|
1
|
17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon. Viruses 2022; 14:v14081806. [PMID: 36016428 PMCID: PMC9415988 DOI: 10.3390/v14081806] [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: 07/11/2022] [Revised: 08/10/2022] [Accepted: 08/16/2022] [Indexed: 11/16/2022] Open
Abstract
Background and Aims: Sex hormones are widely recognised to act as protective factors against several viral infections. Specifically, females infected by the hepatitis C virus display higher clearance rates and reduced disease progression than those found in males. Through modulation of particle release and spread, 17β-oestradiol controls HCV’s life cycle. We investigated the mechanism(s) behind oestrogen’s antiviral effect. Methods: We used cell culture-derived hepatitis C virus in in vitro assays to evaluate the effect of 17β-oestradiol on the innate immune response. Host immune responses were evaluated by enumerating gene transcripts via RT-qPCR in cells exposed to oestrogen in the presence or absence of viral infection. Antiviral effects were determined by focus-forming unit assay or HCV RNA quantification. Results: Stimulation of 17β-oestradiol triggers a pre-activated antiviral state in hepatocytes, which can be maintained for several hours after the hormone is removed. This induction results in the elevation of several innate immune genes, such as interferon alpha and beta, tumour necrosis factor, toll-like receptor 3 and interferon regulatory factor 5. We demonstrated that this pre-activation of immune response signalling is not affected by a viral presence, and the antiviral state can be ablated using an interferon-alpha/beta receptor alpha inhibitor. Finally, we proved that the oestrogen-induced stimulation is essential to generate an antiviral microenvironment mediated by activation of type I interferons. Conclusion: Resulting in viral control and suppression, 17β-oestradiol induces an interferon-mediated antiviral state in hepatocytes. Oestrogen-stimulated cells modulate the immune response through secretion of type I interferon, which can be countered by blocking interferon-alpha/beta receptor alpha signalling.
Collapse
|
|
2
|
El-Kassas M, Awad A. Metabolic aspects of hepatitis C virus. World J Gastroenterol 2022; 28:2429-2436. [PMID: 35979265 PMCID: PMC9258278 DOI: 10.3748/wjg.v28.i22.2429] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/18/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
Many metabolic factors are associated with chronic hepatitis C virus (HCV) infection and can influence the course of the illness and impact the progression of liver and non-liver-related diseases through complex interactions. Several of these factors impact the course of chronic HCV (CHC) and result in the conceptual translation of CHC from a localized to systemic disease. Besides the traditional liver manifestations associated with CHC infection, such as cirrhosis and hepatocellular carcinoma, various extrahepatic disorders are associated with HCV infection, including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases. The coexistence of metabolic disorders and CHC is known to influence the chronicity and virulence of HCV and accelerates the progression to liver fibrosis and hepatocellular carcinoma. Insulin resistance is one of the key factors that have a tremendous metabolic impact on CHC. Therefore, there is a great need to properly evaluate patients with CHC infection and correct the modifiable metabolic risk factors. Furthermore, patients with HCV who achieved a sustained virological response showed an overall improvement in glucose metabolism, but the exact evidence still requires further studies with long-term follow-up. This review delineates the most recent evidence on the main metabolic factors associated with CHC and the possible influence of chronic HCV infection on metabolic features.
Collapse
Affiliation(s)
- Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
| | - Abeer Awad
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
| |
Collapse
|
|
3
|
Bauvin P, Delacôte C, Lassailly G, Ntandja Wandji LC, Gnemmi V, Dautrecque F, Louvet A, Caiazzo R, Raverdy V, Leteurtre E, Pattou F, Deuffic-Burban S, Mathurin P. A tool to predict progression of non-alcoholic fatty liver disease in severely obese patients. Liver Int 2021; 41:91-100. [PMID: 32881244 DOI: 10.1111/liv.14650] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 08/13/2020] [Accepted: 08/18/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Severely obese patients are a growing population at risk of non-alcoholic fatty liver disease (NAFLD). Considering the increasing burden, a predictive tool of NAFLD progression would be of interest. Our objective was to provide a tool allowing general practitioners to identify and refer the patients most at risk, and specialists to estimate disease progression and adapt the therapeutic strategy. METHODS This predictive tool is based on a Markov model simulating steatosis, fibrosis and non-alcoholic steatohepatitis (NASH) evolution. This model was developped from data of 1801 severely obese, bariatric surgery candidates, with histological assessment, integrating duration of exposure to risk factors. It is then able to predict current disease severity in the absence of assessment, and future cirrhosis risk based on current stage. RESULTS The model quantifies the impact of sex, body-mass index at 20, diabetes, age of overweight onset, on progression. For example, for 40-year-old severely obese patients seen by the general practitioners: (a) non-diabetic woman overweight at 20, and (b) diabetic man overweight at 10, without disease assessment, the model predicts their current risk to have NASH or F3-F4: for (a) 5.7% and 0.6%, for (b) 16.1% and 10.0% respectively. If those patients have been diagnosed F2 by the specialist, the model predicts the 5-year cirrhosis risk: 1.8% in the absence of NASH and 6.0% in its presence for (a), 10.3% and 26.7% respectively, for (b). CONCLUSIONS This model provides a decision-making tool to predict the risk of liver disease that could help manage severely obese patients.
Collapse
Affiliation(s)
- Pierre Bauvin
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France
| | - Claire Delacôte
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France
| | - Guillaume Lassailly
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France.,Hôpital Claude Huriez, Services Maladies de l'Appareil Digestif, CHRU Lille, Lille, France
| | | | - Viviane Gnemmi
- Department of Pathology, Centre de Biologie Pathologie, Univ. Lille, CHU Lille, Inserm UMR-S 1172, Lille, France
| | - Flavien Dautrecque
- Hôpital Claude Huriez, Services Maladies de l'Appareil Digestif, CHRU Lille, Lille, France
| | - Alexandre Louvet
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France.,Hôpital Claude Huriez, Services Maladies de l'Appareil Digestif, CHRU Lille, Lille, France
| | - Robert Caiazzo
- Univ. Lille, Inserm, CHU Lille, U1190 - EGID, Lille, France
| | | | - Emmanuelle Leteurtre
- Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPARC - Jean-Pierre Aubert Research Center, Lille, France
| | | | - Sylvie Deuffic-Burban
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France.,Université de Paris, IAME, INSERM, Paris, France
| | - Philippe Mathurin
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France.,Hôpital Claude Huriez, Services Maladies de l'Appareil Digestif, CHRU Lille, Lille, France
| |
Collapse
|
|
4
|
Delacôte C, Bauvin P, Louvet A, Dautrecque F, Ntandja Wandji LC, Lassailly G, Voican C, Perlemuter G, Naveau S, Mathurin P, Deuffic-Burban S. A Model to Identify Heavy Drinkers at High Risk for Liver Disease Progression. Clin Gastroenterol Hepatol 2020; 18:2315-2323.e6. [PMID: 31931181 DOI: 10.1016/j.cgh.2019.12.041] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 12/08/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Alcohol-related liver disease (ALD) causes chronic liver disease. We investigated how information on patients' drinking history and amount, stage of liver disease, and demographic feature can be used to determine risk of disease progression. METHODS We collected data from 2334 heavy drinkers (50 g/day or more) with persistently abnormal results from liver tests who had been admitted to a hepato-gastroenterology unit in France from January 1982 through December 1997; patients with a recorded duration of alcohol abuse were assigned to the development cohort (n=1599; 75% men) or the validation cohort (n=735; 75% men), based on presence of a liver biopsy. We collected data from both cohorts on patient history and disease stage at the time of hospitalization. For the development cohort, severity of the disease was scored by the METAVIR (due to the availability of liver histology reports); in the validation cohort only the presence of liver complications was assessed. We developed a model of ALD progression and occurrence of liver complications (hepatocellular carcinoma and/or liver decompensation) in association with exposure to alcohol, age at the onset of heavy drinking, amount of alcohol intake, sex and body mass index. The model was fitted to the development cohort and then evaluated in the validation cohort. We then tested the ability of the model to predict disease progression for any patient profile (baseline evaluation). Patients with a 5-y weighted risk of liver complications greater than 5% were considered at high risk for disease progression. RESULTS Model results are given for the following patient profiles: men and women, 40 y old, who started drinking at an age of 25 y, drank 150 g/day, and had a body mass index of 22 kg/m2 according to the disease severity at baseline evaluation. For men with baseline F0-F2 fibrosis, the model estimated the probabilities of normal liver, steatosis, or steatohepatitis at baseline to be 31.8%, 61.5% and 6.7%, respectively. The 5-y weighted risk of liver complications was 1.9%, ranging from 0.2% for men with normal liver at baseline evaluation to 10.3% for patients with steatohepatitis at baseline. For women with baseline F0-F2 fibrosis, probabilities of normal liver, steatosis, or steatohepatitis at baseline were 25.1%, 66.5% and 8.4%, respectively; the 5-y weighted risk of liver complications was 3.2%, ranging from 0.5% for women with normal liver at baseline to 14.7% for patients with steatohepatitis at baseline. Based on the model, men with F3-F4 fibrosis at baseline have a 24.5% 5-y weighted risk of complications (ranging from 20.2% to 34.5%) and women have a 30.1% 5-y weighted risk of complications (ranging from 24.7% to 41.0%). CONCLUSIONS We developed a Markov model that integrates data on level and duration of alcohol use to identify patients at high risk of liver disease progression. This model might be used to adapt patient care pathways.
Collapse
Affiliation(s)
- Claire Delacôte
- Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France
| | - Pierre Bauvin
- Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France
| | - Alexandre Louvet
- Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France; Service des maladies de l'appareil digestif et de la nutrition, Centre Hospitalier Universitaire de Lille, Lille, France
| | - Flavien Dautrecque
- Service des maladies de l'appareil digestif et de la nutrition, Centre Hospitalier Universitaire de Lille, Lille, France
| | - Line Carolle Ntandja Wandji
- Service des maladies de l'appareil digestif et de la nutrition, Centre Hospitalier Universitaire de Lille, Lille, France
| | - Guillaume Lassailly
- Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France; Service des maladies de l'appareil digestif et de la nutrition, Centre Hospitalier Universitaire de Lille, Lille, France
| | - Cosmin Voican
- Service d'hépato-gastro-entérologie et nutrition, Hôpital Antoine Béclère, Hôpitaux universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U996, Département Hospitalo-Universitaire Hepatinov, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Clamart, France; Faculté de médecine Paris-Sud, Université Paris Sud-Université Paris Saclay, Le Kremlin-Bicêtre, France
| | - Gabriel Perlemuter
- Service d'hépato-gastro-entérologie et nutrition, Hôpital Antoine Béclère, Hôpitaux universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U996, Département Hospitalo-Universitaire Hepatinov, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Clamart, France; Faculté de médecine Paris-Sud, Université Paris Sud-Université Paris Saclay, Le Kremlin-Bicêtre, France
| | - Sylvie Naveau
- Service d'hépato-gastro-entérologie et nutrition, Hôpital Antoine Béclère, Hôpitaux universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U996, Département Hospitalo-Universitaire Hepatinov, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Clamart, France; Faculté de médecine Paris-Sud, Université Paris Sud-Université Paris Saclay, Le Kremlin-Bicêtre, France
| | - Philippe Mathurin
- Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France; Service des maladies de l'appareil digestif et de la nutrition, Centre Hospitalier Universitaire de Lille, Lille, France.
| | - Sylvie Deuffic-Burban
- Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France; Université de Paris, IAME, INSERM, Paris, France.
