|
1
|
Rzymski P, Brzdęk M, Dobrowolska K, Poniedziałek B, Murawska-Ochab A, Zarębska-Michaluk D, Flisiak R. Like a Rolling Stone? A Review on Spontaneous Clearance of Hepatitis C Virus Infection. Viruses 2024; 16:1386. [PMID: 39339862 PMCID: PMC11435954 DOI: 10.3390/v16091386] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 08/23/2024] [Accepted: 08/29/2024] [Indexed: 09/30/2024] Open
Abstract
Elimination of hepatitis C virus (HCV) without the need for medical intervention, known as spontaneous clearance (SC), occurs at a significantly lower rate than in the case of hepatitis B virus infection and only in selected individuals, such as reportedly in Keith Richards, a guitarist of The Rolling Stones. The present paper provides an updated narrative review of the research devoted to the phenomenon in order to identify and discuss the demographic, lifestyle-related, clinical, viral genotype-related, and host genetic factors underpinning the SC occurrence. The body of evidence indicates that the likelihood of SC is decreased in older individuals, men, Black people, HIV-coinfected subjects, and intravenous drug and alcohol users. In turn, HBV coinfection and specific polymorphism of the genes encoding interferon lambda 3 (particularly at rs8099917) and interferon lambda 4 (particularly at rs12979860) and HLA genes increase the odds of SC. Numerous other host-specific genetic factors could be implicated in SC, but the evidence is limited only to certain ethnic groups and often does not account for confounding variables. SC of HCV infection is a complex process arising from a combination of various factors, though a genetic component may play a leading role in some cases. Understanding factors influencing the likelihood of this phenomenon justifies better surveillance of high-risk groups, decreasing health inequities in particular ethnic groups, and may guide the development of a prophylactic vaccine, which at present is not available, or novel therapeutic strategies. Further research is needed to elucidate the exact mechanisms underlying SC and to explore potential interventions that could enhance this natural antiviral response.
Collapse
Affiliation(s)
- Piotr Rzymski
- Department of Environmental Medicine, Poznań University of Medical Sciences, 60-806 Poznań, Poland
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, 25-317 Kielce, Poland
| | | | - Barbara Poniedziałek
- Department of Environmental Medicine, Poznań University of Medical Sciences, 60-806 Poznań, Poland
| | | | - Dorota Zarębska-Michaluk
- Department of Infectious Diseases and Allergology, Jan Kochanowski University, 25-317 Kielce, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland
| |
Collapse
|
|
2
|
Singh N, Ma M, Montano-Loza AJ, Bhanji RA. Learning from a rare phenomenon — spontaneous clearance of chronic hepatitis C virus post-liver transplant: A case report. World J Hepatol 2022; 14:456-463. [PMID: 35317181 PMCID: PMC8891670 DOI: 10.4254/wjh.v14.i2.456] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 02/26/2021] [Accepted: 02/10/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) can lead to chronic liver damage resulting in cirrhosis and hepatocellular carcinoma. Spontaneous clearance of HCV has been documented after an acute infection in 20%-45% of individuals. However, spontaneously resolved chronic hepatitis C following liver transplant (LT) is rare and has been documented only in a few case reports. The phenomenon of spontaneous clearance of chronic hepatitis C occurs together with other meaningful events, which are typically associated with significant changes in the host immunity.
CASE SUMMARY We report three cases of spontaneous resolution of chronic hepatitis C following liver transplantation. These patients either failed or had no HCV treatment prior to transplant, but had spontaneous resolution of HCV post-LT as documented by undetectable polymerase chain reaction (PCR). Diagnosis of HCV was based on viremia through PCR or liver biopsy. All three patients currently undergo surveillance and have no recurrence of HCV.
CONCLUSION Examining each patient’s clinical course, we learned about many viral, host and cellular-factors that may have enhanced the host’s immunity leading to spontaneous clearance of HCV. Though HCV treatment has excellent cure rates, understanding this mechanism may provide clinicians with insights regarding timing and duration of treatment.
Collapse
Affiliation(s)
- Noreen Singh
- Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton T6G 2X8, Alberta, Canada
| | - Mang Ma
- Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton T6G 2X8, Alberta, Canada
| | - Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton T6G 2X8, Alberta, Canada
| | - Rahima A Bhanji
- Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton T6G 2X8, Alberta, Canada
| |
Collapse
|
|
3
|
Guenifi W, Gasmi A, Lacheheb A. Epidemiological and Clinical Factors Associated with Spontaneous Clearance of Hepatitis C Virus. Middle East J Dig Dis 2021; 13:321-327. [PMID: 36606021 PMCID: PMC9489441 DOI: 10.34172/mejdd.2021.241] [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] [Received: 08/19/2020] [Accepted: 01/28/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND The risk of chronicity is high after acute hepatitis C. The infection remains limited and spontaneously resolves in an average of 30% of subjects. Such subjects are considered recovered and do not require any medical care. This study aims to evaluate the epidemiological and clinical factors associated with spontaneous viral clearance. METHODS We conducted a descriptive retrospective study on patients' files managed for a positive hepatitis C serology who benefited from the research of serum viral RNA by molecular biology. RESULTS The study collected 429 usable files. The mean age of the patients was 50.21 years, and the sex ratio was 0.98. Spontaneous viral clearance was estimated at 17.2%. The univariate analysis showed that clearance was significantly greater in subjects under the age of 50 years, patients without type 2 diabetes, patients co-infected with hepatitis B virus, patients with transfusion, and those diagnosed fortuitously. Multivariate analysis confirmed the relationship between diabetes and the circumstances of the diagnosis. The relationship in the case of hepatitis B co-infection was very close to the statistical significance level (p=0.055). CONCLUSION The presence of hepatitis B co-infection in patients with positive hepatitis C serology predicts a high probability of having spontaneous clearance. However, advanced age and the existence of a history of blood transfusion, type 2 diabetes or suggestive signs of liver damage are associated with persistent viremia.
