|
1
|
Hoffman SB, Magder LS, Viscardi RM. Renal versus cerebral saturation trajectories: the perinatal transition in preterm neonates. Pediatr Res 2022; 92:1437-1442. [PMID: 35177816 DOI: 10.1038/s41390-022-01984-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 01/04/2022] [Accepted: 01/26/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND The aim of this study was to develop reference renal saturation (rSrO2) curves in premature infants, depict how they differ from cerebral saturation (rScO2) curves, and evaluate the effect of blood pressure on these values using near-infrared spectroscopy (NIRS). METHODS This is a prospective cohort study of 57 inborn infants <12 h and <30 weeks gestation. rScO2, rSrO2, fractional tissue oxygen extraction (FTOE), and mean arterial blood pressure (MAP) were continuously monitored every 30 s for 96 h. Quantile regression was used to establish nomograms, and mean saturation values were evaluated for different MAP ranges. RESULTS Median rSrO2 at the start of monitoring was ~10% higher than rScO2. rSrO2 showed a significant decline over time while rScO2 peaked at 26 h. FTOE demonstrated a similar but inverse trend to their saturation counterparts. rScO2 declined as MAP increased, while rSrO2 showed a peak and decline as MAP increased. CONCLUSIONS We provide rSrO2 reference curves for the first 4 days of life, which differ in their trajectory from rScO2 and from what has previously been reported for rSrO2 in the full-term population. In addition, we observed a peak and decline in renal saturation with increasing MAP, suggesting a renovascular response to blood pressure changes. IMPACT This article depicts reference renal saturation curves during the perinatal transition in preterm infants. We show how renal saturation compares to cerebral saturation trends over time. We describe a peak and decline in renal saturation with increasing MAP, suggesting a renovascular response to blood pressure changes.
Collapse
Affiliation(s)
- Suma B Hoffman
- Department of Pediatrics, University of Maryland Baltimore School of Medicine, Baltimore, MD, USA. .,Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Children's National Health System - Neonatology, Washington, DC, USA.
| | - Laurence S Magder
- Department of Epidemiology and Public Health, University of Maryland Baltimore School of Medicine, Baltimore, MD, USA
| | - Rose M Viscardi
- Department of Pediatrics, University of Maryland Baltimore School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
2
|
Ayana DA, Mulu A, Mihret A, Seyoum B, Aseffa A, Howe R. Occult Hepatitis B virus infection among HIV negative and positive isolated anti-HBc individuals in eastern Ethiopia. Sci Rep 2020; 10:22182. [PMID: 33335238 PMCID: PMC7747707 DOI: 10.1038/s41598-020-79392-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 12/02/2020] [Indexed: 01/05/2023] Open
Abstract
The absence of hepatitis B surface antigen (HBsAg) and the presence of antibody to hepatitis B core antigen (anti-HBc) in the blood of apparently healthy individuals may not indicate the absence of circulating hepatitis B virus (HBV) and might be infectious. Despite the risk of HBV transmission, there has been no report from Ethiopia examining this issue; therefore, this study determined occult HBV infection (OBI) among isolated anti-HBc (IAHBc) HIV negative and HIV positive individuals on ART in eastern Ethiopia. A total of 306 IAHBc individuals were included in this study. DNA was extracted, amplified, and detected from plasma using a commercially available RealTime PCR platform (Abbott m2000rt) following the manufacturer's instructions. Data were entered into EPI Data version 3.1, cleaned, and analyzed using Stata version 13. Descriptive analysis was used to calculate prevalence, summarize sociodemographic data and other factors. From the 306 IAHBc individuals (184 HIV positive and 122 HIV negative) included in the study, 183 (59.8%) were female of which 142 (77.6%) were within the reproductive age group. DNA extraction, amplified and detection was conducted in 224 individuals. The overall OBI prevalence was 5.8% (5.6% in HIV negative and 6% in HIV positive) among the IAHBc individuals. The HBV DNA concentration among the occult hepatitis B individuals was < 200 IU/mL, indicating a true occult. This study reported the burden of OBI, which pauses a significant public health problem due to the high burden of HBV infection in the country. OBI may cause substantial risk of HBV transmission from blood transfusion, organ transplantation as well as vertical transmission as screening is solely dependent on HBsAg testing.
Collapse
Affiliation(s)
- Desalegn Admassu Ayana
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia.
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
| | - A Mulu
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - A Mihret
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - B Seyoum
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - A Aseffa
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - R Howe
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| |
Collapse
|
|
3
|
Chen XX, Xiang KH, Zhang HP, Kong XS, Huang CY, Liu YM, Lou JL, Gao ZH, Yan HP. Occult HBV infection in patients with autoimmune hepatitis: A virological and clinical study. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2020; 53:946-954. [DOI: 10.1016/j.jmii.2019.04.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 04/10/2019] [Accepted: 04/26/2019] [Indexed: 02/06/2023]
|
|
4
|
Midorikawa Y, Takayama T, Nakayama H, Higaki T, Moriguchi M, Moriya K, Kanda T, Matsuoka S, Moriyama M. Prior hepatitis B virus infection as a co-factor of chronic hepatitis C patient survival after resection of hepatocellular carcinoma. BMC Gastroenterol 2019; 19:147. [PMID: 31426746 PMCID: PMC6700986 DOI: 10.1186/s12876-019-1069-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 08/15/2019] [Indexed: 02/07/2023] Open
Abstract
Background Prior hepatitis B virus infection (PBI) may increase the risk of developing hepatocellular carcinoma (HCC), but the impact of PBI on clinical outcomes following treatment for HCC remains unknown. The aim of this study was to clarify whether PBI affects clinical outcomes after liver resection for hepatitis C virus (HCV)-related HCC by retrospective cohort study. Methods PBI patients were defined as those negative for hepatitis B surface antigen and positive for anti-hepatitis B core antibody. Surgical outcomes of HCV-related HCC patients with PBI were compared to those without PBI. Survival of patients with non-B non-C HCC with and without PBI were also compared. Results In the HCV group, the median overall survival of 165 patients with PBI was 4.7 years (95% confidence interval [CI], 3.9–5.9), and was significantly shorter compared with 263 patients without PBI (6.6 years [5.3–9.8]; p = 0.015). Conversely, there was no significant difference in recurrence-free survival between the two groups (1.8 years [95% CI, 1.4–2.0] vs 2.0 years [1.7–2.3]; p = 0.205). On Cox proportional hazards regression model, independent factors for overall survival were PBI (hazard ratio 1.38 [95% CI, 1.02–1.87]; p = 0.033), multiple tumors (p = 0.007), tumor size (p = 0.002), and liver cirrhosis (p < 0.001). On the other hand, in the non-B non-C HCC group, both the median overall survival (6.5 years [95% CI, 4.8–7.1]) and recurrence-free survival (2.4 years, [95% CI, 1.5–3.3]) in 104 patients with PBI were not significantly different from those (7.5 years [5.5 − NA; p = 0.932]; and 2.2 years [1.7–2.7; p = 0.983]) in 213 patients without PBI. Conclusions PBI and HCV in conjunction with each other affect the survival of patients that have undergone resection for HCC.
Collapse
Affiliation(s)
- Yutaka Midorikawa
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan.
