaires de GenèveGenevaSwitzerland
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Trindade AJ, Thaniyavarn T, Hashemi N, Coppolino A, Kennedy JC, Mallidi HR, El-Chemaly S, Goldberg HJ. 1-year outcomes for lung transplantation recipients with non-alcoholic fatty liver disease. ERJ Open Res 2021; 7:00103-2021. [PMID: 34435032 PMCID: PMC8381158 DOI: 10.1183/23120541.00103-2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 05/13/2021] [Indexed: 11/09/2022] Open
Abstract
Advanced hepatic fibrosis and cirrhosis are absolute contraindications to lung transplantation. [
1] However, whether fatty liver disease with mild–moderate fibrosis contributes to increased adverse outcomes post-lung transplantation remains unknown. We present a retrospective analysis of patients transplanted at Brigham and Women's Hospital between 2015 and 2017 to identify whether patients with mild–moderate non-alcoholic fatty liver disease (NAFLD) experience increased short-term complications compared to patients with normal liver architecture. Patients with advanced (F3–F4) fibrosis and/or cirrhosis were considered non-suitable transplant candidates, a priori. This study was powered for a difference in index hospital-free days within the first 30 days of 25% (α=0.05, β=0.8). Secondary outcomes included index intensive care unit (ICU)-free days within the first 10 days post-transplant, perioperative blood product transfusion, incidence of index hospitalisation arrhythmias and delirium, need for insulin on discharge post-transplant, tacrolimus dose required to maintain a trough of 8–12 ng·mL−1 at index hospital discharge, and 1-year post-transplant incidence of insulin-dependent diabetes, acute kidney injury, acute cellular rejection, unplanned hospital readmissions and infection. 150 patients underwent lung transplantation between 2015 and 2017 and were included in the analysis; of these patients 40 (27%) had evidence of NAFLD. Median index hospital-free days for patients with NAFLD were non-inferior to those without (16 days, IQR 10.5–19.5 versus 12 days, IQR 0–18.0, p=0.03). Regarding secondary outcomes, both index hospitalisation and 1-year outcomes were non-inferior between patients with NAFLD and those with normal liver architecture. This study demonstrates that mild–moderate severity NAFLD may not be a contraindication to lung transplantation. In this single-centre, retrospective analysis of lung transplant recipients, we identified that mild–moderate non-alcoholic fatty liver disease is associated with acceptable perioperative and 1-year outcomeshttps://bit.ly/36WNzhi
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Affiliation(s)
- Anil J Trindade
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.,Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Tany Thaniyavarn
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Nikroo Hashemi
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Antonio Coppolino
- Division of Thoracic Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - John C Kennedy
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Hari R Mallidi
- Division of Thoracic Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.,Division of Cardiac Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Souheil El-Chemaly
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Hilary J Goldberg
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
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9
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Does fibrosis really regress in HIV/hepatitis C virus co-infected patients after treatment with direct antiviral agents? AIDS 2020; 34:427-432. [PMID: 31996593 DOI: 10.1097/qad.0000000000002433] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the progression of liver stiffness after treatment with direct antiviral agents (DAAs), to identify predictive factors of fibrosis regression and to analyze the changes of scores AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) after treatment. DESIGN Multicenter prospective cohort study of HIV/HCV co-infected patients conducted within the GECMEI cohort, Spain. METHODS Individuals were eligible if they were willing to start DAAs and underwent two transient elastographies: at baseline and after the end of treatment (EOT). All patients with detectable HCV RNA naïve to DAAs were consecutively enrolled from nine medical hospitals. Liver stiffness results were categorized in four Metavir stages (F1: <7.1; F2 : 7.1--9.5; F3 : 9.5--2.4; F4: >12.4 kPa). The APRI and FIB-4 scores were calculated at baseline, EOT and 12 weeks after EOT. RESULTS One hundred and seventy-eight patients were examined throughout a follow-up of 16.3 months (IQR: 12.5-25). The median of liver stiffness decrease was 2.6 kPa (IQR: 0-6.3). A greater improvement was observed in F3-F4 compared with F1-F2, (6.4 vs. 0.91 kPa, P < 0.001; P = 0.001, respectively). A decline between baseline and EOT measures was observed in APRI and FIB-4 (P < 0.001). Sustained virological response (SVR12) achievement was the only predictor of fibrosis regression [OR:17.4 (95% CI: 1.8-164.6; P = 0.013)]. CONCLUSION Most patients experienced a significant reduction of liver stiffness and APRI and FIB-4 scores. This improvement was greater in those with advanced liver disease. SVR12 was the only predictor of fibrosis regression. The significance of this reduction is unclear and could reflect a decline in inflammation rather than true fibrosis regression.
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Diagnostic Accuracy of Noninvasive Markers of Steatosis, NASH, and Liver Fibrosis in HIV-Monoinfected Individuals at Risk of Nonalcoholic Fatty Liver Disease (NAFLD): Results From the ECHAM Study. J Acquir Immune Defic Syndr 2019; 80:e86-e94. [PMID: 30570529 DOI: 10.1097/qai.0000000000001936] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND HIV-monoinfected individuals are at high risk of nonalcoholic fatty liver disease. Noninvasive tests of steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis have been poorly assessed in this population. Using liver biopsy (LB) as a reference, we assessed the accuracy of noninvasive methods for their respective diagnosis: magnetic resonance imaging proton-density-fat-fraction (MRI-PDFF), FibroScan/controlled attenuation parameter (CAP), and biochemical tests. METHODS We enrolled antiretroviral therapy-controlled participants with persistently elevated transaminases and/or metabolic syndrome, and/or lipodystrophy. All had hepatic MRI-PDFF, FibroScan/CAP, FibroTest/NashTest/SteatoTest, APRI, FIB-4, and nonalcoholic fatty liver disease-fibrosis score. A LB was indicated if suspected significant fibrosis (FibroScan ≥7.1 kPa and/or FibroTest ≥0.49). Performance was considered as good if area under a receiver operating characteristic curves (AUROCs) was >0.80. RESULTS Among the 140 patients with suspected significant fibrosis out of the 402 eligible patients, 49 had had a LB: median age of 54 years (53-65), body mass index: 26 kg/m (24-30), steatosis in 37 (76%), NASH in 23 (47%), and fibrosis in 31 (63%) patients [F2: 7 (14%); F3: 6 (12%); and F4: 2 (4%)]. Regarding steatosis, MRI-PDFF had excellent and CAP good performances with AUROCs at 0.98 (95% confidence interval: 0.96 to 1.00) and 0.88 (0.76 to 0.99), respectively, whereas the AUROCs of SteatoTest was 0.68 (0.51 to 0.85). Regarding fibrosis (≥F2), APRI and FIB-4 had good performance with AUROCs at 0.86 (0.74 to 0.98) and 0.81 (0.67 to 0.95). By contrast, FibroScan and FibroTest had poor AUROCs [0.61 (0.43 to 0.79) and 0.61 (0.44 to 0.78)], with very low specificity. Regarding NASH, alanine aminotransferase ≥36 IU/L had good performance with AUROCs of 0.83 (0.71 to 0.94), whereas the NashTest had an AUROC of 0.60 (0.44 to 0.76). CONCLUSIONS In HIV-monoinfected patients, MRI-PDFF and FibroScan/CAP are highly accurate for the diagnosis of steatosis. The alanine aminotransferase level and APRI should be considered for the detection of NASH and fibrosis.
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Abstract
: Elevation of liver transaminases is common in patients infected with the HIV. Although this is usually an incidental finding during regular work-up, HIV-infected patients with transaminase elevations require additional visits for laboratory studies and clinical assessments, and often undergo interruptions and changes in antiretroviral therapy (ART). Alanine aminotransferase is present primarily in the liver, thus being a surrogate marker of hepatocellular injury. Aspartate aminotransferase is present in the liver and other organs, namely cardiac and skeletal muscle, kidney and brain. Serum levels of both liver transaminases predict liver-related mortality. Moreover, serum fibrosis biomarkers based on alanine aminotransferase and aspartate aminotransferase predict all-cause mortality. In a busy clinical setting, a diagnostic approach to elevated liver transaminases could be complicated given the frequency and nonspecificity of this finding. Indeed, HIV-infected individuals present multiple risk factors for liver damage and chronic elevation of transaminases, including coinfection with hepatitis B and C viruses, alcohol abuse, hepatotoxicity due to ART, HIV itself and frequent metabolic comorbidities leading to nonalcoholic fatty liver disease. This review provides an update on epidemiology of elevated liver transaminases, summarizes the main etiologic contributors and discusses the prognostic significance and a pragmatic approach to this frequent finding in the clinical practice of HIV medicine. With the aging of the HIV-infected population following the successful implementation of ART in Western countries, liver-related conditions are now a major comorbidity in this setting. As such, clinicians should be aware of the frequency, clinical significance and diagnostic approach to elevated liver transaminases.
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Nan Y, Niu X, Wang R, Zhao S, Fu N, Du J, Wang Y, Wang B, Zhang Y. microRNA-1273g-3p is a useful non-invasive test for the prediction of liver fibrosis in patients with chronic hepatitis C. Exp Ther Med 2019; 17:1817-1824. [PMID: 30783454 PMCID: PMC6364236 DOI: 10.3892/etm.2018.7114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 07/07/2017] [Indexed: 12/12/2022] Open
Abstract
Previous studies using microRNA (miRNA or miR) microarrays have demonstrated that miR-1273g-3p is upregulated in patients with hepatitis C virus (HCV)-associated fibrosis. As miRNAs have been suggested to be promising non-invasive biomarkers, the aim of the present study was to assess whether miR-1273g-3p may be useful as a potential indicator of fibrosis progression in patients with HCV. Liver biopsies were performed on 112 patients with chronic hepatitis C (CHC) and liver stiffness measurements (LSM) were performed using FibroTouch. Liver fibrosis was determined based on Meta-analysis of Histological Data in Viral Hepatitis classification, and the aspartate aminotransferase (AST)-to-platelet count (PLT) ratio index (APRI) and Fibrosis-4 score (FIB-4) were calculated. The diagnostic performance of miR-1273g-3p, LSM, APRI and FIB-4 in predicting fibrosis stage were evaluated and compared by receiver operating characteristic (ROC) analysis. It was demonstrated that miR-1273g-3p levels were significantly positively correlated with the liver fibrosis stage (r=0.657, P<0.001). The results of LSM, APRI and FIB-4, the three non-invasive diagnostic methods, had good consistency with liver biopsy results, and their correlation coefficients with fibrosis staging were 0.815, 0.417 and 0.522, respectively. The areas under the ROC curves of miR-1273g-3p for F≥2 and F=4 stage samples were 0.841 and 0.933, respectively, which were lower than LSM (0.890 and 0.937), and higher than FIB-4 (0.791 and 0.766) and APRI (0.719 and 0.760). Spearman analysis demonstrated that serum miR-1273g-3p levels were significantly positively correlated with age, body mass index, alanine aminotransferase, AST and total bilirubin (all P<0.05), and negatively correlated with PLT (P<0.05). However, no significant correlation was observed between miR-1273g-3p levels, baseline HCV RNA loads and genotype. Therefore, the results demonstrated that miR-1273g-3p levels, as a novel non-invasive test, may be a useful and easy method for predicting the stage of liver fibrosis in patients with CHC, and has a better diagnostic performance than FIB-4 and APRI. Further prospective studies are required to validate the efficacy of miR-1273g-3p as a predictor of liver fibrosis.
