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Towards the elimination of hepatitis C: identifying the infected population, and remaining hepatitis C related risks after successful treatment
Örebro University, School of Medical Sciences.ORCID iD: 0000-0001-6711-0499
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Chronic Hepatitis C virus (HCV) infection can lead to liver fibrosis and cirrhosis with increased risk of hepatocellular carcinoma (HCC) and liver failure. The World Health Organisation (WHO) has set a goal to eliminate viral hepatitis as a global health threat by 2030. To reach this goal for HCV we need to prevent new infections and identify and treat the infected population. Individuals with pre-treatment cirrhosis still have an elevated risk for HCC after HCV cure. This thesis aims to assess the health outcomes after cured HCV infection, study HCV prevalence and find a way to identify undiagnosed infections.

In Paper I, 97 patients were followed through clinical visits (n=54) or through national registers (n=43) to study the long-term outcomes after cure from HCV and to assess the presence and impact of occult HCV infection (OCI). Three non-cirrhotic patients were diagnosed with HCC 8-11 years after HCV cure. Two patients had OCI at 8-9 years after cure. They had liver fibrosis stage 2, but no association with HCC. In Paper II, pregnant women (n=4,108) and partners (n=1,027) at antenatal clinics in southern Stockholm and Örebro County were tested for HCV and interviewed about risk factors to assess prevalence and evaluate screening strategies to identify undiagnosed infections. Anti-HCV prevalence was 0.7% and 0.4% were viraemic. The most effective risk factor-based screening was to ask for drug use, country of birth, and having a partner with HCV. Paper III presents a nationwide register study of the risk of extrahepatic cancer (EHC) the first 3 years after HCV treatment with direct acting antiviral (DAAs). We compared 4,013 DAA-treated, with 3,071 interferon-treated and 12,601 untreated patients. No increased risk for EHC was found after adjustments for age and comorbidities. An increased EHC risk in DAA-treated compared with general population was seen. Paper IV presents a register based study of the risk of HCC and association with pre-treatment liver stiffness measurement (LSM) in 7,227 HCV infected patients cured by DAAs. We found that pre-treatment LSM values correlated well with HCC risk. The incidence rate for patients with LSM values ≥12.5 kPa and <12.5 kPa was 1.6 and 0.15/100 person years, respectively.

To conclude, cured HCV infection usually leads to regression of fibrosis. The DAAs are safe and highly effective against HCV. However, the HCC risk remains elevated for many years after cure in cirrhotic and sometimes in non-cirrhotic patients. Furthermore, HCV screening of pregnant women and partners is useful to identify patients who would benefit from therapy.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2022. , p. 93
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 259
Keywords [en]
HCV, HCC, epidemiology, MTCT, pregnancy, DAA, OCI
National Category
General Practice
Identifiers
URN: urn:nbn:se:oru:diva-97409ISBN: 9789175294254 (print)OAI: oai:DiVA.org:oru-97409DiVA, id: diva2:1636565
Public defence
2022-04-29, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2022-02-10 Created: 2022-02-10 Last updated: 2022-05-05Bibliographically approved
List of papers
1. Long-term follow-up after cure from chronic hepatitis C virus infection shows occult hepatitis and a risk of hepatocellular carcinoma in noncirrhotic patients
Open this publication in new window or tab >>Long-term follow-up after cure from chronic hepatitis C virus infection shows occult hepatitis and a risk of hepatocellular carcinoma in noncirrhotic patients
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2019 (English)In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 31, no 4, p. 506-513Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Curing hepatitis C virus (HCV) infection primarily aims to prevent severe liver complications. Our objectives were to investigate the long-term presence and impact of occult HCV infection (OCI) and to study the outcomes in terms of liver disease after virological cure.

PATIENTS AND METHODS: A total of 97 patients with achieved sustained virological response (SVR) during 1990-2005 were followed either by a clinical follow-up (FU) visit with blood sampling and liver elastography (n=54) or through national registries for outcomes (n=43). To diagnose OCI among patients with SVR, a highly sensitive method was used to detect HCV-RNA traces in whole blood. The FU duration was a median of 10.5 years, with samples up to 21.5 years after the end of treatment (EOT).

RESULTS: The majority of patients [52 (96%)] were HCV-RNA negative at FU, and regression of fibrosis was statistically significant. OCI was found in two (4%) of them at 8 and 9 years after EOT. These patients had F1 and F2 fibrosis before treatment and F2 at FU, but no other abnormal findings. Three previously noncirrhotic men were diagnosed with hepatocellular carcinoma 8-11 years after EOT.

CONCLUSION: Occult infection could be detected many years after the achievement of SVR but was not associated with the serious liver disease. The majority had persistent viral eradication and regression of fibrosis after SVR. However, an increased risk of hepatocellular carcinoma may persist in the long term after SVR even in noncirrhotic patients. Further studies with FU after direct-acting antiviral therapy and on the long-term impact after cure are needed.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2019
Keywords
chronic hepatitis C, long-term follow-up, sustained virological response
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-70277 (URN)10.1097/MEG.0000000000001316 (DOI)000480690600014 ()30461522 (PubMedID)2-s2.0-85060762793 (Scopus ID)
Funder
Stockholm County CouncilSwedish Research CouncilSwedish Cancer Society
Note

Funding Agency:

Research Committee of Region Örebro County Council  OLL-522501  OLL-590001

Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2025-02-11Bibliographically approved
2. Anti-HCV prevalence and risk factor-based screening for hepatitis C in pregnant women and their partners in Sweden
Open this publication in new window or tab >>Anti-HCV prevalence and risk factor-based screening for hepatitis C in pregnant women and their partners in Sweden
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2020 (English)In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 52, no 11, p. 776-785Article in journal (Refereed) Published
Abstract [en]

Background: The hepatitis C virus (HCV) prevalence in Sweden is estimated to be <0.5%, but unclear in pregnant women. The dominating route of transmission is drug use (DU), blood transfusions constituted a risk before 1992. The aim was to examine the anti-HCV prevalence and risk factors for HCV among pregnant women and their partners to evaluate screening strategies.