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan.
| | - Hisashi Nakayama
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Tokio Higaki
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Masamichi Moriguchi
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Kyoji Moriya
- Department of Infectious Diseases, University of Tokyo Faculty of Medicine, Tokyo, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Shunichi Matsuoka
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Mitsuhiko Moriyama
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
5
|
Yamaji K, Kai K, Komukai S, Koga H, Ide T, Kawaguchi A, Noshiro H, Aishima S. Occult HBV infection status and its impact on surgical outcomes in patients with curative resection for HCV-associated hepatocellular carcinoma. Hepatobiliary Surg Nutr 2018; 7:443-453. [PMID: 30652089 PMCID: PMC6295390 DOI: 10.21037/hbsn.2018.10.01] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 10/09/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND We sought to clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and to determine whether OBI affects the surgical outcomes in curatively resected Japanese patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS A total of 257 patients with HCV-related HCC who underwent curative surgical resection were enrolled. All enrolled patients were serologically negative for HBV surface antigen and positive for HCV antibody. DNA was extracted from formalin-fixed paraffin-embedded liver tissue. OBI was determined by the HBV-DNA amplification of at least two different sets of primers by TaqMan real-time polymerase chain reaction. Surgical outcomes were evaluated according to overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). RESULTS OBI was identified in 15 of the 257 (5.8%) cases. In the multivariate analyses, the factors significantly correlated with OS were BMI >25 (P=0.0416), portal vein invasion (P=0.0065), and multiple tumors (P=0.0064). The only factor significantly correlated with DSS was T-stage (P=0.0275). The factors significantly correlated with DFS were liver fibrosis (P=0.0017) and T-stage (P=0.0001). The status of OBI did not show any significant correlation with OS, DSS or DFS, but a weak association with DSS (P=0.0603) was observed. CONCLUSIONS The prevalence of OBI was 5.8% in 257 cases of HCV-related HCC. Although a weak association between DSS and OBI was observed, and statistical analyses were limited by small number of OBI cases, no significant correlation between OBI and surgical outcomes was detected.
Collapse
Affiliation(s)
- Koutaro Yamaji
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
- Department of Pathology & Microbiology, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Keita Kai
- Department of Pathology, Saga University Hospital, Saga 849-8501, Japan
| | - Sho Komukai
- Clinical Research Center, Saga University Hospital, Saga 849-8501, Japan
| | - Hiroki Koga
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Takao Ide
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Atsushi Kawaguchi
- Center for Comprehensive Community Medicine, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Hirokazu Noshiro
- Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
| | - Shinichi Aishima
- Department of Pathology & Microbiology, Saga University Faculty of Medicine, Saga 849-8501, Japan
- Department of Pathology, Saga University Hospital, Saga 849-8501, Japan
| |
Collapse
|
|
6
|
Joshi SS, Coffin CS. Hepatitis B virus lymphotropism: emerging details and challenges. Biotechnol Genet Eng Rev 2018; 34:139-151. [DOI: 10.1080/02648725.2018.1474324] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Shivali S. Joshi
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada
- Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Carla S. Coffin
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada
- Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada
| |
Collapse
|
|
7
|
Mohraz M, Jafari R, Poortahmasebi V, Sadeghi A, Hajabdolbaghi M, Rasoolinejad M, Forooghi M, Norouzi M, Poorebrahim M, Khamseh A, Karkhaneh M, Alavian SM, Ebrahimian A, Jazayeri SM. Molecular analysis of occult hepatitis B infection among Iranian HIV-positive patients. Future Virol 2016. [DOI: 10.2217/fvl-2016-0032] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Aim: The aims of this study were to find out the prevalence of occult hepatitis B infection (OBI) in HIV-1 patients, as well as to analyze the mutational patterns of OBI-positive individuals. Materials & methods: 172 HBsAg-negative, HIV-1-positive patients were selected according to data extracted from questionnaires. HBV serologic and molecular assays were performed. An extensive mutational analysis was applied using direct sequencing on HBsAg. Results: Thirty-one samples (18%) were OBI positive. Among 24 available OBI-positive samples, 17 (71%) contained at least one mutation only within ‘a’ determinant region of HBsAg. A stretch of mutations was found between amino acid positions 121 and 136. The physicochemical properties of individual amino acid substitutions and their potential impacts on 3D structure of ‘a’ determinant mutants were also determined. Conclusion: HBV serologic assays are not reliable markers to exclude occult HBV infection in HIV-positive patients.
Collapse
Affiliation(s)
- Minoo Mohraz
- Iranian Research Center for HIV AIDS, High Risk Reduction Institute, Tehran, Iran
| | - Rezvaneh Jafari
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Vahdat Poortahmasebi
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmadreza Sadeghi
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mehrnaz Rasoolinejad
- Iranian Research Center for HIV AIDS, High Risk Reduction Institute, Tehran, Iran
| | - Maryam Forooghi
- Iranian Research Center for HIV AIDS, High Risk Reduction Institute, Tehran, Iran
| | - Mehdi Norouzi
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mansour Poorebrahim
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Azam Khamseh
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Karkhaneh
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Moayed Alavian
- Middle East Liver Disease (MELD) Center, No 178, Sepahboud Gharanee St. Tehran 1598976516, Iran
| | - Arefeh Ebrahimian
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | | |
Collapse
|
|
8
|
Raouf HE, Yassin AS, Megahed SA, Ashour MS, Mansour TM. Seroprevalence of occult hepatitis B among Egyptian paediatric hepatitis C cancer patients. J Viral Hepat 2015; 22:103-11. [PMID: 24754376 DOI: 10.1111/jvh.12260] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2013] [Accepted: 03/26/2014] [Indexed: 12/12/2022]
Abstract
Occult hepatitis B infection is characterized by the presence of hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). Prevalence of hepatitis C virus (HCV) infections in Egypt is among the highest in the world. In this study, we aim at analysing the rates of occult HBV infections among HCV paediatric cancer patients in Egypt. The prevalence of occult HBV was assessed in two groups of paediatric cancer patients (HCV positive and HCV negative), in addition to a third group of paediatric noncancer patients, which was used as a general control. All groups were negative for HBsAg and positive for HCV antibody. HBV DNA was detected by nested PCR and real-time PCR. HCV was detected by real-time PCR. Sequencing was carried out in order to determine HBV genotypes to all HBV patients as well as to detect any mutation that might be responsible for the occult phenotype. Occult hepatitis B infection was observed in neither the non-HCV paediatric cancer patients nor the paediatric noncancer patients but was found in 31% of the HCV-positive paediatric cancer patients. All the detected HBV patients belonged to HBV genotype D, and mutations were found in the surface genome of HBV leading to occult HBV. Occult HBV infection seems to be relatively frequent in HCV-positive paediatric cancer patients, indicating that HBsAg negativity is not sufficient to completely exclude HBV infection. These findings emphasize the importance of considering occult HBV infection in HCV-positive paediatric cancer patients especially in endemic areas as Egypt.
