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Attanasi ML, Gregoski MJ, Rockey DC. Racial Differences in Liver Fibrosis Burden. Dig Dis Sci 2025:10.1007/s10620-025-08936-w. [PMID: 40102343 DOI: 10.1007/s10620-025-08936-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 02/15/2025] [Indexed: 03/20/2025]
Abstract
BACKGROUND & AIMS Liver histology is the classic method for staging the severity of liver fibrosis, which in turn is an important predictor of clinical outcome. Here, we have hypothesized that the susceptibility to develop fibrosis varies among racial groups. METHODS We examined the histology of all patients over 18 years of age who underwent liver biopsy at the Medical University of South Carolina from 1/1/2013 to 7/1/2021. Patients with malignancy, liver metastases, or missing data were excluded. Fibrosis was quantified using the Batts-Ludwig system (F0 = no fibrosis to F4 = histological cirrhosis). Racial groups were propensity matched based on age, gender, diabetes, alcohol consumption, and CDC/ATSDR Social Vulnerability Index Themes to mitigate the risk of selection bias. RESULTS We identified 1101 patients with liver biopsy histological fibrosis scores. The cohort included 23% Black patients. After propensity matching, Black patients were significantly more likely to have Hepatitis C (73/228 (32%) vs 45/228 (20%), p < 0.001) and autoimmune hepatitis (34/228 (15%) vs 6/228 (3%), p < 0.001) than White patients, while White patients were significantly more likely to have metabolic dysfunction associated steatotic liver disease (71/228 (31%) vs 18/228 (8%), p < 0.001). White patients were significantly more likely to have cirrhosis than Black patients (White - 89/228 (39%) vs Black - 68/228 (30%), p < 0.05). CONCLUSION White patients had a greater overall burden of advanced fibrosis (F4/cirrhosis) than Black patients, independent of etiology. The data suggest that fibrosis risk and/or progression may be worse in White than Black patients.
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Affiliation(s)
- Michael L Attanasi
- Department of Internal Medicine, North Shore University Hospital, Manhasset, NY, USA
| | - Mathew J Gregoski
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC, USA
| | - Don C Rockey
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC, USA.
- Department of Internal Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 803, Charleston, SC, 29425, USA.
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Zago D, Pozzetto I, Pacenti M, Brancaccio G, Ragolia S, Basso M, Parisi SG. Circulating Genotypes of Hepatitis C Virus in Italian Patients before and after the Application of Wider Access Criteria to HCV Treatment. Open Microbiol J 2022. [DOI: 10.2174/18742858-v16-e2205300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Aims:
The aims of this study were to report a description of the HCV genotype distribution in adult Italians and non-Italians subjects tested in the Microbiology and Virology Unit of the Padova University Hospital from January 2016 (after about one year from the availability of DAAs) to December 2018 and to compare genotype frequencies in the 12-month period before and after the application of the wider access criteria to HCV treatment.
Background:
Hepatitis C virus (HCV) infection is a major health problem, but the availability of direct-acting antivirals (DAAs) has dramatically changed HCV disease natural history because these drugs have excellent tolerability and they can eliminate the virus in almost all treated patients.
Objective:
The objective was to describe the circulating HCV genotypes in high-income countries in order to help health authorities in the future organization of DAAs treatment strategies; this aspect is not limited to drug prescription, but it also includes the identification of infected individuals who are undiagnosed, which is the limiting step to achieve the HCV elimination goal.
Methods:
Adult patients who had HCV genotype performed from 01/01/16 to 31/12/18 in the Microbiology and Virology Unit of the Padova University Hospital were included in the study: the two 12-month periods were April 2016-March 2017 (before period, BEF) and April 2017-March 2018 (after period, AFT).
Results:
Italians were 2168 (91.2%) and non-Italians were 208 (8.8%). Italians median age was 55 years, and females were older. Italians had a lower genotype 1 (p=0.0012) and higher genotype 2 frequencies (p<0.0001) with respect to non-Italians. Most patients aged 38-67 years: Italians were more represented in class age 48-57 years (p=0.0138), 68-77 years (p=0.001) and ≥78 years (p<0.0001); subjects with genotype 3 were the youngest and those with genotype 2 the oldest. Italian patients typed in the AFT and BEF were comparable; only a lower frequency of genotype 1 males and younger age in genotype 3 were found in AFT.
Conclusion:
Italians were older with respect to non-Italians, which implies that a different age based screening program could be applied. Italian genotype 3 subjects represent a cohort to focus on for the risk of therapeutic failure. Patients tested after the extended criteria for HCV treatment were very similar to those tested before, suggesting that HCV burden in Italians is higher than expected.
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Pereira LMS, da Silva Graça Amoras E, da Silva Conde SRS, Demachki S, dos Santos EJM, Lima SS, Ishak R, Rosário Vallinoto AC. NGF (-198C > T, Ala35Val) and p75 NTR (Ser205Leu) gene mutations are associated with liver function in different histopathological profiles of the patients with chronic viral hepatitis in the Brazilian Amazon. Mol Med 2020; 26:12. [PMID: 31996124 PMCID: PMC6990582 DOI: 10.1186/s10020-019-0134-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 12/29/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUNDS Neural growth factor (NGF) is a neurotrophin that can interact with the p75NTR receptor and initiate a cascade of reactions that determines cell survival or death, and both are associated with the physiology of liver tissue. Single nucleotide polymorphisms (SNPs) in the NGF and p75NTR genes have been investigated in different pathologies; however, there are no studies that have analyzed their biological roles in the hepatic microenvironment. In the present study, we evaluated the impact of SNPs in these genes on the maintenance of liver function at different stages of inflammation and fibrosis in patients with chronic viral liver disease in the Brazilian Amazon. METHODS The SNPs -198C > T, Arg80Gln, Val72Met, Ala35Val, Ala18Ala and Ser205Leu were genotyped by real-time PCR in samples from patients with chronic viral hepatitis stratified by stage of inflammation and liver fibrosis. Histopathological, viral load (VL), liver enzyme and comorbidities data were obtained from updated medical records. Other aspects were highlighted by applied epidemiological questionnaires. RESULTS The -198C/T and Ala35Val polymorphisms in NGF were associated with changes in histopathological profiles, VL and liver enzymes. Ser205Leu polymorphism in p75NTR was associated only with changes in VL and liver enzymes. Polymorphic frequencies were variable among different ethnic populations, mainly for biologically relevant polymorphisms. A multifactorial network of interactions has been established based on genetic, virological, behavioral and biochemical aspects. CONCLUSION Mutations in the NGF (-198C > T, Ala35Val) and p75NTR (Ser205Leu) genes, within the list of multifactorial aspects, are associated with liver function in different histopathological profiles of patients with chronic viral liver disease in the Brazilian Amazon.
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Affiliation(s)
- Leonn Mendes Soares Pereira
- Virology Laboratory, Biological Science Institute, Federal University of Pará, Belém, Pará Brazil
- Postgraduate Program in Biology of Infectious and Parasitic Agents, Biological Science Institute, Federal University of Pará, Belém, Pará Brazil
| | | | | | - Sâmia Demachki
- School of Medicine, Health Science Institute, Federal University of Pará, Belém, Pará Brazil
| | - Eduardo José Melo dos Santos
- Postgraduate Program in Biology of Infectious and Parasitic Agents, Biological Science Institute, Federal University of Pará, Belém, Pará Brazil
- Laboartory of Human and Medical Genetics, Biological Science Institute, Federal University of Pará, Belém, Pará Brazil
| | - Sandra Souza Lima
- Virology Laboratory, Biological Science Institute, Federal University of Pará, Belém, Pará Brazil
| | - Ricardo Ishak
- Virology Laboratory, Biological Science Institute, Federal University of Pará, Belém, Pará Brazil
- Postgraduate Program in Biology of Infectious and Parasitic Agents, Biological Science Institute, Federal University of Pará, Belém, Pará Brazil
| | - Antonio Carlos Rosário Vallinoto
- Virology Laboratory, Biological Science Institute, Federal University of Pará, Belém, Pará Brazil
- Postgraduate Program in Biology of Infectious and Parasitic Agents, Biological Science Institute, Federal University of Pará, Belém, Pará Brazil
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4
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Erman A, Krahn MD, Hansen T, Wong J, Bielecki JM, Feld JJ, Wong WWL, Grootendorst P, Thein HH. Estimation of fibrosis progression rates for chronic hepatitis C: a systematic review and meta-analysis update. BMJ Open 2019; 9:e027491. [PMID: 31719068 PMCID: PMC6858137 DOI: 10.1136/bmjopen-2018-027491] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES Mathematical models are increasingly important in planning for the upcoming chronic hepatitis C (CHC) elimination efforts. Such models require reliable natural history inputs to make accurate predictions on health and economic outcomes. Yet, hepatitis C virus disease progression is known to vary widely in the literature and published inputs are currently outdated. The objectives of this study were to obtain updated estimates of fibrosis progression rates (FPR) in treatment-naïve patients with CHC and to explore sources of heterogeneity. DESIGN A systematic review was conducted using Ovid-MEDLINE, Ovid-EMBASE and PubMed databases (January 1990 to January 2018) to identify observational studies of hepatic fibrosis in treatment-naïve patients with CHC. OUTCOMES Stage-constant FPRs were estimated for each study given the reported fibrosis scores and duration of infection. Stage-specific FPRs (ie, F0→F1; F1→F2; F2→F3; F3→F4) were estimated using Markov maximum likelihood estimation. Estimates were pooled using random-effects meta-analysis and heterogeneity was evaluated by stratification and random-effects meta-regression. RESULTS The review identified 111 studies involving 131 groups of patients (n=42 693). The pooled stage-constant FPR was 0.094 (95% CI 0.088 to 0.100); stage-specific FPRs were F0→F1: 0.107 (95% CI 0.097 to 0.118); F1→F2: 0.082 (95% CI 0.074 to 0.091); F2→F3: 0.117 (95% CI 0.107 to 0.129); F3→F4: 0.116 (95% CI 0.104 to 0.131). Stratified analysis revealed substantial variation in progression by study population. Meta-regression indicated associations between progression and infection age, duration, source, viral genotype and study population. Findings indicate that FPRs display substantial heterogeneity across study populations and pooled values from more homogenous subpopulations should be considered when estimating prognosis. CONCLUSIONS This large meta-analysis presents updated prognostic estimates for CHC derived from newer studies using better diagnostic methods and improves estimates for important patient populations in terms of clinical policy (eg, injection drug users, non-clinical populations, liver clinic patients) and should be a valuable resource for patients, clinicians and clinical policymakers.
