|
1
|
Pisaturo M, Alessio L, Starace M, Macera M, Occhiello L, Cordua E, Capuano S, Onorato L, Scotto G, Di Caprio G, Calò F, Monari C, Sagnelli C, Coppola N. Characterization of hepatitis virus co-infections in a cohort of immigrants living in southern Italy. J Med Virol 2023; 95:e28665. [PMID: 36905118 DOI: 10.1002/jmv.28665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 02/22/2023] [Accepted: 03/08/2023] [Indexed: 03/12/2023]
Abstract
To characterize viral hepatitis co-infections in a cohort of immigrants living in southern Italy. In a prospective multicenter study, all undocumented immigrants and low-income refugees consecutively evaluated for a clinical consultation at one of the five first-level clinical centers in southern Italy from January 2012 to February 2020 were enrolled. All subjects included in the study were screened for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) and anti-HIV; the HBsAg-positive were screened also for anti-delta. Of the 2923 subjects enrolled, 257 (8%) were HBsAg-positive alone (Control group B), 85 (2.9%) only anti-HCV-positive (Control group C), 16 (0.5%) HBsAg/anti-HCV-positive (Case group BC), and 8 (0.2%) HBsAg/anti-HDV-positive (Case group BD). Moreover, 57 (1.9%) subjects were anti-HIV-positive. HBV-DNA positivity was found less frequently in the 16 subjects in Case group BC (43%) and in the 8 in Case group BD (12.5%) than in the 257 in Control group B (76%; p = 0.03 and 0.0000, respectively). Similarly, HCV-RNA positivity was more frequent in Case group BC than in Control group C (75% vs. 44.7% p = 0.02). The subjects in Group BC had a lower prevalence of asymptomatic liver disease (12.5%) than Control group B (62.2%, p = 0.0001) and Control group C (62.3%, p = 0.0002). Conversely, liver cirrhosis was more frequently identified in Case group BC (25%) than in Control groups B and C (3.11% and 2.35%, p = 0.0000 and 0.0004, respectively). The present study contributes to the characterization of hepatitis virus co-infections in the immigrant population.
Collapse
Affiliation(s)
- Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Università degli studi della Campania Luigi Vanvitelli, Caserta, Italy
- Medical Center, Centro Sociale ex Canapificio, Caserta, Italy
| | - Loredana Alessio
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Università degli studi della Campania Luigi Vanvitelli, Caserta, Italy
- Medical Center, Centro di Accoglienza "La tenda di Abramo", Caserta, Italy
| | - Mario Starace
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Università degli studi della Campania Luigi Vanvitelli, Caserta, Italy
| | - Margherita Macera
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Università degli studi della Campania Luigi Vanvitelli, Caserta, Italy
- Medical Center, Centro per la Tutela della Salute degli Immigrati, Naples, Italy
| | - Laura Occhiello
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Università degli studi della Campania Luigi Vanvitelli, Caserta, Italy
| | - Emanuele Cordua
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Università degli studi della Campania Luigi Vanvitelli, Caserta, Italy
| | - Salvatore Capuano
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Università degli studi della Campania Luigi Vanvitelli, Caserta, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Università degli studi della Campania Luigi Vanvitelli, Caserta, Italy
- Medical Center, Centro Suore Missionarie della Carità, Naples, Italy
| | - Gaetano Scotto
- Medical Center, Centro Borgoroma, Foggia, Italy
- Infectious Diseases Unit, Foggia, Italy
| | - Giovanni Di Caprio
- Medical Center, Centro Sociale ex Canapificio, Caserta, Italy
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Federica Calò
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Università degli studi della Campania Luigi Vanvitelli, Caserta, Italy
- Medical Center, Centro per la Tutela della Salute degli Immigrati, Naples, Italy
| | - Caterina Monari
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Università degli studi della Campania Luigi Vanvitelli, Caserta, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Università degli studi della Campania Luigi Vanvitelli, Caserta, Italy
- Medical Center, Centro Suore Missionarie della Carità, Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Università degli studi della Campania Luigi Vanvitelli, Caserta, Italy
| |
Collapse
|
|
2
|
Shen C, Jiang X, Li M, Luo Y. Hepatitis Virus and Hepatocellular Carcinoma: Recent Advances. Cancers (Basel) 2023; 15:533. [PMID: 36672482 PMCID: PMC9856776 DOI: 10.3390/cancers15020533] [Citation(s) in RCA: 67] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 01/08/2023] [Accepted: 01/13/2023] [Indexed: 01/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) remains a global health challenge, causing 600,000 deaths each year. Infectious factors, including hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV), have long been considered the major risk factors for the development and progression of HCC. These pathogens induce hepatocyte transformation through a variety of mechanisms, including insertional mutations caused by viral gene integration, epigenetic changes, and the induction of long-term immune dysfunction. The discovery of these mechanisms, while advancing our understanding of the disease, also provides targets for new diagnostic and therapeutic approaches. In addition, the discovery and research of chronic HEV infection over the past decade indicate that this common hepatitis virus also seems to have the potential to induce HCC. In this review, we provide an overview of recent studies on the link between hepatitis virus and HCC, as well as new diagnostic and therapeutic approaches to HCC based on these findings. Finally, we also discuss the potential relationship between HEV and HCC. In conclusion, these associations will further optimize the diagnosis and treatment of infection-associated HCC and call for better management policies.
Collapse
Affiliation(s)
| | | | - Mei Li
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yao Luo
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| |
Collapse
|
|
3
|
Miyasaka A, Yoshida Y, Suzuki A, Masuda T, Okamoto H, Takikawa Y. Hepatitis B virus reactivation after successful treatment of hepatitis C virus with sofosbuvir and ribavirin: A case report and literature review. Medicine (Baltimore) 2020; 99:e22650. [PMID: 33031326 PMCID: PMC7544429 DOI: 10.1097/md.0000000000022650] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
RATIONALE Hepatitis B virus (HBV) reactivation caused by immunosuppressive therapy or chemotherapy is well known. The administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has also been reported to cause HBV reactivation. We report a rare case of HBV reactivation in a patient with HCV infection after DAA therapy. PATIENT CONCERNS In 1996, a 53-year-old female was identified as infected with HCV at a medical check-up, following which she visited our hospital. She was infected with HCV genotype 2b, and at follow up in 1997, was found to be hepatitis B surface antigen (HBsAg) and antibody against HBsAg negative, antibody against HBV core positive. She then experienced malignant lymphoma in 2001 at 58 years of age. Complete remission was achieved following chemotherapy and autologous peripheral blood stem cell transplantation. In 2014, she remained negative for HBsAg and antibody against HBsAg but positive for antibody against HBV core. In 2015, 12 weeks of sofosbuvir and ribavirin treatment for HCV was started. Serum HCV RNA levels rapidly decreased, and HCV elimination was confirmed at 24 weeks after cessation of DAA treatment. Acute hepatitis B developed at 15 weeks post- sustained virological response without any symptoms and physical examination findings. DIAGNOSES This case is speculated to represent HBV reactivation induced by DAA treatment in a patient with previously resolved HBV, based on virologic and clinical status. Genome sequencing revealed the HBV genotype as A2. INTERVENTIONS The patient was treated with nucleotide analog for HBV reactivation once a day. OUTCOMES Serum HBV-DNA levels decreased, and serum liver enzymes improved following initiation of nucleotide analog treatment. Also, adverse events of nucleotide analog treatment were not observed. LESSONS Although the risk may be very low, DAA therapy can cause HBV reactivation in chronic hepatitis C patients with prior HBV infection. Thus, those patients must be closely monitored for serum HBV DNA levels during and after DAA treatment.
Collapse
Affiliation(s)
- Akio Miyasaka
- Division of Hepatology, Department of Internal Medicine
| | | | - Akiko Suzuki
- Division of Hepatology, Department of Internal Medicine
| | - Tomoyuki Masuda
- Department of Pathology, Iwate Medical University School of Medicine, Yahaba-cho, Shiwa-gun, Iwate
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimozuke, Tochigi, Japan
| | | |
Collapse
|
|
4
|
Wu SH, Chu CJ, Huang YH, Hou MC. Successful treatment with sofosbuvir and daclatasvir plus ribavirin in acute hepatitis C-infected patient with hepatic decompensation. J Chin Med Assoc 2019; 82:595-598. [PMID: 31274790 DOI: 10.1097/jcma.0000000000000107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Treatment of chronic hepatitis C virus infection has evolved rapidly in recent years due to the invention of interferon-free direct antiviral agents (DAAs). However, evidence and recommendations for acute hepatitis C (AHC) virus infection by DAAs are still limited, especially for those whose disease presents with hepatic decompensation. Here, we report a case with genotype 1b AHC virus infection, complicated by hepatic decompensation and the patient received sofosbuvir and daclatasvir plus low dose ribavirin for 12 weeks. Serum hepatitis C virus RNA significantly declines after therapy and became undetectable at week 8 and it remained undetectable at 12 weeks after finishing therapy; sustained virological response was impressed. Our findings support that combination of sofosbuvir and daclatasvir plus ribavirin can be used for genotype 1b, AHC virus infection patients with overt hepatic decompensation.