Collapse
Affiliation(s)
- H E Raouf
- Department of Microbiology and Immunology, Faculty of Pharmacy, Modern Sciences and Arts University, Giza, Egypt
| | | | | | | | | |
Collapse
|
|
9
|
Chenari M, Norouzi M, Ghalichi L, Rezaee A, Yari A, Alavian SM, Jazayeri SM. Characterization of overt and occult hepatitis B virus infection among HTLV-1 positive healthy carriers in the Northeast of Iran; AN HTLV-I endemic area. J Med Virol 2014; 86:1861-7. [PMID: 25132488 DOI: 10.1002/jmv.24046] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2014] [Indexed: 12/23/2022]
Abstract
To date, no studies have provided data on hepatitis B virus (HBV) prevalence among asymptomatic, healthy human T-lymphotropic virus (HTLV-I) positive carriers. This sero- and molecular epidemiology study was performed on patients in the Northeast of Iran, which is an endemic area for HTLV-I infection. A total of 109 sera were collected from HTLV-I positive healthy carriers who were admitted to Ghaem Hospital, Mashhad City. All were tested for HBV serology and subsequently, real time PCR was carried out on the samples, regardless of the results of the serology. Standard PCR and direct sequencing were applied on positive samples. All cases were negative for HBsAg, Anti-HBc, and anti-HBs were positive in 34 (31.1%), and 35 (32%) individuals, respectively. There were 19 (17.4%) cases that were positive only for anti-HBs, and they had already received HBV vaccine. 16 (15%) were positive for both anti-HBs and anti-HBc, indicating a past-resolved HBV infection. 18 (16.5%) were isolated as anti-HBc, and 56 (51.3%) were negative for all HBV serological markers. Only one subject (0.9%) had detectable HBV DNA (2153 copy/ml), and assigned as being an occult HBV infection. The low prevalence of HBsAg, despite the high percentage of anti-HBc positive cases, might be related to the suppression effect of HTLV-I on surface protein expression. The low prevalence of HBV infection among HTLV-I positive healthy carriers from an endemic region, indicates that the epidemiology of HTLV-I and HBV coinfection is related to the endemicity of HBV in that region, rather than HTLV-I endemicity.
Collapse
Affiliation(s)
- Maryam Chenari
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | | | | | | | | | | | | |
Collapse
|
|
10
|
Taha SE, El-Hady SA, Ahmed TM, Ahmed IZ. Detection of occult HBV infection by nested PCR assay among chronic hepatitis C patients with and without hepatocellular carcinoma. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2013. [DOI: 10.1016/j.ejmhg.2013.06.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
|
|
11
|
Caviglia GP, Abate ML, Manzini P, Danielle F, Ciancio A, Rosso C, Olivero A, Pellicano R, Touscoz GA, Smedile A, Rizzetto M. Occult hepatitis B virus infection in patients with chronic hepatitis C treated with antiviral therapy. HEPATITIS MONTHLY 2012; 12:e7292. [PMID: 23300497 PMCID: PMC3539061 DOI: 10.5812/hepatmon.7292] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/01/2012] [Revised: 07/10/2012] [Accepted: 07/28/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the liver and/or in the serum of patients with negative results of hepatitis B s antigen (HBsAg) test with or without serological markers of previous viral exposure. The impact of OBI in patients with chronic hepatitis C (CHC) is still unclear. OBJECTIVES The Aim of this study was to assess OBI prevalence and its potential implications on treatment outcome in a cohort of patients with CHC underwent standard antiviral therapy. PATIENTS AND METHODS Baseline serum samples from 137 HBsAg-negative CHC patients treated with pegylated-interferon and ribavirin (73 Responders/74 Non Responders),were retrospectively analyzed for HBV status. RESULTS Seventy-three patients (53.3%) showed markers of previous exposure to HBV. HBV DNA was detected in 2 of 137 serum samples (1.5%), both carrying HBV antibodies. Liver biopsies and post-therapy sera were available for 35 patients (12 Responders/23 Non Responders). HBV DNA sequences were found in 13 of 35 specimens (37.1%), all of patients with HBV DNA negativity in basal and post-therapy serum samples. Among OBI-positive patients, 5 (38.5%) carried serological markers of HBV infection. Regarding therapy outcome, in the OBI-positive group there were 5 of 13 (38.5%) sustained virological responders (SVR) compared to 7 of 22 (31.8%) in the OBI-negative one. CONCLUSIONS Despite the high prevalence rate of liver HBV DNA in patients with CHC, SVR was not affected by occult HBV infection.
Collapse
Affiliation(s)
| | | | - Paola Manzini
- Blood Bank, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Franca Danielle
- Blood Bank, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Alessia Ciancio
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Chiara Rosso
- Department of Internal Medicine, University of Turin, Turin, Italy
| | | | - Rinaldo Pellicano
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Giovanni Antonio Touscoz
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Antonina Smedile
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Mario Rizzetto
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| |
Collapse
|
|
12
|
Shahmoradi S, Yahyapour Y, Mahmoodi M, Alavian SM, Fazeli Z, Jazayeri SM. High prevalence of occult hepatitis B virus infection in children born to HBsAg-positive mothers despite prophylaxis with hepatitis B vaccination and HBIG. J Hepatol 2012; 57:515-521. [PMID: 22617152 DOI: 10.1016/j.jhep.2012.04.021] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2011] [Revised: 04/05/2012] [Accepted: 04/11/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Occult hepatitis B virus (HBV) infection is a well-recognized clinical entity characterized by the detection of HBV DNA in serum and/or liver in the absence of detectable hepatitis B surface antigen (HBsAg). The frequency of the diagnosis depends on the relative sensitivity of both HBsAg and HBV DNA assays. We aimed at determining the prevalence of occult HBV infection in a high risk group of children who developed HBV infection despite immunoprophylaxis. METHODS The sera of 75 children born to HBsAg-positive mothers previously immunized by HBIG and prophylaxic vaccine regimen were assayed for HBV DNA by real-time PCR. Subsequently, the samples were tested using a sensitive standard PCR, with an independent set of primers for all HBV genes, and analyzed by direct sequencing. RESULTS HBV DNA was detected in 21/75 (28%) children, and ranged between 77 and 9240 copies/ml. All were positive for anti-HBs. Five (24%) children were found to be positive for anti-HBc, while anti-HBc-only positive individuals were not observed. Eight isolates (38%) did not carry any mutation. Thirteen infected children (62%) had at least one mutation in regions known to be involved in functional and/or immune epitope activity. Ten had G145R mutations. CONCLUSIONS HBV occult infection seems to be relatively frequent in immunized children born to HBsAg-positive mothers. HBsAg negativity is not sufficient to completely exclude HBV DNA presence. These findings emphasize the importance of considering occult HBV infection in hypo-endemic areas.
Collapse
Affiliation(s)
- Sajad Shahmoradi
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | | | | | | | | | | |
Collapse
|
|
13
|
Occult Hepatitis B (OBH) in Clinical Settings. HEPATITIS MONTHLY 2012. [DOI: 10.5812/hapatmon.6126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
|
|
14
|
Alavian SM, Miri SM, Hollinger FB, Jazayeri SM. Occult Hepatitis B (OBH) in Clinical Settings. HEPATITIS MONTHLY 2012; 12:e6126. [PMID: 23087749 PMCID: PMC3475016 DOI: 10.5812/hepatmon.6126] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/20/2012] [Revised: 06/20/2012] [Accepted: 07/08/2012] [Indexed: 12/11/2022]
Abstract
CONTEXT Occult hepatitis B (OHB), or persistent HBV DNA in patients who are hepatitis B surface antigen (HBsAg) negative, is a recently recognized entity. In an attempt to summarize the issues, this review presents an overview of the current proposed hypothesis on the clinical relevance and also updates the knowledge on the classification of OHB in different clinical settings. EVIDENCE ACQUISITION OHB COULD BE FOUND IN DIFFERENT POPULATION AND CLINICAL BACKGROUNDS INCLUDING: viral co-infections (with either human immunodeficiency or hepatitis C viruses), HBV chronic carriers, dialysis patients, transplantation settings and certain clinical situations (named in here: special clinical settings) with no apparent distinguishable clinical parameters. RESULTS The exact magnitude, pathogenesis, and clinical relevance of OHB are unclear. Even the possible role exerted by this cryptic infection on liver disease outcome, and hepatocellular carcinoma development remains unknown. CONCLUSIONS Monitoring of Individuals with positive anti-HBc, mass immunization programs and improvement in diagnostic tools seem to be important to control the probability of transmission of HBV through cryptic HBV infection.