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Affiliation(s)
- Aysegul Erman
- Toronto Health Economics and Health Technology Assessment (THETA) Collaborative, University Health Network, University of Toronto, Toronto, Ontario, Canada
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
- University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Murray D Krahn
- Toronto Health Economics and Health Technology Assessment (THETA) Collaborative, University Health Network, University of Toronto, Toronto, Ontario, Canada
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
- University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Tawnya Hansen
- University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Josephine Wong
- Toronto Health Economics and Health Technology Assessment (THETA) Collaborative, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Joanna M Bielecki
- Toronto Health Economics and Health Technology Assessment (THETA) Collaborative, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Jordan J Feld
- University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - William W L Wong
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
- University of Waterloo School of Pharmacy, Waterloo, Ontario, Canada
| | - Paul Grootendorst
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
| | - Hla-Hla Thein
- University of Toronto Dalla Lana School of Public Health, Toronto, Ontario, Canada
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5
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Thrift AP, Liu Y, Tsavachidis S, White DL, El-Serag HB. Ancestry and Risk of Hepatic Fibrosis and Inflammation in Patients With HCV Infection. Clin Gastroenterol Hepatol 2019; 17:1912-1914. [PMID: 30342914 PMCID: PMC7050728 DOI: 10.1016/j.cgh.2018.10.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 10/02/2018] [Accepted: 10/15/2018] [Indexed: 02/07/2023]
Abstract
Worldwide, ∼184 million people have chronic hepatitis C virus (HCV) infection.1 Persistent racial disparities in outcomes are observed among HCV-infected patients. Hispanic patients with chronic HCV are more likely than non-Hispanic white (NHW) patients to develop advanced hepatic fibrosis and inflammation.2,3 Conversely, black patients with HCV infection are at lowest risk. The factors that contribute to this racial disparity are multifactorial, including lifestyle, genetics, and medical care. Limited data in other diseases suggest that genetic ancestry determined using ancestry-informative markers (AIMs) may help explain racial and ethnic differences in disease risk or severity.4 AIMs are sets of single-nucleotide polymorphisms (SNPs) that determine a person's ancestral continent of origin and the genetic ancestry proportions assigned to each individual serves as a proxy for his or her genetic ancestral background. We examined the risk of hepatic fibrosis and inflammation in HCV-infected patients according to both genetic ancestry and self-reported race/ethnicity.
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Affiliation(s)
- Aaron P. Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas;,Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Yanhong Liu
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas;,Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Spiridon Tsavachidis
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas;,Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Donna L. White
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas;,Center for Innovations in Quality, Effectiveness and Safety Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas;,Center for Translational Research in Inflammatory Disease, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Hashem B. El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas;,Center for Innovations in Quality, Effectiveness and Safety Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
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6
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Zinc deficiency and advanced liver fibrosis among HIV and hepatitis C co-infected anti-retroviral naïve persons with alcohol use in Russia. PLoS One 2019; 14:e0218852. [PMID: 31246992 PMCID: PMC6597160 DOI: 10.1371/journal.pone.0218852] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 06/11/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND AND AIMS Liver disease in people living with HIV co-infected with hepatitis C virus is a source of morbidity and mortality in Russia. HIV accelerates liver fibrosis in the setting of HCV co-infection and alcohol use. Zinc deficiency is common among people living with HIV and may be a factor that facilitates the underlying mechanisms of liver fibrosis. We investigated the association between zinc deficiency and advanced liver fibrosis in a cohort of HIV/HCV co-infected persons reporting heavy drinking in Russia. METHODS This is a secondary data analysis of baseline data from 204 anti-retroviral treatment naïve HIV/HCV co-infected Russians with heavy drinking that were recruited into a clinical trial of zinc supplementation. The primary outcome of interest in this cross-sectional study was advanced liver fibrosis. Zinc deficiency, the main independent variable, was defined as plasma zinc <0.75 mg/L. Exploratory analyses were performed examining continuous zinc levels and fibrosis scores. Analyses were conducted using multivariable regression models adjusted for potential confounders. RESULTS The prevalence of advanced liver fibrosis was similar for those with zinc deficiency compared to those with normal zinc levels, (27.7% vs. 23.0%, respectively). We did not detect an association between zinc deficiency and advanced liver fibrosis in the adjusted regression model (aOR: 1.28, 95% CI: 0.62-2.61, p = 0.51) nor in exploratory analyses. CONCLUSIONS In this cohort of Russians with HIV/HCV co-infection, who are anti-retroviral treatment naïve and have heavy alcohol use, we did not detect an association between zinc deficiency or zinc levels and advanced liver fibrosis.
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Wang CP, Kuhn J, Shah DP, Schmidt S, Lam YWF, MacCarthy D, Tenner L, Ramirez AG. Metformin modifies disparity in hepatocellular carcinoma incidence in men with type 2 diabetes but without chronic liver diseases. Cancer Med 2019; 8:3206-3215. [PMID: 30993905 PMCID: PMC6558591 DOI: 10.1002/cam4.2142] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2018] [Revised: 03/06/2019] [Accepted: 03/15/2019] [Indexed: 12/18/2022] Open
Abstract
Background We assessed racial/ethnic disparity in hepatocellular carcinoma (HCC) incidence among men with type 2 diabetes (T2D) but without chronic liver diseases (CLD), and whether metformin use modified the disparity. Methods Study cohort: the nationwide Veterans Administration Health Care System electronic medical records among 40‐89 years old men with T2D; without CLD, cancer, cardiovascular or renal diseases previously; insulin and thiazolidinedione naive. Logistic regression analyses compared HCC incidence between race/ethnicity groups under no metformin use adjusted for covariates and inverse propensity score weights (IPSW) for race/ethnicity. The generalizability technique integrated with IPSW was incorporated to compare covariates adjusted odds ratios (aOR) of HCC associated with metformin use among race/ethnicity groups. Results Study cohort: N = 84 433; 79.47% non‐Hispanic white (NHW), 15.5% non‐Hispanic African American (NHAA), 5.03% Hispanics; 36.76% metformin users; follow‐up 6.10 ± 2.87 years; age 67.8 ± 9.8 years, HbA1c 6.57 ± 0.98%; 0.14% HCC cases. Under no metformin use, HCC incidence was lower for NHAA vs NHW (aOR = 0.60 [0.40‐0.92]), similar between NHW and Hispanics. Metformin was associated with reduced HCC risk: aOR = 0.57 (0.40‐0.81) for NHW; aOR = 0.35 (0.25‐0.47) for NHAA; aOR = 0.31 (0.22‐0.43) for Hispanics. Metformin dose >1000 mg/d was neutral for NHW; less effective for NHAA (P = 0.02); more effective for Hispanics (P = 0.002). Conclusions In men with T2D but without CLD nor metformin use, HCC incidence was lower for NHAA compared to NHW or Hispanics; similar between NHW and Hispanics. Metformin use reduced HCC risk and modified the race/ethnicity disparity. Impact Metformin's heterogeneous HCC prevention effect elucidates potential interventions to modify HCC disparity in patients with T2D.
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Affiliation(s)
- Chen-Pin Wang
- Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, Texas
| | - John Kuhn
- Department of Pharmacology, UTHSCSA, San Antonio, Texas
| | - Dimpy P Shah
- Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, Texas.,Institute for Health Promotion Research, UTHSCS, San Antonio, Texas
| | - Susanne Schmidt
- Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, Texas
| | | | - Daniel MacCarthy
- Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, Texas
| | | | - Amelie G Ramirez
- Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, Texas.,Institute for Health Promotion Research, UTHSCS, San Antonio, Texas
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Koc ÖM, Robaeys G, Yildirim B, Posthouwer D, Hens N, Koek GH. The influence of ethnicity on disease outcome in patients with chronic hepatitis B infection. J Med Virol 2018; 91:623-629. [PMID: 30381836 PMCID: PMC6587848 DOI: 10.1002/jmv.25353] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 10/29/2018] [Indexed: 12/18/2022]
Abstract
Since the cultural diversity in Western Europe is growing, this study assessed whether foreign‐born chronic hepatitis B (CHB) patients have more cirrhosis than Dutch‐ or Belgian‐born patients, with a main focus on the Turkish population. Baseline characteristics (eg, socioeconomic status [SES]), biological characteristics, and disease outcome (eg, cirrhosis) were collected for all patients. Between December 2009 and January 2015, 269 CHB patients participated from the outpatient departments of three hospitals in the Netherlands, Belgium, and Turkey. Out of the 269 CHB patients, 210 were foreign‐born and 59 were Dutch‐ or Belgian‐born. Compared with Dutch‐ or Belgian‐born patients, foreign‐born patients had a higher prevalence of low SES (58% vs 31%; P = 0.001) and cirrhosis (27% vs 10%; P = 0.007). Among the Turkish population, there were no significant differences regarding the prevalence of low SES (73% vs 61%; P = 0.170), alcohol abuse (1% vs 5%; P = 0.120), anti‐hepatitis C virus positivity (4% vs 0%; P = 0.344), anti‐hepatitis D virus positivity (1% vs 6%; P = 0.297), and cirrhosis (37% vs 27%; P = 0.262) between patients (n = 102) living in Turkey (local) and Turkish CHB (n = 38) patients living in the Netherlands or Belgium (immigrant). In multivariate analysis, low SES (odds ratio, 5.7; 95% confidence interval, 2.3‐14.5; P < 0.001) was associated with cirrhosis. In this study, foreign‐born CHB patients were associated with more advanced HBV‐related liver disease with 27% having cirrhosis. However, ethnicity was not associated with cirrhosis when SES was included in the multivariate analysis. The similar prevalence of cirrhosis in local Turkish compared to immigrant Turkish CHB patients is novel and warrants further investigation.
