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      Hepatitis B virus-related cryoglobulinemia: Clinical characteristics, virological features, and treatment

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          Highlights

          • •

            The evaluation of HBsAg in cryoglobulins can confirm the diagnosis.

          • •

            HBV-related cryoglobulinemia patients should be treated with antiviral therapy.

          • •

            Corticosteroids and rituximab are effective with closely monitored for therapy-related infection.

          Abstract

          Background

          Hepatitis B virus (HBV) infection is a rare etiology of cryoglobulinemia, and its clinical characteristics, virological features and treatment are poorly understood.

          Methods

          This retrospective study enrolled 23 patients with HBV-related cryoglobulinemia from 497 cryoglobulinemia patients at Peking Union Medical College Hospital between January 2015 and February 2023. We analyzed the clinical characteristics, virological features and management of patients with HBV-related cryoglobulinemia.

          Results

          The 23 patients (13 males; median age 48 years) were all mixed cryoglobulinemia and serological HBsAg positive, while 15 patients exhibited HBV-DNA replication. The presence of HBsAg in cryoglobulins was evaluated in 7 patients, all of whom were positive. The most commonly involved organs were kidneys (69.6%), skin (65.2%), peripheral nerves (21.7%), joints (8.7%), gastrointestinal tract (4.3%), and cardiac (4.3%). Eight patients received antiviral therapy with nucleot (s)ide analogues (NAs) alone, 12 patients received NA- and corticosteroid-based regimens, and 3 patients received NA- and rituximab-based regimens based on the severity of clinical symptoms. After a median follow-up of 44 months, four patients died, and one patient was lost to follow-up. All remaining patients ( n = 18) achieved clinical remission, and HBV-DNA replication was not detected in 16 out of 18 patients. There was no HBV reactivation in patients treated with rituximab. The three-year overall survival and progression-free survival were 87.0% and 80.3%, respectively.

          Conclusions

          HBV-related cryoglobulinemia patients should be treated with antiviral therapy. Corticosteroids and rituximab are effective for severe cases, but patients need to be closely monitored for therapy-related infection.

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          Most cited references27

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          Hepatitis B virus infection.

          Christian Trépo, Henry L Y Chan, Anna Lok (2014)
          Hepatitis B virus infection is a major public health problem worldwide; roughly 30% of the world's population show serological evidence of current or past infection. Hepatitis B virus is a partly double-stranded DNA virus with several serological markers: HBsAg and anti-HBs, HBeAg and anti-HBe, and anti-HBc IgM and IgG. It is transmitted through contact with infected blood and semen. A safe and effective vaccine has been available since 1981, and, although variable, the implementation of universal vaccination in infants has resulted in a sharp decline in prevalence. Hepatitis B virus is not cytopathic; both liver damage and viral control--and therefore clinical outcome--depend on the complex interplay between virus replication and host immune response. Overall, as much as 40% of men and 15% of women with perinatally acquired hepatitis B virus infection will die of liver cirrhosis or hepatocellular carcinoma. In addition to decreasing hepatic inflammation, long-term antiviral treatment can reverse cirrhosis and reduce hepatocellular carcinoma. Development of new therapies that can improve HBsAg clearance and virological cure is warranted.
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            Hepatitis B virus infection--natural history and clinical consequences.

            Don Ganem, Alfred Prince (2004)
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              Mixed cryoglobulinemia: demographic, clinical, and serologic features and survival in 231 patients.

              Clodoveo Ferri, Marco Sebastiani, Dilia Giuggioli … (2004)
              Mixed cryoglobulinemia (MC) is a systemic vasculitis secondary to circulating immune complex deposition in the small vessels. In the overwhelming majority of patients, hepatitis C virus (HCV) infection represents the triggering factor of the disease. MC is characterized by multiple organ involvement, mainly skin, liver, renal, peripheral nerves, and less frequently by widespread vasculitis and cancer. To investigate the demographic, clinical, serologic features, and survival in a large series of MC patients. The study included 231 MC patients recruited between 1972 and 2001 at the Rheumatology Unit of the University of Pisa. All patients underwent wide clinicoserologic and virologic assessment. Cumulative survival rates were computed by the Kaplan-Meier method; moreover, the prognostic relevance of the main variables was investigated by Cox model analysis. In 92% of cases, the presence of HCV infection was demonstrated (anti-HCV antibody, 92%; HCV RNA, 90%), whereas hepatitis B virus (HBV) represented the possible causative agent in only 1.8% of patients (HBV DNA). Clinically, the MC syndrome followed a relatively benign clinical course in over 50% of cases, whereas a moderate-severe clinical course was observed in one third of patients whose prognosis was severely affected by renal and/or liver failure. In a limited, but significant, percentage (15%) of individuals, the disease was complicated by a malignancy, ie, B-cell lymphoma, and less frequently by hepatocellular carcinoma, or thyroid cancer. The survival study by the Kaplan-Meier method revealed a significantly lower cumulative 10th-year survival, calculated from time of diagnosis, in MC patients compared with expected death in the age- and sex-matched general population. Moreover, significantly lower survival rates were observed in males and in subjects with renal involvement. The multivariate analysis by the Cox proportional hazard regression model further supported the above findings: an increased mortality risk of 98% was observed for male gender (male/female hazard ratio, 1.978) and of 197% in patients with, compared with those without, renal involvement (hazard ratio, 2.967). At the end of the follow-up, 97 patients were deceased, and in 79 of 97 patients, the causes of death were ascertained: nephropathy (33%), malignancies (23%), liver involvement (13%), and diffuse vasculitis (13%) were the most frequent causes of death. Careful patient monitoring is recommended for a timely diagnosis of life-threatening MC complications, mainly nephropathy, widespread vasculitis, and B-cell lymphoma or other malignancies.
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                Author and article information

                Contributors
                Xin-xin Cao
                Journal
                Journal ID (nlm-ta): Virus Res
                Journal ID (iso-abbrev): Virus Res
                Title: Virus Research
                Publisher: Elsevier
                ISSN (Print): 0168-1702
                ISSN (Electronic): 1872-7492
                Publication date PMC-release: 28 August 2023
                Publication date Collection: 15 October 2023
                Publication date (Electronic): 28 August 2023
                Volume: 336
                Electronic Location Identifier: 199212
                Affiliations
                [a ]Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [b ]Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
                [c ]State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China
                Author notes
                [* ]Corresponding author at: Department of Hematology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan, Beijing 100730, China. caoxinxin@ 123456126.com
                Article
                Publisher Item ID: S0168-1702(23)00174-0 Publisher ID: 199212
                DOI: 10.1016/j.virusres.2023.199212
                PMC ID: 10474225
                PubMed ID: 37640269
                SO-VID: 5a19430a-a811-40ae-92f8-2e2c1e081023
                Copyright © © 2023 The Authors. Published by Elsevier B.V.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 10 July 2023
                Date revision received : 22 August 2023
                Date accepted : 25 August 2023
                Categories
                Subject: Article

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: cryoglobulinemia,hepatitis b virus,hbsag,nucleot (s)ide analogues,rituximab
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: cryoglobulinemia, hepatitis b virus, hbsag, nucleot (s)ide analogues, rituximab

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