Collapse
Affiliation(s)
- Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Seyed Mohammad Miri
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | | | - Seyed Mohammad Jazayeri
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
| |
Collapse
|
|
15
|
Alavian SM, Carman WF, Jazayeri SM. HBsAg variants: diagnostic-escape and diagnostic dilemma. J Clin Virol 2012; 57:201-8. [PMID: 22789139 DOI: 10.1016/j.jcv.2012.04.027] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2011] [Revised: 01/23/2012] [Accepted: 04/18/2012] [Indexed: 12/11/2022]
Abstract
A wide variety of commercial assays is available for the detection of hepatitis B surface antigen (HBsAg). Clearly, the sensitivity of an assay to detect a variant is dependent on the anti-HBs usage. Thus, it is not surprising that there are examples of variants that cannot be detected by all assays. Data from Europe, Asia and Africa about HBsAg variants which are not recognized by either monoclonal or polyclonal antibodies specific for wild-type group 'a' determinant, but positive by DNA polymerase chain reaction (PCR) in chronic patients and from vaccinated children are increasing. This would impose a challenge for public health issues of hepatitis B virus. In this review we tried to summarize the discrepancies between results of HBsAg assays and to explain some rationales for these inconsistencies.
Collapse
Affiliation(s)
- Seyed Moayed Alavian
- Baqiyatallah University of Medical Sciences, Baqiyatallah Research Centre for Gastroenterology and Liver Disease, Tehran, Iran
| | | | | |
Collapse
|
|
16
|
Audsley J, du Cros P, Goodman Z, McLean C, Mijch A, Lewin SR, Sasadeusz J. HIV replication is associated with increased severity of liver biopsy changes in HIV-HBV and HIV-HCV co-infection. J Med Virol 2012; 84:993-1001. [DOI: 10.1002/jmv.23236] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
|
|
17
|
Thabit AM, Al-Moyed KA, Al-Balushi MS, Hasson SS, Sallam TA. Occult hepatitis B virus among chronic liver disease patients in Yemen. ASIAN PACIFIC JOURNAL OF TROPICAL DISEASE 2012. [DOI: 10.1016/s2222-1808(12)60002-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
|
|
18
|
Alavian SM, Jazayeri SM. Other views of occult hepatitis B in Hepatitis C infected patients. Eur J Intern Med 2011; 22:e67-8. [PMID: 21925047 DOI: 10.1016/j.ejim.2011.05.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2011] [Revised: 05/03/2011] [Accepted: 05/04/2011] [Indexed: 01/05/2023]
|
|
19
|
Selim HS, Abou-Donia HA, Taha HA, El Azab GI, Bakry AF. Role of occult hepatitis B virus in chronic hepatitis C patients with flare of liver enzymes. Eur J Intern Med 2011; 22:187-90. [PMID: 21402251 DOI: 10.1016/j.ejim.2010.12.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2010] [Revised: 10/28/2010] [Accepted: 12/01/2010] [Indexed: 12/12/2022]
Abstract
BACKGROUND Occult HBV infection is defined by detection of HBV DNA in the serum or liver tissue of patients who test negative for HBsAg. The prevalence of occult HBV is higher in hepatitis C virus (HCV) positive patients than HCV negative patients and may have an impact on their clinical outcome. In this study, we evaluated the role of occult hepatitis B virus infection in chronic hepatitis C patients with ALT flare. METHODS Sixty HBsAg negative patients with chronic hepatitis C virus infection were included. Patients were divided into 2 groups according to their ALT level: 30 patients with normal or slightly high ALT and 30 patients with ALT flare (≥ 5 times normal values). Patients in both groups were examined for the detection of anti-HBs, anti-HBc IgM, and anti-HBc IgG. HBV DNA was detected using semi-nested PCR technique. RESULTS In patients with normal or slightly high ALT, HBV DNA was detected in 4 (13.3%) patients, while in those with ALT flare, HBV DNA was detected in 19 (63.3%) patients (p<0.001). No association was found between the presence of HBV DNA and various serology markers of HBV infection. CONCLUSION Presence of occult hepatitis B, with its added deleterious effect, must always be considered in chronic hepatitis C patients especially those with flare in liver enzymes; HBsAg should not be used alone for the diagnosis of HBV infection.
Collapse
Affiliation(s)
- Heba S Selim
- Microbiology Department, High Institute of Public Health, Alexandria University, Egypt
| | | | | | | | | |
Collapse
|
|
20
|
Nan X, Shi S, Yu C, Zhuang H. Meta-analysis of the association between anti-HBc seropositivity and a poor prognosis of chronic HCV infection. Hepatol Res 2010; 40:1176-87. [PMID: 21040276 DOI: 10.1111/j.1872-034x.2010.00733.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM The impact of serological HBsAg- and anti-HBc+ on the prognosis of chronic hepatitis C virus (HCV) infection is unknown. We conducted a systematic review to analyze whether anti-HBc positivity imposes any effect on the course of HCV-related chronic liver disease. METHODS We retrieved references from online databases that included PubMed and EMBASE. Data were gathered with regard to demographic information, disease progression and prognosis, and the results of serological tests. The development of hepatocellular carcinoma (HCC) was the endpoint of follow-up of all cohort studies. RESULTS Eighteen references were included in this study, of which four were cohort studies. Twelve studies were retrospective, observational and non-interventional studies. According to our meta-analysis, the rate of serological HBsAg- and anti-HBc+ was higher among HCC patients compared with non-HCC patients (odds ratio [OR], 1.55; 95% CI, 1.22-1.98). HCV patients that were anti-HBc+ had a greater chance of developing HCC than their anti-HBc- counterparts (OR, 2.15; 95% CI, 1.34-3.47). CONCLUSIONS The serological status of HBsAg- and anti-HBc+ appears to be correlated with a poor prognosis for chronic HCV infection. Though the general quality of these references was low, and multiple confounding factors existed, the likelihood of a poorer outcome of HCV patients that are positive for anti-HBc should be considered by their physicians.