Foreign‐born individuals have a higher prevalence of cirrhosis than Dutch‐ or Belgian‐ born individuals There was a lower socioeconomic status in the foreign‐born individuals No difference in the prevalence of cirrhosis was seen between the local and immigrant Turkish population Socioeconomic status and not ethnicity was an independent predictor of cirrhosis
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Affiliation(s)
- Özgür M Koc
- Department of Internal Medicine, Infectious Diseases and Medical Microbiology, Maastricht University Medical Centre, Maastricht, The Netherlands.,School of Nutrition and Translational Research in Metabolism, University Maastricht, Maastricht, The Netherlands.,Department of Gastroenterology and Hepatology, Ziekenhuis Oost-Limburg, Genk, Belgium.,Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
| | - Geert Robaeys
- Department of Gastroenterology and Hepatology, Ziekenhuis Oost-Limburg, Genk, Belgium.,Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.,Department of Hepatology, UZ Leuven, Leuven, Belgium
| | - Beytullah Yildirim
- Department of Gastroenterology, Ondokuz Mayis University, School of Medicine, Samsun, Turkey
| | - Dirk Posthouwer
- Department of Internal Medicine, Infectious Diseases and Medical Microbiology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Niel Hens
- Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Hasselt, Belgium.,Centre for Health Economic Research and Modelling Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
| | - Ger H Koek
- School of Nutrition and Translational Research in Metabolism, University Maastricht, Maastricht, The Netherlands.,Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands.,Department of Surgery, University Hospital of the RWTH, Aachen, Germany
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9
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Kelly EM, Dodge JL, Bacchetti P, Sarkar M, French AL, Tien PC, Glesby MJ, Golub ET, Augenbraun M, Plankey M, Peters MG. Moderate Alcohol Use Is Not Associated With Fibrosis Progression in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Women: A Prospective Cohort Study. Clin Infect Dis 2018; 65:2050-2056. [PMID: 29020382 DOI: 10.1093/cid/cix716] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 08/15/2017] [Indexed: 02/07/2023] Open
Abstract
Background Heavy alcohol use can lead to progressive liver damage, especially in individuals with chronic hepatitis C (HCV); however, the impact of nonheavy use is not clear. We studied long-term effects of modest alcohol use on fibrosis progression in a large cohort of women coinfected with human immunodeficiency virus (HIV)/HCV. Methods Alcohol intake was ascertained every 6 months and use categorized as abstinent, light (1-3 drinks/week), moderate (4-7 drinks/week), heavy (>7 drinks/week), and very heavy (>14 drinks/week). Fibrosis progression was defined as the change in Fibrosis-4 Index for Liver Fibrosis (FIB-4) units per year using random-intercept, random-slope mixed modeling. Results Among 686 HIV/HCV-coinfected women, 46.0% reported no alcohol use; 26.8% reported light use, 7.1% moderate use, and 19.7% heavy use (6.7% had 8-14 drinks/week and 13.0% had >14 drinks/week) at cohort entry. Median FIB-4 at entry was similar between groups. On multivariable analysis, compared to abstainers, light and moderate alcohol use was not associated with fibrosis progression (0.004 [95% confidence interval {CI}, -.11 to .12] and 0.006 [95% CI, -.18 to .19] FIB-4 units/year, respectively). Very heavy drinking (>14 drinks/week) showed significant fibrosis acceleration (0.25 [95% CI, .01-.49] FIB-4 units/year) compared to abstaining, whereas drinking 8-14 drinks per week showed minimal acceleration of fibrosis progression (0.04 [95% CI, -.19 to .28] FIB-4 units/year). Conclusions Light/moderate alcohol use was not substantially associated with accelerated fibrosis progression, whereas drinking >14 drinks per week showed increased rates of fibrosis progression. Women with HIV/HCV infection should be counseled against heavy alcohol consumption, but complete abstinence may not be required to prevent accelerated liver fibrosis progression.
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Affiliation(s)
- Erin M Kelly
- Department of Medicine, University of Ottawa, Ontario, Canada
| | | | | | | | - Audrey L French
- Department of Medicine, CORE Center/Stroger Hospital of Cook County, Chicago, Illinois
| | - Phyllis C Tien
- Medicine, University of California, San Francisco.,Department of Veterans Affairs Medical Center, San Francisco, California
| | - Marshall J Glesby
- Department of Medicine, Weill Cornell Medical College, New York, New York
| | - Elizabeth T Golub
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Michael Augenbraun
- Department of Medicine, State University of New York, Downstate Medical Center, Brooklyn
| | - Michael Plankey
- Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia
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10
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Matsuda T, McCombs JS, Tonnu-Mihara I, McGinnis J, Fox DS. The Impact of Delayed Hepatitis C Viral Load Suppression on Patient Risk: Historical Evidence from the Veterans Administration. ACTA ACUST UNITED AC 2016; 19:333-351. [DOI: 10.1515/fhep-2015-0041] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Abstract
Background:
The high cost of new hepatitis C (HCV) treatments has resulted in “watchful waiting” strategies being developed to safely delay treatment, which will in turn delay viral load suppression (VLS).
Objective:
To document if delayed VLS adversely impacted patient risk for adverse events and death.
Methods:
187,860 patients were selected from the Veterans Administration’s (VA) clinical registry (CCR), a longitudinal compilation of electronic medical records (EMR) data for 1999–2010. Inclusion criteria required at least 6 months of CCR/EMR data prior to their HCV diagnosis and sufficient data post-diagnosis to calculate one or more FIB-4 scores. Primary outcome measures were time-to-death and time-to-a composite of liver-related clinical events. Cox proportional hazards models were estimated separately using three critical FIB-4 levels to define early and late viral response.
Results:
Achieving an undetectable viral load before the patient’s FIB-4 level exceed pre-specified critical values (1.00, 1.45 and 3.25) effectively reduced the risk of an adverse clinical events by 33–35% and death by 21–26%. However, achieving VLS after FIB-4 exceeds 3.25 significantly reduced the benefit of viral response.
Conclusions:
Delaying VLS until FIB-4 >3.25 reduces the benefits of VLS in reducing patient risk.
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11
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Stubbs A, Naylor P, Ravindran K, Benjaram S, Reddy N, Mutchnick S, May E, Ehrinpreis M, Mutchnick M. Racial diversity in mortality and morbidity in urban patients with hepatitis C. J Viral Hepat 2016; 23:439-46. [PMID: 26818494 DOI: 10.1111/jvh.12504] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 11/24/2015] [Indexed: 12/24/2022]
Abstract
Defining mortality for Caucasians and African American patients with chronic hepatitis C with respect to racial diversity is critical for counselling patients on therapy options. The objective of this study was to define racial diversity influence on mortality and morbidity of 3724 consecutive hepatitis C virus (HCV)-infected patients seen in an urban clinic between 1995 and 2008. Mortality, as of 2011, was defined using the SSA National Death Index and correlated with early visit medical information. The HCV chronically infected patient population consisted of 2879 African Americans (AA), 758 Caucasians and 87 other, and the majority were not treated for their infection prior to 2011. The average time to death from first visit was 5 years, the average age at death was 55 years, and despite racial diversity, AA were just as likely to be reported dead as Caucasians (23% AA vs 22% Caucasians). Cirrhosis and fibrosis (liver biopsy, AST Platelet Ratio Index or Fibrosis-4) at first visit as well as low albumin, diabetes, renal impairment and cardiac symptoms were associated with increased mortality. Treated patients who cleared the virus (sustained viral response (SVR); AA = 59; Caucasians = 40) had lower mortality than patients who were not treated (AA: 5% vs 27%; Caucasians 5% vs 26%). Hence, we find that race is not a factor in the early mortality of patients with chronic HCV infection and achieving a SVR reduced mortality. Unexpectedly, nonresponding AA also benefited by a lower mortality. African American patients with kidney disease and low albumin were at highest risk and should be treated as soon as identified.
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Affiliation(s)
- A Stubbs
- Division of Gastroenterology, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA
| | - P Naylor
- Division of Gastroenterology, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA
| | - K Ravindran
- Division of Gastroenterology, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA
| | - S Benjaram
- Division of Gastroenterology, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA
| | - N Reddy
- Division of Gastroenterology, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA
| | - S Mutchnick
- Division of Gastroenterology, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA
| | - E May
- Division of Gastroenterology, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA
| | - M Ehrinpreis
- Division of Gastroenterology, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA
| | - M Mutchnick
- Division of Gastroenterology, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA
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12
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Abstract
Hepatitis C infection is a common cause of cirrhosis and indication for liver transplantation in the United States. The incidence of chronic hepatitis C has been declining, but rates of cirrhosis and hepatocellular carcinoma are projected to increase. The outcome of chronic hepatitis C is variable. It is estimated that 20% to 25% will develop cirrhosis over a 25-year to 30-year period. The rate of disease progression is influenced by many host, viral, and environmental factors. Few can be modified.
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13
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Reddy N, Naylor P, Hakim Z, Asbahi R, Ravindran K, May E, Ehrinpreis M, Mutchnick M. Effect of Treatment for CHC on Liver Disease Progression and Hepatocellular Carcinoma Development in African Americans. J Clin Transl Hepatol 2015; 3:163-8. [PMID: 26623262 PMCID: PMC4663197 DOI: 10.14218/jcth.2015.00013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Revised: 05/14/2015] [Accepted: 05/18/2015] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND AND AIMS African Americans (AA) historically have a low response rate to hepatitis C therapies, and there is limited information available for this patient population regarding the development and treatment of chronic hepatitis C (CHC). The aim of this study was to evaluate liver disease progression and hepatocellular carcinoma (HCC) development in AA with CHC. METHODS Between 1995 and 2008, 246 AA patients with CHC were identified from a database of patients and followed until 2012-2013 (average 8 years) or the development of HCC after 2008. RESULTS Viral clearance (intent to treat; sustained virus response (SVR)) was achieved in 15% of patients with interferon based therapies with or without ribavirin. AA patients who achieved an SVR (n=22) did not develop HCC or new onset cirrhosis, whereas the HCC incidence in untreated AA patients was 23% (51/203). Patients who achieved an SVR also had improved fibrosis, as defined by the AST Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) score, relative to nonresponders and untreated patients. CONCLUSIONS The severity of liver disease at the first visit (except for cirrhosis) correlated with the development of HCC, but because of the overlap in values between patients, these measurements were not useful for predicting individual risk. Since cirrhosis at the first visit was not a predictive factor, treatment with newer antiviral therapies is the best option for reducing the incidence of advanced liver disease and its harmful outcomes in the AA population.