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Affiliation(s)
- Yuemin Nan
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
- Correspondence to: Professor Yuemin Nan, Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, Hebei 050051, P.R. China, E-mail:
| | - Xuemin Niu
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Rongqi Wang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Suxian Zhao
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Na Fu
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Jinghua Du
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Yang Wang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Baoyu Wang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Yuguo Zhang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
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Abstract
The first clinical application of magnetic resonance elastography (MRE) was in the evaluation of chronic liver disease (CLD) for detection and staging of liver fibrosis. In the past 10 years, MRE has been incorporated seamlessly into a standard magnetic resonance imaging (MRI) liver protocol worldwide. Liver MRE is a robust technique for evaluation of liver stiffness and is currently the most accurate noninvasive imaging technology for evaluation of liver fibrosis. Newer MRE sequences including spin-echo MRE and 3 dimensional MRE have helped in reducing the technical limitations of clinical liver MRE that is performed with 2D gradient recalled echo (GRE) MRE. Advances in MRE technology have led to understanding of newer mechanical parameters such as dispersion, attenuation, and viscoelasticity that may be useful in evaluating pathological processes in CLD and may prove useful in their management.This review article will describe the changes in CLD that cause an increase in stiffness followed by principle and technique of liver MRE. In the later part of the review, we will briefly discuss the advances in liver MRE.
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El-Gohary M, Moore M, Roderick P, Watkins E, Dash J, Reinson T, Newell C, Kim M, Stuart B, Becque T, Sheron N. Local care and treatment of liver disease (LOCATE) - A cluster-randomized feasibility study to discover, assess and manage early liver disease in primary care. PLoS One 2018; 13:e0208798. [PMID: 30576330 PMCID: PMC6303066 DOI: 10.1371/journal.pone.0208798] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 11/23/2018] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Chronic liver disease is an escalating problem both in the United Kingdom and worldwide. In the UK mortality rates have risen sharply over the previous 50 years predominantly due to alcohol, however the increasing prevalence of non-alcohol related fatty liver disease both in the UK and elsewhere is also of concern. Liver disease develops silently hence early detection of fibrosis is essential to prevent progression. Primary care presents an opportunity to identify at risk populations, however assessment largely comprises of indirect markers of fibrosis which have little prognostic value. We hypothesised that setting up nurse-led primary care based liver clinics using additional non-invasive testing would increase the number of new diagnoses of liver disease compared to usual care. METHODS This was a prospective, cluster randomised feasibility trial based in urban primary care in Southampton, United Kingdom. 10 GP practices were randomised to either intervention (liver health nurse) or control (care as usual). Pre recruitment audits were carried out in each practice to ascertain baseline prevalence of liver disease. Participants were subsequently recruited in intervention practices from July 2014-March 2016 via one of 3 pathways: GP referral, nurse led case finding based on risk factors or random AUDIT questionnaire mailouts. Liver assessment included the Southampton Traffic Light test (serum fibrosis markers HA and P3NP) and transient elastography (FibroScan). Cases were ascribed as 'no fibrosis', 'liver warning', 'progressive fibrosis' or 'probable cirrhosis'. Post recruitment audits were repeated and incident liver diagnoses captured from July 2014-September 2016. Each new diagnosis was reviewed in a virtual clinic by a consultant hepatologist. FINDINGS 910 participants were seen in the nurse led clinic-44 (4.8%) probable cirrhosis, 141 (15.5%) progressive fibrosis, 220 (24.2%) liver warning and 505 (55.5%) no evidence of liver fibrosis. 450 (49.5%) cases were due to NAFLD with 356 (39.1%) from alcohol. In the 405 with a liver disease diagnosis, 136 (33.6%) were referred by GP, 218 (53.8%) from nurse led case finding and 51 (12.6%) from the AUDIT mailout. 544 incident cases were identified in the intervention arm compared to 221 in the control arm in the period July 2014-September 2016 (adjusted odds ratio 2.4, 95% CI 2.1 to 2.8). CONCLUSIONS The incorporation of a liver health nurse into GP practices was simple to arrange and yielded a much higher number of new diagnoses of liver disease compared to usual care. Nearly half of all participants recruited had a degree of liver disease. Nurse led case finding and GP referrals were most effective compared to AUDIT questionnaire mailouts in an urban population in identifying unknown disease. Utilising study and previous data allowed quick and effective virtual review by a hepatologist. Identifying those who are at risk of liver disease from harmful alcohol use remains a challenge and needs to be addressed in future work.
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Affiliation(s)
- Magdy El-Gohary
- Primary Care and Population Sciences, School of Medicine, University of Southampton, Southampton, Hampshire, United Kingdom
- * E-mail:
| | - Mike Moore
- Primary Care and Population Sciences, School of Medicine, University of Southampton, Southampton, Hampshire, United Kingdom
| | - Paul Roderick
- Primary Care and Population Sciences, School of Medicine, University of Southampton, Southampton, Hampshire, United Kingdom
| | - Emily Watkins
- National Institute for Health Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, Hampshire, United Kingdom
| | - Joanne Dash
- National Institute for Health Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, Hampshire, United Kingdom
| | - Tina Reinson
- National Institute for Health Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, Hampshire, United Kingdom
| | - Colin Newell
- Primary Care and Population Sciences, School of Medicine, University of Southampton, Southampton, Hampshire, United Kingdom
| | - Miranda Kim
- National Institute for Health Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, Hampshire, United Kingdom
| | - Beth Stuart
- Primary Care and Population Sciences, School of Medicine, University of Southampton, Southampton, Hampshire, United Kingdom
| | - Taeko Becque
- Primary Care and Population Sciences, School of Medicine, University of Southampton, Southampton, Hampshire, United Kingdom
| | - Nick Sheron
- National Institute for Health Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, Hampshire, United Kingdom
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15
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Mazzola G, Adamoli L, Calvaruso V, Macaluso FS, Colletti P, Mazzola S, Cervo A, Trizzino M, Di Lorenzo F, Iaria C, Prestileo T, Orlando A, Di Marco V, Cascio A. Suboptimal performance of APRI and FIB-4 in ruling out significant fibrosis and confirming cirrhosis in HIV/HCV co-infected and HCV mono-infected patients. Infection 2018; 47:409-415. [PMID: 30519966 DOI: 10.1007/s15010-018-1258-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Accepted: 11/27/2018] [Indexed: 12/16/2022]
Abstract
PURPOSE We aimed to assess the diagnostic reliability of two indirect biomarkers, APRI and FIB-4, for the staging of liver fibrosis using transient elastography (TE) as reference standard, among HIV/HCV co-infected and HCV mono-infected patients. METHODS This is an observational, retrospective study on subjects who had access to the RESIST HCV from October 2013 to December 2016, a regional network encompassing 22 hospitals and academic centers throughout Sicily. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) < 9.5 kPa (significant fibrosis) and LSM ≥ 12.5 kPa (cirrhosis) were determined by receiver operator characteristics (ROC) curves. RESULTS 238 HIV/HCV co-infected and 1937 HCV mono-infected patients were included. Performances of FIB-4 and APRI for the detection of significant fibrosis and cirrhosis proved to be unsatisfactory, with very high false negative and false positive rates among both cohorts. No significant differences were found after stratification of HIV/HCV co-infected patients for BMI < or ≥ 25, ALT < or ≥ 40 IU/L, ALT < or ≥ 80 IU/L, and presence/absence of a bright liver echo pattern on ultrasonography. CONCLUSIONS Differently from other studies, we detected the unreliability of APRI and FIB-4 for the assessment of liver fibrosis in both HCV mono-infected and HIV/HCV co-infected patients.
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Affiliation(s)
- Giovanni Mazzola
- Department of Sciences for Health Promotion "G. D'Alessandro", University of Palermo, Palermo, Italy
| | - Lucia Adamoli
- Department of Sciences for Health Promotion "G. D'Alessandro", University of Palermo, Palermo, Italy
| | - Vincenza Calvaruso
- Di.Bi.M.I.S, Section of Gastroenterology, University of Palermo, Palermo, Italy
| | | | - Pietro Colletti
- Department of Sciences for Health Promotion "G. D'Alessandro", University of Palermo, Palermo, Italy
| | - Sergio Mazzola
- Clinical Epidemiology and Cancer Registry Unit, A.O.U.P. "Paolo Giaccone", Palermo, Italy
| | - Adriana Cervo
- Department of Sciences for Health Promotion "G. D'Alessandro", University of Palermo, Palermo, Italy
| | - Marcello Trizzino
- Department of Sciences for Health Promotion "G. D'Alessandro", University of Palermo, Palermo, Italy
| | | | - Chiara Iaria
- ARNAS "Civico-Benefratelli" Hospital, Palermo, Italy
| | | | - Ambrogio Orlando
- IBD Unit, "Villa Sofia-Cervello" Hospital, Via Trabucco 180, 90146, Palermo, Italy
| | - Vito Di Marco
- Di.Bi.M.I.S, Section of Gastroenterology, University of Palermo, Palermo, Italy
| | - Antonio Cascio
- Department of Sciences for Health Promotion "G. D'Alessandro", University of Palermo, Palermo, Italy
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16
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High proportions of liver fibrosis and cirrhosis in an ageing population of people who use drugs in Amsterdam, The Netherlands. Eur J Gastroenterol Hepatol 2018; 30:1168-1176. [PMID: 30028776 DOI: 10.1097/meg.0000000000001213] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND The incidence and prevalence of hepatitis C virus (HCV) infection among people who use drugs (PWUD) peaked in the 1980s in Amsterdam. As liver cirrhosis develops several decades after HCV infection and PWUD have other risk factors for liver fibrosis, we hypothesized that significant liver fibrosis or cirrhosis is now common among PWUD in Amsterdam. METHODS PWUD were recruited from the Amsterdam Cohort Studies, methadone programmes and addiction clinics during 2009-2016. Transient elastography was performed to assess liver stiffness. We estimated METAVIR fibrosis levels on the basis of the following liver stiffness measurements (LSMs) cut-offs: F0-F2 (no/mild) less than 7.65 kPa; F2-F3 (moderate/severe) at least 7.65 to less than 13 kPa; and F4 (cirrhosis) at least 13 kPa. Using linear regression models, we assessed the association between LSM and sociodemographic, clinical and behavioural determinants in (a) all PWUD and (b) chronic hepatitis C virus (cHCV)-infected PWUD. RESULTS For 140 PWUD, the median LSM was 7.6 kPa (interquartile range=4.9-12.0); 26.4% had moderate/severe fibrosis and 22.9% had cirrhosis. Of 104 chronically infected PWUD, 57.7% had evidence of significant fibrosis (≥F2). In multivariable analysis including all PWUD, increased LSM was associated significantly with cHCV monoinfection and HIV/HCV coinfection. In cHCV-infected PWUD, older age was associated significantly with increased LSM. In all groups, longer duration of heavy alcohol drinking was associated with increased LSM. CONCLUSION A high proportion of PWUD had significant fibrosis or cirrhosis that were associated with cHCV infection, HIV/HCV coinfection and duration of heavy alcohol drinking. Increased uptake of HCV treatment and interventions to reduce alcohol use are needed to decrease the liver disease burden in this population.
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Rice DP, Ordoveza MA, Palmer AM, Wu GY, Chirch LM. Timing of treatment initiation of direct-acting antivirals for HIV/HCV coinfected and HCV monoinfected patients. AIDS Care 2018; 30:1507-1511. [PMID: 30021452 DOI: 10.1080/09540121.2018.1499857] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Direct-acting antiviral therapy is safe and cost-effective for the treatment of hepatitis C virus (HCV) infection. However, variability in drug payment rules represents a barrier to treatment that may disproportionately affect certain populations. We conducted a retrospective cohort study among HIV/HCV coinfected and HCV monoinfected patients using Kaplan-Meier and Fisher's exact test to analyze the time from the prescription of a direct-acting antiviral agent to delivery to the patient. Variables with significance p < .20 in univariate analysis were included in a Cox regression model. Factors associated with faster treatment were Infectious Diseases office setting (p = .01), public insurance payer (p = .01), and initial approval of requested regimen (p = .01). The presence of other liver disease was associated with delay in treatment (p = .05). Unrestrictive Medicare and Medicaid regulations resulted in more rapid delivery of medication compared to private payers. Fibrosis level, Child-Pugh class and HIV status did not significantly change time to treatment.