Collapse
Affiliation(s)
- Xiao Nan
- Department of Microbiology Department of Public Health, Peking University Health Science Center, Peking, China
| | | | | | | |
Collapse
|
|
21
|
Lisboa Neto G, Tengan FM, Cavalheiro NDP, Barone AA. [Influence of previous hepatitis B virus infection on liver fibrosis in patients with chronic hepatitis C: a retrospective case series evaluation]. Rev Soc Bras Med Trop 2010; 43:416-20. [PMID: 20802942 DOI: 10.1590/s0037-86822010000400016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2009] [Accepted: 05/25/2010] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Hepatitis C is a major cause of liver disease worldwide. Its evolutionary course is dynamics and may be influenced by several cofactors. Among them, previous hepatitis B virus infection (anti-HBcAg [+] and HBsAg [-]) has been associated with worse histological and therapeutic prognosis. This study had the objective of independently assessing the relationship between previous hepatitis B infection and liver fibrosis in patients with chronic hepatitis C. METHODS The medical records of patients chronically infected with the hepatitis C virus who had been seen consecutively during a one-year period at the infectious and parasitic diseases outpatient clinic of HC FMUSP were retrospectively reviewed in relation to epidemiological, clinical and histological data. Analysis on the independence of the previous hepatitis B infection was performed using the statistical model of multivariate logistic regression. Detection of anti-HBcAg was taken to be the independent variable. The outcome was taken to be grade 3 and 4 histopathological abnormality (septa with nodule formation and cirrhosis). RESULTS 145 subjects were evaluated in this study. 47.2% of them were anti-HBcAg (+). The main risk factor for infection was blood and blood derivative transfusion (35.9%). Findings of anti-HBcAg (+) were not related to advanced liver fibrosis, although piecemeal necrosis has been found frequently in patients with this serological marker. CONCLUSIONS Previous hepatitis B infection does not seem to increase the structural liver damage triggered by chronic hepatitis C virus infection, after statistical control for other co-factors capable to impact the natural history of this infection.
Collapse
Affiliation(s)
- Gaspar Lisboa Neto
- Departamento de Doenças Infecciosas e Parasitárias, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP.
| | | | | | | |
Collapse
|
|
22
|
Kramer ES, Hofmann C, Smith PG, Shiffman ML, Sterling RK. Response to hepatitis A and B vaccine alone or in combination in patients with chronic hepatitis C virus and advanced fibrosis. Dig Dis Sci 2009; 54:2016-25. [PMID: 19517231 DOI: 10.1007/s10620-009-0867-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2009] [Accepted: 05/19/2009] [Indexed: 12/31/2022]
Abstract
Patients with advanced fibrosis are at increased risk of severe outcomes if they develop acute infection with hepatitis A (HAV) or hepatitis B (HBV) viruses. There are no data on the efficacy of combined HAV/HBV vaccination in patients with advanced fibrosis. Our aim was to evaluate the response to the HAV and HBV vaccine alone or in combination for patients with chronic hepatitis C (HCV) and advanced fibrosis and to evaluate the impact of administering the vaccine while patients were receiving peginterferon for treatment of chronic HCV. In this prospective study of patients with advanced fibrosis (Ishak 3-6), those without serologic evidence of prior exposure were vaccinated with either Havrix HAV, Engerix( HBV, or the TWINRIX HAV/HBV combination vaccine as appropriate, and response was defined as the development of anti-HAV or anti-HBV surface antibodies. Of the 162 eligible patients, the prevalence of prior exposure to HAV and HBV was 30 and 18%, respectively. Of the 84 patients vaccinated, 38% received Havrix, 14% Engerix, and 48% TWINRIX. The response to the HAV vaccine was 75% in those receiving Havrix compared to 78% receiving TWINRIX. In contrast, the response to HBV vaccination was 42% in patients receiving Engerix compared to 60% in those vaccinated with TWINRIX (difference 18.3%; OR 0.29; 95% CI: 0.57-7.79). The presence of diabetes was the only risk factor identified for reduced HBV response (P = 0.01). Responses to both HAV and HBV vaccines when administered alone or in combination were lower than expected in patients with HCV and advanced fibrosis, especially in those with diabetes. The observation that the decline in HBV vaccine response was somewhat lower when this was administered alone as opposed to the combination A/B vaccine suggests that the administration of a combination vaccine may enhance the vaccination response to HBV.
Collapse
Affiliation(s)
- Erik Seth Kramer
- Department of Epidemiology and Community Health, Virginia Commonwealth University, Richmond, VA 23298-0341, USA
| | | | | | | | | |
Collapse
|
|
23
|
Coffin CS, Terrault NA. Management of patients co-infected with HBV and HCV. Expert Rev Anti Infect Ther 2009; 7:549-58. [PMID: 19485795 DOI: 10.1586/eri.09.38] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
HBV and HCV are both hepatotrophic pathogens that share common routes of transmission, namely through exposure to infected blood and body fluids. Available natural history studies suggest dual infection with HBV and HCV increases the risk of progressive liver disease, and the risk of cirrhosis and liver cancer. Owing to the dynamic nature of these chronic infections, with fluctuations in viral level and disease activity, close monitoring is needed to determine the appropriate time to intervene with treatment. The clinical profile most commonly encountered is for active HCV infection (HCV RNA-positive) with or without active HBV infection (HBsAg-positive with variable HBV DNA levels). For these patients, treatment with pegylated interferon and ribavirin is the treatment of choice. For those with HBV-predominant disease (and HCV RNA-undetectable), the treatment is identical to that with HBV infection alone. For patients unresponsive to these initial treatments, there are no specific guidelines, and additional studies to define the treatment algorithms for nonresponders or relapsers are needed.
Collapse
Affiliation(s)
- Carla S Coffin
- Liver Unit, Division of Gastroenterology, University of Calgary, Calgary, Canada.
| | | |
Collapse
|
|
24
|
Impact of hepatitis B exposure on sustained virological response rates of highly viremic chronic hepatitis C patients. Gastroenterol Res Pract 2009; 2009:812140. [PMID: 19390651 PMCID: PMC2670987 DOI: 10.1155/2009/812140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2008] [Accepted: 02/09/2009] [Indexed: 11/17/2022] Open
Abstract
AIM To evaluate the impact of hepatitis B core antibody (anti-HBc) seropositivity in sustained virological response (SVR) rates in treatment-naïve, chronic hepatitis C (CHC) patients with high pretreatment viral load (>800000 IU/mL). METHODS 185 consecutive CHC patients (14.4% cirrhotics, 70.2% prior intravenous drug users) treated with pegylated interferon-a2b plus ribavirin, for 24 or 48 weeks based on viral genotype, were retrospectively analyzed. SVR was confirmed by undetectable serum HCV-RNA six months after the end of treatment schedule. RESULTS Thirty percent of CHC/HBsAg-negative patients were anti-HBc-positive. Anti-HBc positivity was more prevalent in cirrhotic, compared to noncirrhotic patients (76.9% versus 19.5%, P < .05). Serum HBV-DNA was detected in the minority of anti-HBc-positive patients (1.97%). Overall, 62.1% of patients exhibited SVR, while 28.6% did not; 71.4% of non-SVRs were infected with genotype 1. In the univariate analysis, the anti-HBc positivity was negatively associated with treatment outcome (P = .065). In the multivariate model, only the advanced stage of liver disease (P = .015) and genotype-1 HCV infection (P = .003), but not anti-HBc-status (P = .726), proved to be independent predictors of non-SVR. CONCLUSION Serum anti-HBc positivity does not affect the SVR rates in treatment-naïve CHC patients with high pretreatment viral load, receiving the currently approved combination treatment.