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Affiliation(s)
- Naveen Reddy
- Department of Internal Medicine/Division of Gastroenterology, Wayne State University School of Medicine, Harper University Hospital, Detroit, MI, USA
| | - Paul Naylor
- Department of Internal Medicine/Division of Gastroenterology, Wayne State University School of Medicine, Harper University Hospital, Detroit, MI, USA
| | - Zaher Hakim
- Department of Internal Medicine/Division of Gastroenterology, Wayne State University School of Medicine, Harper University Hospital, Detroit, MI, USA
| | - Redwan Asbahi
- Department of Internal Medicine/Division of Gastroenterology, Wayne State University School of Medicine, Harper University Hospital, Detroit, MI, USA
| | - Karthik Ravindran
- Department of Internal Medicine/Division of Gastroenterology, Wayne State University School of Medicine, Harper University Hospital, Detroit, MI, USA
| | - Elizabeth May
- Department of Internal Medicine/Division of Gastroenterology, Wayne State University School of Medicine, Harper University Hospital, Detroit, MI, USA
| | - Murray Ehrinpreis
- Department of Internal Medicine/Division of Gastroenterology, Wayne State University School of Medicine, Harper University Hospital, Detroit, MI, USA
| | - Milton Mutchnick
- Department of Internal Medicine/Division of Gastroenterology, Wayne State University School of Medicine, Harper University Hospital, Detroit, MI, USA
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14
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Zhu L, Kong M, Han YP, Bai L, Zhang X, Chen Y, Zheng S, Yuan H, Duan Z. Spontaneous liver fibrosis induced by long term dietary vitamin D deficiency in adult mice is related to chronic inflammation and enhanced apoptosis. Can J Physiol Pharmacol 2015; 93:385-394. [PMID: 25894394 DOI: 10.1139/cjpp-2014-0275] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Epidemiological studies have revealed an association between vitamin D deficiency and various chronic liver diseases. However, it is not known whether lack of vitamin D can induce spontaneous liver fibrosis in an animal model. To study this, mice were fed either a control diet or a vitamin D deficient diet (VDD diet). For the positive control, liver fibrosis was induced with carbon tetrachloride. Here we show, for the first time, that liver fibrosis spontaneously developed in mice fed the VDD diet. Long-term administration of a VDD diet resulted in necro-inflammation and liver fibrosis. Inflammatory mediators including tumor necrosis factor-α, interleulin-1, interleukin-6, Toll-like-receptor 4, and monocyte chemotactic protein-1 were up-regulated in the livers of the mice fed the VDD diet. Conversely, the expression of Th2/M2 markers such as IL-10, IL-13, arginase 1, and heme oxygenase-1 were down-regulated in the livers of mice fed the VDD diet. Transforming growth factor-β1 and matrix metalloproteinase 13, which are important for fibrosis, were induced in the livers of mice fed the VDD diet. Moreover, the VDD diet triggered apoptosis in the parenchymal cells, in agreement with the increased levels of Fas and FasL, and decreased Bcl2 and Bclx. Thus, long-term vitamin D deficiency can provoke chronic inflammation that can induce liver apoptosis, which consequently activates hepatic stellate cells to initiate liver fibrosis.
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Affiliation(s)
- Longdong Zhu
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China
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15
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Njei B, Rotman Y, Ditah I, Lim JK. Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology 2015; 61:191-199. [PMID: 25142309 PMCID: PMC4823645 DOI: 10.1002/hep.27388] [Citation(s) in RCA: 431] [Impact Index Per Article: 43.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2014] [Accepted: 08/19/2014] [Indexed: 02/06/2023]
Abstract
UNLABELLED The rise in incidence of hepatocellular carcinoma (HCC) in the United States has been well documented. The purpose of this analysis was to examine temporal trends in HCC incidence, mortality, and survival within the U.S. population. The Surveillance, Epidemiology, and End Results data were used to examine incidence and incidence-based (IB) mortality in HCC from 1973 to 2011. Secular trends in age-adjusted incidence and IB mortality by sex and cancer stage were characterized using the Joinpoint Regression program. In 1973, HCC incidence was 1.51 cases per 100,000, whereas in 2011, HCC incidence was 6.20 cases per 100,000. Although HCC incidence continues to increase, a slowing of the rate of increase occurs around 2006. In a sensitivity analysis, there was no significant increase in incidence and IB mortality from 2009 to 2011. There was a significant increase in overall median survival from the 1970s to 2000s (2 vs. 8 months; P < 0.001). On multivariable Cox's regression analysis, age, sex, race, tumor grade, stage at diagnosis, lymph/vascular invasion, number of primary tumors, tumor size, and liver transplant were independently associated with mortality. CONCLUSION Our results indicate a deceleration in the incidence of HCC around 2006. Since 2009 and for the first time in four decades, there is no increase in IB mortality and incidence rates for HCC in the U.S. population. The nonsignificant increase in incidence and IB mortality in recent years suggest that the peak of the HCC epidemic may be near. A significant survival improvement in HCC was also noted from 1973 to 2010, which seems to be driven by earlier detection of HCC at a curative stage and greater utilization of curative modalities (especially transplant).
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Affiliation(s)
- Basile Njei
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT
- Department of Medicine, University of Connecticut School of Medicine, Farmington, CT
| | - Yaron Rotman
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
| | - Ivo Ditah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Joseph K. Lim
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT
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16
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Hepatitis C in African Americans. Am J Gastroenterol 2014; 109:1576-84; quiz 1575, 1585. [PMID: 25178700 DOI: 10.1038/ajg.2014.243] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2014] [Accepted: 07/01/2014] [Indexed: 12/11/2022]
Abstract
The care of hepatitis C virus (HCV) in African Americans represents an opportunity to address a major health disparity in medicine. In all facets of HCV infection, African Americans are inexplicably affected, including in the prevalence of the virus, which is higher among them compared with most of the racial and ethnic groups. Ironically, although fibrosis rates may be slow, hepatocellular carcinoma and mortality rates appear to be higher among African Americans. Sustained viral response (SVR) rates have historically significantly trailed behind Caucasians. The reasons for this gap in SVR are related to both viral and host factors. Moreover, low enrollment rates in clinical trials hamper the study of the efficacy of anti-viral therapy. Nevertheless, the gap in SVR between African Americans and Caucasians may be narrowing with the use of direct-acting agents. Gastroenterologists, hepatologists, primary care physicians, and other health-care providers need to address modifiable risk factors that affect the natural history, as well as treatment outcomes, for HCV among African Americans. Efforts need to be made to improve awareness among health-care providers to address the differences in screening and referral patterns for African Americans.
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17
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Racial differences in the progression to cirrhosis and hepatocellular carcinoma in HCV-infected veterans. Am J Gastroenterol 2014; 109:1427-35. [PMID: 25070058 DOI: 10.1038/ajg.2014.214] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Accepted: 06/16/2014] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The race of patients infected with hepatitis C virus (HCV) in the United States may be associated with the risk for cirrhosis and hepatocellular carcinoma (HCC). However, previous studies are too small to provide convincing data regarding the effect of race on cirrhosis and HCC risk after accounting for demographic, clinical, and virological factors. METHODS We used the Veterans Administration (VA) HCV Clinical Case Registry to identify patients with confirmed viremia between 2000 and 2009 and with at least 1 year of follow-up in the VA. We identified cirrhosis and HCC cases through early 2010. Cox proportional hazard regression models were performed to examine the effect of race on the risk for cirrhosis and HCC while adjusting for patients' age, gender, period of service (World War I/II, Vietnam era, post-Vietnam era), HIV coinfection, HBV coinfection, alcohol abuse, diabetes, body mass index, and antiviral treatment receipt and response. RESULTS There were 149,407 patients with active HCV viremia. Of them, 56.3% were non-Hispanic White (NHW), 36.1% were African American (AA), 6.0% were Hispanic, and 1.6% belonged to other racial groups. After an average follow-up of 5.2 years, 13,099 patients were seen to have a recorded diagnosis of cirrhosis and 3,551 had HCC. Hispanics had the highest annual incidence rates of cirrhosis and HCC (28.8 and 7.8%, respectively), whereas AAs had the lowest rates (13.3% and 3.9%, respectively) compared with NHWs (21.6 and 4.7%, respectively). There were differences among NHW, AA, and Hispanic patients in the rates of HIV infection (2.1, 2.5, and 6.0%, respectively), HCV genotype 1 (50.0, 50.6, and 64.2%, respectively), obesity (28.0, 25.4, and 30.9%, respectively), diabetes (8.7, 16.1, and 16.1%, respectively), and absence of antiviral treatment (81.1, 89.6, and 82.1%, respectively). However, adjusting for differences in demographic and clinical factors did not change the magnitude or direction of the race effect. Compared with NHWs, Hispanic patients had a higher risk of having cirrhosis recorded (adjusted hazard ratio (HR)=1.28, 95% confidence interval (CI)=1.21-1.37) and HCC (1.61, 95% CI=1.44-1.80). In contrast, AAs had a lower risk of cirrhosis (HR=0.58, 95% CI=0.55-0.60) and HCC (0.77, 95% CI=0.71-0.83) compared with NHWs. CONCLUSIONS Hispanics with HCV are at a significantly higher risk, whereas AAs are at a considerably lower risk of developing cirrhosis and HCC than are NHWs. These associations persisted even after adjusting for a range of factors including HCV genotype, HCV treatment, diabetes, and body mass index.
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18
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Forde KA, Tanapanpanit O, Reddy KR. Hepatitis B and C in African Americans: current status and continued challenges. Clin Gastroenterol Hepatol 2014; 12:738-48. [PMID: 23811241 PMCID: PMC3947744 DOI: 10.1016/j.cgh.2013.06.006] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Revised: 06/15/2013] [Accepted: 06/17/2013] [Indexed: 02/07/2023]
Abstract
Viral hepatitis remains a public health concern in the United States, resulting in excess morbidity and mortality for the individual and representing a burden to societies as evidenced by billions of dollars in health care expenditures. As with many chronic diseases, race and ethnicity influence various aspects of disease pathogenesis, including mechanisms of persistence, disease progression, disease sequelae, and response to therapy. For hepatitis B and C infections, African Americans disproportionately bear a large burden of disease in the United States. The role and importance of African American race, however, have been less well-characterized in the literature among the population of viral hepatitis-infected individuals. The differences in epidemiology, manifestations of liver disease, response to therapy, and differential trends in liver transplantation in African Americans compared with other racial and ethnic groups deserve special attention. This review will address the current status of hepatitis B and C infection in African Americans in the United States and identify some of the remaining challenges in diagnosis, characterization of natural history, and treatment. For the purposes of this review, the terms African American and black will be used interchangeably throughout the text.
