Treating hepatitis D with bulevirtide-Real-world experience from 114 patients

被引：38

作者：

Dietz-Fricke, Christopher ^{[1
]}

Tacke, Frank ^{[2
]}

Zollner, Caroline ^{[2
]}

Demir, Munevver ^{[2
]}

Schmidt, Hartmut H. ^{[3
]}

Schramm, Christoph ^{[3
]}

Willuweit, Katharina ^{[3
]}

Lange, Christian M. ^{[4
]}

Weber, Sabine ^{[4
]}

Denk, Gerald ^{[4
]}

Berg, Christoph P. ^{[5
]}

Grottenthaler, Julia M. ^{[5
]}

Merle, Uta ^{[6
]}

Olkus, Alexander ^{[6
]}

Zeuzem, Stefan ^{[7
]}

Sprinzl, Kathrin ^{[7
]}

Berg, Thomas ^{[8
]}

van Bommel, Florian ^{[8
]}

Wiegand, Johannes ^{[8
]}

Herta, Toni ^{[8
]}

Seufferlein, Thomas ^{[9
]}

Zizer, Eugen ^{[9
]}

Dikopoulos, Nektarios ^{[9
]}

Thimme, Robert ^{[10
]}

Neumann-Haefelin, Christoph ^{[10
]}

Galle, Peter R. ^{[11
]}

Sprinzl, Martin ^{[11
]}

Lohse, Ansgar W. ^{[12
]}

zur Wiesch, Julian Schulze ^{[12
,21
]}

Kempski, Jan ^{[12
,13
]}

Geier, Andreas ^{[14
]}

Reiter, Florian P. ^{[14
]}

Schlevogt, Bernhard ^{[15
]}

Goediker, Juliana ^{[15
]}

Hofmann, Wolf Peter ^{[16
]}

Buggisch, Peter ^{[17
]}

Kahlhofer, Julia ^{[1
]}

Port, Kerstin ^{[1
]}

Maasoumy, Benjamin ^{[1
]}

Cornberg, Markus ^{[1
,20
,22
,23
]}

Wedemeyer, Heiner ^{[1
,18
,19
,20
]}

Deterding, Katja ^{[1
]}

机构：

[1] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany

[2] Charite Univ Med Berlin, Dept Hepatol & Gastroenterol, Campus Virchow Klinikum CVK & Campus Charite Mitte, Berlin, Germany

[3] Univ Duisburg Essen, Med Fac, Dept Gastroenterol Hepatol & Transplant Med, Essen, Germany

[4] Ludwig Maximilian Univ Munich, Univ Hosp, Dept Med 2, Munich, Germany

[5] Univ Hosp Tuebingen, Dept Gastroenterol Gastrointestinal Oncol Hepatol, Tubingen, Germany

[6] Heidelberg Univ, Dept Internal Med 4, Heidelberg, Germany

[7] Goethe Univ Hosp, Internal Med Dept, Frankfurt, Germany

[8] Univ Leipzig, Med Ctr, Dept Med 2, Div Hepatol, Leipzig, Germany

[9] Univ Ulm, Dept Internal Med 1, Ulm, Germany

[10] Univ Freiburg, Univ Med Ctr Freiburg, Fac Med, Dept Med 2, Freiburg, Germany

[11] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 1, Mainz, Germany

[12] Univ Med Ctr Hamburg Eppendorf, Dept Med, Hamburg, Germany

[13] Univ Med Ctr Hamburg Eppendorf, Mildred Scheel Canc Career Ctr HaTriCS 4, Hamburg, Germany

[14] Univ Hosp Wurzburg, Dept Med 2, Div Hepatol, Wurzburg, Germany

[15] Univ Hosp Munster, Dept Med B, Munster, Germany

[16] MVZ Gastroenterol Bayer Pl, Berlin, Germany

[17] Ifi Inst Interdisciplinary Med, Hamburg, Germany

[18] Hannover Med Sch, Excellence Cluster Resist, Hannover, Germany

[19] German Ctr Infect Res DZ, Hannover Braunschweig, Germany

[20] D SOLVE consortium, EU Horizon Europe Funded Project 101057917, Hannover, Germany

[21] German Ctr Infect Res DZ, Partner Site Hamburg Lubeck Borstel Riems, Hamburg, Germany

[22] Helmholtz Ctr Infect Res HZI, Ctr Individualised Infect Med CiiM, Hannover, Germany

[23] Hannover Med Sch MHH, Hannover, Germany

来源：

JHEP REPORTS | 2023年 / 5卷 / 04期

关键词：

Hepatitis D; Viral hepatitis; Bulevirtide; Real world experience; Antiviral treatment; HDV RNA; VIRUS; LIVER; QUANTIFICATION;