Collapse
Affiliation(s)
- Sih-Hsien Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chi-Jen Chu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| |
Collapse
|
|
5
|
Characteristics of patients with hepatitis B virus and hepatitis C virus dual infection in a Western European country: Comparison with monoinfected patients. Clin Res Hepatol Gastroenterol 2017; 41:656-663. [PMID: 28867077 DOI: 10.1016/j.clinre.2017.05.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Revised: 04/17/2017] [Accepted: 05/09/2017] [Indexed: 02/04/2023]
Abstract
UNLABELLED The epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is continuously evolving. Updated data on dual HBV and HCV infection are still needed. AIMS To assess the main characteristics of patients with HBV and HCV dual infection, to compare these with those of patients infected with either HBV or HCV and, among patients with dual infection, to assess fibrosis according to HCV replication. METHODS Data of 23 patients with dual infection were compared to data from 92 age and sex-matched HBV or HCV monoinfected patients. RESULTS Patients with dual infection were more often immigrants from Africa or Asia than HCV or HBV patients (52% vs. 20% and 22%, respectively, P=0.01). Intravenous drug use was the route of transmission in 22% of patients with dual infection, which was less frequent than in HCV patients (41%) but more frequent than in HBV patients (0%). Extensive fibrosis or cirrhosis was as frequent among dual-infected patients as among those with HCV or chronic hepatitis B infection (19% vs. 29% vs. 14%, respectively, P=0.4), even when fibrosis stage was reported considering the duration of infection. In dual-infected patients, the prevalence of extensive fibrosis or cirrhosis was similar in patients with and without detectable HCV RNA (18% vs. 20%). CONCLUSIONS Patients with HBV and HCV dual infection were more often immigrants from Africa or Asia and had similar fibrosis stages than HCV or HBV monoinfected patients. In patients with dual infection, extensive fibrosis or cirrhosis was not associated with HCV replication.
Collapse
|
|
6
|
Fabbri G, Mastrorosa I, Vergori A, Mazzotta V, Pinnetti C, Grisetti S, Zaccarelli M, Ammassari A, Antinori A. Reactivation of occult HBV infection in an HIV/HCV Co-infected patient successfully treated with sofosbuvir/ledipasvir: a case report and review of the literature. BMC Infect Dis 2017; 17:182. [PMID: 28249574 PMCID: PMC5333431 DOI: 10.1186/s12879-017-2287-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Accepted: 02/23/2017] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Reactivation of occult or inactive Hepatitis B virus (HBV) infection during immunosuppressant treatments is well known and widely described in literature. The same observation has been made in Hepatitis C (HCV)-infected patients previously exposed to HBV and treated with interferon-free DAA treatments. Because of common transmission routes, persons may have been exposed to HCV, HBV and HIV, but few cases have been reported in this scenario to date. Frequency of HBV reactivation in HIV/HCV co-infected patients previously exposed to HBV and treated with DAA remains unclear. Herein, we report an episode of HBV reactivation in an HIV/HCV co-infected patient prescribed with sofosbuvir/ledipasvir for HCV. CASE PRESENTATION The patient is a Caucasian 54-years old female, with HIV/HCV co-infection (genotype 4), and a previous exposure to HBV, documented by negativity of HBsAg and positivity of HBsAb and HBcAb. Her medical history included: myocardial infarct, chronic kidney disease stage 3, chronic obstructive pulmonary disease, and mild pulmonary hypertension. HCV had not been treated with interferon (IFN)-based regimens and liver stiffness was 10.5 KPa (Metavir stage F3) at hepatic elastography. Because of CKD, she was prescribed with a nucleoside reverse transcriptase (NRTI)-sparing regimen including darunavir/ritonavir plus etravirine, and thereafter with sofosbuvir/ledipasvir for 12 weeks. Four weeks after DAA termination, the patient was hospitalized with symptoms of acute hepatitis. Blood tests showed HCV RNA <12 IU/ml, but positivity of HBAg, HBeAg, and of anti-core antibodies (IgM and IgG), while anti-HBs and anti-HBe antibodies were negative. HBV DNA was 6.06 Log10 IU/ml. Entecavir was started obtaining resolution of symptoms, normalization of liver enzymes, as well as reduction of HBV DNA and of quantitative HBV surface antigen. CONCLUSIONS This case-report highlights the risk of HBV reactivation with interferon-free DAA treatment in HIV/HCV co-infected patients previously exposed to HBV and who have contraindications for treatment with nucleoside/nucleotide reverse transcriptase Inhibitors because of comorbid conditions. In the setting of HIV infection, clinicians prescribing DAA should be aware of this risk, and HBV assessment at treatment start as well as virological monitoring during DAA treatment is recommended. Large epidemiological and virological studies are needed to investigate reactivation of occult HBV infection more in depth.
Collapse
Affiliation(s)
- Gabriele Fabbri
- National Institute of Infectious Diseases "Lazzaro Spallanzani", Via Portuense 292, 00152, Rome, Italy.
| | - Ilaria Mastrorosa
- National Institute of Infectious Diseases "Lazzaro Spallanzani", Via Portuense 292, 00152, Rome, Italy
| | - Alessandra Vergori
- National Institute of Infectious Diseases "Lazzaro Spallanzani", Via Portuense 292, 00152, Rome, Italy
| | - Valentina Mazzotta
- National Institute of Infectious Diseases "Lazzaro Spallanzani", Via Portuense 292, 00152, Rome, Italy
| | - Carmela Pinnetti
- National Institute of Infectious Diseases "Lazzaro Spallanzani", Via Portuense 292, 00152, Rome, Italy
| | - Susanna Grisetti
- National Institute of Infectious Diseases "Lazzaro Spallanzani", Via Portuense 292, 00152, Rome, Italy
| | - Mauro Zaccarelli
- National Institute of Infectious Diseases "Lazzaro Spallanzani", Via Portuense 292, 00152, Rome, Italy
| | - Adriana Ammassari
- National Institute of Infectious Diseases "Lazzaro Spallanzani", Via Portuense 292, 00152, Rome, Italy
| | - Andrea Antinori
- National Institute of Infectious Diseases "Lazzaro Spallanzani", Via Portuense 292, 00152, Rome, Italy
| |
Collapse
|
|
7
|
A case of acute hepatitis B in a chronic hepatitis C patient after daclatasvir and asunaprevir combination therapy: hepatitis B virus reactivation or acute self-limited hepatitis? Clin J Gastroenterol 2016. [PMID: 27329484 DOI: 10.1007/s12328-016-0657-410.1007/s12328-016-0657-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Reactivation of hepatitis B virus (HBV) in HBV surface antigen (HBsAg)-positive patients treated with cytotoxic chemotherapy is well known. HBV reactivation in patients with HBV and hepatitis C virus (HCV) coinfection caused by direct-acting antiviral (DAA) therapy has also recently been reported. We report a case of acute hepatitis B in a patient with HCV infection after DAA therapy. An 83-year-old woman was referred for chronic hepatitis C. She was infected with HCV genotype 1b and negative for HBsAg at baseline. She received daclatasvir and asunaprevir therapy, and HCV became negative at 4 weeks and remained negative until 6 months after the end of DAA therapy. Acute hepatitis B developed 5 months after ending DAA therapy. Genome sequencing revealed the subgenotype as B1, and the serological subtype as adr. T118 K mutation at the S region as an immune escape mutant was identified. These virologic features led to HBV reactivation. The presence of hepatitis B core antibody or HBs antibody was not determined before DAA therapy, so prior HBV infection status was unclear. This case is speculated to represent HBV reactivation in a patient with previously resolved HBV induced by DAA therapy, based on virologic analysis and clinical status. The risk might be very low, but DAA therapy can cause HBV reactivation in chronic hepatitis C patients with prior HBV infection. When acute hepatitis emerges in patients who have received DAA therapy for HCV, HBV reactivation should be considered to allow early initiation of anti-HBV therapy.