| |
Collapse
|
|
5
|
Model to Predict Progression of Liver Disease in Heavy Drinkers Is Useful Today and Supports the Future of Deep Learning. Clin Gastroenterol Hepatol 2020; 18:2176-2178. [PMID: 32062043 DOI: 10.1016/j.cgh.2020.02.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 02/09/2020] [Indexed: 02/07/2023]
|
|
6
|
Colombo D, Zullo A, Simoni L, Zagni E. The SURF (Italian observational study for renal insufficiency evaluation in liver transplant recipients): a post-hoc between-sex analysis. BMC Nephrol 2019; 20:475. [PMID: 31870321 PMCID: PMC6929500 DOI: 10.1186/s12882-019-1656-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 12/03/2019] [Indexed: 12/15/2022] Open
Abstract
Background Female sex has been reported as an independent predictor of severe post-liver transplantation (LT) chronic kidney disease. We performed a by sex post-hoc analysis of the SURF study, that investigated the prevalence of renal impairment following LT, aimed at exploring possible differences between sexes in the prevalence and course of post-LT renal damage. Methods All patients enrolled in the SURF study were considered evaluable for this sex-based analysis, whose primary objective was to evaluate by sex the proportion of patients with estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73m2 at inclusion and follow-up visit. Results Seven hundred thirty-eight patients were included in our analysis, 76% males. The proportion of patients with eGFR < 60 mL/min/1.73 m2 was significantly higher in females at initial study visit (33.3 vs 22.8%; p = 0.005), but also before, at time of transplantation (22.9 vs 14.7%; p = 0.0159), as analyzed retrospectively. At follow-up, such proportion increased more in males than in females (33.9 vs 26.0%, p = 0.04). Mean eGFR values decreased over the study in both sexes, with no significant differences. Statistically significant M/F differences in patient distribution by O’Riordan eGFR levels were observed at time of transplant and study initial visit (p = 0.0005 and 0.0299 respectively), but not at follow-up. Conclusions Though the limitation of being performed post-hoc, this analysis suggests potential sex differences in the prevalence of renal impairment before and after LT, encouraging further clinical research to explore such differences more in depth.
Collapse
Affiliation(s)
- Delia Colombo
- Novartis Farma S.p.A, Largo Umberto Boccioni, 21040, Origgio, VA, Italy
| | | | | | - Emanuela Zagni
- Novartis Farma S.p.A, Largo Umberto Boccioni, 21040, Origgio, VA, Italy.
| | | |
Collapse
|
|
7
|
The Course of Hepatitis C Infection and Response to Anti-viral Therapy in Patients with Thalassemia major and Hepatitis C Infection: A Longitudinal, Prospective Study. Mediterr J Hematol Infect Dis 2019; 11:e2019060. [PMID: 31700585 PMCID: PMC6827603 DOI: 10.4084/mjhid.2019.060] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 09/19/2019] [Indexed: 02/06/2023] Open
Abstract
Background The course of hepatitis C infection (HCV) in patients with thalassemia has not been adequately studied, and management has not been optimized. The current prospective longitudinal study assessed the clinical course, outcome, progression, and management of recently acquired HCV in patients with transfusion-dependent thalassemia major versus acute HCV without thalassemia. Methods A well-characterized cohort of patients with thalassemia and recent HCV infection or recent HCV without thalassemia were enrolled and prospectively followed. The blood transfusion needs and chelating agents were determined. Liver functions tests, HCV-RNA, iron, and ferritin levels were measured. Patients with chronic HCV evolution received treatment for HCV. The fibrosis progression rate was determined in chronic HCV patients with or without thalassemia by paired liver biopsies or serial transient elastography (TE), or serum markers of liver fibrosis. Liver iron content (LIC) was assessed by R2 MRI. Results Self-limited acute HCV was observed in 17% of patients with acute HCV and thalassemia versus 35% of patients without thalassemia (P=0.031). The fibrosis progression rates were significantly higher in patients with chronic HCV and thalassemia compared to those with chronic HCV alone (1.14±0.48) and (0.35±0.14) (P<0.0001), respectively. A direct linear correlation was observed between the fibrosis progression rate and each of LIC (R=+0.67; P=0.01) and ferritin (R=0.77; P<0.01). In patients with chronic HCV and thalassemia, the sustained virologic response (SVR) to pegylated interferon-based therapy and direct antiviral agents (DAAS) were 33% and 82% respectively (P<0.0001), while in chronic HCV patients without thalassemia, the SVR rates to PEG-IFN/RBV and DAAs were 51% and 92% respectively. Five patients with concomitant HCV and thalassemia died during the study due to cardiac causes (n=3) and liver cancer (n=2). Conclusions Patients with acute HCV and thalassemia have low rates of spontaneous resolution of HCV infection, and the majority develop chronic HCV. Direct-acting antiviral combinations are associated with high SVR rates and low adverse event in treatment naïve and experienced patients with chronic HCV and thalassemia. Liver fibrosis is accelerated in thalassemia patients with chronic HCV; therefore, early diagnosis, treatment with DAAs, adequate iron chelation, and non-invasive monitoring liver status are recommended to prevent cirrhosis and hepatocellular carcinoma.
Collapse
|
|
8
|
Caldwell H. Preventing, identifying and treating hepatitis C. Nurs Stand 2019; 34:e11321. [PMID: 31468895 DOI: 10.7748/ns.2018.e11321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/30/2018] [Indexed: 06/10/2023]
Abstract
Hepatitis C is a blood-borne virus that, if left untreated, can result in significant liver damage and cancer. Most individuals are unaware that they have been infected with the hepatitis C virus and remain asymptomatic, which makes early diagnosis challenging. While the virus will spontaneously clear in some individuals, the majority will develop chronic hepatitis C. This article provides nurses with an overview of hepatitis C and how it is transmitted. It details the available treatments, and examines the challenges involved in early identification and access to treatment, as well as outlining the barriers to treatment and how these can be overcome. This article also discusses the role of the nurse in the management of people with hepatitis C and in addressing their complex needs.
Collapse
Affiliation(s)
- Helen Caldwell
- Nurse consultant in hepatology, Royal Liverpool University Hospital NHS Trust, Liverpool, England
| |
Collapse
|
|
9
|
2-Methoxyestradiol attenuates liver fibrosis in mice: implications for M2 macrophages. Naunyn Schmiedebergs Arch Pharmacol 2018; 392:381-391. [PMID: 30535572 DOI: 10.1007/s00210-018-1577-2] [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: 08/03/2018] [Accepted: 10/31/2018] [Indexed: 02/06/2023]
Abstract
Liver fibrosis is a major health problem worldwide due to its serious complications including cirrhosis and liver cancer. 2-Methoxyestradiol (2-ME) is an end metabolite of estradiol with anti-proliferative, antioxidant, and anti-inflammatory activities. However, the protective role of 2-ME in liver fibrosis has not been fully investigated. The aim of this study was to determine the protective effect of 2-ME in carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Animals were injected intraperitoneally with CCl4 twice weekly for 6 weeks. 2-ME 50 mg/kg or 100 mg/kg was administrated intraperitoneally every day over the same period. Our data showed that 2-ME reduced the extent of liver toxicity and fibrosis due to CCl4 exposure. It restored the elevated serum liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels and ameliorated oxidative status. In addition, 2-ME significantly reduced collagen deposition and alpha-smooth muscle actin (α-SMA) protein expressions. Furthermore, 2-ME markedly lowered macrophage infiltration and macrophage alternative activation marker chitinase-like molecules (CHI3L3/YM1). The results of this study indicate an important protective activity of 2-ME in liver fibrosis and highlight the role of macrophage recruitment and alternative activation as a possible target.
Collapse
|
|
10
|
The value of mHealth for managing chronic conditions. Health Care Manag Sci 2018; 23:185-202. [DOI: 10.1007/s10729-018-9458-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 09/23/2018] [Indexed: 01/15/2023]
|
|
11
|
St. John TM. Chronic Hepatitis. Integr Med (Encinitas) 2018. [DOI: 10.1016/b978-0-323-35868-2.00021-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
12
|
Kileng H, Bernfort L, Gutteberg T, Moen OS, Kristiansen MG, Paulssen EJ, Berg LK, Florholmen J, Goll R. Future complications of chronic hepatitis C in a low-risk area: projections from the hepatitis c study in Northern Norway. BMC Infect Dis 2017; 17:624. [PMID: 28915795 PMCID: PMC5602833 DOI: 10.1186/s12879-017-2722-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Accepted: 09/08/2017] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Hepatitis C (HCV) infection causes an asymptomatic chronic hepatitis in most affected individuals, which often remains undetected until cirrhosis and cirrhosis-related complications occur. Screening of high-risk subjects in Northern Norway has revealed a relatively low prevalence in the general population (0.24%). Despite this, late complications of HCV infection are increasing. Our object was to estimate the future prevalence and complications of chronic HCV infection in the period 2013-2050 in a low-risk area. METHODS We have entered available data into a prognostic Markov model to project future complications to HCV infection. RESULTS The model extrapolates the prevalence in the present cohort of HCV-infected individuals, and assumes a stable low incidence in the projection period. We predict an almost three-fold increase in the incidence of cirrhosis (68 per 100,000), of decompensated cirrhosis (21 per 100,000) and of hepatocellular carcinoma (4 per 100,000) by 2050, as well as a six-fold increase in the cumulated number of deaths from HCV-related liver disease (170 per 100,000 inhabitants). All estimates are made assuming an unchanged treatment coverage of approximately 15%. The estimated numbers can be reduced by approximately 50% for cirrhosis, and by approximately one third for the other endpoints if treatment coverage is raised to 50%. CONCLUSION These projections from a low-prevalence area indicate a substantial rise in HCV-related morbidity and mortality in the coming years. The global HCV epidemic is of great concern and increased treatment coverage is necessary to reduce the burden of the disease.
Collapse
Affiliation(s)
- H Kileng
- Gastroenterology and Nutrition Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
- Department of Internal Medicine, Section of Gastroenterology, University Hospital of North Norway, Tromsø, Norway.
| | - L Bernfort
- Department of Medical and Health Sciences, University of Linköping, Linköping, Sweden
| | - T Gutteberg
- Research Group for Host-Microbe Interactions, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway
- Department of Microbiology, University Hospital of North Norway, Tromsø, Norway
| | - O S Moen
- Gastroenterology and Nutrition Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
| | | | - E J Paulssen
- Gastroenterology and Nutrition Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
- Department of Internal Medicine, Section of Gastroenterology, University Hospital of North Norway, Tromsø, Norway
| | - L K Berg
- Department of Medicine, Helgeland Hospital, Mo i Rana, Norway
| | - J Florholmen
- Gastroenterology and Nutrition Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
- Department of Internal Medicine, Section of Gastroenterology, University Hospital of North Norway, Tromsø, Norway
| | - R Goll
- Gastroenterology and Nutrition Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
- Department of Internal Medicine, Section of Gastroenterology, University Hospital of North Norway, Tromsø, Norway
| |
Collapse
|
|
13
|
Zeremski M, Dimova RB, Pillardy J, de Jong YP, Jacobson IM, Talal AH. Fibrosis Progression in Patients With Chronic Hepatitis C Virus Infection. J Infect Dis 2016; 214:1164-70. [PMID: 27485356 PMCID: PMC6281340 DOI: 10.1093/infdis/jiw332] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Accepted: 06/17/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Fibrosis progression varies markedly in hepatitis C virus (HCV)-infected individuals. We investigated factors that influence fibrosis progression in chronic HCV infection. METHODS HCV-infected patients who underwent at least 2 liver biopsies were included in this study. Associations between fibrosis progression and epidemiologic, virologic, and disease-associated factors were analyzed using logistic regression and multistate Markov modeling. RESULTS We analyzed 936 biopsy specimens obtained from 378 individuals. Mean age (±SD) at first biopsy was 48.3 ± 9.3 years, 59.3% of patients were male, 59.9% were white, and 86.7% were infected with HCV genotype 1. Fibrosis progression and cirrhosis occurred in 57.4% and 5.8%, respectively. Fibrosis progression between the first and last biopsies was associated with lower fibrosis in the first biopsy specimen (P < .001) and with the occurrence of at least 1 flare in the alanine aminotransferase (ALT) level (>200 U/L; P = .007). We found the highest fibrosis progression rate between stages 0 and 1 and the lowest between stages 2 and 3. Increased necroinflammation and higher ALT level were associated with faster progression. HCV genotype 3-infected patients were more likely to progress to cirrhosis (P < .001). CONCLUSIONS Fibrosis progression in HCV is not linear but varies according to stage, with the highest progression in patients with the lowest fibrosis severity. Patients who experience flares in the ALT level are also more likely to progress.