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Affiliation(s)
- Kimberly A. Forde
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.,Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Orapin Tanapanpanit
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - K. Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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19
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Lisker-Melman M, Walewski JL. The impact of ethnicity on hepatitis C virus treatment decisions and outcomes. Dig Dis Sci 2013; 58:621-9. [PMID: 23065087 DOI: 10.1007/s10620-012-2392-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2011] [Accepted: 08/28/2012] [Indexed: 12/17/2022]
Abstract
Hepatitis C virus infection is a major public health concern. Approximately 4 million people are reported to be infected with the virus in the United States, and the annual death rate due to HCV-associated decompensated liver failure or hepatocellular carcinoma is estimated to be approximately 18,000 within the next decade. Therapeutic success, as measured by a sustained virologic response, is approximately 50 % in G1 patients with pegylated-interferon/ribavirin-based therapies. Independent studies have reported significant variation in response rates depending on the ethnicity or race of the patient, though the underlying reasons are not well understood. Historically, ethnic populations have been underrepresented in most large clinical trials of HCV therapies, even though these populations have disproportionately high rates of HCV infection. Recent clinical trials have investigated genetic variations in key biological pathways that may underlie the mechanisms responsible for the different rates of HCV clearance and treatment outcomes in ethnic populations treated with pegylated-interferon/ribavirin. However, as novel direct-acting antiviral drugs are added to, and eventually replace, existing treatment regimens, the role of the innate immune response in determining treatment outcomes will diminish. Socioeconomic and biological factors can impact rates of HCV infection, disease progression, and treatment outcomes in minority populations. Improved access to health care, novel antiviral treatments, and a better understanding of the host factors that contribute to disparities in treatment outcomes are expected to result in optimized treatment paradigms that directly target the virus, leading to improved outcomes for all patients.
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Affiliation(s)
- Mauricio Lisker-Melman
- Hepatology Program, Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO 63110-1010, USA.
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20
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Albertoni G, Arnoni CP, Latini FRM, Andrade SS, Araújo PRB, Rodrigues FK, Rozenchan PB, Mendes-Correa MC, Leite OHM, Schor N, Girão MJCB, Barreto JA. Altered of apoptotic markers of both extrinsic and intrinsic pathways induced by hepatitis C virus infection in peripheral blood mononuclear cells. Virol J 2012; 9:314. [PMID: 23256595 PMCID: PMC3554545 DOI: 10.1186/1743-422x-9-314] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2012] [Accepted: 12/07/2012] [Indexed: 01/09/2023] Open
Abstract
Background Chronic hepatitis C (CHC) has emerged as a leading cause of cirrhosis in the U.S. and across the world. To understand the role of apoptotic pathways in hepatitis C virus (HCV) infection, we studied the mRNA and protein expression patterns of apoptosis-related genes in peripheral blood mononuclear cells (PBMC) obtained from patients with HCV infection. Methods The present study included 50 subjects which plasma samples were positive for HCV, but negative for human immunodeficiency virus (HIV) or hepatitis B virus (HBV). These cases were divided into four groups according to METAVIR, a score-based analysis which helps to interpret a liver biopsy according to the degree of inflammation and fibrosis. mRNA expression of the studied genes were analyzed by reverse transcription of quantitative polymerase chain reaction (RT-qPCR) and protein levels, analyzed by ELISA, was also conducted. HCV genotyping was also determined. Results HCV infection increased mRNA expression and protein synthesis of caspase 8 in group 1 by 3 fold and 4 fold, respectively (p < 0.05). In group 4 HCV infection increased mRNA expression and protein synthesis of caspase 9 by 2 fold and 1,5 fold, respectively (p < 0.05). Also, caspase 3 mRNA expression and protein synthesis had level augumented by HCV infection in group 1 by 4 fold and 5 fold, respectively, and in group 4 by 6 fold and 7 fold, respectively (p < 0.05). Conclusions HCV induces alteration at both genomic and protein levels of apoptosis markers involved with extrinsic and intrinsic pathways.
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21
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Sarkar M, Bacchetti P, French AL, Tien P, Glesby MJ, Nowicki M, Plankey M, Gange S, Sharp G, Minkoff H, Peters MG. Lower liver-related death in African-American women with human immunodeficiency virus/hepatitis C virus coinfection, compared to Caucasian and Hispanic women. Hepatology 2012; 56:1699-705. [PMID: 22618868 PMCID: PMC3440547 DOI: 10.1002/hep.25859] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2012] [Accepted: 05/15/2012] [Indexed: 12/15/2022]
Abstract
UNLABELLED Among individuals with and without concurrent human immunodeficiency virus (HIV), racial/ethnic differences in the natural history of hepatitis C virus (HCV) have been described. African Americans have lower spontaneous HCV clearance than Caucasians, yet slower rates of liver fibrosis once chronically infected. It is not clear how these differences in the natural history of hepatitis C affect mortality, in either HIV-positive or -negative individuals. We conducted a cohort study of HIV/HCV coinfected women followed in the multicenter Women's Interagency HIV Study to determine the association of self-reported race/ethnicity with all-cause and liver-related mortality. Survival analyses were performed using Cox's proportional hazards models. The eligible cohort (n = 794) included 140 Caucasians, 159 Hispanics, and 495 African Americans. There were 438 deaths and 49 liver-related deaths during a median follow-up of 8.9 years and maximum follow-up of 16 years. African-American coinfected women had significantly lower liver-related mortality, compared to Caucasian (hazard ratio [HR], 0.41; 95% confidence interval [CI]: 0.19-0.88; P = 0.022) and Hispanic coinfected women (HR, 0.38; 95% CI: 0.19-0.76; P = 0.006). All-cause mortality was similar between racial/ethnic groups (HRs for all comparisons: 0.82-1.03; log-rank test: P = 0.8). CONCLUSIONS African-American coinfected women were much less likely to die from liver disease, as compared to Caucasians and Hispanics, independent of other causes of death. Future studies are needed to investigate the reasons for this marked racial/ethnic discrepancy in liver-related mortality.
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Affiliation(s)
- Monika Sarkar
- Department of Medicine, University of California, San Francisco, CA, USA.
| | - Peter Bacchetti
- Epidemiology and Biostatistics, University of California San Francisco
| | - Audrey L. French
- Medicine, CORE Center/Stroger Hospital of Cook County, Chicago, IL
| | - Phyllis Tien
- Medicine, Division of Infectious Diseases, University of California San Francisco
| | - Marshall J. Glesby
- Medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York, NY
| | - Marek Nowicki
- Medicine, University of Southern California, Los Angeles, CA
| | - Michael Plankey
- Medicine, Division of Infectious Diseases, Georgetown University, Washington, DC
| | - Stephen Gange
- Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Gerald Sharp
- Epidemiology Branch, NIH, NIAID, DAIDS, Bethesda, MD
| | - Howard Minkoff
- Obstetrics and Gynecology, Maimonides Medical Center, Brooklyn, NY
| | - Marion G. Peters
- Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco
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22
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White DL, Tavakoli-Tabasi S, Kuzniarek J, Ramsey DJ, El-Serag HB. Racial differences in the association between adiposity measures and the risk of hepatitis C-related liver disease. J Clin Gastroenterol 2012; 46:779-88. [PMID: 22955261 PMCID: PMC3437036 DOI: 10.1097/mcg.0b013e318266f6eb] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND African Americans have lower reported likelihood of hepatitis C virus-related cirrhosis than whites. It is unknown whether relative differences in the distribution of adipose tissue, lean mass, and other anthropometric measurements may explain these observed interethnic differences in disease risk. AIM : To evaluate the association between anthropometric measurements and advanced liver disease in a cross-sectional study of African American and white male veterans. METHODS We used the validated FibroSURE-ActiTest to assess hepatic pathology, and direct segmental multichannel bioelectric impedance analysis for anthropometric measurements. Race-stratified logistic regression was employed to evaluate risk of high fibrosis progression rate (FPR) and advanced inflammation (A2 to A3). RESULTS Among 330 eligible males (59% African American), there were 43 white and 57 African American males with high FPR, and 70 African American and 59 white with advanced inflammation. Percentage body fat (%BF) was a stronger predictor of high FPR risk than was a high body mass index in African Americans [odds ratio (OR)(adj)=2.08; 95% confidence interval (CI),0.83-5.23 for highest %BF vs. lowest tertile and OR(adj)=1.50; 95% CI,0.60-3.75 for obese vs. normal body mass index, respectively], but not in whites. Highest lean leg mass was associated with a nonsignificant increased risk of both high FPR and advanced inflammation in African Americans (OR(highFPRadj)=1.73; 95% CI, 0.73-4.10; OR(AdvancedinflammationAdj)=1.65; 95% CI, 0.76-3.56) versus a decreased risk of both in whites (OR(highFPRadj)=0.62; 95% CI, 0.21-1.79; OR(AdvancedinflammationAdj)=0.58; 95% CI, 0.22-1.48). CONCLUSIONS Interethnic differences in nontraditional anthropometric measurements like %BF suggests their potential role in understanding interethnic differences in hepatitis C virus-related liver disease risk in males.
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Affiliation(s)
- Donna L White
- Clinical Epidemiology and Outcomes Program, Houston VA Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030, USA.
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23
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Aslinia FM, Wasan SK, Mindikoglu AL, Adeyemo OA, Philosophe B, Drachenberg C, Howell CD. End-stage renal disease and African American race are independent predictors of mild liver fibrosis in patients with chronic hepatitis C infection. J Viral Hepat 2012; 19:371-6. [PMID: 22497817 PMCID: PMC3328295 DOI: 10.1111/j.1365-2893.2011.01565.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Recipients of haemodialysis for end-stage renal disease (ESRD) have a higher prevalence of hepatitis C virus (HCV) infection relative to the general US population. However, the natural course of HCV infection in patients with renal failure, including African Americans (AAs) and Caucasian Americans (CAs), is not well known. We compared the degree of liver inflammation and fibrosis in AA and CA patients with HCV infection, with and without ESRD. This was a cross-sectional study of 156 HCV patients with ESRD (130 AAs and 26 CAs) with a liver biopsy between 1992 and 2005. The control group consisted of 138 patients (50 AAs; 88 CAs) with HCV infections and a serum creatinine <1.5 mg/dL with a liver biopsy between 1995 and 1998. Specimens were graded for inflammation and fibrosis using Knodell histological activity index. Compared to patients without renal impairment, HCV patients with renal failure were older and more likely to be AA. Patients with renal impairment had lower mean serum transaminases, a higher mean serum alkaline phosphatase levels (all P < 0.0001) and less hepatic necro-inflammation (Knodell histological activity index -I, II and III; P < 0.05) and fibrosis (Knodell histological activity index -IV; P < 0.0001). There were no racial differences in serum liver chemistry and histology scores among patients with renal failure. In a multivariate analysis, younger age, ESRD, AA race and a lower serum alkaline phosphatase were associated with lower odds for advanced liver fibrosis. Thus, HCV patients with ESRD had a lower degree of hepatic inflammation and fibrosis compared to those without renal disease, independent of race.