Collapse
|
|
8
|
A case of acute hepatitis B in a chronic hepatitis C patient after daclatasvir and asunaprevir combination therapy: hepatitis B virus reactivation or acute self-limited hepatitis? Clin J Gastroenterol 2016; 9:252-6. [PMID: 27329484 DOI: 10.1007/s12328-016-0657-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 05/22/2016] [Indexed: 12/22/2022]
|
|
9
|
Chang IC, Huang SF, Chen PJ, Chen CL, Chen CL, Wu CC, Tsai CC, Lee PH, Chen MF, Lee CM, Yu HC, Lo GH, Yeh CT, Hong CC, Eng HL, Wang J, Tseng HH, Hsiao CH, Wu HDI, Yen TC, Liaw YF. The Hepatitis Viral Status in Patients With Hepatocellular Carcinoma: a Study of 3843 Patients From Taiwan Liver Cancer Network. Medicine (Baltimore) 2016; 95:e3284. [PMID: 27082566 PMCID: PMC4839810 DOI: 10.1097/md.0000000000003284] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the leading cancer death in Taiwan. Chronic viral hepatitis infections have long been considered as the most important risk factors for HCC in Taiwan. The previously published reports were either carried out by individual investigators with small patient numbers or by large endemic studies with limited viral marker data. Through collaboration with 5 medical centers across Taiwan, Taiwan liver cancer network (TLCN) was established in 2005. All participating centers followed a standard protocol to recruit liver cancer patients along with their biosamples and clinical data. In addition, detailed viral marker analysis for hepatitis B virus (HBV) and hepatitis C virus (HCV) were also performed. This study included 3843 HCC patients with available blood samples in TLCN (recruited from November 2005 to April 2011). There were 2153 (56.02%) patients associated with HBV (HBV group); 969 (25.21%) with HCV (HCV group); 310 (8.07%) with both HBV and HCV (HBV+HCV group); and 411 (10.69%) were negative for both HBV and HCV (non-B non-C group). Two hundred two of the 2463 HBV patients (8.20%) were HBsAg(-), but HBV DNA (+). The age, gender, cirrhosis, viral titers, and viral genotypes were all significantly different between the above 4 groups of patients. The median age of the HBV group was the youngest, and the cirrhotic rate was lowest in the non-B non-C group (only 25%). This is the largest detailed viral hepatitis marker study for HCC patients in the English literatures. Our study provided novel data on the interaction of HBV and HCV in the HCC patients and also confirmed that the HCC database of TLCN is highly representative for Taiwan and an important resource for HCC research.
Collapse
Affiliation(s)
- Il-Chi Chang
- From the Liver Research Unit, Chang Gung Memorial Hospital Linko Branch, Chang-Gung University, Taoyuan, Taiwan (I-CC, C-CH, Y-FL), Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan (I-CC, S-FH, C-CH), Department of Pathology, Chang Gung Memorial Hospital Linko Branch, Taoyuan, Taiwan (S-FH), Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan (P-JC, C-LC), Department of General Surgery, Chang Gung Memorial Hospital Kaohsiung Branch, Chang-Gung University, Kaohsiung, Taiwan (C-LC), Department of General Surgery, Taichung Veteran General Hospital, Taichung, Taiwan (C-CW), Department of General Surgery, Kaohsiung Veteran General Hospital, Kaohsiung, Taiwan (C-CT), Department of General Surgery, National Taiwan University Hospital, Taipei, Taiwan (P-HL), Department of General Surgery, Chang Gung Memorial Hospital Linko Branch, Chang-Gung University, Taoyuan, Taiwan (M-FC), Department of Hepato-gastroenterology, Chang Gung Memorial Hospital Kaohsiung Branch, Chang-Gung University, Kaohsiung, Taiwan (C-ML), Department of Hepato-gastroenterology, Kaohsiung Veteran General Hospital, Kaohsiung, Taiwan (H-CY, G-HL), Department of Hepato-gastroenterology, Chang Gung Memorial Hospital Linko Branch, Chang-Gung University, Taoyuan, Taiwan (C-TY), Department of Pathology, Chang Gung Memorial Hospital Kaohsiung Branch, Chang-Gung University, Kaohsiung, Taiwan (H-LE), Department of Pathology, Taichung Veteran General Hospital, Taichung, Taiwan (JW), Department of Pathology, Kaohsiung Veteran General Hospital, Kaohsiung, Taiwan (H-HT), Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan (C-HH), Department of Applied Mathematics and Institute of Statistics, National Chung-Hsing University, TaiChung, Taiwan (H-DIW, T-CY)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
10
|
De Monte A, Courjon J, Anty R, Cua E, Naqvi A, Mondain V, Cottalorda J, Ollier L, Giordanengo V. Direct-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge. J Clin Virol 2016; 78:27-30. [PMID: 26967675 DOI: 10.1016/j.jcv.2016.02.026] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 02/17/2016] [Accepted: 02/28/2016] [Indexed: 01/09/2023]
Abstract
Use of direct-acting antiviral drugs (DAAs) greatly improves management of adults infected with hepatitis C virus (HCV) whether patients are treatment-naive or unsuccessfully pre-treated. Several inhibitors of viral nonstructural proteins (NS3/4A protease, NS5A and NS5B polymerase) allow a rapid HCV clearance and increase rates of sustained virological response. Both the EASL and AASLD guidelines have recently published up-to-date recommendations for their use, addressing each HCV genotype and particular situations. However, management of patients coinfected with hepatitis B virus (HBV) has been developed by these guidelines with reference to cases of HBV reactivation reported during previous anti-HCV regimens containing interferon known active against both HBV and HCV. In the setting of the interferon-free HCV therapies with DAAs only, the possibility of HBV reactivation during treatment of hepatitis C is raised due to viral interferences in HCV/HBV coinfected persons. Herein, we report a case of early HBV reactivation during DAAs-based anti-HCV treatment (ledipasvir/sofosbuvir) in a patient having a resolved HBV infection and chronically infected with HCV genotype 4 and HIV. Moreover, we review similar recent cases of HBV reactivation in patients infected with HBV and HCV genotype 1 during treatment of hepatitis C by regimen incorporating other combination of DAAs (sofosbuvir/simeprevir or daclatasvir/asunaprevir). Due to the potential risk of early HBV reactivation in HCV/HBV-coinfected patients during interferon-free DAAs-based HCV therapies, altogether these cases highlight the necessity to closely monitor HBV coinfection, regardless its stage (chronic, occult, resolved), whatever HCV genotype or class of DAAs used.
Collapse
Affiliation(s)
- Anne De Monte
- Department of Virology, Biological and Pathological Center, Centre Hospitalier Universitaire de Nice, France
| | - Johan Courjon
- Department of Infectious Diseases, Centre Hospitalier Universitaire de Nice, France
| | - Rodolphe Anty
- Digestive Center, Centre Hospitalier Universitaire de Nice, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U895, Team 8, Hepatic Complications in Obesity, France; University of Nice-Sophia-Antipolis, Faculty of Medicine, France
| | - Eric Cua
- Department of Infectious Diseases, Centre Hospitalier Universitaire de Nice, France
| | - Alissa Naqvi
- Department of Infectious Diseases, Centre Hospitalier Universitaire de Nice, France
| | - Véronique Mondain
- Department of Infectious Diseases, Centre Hospitalier Universitaire de Nice, France
| | - Jacqueline Cottalorda
- Department of Virology, Biological and Pathological Center, Centre Hospitalier Universitaire de Nice, France
| | - Laurence Ollier
- Department of Virology, Biological and Pathological Center, Centre Hospitalier Universitaire de Nice, France.
| | - Valérie Giordanengo
- Department of Virology, Biological and Pathological Center, Centre Hospitalier Universitaire de Nice, France; University of Nice-Sophia-Antipolis, Faculty of Medicine, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, France
| |
Collapse
|
|
11
|
Song K, Han C, Dash S, Balart LA, Wu T. MiR-122 in hepatitis B virus and hepatitis C virus dual infection. World J Hepatol 2015; 7:498-506. [PMID: 25848473 PMCID: PMC4381172 DOI: 10.4254/wjh.v7.i3.498] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Revised: 09/06/2014] [Accepted: 12/17/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the most common causes of chronic liver diseases and hepatocelluar carcinomas. Over the past few years, the liver-enriched microRNA-122 (miR-122) has been shown to differentially regulate viral replication of HBV and HCV. It is notable that the level of miR-122 is positively and negatively regulated by HCV and HBV, respectively. Consistent with the well-documented phenomenon that miR-122 promotes HCV accumulation, inhibition of miR-122 has been shown as an effective therapy for the treatment of HCV infection in both chimpanzees and humans. On the other hand, miR-122 is also known to block HBV replication, and HBV has recently been shown to inhibit miR-122 expression; such a reciprocal inhibition between miR-122 and HBV suggests an intriguing possibility that miR-122 replacement may represent a potential therapy for treatment of HBV infection. As HBV and HCV have shared transmission routes, dual infection is not an uncommon scenario, which is associated with more advanced liver disease than either HBV or HCV mono-infection. Thus, there is a clear need to further understand the interaction between HBV and HCV and to delineate the role of miR-122 in HBV/HCV dual infection in order to devise effective therapy. This review summarizes the current understanding of HBV/HCV dual infection, focusing on the pathobiological role and therapeutic potential of miR-122.