Methods: Pregnant women and partners in Örebro County and in southern Stockholm were offered HCV-screening when visiting an antenatal clinic in 2013-2016, and completed a questionnaire concerning the country of birth, knowledge of HCV-status and HCV risk factors.

Results: In Örebro 2,827 pregnant women and 707 partners, and in Stockholm 1,281 pregnant women and 320 partners participated. Anti-HCV was positive in 34 (0.7%) (25 pregnant women) and the associated risk factors were DU (n = 27), partner with HCV (n = 24) and not born in Sweden (n = 8). HCV RNA was positive in 23 (0.4%), 4 previously unknown and 10 who had been lost to follow-up. The most effective risk factor-based screening model for pregnant women included DU, blood transfusions, born in high prevalence country, partner with HCV, resulting in 538 (13%) pregnant women tested with 96% sensitivity, 87% specificity.

Conclusions: In this study of expecting parents in two Swedish regions, the anti-HCV prevalence was 0.7% and 0.4% were viraemic, of which about 60% were previously unknown or lost to follow-up. Awaiting more studies, including cost-benefit analysis evaluating universal screening, we recommend this improved risk factor-based screening model to identify HCV-infected individuals who need follow-up and therapy.

Place, publisher, year, edition, pages
Taylor & Francis, 2020
Keywords
HCV, HCV RNA, pregnancy, MTCT, IDU, risk factor-based
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-84937 (URN)10.1080/23744235.2020.1784456 (DOI)000547624900001 ()32654571 (PubMedID)2-s2.0-85087884129 (Scopus ID)
Funder
Stockholm County Council, SM12152The Karolinska Institutet's Research Foundation
Note

Funding Agencies:

Gilead Nordic Fellowship  01776

Medivir  K1855-2014

Danderyd Hospital 

Grants for research, development and education (ALF) Region Örebro County  OLL-683801 OLL-841771

Available from: 2020-08-25 Created: 2020-08-25 Last updated: 2024-03-05Bibliographically approved
3. Risk of extrahepatic cancer in a nationwide cohort of hepatitis C virus infected persons treated with direct-acting antivirals
Open this publication in new window or tab >>Risk of extrahepatic cancer in a nationwide cohort of hepatitis C virus infected persons treated with direct-acting antivirals
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2021 (English)In: GastroHep, E-ISSN 1478-1239, Vol. 3, no 3, p. 185-195Article in journal (Refereed) Published
Abstract [en]

Background and aims: Direct-acting antivirals (DAAs) against HCV have an immune modulatory effect, this could possibly lead to a decreased tumour control. We, therefore, aimed to assess the risk of extrahepatic cancer (EHC) during and the first years after DAA treatment.

Methods and Results: This is a nationwide cohort study with prospectively collected data for 19 685 persons with HCV, 4013 DAA treated, 3071 interferon (IFN) treated and 12 601 untreated, from 2008 to 2016. Follow-up time was maximum 3 years. The risk for EHC was compared between the groups using Cox regression analyses, with adjustment for age and Charlson Comorbidity Index (CCI). The HCV-infected groups were also compared with matched cohorts without HCV from the general population. In total 341 EHCs were identified, 84, 43 and 214 EHC in the DAA, IFN and untreated group respectively. The EHC risk in DAA treated compared with IFN treated was doubled, but when adjusted for age and CCI the HR was 1.07 (95% CI 0.74-1.56). Compared with the general population, the HR of EHC for the DAA group was 1.45 (CI 1.13-1.86), with the difference remaining statistically significant after adjusting for CCI.

Conclusion: We found no increased risk for EHC associated with DAA therapy after adjustment for age and CCI. An increased risk of EHC in DAA treated compared with the general population was though seen, and attention should be paid to this association in the ageing population with a history of HCV infection.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2021
Keywords
Hepatitis C, HCV, DAA, extrahepatic cancer
National Category
Infectious Medicine
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-95905 (URN)10.1002/ygh2.456 (DOI)
Funder
Region Örebro County, OLL-841771Swedish Cancer SocietyRegion Örebro County, OLL-930212Swedish Cancer Society
Available from: 2021-12-13 Created: 2021-12-13 Last updated: 2022-04-06Bibliographically approved
4. Risk of hepatocellular carcinoma after DAA treatment and association with pretreatment liver stiffness in a national hepatitis C cohort
Open this publication in new window or tab >>Risk of hepatocellular carcinoma after DAA treatment and association with pretreatment liver stiffness in a national hepatitis C cohort
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(English)Manuscript (preprint) (Other academic)
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-98474 (URN)
Available from: 2022-04-06 Created: 2022-04-06 Last updated: 2022-04-07Bibliographically approved

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