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Affiliation(s)
- Florence M Aslinia
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
| | - Sharmeel K Wasan
- Boston Medical Center, Section of Gastroenterology, Boston University School of Medicine, Boston, Massachusetts
| | - Ayse L Mindikoglu
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
| | - Olukemi A Adeyemo
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
| | - Benjamin Philosophe
- Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland
| | - Cinthia Drachenberg
- Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Charles D Howell
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
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Saxena V, Lai JC, O'Leary JG, Verna EC, Brown RS, Stravitz RT, Trotter JF, Krishnan K, Terrault NA, the ConsoRtiUm to Study Health Outcomes in HCV Liver Transplant Recipients (CRUSH-C). Recipient-donor race mismatch for African American liver transplant patients with chronic hepatitis C. Liver Transpl 2012; 18:524-31. [PMID: 22140019 PMCID: PMC3314141 DOI: 10.1002/lt.22461] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
African American (AA) recipient-donor race mismatch has been associated with graft loss and mortality, but studies of an association between race mismatch and hepatitis C virus (HCV) disease severity are lacking. HCV-infected adults from 4 US centers who underwent liver transplantation for the first time (n = 1093) were followed for a median of 3.05 years to determine the rates of advanced HCV disease (bridging fibrosis or cirrhosis) and graft failure; 11% of the patients were AA. The unadjusted cumulative rate of advanced fibrosis was higher in AAs than non-AAs (56% and 40% at 4 years, respectively, (P < 0.01), and 59% and 56% for AA recipient-donor-matched patients and AA recipient-donor-mismatched patients, respectively (P = 0.89). In adjusted models, both AA recipient race [hazard ratio (HR) = 1.47, 95% CI = 1.06-2.03, P = 0.02] and AA recipient-donor mismatch (versus match; HR = 1.48, 95% CI = 1.03-2.12, P = 0.03) were significant predictors of advanced fibrosis; other independent predictors were donor age (HR = 1.21, P < 0.01) and cytomegalovirus infection (HR = 1.55, P < 0.01). The 4-year unadjusted cumulative rates for HCV-associated graft loss were 10% and 17% for non-AAs and AAs, respectively (P < 0.01), and 0% and 21% for AA recipient-donor-matched patients and AA recipient-donor-mismatched patients, respectively (P < 0.01). In adjusted models, AA recipient-donor-mismatched patients had a 62% higher rate of graft loss than non-AA recipients (HR = 1.62, 95% CI = 1.14-2.29, P < 0.01), and AA recipient-donor-matched patients had a 76% lower rate of graft loss/mortality (HR = 0.24, 95% CI = 0.06-0.97, P = 0.05). In conclusion, AA recipient-donor-mismatched patients who are infected with HCV are at high risk for advanced HCV disease and HCV-related graft loss and constitute a patient group that will benefit from new therapeutic strategies for preventing graft loss.
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Affiliation(s)
- Varun Saxena
- Department of Medicine, University of California San Francisco
| | - Jennifer C. Lai
- Department of Medicine, University of California San Francisco
| | | | | | - Robert S. Brown
- Department of Medicine, New York Presbyterian Hospital-Columbia
| | - R. Todd Stravitz
- Department of Medicine, Virginia Commonwealth University Medical Center
| | - James F. Trotter
- Baylor Simmons Transplant Institute, Baylor University Medical Center, Dallas
| | - Kartik Krishnan
- Department of Medicine, University of California San Francisco
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Shores NJ, Maida I, Perez-Saleme L, Núñez M. Virological rather than host factors are associated with transaminase levels among HIV/HCV-coinfected patients. ACTA ACUST UNITED AC 2011; 9:15-9. [PMID: 20071593 DOI: 10.1177/1545109709356356] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Alanine aminotransferase (ALT) is a routine parameter in the assessment and monitoring of chronic hepatitis C viral (HCV) infection. Hepatitis C virus-infected African Americans (AAs) have been reported to have lower ALT levels. In this retrospective, cross-sectional, multicenter study, host and virological factors possibly associated with ALT levels were analyzed by multivariate regression analyses among HIV/HCV-coinfected patients. Of the 289 patients included, 142 were African Americans and 144 Caucasians. In multivariate analysis, only HCV genotype 3 (B 0.2 [95% CI 13.39-52.33]; P = .001) and HCV RNA >500 000 IU/mL (B 3.1 [95% CI 7.67-34.75]; P = .002) were independent predictors of higher ALT levels. Per the American Association for the Study of Liver Disease (AASLD) definition, 18.2% had ALT levels within normal limits. Male sex and HCV RNA <500 000 IU/mL predicted ALT within normal limits. Hepatitis C viral factors rather than race were associated with ALT levels in this HIV/HCV-coinfected population. ALT were within normal limits in 18% of patients, who more often were male and had lower Hepatitis C viral load.
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Affiliation(s)
- Nathan J Shores
- Division on Gastroenterology, Department of Internal Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA
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26
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Moeller M, Zalawadia A, Alrayes A, Divine G, Brown K, Moonka D. The Impact of Donor Race on Recurrent Hepatitis C after Liver Transplantation. Transplant Proc 2010; 42:4175-7. [DOI: 10.1016/j.transproceed.2010.09.079] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2010] [Accepted: 09/20/2010] [Indexed: 11/26/2022]
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Dai CY, Ho CK, Huang JF, Hsieh MY, Hou NJ, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Yu ML, Chuang WL. Hepatitis C virus viremia and low platelet count: a study in a hepatitis B & C endemic area in Taiwan. J Hepatol 2010; 52:160-166. [PMID: 20034694 DOI: 10.1016/j.jhep.2009.11.017] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2009] [Revised: 06/25/2009] [Accepted: 07/27/2009] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV) infection has been shown to be associated with a low platelet count. This study aimed to elucidate the association between virologic status and platelet count in individuals with HCV infection. METHODS A large-scale survey, enrolling 11,239 residents, was conducted in the Kaohsiung area of Taiwan. Serum HCV RNA and non-invasive markers of fibrosis (FibroTest) were tested for antibody to HCV (anti-HCV)-positive subjects. The platelet counts of age- and sex-matched, biopsy-proven, hospital-based patients and community-based patients with minimal fibrosis were compared. RESULTS Anti-HCV was positive in 703 (6.2%) subjects and was significantly associated with older age, female sex, abnormal alanine aminotransferase (ALT) value and low platelet count (<150,000/microl). The independent factors significantly associated with low platelet count were abnormal ALT value (odds ratio [OR]: 3.70, 95% confidence intervals [CI]: 2.18-6.28) and positive HCV RNA (OR: 2.00, 95% CI: 1.01-3.97). After adjustment for the fibrosis, HCV RNA remained significantly associated with platelet counts. CONCLUSIONS Our results evaluating the association between platelet count and HCV viremia and taking the influences of fibrosis into consideration implicate that platelets may be affected directly by HCV.
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Affiliation(s)
- Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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Kallwitz ER, Layden-Almer J, Dhamija M, Berkes J, Guzman G, Lepe R, Cotler SJ, Layden TJ. Ethnicity and body mass index are associated with hepatitis C presentation and progression. Clin Gastroenterol Hepatol 2010; 8:72-8. [PMID: 19686868 DOI: 10.1016/j.cgh.2009.08.009] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2009] [Revised: 07/21/2009] [Accepted: 08/05/2009] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Ethnicity and the metabolic syndrome are believed to affect progression of hepatitis C virus (HCV) infection, but the interaction between these factors is unknown. We evaluated the association between elements of the metabolic syndrome and ethnicity in the histologic progression of HCV in a large, diverse cohort. METHODS We retrospectively evaluated clinical data and liver biopsy samples from 812 patients who had no cause of liver disease other than HCV infection. Liver biopsies were scored for steatosis, necroinflammatory activity, and fibrosis. For each patient with a known risk factor for viral acquisition, fibrosis index was calculated as an indicator of disease progression. RESULTS Hispanics had significantly higher fibrosis index (0.13 +/- 0.09) than non-Hispanic whites (0.11 +/- 0.07) and African Americans (0.10 +/- 0.06; P = .001). Fibrosis index correlated with body mass index (BMI), older age at infection, ethnicity, and degree of steatosis. Cirrhosis was present in 50% of Hispanics, 38% of non-Hispanic whites, and 24% of African Americans (P < .001). The presence of cirrhosis was associated additionally with older age, longer duration of infection, BMI, alcohol consumption, and diabetes. In multivariate analysis, only BMI and ethnicity were associated with both fibrosis index and presentation with cirrhosis. Patients with higher BMIs, diabetes mellitus, and steatosis had higher degrees of necroinflammation. CONCLUSIONS Ethnicity and BMI each were associated with the progression of fibrosis and the presence of cirrhosis. Hispanics had the highest fibrosis index and prevalence of cirrhosis, whereas African Americans had the lowest. Ethnic differences in fibrosis index and cirrhosis persisted after controlling for elements of metabolic syndrome.
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Affiliation(s)
- Eric R Kallwitz
- Department of Medicine, University of Illinois, Chicago, Illinois, USA.
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Terrault NA, Im K, Boylan R, Bacchetti P, Kleiner DE, Fontana RJ, Hoofnagle JH, Belle SH, VIRAHEP-C Study Group. Fibrosis progression in African Americans and Caucasian Americans with chronic hepatitis C. Clin Gastroenterol Hepatol 2008; 6:1403-11. [PMID: 19081528 PMCID: PMC3166617 DOI: 10.1016/j.cgh.2008.08.006] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Collaborators] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2008] [Revised: 07/26/2008] [Accepted: 08/10/2008] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Prior studies suggest the rate of liver fibrosis progression is slower in African Americans (AAs) than Caucasian Americans (CAs) with chronic HCV infection. METHODS With a multi-state Markov model, fibrosis progression was evaluated in a well-characterized cohort of 143 AA and 157 CA adults with untreated chronic HCV genotype 1 infection. In subjects with a history of injection drug use, duration of infection was imputed from a fitted risk model rather than assumed to be the reported first year of use. RESULTS The distribution of Ishak fibrosis stages was 0 (8.7%), 1/2 (55.7%), 3/4 (29.3%), and 5/6 (6.3%) and was similar in AAs and CAs (P = .22). After adjusting for biopsy adequacy, AAs had a 10% lower rate of fibrosis progression than did CAs, but the difference was not statistically significant (hazard ratio, 0.90; 95% confidence interval, 0.72-1.12). The overall 20-year estimates of probabilities of progression from stage 0 to stages 1/2, 3/4, and 5/6 were 59.3%, 28.8%, and 4.7%, respectively. The estimated median time from no fibrosis to cirrhosis was 79 years for the entire cohort and 74 and 83 years for CAs and AAs, respectively. In 3-variable models including race and biopsy adequacy, the factors significantly associated with fibrosis progression were age when infected, steatosis, ALT level, and necroinflammatory score. CONCLUSIONS The rates of fibrosis progression were slow and did not appear to differ substantially between AAs and CAs.