Collapse
Affiliation(s)
- Wahiba Guenifi
- Department of infectious diseases, Faculty of medicine, University FERHAT Abbes, Setif 1-Algeria
| | - Abdelkader Gasmi
- Department of infectious diseases, Faculty of medicine, University FERHAT Abbes, Setif 1-Algeria
| | - Abdelmadjid Lacheheb
- Department of infectious diseases, Faculty of medicine, University FERHAT Abbes, Setif 1-Algeria
| |
Collapse
|
|
4
|
Giang J, Harrison DS, Hansen BK, Fried MW, Darling JM. Killing Two Birds With No Stone. Clin Liver Dis (Hoboken) 2021; 17:371-374. [PMID: 34136144 PMCID: PMC8177831 DOI: 10.1002/cld.1064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Revised: 10/13/2020] [Accepted: 10/25/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Jane Giang
- Department of PharmacyThe University of North Carolina at Chapel HillChapel HillNC
| | - Dawn S. Harrison
- School of MedicineDivision of Gastroenterology and HepatologyThe University of North Carolina at Chapel HillChapel HillNC
| | | | - Michael W. Fried
- School of MedicineDivision of Gastroenterology and HepatologyThe University of North Carolina at Chapel HillChapel HillNC
| | - Jama M. Darling
- School of MedicineDivision of Gastroenterology and HepatologyThe University of North Carolina at Chapel HillChapel HillNC
| |
Collapse
|
|
5
|
Mori Ubaldini F, Stratta RJ, Nunez M. Delayed spontaneous hepatitis C virus elimination in a renal transplant patient following graft rejection. Transpl Infect Dis 2019; 21:e13079. [PMID: 30882950 DOI: 10.1111/tid.13079] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Revised: 02/10/2019] [Accepted: 03/03/2019] [Indexed: 02/03/2023]
Abstract
While elimination of the hepatitis C virus (HCV) following acute infection is not uncommon, spontaneous clearance once the infection becomes chronic is extremely rare. The mechanisms involved in the clearance of chronic HCV infection without intervening antiviral therapy are not well known. Herein we describe a case of a renal transplant recipient who acquired HCV infection while immunosuppressed, experienced a rapid histological progression, and thereafter cleared the virus spontaneously long after withdrawal of immunosuppression following kidney graft rejection and failure. We review the literature and summarize the reports of spontaneous clearance of chronic HCV infection in various settings.
Collapse
Affiliation(s)
- Francesca Mori Ubaldini
- Section on Infectious Diseases, Department of Internal Medicine, Wake Forest School of Medicine, Winston Salem, North Carolina
| | - Robert J Stratta
- Department of Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina
| | - Marina Nunez
- Section on Infectious Diseases, Department of Internal Medicine, Wake Forest School of Medicine, Winston Salem, North Carolina
| |
Collapse
|
|
6
|
Papadopoulos N, Papavdi M, Pavlidou A, Konstantinou D, Kranidioti H, Kontos G, Koskinas J, Papatheodoridis GV, Manolakopoulos S, Deutsch M. Hepatitis B and C coinfection in a real-life setting: viral interactions and treatment issues. Ann Gastroenterol 2018; 31:365-370. [PMID: 29720863 PMCID: PMC5924860 DOI: 10.20524/aog.2018.0255] [Citation(s) in RCA: 5] [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: 10/09/2017] [Accepted: 02/18/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Only limited data concerning hepatitis B (HBV) and C viruses (HCV) coinfection are available. Direct-acting antivirals (DAAs) may be more effective for HCV clearance than interferon (IFN)-based regimens with a risk of HBV reactivation. METHODS We retrospectively enrolled 40 HBV/HCV-coinfected patients to evaluate their clinical profile and treatment outcomes. RESULTS Chronic dual infection was present in 25/40 (62.5%) patients, acute HCV superinfection in 5/40 (12.5%) patients and acute HBV superinfection in 10/40 (25%). Twenty-five patients (62.5%) were treated: 16/25 (64%) with IFN, 4/25 (16%) with nucleot(s)ide analogs (NUCs) and 5/25 (20%) with DAAs. Of the 16 patients treated with IFN-based therapy, 6 (37.5%) achieved both sustained virological response (SVR) and HBsAg clearance. Of the 4 patients treated with NUCs, one (25%) achieved both SVR and HBsAg clearance. All five patients treated with DAAs (100%) achieved SVR, while one case of HBV reactivation was recorded. Fifteen of the 40 patients (37.5%) did not receive any treatment. Eight of them (53.5%) presented with acute HBV superinfection: spontaneous HCV clearance was recorded in 5/8 (62.5%), while HBsAg clearance occurred in 6/8 (75%). Three of them (20%) presented with acute HCV superinfection; spontaneous HCV clearance was recorded in one of the three (33.5%). The other four patients (26.5%) presented with dual HBV/HCV infection. CONCLUSIONS A significant proportion of patients presented with active HBV replication. Treatment with DAAs seems to be efficacious for HCV eradication. However, clinicians should be aware of HBV reactivation. HBV superinfection may lead to both HBsAg and HCV clearance.