Collapse
Affiliation(s)
- Marija Zeremski
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College
| | - Rositsa B. Dimova
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine
- Department of Biostatistics, State University of New York, Buffalo
| | | | - Ype P. de Jong
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College
| | | | - Andrew H. Talal
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine
| |
Collapse
|
|
14
|
Buhler S, Giostra E, Gbame C, de Rham C, Mullhaupt B, Dufour JF, Majno P, Negro F, Bochud PY, Villard J. A significant effect of the killer cell immunoglobulin-like receptor ligand human leucocyte antigen-C on fibrosis progression in chronic C hepatitis with or without liver transplantation. Liver Int 2016; 36:1331-9. [PMID: 26717049 DOI: 10.1111/liv.13057] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Accepted: 12/18/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The interaction of killer cell immunoglobulin-like receptors with their human leucocyte antigen ligands drives the activation and inhibition of natural killer cells. Natural killer cells could be implicated in the development of liver fibrosis in chronic hepatitis C. METHODS We analysed 206 non-transplanted and 53 liver transplanted patients, selected according to their Metavir fibrosis stage. Several variables such as the number of activator killer cell immunoglobulin-like receptors or the human leucocyte antigen ligands were considered in multinomial and logistic regression models. Possible confounding variables were also investigated. RESULTS The killer cell immunoglobulin-like receptors were not significant predictors of the fibrosis stage. Conversely, a significant reduction of the human leucocyte antigen-C1C2 genotype was observed in the most advanced fibrosis stage group (F4) in both cohorts. Furthermore, the progression rate of fibrosis was almost 10 times faster in the subgroup of patients after liver transplantation, and human leucocyte antigen-C1C2 was significantly reduced in this cohort compared with non-transplanted patients. CONCLUSION This study suggests a possible role of killer cell immunoglobulin-like receptors and their ligands in the development of liver damage. The absence of C1 and C2 ligands heterozygosity could lead to less inhibition of natural killer cells and a quicker progression to a high level of fibrosis in patients infected with hepatitis C virus, especially following liver transplantation.
Collapse
Affiliation(s)
- Stéphane Buhler
- Transplantation Immunology Unit, Service of Nephrology, Department of Internal Medicine Specialties and Genetic and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.,Laboratory of Anthropology, Genetics and Peopling History, Department of Genetics and Evolution - Anthropology Unit, University of Geneva, Geneva, Switzerland
| | - Emiliano Giostra
- Service of Transplantation, Geneva University Hospitals, Geneva, Switzerland
| | - Corinne Gbame
- Transplantation Immunology Unit, Service of Nephrology, Department of Internal Medicine Specialties and Genetic and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Casimir de Rham
- Transplantation Immunology Unit, Service of Nephrology, Department of Internal Medicine Specialties and Genetic and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Beat Mullhaupt
- Division of Gastroenterology and Hepatology, Zurich University Hospital, Zurich, Switzerland
| | - Jean-François Dufour
- University Clinic of Visceral Surgery and Medicine Inselspital, Bern, Switzerland
| | - Pietro Majno
- Service of Transplantation, Geneva University Hospitals, Geneva, Switzerland
| | - Francesco Negro
- Service of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva, Switzerland.,Service of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland
| | | | - Jean Villard
- Transplantation Immunology Unit, Service of Nephrology, Department of Internal Medicine Specialties and Genetic and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland
| | | |
Collapse
|
|
15
|
Marotta P, Bailey R, Elkashab M, Farley J, Feinman SV, Peltekian K, Poliquin M, Witt-Sullivan H, Rampakakis E, Drolet M, Cooper C. Real-world effectiveness of peginterferon α-2b plus ribavirin in a Canadian cohort of treatment-naïve chronic hepatitis C patients with genotypes 2 or 3: results of the PoWer and RediPEN studies. Eur J Clin Microbiol Infect Dis 2016; 35:597-609. [PMID: 26851949 PMCID: PMC4819461 DOI: 10.1007/s10096-016-2576-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2015] [Accepted: 01/04/2016] [Indexed: 01/02/2023]
Abstract
The purpose of this investigation was to assess the real-life effectiveness of pegylated interferon (peg-IFN) α-2b with ribavirin (RBV) in a cohort of treatment-naïve patients with chronic genotypes 2 (G2) or 3 (G3) hepatitis C virus (HCV) infection. A post-hoc pooled analysis of two Canadian multicenter, observational studies, RediPEN and PoWer, was carried out. A total of 1242 G2- or G3-infected patients were included. The primary outcome was sustained virologic response (SVR). Secondary endpoints included early virologic response (EVR), end-of-treatment (EOT) response, and relapse. Multivariate logistic regression was used to identify independent predictors of treatment response. SVR in G2 and G3 was 74.4 % and 63.6 %, respectively. Relapse occurred in 12.7 % and 19.1 % of G2- and G3-infected patients achieving EOT response, respectively. Overall, G3 was found to independently predict reduced SVR [odds ratio (OR) = 0.20; p = 0.007] and increased relapse (OR = 6.84; p = 0.022). Among G3-infected patients, increasing fibrosis score was the most important factor predicting reduced SVR [F2 vs. F0/F1 (OR = 0.41; p = 0.009); F3 vs. F0/F1 (OR = 0.72; p = 0.338); F4 vs. F0/F1 (OR = 0.27; p = 0.001)]. Male gender (OR = 13.16; p = 0.020) and higher fibrosis score [F2 vs. F0/F1 (OR = 9.72; p = 0.016); F3/F4 vs. F0/F1 (OR = 4.23; p = 0.113)] were associated with increased relapse in G3 patients. These results support the real-life effectiveness of peg-IFN α-2b plus ribavirin in HCV G2- and G3-infected patients. Overall, genotype was identified as the most significant predictor of treatment outcome. Fibrosis score and gender were key outcome predictors in the G3-infected population. In clinical settings, peg-INF/RBV offers an alternative for patients without access to all oral direct-acting antivirals.
Collapse
Affiliation(s)
- P Marotta
- London Health Sciences Center, London, ON, Canada
| | - R Bailey
- University of Alberta, Edmonton, AB, Canada
| | - M Elkashab
- Toronto Liver Centre, Toronto, ON, Canada
| | - J Farley
- Dr. John Farley Inc., Vancouver, BC, Canada
| | | | - K Peltekian
- Atlantic Hepatology Services, Halifax, NS, Canada
| | - M Poliquin
- Clinique Médicale L'Actuel, Montreal, QC, Canada
| | | | - E Rampakakis
- JSS Medical Research Inc., St-Laurent, QC, Canada.
| | - M Drolet
- Merck Canada Inc., Kirkland, QC, Canada
| | - C Cooper
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| |
Collapse
|
|
16
|
Yu L, Boyle PA, Leurgans S, Schneider JA, Kryscio RJ, Wilson RS, Bennett DA. Effect of common neuropathologies on progression of late life cognitive impairment. Neurobiol Aging 2015; 36:2225-2231. [PMID: 25976345 DOI: 10.1016/j.neurobiolaging.2015.04.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2014] [Revised: 03/24/2015] [Accepted: 04/15/2015] [Indexed: 11/27/2022]
Abstract
Brain pathologies of Alzheimer's (AD), cerebrovascular, and Lewy body diseases are common in old age, but the relationship of these pathologies with progression from normal cognitive function to the various stages of cognitive impairment is unknown. In this study, we fit latent Markov models from longitudinal cognitive data to empirically derive 3 latent stages corresponding to no impairment, mild impairment, and moderate impairment; then, we examined the associations of common neuropathologies with the rates of transition among these stages. Cognitive and neuropathological data were available from 653 autopsied participants in 2 ongoing cohort studies of aging who were cognitively healthy at baseline (mean baseline age 79.1 years) and had longitudinal cognitive data. On average, participants in these analyses developed mild impairment 5 years after enrollment, progressed to moderate impairment after an additional 3.4 years, and stayed impaired for 2.8 years until death. AD and chronic macroscopic infarcts were associated with a higher risk of progression to mild impairment and subsequently to moderate impairment. By contrast, Lewy bodies were associated only with progression from mild to moderate impairment. The 5-year probability of progression to mild or moderate impairment was 20% for persons without any of these 3 pathologies, 38% for AD only, 51% for AD and macroscopic infarcts, and 56% for AD, infarcts, and Lewy bodies. Thus, the presence of AD pathology alone nearly doubles the risk of developing cognitive impairment in late life, and the presence of multiple pathologies further increases this risk over multiple years before death.
Collapse
Affiliation(s)
- Lei Yu
- Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
| | - Patricia A Boyle
- Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA
| | - Sue Leurgans
- Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Department of Preventive Medicine, Rush University Medical Center, Chicago, IL, USA
| | - Julie A Schneider
- Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Department of Pathology, Rush University Medical Center, Chicago, IL, USA
| | - Richard J Kryscio
- Department of Statistics, University of Kentucky, Lexington, KY, USA
| | - Robert S Wilson
- Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA
| | - David A Bennett
- Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
| |
Collapse
|
|
17
|
Hatzakis A, Chulanov V, Gadano AC, Bergin C, Ben-Ari Z, Mossong J, Schréter I, Baatarkhuu O, Acharya S, Aho I, Anand AC, Andersson MI, Arendt V, Arkkila P, Barclay K, Bessone F, Blach S, Blokhina N, Brunton CR, Choudhuri G, Cisneros L, Croes EA, Dahgwahdorj YA, Dalgard O, Daruich JR, Dashdorj NR, Davaadorj D, de Knegt RJ, de Vree M, Estes C, Flisiak R, Gane E, Gower E, Halota W, Henderson C, Hoffmann P, Hornell J, Houlihan D, Hrusovsky S, Jarčuška P, Kershenobich D, Kostrzewska K, Kristian P, Leshno M, Lurie Y, Mahomed A, Mamonova N, Mendez-Sanchez N, Norris S, Nurmukhametova E, Nymadawa P, Oltman M, Oyunbileg J, Oyunsuren T, Papatheodoridis G, Pimenov N, Prabdial-Sing N, Prins M, Radke S, Rakhmanova A, Razavi-Shearer K, Reesink HW, Ridruejo E, Safadi R, Sagalova O, Sanchez Avila JF, Sanduijav R, Saraswat V, Seguin-Devaux C, Shah SR, Shestakova I, Shevaldin A, Shibolet O, Silva MO, Sokolov S, Sonderup M, Souliotis K, Spearman CW, Staub T, Stedman C, Strebkova EA, Struck D, Sypsa V, Tomasiewicz K, Undram L, van der Meer AJ, van Santen D, Veldhuijzen I, Villamil FG, Willemse S, Zuckerman E, Zuure FR, Puri P, Razavi H. The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2. J Viral Hepat 2015; 22 Suppl 1:26-45. [PMID: 25560840 DOI: 10.1111/jvh.12351] [Citation(s) in RCA: 104] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.