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Affiliation(s)
- Donald P Rice
- a University of Connecticut School of Medicine , Farmington , CT , USA
| | | | - Ann M Palmer
- a University of Connecticut School of Medicine , Farmington , CT , USA
| | - George Y Wu
- b University of Connecticut Health Center , Farmington , CT , USA
| | - Lisa M Chirch
- b University of Connecticut Health Center , Farmington , CT , USA
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Clutterbuck D, Asboe D, Barber T, Emerson C, Field N, Gibson S, Hughes G, Jones R, Murchie M, Nori AV, Rayment M, Sullivan A. 2016 United Kingdom national guideline on the sexual health care of men who have sex with men. Int J STD AIDS 2018:956462417746897. [PMID: 29334885 DOI: 10.1177/0956462417746897] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2024]
Abstract
This guideline is intended for use in UK Genitourinary medicine clinics and sexual health services but is likely to be of relevance in all sexual health settings, including general practice and Contraception and Sexual Health (CASH) services, where men who have sex with men (MSM) seek sexual health care or where addressing the sexual health needs of MSM may have public health benefits. For the purposes of this document, MSM includes all gay, bisexual and all other males who have sex with other males and both cis and trans men. This document does not provide guidance on the treatment of particular conditions where this is covered in other British Association for Sexual Health and HIV (BASHH) Guidelines but outlines best practice in multiple aspects of the sexual health care of MSM. Where prevention of sexually transmitted infections including HIV can be addressed as an integral part of clinical care, this is consistent with the concept of combination prevention and is included. The document is designed primarily to provide guidance on the direct clinical care of MSM but also makes reference to the design and delivery of services with the aim of supporting clinicians and commissioners in providing effective services. Methodology This document was produced in accordance with the guidance set out in the BASHH CEG's document 'Framework for guideline development and assessment' published in 2010 at http://www.bashh.org/guidelines and with reference to the Agree II instrument. Following the production of the updated framework in April 2015, the GRADE system for assessing evidence was adopted and the draft recommendations were regraded. Search strategy (see also Appendix 1) Ovid Medline 1946 to December 2014, Medline daily update, Embase 1974 to December 2014, Pubmed NeLH Guidelines Database, Cochrane library from 2000 to December 2014. Search language English only. The search for Section 3 was conducted on PubMed to December 2014. Priority was given to peer-reviewed papers published in scientific journals, although for many issues evidence includes conference abstracts listed on the Embase database. In addition, for 'Identification of problematic recreational drug and alcohol use' section and 'Sexual problems and dysfunctions in MSM' section, searches included PsycINFO. Methods Article titles and abstracts were reviewed and if relevant the full text article was obtained. Priority was given to randomised controlled trial and systematic review evidence, and recommendations made and graded on the basis of best available evidence. Piloting and feedback The first draft of the guideline was circulated to the writing group and to a small group of relevant experts, third sector partners and patient representatives who were invited to comment on the whole document and specifically on particular sections. The revised draft was reviewed by the CEG and then reviewed by the BASHH patient/public panel and posted on the BASHH website for public consultation. The final draft was piloted before publication. Guideline update The guidelines will be reviewed and revised in five years' time, 2022.
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Affiliation(s)
| | - David Asboe
- 2 Chelsea and Westminster Healthcare NHS Foundation Trust, London, UK
| | - Tristan Barber
- 2 Chelsea and Westminster Healthcare NHS Foundation Trust, London, UK
| | | | - Nigel Field
- 4 Public Health England, London, UK
- 5 University College London, London, UK
| | | | | | - Rachael Jones
- 2 Chelsea and Westminster Healthcare NHS Foundation Trust, London, UK
| | | | - Achyuta V Nori
- 8 8945 Guy's and St Thomas' NHS Foundation Trust , London, UK
| | - Michael Rayment
- 2 Chelsea and Westminster Healthcare NHS Foundation Trust, London, UK
| | - Ann Sullivan
- 9 BASHH CEG, BASHH 2017 Registered Office, Macclesfield, UK
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Vuppalanchi R, Siddiqui MS, Van Natta ML, Hallinan E, Brandman D, Kowdley K, Neuschwander-Tetri BA, Loomba R, Dasarathy S, Abdelmalek M, Doo E, Tonascia JA, Kleiner DE, Sanyal AJ, Chalasani N. Performance characteristics of vibration-controlled transient elastography for evaluation of nonalcoholic fatty liver disease. Hepatology 2018; 67:134-144. [PMID: 28859228 PMCID: PMC5739967 DOI: 10.1002/hep.29489] [Citation(s) in RCA: 196] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Revised: 07/05/2017] [Accepted: 08/29/2017] [Indexed: 12/14/2022]
Abstract
Vibration-controlled transient elastography estimates liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), which are noninvasive assessments of hepatic fibrosis and steatosis, respectively. However, prior vibration-controlled transient elastography studies reported high failure rates in patients with nonalcoholic fatty liver disease. We examined the performance characteristics of the FibroScan 502 Touch with two probes, medium (M+) and extra large (XL+), in patients with nonalcoholic fatty liver disease in a multicenter setting. A total of 1,696 exams were attempted in 992 patients (body mass index, 33.6 ± 6.5 kg/m2 ) with histologically confirmed nonalcoholic fatty liver disease. Simultaneous assessment of LSM and CAP was performed using the FibroScan 502 Touch with an automatic probe selection tool. Testing was conducted twice in patients by either a single operator (87%) or two operators (13%). Failure was defined as the inability to obtain a valid examination. An examination was considered unreliable if LSM interquartile range/median was >30%. Significant disagreement between two readings was defined as >95% limits of agreement between two readings. A total of 1,641 examinations yielded valid results with a failure rate of 3.2% (55/1,696). The proportion of unreliable scans for LSM was 3.9%. The proportion of unreliable scans with operator experience in the top quartile (≥59 procedures) was significantly lower than that in the lower three quarters combined (1.6% versus 4.7%, P = 0.02 by Fisher's exact test). The significant disagreement between first and second readings for LSM and CAP when obtained back to back was 18% and 11%, respectively. CONCLUSION Vibration-controlled transient elastography for estimation of LSM and CAP can be successfully deployed in a multicenter setting with low failure (3.2%) and high reliability (>95%) rates and high reproducibility. (Hepatology 2018;67:134-144).
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Affiliation(s)
| | | | | | - Erin Hallinan
- The Johns Hopkins University School of Public Health, Baltimore,
MD
| | | | | | | | - Rohit Loomba
- University of California San Diego, San Diego, CA
| | | | | | - Edward Doo
- Liver Disease Branch, NIDDK, National Institutes of Health,
Bethesda, MD
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20
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Abstract
Patients with HIV have a proclivity to develop liver fibrosis, especially when associated with other conditions such as HCV, HBV, and NAFLD. Identifying HIV-infected patients with significant fibrosis or cirrhosis plays an important role in clinical and therapeutic decision-making. Liver biopsy is currently considered as the gold standard for fibrosis assessment but carries many shortcomings (cost, invasiveness, complications, false negative rate of 20 %). Multiple non-invasive methods of liver fibrosis assessment have been developed, but not all have been studied in HIV-infected individuals. Non-invasive liver fibrosis tools include both serologic-based testing scores (rely on direct and/or indirect markers) such as APRI, FIB4, FibroTest, FibroSpect II, HepaScore, or imaging-based methods such as vibration controlled liver elastography. There is validated data to support the use of non-invasive modalities of fibrosis assessment in HIV-HCV co-infected individuals for the exclusion of cirrhosis, but may be poorly reliable or not enough data exists for the assessment of other co-morbid disease processes.
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21
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Sherman KE, Peters MG, Thomas D. Human immunodeficiency virus and liver disease: A comprehensive update. Hepatol Commun 2017; 1:987-1001. [PMID: 30838978 PMCID: PMC5721407 DOI: 10.1002/hep4.1112] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 08/29/2017] [Accepted: 09/19/2017] [Indexed: 12/16/2022] Open
Abstract
Among persons living with human immunodeficiency virus (HIV) infection, liver disease remains a major cause of morbidity and mortality. While the etiologies are varied and often overlapping in the individual patient, the underlying mechanisms, including oxidative stress, direct activation of stellate cells, HIV interaction with hepatocytes, and bacterial translocation with systemic immune activation, seem to be unifying characteristics. Early and fully suppressive HIV antiretroviral therapy is a mainstay of management either before or concurrent with treatment of etiologic cofactors, including hepatitis C virus, hepatitis B virus, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Significant barriers to care that still exist include liver disease recognition, appropriate linkage to care, ongoing substance abuse, and psychiatric comorbidities in the HIV-infected population. Emerging issues in these patients include acute and chronic hepatitis E, underreported hepatitis D, and a rising incidence of hepatocellular carcinoma. (Hepatology Communications 2017;1:987-1001).
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Cao Z, Li Z, Wang H, Liu Y, Xu Y, Mo R, Ren P, Chen L, Lu J, Li H, Zhuang Y, Liu Y, Wang X, Zhao G, Tang W, Xiang X, Cai W, Liu L, Bao S, Xie Q. Algorithm of Golgi protein 73 and liver stiffness accurately diagnoses significant fibrosis in chronic HBV infection. Liver Int 2017; 37:1612-1621. [PMID: 28772348 DOI: 10.1111/liv.13536] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Accepted: 07/26/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Serum Golgi protein 73 (GP73) is a potential biomarker for fibrosis assessment. We aimed to develop an algorithm based on GP73 and liver stiffness (LS) for further improvement of accuracy for significant fibrosis in patients with antiviral-naïve chronic hepatitis B virus (HBV) infection. METHODS Diagnostic accuracy evaluation of GP73 and development of GP73-LS algorithm was performed in training cohort (n = 267) with an independent cohort (n = 133) for validation. RESULTS A stepwise increasing pattern of serum GP73 was observed across fibrosis stages in patients with antiviral-naïve chronic HBV infection. Serum GP73 significantly correlated (rho = 0.48, P < .001) with fibrosis stage and was an independent predictor for the presence of significant fibrosis (OR, 95%CI: 1.02, 1.01-1.03, per increase in 1 ng/mL, P < .001). Both LS (AUROC, 95%CI: 0.82, 0.77-0.87, accuracy: 74.7%) and GP73 (AUROC, 95%CI: 0.76, 0.71-0.82, accuracy: 71.5%) well-predicted significant fibrosis and outperformed APRI (AUROC, 95%CI: 0.69, 0.63-0.76, accuracy: 66%) and FIB-4 (AUROC, 95%CI: 0.66, 0.60-0.73, accuracy: 63.6%). Using GP73-LS algorithm, GP73 < 63 in agreement with LS < 8.5 provided accuracy of 81.7% to excluded significant fibrosis. GP73 ≥ 63 in agreement with LS ≥ 8.5 provided accuracy of 93.3% to confirm significant fibrosis. Almost 64% or 68% of patients in the training or validation cohort could be accurately classified. CONCLUSIONS Serum GP73 is a robust biomarker for significant fibrosis diagnosis. GP73-LS algorithm provided better diagnostic accuracy than currently available approaches. More than 60% antiviral naïve CHB patients could use this algorithm without resorting to liver biopsy.