Collapse
|
|
12
|
Gentile I, Buonomo AR, Zappulo E, Borgia G. Interferon-free therapies for chronic hepatitis C: toward a hepatitis C virus-free world? Expert Rev Anti Infect Ther 2015; 12:763-73. [PMID: 24918116 DOI: 10.1586/14787210.2014.929497] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
About 2% of the world's population is estimated to be chronically infected with hepatitis C virus (HCV). These chronic carriers are at risk of developing liver cirrhosis and its complications. Successful treatment of HCV infection is associated with improved quality of life and increased survival. Antiviral approaches were formerly based on interferon and therefore all patients with a contraindication to interferon were excluded from treatment (e.g., patients with decompensated disease, severe impairment of other organs). Very recently, interferon-free combinations have become available for genotypes 2 and 3. This review focuses on the most recently reported data on the various interferon-free combinations used (namely, sofosbuvir-based combinations, the ABT-450/ombitasvir/dasabuvir/ribavirin combination, the daclatasvir/asunaprevir combination, and the MK-5172/MK-8742 combination). All these combinations yielded amazing results in terms of efficacy (90-100%), tolerability and safety. If the problem of the high cost is overcome, interferon-free therapies will lead to what has long been a chimera, namely, an HCV-free world.
Collapse
Affiliation(s)
- Ivan Gentile
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", via S. Pansini 5, I-80131 Naples, Italy
| | | | | | | |
Collapse
|
|
13
|
Dong Y, Qiu C, Xia X, Wang J, Zhang H, Zhang X, Xu J. Hepatitis B virus and hepatitis C virus infection among HIV-1-infected injection drug users in Dali, China: prevalence and infection status in a cross-sectional study. Arch Virol 2015; 160:929-36. [PMID: 25616842 DOI: 10.1007/s00705-014-2311-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Accepted: 12/10/2014] [Indexed: 01/21/2023]
Abstract
To assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and to investigate their mutual influences on infection status among human immunodeficiency virus type 1 (HIV-1)-seropositive injection drug users (IDUs). A cross-sectional study was conducted among HIV infected IDUs in Dali, China. The participants were tested for serological markers of HBV and HCV infection, alanine transaminase (ALT) activity and CD4(+) T cell count. HCV genotype was determined by sequencing. Of 529 patients, 498 (94.1 %) HIV infected IDUs agreed to participate. The overall prevalence of HCV infection (anti-HCV antibody positive) and spontaneous HCV clearance were 90.8 % (452/498) and 21.5 % (97/452), respectively. Of 411 subjects who had not received HBV vaccine, 296 (72.0 %) were positive for antibody against HBV core antigen (HBcAb), while 274 (66.7 %) were positive for both HCV antibody and HBcAb. HBV antigens were detected in 52 of the HBV-infected subjects (17.6 %). HCV clearance was associated with HBV antigenemia (p = 0.0002) and higher CD4(+) T cell count (p = 0.0294). Resolved HBV infection was associated with HCV genotype 3 (p = 0.0365). HBV and HCV infection are highly prevalent and mutually influence infection status in HIV-1 infected IDUs in Dali, China.
Collapse
Affiliation(s)
- Yuan Dong
- Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health at Shanghai Medical College, Fudan University, Research Bldg, Rm 308, 2901 Caolang Road, Jinshan District, Shanghai, 201508, China
| | | | | | | | | | | | | |
Collapse
|
|
14
|
Coppola N, Sagnelli C, Pisaturo M, Minichini C, Messina V, Alessio L, Starace M, Signoriello G, Gentile I, Filippini P, Sagnelli E. Clinical and virological characteristics associated with severe acute hepatitis B. Clin Microbiol Infect 2014; 20:O991-O997. [PMID: 24930916 DOI: 10.1111/1469-0691.12720] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2014] [Revised: 06/08/2014] [Accepted: 06/10/2014] [Indexed: 12/16/2022]
Abstract
To identify early predictors of a severe or fulminant course in patients with acute viral hepatitis B (AVH-B). One hundred and thirty-eight patients with symptomatic acute hepatitis B observed from 1999 to 2012 were enrolled. For each patient, the demographics, risk factors for the acquisition of hepatitis B virus (HBV) infection, clinical, biochemical and virological data (HBV DNA, HBV DNA sequences) were recorded and analysed. The HBV mutants in the polymerase region were sought in 110 (87%) patients by direct sequencing, and the rtM204V/I mutations also by an allele-specific PCR. AVH-B was severe in 13 (9.4%) of the 138 patients enrolled, fulminant in 6 (4.3%) and with a normal clinical course in 119. The 19 patients with severe or fulminant AVH-B more frequently than the 119 with a normal course stated intravenous drug use (63.2% versus 36.1%, p 0.04) and were HBV-DNA negative (31.6% versus 11.8%, p 0.03) and anti-hepatitis C virus (HCV) positive (57.9% versus 19.3%, p 0.0008); the prevalences of different HBV genotypes and of the rtM204V/I mutant were similar in these three forms of AVH-B. A multivariate logistic regression analysis identified a pre-existing HCV chronic infection as the only factor independently associated with a severe or fulminant clinical course of AVH-B (OR 4.89, 95% CI 1.5-15.94, p 0.01). A pre-existing HCV chronic infection was identified as the only factor independently associated with a severe clinical presentation of acute hepatitis B, an association most probably due to the combination of the liver lesions caused by acute hepatitis B and the pre-existing histological abnormalities related to HCV chronic infection.
Collapse
Affiliation(s)
- N Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Naples, Italy
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
15
|
Caccamo G, Saffioti F, Raimondo G. Hepatitis B virus and hepatitis C virus dual infection. World J Gastroenterol 2014; 20:14559-14567. [PMID: 25356020 PMCID: PMC4209523 DOI: 10.3748/wjg.v20.i40.14559] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 03/24/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) share common mode of transmission and both are able to induce a chronic infection. Dual HBV/HCV chronic coinfection is a fairly frequent occurrence, especially in high endemic areas and among individuals at high risk of parenterally transmitted infections. The intracellular interplay between HBV and HCV has not yet been sufficiently clarified, also due to the lack of a proper in vitro cellular model. Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients. Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma. Despite the clinical importance, solid evidence and clear guidelines for treatment of this special population are still lacking. This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection, and highlights the aspects that need to be better clarified.
Collapse
MESH Headings
- Antiviral Agents/therapeutic use
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/epidemiology
- Carcinoma, Hepatocellular/prevention & control
- Carcinoma, Hepatocellular/virology
- Coinfection
- Disease Progression
- Hepacivirus/drug effects
- Hepacivirus/pathogenicity
- Hepatitis B virus/drug effects
- Hepatitis B virus/pathogenicity
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/drug therapy
- Hepatitis B, Chronic/epidemiology
- Hepatitis B, Chronic/virology
- Hepatitis C, Chronic/diagnosis
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/epidemiology
- Hepatitis C, Chronic/virology
- Host-Pathogen Interactions
- Humans
- Liver Neoplasms/diagnosis
- Liver Neoplasms/epidemiology
- Liver Neoplasms/prevention & control
- Liver Neoplasms/virology
- Risk Assessment
- Risk Factors
Collapse
|
|
16
|
Sagnelli E, Santantonio T, Coppola N, Fasano M, Pisaturo M, Sagnelli C. Acute hepatitis C: clinical and laboratory diagnosis, course of the disease, treatment. Infection 2014; 42:601-610. [PMID: 24619833 DOI: 10.1007/s15010-014-0608-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Accepted: 02/24/2014] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Acute hepatitis C (AHC) is asymptomatic in about 70-80 % of cases and, therefore, is usually undiagnosed. Although the clinical course is typically mild, AHC has a high rate of transition to chronicity. MATERIAL AND METHODS We evaluated the literature data concerning risk factors for HCV transmission, diagnosis, natural history, and antiviral treatment of AHC. RESULTS Although new methods have been developed, anti-HCV seroconversion remains the gold standard for the diagnosis of AHC. This phenomenon, however, is identifiable in less than half of cases in the everyday clinical practice, since most AHC patients do not know their previous anti-HCV/HCV-RNA status. An early short-term interferon treatment in AHC patients prevents progression to chronicity in most of treated patients. CONCLUSION The literature data give evidence of the clinical relevance of an early diagnosis of AHC for an early short-term interferon treatment. There is also the suggestion to use newly developed laboratory methods to distinguish AHC from an acute exacerbation of a chronic HCV infection.
