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Long-term follow-up after cure from chronic hepatitis C virus infection shows occult hepatitis and a risk of hepatocellular carcinoma in noncirrhotic patients
Örebro University, School of Medical Sciences. Department of Infectious Diseases.
Department of Laboratory Medicine, Division of Clinical Microbiology.
Department of Laboratory Medicine, Division of Clinical Microbiology.
Örebro University, School of Medical Sciences. Clinical Epidemiology Unit; Department of Epidemiology and Public Health, University College London, London, UK. (Clinical Epidemiology and Biostatistics)ORCID iD: 0000-0001-6328-5494
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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. Vol. 31, no 4, p. 506-513
Keywords [en]
chronic hepatitis C, long-term follow-up, sustained virological response
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-70277DOI: 10.1097/MEG.0000000000001316ISI: 000480690600014PubMedID: 30461522Scopus ID: 2-s2.0-85060762793OAI: oai:DiVA.org:oru-70277DiVA, id: diva2:1265281
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: 2022-05-05Bibliographically approved
In thesis
1. Towards the elimination of hepatitis C: identifying the infected population, and remaining hepatitis C related risks after successful treatment
Open this publication in new window or tab >>Towards the elimination of hepatitis C: identifying the infected population, and remaining hepatitis C related risks after successful treatment
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
HCV, HCC, epidemiology, MTCT, pregnancy, DAA, OCI
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-97409 (URN)9789175294254 (ISBN)
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

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Lybeck, CharlotteMontgomery, ScottDuberg, Ann-Sofi

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