Collapse
|
|
25
|
Georgiadou SP, Zachou K, Liaskos C, Gabeta S, Rigopoulou EI, Dalekos GN. Occult hepatitis B virus infection in patients with autoimmune liver diseases. Liver Int 2009; 29:434-42. [PMID: 18694399 DOI: 10.1111/j.1478-3231.2008.01851.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND Occult hepatitis B virus (HBV) infection is characterized by undetectable serum HBV surface antigen (HBsAg) but detectable HBV-DNA in serum or liver. AIMS To determine the prevalence and clinical impact of occult HBV in autoimmune liver diseases as similar data are missing. METHODS One hundred and ninety-six sera samples from HBsAg-negative patients, including 66 autoimmune hepatitis (AIH), 93 primary biliary cirrhosis (PBC) and 37 primary sclerosing cholangitis (PSC), were investigated for HBV-DNA using the polymerase chain reaction (PCR) before treatment initiation. One hundred and three serial samples from 38 AIH patients under immunosuppression and 282 selected blood donors (HBsAg negative; antibodies to HBV-core antigen positive) were also investigated. Fourteen available paraffin-embedded AIH liver samples were also investigated for HBV-DNA by nested-PCR. RESULTS Hepatitis B virus DNA was detected in the serum of 24/196 patients (12.2%) and 0/282 donors (P=0.0000). Nine patients had AIH (13.6%), eight had PBC (8.6%) and seven had PSC (18.9%) (P=0.0000 vs healthy). HBV-DNA detection in AIH livers was higher than in serum. HBV-DNA was associated neither with HBV markers nor with epidemiological, laboratory and clinical data. Serial testing of AIH patients revealed two HBV-DNA-negative patients before treatment becoming positive during treatment, while all HBV-DNA-positive patients before immunosuppression became negative. CONCLUSION Based mainly on serum HBV-DNA, we found a significant proportion of autoimmune liver disease patients with occult HBV compared with donors. However, taking into account our results in a small number of liver tissues, it should be emphasized that occult HBV could be even higher when both serum and liver specimens are investigated. Occult HBV does not seem to affect the clinical and laboratory features of the diseases, while AIH patients with occult HBV under immunosuppression do not deteriorate during follow-up.
Collapse
Affiliation(s)
- Sarah P Georgiadou
- Department of Medicine, Academic Liver Unit, Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
| | | | | | | | | | | |
Collapse
|
|
26
|
Carvalho-Filho RJ, de Lucca Schiavon L, Narciso-Schiavon JL, Sampaio JP, Lanzoni VP, Gomes Ferraz ML, Benedito Silva AE. Clinical and histological impact of previous hepatitis B virus infection in patients with chronic hepatitis C. Liver Int 2009; 29:133-140. [PMID: 18507759 DOI: 10.1111/j.1478-3231.2008.01786.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND Recent reports suggest that hepatitis C virus (HCV) carriers with serological markers of prior hepatitis B virus (HBV) infection have more advanced liver fibrosis, irrespective of HBV-DNA detection. AIMS We sought to assess the prevalence and impact of previous HBV infection in patients with HCV chronic infection. METHODS This cross-sectional study included hepatitis B surface antigen- and human immunodeficiency virus-negative subjects with positive HCV-RNA. All patients had prior parenteral exposure as the probable source of HCV infection. Serum samples were tested for HBV-DNA using a commercial assay. The METAVIR system was used for histological analysis. RESULTS One-hundred and eleven patients were evaluated. Thirty-one out of 111 patients (28%) tested positive for antihepatitis B core antigen (anti-HBc). HBV-DNA was not detected in any sample. Anti-HBc-positive patients showed higher histological grading, staging and a higher fibrosis progression rate. By multivariate analysis, anti-HBc-positivity was predictive of moderate to severe activity [odds ratio (OR)=3.532; P=0.032] and significant hepatic fibrosis (OR=3.364; P=0.017). After approximately 20 years of infection, advanced liver fibrosis (F3/F4) can be expected in 13% of anti-HBc-negative subjects who acquired HCV before the age of 30 and in 57% of those anti-HBc-positive patients who were infected by HCV after 30 years of age (P<0.001). CONCLUSION Previous HBV infection is common among HCV carriers and may exert a negative impact on the natural history of HCV infection, independently of the presence of significant HBV replication.
Collapse
Affiliation(s)
- Roberto J Carvalho-Filho
- Division of Gastroenterology, Hepatitis Section, Federal University of Sao Paulo, Sao Paulo, Brazil.
| | | | | | | | | | | | | |
Collapse
|
|
27
|
Narciso-Schiavon JL, Schiavon LL, Carvalho-Filho RJ, Cardoso JR, Freire FCF, Sampaio JP, Bordin JO, Soares MA, Silva AEB, Ferraz MLG. Anti-HCV reactive blood donors: clinical and epidemiological factors associated with false-reactive results. Eur J Gastroenterol Hepatol 2008; 20:1071-1076. [PMID: 19047838 DOI: 10.1097/meg.0b013e328303e1d6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND In certain clinical settings, false-reactive anti-hepatitis C virus (HCV) results are rare because the majority of persons being tested have evidence of liver disease and the specificity of the screening assays is high. However, among healthy populations, such as blood donors, mainly in regions with a low prevalence of HCV infection, this situation does occur. In this study, we sought to assess clinical, epidemiological, and laboratory characteristics of blood donors with false-reactive anti-HCV screening tests. METHODS This retrospective cross-sectional study included 537 anti-HCV reactive blood donors referred to a tertiary care centre for liver diseases. RESULTS The mean age was 36.5+/-11.2 years and 71.8% were men. Blood donors of older age (P=0.010), history of alcohol abuse (P=0.039), past transfusion (P<0.001), intravenous drug use (P<0.001), and with antibody against core antigen of hepatitis B virus reactivity (P=0.003) were less likely to have a false-reactive anti-HCV result. By multivariate analysis, only the absence of parenteral risk factors (prior transfusion and intravenous drug use) was independently associated with false-reactive anti-HCV tests. CONCLUSION Blood donors with reactive anti-HCV screening tests with no risk factors for parenterally acquired HCV infection are more likely to present with false-reactive results.
Collapse
|
|
28
|
Adachi S, Shibuya A, Miura Y, Takeuchi A, Nakazawa T, Saigenji K. Impact of occult hepatitis B virus infection and prior hepatitis B virus infection on development of hepatocellular carcinoma in patients with liver cirrhosis due to hepatitis C virus. Scand J Gastroenterol 2008; 43:849-56. [PMID: 18584524 DOI: 10.1080/00365520801935459] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Although hepatitis B virus (HBV) DNA can be detected in liver or sera of patients without serum hepatitis B surface antigen (HBsAg), its clinical relevance in hepatocarcinogenesis remains controversial. This observational cohort study was conducted to clarify the risk factors, including the presence of serum HBV DNA and hepatitis B core antibody (anti-HBc), for hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). MATERIAL AND METHODS The study comprised 123 patients with LC due to HCV, and negative for HBsAg. The risk factors for HCC development were analyzed by univariate and multivariate analysis. Serum samples were assayed for HBV DNA using real-time polymerase chain reaction. RESULTS Serum HBV DNA was detectable in 14 patients (11.4%) and serum anti-HBc in 96 (78.0%). During the follow-up period (mean 53.3 months), 80 patients (65.0%) developed HCC. The cumulative HCC development rate was significantly higher in the anti-HBc-positive group than in the anti-HBc-negative group (p=0.0039), but did not differ between the serum HBV DNA-positive and -negative groups (p=0.8570). The multivariate analysis indicated that male gender, alpha-fetoprotein (AFP) 20 ng/ml or greater, average serum alanine aminotransferase (ALAT) 80 IU/l or greater and the presence of anti-HBc were independent risk factors for development of HCC (p=0.038, p=0.013, p=0.020 and p=0.001, respectively). CONCLUSIONS Serum anti-HBc, which indicates a previous HBV infection, has clinical significance in hepatocarcinogenesis in patients with HCV-related LC, but serum HBV DNA does not. Therefore, anti-HBc in serum is a significant predictor for HCC.