D O I：

10.1016/j.jhepr.2023.100686

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & Aims: Bulevirtide is a first-in-class entry inhibitor of hepatitis B surface antigen. In July 2020, bulevirtide was conditionally approved for the treatment of hepatitis D, the most severe form of viral hepatitis, which frequently causes end -stage liver disease and hepatocellular carcinoma. Herein, we report the first data from a large multicenter real-world cohort of patients with hepatitis D treated with bulevirtide at a daily dose of 2 mg without additional interferon. Methods: In a joint effort with 16 hepatological centers, we collected anonymized retrospective data from patients treated with bulevirtide for chronic hepatitis D. Results: Our analysis is based on data from 114 patients, including 59 (52%) with cirrhosis, receiving a total of 4,289 weeks of bulevirtide treatment. A virologic response defined as an HDV RNA decline of at least 2 log or undetectable HDV RNA was observed in 87/114 (76%) cases with a mean time to virologic response of 23 weeks. In 11 cases, a virologic breakthrough (>1 log-increase in HDV RNA after virologic response) was observed. After 24 weeks of treatment, 19/33 patients (58%) had a virologic response, while three patients (9%) did not achieve a 1 log HDV RNA decline. No patient lost hepatitis B surface antigen. Alanine aminotransferase levels improved even in patients not achieving a virologic response, including five patients who had decompensated cirrhosis at the start of treatment. Treatment was well tolerated and there were no reports of drug -related serious adverse events. Conclusions: In conclusion, we confirm the safety and efficacy of bulevirtide monotherapy in a large real-world cohort of patients with hepatitis D treated in Germany. Future studies need to explore the long-term benefits and optimal duration of bulevirtide treatment. Impact and implications: Clinical trials proved the efficacy of bulevirtide for chronic hepatitis D and led to conditional approval by the European Medical Agency. Now it is of great interest to investigate the effects of bulevirtide treatment in a real-world setting. In this work, we included data from 114 patients with chronic hepatitis D who were treated with bulevirtide at 16 German centers. A virologic response was seen in 87/114 cases. After 24 weeks of treatment, only a small proportion of patients did not respond to treatment. At the same time, signs of liver inflammation improved. This observation was independent from changes in hepatitis D viral load. The treatment was generally well tolerated. In the future, it will be of interest to investigate the long-term effects of this new treatment. (c) 2023 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页数：10

共 42 条

[1] Chronic hepatitis D and hepatocellular carcinoma: A systematic review and meta-analysis of observational studies [J].

Alfaiate, Dulce ;

Clement, Sophie ;

Gomes, Diana ;

Goossens, Nicolas ;

Negro, Francesco .

JOURNAL OF HEPATOLOGY, 2020, 73 (03) :533-539

[2]

Allweiss L, 2019, Z GASTROENTEROL, V57, P6

[3]

Allweiss L, 2021, HEPATOLOGY, V74, p148A

[4]

Anolli M, 2022, J HEPATOL, V77

[5]

[Anonymous], 2018, LANG ENV STAT COMP

[6] High rates of cirrhosis and severe clinical events in patients with HBV/HDV co-infection: longitudinal analysis of a German cohort [J].

Bockmann, Jan-Hendrik ;

Grube, Marcel ;

Hamed, Vanessa ;

von Felden, Johann ;

Landahl, Johanna ;

Wehmeyer, Malte ;

Giersch, Katja ;

Hall, Michaela T. ;

Murray, John M. ;

Dandri, Maura ;

Lueth, Stefan ;

Lohse, Ansgar W. ;

Luetgehetmann, Marc ;

Schulze Zur Wiesch, Julian .

BMC GASTROENTEROLOGY, 2020, 20 (01)

[7] Automated nucleic acid isolation methods for HDV viral load quantification can lead to viral load underestimation [J].

Bremer, Birgit ;

Anastasiou, Olympia E. ;

Ciesek, Sandra ;

Weelemeyer, Heiner .

ANTIVIRAL THERAPY, 2019, 24 (02) :117-123

[8] Shaping macrophages function and innate immunity by bile acids: Mechanisms and implication in cholestatic liver diseases [J].

Calmus, Yvon ;

Poupon, Raoul .

CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY, 2014, 38 (05) :550-556

[9] Taurodeoxycholate Increases the Number of Myeloid-Derived Suppressor Cells That Ameliorate Sepsis in Mice [J].

Chang, Sooghee ;

Kim, Youn-Hee ;

Kim, Young-Joo ;

Kim, Young-Woo ;

Moon, Sungyoon ;

Lee, Yong Yook ;

Jung, Jin Sun ;

Kim, Youngsoo ;

Jung, Hi-Eun ;

Kim, Tae-Joo ;

Cheong, Taek-Chin ;

Moon, Hye-Jung ;

Cho, Jung-Ah ;

Kim, Hang-Rae ;

Han, Dohyun ;

Na, Yirang ;

Seok, Seung-Hyeok ;

Cho, Nam-Hyuk ;

Lee, Hai-Chon ;

Nam, Eun-Hee ;

Cho, Hyosuk ;

Choi, Murim ;

Minato, Nagahiro ;

Seong, Seung-Yong .

FRONTIERS IN IMMUNOLOGY, 2018, 9

[10]

Deterding K, 2022, J HEPATOL, V77, pS857

← 1 2 3 4 5 →