Collapse
Affiliation(s)
- Nikolaos Papadopoulos
- 1 Department of Internal Medicine, 417 Army Share Fund Hospital of Athens (Nikolaos Papadopoulos, Anna Pavlidou), Athens, Greece
| | - Maria Papavdi
- 2 Academic Department of Internal Medicine, Medical School National and Kapodistrian University of Athens, Hippokration Hospital (Maria Papavdi, Dimitris Konstantinou, Hariklia Kranidioti, George Kontos, John Koskinas, Spilios Manolakopoulos, Melanie Deutsch), Athens, Greece
| | - Anna Pavlidou
- 1 Department of Internal Medicine, 417 Army Share Fund Hospital of Athens (Nikolaos Papadopoulos, Anna Pavlidou), Athens, Greece
| | - Dimitris Konstantinou
- 2 Academic Department of Internal Medicine, Medical School National and Kapodistrian University of Athens, Hippokration Hospital (Maria Papavdi, Dimitris Konstantinou, Hariklia Kranidioti, George Kontos, John Koskinas, Spilios Manolakopoulos, Melanie Deutsch), Athens, Greece
| | - Hariklia Kranidioti
- 2 Academic Department of Internal Medicine, Medical School National and Kapodistrian University of Athens, Hippokration Hospital (Maria Papavdi, Dimitris Konstantinou, Hariklia Kranidioti, George Kontos, John Koskinas, Spilios Manolakopoulos, Melanie Deutsch), Athens, Greece
| | - George Kontos
- 2 Academic Department of Internal Medicine, Medical School National and Kapodistrian University of Athens, Hippokration Hospital (Maria Papavdi, Dimitris Konstantinou, Hariklia Kranidioti, George Kontos, John Koskinas, Spilios Manolakopoulos, Melanie Deutsch), Athens, Greece
| | - John Koskinas
- 2 Academic Department of Internal Medicine, Medical School National and Kapodistrian University of Athens, Hippokration Hospital (Maria Papavdi, Dimitris Konstantinou, Hariklia Kranidioti, George Kontos, John Koskinas, Spilios Manolakopoulos, Melanie Deutsch), Athens, Greece
| | - George V. Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital (George V. Papatheodoridis), Athens, Greece
| | - Spilios Manolakopoulos
- 2 Academic Department of Internal Medicine, Medical School National and Kapodistrian University of Athens, Hippokration Hospital (Maria Papavdi, Dimitris Konstantinou, Hariklia Kranidioti, George Kontos, John Koskinas, Spilios Manolakopoulos, Melanie Deutsch), Athens, Greece
| | - Melanie Deutsch
- 2 Academic Department of Internal Medicine, Medical School National and Kapodistrian University of Athens, Hippokration Hospital (Maria Papavdi, Dimitris Konstantinou, Hariklia Kranidioti, George Kontos, John Koskinas, Spilios Manolakopoulos, Melanie Deutsch), Athens, Greece
| |
Collapse
|
|
7
|
Bulteel N, Partha Sarathy P, Forrest E, Stanley AJ, Innes H, Mills PR, Valerio H, Gunson RN, Aitken C, Morris J, Fox R, Barclay ST. Factors associated with spontaneous clearance of chronic hepatitis C virus infection. J Hepatol 2016; 65:266-72. [PMID: 27155531 DOI: 10.1016/j.jhep.2016.04.030] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 04/25/2016] [Accepted: 04/26/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Spontaneous clearance of chronic hepatitis C virus (HCV) infection (CHC) is rare. We conducted a retrospective case-control study to identify rates and factors associated with spontaneous clearance of CHC. METHODS We defined cases as individuals who spontaneously resolved CHC, and controls as individuals who remained chronically infected. We used data obtained on HCV testing between 1994 and 2013 in the West of Scotland to infer case/control status. Specifically, untreated patients with ⩾2 sequential samples positive for HCV RNA ⩾6months apart followed by ⩾1 negative test, and those with ⩾2 positive samples ⩾6months apart with no subsequent negative samples were identified. Control patients were randomly selected from the second group (4/patient of interest). Case notes were reviewed and patient characteristics obtained. RESULTS 25,113 samples were positive for HCV RNA, relating to 10,318 patients. 50 cases of late spontaneous clearance were identified, contributing 241 person-years follow-up. 2,518 untreated, chronically infected controls were identified, contributing 13,766 person-years follow-up, from whom 200 controls were randomly selected. The incidence rate of spontaneous clearance was 0.36/100 person-years follow-up, occurring after a median 50months' infection. Spontaneous clearance was positively associated with female gender, younger age at infection, lower HCV RNA load and co-infection with hepatitis B virus. It was negatively associated with current intravenous drug use. CONCLUSIONS Spontaneous clearance of CHC occurs infrequently but is associated with identifiable host and viral factors. More frequent HCV RNA monitoring may be appropriate in selected patient groups. LAY SUMMARY Clearance of hepatitis C virus infection without treatment occurs rarely once chronic infection has been established. We interrogated a large Scottish patient cohort and found that it was more common in females, patients infected at a younger age or with lower levels of HCV in the blood, and patients co-infected with hepatitis B virus. Patients who injected drugs were less likely to spontaneously clear chronic infection.