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Affiliation(s)
- Norah A Terrault
- Department of Medicine, University of California San Francisco, San Francisco, California 94143-0538, USA.
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Collaborators
Nezam Afdhal, Tiffany Geahigan, Robert S Brown, Lorna Dove, Shana Stovel, Norah Terrault, Stephanie Straley, Eliana Agudelo, Melissa Hinds, Thelma E Wiley, Monique Williams, Charles D Howell, Karen Callison, Lennox J Jeffers, Shvawn McPherson Baker, Maria DeMedina, Carol Hermitt, Hari S Conjeevaram, Robert J Fontana, Donna Harsh, Michael W Fried, Scott R Smith, Dickens Theodore, Steven Zacks, Roshan Shrestha, Karen Dougherty, Paris Davis, Shirley Brown, John E Tavis, Adrian Di Bisceglie, Ermei Yao, Maureen Donlin, Nathan Cannon, Ping Wang, Huiying Yang, George Tang, Dai Wang, Hugo R Rosen, James R Burton, Jared Klarquist, Scott Weston, Milton W Taylor, Corneliu Sanda, Joel Schaley, Mary Ferris, Steven H Belle, Geoffrey Block, Jennifer Cline, KyungAh Im, Stephanie Kelley, Laurie Koozer, Sharon Lawlor, Stephen B Thomas, Abdus Wahed, Yuling Wei, Leland J Yee, Patricia Robuck, James Everhart, Jay H Hoofnagle, Edward Doo, T Jake Liang, Leonard B Seeff, David E Kleiner, Raymond S Koff,
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Abstract
Purpose Recent studies suggest that African Americans (AA) with chronic hepatitis C (CHC) differ from non-Hispanic whites (NHW) with respect to the natural history and mortality resulting from the complications of chronic liver disease. The aim of this study was to examine the demographics of a large cohort of CHC patients and identify potential differences between AA and NHW. Methods This is a retrospective analysis, consisting of 2,739 hepatitis C antibody-positive patients seen at Wayne State University between 1995 and 2005. Patient demographics, risk factors, comorbidities, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum hepatitis C (HCV) RNA levels, genotype, and liver biopsy results were recorded. Results AA constituted 75.4%, NHW 22.5%, and Asians or Hispanics 2.1% of the patients. Males predominated (58%), and the mean age of AA and NHW was 50.0 and 45.3 years, respectively (P ≤ 0.001). The most common risk factor was injection drug use in 55.3% (AA 57.1% vs. NHW 49.7%; P ≤ 0.002). HCV RNA by PCR obtained in 2,407 patients was positive in 94.8%, with a high viral load in 61%. Genotype 1 was significantly more frequent in AA (92.6%) than in NHW (70.6%, P ≤ 0.001). AA had lower median ALT levels (P ≤ 0.001). In those patients who were biopsied, there was no significant difference in fibrosis between the two groups. Aspartate to platelet index calculated in those patients who were not biopsied showed significantly lower fibrosis scores in AA. Conclusions In this large cohort of CHC patients from a single institution, AA were older at presentation, had a higher prevalence of genotype 1, but significantly lower ALT levels than NHW.
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Abstract
Chronic liver disease is a major source of morbidity and mortality in the United States today. There is little information on the interethnic variation in the clinical presentation, therapeutic responses and prognosis of individuals with liver disease. This review will discuss the ethnic variations and implications of the most common liver diseases.
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Abstract
Black patients receiving dialysis for end-stage renal disease in the United States have lower mortality rates than white patients. Whether racial differences exist in mortality after acute renal failure is not known. We studied acute renal failure in patients hospitalized between 2000 and 2003 using the Nationwide Inpatient Sample and found that black patients had an 18% (95% confidence interval [CI] 16 to 21%) lower odds of death than white patients after adjusting for age, sex, comorbidity, and the need for mechanical ventilation. Similarly, among those with acute renal failure requiring dialysis, black patients had a 16% (95% CI 10 to 22%) lower odds of death than white patients. In stratified analyses of patients with acute renal failure, black patients had significantly lower adjusted odds of death than white patients in settings of coronary artery bypass grafting, cardiac catheterization, acute myocardial infarction, congestive heart failure, pneumonia, sepsis, and gastrointestinal hemorrhage. Black patients were more likely than white patients to be treated in hospitals that care for a larger number of patients with acute renal failure, and black patients had lower in-hospital mortality than white patients in all four quartiles of hospital volume. In conclusion, in-hospital mortality is lower for black patients with acute renal failure than white patients. Future studies should assess the reasons for this difference.
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Affiliation(s)
- Sushrut S Waikar
- Department of Medicine, Brigham and Women's Hospital, MRB-4, 75 Francis Street, Boston, MA 02115, USA.
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Rosen HR, Weston SJ, Im K, Yang H, Burton JR, Erlich H, Klarquist J, Belle SH. Selective decrease in hepatitis C virus-specific immunity among African Americans and outcome of antiviral therapy. Hepatology 2007; 46:350-8. [PMID: 17659573 DOI: 10.1002/hep.21714] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
UNLABELLED Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, end-stage liver disease, and hepatocellular carcinoma throughout the world. Considerable evidence indicates that the risk of viral persistence, natural history, and response to antiviral therapy varies among racial groups, but limited data exist on potential mechanisms to account for these differences. Type 1 helper (Th1) responses to HCV proteins and cytomegalovirus (CMV) antigens were examined using a sensitive interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) assay in 187 Caucasian American (CA) and 187 African American (AA) patients with chronic genotype 1 infection. ELISPOT responses were examined relative to human leukocyte antigen (HLA) class II alleles and outcome of therapy with pegylated IFN and ribavirin. Th1 responses specific to hepatitis C core protein and combined HCV antigens were significantly lower in AAs compared to CAs, but CMV responses were comparable in the 2 races. The HCV difference in immunity remained after adjusting for gender, serum alanine aminotransferase, histologic severity, and viral level, and was not accounted for by the differential prevalence of human leukocyte antigen class II alleles. Pretreatment total HCV-specific CD4+ T cell response was associated with sustained virologic response (SVR) to pegylated IFN and ribavirin; 43% of patients who had more than 168 ELISPOTs/10(6) peripheral blood mononuclear cells (above background) experienced SVR compared to 28% of those who did not (P= 0.007). ELISPOT response was independently associated with SVR by multivariable analysis. CONCLUSION Compared to CAs, AAs have weaker HCV-specific immunity. Pretreatment HCV-specific immunity is associated with response to combination antiviral therapy.
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Affiliation(s)
- Hugo R Rosen
- Integrated Program in Immunology and Hepatitis C Research Center, Division of Gastroenterology and Hepatology, University of Colorado, Denver, CO, USA.
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Yee LJ, Tang YM, Kleiner DE, Wang D, Im K, Wahed A, Tong X, Rhodes S, Su X, Whelan RM, Fontana RJ, Ghany MG, Borg B, Liang TJ, Yang H. Myxovirus-1 and protein kinase haplotypes and fibrosis in chronic hepatitis C virus. Hepatology 2007; 46:74-83. [PMID: 17526009 DOI: 10.1002/hep.21636] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
UNLABELLED Candidate genes, including myxovirus resistance-1 (Mx1), protein kinase (PKR), transforming growth factor-beta1 (TGF-beta), interleukin-10 (IL-10), and interferon-gamma (IFN-gamma), were evaluated for associations with liver fibrosis in 374 treatment-naive patients with genotype-1 chronic HCV infection [194 Caucasian Americans (CAs) and 180 African Americans (AAs)], using a genetic haplotype approach. Among the 18 haplotypes that occurred with a frequency >or=5% in the cohort overall, the Mx1-(-123C)-(+6886A)-(+19820G(379V))-(+38645T) (abbreviated Mx1-CAGT), and PKR-(+110T)-(+7949G)-(+13846A)-(+22937T)-(+40342T) (abbreviated PKR-TGATT) haplotypes were independently associated with less severe hepatic fibrosis (Ishak >or= 3 versus <3). These associations persisted after adjustment for potential confounders such as alcohol use, sex, age (which is strongly correlated with the estimated duration of HCV infection [Spearman's correlation coefficient (r(s)) = 0.6)], and race (for Mx1-CAGT: OR = 0.33; 95% CI: 0.16-0.68; P = 0.0027; and for PKR-TGATT: OR = 0.56; 95% CI: 0.32-0.98; P = 0.0405). Population structure was evaluated using the structured association method using data from 161 ancestry-informative markers and did not affect our findings. We used an independent cohort of 34 AA and 160 CA in an attempt to validate our findings, although notable differences were found in the characteristics of the two patient groups. Although we observed a similar protective trend for the Mx1-CAGT haplotype in the validation set, the association was not statistically significant. CONCLUSION In addition to other factors, polymorphisms in cytokine genes may play a role in the progression of HCV-related fibrosis; however, further studies are needed.
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Affiliation(s)
- Leland J Yee
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
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Sanyal AJ, Fontana RJ, Di Bisceglie AM, Everhart JE, Doherty MC, Everson GT, Donovan JA, Malet PF, Mehta S, Sheikh MY, Reid AE, Ghany MG, Gretch DR. The prevalence and risk factors associated with esophageal varices in subjects with hepatitis C and advanced fibrosis. Gastrointest Endosc 2006; 64:855-64. [PMID: 17140886 DOI: 10.1016/j.gie.2006.03.007] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2005] [Accepted: 03/13/2006] [Indexed: 01/04/2023]
Abstract
BACKGROUND The factors predictive of the presence or the absence of esophageal varices in hepatitis C virus (HCV) and advanced fibrosis have not been defined. OBJECTIVES To define the prevalence of esophageal varices and the factors that are positively and negatively with such varices in hepatitis C and advanced fibrosis. DESIGN A prospective study of esophageal varices and associated risk factors in subjects with hepatitis C and advanced fibrosis. SETTING Prerandomization data from the HALT-C (hepatitis C long-term antiviral treatment against cirrhosis) clinical trial. PATIENTS AND INTERVENTION Subjects with bridging fibrosis or cirrhosis, who were virologic nonresponders to treatment with pegylated interferon alpha 2a and ribavirin, underwent endoscopy. RESULTS Sixteen percent of subjects with bridging fibrosis (95/598) and 39% of subjects with cirrhosis (164/418) had varices (P < .0001); 2% of subjects with bridging fibrosis (13/598) and 11% of those with cirrhosis (48/418) had medium or large varices. Subjects with bridging fibrosis and varices had a significantly lower platelet count and higher bilirubin and international normalized ratio (INR) compared with those without varices, suggesting that the biopsy may have underestimated the severity of fibrosis. A platelet count >150,000/mm(3) was associated with a negative predictive value of 99% for esophageal varices. By logistic regression modeling, African American race and female sex were protective, whereas a lower platelet count and higher bilirubin and INR predicted varices (c statistic, 0.758). CONCLUSIONS The risk of having varices increases with decreasing platelet counts, increasing bilirubin, and INR. The probability of having medium or large varices at platelet counts >150,000/mm(3) is negligible in this population.