Collapse
Affiliation(s)
- E Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, via L. Armanni, No. 3, 80135, Naples, Italy,
| | | | | | | | | | | |
Collapse
|
|
17
|
Coppola N, Zampino R, Sagnelli C, Bellini G, Marrone A, Stanzione M, Capoluongo N, Boemio A, Minichini C, Adinolfi LE, Maione S, Giudice EMD, Sagnelli E, Rossi F. Cannabinoid receptor 2-63 QQ variant is associated with persistently normal aminotransferase serum levels in chronic hepatitis C. PLoS One 2014; 9:e99450. [PMID: 24940753 PMCID: PMC4062424 DOI: 10.1371/journal.pone.0099450] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2014] [Accepted: 05/14/2014] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND AND AIM To evaluate in anti-HCV-positive patients the clinical impact of the rs35761398 variant of the CNR2 gene leading to the substitution of Gln (Q) of codon 63 of the cannabinoid receptor 2 (CB2) with Arg (R). PATIENTS AND METHODS 253 consecutive anti-HCV-/HCV-RNA-positive patients were enrolled, of whom 53 were HCV carriers with persistently normal ALT (PNALT group) and 200 had a history of steadily abnormal serum ALT values (abnormal ALT group). All patients were naive for antiviral therapy and were screened for the CNR2 rs35761398 polymorphism by a TaqMan assay. RESULTS Subjects in the PNALT group, compared with those in the abnormal ALT group were older (58.5±12 vs. 50.7±12.4 years, p = 0.001), more frequently female (66% vs. 42%, p = 0.003), with lower body mass index (BMI) (24.5±3.1 vs. 26.6±4.6, p = 0.003), and more frequently with HCV genotype 2 (43.1% vs 17.7%, p = 0.0002) and CB2-63 QQ variant (34% vs. 11%, p = 0.0001). Considering all 253 patients, no difference in the demographic, biochemical, or virological data was observed between patients in the different CB2-63 variants. The logistic regression analysis identified CB2-63 QQ, HCV genotype 2, older age and lower BMI as independent predictors of PNALT (p<0.00001). DISCUSSION The CB2-63 QQ variant in HCV patients was independently associated with the PNALT status.
Collapse
Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Rosa Zampino
- Internal Medicine and Hepatology, Second University of Naples, Naples, Italy
| | - Caterina Sagnelli
- Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy
| | - Giulia Bellini
- Department of Experimental Medicine, Second University of Naples, Naples, Italy
| | - Aldo Marrone
- Internal Medicine and Hepatology, Second University of Naples, Naples, Italy
| | - Maria Stanzione
- Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy
| | - Nicolina Capoluongo
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Adriana Boemio
- Internal Medicine and Hepatology, Second University of Naples, Naples, Italy
| | - Carmine Minichini
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Luigi Elio Adinolfi
- Internal Medicine and Hepatology, Second University of Naples, Naples, Italy
| | - Sabatino Maione
- Department of Experimental Medicine, Second University of Naples, Naples, Italy
| | | | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Francesca Rossi
- Department of Pediatrics, Second University of Naples, Naples, Italy
| |
Collapse
|
|
18
|
Sagnelli E, Sagnelli C, Pisaturo M, Coppola N. Hepatic flares in chronic hepatitis C: spontaneous exacerbation vs hepatotropic viruses superinfection. World J Gastroenterol 2014; 20:6707-6715. [PMID: 24944463 PMCID: PMC4051912 DOI: 10.3748/wjg.v20.i22.6707] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 01/13/2014] [Accepted: 04/01/2014] [Indexed: 02/06/2023] Open
Abstract
The hepatitis C virus (HCV) causes an acute infection that is frequently asymptomatic, but a spontaneous eradication of HCV infection occurs only in one-third of patients. The remaining two-thirds develop a chronic infection that, in most cases, shows an indolent course and a slow progression to the more advanced stages of the illness. Nearly a quarter of cases with chronic hepatitis C (CHC) develop liver cirrhosis with or without hepatocellular carcinoma. The indolent course of the illness may be troubled by the occurrence of a hepatic flare, i.e., a spontaneous acute exacerbation of CHC due to changes in the immune response, immunosuppression and subsequent restoration, and is characterized by an increase in serum aminotransferase values, a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment. A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses, namely hepatitis B virus (HBV), HBV plus hepatitis D virus, hepatitis E virus, cytomegalovirus, particularly in geographical areas with high endemicity levels. The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.
Collapse
|
|
19
|
Coppola N, Marrone A, Pisaturo M, Starace M, Signoriello G, Gentile I, Adinolfi LE, Sagnelli E, Zampino R. Role of interleukin 28-B in the spontaneous and treatment-related clearance of HCV infection in patients with chronic HBV/HCV dual infection. Eur J Clin Microbiol Infect Dis 2014; 33:559-67. [PMID: 24081499 DOI: 10.1007/s10096-013-1985-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2013] [Accepted: 09/11/2013] [Indexed: 12/27/2022]
Abstract
The purpose of this investigation was to evaluate the role of IL28-B polymorphism in the clearance of hepatitis C virus (HCV) in chronic hepatitis B virus (HBV)/HCV coinfection during a long-term follow-up. Thirty-four consecutive patients with HBV surface antigen (HBsAg)-positive/anti-HCV-positive chronic hepatitis were retrospectively enrolled at their first liver biopsy (LB). For all patients, a documented clinical, serological and virological follow-up of at least 3 years (range 3-16 years) after LB and a sample of whole blood for genetic evaluation were available. Of the 24 patients with detectable serum HBV-DNA and HCV-RNA at their first observation, three cleared both HBV-DNA and HCV-RNA, 12 HCV-RNA and five HBV-DNA. Of the seven HBV DNA-positive/HCV RNA-negative patients at enrolment, three cleared HBV-DNA and one remained HBV DNA-positive and became HCV RNA-positive. All three HBV DNA-negative/HCV RNA-positive patients remained unchanged. Compared with the 12 patients with HCV persistence, the 15 patients who cleared HCV were younger, had lower serum alanine aminotransferase (ALT), HCV load, and histological activity index (HAI) and fibrosis score, more frequently had IL28-B CC variant, had been receiving an interferon-based treatment and less frequently cleared serum HBV-DNA. To investigate the relationship between the IL28-B variants and clearance of HCV, excluding the confounding effect of interferon-based treatment, the Mantel-Haenszel test was used, which indicated an association between HCV clearance and IL28-B variants (p = 0.009). In chronic HBV/HCV coinfection, a long-term follow-up showed a frequent spontaneous or treatment-related clearance of active replication of one or both viruses and identified the IL28-B CC genotype as an independent predictor of HCV clearance.
Collapse
Affiliation(s)
- N Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Via L. Armanni 5, 80133, Naples, Italy,
| | | | | | | | | | | | | | | | | |
Collapse
|
|
20
|
Coppola N, Zampino R, Bellini G, Macera M, Marrone A, Pisaturo M, Boemio A, Nobili B, Pasquale G, Maione S, Adinolfi LE, Perrone L, Sagnelli E, Miraglia Del Giudice E, Rossi F. Association between a polymorphism in cannabinoid receptor 2 and severe necroinflammation in patients with chronic hepatitis C. Clin Gastroenterol Hepatol 2014; 12:334-40. [PMID: 23707465 DOI: 10.1016/j.cgh.2013.05.008] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2013] [Revised: 04/15/2013] [Accepted: 05/04/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The cannabinoid receptor 2 (CB2) has been implicated in liver disease. The single-nucleotide polymorphism rs35761398 in cannabinoid receptor 2 gene (CNR2), which encodes the CB2, substitutes glutamine (Q) 63 with arginine (R), and reduces the function of the gene product. We investigated the effects of CNR2 rs35761398 in patients with hepatitis C virus (HCV) infection. METHODS We studied 169 consecutive patients with asymptomatic chronic hepatitis (tested positive for anti-HCV and HCV RNA) at 2 liver units in southern Italy. First, liver biopsy samples were collected from July 2009 through December 2011. All patients were naive to antiviral therapy; CNR2 genotype was determined by polymerase chain reaction analysis. RESULTS Patients with the CB2-63 QQ variant had higher serum levels of aminotransferase than those with the CB2-63 QR or RR variants; they also had higher histologic activity index (HAI) scores (8.6 ± 3.8) than patients without the CB2-63 RR variant (5.3 ± 3.6; P < .005) or those with the CB2-63 QR variant (5.8 ± 3.3; P < .001). Patients with the different variants of CNR2 did not differ in fibrosis stage or steatosis score. Moderate or severe chronic hepatitis (HAI score, >8) was identified more frequently (55.5%) in patients with the CB2-63 QQ variant than in those with the 63 QR (20%; P < .005) or RR variants (17.4%; P < .005). In logistic regression analysis, the CB2-63 QQ variant and fibrosis score were independent predictors of moderate or severe chronic hepatitis (HAI score, >8; P < .0001). CONCLUSIONS The CB2-63 QQ variant of CNR2 is associated with more severe inflammation and hepatocellular necrosis in patients with HCV infection.
