DÄ internationalArchive46/2021Declining Numbers of Hepatitis C Virus-Associated Liver Transplantations in Germany

Research letter

Declining Numbers of Hepatitis C Virus-Associated Liver Transplantations in Germany

Dtsch Arztebl Int 2021; 118: 797-8. DOI: 10.3238/arztebl.m2021.0318

Wedemeyer, H; Herzer, K; Serfert, Y; Taubert, R; Trautwein, C; Eurich, D; Strassburg, C P; Lang, M; Weiss, K H; Berg, T; Galle, P R; Heinzow, H; Zeuzem, S; Collaborators

LNSLNS

In Germany, the anti-HCV prevalence in the general population is between 0.2 and 1.9% (1). Infection with the hepatitis C virus (HCV) can result in chronic liver disease, the complications of which are liver cirrhosis and hepatocellular carcinoma (HCC). Thus, for many years, HCV infection was one of the most common indications for liver transplantation secondary to decompensated cirrhosis or HCC. Over the past ten years, between 800 and 1200 liver transplantations have been performed in Germany each year. With the introduction of highly effective and safe direct antiviral agents (DAAs) against HCV in 2014, the question arose as to what extent the need for HCV-related liver transplantations has decreased since then. In an initial analysis involving eleven German transplant centers, we already found evidence in 2016 that the proportion of patients with HCV-related liver transplantation was in decline after the introduction of DAA in Germany (2). In this paper we present a follow-up of this study.

Methods

Questionnaire-based retrospective data on waiting lists and transplantations performed between 2010 and 2020 were collected at eleven German transplant centers: the number of adult (≥18 years) patients (with and without HCV infection) on the waiting list for liver transplantation, the number of liver transplanted patients (with and without HCV infection), the number of patients on the waiting list receiving antiviral treatment with DAA, as well as the number of cured patients, and the number of therapy discontinuations. More than 55% of all liver transplantations performed in Germany were assessed. The questionnaire was anonymized and did not contain any personal patient data, so that an ethics opinion was not required for this evaluation.

Results

Decline in the number of listed and transplanted patients with hepatitis C

At the centers that participated in the survey, between 632 and 1135 new adult patients were added to the list for liver transplantation each year between 2010 and 2020, and between 434 and 687 patients underwent transplantation. This amounts to more than half of the total number of listed or transplanted patients in Germany during this period. During the study period, between 110 and 285 patients on the waiting list died each year. During the same period, between 43 and 187 new adult patients infected with HCV were added to the list each year. The proportion of patients with hepatitis C out of the total number of patients listed is shown in Figure 1a. Between 2010 and 2013, more than 15% of patients were listed due to hepatitis C each year. This figure has fallen steadily over the period 2014 to 2020. In 2020, only 43/734 (5.9%, 95% confidence interval [4.3; 7.7]) of all patients were still listed for hepatitis C. There was also a dramatic decline in patients who were HCV RNA positive at the time of listing (2013: 108/878; 12% [10; 15]; 2020: 13/374; 1.8% [1.0; 2.9]). A similar trend was also evident for patients who had undergone transplantation (Figure 1b). The proportion of HCV RNA-positive patients in 2020 was only 9/435 (2.1% [1.0; 3.7]).

Participating centers during the period 2010–2020
Figure
Participating centers during the period 2010–2020

Antiviral therapy and waiting list

From 2010 to 2013, only a small proportion of patients on the waiting list with HCV received antiviral therapy (34/187; 18% [13; 24] in 2010 and 26/128; 20% [14; 28] in 2013). This proportion increased temporarily from 2014 to 2017, only to drop to <10% thereafter. Accordingly, cure rates have increased significantly in recent years, reaching 100% in both 2019 and 2020. Accordingly most recently, the proportion of listed HCV patients with an active replicative infection at the time of liver transplantation has decreased significantly (Figure 1c).

Proportion of transplanted patients with hepatitis C and hepatocellular carcinoma

Whereas in the years 2010 to 2013, about 50% of all listed patients with HCV were transplanted for HCC each year, in recent years this proportion has significantly increased. In 2020, 21/26 (81% [63; 92]) of newly listed patients with HCV and HCC underwent liver transplantation.