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Affiliation(s)
- Zhujun Cao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ziqiang Li
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hui Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhan Liu
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yumin Xu
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ruidong Mo
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Peipei Ren
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lichang Chen
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Lu
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong Li
- Department of Infectious Disease, The Third Hospital of Changzhou, Jiangsu, China
| | - Yan Zhuang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yunye Liu
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaolin Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Gangde Zhao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiliang Tang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaogang Xiang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Cai
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Longgen Liu
- Department of Infectious Disease, The Third Hospital of Changzhou, Jiangsu, China
| | - Shisan Bao
- Discipline of Pathology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW, Australia
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Steininger K, Boyd A, Dupke S, Krznaric I, Carganico A, Munteanu M, Neifer S, Schuetze M, Obermeier M, Arasteh K, Baumgarten A, Ingiliz P. HIV-positive men who have sex with men are at high risk of development of significant liver fibrosis after an episode of acute hepatitis C. J Viral Hepat 2017; 24:832-839. [PMID: 28439936 DOI: 10.1111/jvh.12707] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Accepted: 02/01/2017] [Indexed: 12/17/2022]
Abstract
Acute hepatitis C virus infection remains a major health concern in human immunodeficiency virus(HIV)-infected men who have sex with men (MSM). New direct-acting antiviral agent (DAA) combination therapy has not yet been approved for the treatment for acute hepatitis C virus(HCV), thereby potentially causing deferral of HCV treatment. Therefore, we aimed to study the course of liver disease after an episode of acute HCV. This study is a retrospective single-centre cohort of HIV-positive MSM with acute HCV infection. Liver fibrosis was estimated by Fibroscan® and Fibrotest® . Liver-related and non-liver-related outcomes were documented. Overall 213 episodes of acute HCV infection in 178 men were documented. Median follow-up for all included patients was 38.7 months. Spontaneous HCV clearance was found in 10.8% of patients, which was significantly associated with older age, lower HCV RNA levels, and higher ALT levels upon initial acute HCV diagnosis. Treatment with interferon-based therapy was initiated in 86.3% of cases, resulting in a sustained virological response(SVR) rate of 70.7%. After 3 years' follow-up, significant liver fibrosis of METAVIR F2 stage or higher was found in 39.4% of patients after first acute HCV diagnosis. Higher age, physician-declared alcoholism, and nonresponse to acute HCV therapy were independently associated with higher fibrosis stages. Ten patients died during the observation period (IR 1.4/100 patient-years) and four during interferon treatment. Significant liver fibrosis is a common finding in HIV-positive MSM following acute HCV infection despite high treatment uptake and cure rates, suggesting the need for close liver disease monitoring particularly if HCV treatment is deferred.
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Affiliation(s)
- K Steininger
- Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - A Boyd
- Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM UMR_S 1136, Paris, France
| | - S Dupke
- Center for Infectiology, Berlin, Germany
| | - I Krznaric
- Center for Infectiology, Berlin, Germany
| | | | | | - S Neifer
- Center for Microbiology Dr. Neifer, Berlin, Germany
| | | | | | - K Arasteh
- Department of Infectiology, Vivantes Auguste-Viktoria-Hospital, Berlin, Germany
| | | | - P Ingiliz
- Center for Infectiology, Berlin, Germany
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A Single Test Combining Blood Markers and Elastography is More Accurate Than Other Fibrosis Tests in the Main Causes of Chronic Liver Diseases. J Clin Gastroenterol 2017; 51:639-649. [PMID: 28692443 DOI: 10.1097/mcg.0000000000000788] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND GOAL International guidelines suggest combining a blood test and liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the accuracies of these tests between the main etiologies of chronic liver diseases. STUDY Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM (Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index (OI) and accessorily with area under the receiver operating characteristics (F≥2, F≥3, cirrhosis). RESULTS OIs in CHC were: FibroMeters: 0.812, FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM: 0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate than NAFLD-specific tests. The combined FibroMeters had significantly higher accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1 diagnostic target in all etiologies, except in ALD where LSM had the highest OI, and in 3 diagnostic targets (OIs and 2 area under the receiver operating characteristics) in CHC and NAFLD. CONCLUSIONS Some tests developed in CHC outperformed other tests in their specific etiologies. Tests combining blood markers and LSM outperformed single tests, validating recent guidelines and extending them to main etiologies. Noninvasive fibrosis evaluation can thus be simplified in the main etiologies by using a unique test: either LSM alone, especially in ALD, or preferably combined to blood markers.
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25
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A stepwise algorithm using an at-a-glance first-line test for the non-invasive diagnosis of advanced liver fibrosis and cirrhosis. J Hepatol 2017; 66:1158-1165. [PMID: 28088581 DOI: 10.1016/j.jhep.2017.01.003] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Revised: 12/29/2016] [Accepted: 01/03/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Chronic liver diseases (CLD) are common, and are therefore mainly managed by non-hepatologists. These physicians lack access to the best non-invasive tests of liver fibrosis, and consequently cannot accurately determine the disease severity. Referral to a hepatologist is then needed. We aimed to implement an algorithm, comprising a new first-line test usable by all physicians, for the detection of advanced liver fibrosis in all CLD patients. METHODS Diagnostic study: 3754 CLD patients with liver biopsy were 2:1 randomized into derivation and validation sets. Prognostic study: longitudinal follow-up of 1275 CLD patients with baseline fibrosis tests. RESULTS Diagnostic study: the easy liver fibrosis test (eLIFT), an "at-a-glance" sum of points attributed to age, gender, gamma-glutamyl transferase, aspartate aminotransferase (AST), platelets and prothrombin time, was developed for the diagnosis of advanced fibrosis. In the validation set, eLIFT and fibrosis-4 (FIB4) had the same sensitivity (78.0% vs. 76.6%, p=0.470) but eLIFT gave fewer false positive results, especially in patients ≥60years old (53.8% vs. 82.0%, p<0.001), and was thus more suitable as screening test. FibroMeter with vibration controlled transient elastography (VCTE) was the most accurate among the eight fibrosis tests evaluated. The sensitivity of the eLIFT-FMVCTE algorithm (first-line eLIFT, second-line FibroMeterVCTE) was 76.1% for advanced fibrosis and 92.1% for cirrhosis. Prognostic study: patients diagnosed as having "no/mild fibrosis" by the algorithm had excellent liver-related prognosis with thus no need for referral to a hepatologist. CONCLUSION The eLIFT-FMVCTE algorithm extends the detection of advanced liver fibrosis to all CLD patients and reduces unnecessary referrals of patients without significant CLD to hepatologists. LAY SUMMARY Blood fibrosis tests and transient elastography accurately diagnose advanced liver fibrosis in the large population of patients having chronic liver disease, but these non-invasive tests are only currently available in specialized centers. We have developed an algorithm including the easy liver fibrosis test (eLIFT), a new simple and widely available blood test. It is used as a first-line procedure that selects at-risk patients who need further evaluation with the FibroMeterVCTE, an accurate fibrosis test combining blood markers and transient elastography result. This new algorithm, called the eLIFT-FMVCTE, accurately identifies the patients with advanced chronic liver disease who need referral to a specialist, and those with no or mild liver lesions who can remain under the care of their usual physician. CLINICAL TRIAL REGISTRATION No registration (analysis of pooled data from previously published diagnostic studies).
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Wang S, Zhang W, Zhang F, Qian Z, Wang LF, Ren LJ, Yang S. Value of FibroScan and aspartate aminotransferase-to-platelet ratio index, alone or in combination, in predicting esophagogastric variceal bleeding in patients with liver cirrhosis. Shijie Huaren Xiaohua Zazhi 2017; 25:1287-1291. [DOI: 10.11569/wcjd.v25.i14.1287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the value of FibroScan and aspartate aminotransferase-to-platelet ratio index (APRI), alone or in combination, in predicting the risk of esophagogastric variceal bleeding in patients with liver cirrhosis.
METHODS Two hundred and ten patients with posthepatitic cirrhosis were divided into a non-bleeding group (n = 153) and a bleeding group (n = 57) according to the presence of esophagogastric variceal bleeding or not. FibroScan values (LSM values) and APRI values were obtained within a week and compared between the two groups using t-tests. Receiver operating characteristic curve (ROC) analysis was used to assess the accuracy of LSM alone, APRI alone, and LSM + APRI in predicting the risk of esophagogastric variceal bleeding.
RESULTS The LSM values of the patients with and without bleeding were 28.49 kPa ± 9.46 kPa and 22.87 kPa ± 6.95 kPa, respectively, and the APRI values were 2.99 ± 1.11 and 2.13 ± 1.01, respectively, both of which showed a significant difference between the two groups. The AUCs of LSM alone, APRI alone, and LSM + APRI in predicting the risk of bleeding were 0.669, 0.727 and 0.722, respectively, suggesting that APRI alone and LSM + APRI had good diagnostic value in esophagogastric variceal bleeding.
CONCLUSION APRI alone and FibroScan combined with APRI have good predictive value for the risk of esophageal variceal bleeding in patients with liver cirrhosis.
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d'Arminio Monforte A, Cozzi-Lepri A, Ceccherini-Silberstein F, De Luca A, Lo Caputo S, Castagna A, Mussini C, Cingolani A, Tavelli A, Shanyinde M, Gori A, Girardi E, Andreoni M, Antinori A, Puoti M. Access and response to direct antiviral agents (DAA) in HIV-HCV co-infected patients in Italy: Data from the Icona cohort. PLoS One 2017; 12:e0177402. [PMID: 28520749 PMCID: PMC5435319 DOI: 10.1371/journal.pone.0177402] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 04/26/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Real-life data on access and response to direct antiviral agents (DAA) in HIV-HCV coinfected individuals are lacking. METHODS HCV viremic, HIV-positive patients from Icona and Hepaicona cohorts naïve to DAA by January 2013 were included. Access and predictors of starting DAA were evaluated. Switches of antiretroviral drugs at starting DAA were described. We calculated sustained virological response (SVR12) in those reaching 12 weeks after end-of-treatment (EOT), and defined treatment failure (TF) as discontinuation of DAA before EOT or non-SVR12. Statistical analyses included Kaplan-Meier curves, univariable and multivariable analyses evaluating predictors of access to DAA and of treatment outcome (non-SVR and TF). RESULTS 2,607 patients included. During a median follow-up of 38 (IQR:30-41) months, 920 (35.3%) patients started DAA. Eligibility for reimbursement was the strongest predictor to access to treatment: 761/1,090 (69.8%) eligible and 159/1,517 (10.5%) non-eligible to DAA reimbursement. Older age, HIV-RNA≤50 copies/mL were associated to faster DAA initiation, higher CD4 count and HCV-genotype 3 with delayed DAA initiation in those eligible to DAA reimbursement. Up to 28% of patients (36% of those on ritonavir-boosted protease inhibitors, PI/r) underwent antiretroviral (ART) modification at DAA initiation. 545/595 (91.6%) patients reaching EOT achieved SVR12. Overall, TF occurred in 61/606 patients (10.1%), with 11 discontinuing DAA before EOT. Suboptimal DAA was the only independent predictor of both non-SVR12 (AHR 2.52, 95%CI:1.24-5.12) and TF (AHR: 2.19; 95%CI:1.13-4.22). CONCLUSIONS Only 35.3% had access to HCV treatment. Despite excellent rates of SVR12 rates (91.6%), only 21% (545/2,607) of our HIV-HCV co-infected patients are cured.