Collapse
Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.
| | - Rosa Zampino
- Internal Medicine and Hepatology, Second University of Naples, Naples, Italy
| | - Giulia Bellini
- Department of Experimental Medicine, Second University of Naples, Naples, Italy
| | - Margherita Macera
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Aldo Marrone
- Internal Medicine and Hepatology, Second University of Naples, Naples, Italy
| | | | - Adriana Boemio
- Internal Medicine and Hepatology, Second University of Naples, Naples, Italy
| | - Bruno Nobili
- Department of Pediatrics, Second University of Naples, Naples, Italy
| | - Giuseppe Pasquale
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Sabatino Maione
- Department of Experimental Medicine, Second University of Naples, Naples, Italy
| | - Luigi Elio Adinolfi
- Internal Medicine and Hepatology, Second University of Naples, Naples, Italy
| | - Laura Perrone
- Department of Pediatrics, Second University of Naples, Naples, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | | | - Francesca Rossi
- Department of Pediatrics, Second University of Naples, Naples, Italy
| |
Collapse
|
|
21
|
|
|
22
|
Amaku M, Coutinho FAB, Chaib E, Massad E. The impact of hepatitis A virus infection on hepatitis C virus infection: a competitive exclusion hypothesis. Bull Math Biol 2012. [PMID: 23192400 DOI: 10.1007/s11538-012-9795-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
We address the observation that, in some cases, patients infected with the hepatitis C virus (HCV) are cleared of HCV when super-infected with the hepatitis A virus (HAV). We hypothesise that this phenomenon can be explained by the competitive exclusion principle, including the action of the immune system, and show that the inclusion of the immune system explains both the elimination of one virus and the co-existence of both infections for a certain range of parameters. We discuss the potential clinical implications of our findings.
Collapse
Affiliation(s)
- Marcos Amaku
- School of Veterinary Medicine, University of São Paulo, São Paulo, Brazil
| | | | | | | |
Collapse
|
|
23
|
Delladetsima I, Papatheodoridis GV, Tiniakos DG, Hatzakis A, Tassopoulos NC. Significance of liver histology in HBsAg-positive, IgM anti-HBc-negative acute hepatitis B virus-related hepatitis. Histopathology 2012; 61:881-8. [PMID: 22882633 DOI: 10.1111/j.1365-2559.2012.04294.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
AIMS The natural course of HBsAg-positive, IgM anti-HBc-negative acute hepatitis B virus (HBV)-related hepatitis is unclear. The aim of this study was to evaluate the prognostic significance of histological features and hepatic expression of HBV antigens in such patients. METHODS AND RESULTS Fifty patients with HBsAg-positive, IgM anti-HBc-negative acute hepatitis B who underwent liver biopsy during the acute hepatitis episode were studied [HBeAg seroconversion (n = 16), persistently positive for HBeAg (n = 9), and persistently negative for HBeAg (n = 25)]. Twenty-six cases had features of typical acute hepatitis only (group A), and 24 cases had changes suggesting pre-existing chronic hepatitis (group B). HBcAg and/or HBsAg immunoreactivity was detected less frequently in group A than in group B (31% versus 79%, P = 0.01). HBsAg clearance was observed in 24% of patients, almost exclusively in cases with HBeAg seroconversion. HBsAg loss was significantly more frequent in group A than in group B (52% versus 0%, P < 0.001), and in cases without rather than with immunohistochemical expression of HBV antigens (55% versus 0%, P < 0.001). In group A, HBsAg clearance was observed in 80%, 54% and 0% of patients with mild, moderate or severe acute hepatitis, respectively (P < 0.034). CONCLUSIONS Histological information is very important for the prognosis of HBsAg-positive, IgM anti-HBc-negative acute hepatitis B. HBeAg seroconversion with underlying typical acute hepatitis changes of mild to moderate severity without hepatic expression of HBV antigens strongly predicts subsequent HBsAg loss.
Collapse
Affiliation(s)
- Ioanna Delladetsima
- 1st Department of Pathology 2nd, Medical School, National & Kapodistrian University of Athens, Athens, Greece
| | | | | | | | | |
Collapse
|
|
24
|
Pham TNQ, Coffin CS, Churchill ND, Urbanski SJ, Lee SS, Michalak TI. Hepatitis C virus persistence after sustained virological response to antiviral therapy in patients with or without past exposure to hepatitis B virus. J Viral Hepat 2012; 19:103-11. [PMID: 21699630 DOI: 10.1111/j.1365-2893.2011.01442.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hepatitis C virus (HCV) and hepatitis B virus (HBV) frequently coinfect and persist long after clinical resolution. We assessed the incidence of low-level (occult) HCV infection (OCI) after sustained virological response (SVR) to standard anti-HCV therapy in individuals with or without past exposure to HBV to recognize whether HBV could influence the prevalence of OCI, HCV level and hepatic histology. Plasma and peripheral blood mononuclear cells (PBMC) were collected from 24 individuals at 6- to 12-month intervals for up to 72 months after SVR. Liver histology was available for nine patients. HCV and HBV genomes were detected with sensitivity <10 genome copies/mL. In individuals without HBV exposure (n = 15), comprehensive analyses of sequential plasma and PBMC samples revealed HCV RNA in all 15 cases (75% plasma and 61% PBMC). In the group with HBV exposure (n = 9), evidenced by circulating anti-HBc and/or HBV DNA detection by a highly sensitive assay, HCV RNA was identified in all cases (83% plasma and 59% PBMC), at levels similar to those in HBV nonexposed individuals. In both groups of patients, most liver biopsies included those reactive for viral genomes displayed low-grade inflammation (8 of 9) and fibrosis (7 of 9). Sequence polymorphisms at the 5`-UTR between PBMC and liver or plasma, as well as circulating HCV virion-like particles, were observed in patients with or without HBV exposure. In conclusion, the prevalence of OCI after SVR is comparable in individuals with or without past exposure to HBV. HCV loads and liver alterations in OCI appear to be unaffected by low-level HBV DNA carriage.
Collapse
Affiliation(s)
- T N Q Pham
- Molecular Virology and Hepatology Research Group, Memorial University, St. John's, NF, Canada
| | | | | | | | | | | |
Collapse
|
|
25
|
Jain MK, Seremba E, Bhore R, Dao D, Joshi R, Attar N, Yuan HJ, Lee WM. Change in fibrosis score as a predictor of mortality among HIV-infected patients with viral hepatitis. AIDS Patient Care STDS 2012; 26:73-80. [PMID: 22239101 DOI: 10.1089/apc.2011.0191] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Noninvasive markers of liver fibrosis, measured at baseline, have been shown to predict liver-related mortality. It remains unknown if a change in the value of the scores over time predicts mortality in patients with HIV and viral hepatitis. In this retrospective study, survival in HIV/hepatitis B virus (HBV; n = 67), HIV/hepatitis C virus (HCV; n = 43), and HIV/HBV/HCV (n = 41) patients was examined using Kaplan-Meier life table analysis. Aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and FIB-4 scores, two noninvasive markers of liver fibrosis, were calculated at baseline and at last available clinical follow-up to determine the change in fibrosis score. Factors associated with mortality were assessed by Cox proportional hazards, including the change in the noninvasive marker score between the two time points. All-cause mortality was determined by Social Security Death Index and chart review. Sixty-seven were coinfected with HIV/HBV, 43 with HIV/HCV, and 41 were triply infected (HIV/HBV/HCV). Kaplan-Meier analysis showed similar survival for the three groups at 7 years of follow-up (p = 0.10). However, median length of follow-up was lower in HIV/HCV (60.5; range 0-102) compared to HIV/HBV (75.7; 12.3-126.5) and HIV/HBV/HCV (80.0; 2.7-123) months, respectively, p = 0.02. Baseline fibrosis score (p = 0.002), an increase in the value for noninvasive measurements for fibrosis (p < 0.001), and the presence of HIV/HCV coinfection (p = 0.041) were each associated with higher risk for mortality. Baseline fibrosis score (p = 0.03) and an increase in FIB-4 score (p = 0.05) were independent predictors of all-cause mortality, but liver-related mortality was not evaluated. In this study, baseline fibrosis score was predictive of 7-year all-cause mortality. Further studies are needed in a prospective cohort to evaluate the predictive value of monitoring changes in fibrosis scores over time to predict mortality in patients with viral hepatitis.
Collapse
Affiliation(s)
- Mamta K. Jain
- Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
| | - Emmanuel Seremba
- Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
| | - Rafia Bhore
- Department of Clinical Sciences, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
| | - Doan Dao
- Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
| | - Reeti Joshi
- Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
| | - Nahid Attar
- Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
| | - He-Jun Yuan
- Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
| | - William M. Lee
- Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
| |
Collapse
|
|
26
|
Tan YW. Antiviral treatment of hepatitis B virus and hepatitis C virus co-infection. Shijie Huaren Xiaohua Zazhi 2011; 19:1614-1619. [DOI: 10.11569/wcjd.v19.i15.1614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most common causes of advanced chronic liver disease worldwide. HBV/HCV co-infection is not uncommon with an estimated 7-20 million individuals affected worldwide. Patients with HBV/HCV co-infection have an increased risk of cirrhosis, hepatocellular carcinoma (HCC), and even death. The pathophysiology of HBV/HCV co-infection is complex, as different patterns of virological dominance may occur, which can even fluctuate over time. Recently, combination of pegylated interferon (PEG-IFN) plus ribavirin has been explored in HBV/HCV-coinfected patients who are positive for HCV-RNA. In this paper, we summarize the epidemiology, viral interaction and clinical features of HBV/HCV co-infection and the available treatment options. Detailed serological and virological evaluations are required for HBV/HCV-co-infected patients before initiation of antiviral therapy. At present, PEG-IFN-a plus ribavirin should be the treatment of choice in patients with dominant HCV replication. However, HBV rebound may occur after elimination of HCV, and thus close monitoring for both viruses is recommended even for patients with initially suppressed HBV DNA.