Collapse
Affiliation(s)
- Naomi Bulteel
- MRC, University of Glasgow Centre for Virus Research, Glasgow, UK.
| | | | - Ewan Forrest
- The Walton Liver Clinic, Glasgow Royal Infirmary, Glasgow, UK
| | | | - Hamish Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
| | | | - Heather Valerio
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Blood-borne Viruses and Sexually Transmitted Infections Section, Health Protection Scotland, Glasgow, UK
| | - Rory N Gunson
- West of Scotland Specialist Virology Centre, Glasgow Royal Infirmary, Glasgow, UK
| | - Celia Aitken
- West of Scotland Specialist Virology Centre, Glasgow Royal Infirmary, Glasgow, UK
| | - Jude Morris
- Department of Gastroenterology, Southern General Hospital, Glasgow, UK
| | - Ray Fox
- Gartnavel General Hospital, Glasgow, UK
| | | |
Collapse
|
|
8
|
Minami T, Tateishi R, Shiina S, Fujiwara N, Mikami S, Sato M, Uchino K, Enooku K, Asaoka Y, Kondo Y, Yoshida H, Koike K. Spontaneous clearance of serum hepatitis C virus RNA during the clinical course of hepatocellular carcinoma in patients with chronic hepatitis C. Hepatol Res 2014; 44:E32-7. [PMID: 23841664 DOI: 10.1111/hepr.12203] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2012] [Revised: 06/26/2013] [Accepted: 07/07/2013] [Indexed: 02/08/2023]
Abstract
AIM Spontaneous clearance of serum hepatitis C virus (HCV) RNA in chronic HCV carriers is assumed to be rare especially after development of hepatocellular carcinoma (HCC). We analyzed patients with chronic hepatitis C who spontaneously resolved serum HCV RNA after the treatment for HCC. METHODS A database search was performed to identify patients with HCC in whom serum HCV RNA was positive before the treatment for HCC and became negative during the clinical course. Those who received interferon therapy were excluded. RESULTS A total of 1145 patients with HCC who had not received interferon therapy were positive for HCV RNA before the treatment. Among them, five patients (M/F = 4/1) spontaneously resolved viremia during the clinical course, with the incidence rate of at least 0.11%/person-year (95% confidence interval: 0.05%-0.26%). The mean age at the time of negative test for HCV RNA was 77 (range: 52-84). Three and two were infected with HCV genotype 1 and 2, respectively. The mean initial viral load was 9.0 K IU/mL (range: 1.6-31.6). The alanine aminotransferase level decreased to within the normal range in all patients after the clearance of serum HCV RNA. Fibrosis grade of background liver, evaluated according to METAVIR classification, was F1 in 1, F2 in 1, F4 in 2, and unknown in 1. All patients survived more than 7 years after the initial treatment for HCC. CONCLUSION Spontaneous clearance of serum HCV RNA after HCC development possibly occurs even in elderly patients. The prognosis was good probably due to improved inflammation in the liver.
Collapse
Affiliation(s)
- Tatsuya Minami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
9
|
Sagnelli E, Pisaturo M, Martini S, Sagnelli C, Filippini P, Coppola N. Advances in the treatment of hepatitis B virus/hepatitis C virus coinfection. Expert Opin Pharmacother 2014; 15:1337-49. [PMID: 24773464 DOI: 10.1517/14656566.2014.913571] [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] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Patients with chronic hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection are at a high risk of developing liver cirrhosis and hepatocellular carcinoma, and consequently, warrant effective treatment. AREAS COVERED Effective treatment should eradicate HCV infection and inhibit HBV replication but without serious adverse reactions. Careful evaluation of disease progression, predominance of one virus over another, comorbidities and concomitant hepatitis delta virus and/or HIV infection are essential for better therapy choices. In the case of HCV predominance, Peg-interferon plus ribavirin with or without a first-generation directly acting antiviral (DAA) should be the first choice, but future treatments will be DAA-based and interferon-free. In the case of HBV predominance, tenofovir or entecavir should be part of treatment. Patients should be closely monitored for early identification and treatment of HCV or HBV reactivation. EXPERT OPINION High potency and high genetic barrier nucleos(t)ide analogues to inhibit HBV replication have been used for years, with no urgency for new drugs. Several DAAs for interferon-free therapy for HCV eradication will be available in the near future. We hope that the high cost of these drugs will not be a limitation to their use in developing countries. Further investigation of HBV/HCV interaction is needed before and during the administration of new therapies.
Collapse
Affiliation(s)
- Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Division of Infectious Diseases, Second University of Naples , Naples , Italy +39 81 5560885 ; +39 81 5666207 ; ,
| | | | | | | | | | | |
Collapse
|
|
10
|
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: 04/03/2014] [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
|
|
11
|
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
|
|
12
|
Biliotti E, Zacharia S, Grieco S, Spaziante M, Giusto M, Merli M, Gallinaro V, Taliani G. Acute hepatitis B in a patient with OLT during treatment with peg-interferon and ribavirin for hepatitis C recurrence. J Chemother 2012; 24:369-72. [PMID: 23174103 DOI: 10.1179/1973947812y.0000000046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
The course and outcome of acute viral hepatitis in liver transplanted patients with hepatitis C recurrence are unknown. Here we describe a patient who presented with acute hepatitis B infection while on treatment with peg-interferon and ribavirin for hepatitis C recurrence after liver transplantation. A nucleoside analogue was added (entecavir) and the patient cleared hepatitis C virus (HCV) infection and seroconverted to anti-HBs. In this case, the acute hepatitis B virus (HBV) infection might have contributed to the clearance of HCV, the concomitant immunosuppression might have lead to the slow clearance of HBV infection, and the combined antiviral therapy has helped in the resolution of both infections. Hepatitis B vaccination should be recommended in susceptible patients waiting for liver transplantation.