Collapse
Affiliation(s)
- Shigeru Adachi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
| | | | | | | | | | | |
Collapse
|
|
29
|
Branco F, Mattos AAD, Coral GP, Vanderborght B, Santos DE, França P, Alexandre C. Occult hepatitis B virus infection in patients with chronic liver disease due to hepatitis C virus and hepatocellular carcinoma in Brazil. ARQUIVOS DE GASTROENTEROLOGIA 2008; 44:58-63. [PMID: 17639185 DOI: 10.1590/s0004-28032007000100013] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Received: 03/28/2006] [Accepted: 07/21/2006] [Indexed: 11/21/2022]
Abstract
BACKGROUND The prevalence and consequences of occult HBV infection in patients with chronic liver disease by HCV remain unknown. AIMS To evaluate the prevalence of occult HBV infection in a population of HCV-infected patients with hepatocellular carcinoma. METHODS The serum samples were tested for HBV DNA by nested PCR and liver tissue analysis was carried out using the immunohistochemical technique of 66 HBsAg-negative patients: 26 patients with chronic hepatitis by HCV (group 1), 20 with hepatocellular carcinoma related to chronic infection by HCV (group 2) and 20 with negative viral markers for hepatitis B and C (control group). RESULTS Occult HBV infection was diagnosed in the liver tissue of 9/46 (19.5%) HCV-infected patients. Prevalence of occult B infection was evaluated in the HCV-infected patients with and without hepatocellular carcinoma, and there were seven (77.7%) of whom from group 2, conferring a 35% prevalence of this group. No serum sample was positive for HBV DNA in the three groups. CONCLUSION Occult infection B is frequently detected in liver tissue of HCV-infected patients, especially in cases of hepatocellular carcinoma. However large studies are needed to confirm that co-infection could determine a worse progress of chronic liver disease in this population.
Collapse
Affiliation(s)
- Fernanda Branco
- Gastroenterology and Hepatology Service, Complexo Hospitalar Santa Casa, Porto Alegre, RS.
| | | | | | | | | | | | | |
Collapse
|
|
30
|
Alencar R, Gomes M, Sitnik R, Pinho J, Malta F, Mello I, Mello E, Bacchella T, Machado M, Alves V, Carrilho F. Low occurrence of occult hepatitis B virus infection and high frequency of hepatitis C virus genotype 3 in hepatocellular carcinoma in Brazil. Braz J Med Biol Res 2007; 41:235-40. [DOI: 10.1590/s0100-879x2006005000197] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2006] [Accepted: 09/17/2007] [Indexed: 12/13/2022] Open
Affiliation(s)
| | - M.M.S. Gomes
- Universidade de São Paulo; Universidade de São Paulo, Brasil
| | - R. Sitnik
- Hospital Israelita Albert Einstein, Brasil
| | - J.R.R. Pinho
- Universidade de São Paulo; Universidade de São Paulo, Brasil; Hospital Israelita Albert Einstein, Brasil
| | - F.M. Malta
- Universidade de São Paulo; Universidade de São Paulo, Brasil
| | | | | | | | | | | | | |
Collapse
|
|
31
|
Mrani S, Chemin I, Menouar K, Guillaud O, Pradat P, Borghi G, Trabaud MA, Chevallier P, Chevallier M, Zoulim F, Trépo C. Occult HBV infection may represent a major risk factor of non-response to antiviral therapy of chronic hepatitis C. J Med Virol 2007; 79:1075-81. [PMID: 17596829 DOI: 10.1002/jmv.20943] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Occult hepatitis B virus (HBV) infection is common in chronic hepatitis C patient. However, its significance and consequences are still unclear. The aim of this study was to evaluate the prevalence of occult HBV among HCV chronic carriers in France and to assess its impact on liver histology and response to antiviral therapy. To this end a cohort of 203 patients with chronic hepatitis C without hepatitis B surface antigen (HBsAg) has been examined. Serum HBV-DNA was detected using a highly sensitive PCR with primers located in the S and X genes. HBV viraemia levels were further determined by real-time PCR. Results showed that 47 of 203 (23%) patients had occult HBV infection with a low HBV load (10(2)-10(4) copies/ml) but significantly higher HCV-RNA titers (P < 0.05). No significant difference in age, gender, serum ALT level, HCV genotypes, and the presence of anti-HBc was observed between patients with or without HBV-DNA. When compared histologically, patients with occult HBV infection had higher activity (A2-A3 in 53% vs. 38%, P < 0.01) and more advanced fibrosis (60% vs. 33%, P < 0.001) than HBV-DNA negative cases. Sustained response to combination therapy against Chronic hepatitis C was achieved in 11 (28%) of 40 HBV-DNA positive cases, compared with 65 (45%) of the 144 HBV-DNA negative cases (P < 0.05). Among the 144 HBV-DNA negative HCV patients those with genotype 1 responded less frequently to therapy as compared to other genotypes infected patients (38% vs. 55%, P < 0.05). Surprisingly, when considering all patients studied, irrespective to the HBV-DNA status no significant difference was observed in response to combination therapy regarding HCV genotypes (39% vs. 44%, P > 0.05). In conclusion, HBV-DNA is found in 1/4 of French chronic hepatitis C patients regardless of the presence of anti-HBc. Such an occult HBV co-infection is associated with more severe liver disease, higher HCV viral load and decreased response to antiviral therapy irrespective of HCV genotypes.
Collapse
Affiliation(s)
- S Mrani
- INSERM U271, 151 Cours A Thomas, 69003 Lyon, France
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Rodríguez-Torres M, Gonzalez-Garcia J, Bräu N, Solá R, Moreno S, Rockstroh J, Smaill F, Mendes-Correa MC, DePamphilis J, Torriani FJ. Occult hepatitis B virus infection in the setting of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection: Clinically relevant or a diagnostic problem? J Med Virol 2007; 79:694-700. [PMID: 17457912 DOI: 10.1002/jmv.20836] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The clinical relevance of occult hepatitis B virus (HBV) infection, defined as detectable HBV DNA serum/liver, in the absence of hepatitis B surface antigen (HBsAg), is unclear. We determined the prevalence of serum occult HBV infection in HIV/HCV co-infected patients enrolled in APRICOT, a randomized multinational trial that investigated the efficacy and safety of peginterferon alfa-2a (40 kDa) plus ribavirin for treatment of HCV. We also examined the effect of prior HBV exposure to liver histology at baseline. Only HBsAg-negative patients were eligible. At screening, serum HBV DNA was assessed by commercial assay (detection limit = 200 copies/mL). Patients were divided into four serological groups: anti-HBs+/anti-HBc+; anti-HBs-/anti-HBc+; anti-HBs+/ anti-HBc-; anti-HBs-/anti-HBc-. Baseline liver biopsy grade and stage were compared among groups. Serum HBV DNA was undetectable in all patients, (n = 866). Results of anti-HBs and anti-HBc was available for 176 patients: 60 (34.1%) anti-HBs+/anti-HBc+; 60 (34.1%) anti-HBs-/anti-HBc+; 11 (6.3%) anti-HBs+/anti-HBc-; 45 (25.6%) anti-HBs-/anti-HBc-. There were no differences among the groups in the histological grade or stage at baseline liver biopsies. Occult HBV infection in serum was not detected in this large immunocompetent cohort. Moreover, prior exposure to HBV did not appear to have any affect on baseline liver histology.