Collapse
|
|
27
|
Yang RR, Gui X, Chen XY, Zhu Y. Interference of replication between hepatitis B and C viruses in patients infected with HIV. J Med Virol 2011; 83:1159-64. [DOI: 10.1002/jmv.22102] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
|
|
28
|
Serological and molecular expression of Hepatitis B infection in patients with chronic Hepatitis C from Tunisia, North Africa. Virol J 2010; 7:229. [PMID: 20843308 PMCID: PMC2949834 DOI: 10.1186/1743-422x-7-229] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2010] [Accepted: 09/15/2010] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND This study reports the prevalence and the viral aspects of HBV infection in HCV-positive patients from Tunisia, a country with intermediate and low endemicity for hepatitis B and C, respectively. RESULTS HBV infection was assessed in the serum samples of 361 HCV-positive patients and compared to a group of HCV negative individuals. Serological markers were determined by ELISA tests and HBV DNA by real-time PCR. HBV serological markers were found in 43% and 44% of patients and controls, respectively. However, the serological and molecular expression of HBV infection differed in the two groups: The group of patients included more individuals with ongoing HBV infection, as defined by the presence of detectable HBsAg and or HBV DNA (17% and 12%, respectively). Furthermore, while most of the controls with ongoing HBV infection expressed HBsAg, the majority of HCV and HBV positive patients were HBsAg negative and HBV DNA positive. Genotyping of HCV isolates showed large predominance of subtype 1b as previously reported in Tunisia. Comparison of the replicative status of the two viruses found low HBV viral load in all co-infected patients as compared to patients with single HBV infection. In contrast, high levels of HCV viremia levels were observed in most of cases with no difference between the group of co-infected patients and the group with single HCV infection. CONCLUSIONS This study adds to the knowledge on the prevalence and the virological presentation of HCV/HBV dual infection, providing data from the North African region. It shows that, given the local epidemiology of the two viruses, co-infected patients are likely to have low replication levels of HBV suggesting a suppressive effect of HCV on HBV. In contrast, high replication levels for HCV were fond in most cases which indicate that the presence of circulating HBV-DNA does not necessarily influence HCV replication.
Collapse
|
|
29
|
Abstract
IMPORTANCE OF THE FIELD Hepatitis B (HBV) and hepatitis C (HCV) virus infections are among the most common causes of advanced chronic liver disease worldwide. HBV/HCV coinfection is not uncommon with an estimated 7 - 20 million individuals affected worldwide. Patients with HBV/HCV coinfection have an increased risk for cirrhosis, hepatocellular carcinoma (HCC) and even death. AREAS COVERED IN THIS REVIEW The pathophysiology of HBV/HCV coinfection is complex, as different patterns of virological dominance may occur, which can even fluctuate over time. Recently, combination of pegylated interferon (PEG-IFN) plus ribavirin has been explored in HBV/HCV coinfected patients who are positive for HCV-RNA. HBV polymerase inhibitors may be indicated if HBV-DNA concentrations are above 2000 IU/ml. In this review, we summarize the epidemiology, viral interaction, its clinical features and the available treatment options. WHAT THE READER WILL GAIN Insights into viral interaction of HBV/HCV coinfection and treatment individualization strategies are provided in the review. TAKE HOME MESSAGE Detailed serological and virological evaluations are required for HBV/HCV coinfected patients before initiation of antiviral therapy. At present, PEG-IFN-alpha plus ribavirin should be the treatment of choice in patients with dominant HCV replication. However, HBV rebound may occur after elimination of HCV, and thus close monitoring for both viruses is recommended even for patients with initially suppressed HBV-DNA.
Collapse
Affiliation(s)
- Andrej Potthoff
- Hannover Medical School, Medizinische Hochschule Hannover, Department of Gastroenterology, Hepatology and Endocrinology, Carl Neuberg Str. 1, D-30625 Hannover, Germany
| | | | | |
Collapse
|
|
30
|
Sagnelli E, Coppola N, Pisaturo M, Masiello A, Tonziello G, Sagnelli C, Messina V, Filippini P. HBV superinfection in HCV chronic carriers: a disease that is frequently severe but associated with the eradication of HCV. Hepatology 2009; 49:1090-1097. [PMID: 19263473 DOI: 10.1002/hep.22794] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
UNLABELLED The impact of hepatitis B virus (HBV) superinfection in hepatitis C virus (HCV) chronic carriers was evaluated in a long-term follow-up study on 29 chronic anti-HCV carriers with acute hepatitis B (AVH-B) (Case group BC) and 29 anti-HCV negative patients with AVH-B (Control group B), pair-matched for age (+/-5 years), sex, and risk factors for the acquisition of HBV infection. Patients in Case group BC and those in Control group B showed similar initial HBV viral load and a similar trend of becoming negative for HBV-DNA. AVH-B showed a severe course more frequently in Case group BC than in Control group B (34.5% versus 6.9%, P < 0.05). Of the 28 patients in Case group BC alive at the end of the acute illness (one death from liver failure), 24 were followed up for 2-6 years, median 5 years: 22 patients became HBsAg-negative and two progressed to HBsAg-positive chronic hepatitis. HCV-RNA was undetectable in all patients during AVH-B; in the 24 patients with a long-term follow-up, HCV-RNA was detected in seven (29.2%) after 1 year, in 14 (58.3%) after 2 years, and in 18 (75%) after 3-6 years. The six patients who eradicated chronic HCV infection, compared with 18 showing reactivation of HCV replication, had higher values of aspartate aminotransferase and alanine aminotransferase and a higher prevalence of cases with severe AVH-B (83.3% versus 22.2%, P < 0.05). CONCLUSIONS Although it can be life-threatening, HBV superinfection in HCV chronic carriers may lead to clearance of chronic HCV infection, especially in patients with severe AVH-B.
Collapse
Affiliation(s)
- Evangelista Sagnelli
- Department of Public Medicine, Section of Infectious Diseases, 2nd University of Naples, Naples, Italy.
| | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Yataco ML, Dickson RC, Bonatti H, Aranda-Michel J, Mendez J, Ghabril M, Nguyen J. Dual hepatitis virus infections in liver transplant: case report and a review of the literature. Clin Transplant 2009; 23:282-8. [DOI: 10.1111/j.1399-0012.2008.00929.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
|
|
32
|
Biliotti E, Kondili LA, Furlan C, Ferretti G, Zacharia S, De Angelis M, Guidi S, Gusman N, Taliani G. Acute hepatitis B in patients with or without underlying chronic HCV infection. J Infect 2008; 57:152-7. [PMID: 18538412 DOI: 10.1016/j.jinf.2008.04.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2007] [Revised: 01/28/2008] [Accepted: 04/18/2008] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM Acute hepatitis B course may be significantly modified by underlying chronic hepatitis C. The aim of this study was to compare clinical and virological characteristics of acute hepatitis B in patients with or without chronic hepatitis C virus (HCV) infection. MATERIALS AND METHODS Twenty-seven patients with symptomatic acute hepatitis B were enrolled: 14 with underlying chronic HCV (Group A) and 13, matched by age and gender, with single hepatitis B (Group B). All patients were followed-up until HBsAg negativization. RESULTS Group A patients were HCV-RNA-negative on hospital admission and all but one remained negative during follow-up. HBeAg tested positive in 92.9% and 84.6% of Groups A and B patients, respectively. ALT, bilirubin, prothrombin time values and HBsAg titer were similar in both groups. Nevertheless, lower mean HBV-DNA levels (p=0.03), a shorter duration of HBsAg positivity (p<0.01) and of symptoms before ALT peak (p=0.014), and significantly lower peak ALT values (p=0.03) were observed in Group A compared to Group B patients. CONCLUSIONS Acute HBV infection suppressed HCV replication. Conversely, the underlying HCV infection exerted a modulatory effect on HBV replication which influenced the course, though not the outcome, of the acute disease. Although acute hepatitis B showed a mild clinical course in both groups of patients, HBV vaccination should be suggested to risk subjects.