Collapse
Affiliation(s)
- Elisa Biliotti
- Infectious and Tropical Diseases Unit, Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | | | | | | | | | | | | | | |
Collapse
|
|
13
|
Lambotin M, Barth H, Moog C, Habersetzer F, Baumert TF, Stoll-Keller F, Fafi-Kremer S. Challenges for HCV vaccine development in HIV-HCV coinfection. Expert Rev Vaccines 2012; 11:791-804. [PMID: 22913257 DOI: 10.1586/erv.12.52] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
It is estimated that 4-5 million HIV-infected patients are coinfected with HCV. The impact of HIV on the natural course of HCV infection is deleterious. This includes a higher rate of HCV persistence and a faster rate of fibrosis progression. Coinfected patients show poor treatment outcome following standard HCV therapy. Although direct antiviral agents offer new therapeutic options, their use is hindered by potential drug interactions and toxicity in HIV-infected patients under HAART. Overtime, a large reservoir of HCV genotype 1 patients will accumulate in resource poor countries where the hepatitis C treatment is not easily affordable and HIV therapy remains the primary health issue for coinfected individuals. HCV vaccines represent a promising strategy as an adjunct or alternative to current HCV therapy. Here, the authors review the pathogenesis of hepatitis C in HIV-infected patients, with a focus on the impact of HIV on HCV-specific immune responses and discuss the challenges for vaccine development in HIV-HCV coinfection.
Collapse
|
|
14
|
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
|
|
15
|
Raghuraman S, Park H, Osburn WO, Winkelstein E, Edlin BR, Rehermann B. Spontaneous clearance of chronic hepatitis C virus infection is associated with appearance of neutralizing antibodies and reversal of T-cell exhaustion. J Infect Dis 2012; 205:763-71. [PMID: 22293431 DOI: 10.1093/infdis/jir835] [Citation(s) in RCA: 123] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) readily establishes chronic infection with exhaustion of HCV-specific T cells and escape from neutralizing antibodies. Spontaneous recovery from chronic infection is rare and has never to our knowledge been studied immunologically. METHODS We prospectively studied, from prior to infection through >2 years of follow-up, cytokines, HCV-specific T cells, and antibodies, as well as viral sequence evolution in a white male who spontaneously cleared HCV genotype 1a after 65 weeks. RESULTS Significant alanine aminotransferase and plasma cytokine elevation and broad HCV-specific T-cell responses did not result in HCV clearance in the acute phase. Frequency and effector function of HCV-specific T cells decreased thereafter, and HCV titers stabilized as is typical for the chronic phase. HCV clearance after 65 weeks followed the appearance of neutralizing antibodies at week 48 and was associated with reversal of HCV-specific T-cell exhaustion, as evidenced by reduced programmed death-1 (PD-1) expression and improved T-cell function. Clearance occurred without inflammation or superinfection with hepatitis B virus, human cytomegalovirus virus, influenza, and Epstein-Barr virus. CONCLUSIONS T-cell exhaustion is reversible at least in the first 2 years of chronic HCV infection, and this reversion in conjunction with neutralizing antibodies may clear HCV. These findings are relevant for immunotherapy of chronic infections.
Collapse
Affiliation(s)
- Sukanya Raghuraman
- Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Department of Health and Human Services (DHHS), Bethesda, MD, USA
| | | | | | | | | | | |
Collapse
|
|
16
|
Hu ML, Zheng Q, Jiang JJ. Kinetics of immune responses to hepatitis B virus infection. Shijie Huaren Xiaohua Zazhi 2011; 19:1381-1388. [DOI: 10.11569/wcjd.v19.i13.1381] [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
The pathogenesis of hepatitis B is mainly triggered by the host's cellular immune responses to hepatitis B virus (HBV) infection, and the immune responses against the virus depends on the interaction of various immune cells. Current research of immunity to hepatitis B infection mainly focuses on understanding the differences between patients who can control HBV infection and those with persistent infection. In this paper, we analyze how immunological events influence the development of innate and adaptive immunity needed to control HBV infection and explore the mechanisms by which high levels of viral antigens, CD4+ T cells, programmed death 1 (PD-1), the presence of regulatory T cells, and impaired dendritic cell functions maintain the HBV-specific immunological failure.
Collapse
|
|
17
|
Peyrière H, Tatem L, Bories C, Pageaux GP, Blayac JP, Larrey D. Hepatitis After Intravenous Injection of Sublingual Buprenorphine in Acute Hepatitis C Carriers: Report of Two Cases of Disappearance of Viral Replication After Acute Hepatitis. Ann Pharmacother 2009; 43:973-7. [DOI: 10.1345/aph.1l628] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Objective To report 2 cases of acute hepatitis related to intravenous administration of buprenorphine in hepatitis C–infected patients. Case Summary Two patients, aged 33 and 50 years, respectively, who were hepatitis C virus (HCV) carriers were treated with sublingual buprenorphine 8 mg/day for addiction. Several years after initiation of buprenorphine, they were hospitalized because of clinical hepatitis with jaundice that developed after intravenous injection of buprenorphine. Serum alanine aminotransferase rose to 100 times the upper limit of normal (ULN) in the first patient and to 21 times the ULN in the second. As cofactors, the first patient had consumed alcohol, and the second patient took aspirin 600 mg in addition to the injection of buprenorphine 20 mg 4 days before the onset of jaundice. After stopping the intravenous injections, both patients continued sublingual buprenorphine therapy, with no relapse of hepatitis. Interestingly, in these 2 patients, buprenorphine-induced hepatitis was followed by the disappearance of HCV RNA. Discussion Most cases of hepatotoxicity related to buprenorphine have occurred in hepatitis C–infected patients. The main mechanism for buprenorphine-induced hepatitis is a mitochondrial defect, exacerbated by cofactors with additional potential to induce mitochondria dysfunction (eg, HCV, alcohol, concomitant medications). According to the Naranjo probability scale, buprenorphine was found to be the probable cause of acute hepatitis in both patients. In addition, we assessed the relationship between intravenous buprenorphine and acute hepatitis using 2 scales for causality assessment of hepatotoxicity (the Council for International Organizations of Medical Sciences scale and the Maria & Victorino scale). The diagnosis of intravenous buprenorphine-induced hepatitis was classified as probable in both cases. In addition, these 2 cases illustrate that acute hepatitis in a carrier of chronic HCV may occasionally facilitate the clearance of virus. Conclusions Although buprenorphine is well tolerated when used at recommended sublingual doses, patients should be informed about the risk of acute hepatitis with misuse of the drug by the intravenous route. These cases illustrate that, in carriers of chronic HCV, acute hepatitis may modify the host's immunotolerance and facilitate clearance of the virus.