Discussion

The present evaluation from eleven German transplant centers impressively demonstrates the impact of the introduction of highly effective and safe hepatitis C treatment using DAA on the German transplant scene. It was shown that there is a strong association between the need for HCV-related liver transplantation and the introduction of direct antiviral agents. This results in patients with other liver diseases having an increased chance of receiving a transplant. In 2020, almost 50 more organs were available for other indications in the participating centers as compared with 2013.

The present data are consistent with observations from other countries (3). Currently, it must be noted that, with a few exceptions, a patient with HCV ultimately only needs a transplant if they develop HCC. Against this background, it is important to note that after recovery from the HCV infection, the risk of developing HCC is reduced, but not completely eliminated (4).

In the present work, it cannot be ruled out that slight biases have arisen over the years due to patient transfers between centers whose numbers were considered for the analysis and centers that did not participate in the survey.

We recommend that all patients with HCV, even if they have hepatocellular carcinoma where curative therapy is available, receive antiviral therapy or that therapy is initiated following liver transplantation. However, an indication for therapy should be made with caution if a lab MELD score >20 is present (5).

Heiner Wedemeyer, Kerstin Herzer, Yvonne Serfert, Richard Taubert, Christian Trautwein, Dennis Eurich, Christian P. Strassburg, Melanie Lang, Karl Heinz Weiss, Thomas Berg, Peter R. Galle, Hauke Heinzow, Stefan Zeuzem

Collaborators

Katharina Willuweit, Theresa Kirchner, Cennet Sahin, Julius Plewe, Ulrich Spengler, Martin-Walter Welker, Martina Sterneck, Arianeb Mehrabi, Adam Herber, Tim Zimmermann, Hartmut Schmidt

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical

School, Hannover (Wedemeyer, Taubert, Kirchner) wedemeyer.heiner@mh-hannover.de

Leberstiftungs-GmbH Deutschland, Hannover (Wedemeyer, Serfert)

Department of Gastroenterology and Hepatology, Essen University Hospital, Duisburg-Essen University, Essen (Herzer, Willuweit, Schmidt)

Knappschafts-Klinik, Bad Neuenahr, Germany (Herzer)

Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen (Trautwein, Sahin) (Strassburg, Spengler)

Department of Surgery Charité-Universitätsmedizin Berlin, Berlin (Eurich, Plewe)

Department of Internal Medicine I, University Hospital Bonn (UKB), Bonn (Strassburg, Spengler)

Department of Medicine I, University Medical Center Hamburg-Eppendorf (UKE) (Lang, Sterneck)

Department for General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg (Weiss, Mehrabi)

Dept. of Internal Medicine, Salem Medical Center Heidelberg, Heidelberg (Weiss)

Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig (Berg, Herber)

I. Department of Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz (Galle, Zimmerman)

Department of Medicine B, Münster University Hospital (UKM), Münster (Heinzow, Schmidt)

Medical Department 1, Merciful Brothers Hospital Trier, Trier, Germany (Heinzow)

Medical Department 1, Goethe University Hospital, Frankfurt am Main (Zeuzem,

Welker)

Klinik für Innere Medizin I, Kreisklinik Groß-Umstadt, Groß-Umstadt (Welker)

Medizinische Klinik II, Klinikum Worms, Worms (Zimmermann)

Conflict of interest statement
Prof. Wedemeyer received consultancy fees from Abbvie, Alogos, Altimmune, Biotest, BMS, BTG, Dicerna, Enanta, Gilead, Janssen, Merck/MSD, MYR GmbH, Roche and Vir Biotechnology. Presentations were remunerated by Abbvie, Biotest, Gilead and Merck/MSD. Study support (third-party funding) was provided to him by Abbvie, Altimmune, BMS, Gilead, Janssen, Merck/MSD, MYR GmbH, Novartis, Vir Biotechnology, Biotest and Roche.

Prof. Herzer received fees for consultancy work from Novartis and Chiesi. She received congress fees and travel expense reimbursement from Gilead. She has been remunerated for lectures by Novartis, Astellas, Chiesi and Biotest.

University Lecturer Dr. Taubert received congress fees and travel expense reimbursement from Astellas. He received lecture fees from MSD and Abbvie.

University Lecturer Dr. Eurich received congress fees and travel expense reimbursement from Gilead and Janssen. He was reimbursed for presentations by BMS.

Prof. Strassburg was reimbursed for presentations by BMS, Janssen and Gilead.