Collapse
Affiliation(s)
- E Biliotti
- Department of Infectious and Tropical Diseases, University La Sapienza of Rome, Italy
| | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Operskalski EA, Mack WJ, Strickler HD, French AL, Augenbraun M, Tien PC, Villacres MC, Spencer LY, Degiacomo M, Kovacs A. Factors associated with hepatitis C viremia in a large cohort of HIV-infected and -uninfected women. J Clin Virol 2008; 41:255-63. [PMID: 18243785 PMCID: PMC3493623 DOI: 10.1016/j.jcv.2007.08.021] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2007] [Accepted: 08/28/2007] [Indexed: 12/17/2022]
Abstract
BACKGROUND Co-infection with hepatitis C virus (HCV) is common among HIV-infected women. OBJECTIVE To further our understanding of the risk factors for HCV viremia and the predictors of HCV viral load among women. STUDY DESIGN We investigated sociodemographic, immunologic, and virologic factors associated with presence and level of HCV viremia among 1049 HCV-seropositive women, 882 of whom were HIV-infected and 167 HIV-uninfected at their entry into the Women's Interagency HIV Study. RESULTS Plasma HCV RNA was detected in 852 (81%) of these 1049 women (range: 1.2-7.8 log(10)copies/ml). HCV-viremic women were more likely to have an HIV RNA level >100,000 copies/ml (P=0.0004), to have reported smoking (P=0.01), or to be Black (P=0.005). They were less likely to have current or resolved hepatitis B infection. HCV RNA levels were higher in women who were >35 years old, or HIV-infected. Current smoking and history of drug use (crack/freebase cocaine, marijuana, amphetamines, or heroin) were each associated with both presence and level of viremia. CONCLUSIONS Substance abuse counseling aimed at eliminating ongoing use of illicit drugs and tobacco may reduce clinical progression, improve response to treatment, and decrease HCV transmission by lowering levels of HCV viremia in women.
Collapse
Affiliation(s)
- Eva A Operskalski
- Maternal Child and Adolescent Center for Infectious Diseases and Virology, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
34
|
Coppola N, Pisapia R, Tonziello G, Martini S, Imparato M, Piai G, Stanzione M, Sagnelli C, Filippini P, Piccinino F, Sagnelli E. Virological pattern in plasma, peripheral blood mononuclear cells and liver tissue and clinical outcome in chronic hepatitis B and C virus coinfection. Antivir Ther 2008; 13:307-318. [PMID: 18505182 DOI: 10.1177/135965350801300216] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2025]
Abstract
BACKGROUND We aim to evaluate in chronic hepatitis B virus-hepatitis C virus (HBV-HCV) coinfection the interplay of these viruses in liver tissue, peripheral blood mononuclear cells (PBMC), and plasma and to analyze the effect on disease course and response to treatment. METHODS We enrolled 19 patients with chronic HBV-HCV coinfection, 20 with chronic HCV and 20 with chronic HBV infection at their first liver biopsy, all were naive for antiviral therapy. The patients' plasma, PBMC and liver biopsy samples were tested for HBV DNA and/or HCV RNA by real-time PCR, according to the presence/absence of hepatitis B surface antigen and antibodies against HCV in the serum. RESULTS Contemporary presence of HBV DNA and HCV RNA was rare in plasma (5.3% of cases) and PBMC (10.6%), but frequent in liver tissue (52.6%). Of 10 cases circulating only HCV RNA and treated with pegylated interferon (PEG-IFN) plus ribavirin for 12 months, two showed a sustained response, and eight cleared HCV RNA but became HBV-DNA-positive in plasma; these eight had detectable HBV DNA in liver at baseline. One patient, who was plasma HBV-DNA-positive/HCV-RNA-negative at baseline, showed a sustained response after 18 months of PEG-IFN treatment; another, who was plasma HBV-DNA/HCV-RNA-positive at baseline, cleared only HCV RNA during 12 months of PEG-IFN plus ribavirin treatment. Seven cases remained untreated. CONCLUSION Despite a reciprocal inhibition in plasma, HBV and HCV frequently coexist in liver tissue, a condition to be taken into consideration when deciding therapy.
Collapse
Affiliation(s)
- Nicola Coppola
- Department of Public Medicine, Second University of Naples, Italy
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Sherman KE, Fleischer R, Laessig K, Murray J, Tauber W, Birnkrant D. Development of novel agents for the treatment of chronic hepatitis C infection: Summary of the FDA Antiviral Products Advisory Committee recommendations. Hepatology 2007; 46:2014-20. [PMID: 18027878 DOI: 10.1002/hep.21985] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Affiliation(s)
- Kenneth E Sherman
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0595, USA.
| | | | | | | | | | | | | |
Collapse
|
|
36
|
Filippini P, Coppola N, Pisapia R, Martini S, Marrocco C, Di Martino F, Sagnelli C, Filippini A, Sagnelli E. Virological and clinical aspects of HBV-HCV coinfection in HIV positive patients. J Med Virol 2007; 79:1679-1685. [PMID: 17854026 DOI: 10.1002/jmv.20992] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
In a long-term follow-up study the clinical and virological presentation of HBV/HCV coinfection in anti-HIV positive patients was evaluated. Plasma HBV-DNA, HCV-RNA, and HIV-RNA were determined by PCR in 5 HBsAg/anti-HCV/anti-HIV positive patients, in 4 HBsAg/anti-HIV positive patients and in 82 anti-HCV/anti-HIV positive patients first observed at a Unit of Infectious Diseases in Naples (Italy) from 1990 to 2000 (follow up 6-16 years). All five hepatitis B and C coinfected patients showed reciprocal inhibition of viral replication on admission and during the follow up. At the end of the follow up a clearance of HBsAg from serum was observed in four patients and a clearance of anti-HCV in one of them. In two patients after clearance of HBsAg, evidence of occult HBV infection was observed, at times associated with a hepatic flare. None of the four patients with HIV/HBV coinfection lost HBsAg and none of the 82 with HIV/HCV coinfection lost anti-HCV during the follow up. In anti-HIV positive patients HBV/HCV coinfection is characterized by reciprocal inhibition of viral replication, more evident in HBV expression in plasma and at times by progression to occult HBV infection.
Collapse
Affiliation(s)
- Pietro Filippini
- Department of Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy
| | | | | | | | | | | | | | | | | |
Collapse
|
|
37
|
Wietzke-Braun P, Manhardt LB, Rosenberger A, Uy A, Ramadori G, Mihm S. Spontaneous elimination of hepatitis C virus infection: A retrospective study on demographic, clinical, and serological correlates. World J Gastroenterol 2007; 13:4224-9. [PMID: 17696252 PMCID: PMC4250622 DOI: 10.3748/wjg.v13.i31.4224] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [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 find correlates to spontaneous clearance of hepatitis C virus (HCV) infection, this study compared individuals with self-limited and chronic infection with regard to clinical, demographic, and serological parameters.
METHODS: Sixty-seven anti-HCV positive and repeatedly HCV RNA negative individuals were considered to have resolved HCV infection spontaneously. To determine the viral genotype these patients had been infected with HCV serotyping was performed. For comparison reasons, 62 consecutive patients with chronic hepatitis C were enrolled. Cases and controls were compared stratified for age and sex.
RESULTS: Retrospective analysis showed (1) a lower humoral reactivity to HCV in patients with self-limited compared to chronic HCV-infection and (2) that younger age, history of iv drug use, and acute/post-acute hepatitis A or B co-infections, but not viral genotypes, are independent correlates for spontaneous HCV clearance.
CONCLUSION: The stronger humoral reactivity to HCV in patients with persistent infections and in those with a history of iv drug use is supposed to be due to continuous or repeated contact(s) to the antigen. Metachronous hepatitis A or hepatitis B infections might favor HCV clearance.
Collapse
Affiliation(s)
- Perdita Wietzke-Braun
- Department of Gastroenterology and Endocrinology, Georg-August-Universitat, Robert-Koch-Strasse 40, Gottingen 37075, Germany
| | | | | | | | | | | |
Collapse
|
|
38
|
Coppola N, Genovese D, Pisaturo M, Taffon S, Argentini C, Pasquale G, Sagnelli C, Piccinino F, Rapicetta M, Sagnelli E. Acute hepatitis with severe cholestasis and prolonged clinical course due to hepatitis A virus Ia and Ib coinfection. Clin Infect Dis 2007; 44:e73-e77. [PMID: 17407028 DOI: 10.1086/513430] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2006] [Accepted: 01/27/2007] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Acute viral hepatitis due to hepatitis A virus is a self-limited illness that infrequently has a severe clinical course. METHODS We analyzed the virological characteristics of acute hepatitis A in a patient with a severe clinical presentation (peak total and conjugated bilirubin levels, 65.5 mg/dL and 40.1 mg/dL, respectively) and a course of disease that lasted 7 months. RESULTS Hepatitis A virus sequencing revealed coinfection with 2 subgenotypes of hepatitis A virus (Ia and Ib) as etiological factors of the illness. CONCLUSIONS Hepatitis A virus Ia and Ib coinfection may have accounted for the prolonged and severe course of illness.
Collapse
Affiliation(s)
- Nicola Coppola
- Department of Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
39
|
Dai CY, Huang JF, Hsieh MY, Lee LP, Ho CK, Chuang WL, Yu ML. The role of gender on clearance of hepatitis C virus: a different story in an area endemic for hepatitis B and C. Gut 2007; 56:737-738. [PMID: 17440195 PMCID: PMC1942145 DOI: 10.1136/gut.2006.116384] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
|