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Affiliation(s)
- Antonella d'Arminio Monforte
- Clinic of Infectious and Tropical Diseases, Department of Health Sciences, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy
| | - Alessandro Cozzi-Lepri
- Department of Infection and Population Health, Division of Population Health, UCL Medical School, Royal Free Campus, London, United Kingdom
| | | | - Andrea De Luca
- UOC of Infectious Diseases, Dipartimento di Biotecnologie Mediche, University of Siena, Siena, Italy
| | | | - Antonella Castagna
- Department of Infectious Diseases, San Raffaele Scientific Institute, University Vita-Salute San Raffaele, Milan, Italy
| | - Cristina Mussini
- Infectious Disease Clinic, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Antonella Cingolani
- Institute of Clinical Infectious Diseases, Department of Public Health, Catholic University of Sacred Hearth, Rome, Italy
| | | | - Milensu Shanyinde
- Department of Infection and Population Health, Division of Population Health, UCL Medical School, Royal Free Campus, London, United Kingdom
| | - Andrea Gori
- Division of Infectious Diseases, ASST Monza-Brianza- San Gerardo Hospital, University Milano-Bicocca, Monza, Italy
| | - Enrico Girardi
- Department of Epidemiology, National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy
| | - Massimo Andreoni
- Clinical Infectious Diseases, Department of Systems Medicine, University of Rome—Tor Vergata, Rome, Italy
| | - Andrea Antinori
- HIV/AIDS Department, National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy
| | - Massimo Puoti
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
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Singh S, Muir AJ, Dieterich DT, Falck-Ytter YT. American Gastroenterological Association Institute Technical Review on the Role of Elastography in Chronic Liver Diseases. Gastroenterology 2017; 152:1544-1577. [PMID: 28442120 DOI: 10.1053/j.gastro.2017.03.016] [Citation(s) in RCA: 204] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Chronic liver diseases (CLDs), due to chronic hepatitis C; hepatitis B; nonalcoholic fatty liver diseases (NAFLD); and alcoholic liver disease, are a leading cause of morbidity and mortality globally. Early identification of patients with cirrhosis at high risk of progression to liver-related complications may facilitate timely care and improve outcomes. With risks and misclassification associated with invasive tests, such as liver biopsy, noninvasive imaging modalities for liver fibrosis assessment have gained popularity. Therefore, the American Gastroenterological Association prioritized clinical guidelines on the role of elastography in CLDs, focusing on vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE). To inform these clinical guidelines, the current technical review was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for diagnostic accuracy studies. This technical review addresses focused questions related to: (1) comparative diagnostic performance of VCTE and MRE relative to nonproprietary, serum-based fibrosis markers for detection of cirrhosis in patients with hepatitis C virus (HCV), hepatitis B virus (HBV), NAFLD, and alcoholic liver diseases; (2) performance of specific VCTE-defined liver stiffness cutoffs as a test replacement strategy (to replace liver biopsy) in making key decisions in the management of patients with CLDs; and (3) performance of specific VCTE-defined liver stiffness cutoffs as a triage test to identify patients with low likelihood of harboring high-risk esophageal varices (EVs) or having clinically significant portal hypertension (for presurgical risk stratification). This technical review does not address performance of other noninvasive modalities for assessing fibrosis (eg, acoustic radiation force pulse imaging or shear wave elastography) or steatosis (controlled attenuation parameter or magnetic resonance imaging-estimated proton density fat fraction).
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - Andrew J Muir
- Division of Gastroenterology, Duke University School of Medicine, Durham, North Carolina
| | | | - Yngve T Falck-Ytter
- Division of Gastroenterology and Hepatology, Cleveland VA Medical Center and University Hospitals, Case Western Reserve University, Cleveland, Ohio
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Bailey H, Nizova N, Martsynovska V, Volokha A, Malyuta R, Cortina-Borja M, Thorne C. HCV co-infection and markers of liver injury and fibrosis among HIV-positive childbearing women in Ukraine: results from a cohort study. BMC Infect Dis 2016; 16:755. [PMID: 27955711 PMCID: PMC5153905 DOI: 10.1186/s12879-016-2089-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 12/03/2016] [Indexed: 12/18/2022] Open
Abstract
Background Ukraine’s injecting drug use-driven HIV epidemic is among the most severe in Europe with high burden of HCV co-infection. HIV/HCV co-infected individuals are at elevated risk of HCV-related morbidity, but little is known about burden of liver disease and associated factors in the HIV-positive population in Ukraine, particularly among women. Methods Characteristics of 2050 HIV-positive women enrolled into the Ukrainian Study of HIV-infected Childbearing Women were described by HCV serostatus. Aspartate transaminase (AST) to platelet ratio (APRI) and FIB-4 scores were calculated and exact logistic regression models fitted to investigate factors associated with significant fibrosis (APRI >1.5) among 762 women with an APRI score available. Results Of 2050 HIV-positive women (median age 27.7 years, IQR 24.6-31.3), 33% were HCV co-infected (79% of those with a history of injecting drug use vs 23% without) and 17% HBsAg positive. A quarter were on antiretroviral therapy at postnatal cohort enrolment. 1% of the HIV/HCV co-infected group had ever received treatment for HCV. Overall, 24% had an alanine aminotransferase level >41 U/L and 34% an elevated AST (53% and 61% among HIV/HCV co-infected). Prevalence of significant fibrosis was 4.5%; 2.5% among 445 HIV mono-infected and 12.3% among 171 HIV/HCV co-infected women. 1.2% had a FIB-4 score >3.25 indicating advanced fibrosis. HCV RNA testing in a sub-group of 56 HIV/HCV co-infected women indicated a likely spontaneous clearance rate of 18% and predominance of HCV genotype 1, with one-third having genotype 3 infection. Factors associated with significant fibrosis were HCV co-infection (AOR 2.53 95%CI 1.03-6.23), history of injecting drug use (AOR 3.51 95%CI 1.39-8.89), WHO stage 3-4 HIV disease (AOR 3.47 95%CI 1.51-7.99 vs stage 1-2 HIV disease) and not being on combination antiretroviral therapy (AOR 3.08 95%CI 1.23-7.74), adjusted additionally for HBV co-infection, smoking and age. Conclusions Most HIV/HCV co-infected women had elevated liver enzymes and 12% had significant fibrosis according to APRI. Risk factors for liver fibrosis in this young HIV-positive population include poorly controlled HIV and high burden of HCV. Results highlight the importance of addressing modifiable risk factors and rolling out HCV treatment to improve the health outcomes of this group.
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Affiliation(s)
- Heather Bailey
- Population, Policy and Practice Programme, UCL Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
| | - Nataliya Nizova
- The Public Health Center of the Ministry of Health of Ukraine, Kyiv, Ukraine
| | - Violeta Martsynovska
- The Public Health Center of the Ministry of Health of Ukraine, Kyiv, Ukraine.,Institute of Epidemiology and Infectious Diseases of NAMS, Kiev, Ukraine
| | - Alla Volokha
- Shupyk National Medical Academy of Postgraduate Education, Kiev, Ukraine
| | - Ruslan Malyuta
- Perinatal Prevention of AIDS Initiative, Odessa, Ukraine
| | - Mario Cortina-Borja
- Population, Policy and Practice Programme, UCL Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK
| | - Claire Thorne
- Population, Policy and Practice Programme, UCL Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK
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Njei B, McCarty TR, Luk J, Ewelukwa O, Ditah I, Lim JK. Use of transient elastography in patients with HIV-HCV coinfection: A systematic review and meta-analysis. J Gastroenterol Hepatol 2016; 31:1684-1693. [PMID: 26952020 PMCID: PMC5014713 DOI: 10.1111/jgh.13337] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Revised: 02/23/2016] [Accepted: 02/28/2016] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND AIM Patients with HIV-hepatitis C virus (HCV) coinfection progress towards liver fibrosis and cirrhosis more rapidly compared with HCV mono-infected individuals. This necessitates an accurate assessment of liver stiffness with transient elastography to guide treatment. METHODS Searches of PubMed, EMBASE, Web of Science, and the Cochrane Library databases were performed through January 2016 to assess the diagnostic accuracy of transient elastography for liver stiffness in the HIV-HCV population. Included studies were analyzed according to the Cochrane DTA Working Group methodology. Bivariate and hierarchical models were used to compute pooled sensitivity and specificity. Positive and negative likelihood ratios were also determined. A Fagan nomogram was constructed. Meta-regression analysis was performed with assessment of publication bias using Deeks' funnel plot asymmetry testing. RESULTS A total of six studies (n = 756) met the inclusion criteria. The diagnostic accuracy of elastography for the diagnosis of moderate (≥F2) fibrosis was 88% (95% confidence interval [CI], 0.85-0.90). The pooled sensitivity and specificity of moderate fibrosis was 97% (95% CI, 0.82-0.91) and 64% (95% CI, 0.45-0.79), respectively. The diagnostic accuracy of elastography for the assessment of cirrhosis was 94% (95% CI, 0.91-0.95). The pooled sensitivity and specificity for cirrhosis was 90% (95% CI, 0.74-0.97) and 87% (95% CI, 0.80-0.92), respectively. Meta-regression analysis demonstrated that CD4 cell count did not impact diagnostic accuracy of elastography. CONCLUSIONS Transient elastography is a noninvasive imaging modality with excellent ability to assess for cirrhosis in patients with HIV-HCV coinfection.
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Affiliation(s)
- Basile Njei
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA.
- Investigative Medicine Program, Yale Center of Clinical Investigation, New Haven, CT, USA.
| | - Thomas R McCarty
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Jeffrey Luk
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Oforbuike Ewelukwa
- Gastroenterology and Hepatology, University of Florida, Gainesville, FL, USA
| | - Ivo Ditah
- Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Joseph K Lim
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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Hull M, Shafran S, Wong A, Tseng A, Giguère P, Barrett L, Haider S, Conway B, Klein M, Cooper C. CIHR Canadian HIV Trials Network Coinfection and Concurrent Diseases Core Research Group: 2016 Updated Canadian HIV/Hepatitis C Adult Guidelines for Management and Treatment. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2016; 2016:4385643. [PMID: 27471521 PMCID: PMC4947683 DOI: 10.1155/2016/4385643] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Accepted: 12/15/2015] [Indexed: 12/13/2022]
Abstract
Background. Hepatitis C virus (HCV) coinfection occurs in 20-30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Purpose. To update national standards for management of HCV-HIV coinfected adults in the Canadian context with evolving evidence for and accessibility of effective and tolerable DAA therapies. The document addresses patient workup and treatment preparation, antiviral recommendations overall and in specific populations, and drug-drug interactions. Methods. A standing working group with HIV-HCV expertise was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published HCV antiviral data and update Canadian HIV-HCV Coinfection Guidelines. Results. The gap in sustained virologic response between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All coinfected individuals should be assessed for interferon-free, Direct Acting Antiviral HCV therapy. Regimens vary in content, duration, and success based largely on genotype. Reimbursement restrictions forcing the use of pegylated interferon is not acceptable if optimal patient care is to be provided. Discussion. Recommendations may not supersede individual clinical judgement. Treatment advances published since December 2015 are not considered in this document.
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Affiliation(s)
- Mark Hull
- British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia, Vancouver, BC, Canada V6T 1Z4
| | | | - Alex Wong
- Regina Qu'Appelle Health Region, Regina, SK, Canada S4P 1E2
| | - Alice Tseng
- Toronto General Hospital, Toronto, ON, Canada M5G 2C4
| | | | - Lisa Barrett
- Dalhousie University, Halifax, NS, Canada B3H 4R2
| | | | - Brian Conway
- Vancouver Infectious Diseases Centre, Vancouver, BC, Canada V6Z 2C7
| | | | - Curtis Cooper
- The Ottawa Hospital, General Campus, G12, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6
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Lu Q, Lu C, Li J, Ling W, Qi X, He D, Liu J, Wen T, Wu H, Zhu H, Luo Y. Stiffness Value and Serum Biomarkers in Liver Fibrosis Staging: Study in Large Surgical Specimens in Patients with Chronic Hepatitis B. Radiology 2016; 280:290-299. [PMID: 26885682 DOI: 10.1148/radiol.2016151229] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Purpose To investigate the capabilities of stiffness value and serum biomarkers in the staging of liver fibrosis in patients with chronic hepatitis B (CHB), with pathologic findings in large surgical specimens serving as the reference standard. Materials and Methods This study was approved by the institutional review board, and informed consent was obtained from all patients. Liver stiffness (determined by means of ultrasonography-based elastography point quantification), aspartate aminotransferase-platelet ratio index (APRI), and fibrosis index (based on the four-factor Fibrosis-4 [FIB-4] calculation) were obtained in 386 patients with CHB. With pathologic fibrosis stages in large surgical specimens as the reference standard, capabilities and cutoffs of stiffness and serum biomarkers were first investigated in a cohort of 284 patients and then validated in an independent cohort of 102 patients by means of area under the receiver operating characteristic curve (AUC) analysis. Results Liver stiffness demonstrated significantly stronger correlation with fibrosis stages than did APRI and FIB-4 (r = 0.738 vs r = 0.477 vs r = 0.427, respectively; P < .05 for all). In the development cohort, liver stiffness had significantly higher AUCs in identifying fibrosis of stage 1 or higher, stage 2 or higher, stage 3 or higher, and stage 4 or higher (0.97, 0.96, 0.91, and 0.87, respectively) than APRI (0.89, 0.84, 0.73, and 0.74, respectively) and FIB-4 (0.82, 0.79, 0.70, and 0.72, respectively). In the validation cohort, liver stiffness was validated as showing significantly higher AUCs in identifying fibrosis of stage 1 or higher, stage 2 or higher, stage 3 or higher, and stage 4 or higher (0.99, 0.95, 0.89, and 0.88, respectively) than APRI (0.83, 0.76, 0.78, and 0.68, respectively) and FIB-4 (0.76, 0.69, 0.75, and 0.67, respectively). Conclusion Liver stiffness demonstrated considerable capability in identifying each stage of liver fibrosis in patients with CHB, whereas serum biomarkers showed limited capabilities. (©) RSNA, 2016 Online supplemental material is available for this article.