Collapse
|
|
33
|
Helmy A, Al-Sebayel MI. Isolated antibody to hepatitis B core antigen in patients with chronic hepatitis C virus infection. World J Gastroenterol 2006; 12:4406-10. [PMID: 16865787 PMCID: PMC4087756 DOI: 10.3748/wjg.v12.i27.4406] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the prevalence of isolated anti-HBc in patients with chronic hepatitis C virus (HCV) infection, and its relation to disease severity.
METHODS: We screened all patients with chronic HCV infection referred to King Faisal Specialist Hospital and Research Center for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and anti-HBc. One hundred and sixty nine patients who tested negative for both HBsAg and anti-HBs were included in this study.
RESULTS: Pathologically, 59 had biopsy-proven cirrhosis and 110 had chronic active hepatitis (CAH). Of these 169 patients, 85 (50.3%) tested positive for anti-HBc. Patients with CAH had significantly higher prevalence of isolated anti-HBc than patients with cirrhosis, 71 (64.5%) and 14 (23.7%) respectively (P < 0.001). Twenty-five patients were tested for HBV DNA by qualitative PCR. The test was positive in 3 of them (12%; occult HBV infection).
CONCLUSION: Isolated anti-HBc alone is common in Saudi patients with chronic HCV infection, and is significantly more common in those with CAH than those with cirrhosis. Therefore, a screening strategy that only tests for HBsAg and anti-HBs in these patients will miss a large number of individuals with isolated anti-HBc, who may be potentially infectious.
Collapse
Affiliation(s)
- Ahmed Helmy
- Department of Liver Transplantation, Hepatobiliary and Pancreatic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
| | | |
Collapse
|
|
34
|
Goral V, Ozkul H, Tekes S, Sit D, Kadiroglu AK. Prevalence of occult HBV infection in haemodialysis patients with chronic HCV. World J Gastroenterol 2006; 12:3420-4. [PMID: 16733862 PMCID: PMC4087876 DOI: 10.3748/wjg.v12.i21.3420] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [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 study the prevalence and clinical effects of occult HBV infection in haemodialysis patients with chronic HCV.
METHODS: Fifty chronic hemodialysis patients with negative HbsAg, and positive anti-HCV were included in the study. These patients were divided into two groups: HCV-RNA positive and HCV-RNA negative, based on the results of HCV-RNA PCR. HBV-DNA was studied using the PCR method in both groups.
RESULTS: None of the 22 HCV-RNA positive patients and 28 HCV-RNA negative patients revealed HBV-DNA in serum by PCR method. The average age was 47.2 ± 17.0 in the HCV-RNA positive group and 39.6 ± 15.6 in the HCV-RNA negative group.
CONCLUSION: The prevalence of occult HBV infection is not high in haemodialysis patients with chronic HCV in our region. This result of our study has to be evaluated in consideration of the interaction between HBsAg positivity (8%-10%) and frequency of HBV mutants in our region.
Collapse
Affiliation(s)
- Vedat Goral
- Department of Gastroenterology, Dicle University School of Medicine, Diyarbakir, Turkey.
| | | | | | | | | |
Collapse
|
|
35
|
Hasegawa I, Orito E, Tanaka Y, Hirashima N, Sakakibara K, Sakurai M, Suzuki S, Sugauchi F, Ohno T, Ueda R, Mizokami M. Impact of occult hepatitis B virus infection on efficacy and prognosis of interferon-alpha therapy for patients with chronic hepatitis C. Liver Int 2005; 25:247-253. [PMID: 15780046 DOI: 10.1111/j.1478-3231.2005.1096.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND/AIMS It is reported that some patients with undetectable hepatitis B surface antigen (HBsAg) have serum hepatitis B virus (HBV) DNA in patients with chronic hepatitis C (HCV). The aim of this study was to elucidate the impact of occult HBV infection on the efficacy and prognosis of interferon-alpha (IFN) therapy in HCV patients. METHODS One hundred and forty HCV patients without HBsAg who received IFN therapy were studied. Serum HBV DNA was quantified by real-time detection polymerase chain reaction. RESULTS Of 140 patients, 11 (7.9%) were HBV DNA-positive before IFN therapy. The serum HBV DNA levels ranged from 106 to 884 copies/ml. Four of these 11 patients showed a sustained virologic response by IFN, compared with 39 of 129 without HBV DNA (P = NS). Interestingly, two of the 11 patients developed hepatocellular carcinoma (HCC) after therapy, compared with 16 of 129 without HBV DNA (P = NS). In the serial study, serum HBV DNA was transiently undetectable during and after IFN; however, most became positive during follow-up. CONCLUSIONS Occult HBV infection may not have a significant impact on response to IFN therapy for chronic HCV and development of HCC after therapy. Occult HBV may be sensitive to IFN although HBV is not completely eradicated.
Collapse
Affiliation(s)
- Izumi Hasegawa
- Department of Internal Medicine, Nagoya City University, Graduate School of Medical Sciences, Nagoya 467-8601, Japan
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Georgiadou SP, Zachou K, Rigopoulou E, Liaskos C, Mina P, Gerovasilis F, Makri E, Dalekos GN. Occult hepatitis B virus infection in Greek patients with chronic hepatitis C and in patients with diverse nonviral hepatic diseases. J Viral Hepat 2004; 11:358-65. [PMID: 15230859 DOI: 10.1111/j.1365-2893.2004.00513.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Occult hepatitis B virus (HBV) infection has been reported in patients with chronic hepatitis C who are negative for HBV surface antigen (HBsAg). However, the significance of 'silent' HBV in hepatitis C virus (HCV) infection is unknown. We investigated 540 subjects for the presence of occult HBV in Greek HCV patients, patients with nonviral liver diseases and healthy donors in an attempt to determine the frequency and importance of this phenomenon. One hundred and eighty-seven anti-HCV(+)/HBsAg(-) patients' sera were investigated for the presence of HBV-DNA by polymerase chain reaction. Two hundred and eighty-two selected blood donors (positive for antibodies to HBV core antigen) and 71 patients with various nonviral hepatic diseases consisted the control groups [both controls were anti-HCV(-)/HBsAg(-)]. HBV-DNA was detected in 26.2% of HCV-infected patients vs 8.5% of patients with nonviral diseases (P = 0.003) and 0/282 of donors (P = 0.0000). HBV-DNA was neither associated with HBV markers, nor with the clinical status of HCV and nonHCV patients. Neither epidemiological, histologic and virologic data nor the response to therapy were associated with the HBV-DNA detection. Hence one quarter of HCV-infected patients had occult HBV infection. Similar findings were not found in both control groups. Occult HBV infection in Greek patients with chronic hepatitis C does not seem to modify the progression of chronic liver disease. Further studies of longer duration are needed in order to clarify the role of 'silent' HBV infection in HCV-infected patients.
Collapse
Affiliation(s)
- S P Georgiadou
- Research Laboratory of Internal Medicine, Medical School, University of Thessaly Larissa, Thessaly, Greece
| | | | | | | | | | | | | | | |
Collapse
|