Prof. Weiss received congress fees reimbursement from Gilead and Abbvie, travel expense reimbursement from Gilead, and was reimbursed for presentations by Abbvie.

Prof. Berg received consultancy fees, travel reimbursement, lecture fees and study support (third-party funding) from Abbvie, Gilead, Janssen and MSD/Merck.

Prof. Galle received study support (third-party funding) from Abbvie and Gilead.

Prof Heinzow received consultancy fees, congress fee and travel expense reimbursement from Abbvie and Gilead.

Prof. Zeuzem received consultancy fees from Abbvie, Gilead, Intercept, Janssen and SoBi. He was reimbursed for presentations by Abbvie, MSD and SoBi. He received support from various companies for more than 50 studies in the fields of endocrinology, gastroenterology and hepatology.

Dr. Serfert, Prof. Trautwein and Dr. Lang confirm that there are no conflicts of interest.

Manuscript received on 31 May 2021, revised version accepted on 12 August 2021

Translated from the original German by Dr. Grahame Larkin, MD

References

Cite this as:
Wedemeyer H, Herzer K, Serfert Y, Taubert R, Trautwein C, Eurich D, Strassburg CP, Lang M, Weiss KH, Berg T, Galle PR, Heinzow H, Zeuzem S: Declining numbers of hepatitis-C-virus-associated liver transplantations in Germany. Dtsch Arztebl Int 2021; 118: 797–8. DOI: 10.3238/arztebl.m2021.0318

1.
Sperle I, Steffen G, Leendertz SA, et al.: Prevalence of Hepatitis B, C, and D in Germany: results from a scoping review. Front Public Health 2020; 8: 424 CrossRef MEDLINE PubMed Central
2.
Herzer K, Gerken G, Kroy D, et al.: Impact of direct-acting antiviral therapy on the need for liver transplantation related to hepatitis C in Germany. J Hepatol 2018; 69: 982–4 CrossRef MEDLINE
3.
Sahakyan Y, Lee-Kim V, Bremner KE, Bielecki JM, Krahn MD: Impact of direct-acting antiviral regimens on mortality and morbidity outcomes in patients with chronic CrossRef hepatitis C: systematic review and meta-analysis. J Viral Hepat 2021; 28: 739–54 MEDLINE
4.
Ebel F, Deterding K, Port K, et al.: Letter: a 5-year long-term follow-up study after DAA treatment confirms a reduced HCC risk in a central European cohort of HCV patients with liver cirrhosis. Aliment Pharmacol Ther 2020; 51: 194–5 CrossRef MEDLINE
5.
Sarrazin C, Zimmermann T, Berg T, et al.: S3-Leitlinie „Prophylaxe, Diagnostik und Therapie der Hepatitis-C-Virus(HCV)-Infektion“. Z Gastroenterol 2020; 58: 1110–31 CrossRef MEDLINE
Participating centers during the period 2010–2020
Figure
Participating centers during the period 2010–2020
1.Sperle I, Steffen G, Leendertz SA, et al.: Prevalence of Hepatitis B, C, and D in Germany: results from a scoping review. Front Public Health 2020; 8: 424 CrossRef MEDLINE PubMed Central
2.Herzer K, Gerken G, Kroy D, et al.: Impact of direct-acting antiviral therapy on the need for liver transplantation related to hepatitis C in Germany. J Hepatol 2018; 69: 982–4 CrossRef MEDLINE
3.Sahakyan Y, Lee-Kim V, Bremner KE, Bielecki JM, Krahn MD: Impact of direct-acting antiviral regimens on mortality and morbidity outcomes in patients with chronic CrossRef hepatitis C: systematic review and meta-analysis. J Viral Hepat 2021; 28: 739–54 MEDLINE
4.Ebel F, Deterding K, Port K, et al.: Letter: a 5-year long-term follow-up study after DAA treatment confirms a reduced HCC risk in a central European cohort of HCV patients with liver cirrhosis. Aliment Pharmacol Ther 2020; 51: 194–5 CrossRef MEDLINE
5.Sarrazin C, Zimmermann T, Berg T, et al.: S3-Leitlinie „Prophylaxe, Diagnostik und Therapie der Hepatitis-C-Virus(HCV)-Infektion“. Z Gastroenterol 2020; 58: 1110–31 CrossRef MEDLINE