Collapse
Affiliation(s)
- Hélène Peyrière
- Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier, France
| | - Ludmilla Tatem
- Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital
| | - Camille Bories
- Department of Gastro-Enterology and Hepatology and Liver Transplantation, Saint-Eloi Hospital, Montpellier
| | | | | | - Dominique Larrey
- Department of Gastro-Enterology and Hepatology and Liver Transplantation, Saint-Eloi Hospital
| |
Collapse
|
|
18
|
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; 49:1090-7. [PMID: 19263473 DOI: 10.1002/hep.22794] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [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
|
|
19
|
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
|
|
20
|
Clearance of chronic HCV infection during acute delta hepatitis. Infection 2007; 37:159-62. [PMID: 18084714 DOI: 10.1007/s15010-007-7204-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2007] [Accepted: 09/12/2007] [Indexed: 02/08/2023]
Abstract
The course of chronic hepatitis C in acute HDV/HBV superinfection is unknown. Here, we report a patient with chronic hepatitis C who cleared HCV during acute self-limited hepatitis B/D superinfection. Recovery from HCV was associated with the appearance of a strong and multispecific HDV-specific memory CD4+ and CD8+ T cell response - but only weak HCV-specific CD4+ T cell responses. These data suggest that HCV can be cleared by bystander mechanisms during acute infections with other pathogens which may be considered in the development of immunotherapies for hepatitis C.
Collapse
|
|
21
|
Rallón NI, Soriano V, Benito JM. [Adaptive cell immune response against the hepatitis C virus infection]. Med Clin (Barc) 2007; 129:469-76. [PMID: 17953913 DOI: 10.1157/13111005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Hepatitis C virus (HCV) infects around 175 million people worldwide and is one of the leading causes of chronic liver disease. Less than one third of patients infected with HCV are able to spontaneously clear the virus during acute infection, while most patients evolve to chronic infection. Control of viral replication has been associated to the cellular component of the host immune response. It is not fully understood what distinguish a successful cellular immune response. An integral interpretation of the numerous experimental findings may allow a better understanding of the immune mechanisms involved in the inability of the immune system to successfully control chronic HCV infection.
Collapse
Affiliation(s)
- Norma Ibón Rallón
- Laboratorio de Biología Molecular, Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, España
| | | | | |
Collapse
|
|
22
|
Isaguliants MG. Functionality of the immune system in patients with chronic hepatitis C: trial by superinfections and vaccinations. Expert Rev Vaccines 2007; 6:527-37. [PMID: 17669007 DOI: 10.1586/14760584.6.4.527] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Viral infections, specifically chronic, markedly influence the host response to subsequent infections and vaccinations. Does this apply to chronic hepatitis C (CHC)? The review considers this question with implications for the immune status and functionality of the immune system of a chronically HCV-infected host. The data collected here indicate that CHC may increase the risk of viral superinfections and modify their course by immunocompromising the host. Patients with CHC do not lose the 'memory' of previous infections and vaccinations but, apparently, have problems with building such immunity anew, as illustrated by their impaired response to hepatitis A and B vaccinations. This underlines the necessity of extra protection of CHC patients against blood-borne diseases, hepatitis A, possibly also varicella, influenza, tetanus, and diphtheria - immunity to which, in the Western population, appears to falter. Such immune protection has to be adapted to selective impairments of immune response characteristic to CHC. Some approaches to this are reviewed here and more need to be elaborated. Special attention has to be given to CHC patients who do not respond to common vaccines; further studies in this field are of great interest.
Collapse
Affiliation(s)
- Maria G Isaguliants
- Swedish Institute for Infectious Disease Control, Department of Virology, Stockholm, SE 17182, Sweden; and, Ivanovsky Institute of Virology, Moscow, 123098, Russia.
| |
Collapse
|
|
23
|
Abstract
An inefficient cellular immune response likely leads to chronic hepatitis C virus (HCV) infection. Resolution of chronic HCV infection in the absence of treatment is a rare occurrence. We report the case of a 39-year old white male with a 17-year history of chronic HCV infection, who eradicated HCV following a serious illness due to co-infection with Babesia (babesiosis), Borriela Borgdorferi (Lyme disease) and Ehrlichia (human granulocytic ehrlichiosis). We hypothesize that the cellular immune response mounted by this patient in response to his infection with all three agents but in particular Babesia was sufficient to eradicate HCV.