Collapse
Affiliation(s)
- A Hatzakis
- Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School, Athens, Greece
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
18
|
Abstract
There has long been evidence that hepatitis C can lead to persistent infection in a high proportion of infected individuals, and can progress to chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). The transition from acute to chronic hepatitis C is usually sub-clinical. Accurate studies of the time course for clearance of acute hepatitis C are difficult to carry out because of the silent onset of the acute disease. The likelihood of spontaneous HCV resolution is associated with several genetic factors, including IL28B inheritance and the DQB1*0301 allele of the major histocompatibility complex class II. Most data suggest that resolution in the acute phase without progression to chronic disease is not accompanied by significant disease, but minor histological lesions have been observed in anti-HCV positive, HCV RNA negative individuals. The risk of reinfection remains a possibility after clearance of acute hepatitis C. High rates of sexually-transmitted infection are being reported in HIV positive men who have sex with men (MSM). Chronic infection with HCV is the leading cause of end-stage liver disease, hepatocellular carcinoma (HCC) and liver related death in the Western world. The natural history of the chronic disease remains incompletely defined. It is generally a slowly progressive disease characterized by persistent hepatic inflammation, leading to the development of cirrhosis in approximately 10-20% of patients over 20-30 years of HCV infection. However, the published data indicate varying progression rates to cirrhosis. Overall, once cirrhosis has developed there is a 1-5% annual risk of HCC and a 3-6% annual risk of hepatic decompensation. Following an episode of decompensation the risk of death in the following year is between 15% and 20%. The high number of chronically infected individuals, the burden of disease, and the absence of a vaccine indicates that treatment will form part of the disease control but the impact, effectiveness and outcomes of treatment in various groups remain uncertain. Several studies and meta-analysis have concluded that eradication of HCV with antiviral therapy reduces the risk of HCC in patients with chronic hepatitis C, independent of fibrosis stage, but the risk is not eliminated.
Collapse
|
|
19
|
Helal SF, Gomaa HE, Thabet EH, Younan MA, Helmy NA. Impact of IL-10 (-1082) promoter-single nucleotide polymorphism on the outcome of hepatitis C virus genotype 4 infection. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2014; 7:19-24. [PMID: 24833945 PMCID: PMC4019231 DOI: 10.4137/cgast.s13658] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2013] [Revised: 01/23/2014] [Accepted: 01/27/2014] [Indexed: 12/18/2022]
Abstract
UNLABELLED Immunoregulatory cytokines may influence the hepatitis C virus (HCV) infection outcome. This study aimed to determine the genotypic and allelic frequencies of the interleukin (IL)-10 (-1082) G/A polymorphism, and its association with chronicity or resolution of HCV genotype 4 infection in Egypt. The frequencies of different dimorphic polymorphisms based on single nucleotide substitution in chronic HCV patients (50) and resolved HCV patients (50) were: IL-10 (-1082) G/G 22 (44%) and 18 (36%), G/A 19 (38%) and 24 (48%), and A/A 9 (18%), and 8 (16%), respectively. In the sustained virologic response (SVR) (36) and spontaneously resolved subjects (14) groups, the frequencies were: IL-10 (-1082) G/G 11 (30.6%) and 7 (50%) G/A 18 (50%) and 6 (42.9%), A/A 7 (19.4%) and 1 (7.1%), respectively. An association between male gender and chronic hepatitis C outcome (P value 0.041) was found. However, no significant gender difference was found when we compared females versus males with elevated alanine transaminase (ALT) levels in the chronic HCV patient group (P value = 1). CONCLUSION No significant difference in the frequency of IL-10 single nucleotide polymorphism (SNP) at position 1082 was found between chronic and resolved HCV subjects.
Collapse
Affiliation(s)
- Soheir F Helal
- Virology and Clinical Pathology Department, Cairo University, Egypt
| | - Howayda E Gomaa
- Clinical and Chemical Pathology Department, National Research Centre, Cairo, Egypt
| | - Eman H Thabet
- Clinical and Chemical Pathology Department, National Research Centre, Cairo, Egypt
| | - Mariam A Younan
- Virology and Clinical Pathology Department, Cairo University, Egypt
| | - Neveen A Helmy
- Clinical and Chemical Pathology Department, National Research Centre, Cairo, Egypt
| |
Collapse
|
|
20
|
Macaluso FS, Maida M, Minissale MG, Li Vigni T, Attardo S, Orlando E, Petta S. Metabolic factors and chronic hepatitis C: a complex interplay. BIOMED RESEARCH INTERNATIONAL 2013; 2013:564645. [PMID: 23956991 PMCID: PMC3730187 DOI: 10.1155/2013/564645] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2013] [Accepted: 06/29/2013] [Indexed: 12/15/2022]
Abstract
In the last years, several lines of evidence showed how metabolic factors may influence the natural history of patients with chronic hepatitis C. Chronic HCV infection is able to perturb the metabolic homeostasis of the host, in a context of complex interactions where pre-existent metabolic status and genetic background play an important role, allowing us to state that HCV infection is a systemic disease. In this review, we discuss the most recent lines of evidence on the main metabolic factors that are known to be associated with CHC, namely, insulin resistance/type 2 diabetes, steatosis, visceral obesity, atherosclerosis, vitamin D, menopause, fructose and coffee intake, lipoproteins, methylenetetrahydrofolate reductase status, and hyperuricaemia. In particular, we focus on the pathophysiological mechanisms underlying the correlation between HCV infection and metabolic disorders, the impact of metabolic factors on the progression of liver and non-liver-related diseases, and, on the contrary, the possible influence of chronic HCV infection on metabolic features. In this setting, the importance of a multifaceted evaluation of CHC patients and a prompt correction of modifiable metabolic risk factors should be emphasized.
Collapse
Affiliation(s)
- Fabio Salvatore Macaluso
- Section of Gastroenterology, DiBiMIS, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy.
| | | | | | | | | | | | | |
Collapse
|
|
21
|
Eckman MH, Talal AH, Gordon SC, Schiff E, Sherman KE. Cost-effectiveness of screening for chronic hepatitis C infection in the United States. Clin Infect Dis 2013; 56:1382-93. [PMID: 23392392 DOI: 10.1093/cid/cit069] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the United States and will become an increasing source of morbidity and mortality with aging of the infected population. Our objective was to develop decision analytic models to explore the cost-effectiveness of screening in populations with varying prevalence of HCV and risks for fibrosis progression. METHODS We developed a Markov state transition model to examine screening of an asymptomatic community-based population in the United States. The base case was an ethnically and gender-mixed adult population with no prior knowledge of HCV status. Interventions were screening followed by guideline-based treatment, or no screening. Effectiveness was measured in quality-adjusted life-years (QALYs), and costs were measured in 2011 US dollars. RESULTS In the base case (US population, 49% male, 78% white, 13% African American, and 9% Hispanic, mean age, 46 years), screening followed by guideline-based treatment (using boceprevir as the direct-acting antiviral agent) of those with chronic HCV infection costs $47 276 per QALY. The overall HCV prevalence in the United States is reported to be 1.3%-1.9%, but prevalence varies markedly among patients with different numbers and types of risk factors. The marginal cost-effectiveness ratio (mCER) of screening decreases as prevalence increases. Below a prevalence of 0.84%, the mCER is greater than the generally accepted societal willingness-to-pay threshold of $50 000 per QALY and thus is not considered highly cost-effective. CONCLUSIONS Targeted screening is cost-effective when prevalence of HCV exceeds 0.84%. Prospective evaluation of a screening tool is warranted and should include comparisons with other screening strategies.
Collapse
Affiliation(s)
- Mark H Eckman
- Division of General Internal Medicine and the Center for Clinical Effectiveness, OH, USA.
| | | | | | | | | |
Collapse
|
|
22
|
Burra P, De Martin E, Gitto S, Villa E. Influence of age and gender before and after liver transplantation. Liver Transpl 2013; 19:122-34. [PMID: 23172830 DOI: 10.1002/lt.23574] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2012] [Accepted: 11/08/2012] [Indexed: 12/15/2022]
Abstract
Women constitute a particular group among patients with chronic liver disease and in the post-liver transplantation (LT) setting: they are set apart not only by traditional differences with respect to men (ie, body mass index, different etiologies of liver disease, and accessibility to transplantation) but also in increasingly evident ways related to hormonal changes that characterize first the fertile age and subsequently the postmenopausal period (eg, disease course variability and responses to therapy). The aim of this review is, therefore, to evaluate the role of the interplay of factors such as age, gender, and hormones in influencing the natural history of chronic liver disease before and after LT and their importance in determining outcomes after LT. As the population requiring LT ages and the mean age at transplantation increases, older females are being considered for transplantation. Older patients are at greater risk for nonalcoholic steatohepatitis, osteoporosis, and a worse response to antiviral therapy. Female gender per se is associated with a greater risk for osteoporosis because of metabolic changes after menopause, the bodily structure of females, and, in the population of patients with chronic liver disease, the greater prevalence of cholestatic and autoimmune liver diseases. With menopause, the fall of protective estrogen levels can lead to increased fibrosis progression, and this represents a negative turning point for women with chronic liver disease and especially for patients with hepatitis C. Therefore, the notion of gender as a binary female/male factor is now giving way to the awareness of more complex disease processes within the female gender that follow hormonal, social, and age patterns and need to be addressed directly and specifically.
Collapse
Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy.
| | | | | | | |
Collapse
|
|
23
|
Villa E, Vukotic R, Cammà C, Petta S, Di Leo A, Gitto S, Turola E, Karampatou A, Losi L, Bernabucci V, Cenci A, Tagliavini S, Baraldi E, De Maria N, Gelmini R, Bertolini E, Rendina M, Francavilla A. Reproductive status is associated with the severity of fibrosis in women with hepatitis C. PLoS One 2012; 7:e44624. [PMID: 22970270 PMCID: PMC3438179 DOI: 10.1371/journal.pone.0044624] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2012] [Accepted: 08/06/2012] [Indexed: 01/05/2023] Open
Abstract
Introduction Chronic hepatitis C is the main cause of death in patients with end-stage liver disease. Prognosis depends on the increase of fibrosis, whose progression is twice as rapid in men as in women. Aim of the study was to evaluate the effects of reproductive stage on fibrosis severity in women and to compare these findings with age-matched men. Materials and Methods A retrospective study of 710 consecutive patients with biopsy-proven chronic hepatitis C was conducted, using data from a clinical database of two tertiary Italian care centers. Four age-matched groups of men served as controls. Data about demographics, biochemistry, liver biopsy and ultrasonography were analyzed. Contributing factors were assessed by multivariate logistic regression analysis. Results Liver fibrosis was more advanced in the early menopausal than in the fully reproductive (P<0.0001) or premenopausal (P = 0.042) group. Late menopausal women had higher liver fibrosis compared with the other groups (fully reproductive, P<0.0001; premenopausal, P = <0.0001; early menopausal, P = 0.052). Multivariate analyses showed that male sex was independently associated with more severe fibrosis in the groups corresponding to premenopausal (P = 0.048) and early menopausal (P = 0.004) but not late menopausal pairs. In women, estradiol/testosterone ratio decreased markedly in early (vs. reproductive age: P = 0.002 and vs. premenopausal: P<0.0001) and late menopause (vs. reproductive age: P = 0.001; vs. premenopausal: P<0.0001). In men age-matched with menopausal women, estradiol/testosterone ratio instead increased (reproductive age group vs. early: P = 0.002 and vs. late M: P = 0.001). Conclusions The severity of fibrosis in women worsens in parallel with increasing estrogen deprivation and estradiol/testosterone ratio decrease. Our data provide evidence why fibrosis progression is discontinuous in women and more linear and severe in men, in whom aging-associated estradiol/testosterone ratio increase occurs too late to noticeably influence the inflammatory process leading to fibrosis.