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Affiliation(s)
- Qiang Lu
- From the Departments of Ultrasound (Q.L., J. Li, W.L., X.Q., Y.L.), Pathology (C.L., D.H., J. Liu), and Hepatobiliary Surgery (T.W., H.W.), West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China; and Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China (H.Z.)
| | - Changli Lu
- From the Departments of Ultrasound (Q.L., J. Li, W.L., X.Q., Y.L.), Pathology (C.L., D.H., J. Liu), and Hepatobiliary Surgery (T.W., H.W.), West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China; and Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China (H.Z.)
| | - Jiawu Li
- From the Departments of Ultrasound (Q.L., J. Li, W.L., X.Q., Y.L.), Pathology (C.L., D.H., J. Liu), and Hepatobiliary Surgery (T.W., H.W.), West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China; and Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China (H.Z.)
| | - Wenwu Ling
- From the Departments of Ultrasound (Q.L., J. Li, W.L., X.Q., Y.L.), Pathology (C.L., D.H., J. Liu), and Hepatobiliary Surgery (T.W., H.W.), West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China; and Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China (H.Z.)
| | - Xiaoying Qi
- From the Departments of Ultrasound (Q.L., J. Li, W.L., X.Q., Y.L.), Pathology (C.L., D.H., J. Liu), and Hepatobiliary Surgery (T.W., H.W.), West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China; and Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China (H.Z.)
| | - Du He
- From the Departments of Ultrasound (Q.L., J. Li, W.L., X.Q., Y.L.), Pathology (C.L., D.H., J. Liu), and Hepatobiliary Surgery (T.W., H.W.), West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China; and Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China (H.Z.)
| | - Jianping Liu
- From the Departments of Ultrasound (Q.L., J. Li, W.L., X.Q., Y.L.), Pathology (C.L., D.H., J. Liu), and Hepatobiliary Surgery (T.W., H.W.), West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China; and Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China (H.Z.)
| | - Tianfu Wen
- From the Departments of Ultrasound (Q.L., J. Li, W.L., X.Q., Y.L.), Pathology (C.L., D.H., J. Liu), and Hepatobiliary Surgery (T.W., H.W.), West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China; and Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China (H.Z.)
| | - Hong Wu
- From the Departments of Ultrasound (Q.L., J. Li, W.L., X.Q., Y.L.), Pathology (C.L., D.H., J. Liu), and Hepatobiliary Surgery (T.W., H.W.), West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China; and Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China (H.Z.)
| | - Hongguang Zhu
- From the Departments of Ultrasound (Q.L., J. Li, W.L., X.Q., Y.L.), Pathology (C.L., D.H., J. Liu), and Hepatobiliary Surgery (T.W., H.W.), West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China; and Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China (H.Z.)
| | - Yan Luo
- From the Departments of Ultrasound (Q.L., J. Li, W.L., X.Q., Y.L.), Pathology (C.L., D.H., J. Liu), and Hepatobiliary Surgery (T.W., H.W.), West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China; and Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China (H.Z.)
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Pan Y, Muheremu A, Wu X, Liu J. Relationship between platelet parameters and hepatic pathology in patients with chronic hepatitis B infection - a retrospective cohort study of 677 patients. J Int Med Res 2016; 44:779-86. [PMID: 27329384 PMCID: PMC5536628 DOI: 10.1177/0300060516650076] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 04/25/2016] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE A retrospective study to determine the relationships between platelet parameters and inflammation and fibrosis of the liver in patients with chronic hepatitis B virus infection (CHB). METHODS Patients with liver biopsy-confirmed CHB were included in the study. Liver fibrosis and inflammation were assessed by histopathology of biopsied liver tissue. Platelet count (PLT), platelet distribution width (PDW) and mean platelet volume (MPV) were determined as part of routine blood tests. The relationship between inflammation and fibrosis and platelet parameters were analysed by multiple linear regression. RESULTS The study included 677 patients. PLT and PDW accounted for 20.5% of liver inflammation. PLT and PDW accounted for 18.4% of liver fibrosis. CONCLUSION Platelet parameters can provide valuable information for the assessment of hepatic inflammation and fibrosis.
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Affiliation(s)
- Ye Pan
- Department of Infectious Diseases, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | | | - Xiaolu Wu
- Department of Infectious Diseases, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Jiajun Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Xiamen University, Xiamen, China
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Chin JL, Pavlides M, Moolla A, Ryan JD. Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy? Front Pharmacol 2016; 7:159. [PMID: 27378924 PMCID: PMC4913110 DOI: 10.3389/fphar.2016.00159] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Accepted: 05/31/2016] [Indexed: 12/13/2022] Open
Abstract
Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care.
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Affiliation(s)
- Jun L Chin
- School of Medicine and Medical Science, University College Dublin Dublin, Ireland
| | - Michael Pavlides
- Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford Oxford, UK
| | - Ahmad Moolla
- Radcliffe Department of Medicine, University of Oxford Oxford, UK
| | - John D Ryan
- Translational Gastroenterology Unit, University of Oxford Oxford, UK
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Gjærde LI, Shepherd L, Jablonowska E, Lazzarin A, Rougemont M, Darling K, Battegay M, Braun D, Martel-Laferriere V, Lundgren JD, Rockstroh JK, Gill J, Rauch A, Mocroft A, Klein MB, Peters L. Trends in Incidences and Risk Factors for Hepatocellular Carcinoma and Other Liver Events in HIV and Hepatitis C Virus-coinfected Individuals From 2001 to 2014: A Multicohort Study. Clin Infect Dis 2016; 63:821-829. [PMID: 27307505 DOI: 10.1093/cid/ciw380] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Accepted: 05/25/2016] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND While liver-related deaths in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected individuals have declined over the last decade, hepatocellular carcinoma (HCC) may have increased. We describe the epidemiology of HCC and other liver events in a multicohort collaboration of HIV/HCV-coinfected individuals. METHODS We studied HCV antibody-positive adults with HIV in the EuroSIDA study, the Southern Alberta Clinic Cohort, the Canadian Co-infection Cohort, and the Swiss HIV Cohort study from 2001 to 2014. We calculated the incidence of HCC and other liver events (defined as liver-related deaths or decompensations, excluding HCC) and used Poisson regression to estimate incidence rate ratios. RESULTS Our study comprised 7229 HIV/HCV-coinfected individuals (68% male, 90% white). During follow-up, 72 cases of HCC and 375 other liver events occurred, yielding incidence rates of 1.6 (95% confidence interval [CI], 1.3, 2.0) and 8.6 (95% CI, 7.8, 9.5) cases per 1000 person-years of follow-up, respectively. The rate of HCC increased 11% per calendar year (95% CI, 4%, 19%) and decreased 4% for other liver events (95% CI, 2%, 7%), but only the latter remained statistically significant after adjustment for potential confounders. Older age, cirrhosis, and low current CD4 cell count were associated with a higher incidence of both HCC and other liver events. CONCLUSIONS In HIV/HCV-coinfected individuals, the crude incidence of HCC increased from 2001 to 2014, while other liver events declined. Individuals with cirrhosis or low current CD4 cell count are at highest risk of developing HCC or other liver events.
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Affiliation(s)
- Lars I Gjærde
- Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Leah Shepherd
- Department of Infection and Population Health, University College London, United Kingdom
| | - Elzbieta Jablonowska
- Department of Infectious Diseases and Hepatology, Medical University of Lodz, Poland
| | - Adriano Lazzarin
- Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy
| | | | | | - Manuel Battegay
- Divisions of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel
| | - Dominique Braun
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland
| | - Valerie Martel-Laferriere
- Department of Microbiology and Infectious Diseases, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Canada
| | - Jens D Lundgren
- Centre for Health & Infectious Disease Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark
| | | | - John Gill
- Department of Medicine, University of Calgary, Alberta, Canada
| | - Andri Rauch
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Amanda Mocroft
- Department of Infection and Population Health, University College London, United Kingdom
| | - Marina B Klein
- Department of Medicine, Chronic Viral Illness Service, McGill University Health Center, Montreal, Canada
| | - Lars Peters
- Centre for Health & Infectious Disease Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark
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Verlinden W, Bourgeois S, Gigase P, Thienpont C, Vonghia L, Vanwolleghem T, Michielsen P, Francque S. Liver Fibrosis Evaluation Using Real-time Shear Wave Elastography in Hepatitis C-Monoinfected and Human Immunodeficiency Virus/Hepatitis C-Coinfected Patients. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2016; 35:1299-1308. [PMID: 27151906 DOI: 10.7863/ultra.15.08066] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 09/30/2015] [Indexed: 06/05/2023]
Abstract
OBJECTIVES A few studies have evaluated real-time shear wave elastography (SWE) for assessing liver fibrosis by measuring liver stiffness in patients with chronic hepatitis C virus (HCV) infection, but they excluded human immunodeficiency virus/HCV-coinfected patients. We investigated the diagnostic performance of liver stiffness measured by SWE as a noninvasive predictor of liver fibrosis in HCV using liver biopsy as a reference standard, including monoinfected and coinfected patients. METHODS We measured liver stiffness in patients with HCV undergoing liver biopsy (METAVIR fibrosis staging). RESULTS Eighty patients (53 monoinfected and 27 coinfected) were included. There was a significant correlation between liver stiffness and fibrosis stage (ρ = 0.685; P < .001). Areas under the receiver operating characteristic curve were 0.841, 0.879, and 0.975 when comparing fibrosis stages F0-F1 versus F2-F4, F0-F2 versus F3-F4, and F0-F3 versus F4, respectively. Suggested cutoff values were 8.5 kPa for F2, 10.4 kPa for F3, and 11.3 kPa for F4, with sensitivity and specificity of 81% and 84%, 81% and 95%, and 100% and 90%. There was no significant difference between the liver stiffness of monoinfected and coinfected patients (P = .453). When combining SWE with the fibrosis-4 score, accuracy increased from 82% to 88% and from 88% to 96%, with incongruent results of 26% and 29%, for F0-F1 versus F2-F4 and F0-F2 versus F3-F4. CONCLUSIONS Shear wave elastography of the liver is an effective noninvasive predictor of liver fibrosis in patients with HCV. There was no significant difference between monoinfected and coinfected patients; hence, the same cutoff values can be used for both groups. Combination of SWE with the fibrosis-4 score leads to higher accuracy, although at the expense of inconclusive results in some patients.