Collapse
Affiliation(s)
- Valerie Byrnes
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | | | | |
Collapse
|
|
24
|
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
|
|
25
|
Coffin CS, Mulrooney-Cousins PM, Lee SS, Michalak TI, Swain MG. Profound suppression of chronic hepatitis C following superinfection with hepatitis B virus. Liver Int 2007; 27:722-6. [PMID: 17498260 DOI: 10.1111/j.1478-3231.2007.01477.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) and hepatitis C virus (HCV) share similar transmission routes; thus, coinfection is frequent. The consequences of acute HBV infection in patients with chronic hepatitis C are unknown. METHODS We describe a 47-year-old male with chronic hepatitis C who acquired HBV and then spontaneously and apparently completely cleared HCV but developed chronic hepatitis B. Five serum samples collected over 14 months and lymphoid cells obtained after acquiring HBV were tested for HCV and HBV by both standard assays and ultra-sensitive polymerase chain reaction/nucleic acid hybridization (PCR/NAH) (sensitivity approximately 2 IU/ml). RESULTS After superinfection with HBV, HBV surface antigen-positive chronic hepatitis developed with readily detectable HBV DNA. All sera collected after acquisition of HBV, which tested negative for HCV RNA by standard laboratory assay, were positive for HCV genomes when analysed by PCR/NAH. Peripheral lymphoid cells carried HBV DNA and covalently closed circular DNA, but were negative for HCV. CONCLUSIONS This is the first reported case of profound suppression of chronic hepatitis C after superinfection with HBV and establishment of chronic hepatitis B. It is hypothesized that HBV infection precipitated generalized and/or virus-specific cellular immune responses that profoundly suppressed HCV replication and yet failed to inhibit progression to chronic hepatitis B.
Collapse
Affiliation(s)
- Carla S Coffin
- Liver Unit, Division of Gastroenterology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
| | | | | | | | | |
Collapse
|
|
26
|
Ersoz G, Tekin F, Bademkiran F. Chronic inflammatory demyelinating polyneuropathy in an HCV-related cirrhotic patient with acute hepatitis B superinfection. Eur J Intern Med 2007; 18:257. [PMID: 17449405 DOI: 10.1016/j.ejim.2006.09.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2006] [Revised: 07/25/2006] [Accepted: 09/21/2006] [Indexed: 11/28/2022]
Affiliation(s)
- Galip Ersoz
- Ege University Medical School, Department of Gastroenterology, Izmir, Turkey
| | | | | |
Collapse
|
|
27
|
Hogan LH, Co DO, Karman J, Heninger E, Suresh M, Sandor M. Virally activated CD8 T cells home to Mycobacterium bovis BCG-induced granulomas but enhance antimycobacterial protection only in immunodeficient mice. Infect Immun 2006; 75:1154-66. [PMID: 17178783 PMCID: PMC1828579 DOI: 10.1128/iai.00943-06] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
The effect of secondary infections on CD4 T-cell-regulated chronic granulomatous inflammation is not well understood. Here, we have investigated the effect of an acute viral infection on the cellular composition and bacterial protection in Mycobacterium bovis strain bacille Calmette-Guérin (BCG)-induced granulomas using an immunocompetent and a partially immunodeficient murine model. Acute lymphocytic choriomeningitis virus (LCMV) coinfection of C57BL/6 mice led to substantial accumulation of gamma interferon (IFN-gamma)-producing LCMV-specific T cells in liver granulomas and increased local IFN-gamma. Despite traffic of activated T cells that resulted in a CD8 T-cell-dominated granuloma, the BCG liver organ load was unaltered from control levels. In OT-1 T-cell-receptor (TCR) transgenic mice, ovalbumin (OVA) immunization or LCMV coinfection of BCG-infected mice induced CD8 T-cell-dominated granulomas containing large numbers of non-BCG-specific activated T cells. The higher baseline BCG organ load in this CD8 TCR transgenic animal allowed us to demonstrate that OVA immunization and LCMV coinfection increased anti-BCG protection. The bacterial load remained substantially higher than in mice with a more complete TCR repertoire. Overall, the present study suggests that peripherally activated CD8 T cells can be recruited to chronic inflammatory sites, but their contribution to protective immunity is limited to conditions of underlying immunodeficiency.
Collapse
Affiliation(s)
- Laura H Hogan
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, 1300 University Ave., Madison, WI 53706, USA
| | | | | | | | | | | |
Collapse
|
|
28
|
Jessner W, Strasser M, Graziadei I, Berr F, Vogel W. Sustained remission of chronic hepatitis C after acute hepatitis B superinfection. ACTA ACUST UNITED AC 2006; 38:818-21. [PMID: 16938741 DOI: 10.1080/00365540600606523] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
We observed acute HBV superinfection on chronic HCV genotype 1 infection in a 29-y-old injection drug user. On presentation HCV-RNA was already negative and remained so for at least 7 months thereafter. We speculate that clearance of HCV-HBV coinfected cells by HBV-specific immunity might be a mechanism of HCV eradication.