Collapse
Affiliation(s)
- Erica Villa
- Department of Gastroenterology, Azienda Ospedaliero-Universitaria & University of Modena and Reggio Emilia, Modena, Italy.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
24
|
Estimating complex multi-state misclassification rates for biopsy-measured liver fibrosis in patients with hepatitis C. Int J Biostat 2012; 5:Article 5. [PMID: 20104258 DOI: 10.2202/1557-4679.1139] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
For both clinical and research purposes, biopsies are used to classify liver damage known as fibrosis on an ordinal multi-state scale ranging from no damage to cirrhosis. Misclassification can arise from reading error (misreading of a specimen) or sampling error (the specimen does not accurately represent the liver). Studies of biopsy accuracy have not attempted to synthesize these two sources of error or to estimate actual misclassification rates from either source. Using data from two studies of reading error and two of sampling error, we find surprisingly large possible misclassification rates, including a greater than 50% chance of misclassification for one intermediate stage of fibrosis. We find that some readers tend to misclassify consistently low or consistently high, and some specimens tend to be misclassified low while others tend to be misclassified high. Non-invasive measures of liver fibrosis have generally been evaluated by comparison to simultaneous biopsy results, but biopsy appears to be too unreliable to be considered a gold standard. Non-invasive measures may therefore be more useful than such comparisons suggest. Both stochastic uncertainty and uncertainty about our model assumptions appear to be substantial. Improved studies of biopsy accuracy would include large numbers of both readers and specimens, greater effort to reduce or eliminate reading error in studies of sampling error, and careful estimation of misclassification rates rather than less useful quantities such as kappa statistics.
Collapse
|
|
25
|
Baur K, Mertens JC, Schmitt J, Iwata R, Stieger B, Eloranta JJ, Frei P, Stickel F, Dill MT, Seifert B, Ferrari HAB, von Eckardstein A, Bochud PY, Müllhaupt B, Geier A. Combined effect of 25-OH vitamin D plasma levels and genetic vitamin D receptor (NR 1I1) variants on fibrosis progression rate in HCV patients. Liver Int 2012; 32:635-43. [PMID: 22151003 DOI: 10.1111/j.1478-3231.2011.02674.x] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2011] [Accepted: 10/12/2011] [Indexed: 12/21/2022]
Abstract
BACKGROUND Decreased vitamin D levels have been described in various forms of chronic liver disease and associated with advanced fibrosis. Whether this association is a cause or consequence of advanced fibrosis remains unclear to date. AIMS To analyse combined effects of 25-OH vitamin D plasma levels and vitamin D receptor gene (VDR; NR1I1) polymorphisms on fibrosis progression rate in HCV patients. METHODS 251 HCV patients underwent VDR genotyping (bat-haplotype: BsmI rs1544410 C, ApaI rs7975232 A and TaqI rs731236 A). Plasma 25-OH vitamin D levels were quantified in a subgroup of 97 patients without advanced fibrosis. The VDR haplotype and genotypes as well as plasma 25-OH vitamin D levels were associated with fibrosis progression. RESULTS The bAt[CCA]-haplotype was significantly associated with fibrosis progression >0.101 U/year (P = 0.007; OR = 2.02) and with cirrhosis (P = 0.022; OR = 1.84). Forty-five percent of bAt[CCA]-haplotype patients were rapid fibrosers, 21.1% were cirrhotic. Likewise, ApaI rs7975232 CC genotype was significantly associated with fibrosis progression and cirrhosis. Lower plasma 25-OH vitamin D levels were significantly associated with fibrosis progression >0.101 U/year in F0-2 patients (P = 0.013). Combined analysis of both variables revealed a highly significant additive effect on fibrosis progression with 45.5% rapid fibrosers for bAt[CCA]-haplotype and 25-OH vitamin D < 20 μg/L compared with only 9.1% for the most favourable combination (P = 0.006). In multivariate analysis, the bAt-haplotype was an independent risk factor for fibrosis progression (P = 0.001; OR = 2.83). CONCLUSION Low 25-OH vitamin D plasma levels and the unfavourable VDR bAt[CCA]-haplotype are associated with rapid fibrosis progression in chronic HCV patients. In combination, both variables exert significant additive effects on fibrosis progression.
Collapse
Affiliation(s)
- Katharina Baur
- Division of Gastroenterology & Hepatology, University Hospital Zurich (USZ), Zurich, Switzerland
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
26
|
Rao HY, Sun DG, Yang RF, Liu F, Wang J, Feng B, Wu N, Fang JL, Song GJ, Ma H, Guo F, Wang JH, Li XB, Jin Q, Qin H, Zhuang H, Wei L. Outcome of hepatitis C virus infection in Chinese paid plasma donors: a 12-19-year cohort study. J Gastroenterol Hepatol 2012; 27:526-32. [PMID: 21871021 DOI: 10.1111/j.1440-1746.2011.06880.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Commercial plasma donation was introduced in China in the 1970s. Cases of non-A, non-B hepatitis (hepatitis C) continued to occur, with multiple outbreaks among plasma donors in Guan county, Hebei province between 1972 and 1990. The outcomes of hepatitis C virus (HCV) infection in these paid plasma donors from six villages of Guan county were followed up for 12-19 years. METHODS A total of 402 plasma donors with HCV infection were enrolled since anti-HCV-positive in 1991 or 1998. Follow up was maintained until death or the end of the observation period. No antiviral treatment was applied during the period of infection. RESULTS Follow up was lost in 23 cases. After a 12-19-year follow up, 31 donors died, with the cause of death directly related to liver disease in 15 cases, and an overall mortality of 8.18% (31/379). The incidence of liver cirrhosis was 10.03%, and hepatocellular carcinoma (HCC) was 2.90%. The rate of viral spontaneous clearing was 20.32% (77/379), and 13.69% (23/168) in males and 25.59% (54/211) in females. In May 2010, detections were performed in 348 cases. Abnormality of liver function was related to HCV viremia. Sex and alcohol intake impacted the outcome of HCV infection. There was no correlation between the viral spontaneous clearance with age of infection and genotype. CONCLUSIONS This area has a high rate of chronicity in HCV infection due to plasma donation. Twenty-five years after virus infection, liver cirrhosis or HCC developed in one-tenth of patients, with an overall mortality of 8.18%.
Collapse
Affiliation(s)
- Hui-Ying Rao
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
27
|
Ripoli M, Pazienza V. Impact of HCV genetic differences on pathobiology of disease. Expert Rev Anti Infect Ther 2012; 9:747-59. [PMID: 21905784 DOI: 10.1586/eri.11.94] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Multiple HCV genotypes have been isolated worldwide. Genotype seems to be involved in the main pathological aspects of HCV infection. Insulin resistance, steatosis and progression toward cirrhosis, fibrosis and hepatocellular carcinoma establish and develop following genotype-specific mechanisms. Moreover genotype influences pharmacological treatment in term of dose and duration. Pathways involved in cell proliferation, apoptosis, lipid metabolism, insulin and interferon signaling are impaired to a different extent among genotypes, leading to distinct pathological settings. Genotype 1 is associated with a more aggressive disease with increased insulin resistance, worst response to therapy, higher risk of cirrhosis and hepatocellular carcinoma development, while genotype 3 is associated with increased steatosis and fibrosis. The identification and characterization of HCV types and subtypes provides insight into the different outcome of HCV infection and responsiveness to therapy. In the present article, we focused on the pathogenicity of HCV genotypes and their effect on disease progression and treatment.
Collapse
Affiliation(s)
- Maria Ripoli
- Gastroenterology Unit IRCCS Casa Sollievo della Sofferenza Hospital, viale dei Cappuccini n.1, 71013 San Giovanni Rotondo, Italy
| | | |
Collapse
|
|
28
|
Sanai FM, Helmy A, Dale C, Al-Ashgar H, Abdo AA, Katada K, AlMana H, Saadeh M, Al-Hussaini H, AlQuaiz M, Hashem A, AlSwat K, Bzeizi KI, Marotta PJ. Updated thresholds for alanine aminotransferase do not exclude significant histological disease in chronic hepatitis C. Liver Int 2011; 31:1039-46. [PMID: 21733094 DOI: 10.1111/j.1478-3231.2011.02551.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND AND AIM Histological changes in hepatitis C virus (HCV)-infected patients with persistently normal alanine aminotransferase (PNALT) have not been evaluated for updated upper limits of normal (ULN; ≤ 19/30 U/L for females/males). We assessed significant fibrosis (≥ F2, METAVIR) in patients with PNALT and persistently elevated alanine aminotransferase (PEALT). PATIENTS AND METHODS Nine hundred and twenty consecutive, unselected HCV patients were stratified into four groups: Group I: (n = 124) PNALT within the updated ULN [0.5 × ULN (corresponding to ≤ 19 U/L) for females; 0.75 × ULN (corresponding to ≤ 30 U/L) for males]; Group II (n = 173): PNALT ≤ 1 × ULN but greater than Group I; Group III (n = 313): PEALT 1-2 × ULN; and Group IV (n = 310): PEALT > 2 × ULN. PNALT was defined as ≥ 3 determinations within the normal range over ≥ 6 months. RESULTS Advanced ≥ F3 and ≥ F2 fibrosis increased incrementally across Groups I; II; III; and IV: 24.2 and 45.2%; 25.4 and 56.1%; 36.1 and 64.2%; and 50 and 77.1% respectively (P<0.0001 for both). Multivariable logistic regression analysis identified age [odds ratio (OR), 1.05; 95% confidence intervals (CI): 1.02-1.08; P<0.0001], alanine aminotransferase (ALT) groups (OR 1.38; 95% CI: 1.03-1.83; P = 0.030), presence of moderate-severe steatosis (OR 2.70; 95% CI: 1.19-6.15; P = 0.018) and ≥ A2 necroinflammation (OR 17.9; 95% CI: 8.88-36.20; P < 0.0001) as independent predictors of ≥ F2 fibrosis. Updated ULN for ALT were better at excluding ≥ F2 fibrosis compared with traditional ULN (90.6 vs. 74.2%, P = 0.0041) but less specific (20.8 vs. 44%, P = 0.0007) with similar positive/negative predictive values. CONCLUSIONS HCV patients with 'updated' normal ALT have the lowest prevalence of significant fibrosis, although utilizing these levels without resorting to biopsy would miss significant fibrosis in almost one-half of such patients.
Collapse
Affiliation(s)
- Faisal M Sanai
- Department of Medicine, Division of Hepatology, Riyadh Military Hospital, Riyadh, Saudi Arabia.
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Di Martino V, Crouzet J, Hillon P, Thévenot T, Minello A, Monnet E. Long-term outcome of chronic hepatitis C in a population-based cohort and impact of antiviral therapy: a propensity-adjusted analysis. J Viral Hepat 2011; 18:493-505. [PMID: 21692956 DOI: 10.1111/j.1365-2893.2011.01476.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This population-based study aimed to assess the determinants of the outcome of chronic hepatitis C with analysis of the impact of antiviral therapy with or without sustained virological response (SVR) on cirrhosis decompensation, hepatocellular carcinoma, liver-related and non-liver-related mortality. A total of 1159 HCV-positive patients newly detected between 1994 and 2001 were included. For each outcome, the prognostic effect of patients' baseline characteristics was estimated by time-dependent Cox models using age as the time-scale and adjusting for treatment received during follow-up. The impact of antiviral therapy was assessed by using a propensity score in a sample including 184 patients treated in the first 24 months following diagnosis who were matched to 184 untreated patients. At the end of a 59-month median follow-up, 100 cases of compensated disease, 58 liver cancer and 163 deaths (55 liver related) were recorded. The 5-year rates of decompensated cirrhosis, hepatocellular carcinoma, liver-related and non-liver-related death were 4.4%, 2.7%, 5.0% and 8.9%, respectively. Multivariate analyses identified two variables with pejorative influence: alcohol consumption (RR = 4.29 for CD; RR = 5.76 for HCC; RR = 6.69 for liver-related death; P < 0.0001); HCV diagnosis unrelated to systematic screening (RR = 2.25 for CD; RR = 3.05 for HCC; RR = 4.31 for liver-related death, P < 0.03). In the matched subset, no significant benefit of antiviral therapy was observed. Nevertheless, among the 144 patients who achieved SVR, no death was observed. This population-based study showed substantial rates of decompensated cirrhosis, hepatocellular carcinoma and non-liver-related mortality. Alcohol consumption and absence of systematic screening were significant determinants of poor outcome, whereas treatment did not have significant influence.