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Affiliation(s)
- Wim Verlinden
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, BelgiumLaboratory of Experimental Medicine and Pediatrics, University of Antwerp, Edegem, Belgium
| | - Stefan Bourgeois
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, BelgiumDepartment of Gastroenterology, Ziekenhuisnetwerk Antwerpen Stuivenberg Hospital, Antwerp, Belgium
| | - Pierre Gigase
- Department of Gastroenterology, Ziekenhuisnetwerk Antwerpen Stuivenberg Hospital, Antwerp, Belgium
| | - Clara Thienpont
- Department of Gastroenterology, Ziekenhuisnetwerk Antwerpen Stuivenberg Hospital, Antwerp, Belgium
| | - Luisa Vonghia
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium
| | - Thomas Vanwolleghem
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, BelgiumLaboratory of Experimental Medicine and Pediatrics, University of Antwerp, Edegem, Belgium
| | - Peter Michielsen
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium
| | - Sven Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, BelgiumLaboratory of Experimental Medicine and Pediatrics, University of Antwerp, Edegem, Belgium
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Enhanced liver fibrosis marker as a noninvasive predictor of mortality in HIV/hepatitis C virus-coinfected women from a multicenter study of women with or at risk for HIV. AIDS 2016; 30:723-9. [PMID: 26595542 DOI: 10.1097/qad.0000000000000975] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Coinfection with hepatitis C virus (HCV) is a major cause of morbidity and mortality among individuals with HIV. Our objective was to assess the prognostic performance of noninvasive measures of liver fibrosis in predicting all-cause mortality in women with HIV/HCV coinfection. DESIGN We studied HCV/HIV coinfected women enrolled in the prospective, multicenter Women's Interagency HIV Study. Aspartate aminotransferase to platelet ratio and FIB-4 were used to identify women without fibrosis at all visits and women who progressed to severe fibrosis. METHODS Enhanced liver fibrosis (ELF), which utilizes direct measures of fibrosis, hyaluronic acid, procollagen III aminoterminal peptide and tissue inhibitor of matrix metalloproteinase was performed. RESULTS Included were 381 women with 2296 ELF measurements, with mean follow-up 8.3 ± 3.3 years. There were 134 deaths (60% with severe liver fibrosis). Receiver operator characteristic curves at fixed time windows prior to death or at end of follow-up showed that ELF was best at predicting mortality when tested within a year of death (area under the curve for ELF 0.85 vs. APRI 0.69, P < 0.0001 and vs. FIB-4 0.75, P = 0.0036); and 1-3 years prior (ELF 0.71 vs. APRI 0.61, P = 0.005 and vs. FIB-4 0.65, P = 0.06). Use of all three measures did not improve on ELF alone. In multivariate logistic regression models controlling for CD4 cell count, HIV viral load, antiretroviral use and age, ELF continued to perform better than APRI and FIB-4. CONCLUSION ELF predicted all-cause mortality and was superior to APRI and FIB-4 in HIV/HCV coinfected women.
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Frankis J, Goodall L, Clutterbuck D, Abubakari AR, Flowers P. Regular STI testing amongst men who have sex with men and use social media is suboptimal - a cross-sectional study. Int J STD AIDS 2016; 28:573-583. [PMID: 26945592 DOI: 10.1177/0956462416636780] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Sexually transmitted infections (STIs) disproportionately affect men who have sex with men, with marked increases in most STIs in recent years. These are likely underpinned by coterminous increases in behavioural risks which have coincided with the development of Internet and geospatial sociosexual networking. Current guidelines advocate regular, annual sexually transmitted infection testing amongst sexually active men who have sex with men (MSM), as opposed to symptom-driven testing. This paper explores sexually transmitted infection testing regularity amongst MSM who use social and sociosexual media. Data were collected from 2668 men in Scotland, Wales, Northern Ireland and the Republic of Ireland, recruited via social and gay sociosexual media. Only one-third of participants report regular (yearly or more frequent) STI testing, despite relatively high levels of male sex partners, condomless anal intercourse and high-risk unprotected anal intercourse. The following variables were associated with regular STI testing; being more 'out' (adjusted odds ratio = 1.79; confidence interval = 1.20-2.68), HIV-positive (adjusted odds ratio = 14.11; confidence interval = 7.03-28.32); reporting ≥10 male sex partners (adjusted odds ratio = 2.15; confidence interval = 1.47-3.14) or regular HIV testing (adjusted odds ratio = 48.44; confidence interval = 28.27-83.01). Men reporting long-term sickness absence from work/carers (adjusted odds ratio = 0.03; confidence interval = 0.00-0.48) and men aged ≤25 years (adjusted odds ratio = 0.36; 95% confidence interval = 0.19-0.69) were less likely to test regularly for STIs. As such, we identify a complex interplay of social, health and behavioural factors that each contribute to men's STI testing behaviours. In concert, these data suggest that the syndemics placing men at elevated risk may also mitigate against access to testing and prevention services. Moreover, successful reduction of STI transmission amongst MSM will necessitate a comprehensive range of approaches which address these multiple interrelated factors that underpin MSM's STI testing.
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Affiliation(s)
- Jamie Frankis
- 1 School of Health and Life Sciences, Glasgow Caledonian University, Glasgow
| | - Lisa Goodall
- 2 Cobridge Sexual Health Centre, Church Terrace, Cobridge, Stoke on Trent
| | | | - Abdul-Razak Abubakari
- 4 School of Health and Life Sciences, GCU London, Glasgow Caledonian University, Glasgow
| | - Paul Flowers
- 1 School of Health and Life Sciences, Glasgow Caledonian University, Glasgow
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Chang PE, Goh GBB, Ngu JH, Tan HK, Tan CK. Clinical applications, limitations and future role of transient elastography in the management of liver disease. World J Gastrointest Pharmacol Ther 2016; 7:91-106. [PMID: 26855815 PMCID: PMC4734958 DOI: 10.4292/wjgpt.v7.i1.91] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 09/05/2015] [Accepted: 10/27/2015] [Indexed: 02/06/2023] Open
Abstract
Transient elastography (TE) is a reliable tool for the non-invasive assessment of liver fibrosis in routine clinical practice. TE is currently approved for use in Europe, Asia and the United States. The widespread adoption of this technology is certain to increase the use of TE worldwide. Although TE has been well validated in chronic viral hepatitis, its clinical role in other liver diseases remains less clear. The advent of new treatment for chronic hepatitis C and emerging prevalence of non-alcoholic steatohepatitis raises new questions on the role of TE in current clinical practice. This review aims to examine the clinical applications, limitations and future role of TE in current clinical practice in light of the changing epidemiology of liver diseases and new clinical management paradigms. In current clinical practice, TE is the most accurate non-invasive method for diagnosis of liver cirrhosis. TE is useful to rule out fibrosis and cirrhosis but does not have sufficient accuracy to discern between various stages of fibrosis. The clinical role of TE has evolved from cross-sectional point-in-time assessment of fibrosis and cirrhosis to the more relevant role of prediction of vital clinical end-points. This provides clinicians with the ability to modify treatment strategies based on the information provided by TE. TE has evolved over the past decade to become an essential tool to assist the clinician in the management of chronic liver disease.
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Kliemann DA, Wolff FH, Tovo CV, Alencastro PR, Ikeda MLR, Brandão ABM, Barcellos N, Fuchs SC. Biochemical non-invasive assessment of liver fibrosis cannot replace biopsy in HIV-HCV coinfected patients. Ann Hepatol 2016; 15:27-32. [PMID: 26626637 DOI: 10.5604/16652681.1184197] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND RATIONALE The liver biopsy has been considered the gold standard for the diagnosis and quantification of fibrosis. However, this method presents limitations. In addition, the non-invasive evaluation of liver fibrosis is a challenge. The aim of this study was to validate the fibrosis cirrhosis index (FCI) index in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, and compare to AST/ALT ratio (AAR), AST to platelet ratio index (APRI) and FIB-4 scores, as a tool for the assessment of liver fibrosis in coinfected patients. MATERIAL AND METHODS Retrospective cross sectional study including 92 HIV-HCV coinfected patients evaluated in two reference centers for HIV treatment in the Public Health System in Southern Brazil. Patients who underwent liver biopsy for any indication and had concomitant laboratory data in the 3 months prior to liver biopsy, to allow the calculation of studied noninvasive markers (AAR, APRI, FIB-4 and FCI) were included. RESULTS APRI < 0.5 presents the higher specificity to detect no or minimal fibrosis, whereas APRI > 1.5 presents the best negative predictive value and FCI > 1.25 the best specificity to detect significant fibrosis. The values of noninvasive markers for each Metavir fibrosis stage showed statistically significant differences only for APRI. In conclusion, until better noninvasive markers for liver fibrosis are developed and validated for HIV-HCV coinfected patients, noninvasive serum markers should be used carefully in this population.
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Affiliation(s)
- Dimas A Kliemann
- Post-Graduate Program: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Fernando H Wolff
- Postgraduate Program Studies in Epidemiology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Cristiane V Tovo
- Post-Graduate Program: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | | | - Maria L R Ikeda
- Therapeutic Attention Service, Sanatorio Partenon Hospital, Brazil
| | - Ajácio B M Brandão
- Post-Graduate Program: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Nêmora Barcellos
- Therapeutic Attention Service, Sanatorio Partenon Hospital, Brazil
| | - Sandra C Fuchs
- Postgraduate Program Studies in Epidemiology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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Scheiner B, Mandorfer M, Schwabl P, Payer BA, Bucsics T, Bota S, Aichelburg MC, Grabmeier-Pfistershammer K, Stättermayer A, Ferenci P, Trauner M, Peck-Radosavljevic M, Reiberger T. The Impact of PNPLA3 rs738409 SNP on Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection. PLoS One 2015; 10:e0143429. [PMID: 26599080 PMCID: PMC4658167 DOI: 10.1371/journal.pone.0143429] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Accepted: 11/04/2015] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Faster fibrosis progression and hepatic steatosis are hallmarks of HIV/HCV coinfection. A single nucleotide polymorphism (SNP) of the PNPLA3-gene is associated with development of non-alcoholic steatohepatitis and a worse outcome in alcoholic liver disease. However, the role of PNPLA3 rs738409 SNP on liver fibrosis and steatosis, portal hypertension, and virological response in HIV/HCV coinfection remains unclear. METHODS In this cross-sectional study PNPLA3 (rs738409) and IL28B (rs12979860) SNPs were determined in 177 HIV/HCV coinfected patients. Liver fibrosis and steatosis-staged by liver biopsy and transient elastography using the Controlled Attenuation Parameter (CAP)-and portal hypertension (hepatic venous pressure gradient, HVPG) were compared across PNPLA3 genotypes. RESULTS 75 (42.4%) patients tested positive for a PNPLA3 minor/major risk allele (G/C:66; G/G:9) showed comparable fibrosis stages (median F2 vs. F2; p = 0.292) and similar amounts of hepatic steatosis (CAP: 203.5 ± 41.9 vs. 215.5 ± 59.7 dB/m; p = 0.563) as compared to patients without a PNPLA3 risk allele. Advanced liver fibrosis was neither associated with PNPLA3 (p = 0.253) nor IL28B-genotype (p = 0.628), but with HCV-GT3 (p = 0.003), higher BMI (p = 0.008) and higher age (p = 0.007). Fibrosis progression rate (0.27 ± 0.41 vs. 0.20 ± 0.26 units/year; p = 0.984) and HVPG (3.9 ± 2.6 vs. 4.4 ± 3.0 mmHg; p = 0.472) were similar in patients with and without PNPLA3 risk alleles. SVR rates to PEGIFN/RBV therapy were similar across PNPLA3 genotypes. CONCLUSIONS The presence of a PNPLA3 risk allele had no independent impact on liver disease or virological response rates to PEGIFN/RBV therapy in our cohort of HIV/HCV coinfected patients.
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Affiliation(s)
- Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Berit Anna Payer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Simona Bota
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Maximilian C. Aichelburg
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
- Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Katharina Grabmeier-Pfistershammer
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
- Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Albert Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Peter Ferenci
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
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Sagnelli C, Martini S, Pisaturo M, Pasquale G, Macera M, Zampino R, Coppola N, Sagnelli E. Liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfection: Diagnostic methods and clinical impact. World J Hepatol 2015; 7:2510-2521. [PMID: 26523204 PMCID: PMC4621465 DOI: 10.4254/wjh.v7.i24.2510] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 07/18/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Several non-invasive surrogate methods have recently challenged the main role of liver biopsy in assessing liver fibrosis in hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients, applied to avoid the well-known side effects of liver puncture. Serological tests involve the determination of biochemical markers of synthesis or degradation of fibrosis, tests not readily available in clinical practice, or combinations of routine tests used in chronic hepatitis and HIV/HCV coinfection. Several radiologic techniques have also been proposed, some of which commonly used in clinical practice. The studies performed to compare the prognostic value of non-invasive surrogate methods with that of the degree of liver fibrosis assessed on liver tissue have not as yet provided conclusive results. Each surrogate technique has shown some limitations, including the risk of over- or under-estimating the extent of liver fibrosis. The current knowledge on liver fibrosis in HIV/HCV-coinfected patients will be summarized in this review article, which is addressed in particular to physicians involved in this setting in their clinical practice.