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Affiliation(s)
- Arun J Sanyal
- Division of Gastroenterology, Virginia Commonwealth University Health System, Richmond, Virginia, USA
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Abstract
Hepatitis C virus (HCV) is a major cause of liver disease worldwide and is the most common chronic blood-borne infection in the United States. Experience has shown that the epidemiology and the response to treatment of HCV vary in certain patient groups. Differences have been observed in people from different racial and ethnic groups and in patients who have HIV and end-stage renal disease. These groups generally were not included in the early large clinical trials of HCV treatment. This article reviews recent findings in these patients groups and examines future directions.
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Affiliation(s)
- Meera Ramamurthy
- Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
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Fontana RJ, Kleiner DE, Bilonick R, Terrault N, Afdhal N, Belle SH, Jeffers LJ, Ramcharran D, Ghany MG, Hoofnagle JH. Modeling hepatic fibrosis in African American and Caucasian American patients with chronic hepatitis C virus infection. Hepatology 2006; 44:925-35. [PMID: 17006909 DOI: 10.1002/hep.21335] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Assessment of histological stage is an integral part of disease management in patients infected with the hepatitis C virus (HCV). The aim of this study was to develop a model incorporating objective clinical and laboratory parameters to estimate the probability of severe fibrosis (i.e., Ishak fibrosis > or = 3) in previously untreated African American (AA) and Caucasian American (CA) patients with HCV genotype 1. The Ishak fibrosis scores of 205 CA and 194 AA patients enrolled in the Viral Resistance to Antiviral Therapy of Chronic Hepatitis C study (Virahep-C) were modeled using simple and multiple logistic regression. The model was then validated in an independent cohort of 461 previously untreated patients with HCV. The distribution of fibrosis scores was similar in the AA and CA patients as was the proportion of patients with severe fibrosis (35% vs. 39%, P = .47). After accounting for the number of portal areas in the biopsy, patient age, serum aspartate aminotransferase, alkaline phosphatase, and platelet count were independently associated with severe fibrosis in the overall cohort, and the relationship with fibrosis was similar in both the AA and CA subgroups. The area under the receiver operating characteristic curve (AUROC) of the Virahep-C model (0.837) was significantly better than in other published models (P = .0003). The AUROC of the Virahep-C model was 0.851 in the validation population. In conclusion, a model consisting of widely available clinical and laboratory features predicted severe hepatic fibrosis equally well in AA and CA patients with HCV genotype 1 and was superior to other published models. The excellent performance of the Virahep-C model in an external validation cohort suggests the findings are replicable and potentially generalizable.
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Affiliation(s)
- Robert J Fontana
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
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Brady CW, Muir AJ. The impact of race and ethnicity on the treatment of hepatitis C disease. ACTA ACUST UNITED AC 2006. [DOI: 10.1007/s11901-006-0009-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Dienstag JL, McHutchison JG. American Gastroenterological Association technical review on the management of hepatitis C. Gastroenterology 2006; 130:231-64; quiz 214-7. [PMID: 16401486 DOI: 10.1053/j.gastro.2005.11.010] [Citation(s) in RCA: 270] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Jules L Dienstag
- Gastrointestinal Unit (Medical Services) Massachusetts General Hospital, Department of Medicine and Office of the Dean for Medical Education, Harvard Medical School, Boston, Massachusetts, USA
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Pearlman BL. Hepatitis C virus infection in African Americans. Clin Infect Dis 2005; 42:82-91. [PMID: 16323096 DOI: 10.1086/498512] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2005] [Accepted: 08/07/2005] [Indexed: 12/26/2022] Open
Abstract
Hepatitis C is more prevalent among African Americans than among persons of any other racial group in the United States. However, comparatively little data are available on the natural history and treatment of hepatitis C in this population. Compared with white persons, African American persons have a lower rate of viral clearance and, consequently, a higher rate of chronic hepatitis C. Nonetheless, African American persons may have a lower rate of fibrosis progression than do white persons. African American persons with hepatitis C-related cirrhosis have higher rates of both hepatocellular carcinoma and liver cancer-related mortality than do white persons with hepatitis C-related cirrhosis. In nearly all treatment trials that enrolled a significant proportion of African American subjects, such patients had inferior treatment responses, compared with those of white subjects. The prevalence of infection with hepatitis C virus genotype 1 is higher among African American patients than white patients, although this difference does not account for a greatly dissimilar response to therapy. Some of the postulated mechanisms for these disparate treatment responses and natural histories of infection are also reviewed.
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Affiliation(s)
- Brian L Pearlman
- Center for Hepatitis C, Atlanta Medical Center, Medical College of Georgia, Atlanta, GA, USA.
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Murray KF, Finn LS, Taylor SL, Seidel KD, Larson AM. Liver histology and alanine aminotransferase levels in children and adults with chronic hepatitis C infection. J Pediatr Gastroenterol Nutr 2005; 41:634-8. [PMID: 16254522 DOI: 10.1097/01.mpg.0000179758.82919.1f] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND Chronic hepatitis C is often a mild disease in children, but whether this is related to younger age or shorter duration of infection is unclear. Histologic severity has been shown to correlate with duration of infection regardless of age. OBJECTIVES We compared histologic findings in children and adults with chronic hepatitis C while controlling for sex, duration of infection, hepatitis C virus (HCV)-RNA level, and genotype. METHODS Twenty-one children and 52 adults whose infection was less than 20 years in duration and who had undergone a liver biopsy were included. Two blinded liver pathologists reviewed the liver biopsies and scored inflammatory activity and fibrosis using the modified Knodell scoring system. RESULTS The groups were the same with respect to HCV-RNA level (P=0.8), and genotype (P=0.6) but differed in duration of disease (P=0.01) and sex composition (P=0.005). Covariate analysis showed no influence of genotype, duration of infection, or HCV-RNA level on outcome. In controlling for sex, children had significantly milder liver disease and alanine aminotransferase (ALT) elevations. CONCLUSIONS With equal duration of infection, HCV-RNA level, and genotype, children have lower serum ALT levels and less severe liver disease than adults infected with HCV.
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Affiliation(s)
- Karen F Murray
- Division of Gastroenterology and Nutrition, Department of Pediatrics, Children's Hospital and Regional Medical Center, Seattle, WA 98195-6174, USA
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Cheung RC, Currie S, Shen H, Ho SB, Bini EJ, Anand BS, Bräu N, Wright TL. Chronic hepatitis C in Latinos: natural history, treatment eligibility, acceptance, and outcomes. Am J Gastroenterol 2005; 100:2186-93. [PMID: 16181367 DOI: 10.1111/j.1572-0241.2005.00240.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The natural history of chronic hepatitis C and treatment response are different between blacks and Caucasians, but little comparable data is available about Latinos. METHODS A cross-sectional secondary analysis to investigate differences between 421 anti-HCV-positive, treatment-naïve, HCV-viremic Latinos and 2,510 Caucasians in 24 VA medical centers enrolled in a prospective study. RESULTS Latinos were infected at a younger age and were less likely to have blood contact during combat, surgery, and needle stick injury, but were more frequently HIV coinfected (20.4%vs 3.9%, p < 0.0001) and prior HAV infection (39.9%vs 26.4%, p= 0.0001). Latinos were more likely to be treatment candidates, but less likely to actually initiate treatment. Liver histology (123 Latinos, 743 Caucasians) showed no difference in fibrosis or fibrosis rate, but steatosis (54.7%vs 43.2%, p= 0.038) was more common in Latinos. Eighty-eight Latinos and 481 Caucasians were subsequently treated with interferon-ribavirin: body mass index (BMI), duration of infection, baseline tests, liver histology and genotype distribution were similar. Compared with Caucasians, Latinos discontinued treatment prematurely more often (39.8%vs 28.9%, p= 0.043) and tended to have lower sustained virological response (SVR) rates (14.8%vs 22.5%, p= 0.10). Multivariate analysis found Latino race and history of recent alcohol use to be associated with early treatment discontinuation, whereas genotype and viral load but not ethnicity to be associated with SVR. CONCLUSIONS Latinos were infected younger, more frequently HIV coinfected, more likely to meet criteria for antiviral therapy yet less likely to initiate treatment and had a trend toward lower SVR rates than Caucasians, but not in severity of liver disease. Latino ethnicity was associated with early discontinuation but not as an independent predictor of SVR.
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Affiliation(s)
- Ramsey C Cheung
- VA Palo Alto Healthcare System and Stanford University School of Medicine, Palo Alto, California 94304, USA
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Liu M, Zhang SL, Cheng J, Liu Y, Wang L, Shao Q, Zhang J, Lin SM. Genes transactivated by hepatitis C virus core protein, a microarray assay. World J Gastroenterol 2005; 11:3351-6. [PMID: 15948238 PMCID: PMC4315987 DOI: 10.3748/wjg.v11.i22.3351] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the new target genes transactivated by hepatitis C virus (HCV) core protein and to elucidate the pathogenesis of HCV infection.
METHODS: Reverse transcribed cDNA was subjected to microarray assay. The coding gene transactivated by HCV core protein was cloned and analyzed with bioinformatics methods.
RESULTS: The expressive vector of pcDNA3.1(-)-core was constructed and confirmed by restriction enzyme digestion and DNA sequencing and approved correct. mRNA was purified from HepG2 and HepG2 cells transfected with pcDNA3.1(-)-core, respectively. The cDNA derived was subjected to microarray assay. A new gene named HCTP4 was cloned with molecular biological method in combination with bioinformatics method.
CONCLUSION: HCV core is a potential transactivator. Microarray is an efficient and convenient method for analysis of differentially expressed genes.
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Affiliation(s)
- Min Liu
- Department of Infectious Diseases, The First Affilated, Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
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