Collapse
Affiliation(s)
- V Di Martino
- Service d'hépatologie, CHU Jean Minjoz, Besançon, France. vdimartino@chu
| | | | | | | | | | | |
Collapse
|
|
30
|
Bacchetti P, Boylan R, Astemborski J, Shen H, Mehta SH, Thomas DL, Terrault NA, Monto A. Progression of biopsy-measured liver fibrosis in untreated patients with hepatitis C infection: non-Markov multistate model analysis. PLoS One 2011; 6:e20104. [PMID: 21637766 PMCID: PMC3103523 DOI: 10.1371/journal.pone.0020104] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2010] [Accepted: 04/25/2011] [Indexed: 12/19/2022] Open
Abstract
Background Fibrosis stages from liver biopsies reflect liver damage from hepatitis C infection, but analysis is challenging due to their ordered but non-numeric nature, infrequent measurement, misclassification, and unknown infection times. Methods We used a non-Markov multistate model, accounting for misclassification, with multiple imputation of unknown infection times, applied to 1062 participants of whom 159 had multiple biopsies. Odds ratios (OR) quantified the estimated effects of covariates on progression risk at any given time. Results Models estimated that progression risk decreased the more time participants had already spent in the current stage, African American race was protective (OR 0.75, 95% confidence interval 0.60 to 0.95, p = 0.018), and older current age increased risk (OR 1.33 per decade, 95% confidence interval 1.15 to 1.54, p = 0.0002). When controlled for current age, older age at infection did not appear to increase risk (OR 0.92 per decade, 95% confidence interval 0.47 to 1.79, p = 0.80). There was a suggestion that co-infection with human immunodeficiency virus increased risk of progression in the era of highly active antiretroviral treatment beginning in 1996 (OR 2.1, 95% confidence interval 0.97 to 4.4, p = 0.059). Other examined risk factors may influence progression risk, but evidence for or against this was weak due to wide confidence intervals. The main results were essentially unchanged using different assumed misclassification rates or imputation of age of infection. Discussion The analysis avoided problems inherent in simpler methods, supported the previously suspected protective effect of African American race, and suggested that current age rather than age of infection increases risk. Decreasing risk of progression with longer time already spent in a stage was also previously found for post-transplant progression. This could reflect varying disease activity, with recent progression indicating active disease and high risk, while longer time already spent in a stage indicates quiescent disease and low risk.
Collapse
Affiliation(s)
- Peter Bacchetti
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America
- * E-mail:
| | - Ross Boylan
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America
| | - Jacquie Astemborski
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
| | - Hui Shen
- Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
- Division of Gastroenterology, San Francisco Veterans Affairs Medical Center, San Francisco, California, United States of America
| | - Shruti H. Mehta
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
| | - David L. Thomas
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Norah A. Terrault
- Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
- Department of Surgery, University of California San Francisco, San Francisco, California, United States of America
| | - Alexander Monto
- Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
- Division of Gastroenterology, San Francisco Veterans Affairs Medical Center, San Francisco, California, United States of America
| |
Collapse
|
|
31
|
Bailey J. An Assessment of the Use of Chimpanzees in Hepatitis C Research Past, Present and Future: 2. Alternative Replacement Methods. Altern Lab Anim 2010; 38:471-94. [DOI: 10.1177/026119291003800602] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The use of chimpanzees in hepatitis C virus (HCV) research was examined in the report associated with this paper ( 1: Validity of the Chimpanzee Model), in which it was concluded that claims of past necessity of chimpanzee use were exaggerated, and that claims of current and future indispensability were unjustifiable. Furthermore, given the serious scientific and ethical issues surrounding chimpanzee experimentation, it was proposed that it must now be considered redundant — particularly in light of the demonstrable contribution of alternative methods to past and current scientific progress, and the future promise that these methods hold. This paper builds on this evidence, by examining the development of alternative approaches to the investigation of HCV, and by reviewing examples of how these methods have contributed, and are continuing to contribute substantially, to progress in this field. It augments the argument against chimpanzee use by demonstrating the comprehensive nature of these methods and the valuable data they deliver. The entire life-cycle of HCV can now be investigated in a human (and much more relevant) context, without recourse to chimpanzee use. This also includes the testing of new therapies and vaccines. Consequently, there is no sound argument against the changes in public policy that propose a move away from chimpanzee use in US laboratories.
Collapse
Affiliation(s)
- Jarrod Bailey
- New England Anti-Vivisection Society, Boston, MA, USA
| |
Collapse
|
|
32
|
Sweeting MJ, Farewell VT, De Angelis D. Multi-state Markov models for disease progression in the presence of informative examination times: an application to hepatitis C. Stat Med 2010; 29:1161-74. [PMID: 20437454 DOI: 10.1002/sim.3812] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
In many chronic diseases it is important to understand the rate at which patients progress from infection through a series of defined disease states to a clinical outcome, e.g. cirrhosis in hepatitis C virus (HCV)-infected individuals or AIDS in HIV-infected individuals. Typically data are obtained from longitudinal studies, which often are observational in nature, and where disease state is observed only at selected examinations throughout follow-up. Transition times between disease states are therefore interval censored. Multi-state Markov models are commonly used to analyze such data, but rely on the assumption that the examination times are non-informative, and hence the examination process is ignorable in a likelihood-based analysis. In this paper we develop a Markov model that relaxes this assumption through the premise that the examination process is ignorable only after conditioning on a more regularly observed auxiliary variable. This situation arises in a study of HCV disease progression, where liver biopsies (the examinations) are sparse, irregular, and potentially informative with respect to the transition times. We use additional information on liver function tests (LFTs), commonly collected throughout follow-up, to inform current disease state and to assume an ignorable examination process. The model developed has a similar structure to a hidden Markov model and accommodates both the series of LFT measurements and the partially latent series of disease states. We show through simulation how this model compares with the commonly used ignorable Markov model, and a Markov model that assumes the examination process is non-ignorable.
Collapse
Affiliation(s)
- M J Sweeting
- MRC Biostatistics Unit, Institute of Public Health, Robinson Way, Cambridge CB2 0SR, UK.
| | | | | |
Collapse
|
|
33
|
Jovanović M, Jovanović B, Potić M, Konstantinović L, Vrbić M, Radovanović-Dinić B, Kostić V. Characteristics of chronic hepatitis C among intravenous drug users: a comparative analysis. Bosn J Basic Med Sci 2010; 10:153-7. [PMID: 20507297 DOI: 10.17305/bjbms.2010.2715] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
Hepatitis C virus (HCV) usually evades the host's immune system and persists as a chronic infection. Intravenous drug users (IVDU) represent the majority of patients infected with HCV. Combined therapy of chronic hepatitis C (CHC) with peginterferon alpha-2a and ribavirin can be successful even when patients continue the intravenous drug use. In this study, we compared the characteristics of age, gender, genotype, and stage of fibrosis and the therapy outcome among IVDU and patients with no history of drug use. The study included 69 patients diagnosed with chronic hepatitis C, evaluated and treated at the Clinic for infectious diseases in Nis from 2005 to 2009. HCV RNA was detected by a polymerase chain reaction and the determination of genotypes was undertaken. Liver biopsies were examined histopathologically. Patients received a combined treatment of peginterferon alfa-2a and ribavirin. Therapy efficiency was evaluated based on the achievement of the sustained virological response (SVR). A comparison of characteristics was performed with the use of Mann-Whitney U test, chi-square (chi2) test and logistic regression. IVDU were significantly younger than patients in the control group. Prevalence of stage 1 fibrosis was significantly higher among IVDU. The therapy outcome is influenced by the patient's age and HCV genotypes. Each year added to one patient decreased the therapy efficiency by 8.1%, while genotypes 2 and 3 experienced a therapy which was 2.08 times more efficient than in other cases. IVDU represent a specific population different from non-using patients. However, they can be treated effectively if an adequate patient-doctor relationship is established.
Collapse
Affiliation(s)
- Maja Jovanović
- Clinic for infectious diseases, University of Nis Clinics Centre, Zoran Djindjić Boulevard 48, Nis, Serbia
| | | | | | | | | | | | | |
Collapse
|
|
34
|
Non-Markov multistate modeling using time-varying covariates, with application to progression of liver fibrosis due to hepatitis C following liver transplant. Int J Biostat 2010; 6:Article 7. [PMID: 20305705 DOI: 10.2202/1557-4679.1213] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Multistate modeling methods are well-suited for analysis of some chronic diseases that move through distinct stages. The memoryless or Markov assumptions typically made, however, may be suspect for some diseases, such as hepatitis C, where there is interest in whether prognosis depends on history. This paper describes methods for multistate modeling where transition risk can depend on any property of past progression history, including time spent in the current stage and the time taken to reach the current stage. Analysis of 901 measurements of fibrosis in 401 patients following liver transplantation found decreasing risk of progression as time in the current stage increased, even when controlled for several fixed covariates. Longer time to reach the current stage did not appear associated with lower progression risk. Analysis of simulation scenarios based on the transplant study showed that greater misclassification of fibrosis produced more technical difficulties in fitting the models and poorer estimation of covariate effects than did less misclassification or error-free fibrosis measurement. The higher risk of progression when less time has been spent in the current stage could be due to varying disease activity over time, with recent progression indicating an "active" period and consequent higher risk of further progression.
Collapse
|
|
35
|
Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C. J Hepatol 2009; 51:655-66. [PMID: 19665246 DOI: 10.1016/j.jhep.2009.05.016] [Citation(s) in RCA: 203] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2009] [Revised: 04/09/2009] [Accepted: 05/05/2009] [Indexed: 02/08/2023]
Abstract
BACKGROUND/AIMS While several risk factors for the histological progression of chronic hepatitis C have been identified, the contribution of HCV genotypes to liver fibrosis evolution remains controversial. The aim of this study was to assess independent predictors for fibrosis progression. METHODS We identified 1189 patients from the Swiss Hepatitis C Cohort database with at least one biopsy prior to antiviral treatment and assessable date of infection. Stage-constant fibrosis progression rate was assessed using the ratio of fibrosis Metavir score to duration of infection. Stage-specific fibrosis progression rates were obtained using a Markov model. Risk factors were assessed by univariate and multivariate regression models. RESULTS Independent risk factors for accelerated stage-constant fibrosis progression (>0.083 fibrosis units/year) included male sex (OR=1.60, [95% CI 1.21-2.12], P<0.001), age at infection (OR=1.08, [1.06-1.09], P<0.001), histological activity (OR=2.03, [1.54-2.68], P<0.001) and genotype 3 (OR=1.89, [1.37-2.61], P<0.001). Slower progression rates were observed in patients infected by blood transfusion (P=0.02) and invasive procedures or needle stick (P=0.03), compared to those infected by intravenous drug use. Maximum likelihood estimates (95% CI) of stage-specific progression rates (fibrosis units/year) for genotype 3 versus the other genotypes were: F0-->F1: 0.126 (0.106-0.145) versus 0.091 (0.083-0.100), F1-->F2: 0.099 (0.080-0.117) versus 0.065 (0.058-0.073), F2-->F3: 0.077 (0.058-0.096) versus 0.068 (0.057-0.080) and F3-->F4: 0.171 (0.106-0.236) versus 0.112 (0.083-0.142, overall P<0.001). CONCLUSIONS This study shows a significant association of genotype 3 with accelerated fibrosis using both stage-constant and stage-specific estimates of fibrosis progression rates. This observation may have important consequences for the management of patients infected with this genotype.