Collapse
Affiliation(s)
- Wolfgang Jessner
- Department of Gastroenterology and Hepatology, Medical University Innsbruck, Austria.
| | | | | | | | | |
Collapse
|
|
29
|
Lin L, Verslype C, van Pelt JF, van Ranst M, Fevery J. Viral interaction and clinical implications of coinfection of hepatitis C virus with other hepatitis viruses. Eur J Gastroenterol Hepatol 2006; 18:1311-9. [PMID: 17099381 DOI: 10.1097/01.meg.0000243881.09820.09] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Coinfection with other hepatitis viruses modifies the viral profile in serum and leads to more liver damage and more rapid progression during the course of hepatitis C virus infection. The viral interference is not only carried out by virus-virus or by virus-cell interactions but also by an enhanced immune response. A superinfecting viral infection does not crossactivate protective immune responses to the pre-existing virus albeit the latter can become undetectable. The induced cytokine stimulation might enhance the hepatic inflammation. Moreover, hepatitis B virus coinfection increases the risk of development of hepatocellular carcinoma in hepatitis C virus patients through common necro-inflammatory pathways or by direct oncogenic activity of hepatitis B virus. Viral interaction also complicates the management of the coinfection because hepatitis C virus impairs the humoral response to hepatitis A virus and hepatitis B virus vaccines, and because pharmacological suppression of hepatitis C virus endangers dually infected patients with reactivation of coinfected hepatitis B virus. Optimized strategies and follow-up are thus necessary in the treatment of infection with multiple viruses. It seems thus necessary to look for markers of hepatitis B virus and/or hepatitis D virus infection in chronic hepatitis patients positive for hepatitis C virus antibodies but negative for hepatitis C virus RNA, and equally well to search for hepatitis C virus RNA in HBsAg-negative/anti-HBc-positive patients with a low level of serum hepatitis B virus DNA.
Collapse
Affiliation(s)
- Lan Lin
- Department of Hepatology, University Hospital Gasthuisberg, Leuven, Belgium
| | | | | | | | | |
Collapse
|
|
30
|
Deterding K, Tegtmeyer B, Cornberg M, Hadem J, Potthoff A, Böker KHW, Tillmann HL, Manns MP, Wedemeyer H. Hepatitis A virus infection suppresses hepatitis C virus replication and may lead to clearance of HCV. J Hepatol 2006; 45:770-8. [PMID: 17034895 DOI: 10.1016/j.jhep.2006.07.023] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2006] [Revised: 06/29/2006] [Accepted: 07/06/2006] [Indexed: 12/24/2022]
Abstract
BACKGROUND/AIMS The significance of hepatitis A virus (HAV) super-infection in patients with chronic hepatitis C had been a matter of debate. While some studies suggested an incidence of fulminant hepatitis A of up to 35%, this could not be confirmed by others. METHODS We identified 17 anti-HCV-positive patients with acute hepatitis A from a cohort of 3170 anti-HCV-positive patients recruited at a single center over a period of 12 years. RESULTS Importantly, none of the anti-HCV-positive patients had a fulminant course of hepatitis A. HCV-RNA was detected by PCR in 84% of the anti-HCV-positive/anti-HAV-IgM-negative patients but only in 65% of anti-HCV-positive patients with acute hepatitis A (p=0.03), indicating suppression of HCV replication during hepatitis A. Previous HAV infection had no effect on HCV replication. After recovery from hepatitis A, an increased HCV replication could be demonstrated for 6 out of 9 patients with serial quantitative HCV-RNA values available while 2 patients remained HCV-RNA negative after clearance of HAV throughout follow-up of at least 2 years. CONCLUSIONS HAV super-infection is associated with decreased HCV-RNA replication which may lead to recovery from HCV in some individuals. Fulminant hepatitis A is not frequent in patients with chronic hepatitis C recruited at a tertiary referral center.
Collapse
Affiliation(s)
- Katja Deterding
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg Str.1, 30625 Hannover, Germany
| | | | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Lauer GM, Kim AY. Spontaneous resolution of chronic hepatitis C virus infection: are we missing something? Clin Infect Dis 2006; 42:953-4. [PMID: 16511758 DOI: 10.1086/500944] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2005] [Accepted: 12/12/2005] [Indexed: 01/05/2023] Open
|
|
32
|
Boni C, Amadei B, Urbani S, Fisicaro P, Zerbini A, Mori C, Missale G, Bertoni R, Azzurri A, Del Prete G, Ferrari C. Antiviral CD8-mediated responses in chronic HCV carriers with HBV superinfection. Hepatology 2004; 40:289-99. [PMID: 15368433 DOI: 10.1002/hep.20332] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatitis B virus (HBV) superinfection in chronic hepatitis C represents a natural model to investigate whether or not hepatitis C virus (HCV) can influence priming and maturation of antiviral T cells; whether or not HBV superinfection, which is known to determine control of HCV replication, can restore HCV-specific T cell responsiveness; and whether or not cytokines stimulated by HBV infection can contribute to HCV control. To address these issues, the function of CD8 cells specific for HBV and HCV was studied longitudinally in two chronic HCV patients superinfected with HBV. Patients with acute hepatitis B were also examined. Frequency and function of HBV tetramer+ CD8 cells were comparable in patients acutely infected with HBV with or without chronic HCV infection. HBV-specific CD8 cell function was efficiently expressed irrespective of serum HCV-RNA levels. Moreover, fluctuations of HCV viremia at the time of HBV superinfection were not associated with evident changes of CD8 responsiveness to HCV. Finally, no correlation was found between serum levels of interferon alpha, interleukin (IL)-12, IL-10, or IL-18 and control of HCV replication. In conclusion, HCV did not affect the induction of primary and memory HBV-specific CD8 responses. HCV-specific CD8 responses were undetectable when HCV-RNA was negative, showing that inhibition of HCV replication in the setting of a HBV superinfection was not sufficient to induce a restoration of CD8 reactivity against HCV.
Collapse
Affiliation(s)
- Carolina Boni
- Divisione Malattie Infettive ed Epatologia (Division of Infectious Diseases and Hepatology), Azienda Ospedaliera Universitaria di Parma, Parma, Italy
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|