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Affiliation(s)
- Caterina Sagnelli
- Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy
| | - Salvatore Martini
- Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy
| | - Mariantonietta Pisaturo
- Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy
| | - Giuseppe Pasquale
- Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy
| | - Margherita Macera
- Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy
| | - Rosa Zampino
- Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy
| | - Nicola Coppola
- Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy
| | - Evangelista Sagnelli
- Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara, Second University of Naples, 80131 Naples, Italy
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Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy. PLoS One 2015; 10:e0138838. [PMID: 26418061 PMCID: PMC4587859 DOI: 10.1371/journal.pone.0138838] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Accepted: 09/03/2015] [Indexed: 12/15/2022] Open
Abstract
Objectives To evaluate the diagnostic performance of seven non-invasive tests (NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients. Methods Transient elastography (TE) and six blood tests were compared to histopathological fibrosis stage (METAVIR). Participants were followed over three years with NITs at yearly intervals. Results Area under the receiver operating characteristic curve (AUROC) for significant fibrosis (> = F2) in 105 participants was highest for TE (0.85), followed by FIB-4 (0.77), ELF-Test (0.77), APRI (0.76), Fibrotest (0.75), hyaluronic acid (0.70), and Hepascore (0.68). AUROC for cirrhosis (F4) was 0.97 for TE followed by FIB-4 (0.91), APRI (0.89), Fibrotest (0.84), Hepascore (0.82), ELF-Test (0.82), and hyaluronic acid (0.79). A three year follow-up was completed by 87 participants, all on antiretroviral therapy and in 20 patients who completed HCV treatment (9 with sustained virologic response). TE, APRI and Fibrotest did not significantly change during follow-up. There was weak evidence for an increase of FIB-4 (mean increase: 0.22, p = 0.07). 42 participants had a second liver biopsy: Among 38 participants with F0-F3 at baseline, 10 were progessors (1-stage increase in fibrosis, 8 participants; 2-stage, 1; 3-stage, 1). Among progressors, mean increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results did not change over 3 years. Conclusion TE was the best NIT for liver fibrosis staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good as more expensive tests. NITs did not change significantly during a follow-up of three years, suggesting slow liver disease progression in a majority of HIV/HCV co-infected persons on antiretroviral therapy.
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EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015; 63:237-64. [PMID: 25911335 DOI: 10.1016/j.jhep.2015.04.006] [Citation(s) in RCA: 1317] [Impact Index Per Article: 131.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Accepted: 04/09/2015] [Indexed: 02/06/2023]
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Kassaye S, Li Y, Huhn G, Peters MG, French AL, Tien PC, Luxon B, Plankey MW. Direct and Indirect Serum Markers of Liver Fibrosis Compared with Transient Elastography among Women in the Women's Interagency HIV Study. JOURNAL OF AIDS & CLINICAL RESEARCH 2015; 6:446. [PMID: 26251759 PMCID: PMC4524652 DOI: 10.4172/2155-6113.1000446] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The aim of this study was to determine the test characteristics of direct and indirect biomarkers for liver fibrosis compared with transient elastography (TE) among a group of human immunodeficiency virus (HIV)-infected and uninfected women with or without Hepatitis C virus (HCV) infection. METHODS Women enrolled in the Women's Interagency HIV Study (WIHS) from Washington DC, San Francisco, and Chicago with a body mass index (BMI)<35 underwent liver stiffness measurement using TE between October, 2010 and September, 2012. Serum samples were tested for hyaluronic acid to calculate the SHASTA and aspartate aminotransferase to platelet ratio index (APRI). Receiver operator characteristics (ROC) of significant liver fibrosis (liver stiffness ≥ 7.1 kPa by TE, correlating with a METAVIR fibrosis score of F2-F4) predicted by SHASTA and APRI were compared. RESULTS Among 308 women, the median age was 48 years, BMI was 25.6, 67% were non-Hispanic black, 27% HCV+, and 78% HIV+. The overall prevalence of significant liver fibrosis was 20%, and among HIV+ women, 22%. Overall, there was no statistically significant difference in the area under ROC curve (AUROC) between SHASTA and APRI relative to significant fibrosis by TE. Among HCV+ women (with or without HIV), the AUROC ranged from 0.70-0.73 for both the SHASTA and APRI compared to TE. Both SHASTA and APRI were associated with significant misclassification with a false negative rate of 33-40% for significant fibrosis compared with TE among women with HCV infection, with or without HIV. CONCLUSION Both the SHASTA and APRI, direct and indirect serum biomarkers of liver fibrosis respectively, are comparable at detection of significant liver fibrosis among women with HCV infection, regardless of HIV status. However, there was a high false negative rate in detection of significant liver fibrosis of up to 40% which is a significant limitation of use of these biomarkers.
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Affiliation(s)
- Seble Kassaye
- Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Ying Li
- Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Gregory Huhn
- CORE Center/Department of Medicine, Stroger Hospital of Cook County, Chicago, Illinois, USA
| | - Marion G Peters
- Department of Medicine, University of California, San Francisco, California, USA
| | - Audrey L French
- CORE Center/Department of Medicine, Stroger Hospital of Cook County, Chicago, Illinois, USA
| | - Phyllis C Tien
- Department of Medicine, University of California, San Francisco, California, USA
- Medical Service, Department of Veterans Affairs Medical Center, San Francisco, California, USA
| | - Bruce Luxon
- Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Michael W Plankey
- Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
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Mandorfer M, Payer BA, Schwabl P, Steiner S, Ferlitsch A, Aichelburg MC, Stättermayer AF, Ferenci P, Obermayer-Pietsch B, Grabmeier-Pfistershammer K, Trauner M, Peck-Radosavljevic M, Reiberger T. Revisiting liver disease progression in HIV/HCV-coinfected patients: the influence of vitamin D, insulin resistance, immune status, IL28B and PNPLA3. Liver Int 2015; 35:876-885. [PMID: 24905495 DOI: 10.1111/liv.12615] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Accepted: 05/22/2014] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS To perform a comprehensive study on independent modulators of liver fibrosis progression and determinants of portal pressure considering immune status, insulin resistance (IR), serum 25-hydroxyvitamin D (25(OH)D) levels, genetic variants of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documented cohort of HIV/hepatitis C-coinfected (HIV/HCV) patients. PATIENTS & METHODS 25(OH)D deficiency (25(OH)DDEF), IR and low CD4(+) T-lymphocyte nadir (lowCD4NAD) were defined as 25(OH)D <20 ng × ml(-1) , HOMA-IR >2 and CD4nadir <200 cells × μl(-1) respectively. Liver fibrosis progression rate (FPR) was calculated as METAVIR F units divided by the number of years since HCV infection. Patients with a FPR > median FPR were assigned to the highFPR group. RESULTS Among 86 HIV/HCV, the median FPR was 0.167 units × years(-1) . While the prevalence of prior alcohol abuse, lowCD4NAD and 25(OH)DDEF was higher among highFPR patients, the prevalence of IR was comparable. The association between 25(OH)DDEF and FPR was confirmed in a subgroup of patients with METAVIR stage F0/F1/F2 in which 25(OH)D levels are not affected by the severity of liver disease. The distribution of IL28B C/C and PNPLA3 non-C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR patients. LowCD4NAD (OR: 2.95; 95% CI: 1.05-8.24; P = 0.039) and 25(OH)DDEF (OR: 5.62; 95% CI: 2.05-15.38; P = 0.001) were independently associated with highFPR and showed an additive effect. Portal pressure correlated with prior alcohol abuse, HCV-genotype 3, CD4(+) nadir and 25(OH)D levels. CONCLUSIONS Two potentially modifiable factors, CD4(+) nadir and 25(OH)D levels, were both independent modulators of liver fibrosis progression and determinants of portal pressure. Further studies are warranted to assess the relevance of PNPLA3 for FPR in HIV/HCV.
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Affiliation(s)
- Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna HIV & Liver Study Group, Vienna, Austria
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Patel K, Wilder J. Fibroscan. Clin Liver Dis (Hoboken) 2014; 4:97-101. [PMID: 30992931 PMCID: PMC6448744 DOI: 10.1002/cld.407] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2013] [Revised: 06/14/2014] [Accepted: 06/20/2014] [Indexed: 02/04/2023] Open
Affiliation(s)
- Keyur Patel
- Duke Clinical Research Institute and Duke University Medical CenterDurhamNC
| | - Julius Wilder
- Duke Clinical Research Institute and Duke University Medical CenterDurhamNC
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Noncommunicable diseases in HIV infection in low- and middle-income countries: gastrointestinal, hepatic, and nutritional aspects. J Acquir Immune Defic Syndr 2014; 67 Suppl 1:S79-86. [PMID: 25117963 DOI: 10.1097/qai.0000000000000260] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The purpose of this review was to outline the interaction between HIV and noncommunicable diseases affecting the gastrointestinal (GI) tract, liver, and nutritional disorders in low- and middle-income countries (LMICs), and to identify research priorities. Noncommunicable GI tract disorders are only moderately influenced by HIV, and peptic ulceration is actually less common. However, the impact of HIV on GI cancers needs further investigation. HIV interacts strongly with environmental enteropathy, exacerbating malabsorption of nutrients and drugs. HIV has 2 major effects on noncommunicable liver disease: drug-induced liver injury and nonalcoholic fatty liver disease (particularly in persons of African genetic descent). The effect of HIV on nutrition was one of the first markers of the epidemic in the 1980s, and HIV continues to have major nutritional consequences. Childhood malnutrition and HIV frequently coexist in some regions, for example, southern Africa, resulting in powerful negative interactions with poorer responses to standard nutritional rehabilitation. HIV and nutritional care need to be better integrated, but many questions on how best to do this remain unanswered. Across the spectrum of GI, hepatic, and nutritional disorders in HIV infection, there is increasing evidence that the microbiome may play an important role in disease pathogenesis, but work in this area, especially in low- and middle-income countries, is in its infancy.
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Mazzocato S, Orsetti E, Gesuita R, Piraccini F, Drenaggi D, Barchiesi F. Comparison of liver fibrosis progression in HIV/HCV co-infected and HCV mono-infected patients by transient elastometry. ACTA ACUST UNITED AC 2014; 46:797-802. [PMID: 25244675 DOI: 10.3109/00365548.2014.952245] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Monitoring of liver fibrosis (LF) is an essential tool for preventing liver-related complications in HIV/HCV co-infected patients. In this study, we compared LF progression by transient elastometry (TE) in 50 HIV/HCV co-infected and 115 HCV mono-infected patients followed in our institution between June 2006 and December 2011. Patients naive to interferon therapy and with at least two measurements of liver stiffness by TE were included. In all, 76% of HIV/HCV co-infected and 75% of HCV mono-infected patients remained in the same stage of LF over time. Conversely, 19% and 15% of HIV/HCV co-infected and HCV mono-infected subjects, respectively, had progression to advanced LF (≥ F3). Our study found a similar proportion of HIV/HCV co-infected and HCV mono-infected patients that developed an advanced LF during the follow-up time considered. Alcohol abuse was the only factor significantly associated with the progression as evidenced by multiple quantile regression analysis.
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Affiliation(s)
- Susanna Mazzocato
- From the Clinica di Malattie Infettive, Università Politecnica delle Marche , Ancona , Italy
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