Collapse
|
|
36
|
Abstract
In the late 1960's, only types A and B hepatitis were believed to exist, distinguished by circumstances of exposure and incubation periods. In the early 1970's, studies of transfusion recipients were begun with the belief that hepatitis B would be responsible should transfusion-associated hepatitis develop. After discovery of the viruses of hepatitis A and B, neither agent was found responsible, hence non-A, non-B (NANB) hepatitis. Initial follow-up of these cases showed that approximately 50% developed chronic hepatitis based on persistence of serum enzymes for at least 6 months. Approximately 15 years later, after the hepatitis C virus had been identified as the cause for NANB hepatitis, chronic hepatitis was found to develop more frequently as indicated by persistent viral infection in over 80% of infected adults but in only about 50% of infected children or young women. Follow-up over 2 to 4 decades indicated that many infected persons developed progressive hepatic fibrosis, sometimes culminating in cirrhosis and/or liver cancer. Long-term natural history studies have proved to be challenging because disease onset is often silent and progression extremely slow. Differing strategies have been used to determine the natural history, the descriptions and results of which are presented in this review.
Collapse
Affiliation(s)
- Leonard B. Seeff
- National Institute of Diabetes and Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| |
Collapse
|
|
37
|
PATEL H, HEATHCOTE EJ. When to treat and the benefits of treating hepatitis C in patients with haemophilia. Haemophilia 2009; 15:20-32. [DOI: 10.1111/j.1365-2516.2008.01917.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
|
|
38
|
Cua IHY, Hui JM, Kench JG, George J. Genotype-specific interactions of insulin resistance, steatosis, and fibrosis in chronic hepatitis C. Hepatology 2008; 48:723-31. [PMID: 18688878 DOI: 10.1002/hep.22392] [Citation(s) in RCA: 89] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED The interaction between insulin resistance (IR), steatosis and genotype to fibrosis in chronic hepatitis C virus (HCV) infection has not been comprehensively assessed. We hypothesized that IR is a key mediator for the development of both steatosis and fibrosis in 346 untreated, nondiabetic patients solely infected with either genotype 1 or 3. We examined for genotype-specific interactions between IR, steatosis and fibrosis by performing subgroup analyses. Because cirrhosis is known to cause IR, we repeated the analysis in a cohort of 313 noncirrhotic HCV-infected patients. We confirmed the impact of IR on fibrosis by analysis of 153 lean subjects in whom any effect of steatosis would be minimized. In HCV genotype 3 patients, increased steatosis was linked to high viral load (P = 0.001), and was not associated with fibrosis (P = 0.1). In contrast, body mass index (P = 0.04) and homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.01) contributed directly to steatosis in HCV genotype 1. HOMA-IR rather than steatosis was independently associated with fibrosis for both HCV genotype 1 (OR, 3.22; P = 0.02) and genotype 3 (OR, 3.17; P = 0.04). Exclusion of cirrhotic subjects did not alter the findings with respect to the greater contribution of IR compared to hepatic steatosis, as a predictor of fibrosis (P = 0.02). Genotype-specific subgroup analyses did not alter this finding. The extent of HOMA-IR remained significantly associated with fibrosis in lean patients, independent of the confounding effect of body mass index on IR (OR, 8.02; P = 0.003). CONCLUSION IR is a major independent determinant of fibrosis in chronic HCV infection, regardless of the genotype and the severity of liver damage.
Collapse
Affiliation(s)
- Ian Homer Y Cua
- Storr Liver Unit, Westmead Millennium Institute and Department of Gastroenterology and Hepatology, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
| | | | | | | |
Collapse
|
|
39
|
Thein HH, Yi Q, Dore GJ, Krahn MD. Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression. Hepatology 2008; 48:418-31. [PMID: 18563841 DOI: 10.1002/hep.22375] [Citation(s) in RCA: 620] [Impact Index Per Article: 36.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
UNLABELLED Published estimates of liver fibrosis progression in individuals with chronic hepatitis C virus (HCV) infection are heterogeneous. We aimed to estimate stage-specific fibrosis progression rates and their determinants in these individuals. A systematic review of published prognostic studies was undertaken. Study inclusion criteria were as follows: (1) presence of HCV infection determined by serological assays; (2) available information about age at assessment of liver disease or HCV acquisition; (3) duration of HCV infection; and (4) histological and/or clinical diagnosis of cirrhosis. Annual stage-specific transition probabilities (F0-->F1, ... , F3-->F4) were derived using the Markov maximum likelihood estimation method and a meta-analysis was performed. The impact of potential covariates was evaluated using meta-regression. A total of 111 studies of individuals with chronic HCV infection (n = 33,121) were included. Based on the random effects model, the estimated annual mean (95% confidence interval) stage-specific transition probabilities were: F0-->F1 0.117 (0.104-0.130); F1-->F2 0.085 (0.075-0.096); F2-->F3 0.120 (0.109-0.133); and F3-->F4 0.116 (0.104-0.129). The estimated prevalence of cirrhosis at 20 years after the infection was 16% (14%-19%) for all studies, 18% (15%-21%) for cross-sectional/retrospective studies, 7% (4%-14%) for retrospective-prospective studies, 18% (16%-21%) for studies conducted in clinical settings, and 7% (4%-12%) for studies conducted in nonclinical settings. Duration of infection was the most consistent factor significantly associated with progression of fibrosis. CONCLUSION Our large systematic review provides increased precision in estimating fibrosis progression in chronic HCV infection and supports nonlinear disease progression. Estimates of progression to cirrhosis from studies conducted in clinical settings were lower than previous estimates.
Collapse
Affiliation(s)
- Hla-Hla Thein
- University Health Network, Division of Clinical Decision-Making and Health Care Research, Toronto, Ontario, Canada.
| | | | | | | |
Collapse
|
|
40
|
Bacchetti P, Tien PC, Seaberg EC, O'Brien TR, Augenbraun MH, Kral AH, Busch MP, Edlin BR. Estimating past hepatitis C infection risk from reported risk factor histories: implications for imputing age of infection and modeling fibrosis progression. BMC Infect Dis 2007; 7:145. [PMID: 18070362 PMCID: PMC2238758 DOI: 10.1186/1471-2334-7-145] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2007] [Accepted: 12/10/2007] [Indexed: 01/16/2023] Open
Abstract
Background Chronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure. Study of fibrosis progression often relies on imputing the time of infection, often as the reported age of first injection drug use. We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates. Methods We analyzed cross-sectional data on hepatitis C antibody status and reported risk factor histories from two large studies, the Women's Interagency HIV Study and the Urban Health Study, using modern survival analysis methods for current status data to model past infection risk year by year. We compared fitted distributions of past infection risk to reported age of first injection drug use. Results Although injection drug use appeared to be a very strong risk factor, models for both studies showed that many subjects had considerable probability of having been infected substantially before or after their reported age of first injection drug use. Persons reporting younger age of first injection drug use were more likely to have been infected after, and persons reporting older age of first injection drug use were more likely to have been infected before. Conclusion In cross-sectional studies of fibrosis progression where date of HCV infection is estimated from risk factor histories, modern methods such as multiple imputation should be used to account for the substantial uncertainty about when infection occurred. The models presented here can provide the inputs needed by such methods. Using reported age of first injection drug use as the time of infection in studies of fibrosis progression is likely to produce a spuriously strong association of younger age of infection with slower rate of progression.
Collapse
Affiliation(s)
- Peter Bacchetti
- Box 0560, Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143, USA.
| | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Chauvel O, Lacombe K, Bonnard P, Lascoux-Combe C, Molina JM, Miailhes P, Girard PM, Carrat F. Risk Factors for Acute Liver Enzyme Abnormalities in HIV-Hepatitis B Virus-Coinfected Patients on Antiretroviral Therapy. Antivir Ther 2007. [DOI: 10.1177/135965350701200706] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Background Little is known about the prognostic factors of acute liver enzyme variations in HIV-hepatitis B virus (HBV)-coinfected patients. Objectives To identify prognostic factors of acute liver enzyme abnormalities in HIV-HBV-coinfected patients with a focus on the putative role of antiretroviral drugs. Design Data from a 3-year, prospective, multicentre cohort study involving HIV-HBV patients were used. Methods A Markov model was used to identify prognostic factors of acute episodes of cytolysis and cholestasis in 300 HIV-HBV-coinfected patients. The effect of antiretroviral therapy was analysed according to the classes of drugs, duration of treatment and treatment modifications. Results The incidence rates of acute episodes of cytolysis and cholestasis were 13.4 per 100 patient-years (95% confidence interval [CI] 9.5–17.3) and 7.1 per 100 patient-years (95% CI 4.2–10.0), respectively (median follow up 34.1 months). Independent risk factors for cytolysis were a high level of HBV or HIV replication, as well as a low of CD4+ T-cell count. No antiretroviral drug was associated with cytolysis, whereas protease inhibitors seemed to be independently associated with cholestasis, along with treatment modifications and the duration of HIV infection. Conclusion Acute and reversible episodes of cytolysis or cholestasis were common and associated with virus- and host-related determinants. The choice of the optimal antiretroviral combination in HIV-HBV-coinfected patients must take into account the necessity of exerting an efficient control of HIV and HBV replication (associated with transient cytolysis) and the risk of inducing cholestasis (associated with the use of protease inhibitors and treatment modifications).
Collapse
Affiliation(s)
- Olivia Chauvel
- AP-HP, Hôpital Saint-Antoine, Service de Maladies Infectieuses et Tropicales, Paris, France
- Université Pierre et Marie Curie, Paris, France
- Inserm, U707, Paris, France
| | - Karine Lacombe
- AP-HP, Hôpital Saint-Antoine, Service de Maladies Infectieuses et Tropicales, Paris, France
- Université Pierre et Marie Curie, Paris, France
- Inserm, U707, Paris, France
| | - Philippe Bonnard
- AP-HP, Hôpital Tenon, Service de Maladies Infectieuses et Tropicales, Paris, France
| | | | - Jean-Michel Molina
- AP-HP, Hôpital Saint-Louis, Service de Maladies Infectieuses et Tropicales, Paris, France
| | - Patrick Miailhes
- Hospices Civils de Lyon, Service d'hépatologie, Hôtel-Dieu, Lyon, France
| | - Pierre-Marie Girard
- AP-HP, Hôpital Saint-Antoine, Service de Maladies Infectieuses et Tropicales, Paris, France
| | | |
Collapse
|
|
42
|
Cadranel JF, Lahmek P, Causse X, Bellaiche G, Bettan L, Fontanges T, Medini A, Henrion J, Chousterman M, Condat B, Hervio P, Periac P, Eugène C, Moindrot H, Grasset D, Nouel O, Pilette C, Szostak-Talbodec N, Cayla JM, Si-Ahmed SN, Dumouchel P, Pariente A, Lesgourgues B, Denis J. Epidemiology of chronic hepatitis B infection in France: risk factors for significant fibrosis--results of a nationwide survey. Aliment Pharmacol Ther 2007; 26:565-76. [PMID: 17661760 DOI: 10.1111/j.1365-2036.2007.03400.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Epidemiological data concerning hepatitis B are scarce in France. AIM To describe epidemiological, clinical, virological and histological features of HBsAg-positive patients followed at non-academic hospitals in France. METHODS Clinical, biological, virological and histological data of all HBsAg-positive consecutive patients observed from April 1, 2001 to May 31, 2002 in participating centres were recorded prospectively. Multivariate analyses of factors associated with significant fibrosis and cirrhosis were performed. RESULTS Nearly 1166 HBsAg-positive patients were seen in the 58 centres: 671 males and 495 females from metropolitan France (32%) and from outside metropolitan France (68%); mean age 41 +/- 15 years. Twenty-nine percent of patients were probable HBsAg inactive carriers, while 50% had chronic hepatitis; 43% of these were HBeAg-positive and 57% HBeAg-negative. Liver biopsy had been performed in 558 (51%) patients; 205 (17.6%) patients had cirrhosis. By multivariate analysis, factors associated with significant fibrosis were: age >40 years (P < 0.05), HBeAg-negative status (P < 0.02) and histological activity (P < 0.0001). Factors associated with cirrhosis: age (P < 0.0001), platelet count <150 000/mm(3) (P < 0.0001) and viral co-infection (P < 0.03). CONCLUSION HBV infection represents a significant workload for hepatogastroenterologists at non-academic hospitals in France.
Collapse
Affiliation(s)
- J-F Cadranel
- Hepato-gastroenterology and Diabetology Section, Centre Hospitalier Laennec, 60109 Creil, France.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
43
|
Baillargeon J, Soloway RD, Paar D, Giordano TP, Murray O, Grady J, Williams B, Pulvino J, Raimer BG. End-stage liver disease in a state prison population. Ann Epidemiol 2007; 17:808-13. [PMID: 17689260 DOI: 10.1016/j.annepidem.2007.04.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2007] [Revised: 04/11/2007] [Accepted: 04/12/2007] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Information on the epidemiology of end-stage liver disease (ESLD) in US correctional populations is limited. We examined the prevalence, mortality and clinical characteristics of ESLD in the nation's second largest state prison system. METHODS We collected and analyzed medical and demographic data from 370,511 offenders incarcerated in Texas' prison system during a 3.5-year period. RESULTS ESLD was diagnosed in 484 inmates (131/100,000); 213 (57/100,000) died of ESLD. Offenders who were Hispanic, 30-49 years of age, > or =50 years of age, HIV monoinfected, hepatitis C virus (HCV) monoinfected, or HIV/HCV coinfected had elevated ESLD prevalence and mortality rates. CONCLUSIONS ESLD mortality in Texas' prison population is approximately 3 times higher than that of the general population, reflecting elevated rates of HCV and HIV/HCV coinfection among prisoners. Ultimately, the only viable treatment option for many prisoners with ESLD will be liver transplantation. The enormous costs of organ transplantation and immunosuppressive therapy are staggering and have the potential to decimate the healthcare budgets of most prison systems. Consequently, it is imperative that correctional healthcare programs expand HCV treatment and prevention strategies.
Collapse
Affiliation(s)
- Jacques Baillargeon
- Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX 77555, USA.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Bialek SR, Terrault NA. The changing epidemiology and natural history of hepatitis C virus infection. Clin Liver Dis 2006; 10:697-715. [PMID: 17164113 DOI: 10.1016/j.cld.2006.08.003] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Injection drug use remains the predominant mode of transmission of hepatitis C virus (HCV) infection. Growing numbers of persons who have been chronically infected with HCV for 20 or more years are coming to medical attention and are at risk for serious complications of chronic infection, including cirrhosis and hepatocellular carcinoma. Factors linked with the development of advanced fibrosis and cirrhosis include age at infection, duration of infection, heavy alcohol use, coinfections with HIV or hepatitis B virus, and male sex. Emerging risk factors for disease progression include steatosis, insulin resistance (and factors associated with the metabolic syndrome), and host genetics.
Collapse
Affiliation(s)
- Stephanie R Bialek
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA
| | | |
Collapse
|
|
45
|
Zarski JP, Marcellin P, Leroy V, Trepo C, Samuel D, Ganne-Carrie N, Barange K, Canva V, Doffoel M, Cales P. Characteristics of patients with chronic hepatitis B in France: predominant frequency of HBe antigen negative cases. J Hepatol 2006; 45:355-60. [PMID: 16750585 DOI: 10.1016/j.jhep.2006.03.007] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2005] [Revised: 02/23/2006] [Accepted: 03/06/2006] [Indexed: 12/17/2022]
Abstract
BACKGROUND/AIMS An increasing prevalence of HBe antigen (HBeAg) negative chronic hepatitis B has been recently reported in many countries. The aim of this study was to analyze the frequency and the characteristics of HBeAg-negative as compared with HBeAg-positive chronic hepatitis B in France. METHODS Eight hundred and sixty-five patients with histologically proven chronic hepatitis B seen in 26 University centers were included. The proportion with HBeAg-negative chronic hepatitis B was 72% and higher in patients born in Africa, Middle East, Eastern, and Southern Europe than in those of French or Asian origin. HBeAg-negative patients were significantly older (p<0.001) and had lower ALT levels and HBV DNA serum levels (p<0.01) than HBeAg-positive patients. An unknown source of infection was more prevalent in HBeAg-negative patients (p<0.05). Fibrosis score (p<0.05) and proportion of cirrhosis (p<0.01) were significantly higher in HBeAg-negative patients. Age older than 50 years, male gender and viral load lower than 5 logs10 copies/mL were independently associated with cirrhosis. RESULTS HBeAg-negative chronic hepatitis B is predominant in France. This observation is important for an optimized clinical management and future therapeutic trials in chronic hepatitis B.
Collapse
Affiliation(s)
- Jean-Pierre Zarski
- Département d'Hépato-gastroentérologie, CHU de Grenoble-BP 217-38043 Grenoble CEDEX 9, France.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Massard J, Ratziu V, Thabut D, Moussalli J, Lebray P, Benhamou Y, Poynard T. Natural history and predictors of disease severity in chronic hepatitis C. J Hepatol 2006; 44:S19-24. [PMID: 16356583 DOI: 10.1016/j.jhep.2005.11.009] [Citation(s) in RCA: 153] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Cirrhosis is the end-stage consequence of fibrosis progression in patients with chronic hepatitis C. The median time from infection to cirrhosis is 30 years, with a high inter-individual variability, which is now better understood. Several factors have been clearly shown to be associated with fibrosis progression rate: duration of infection, age, male gender, alcohol consumption, HIV co-infection and low CD4 count. Metabolic conditions such as steatosis, being overweight and diabetes are emerging as independent co-factors of fibrogenesis. The recent validation of non-invasive biomarkers should facilitate the study of fibrosis progression in large populations.
Collapse
Affiliation(s)
- Julien Massard
- Service d'Hépato-Gastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, 47 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France
| | | | | | | | | | | | | |
Collapse
|
|
47
|
Vermeer KA, Vos FM, Lo B, Zhou Q, Lemij HG, Vossepoel AM, van Vliet LJ. Modeling of scanning laser polarimetry images of the human retina for progression detection of glaucoma. IEEE TRANSACTIONS ON MEDICAL IMAGING 2006; 25:517-28. [PMID: 16689257 DOI: 10.1109/tmi.2006.871433] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
The development of methods to detect slowly progressing diseases is often hampered by the time-consuming acquisition of a sufficiently large data set. In this paper, a method is presented to model the change in images acquired by scanning laser polarimetry, for the detection of glaucomatous progression. The model is based on image series of 23 healthy eyes and incorporates colored noise, incomplete cornea compensation and masking by the retinal blood vessels. Additionally, two methods for detecting progression, taking either one or two follow-up visits into account, are discussed and tested on these simulated images. Both methods are based on Student's t-tests, morphological operations and anisotropic filtering. The images simulated by the model are visually pleasing, show corresponding statistical properties to the real images and are used to optimize the detection methods. The results show that detecting progression based on two follow-up visits greatly improves the sensitivity without adversely affecting the specificity.
Collapse
Affiliation(s)
- Koen A Vermeer
- Glaucoma Service, Rotterdam Eye Hospital, Schiedamsevest 180, NL-3011 BH Rotterdam, The Netherlands.
| | | | | | | | | | | | | |
Collapse
|
|
48
|
Sweeting MJ, De Angelis D, Neal KR, Ramsay ME, Irving WL, Wright M, Brant L, Harris HE. Estimated progression rates in three United Kingdom hepatitis C cohorts differed according to method of recruitment. J Clin Epidemiol 2006; 59:144-52. [PMID: 16426949 DOI: 10.1016/j.jclinepi.2005.06.008] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2005] [Revised: 05/19/2005] [Accepted: 06/20/2005] [Indexed: 12/20/2022]
Abstract
OBJECTIVES To estimate hepatitis C virus (HCV) progression rates between disease stages prior to cirrhosis, using data from liver biopsies in three observational cohorts. To demonstrate how the method of cohort recruitment can influence the estimation of HCV-progression rates. STUDY DESIGN AND SETTING Data came from three United Kingdom observational cohorts, assembled from different referral sources. In total, 987 HCV-infected patients with an estimated (or known) date of infection and at least one histologically scored liver biopsy were eligible for inclusion in the analysis. Liver biopsy scores were used to determine the stage of HCV-related liver disease. A three-state continuous time Markov model was used to estimate covariate-specific average probabilities of progression of disease. RESULTS After adjusting for confounders, considerably different rates of disease progression were estimated in the three cohorts. For a group of patients with the same demographics, the estimated 20-year probability of progression to cirrhosis was 12% (95% confidence interval CI = 6-22) in a hospital-based cohort, 6% (95% CI = 3-13) in a posttransfusion cohort, and 23% (95% CI = 14-37) in a cohort recruited from a tertiary referral center. CONCLUSION Researchers using estimates of disease progression should be aware that the method of cohort recruitment has considerable influence on the progression rates that are derived.
Collapse
Affiliation(s)
- Michael J Sweeting
- MRC Biostatistics Unit, Institute of Public Health, Robinson Way, Cambridge CB2 2SR, United Kingdom.
| | | | | | | | | | | | | | | |
Collapse
|
|
49
|
Poynard T, Ratziu V, Kim N, Deuffic-Burban S. Age and gender will survive to competing risks as fibrosis factors. Gastroenterology 2005; 128:519-20; author reply 520-1. [PMID: 15685574 DOI: 10.1053/j.gastro.2004.12.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
|
|
50
|
Abstract
Chronic hepatitis C is a leading cause of cirrhosis, hepatocellular carcinoma, digestive tract haemorrhage and hepatic insufficiency. The present best strategy to prevent severe complications of chronic hepatitis C is the decrease of fibrosis progression. Recently, pegylated interferon combination treatments of chronic hepatitis C have made it possibly to obtain 60% sustained virological responses. Pooled individual data from 3,010 naïve patients with pre-treatment and post-treatment biopsies from 4 randomised trials have shown that all regimens significantly reduced the fibrosis progression rates in comparison to the pre-treatment ones. Six factors were independently associated with the absence of significant fibrosis after treatment: baseline fibrosis stage, sustained viral response, age <40 years, body mass index <27 kg/m2, no or minimal baseline activity, and viral load <3.5 x 10(6) copies/ml. In virological non-responders after the combination of ribavirin and pegylated interferon, the best strategy is still unknown. From a scientific point of view these patients should be included in randomised trials of maintenance therapy. From a pragmatic point of view, if inclusion in a trial is not possible, treatment with low-dose pegylated interferon can be considered in patients with rapid fibrosis progression rates or high risk factors. Non-invasive biochemical markers of liver fibrosis should facilitate the management.
Collapse
Affiliation(s)
- Thierry Poynard
- Service d'Hépato-Gastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
| |
Collapse
|