scholarly journals Putative Repurposing of Lamivudine, a Nucleoside/Nucleotide Analogue and Antiretroviral to Improve the Outcome of Cancer and COVID-19 Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
José J. García-Trejo ◽  
Raquel Ortega ◽  
Mariel Zarco-Zavala

Lamivudine, also widely known as 3TC belongs to a family of nucleotide/nucleoside analogues of cytidine or cytosine that inhibits the Reverse Transcriptase (RT) of retroviruses such as HIV. Lamivudine is currently indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection or for chronic Hepatitis B (HBV) virus infection associated with evidence of hepatitis B viral replication and active liver inflammation. HBV reactivation in patients with HBV infections who receive anticancer chemotherapy can be a life-threatening complication during and after the completion of chemotherapy. Lamivudine is used, as well as other antiretrovirals, to prevent the reactivation of the Hepatitis B virus during and after chemotherapy. In addition, Lamivudine has been shown to sensitize cancer cells to chemotherapy. Lamivudine and other similar analogues also have direct positive effects in the prevention of cancer in hepatitis B or HIV positive patients, independently of chemotherapy or radiotherapy. Recently, it has been proposed that Lamivudine might be also repurposed against SARS-CoV-2 in the context of the COVID-19 pandemic. In this review we first examine recent reports on the re-usage of Lamivudine or 3TC against the SARS-CoV-2, and we present docking evidence carried out in silico suggesting that Lamivudine may bind and possibly work as an inhibitor of the SARS-CoV-2 RdRp RNA polymerase. We also evaluate and propose assessment of repurposing Lamivudine as anti-SARS-CoV-2 and anti-COVID-19 antiviral. Secondly, we summarize the published literature on the use of Lamivudine or (3TC) before or during chemotherapy to prevent reactivation of HBV, and examine reports of enhanced effectiveness of radiotherapy in combination with Lamivudine treatment against the cancerous cells or tissues. We show that the anti-cancer properties of Lamivudine are well established, whereas its putative anti-COVID effect is under investigation. The side effects of lamivudine and the appearance of resistance to 3TC are also discussed.

2019 ◽  
Vol 14 (12) ◽  
pp. 791-798
Author(s):  
Ivailo Alexiev ◽  
Elitsa Golkocheva-Markova ◽  
Asya Kostadinova ◽  
Reneta Dimitrova ◽  
Lora Nikolova ◽  
...  

Aim: To evaluate hepatitis B virus (HBV) and hepatitis C virus (HCV) among individuals with HIV/AIDS in Bulgaria diagnosed between 2010 and 2015. Materials & methods: A total of 1158 individuals were diagnosed with HIV/AIDS during the study period. Different transmission groups were tested with ELISA and real-time PCR for HBV and HCV markers. Results: Hepatitis B surface antigen and hepatitis C virus antiboby were found in 9.3 and 23.2% of the tested. HBV DNA and HCV RNA has been found in 47.4 and 69.6%. Hepatitis B and C co-infections were predominant in multiple risk behavior groups, including people who inject drugs, men who have sex with men, prisoners and Roma individuals. Conclusion: HIV prevalence in Bulgaria is low but the rates of hepatitis B and C co-infections among these patients fall within the upper range reported in Europe.


2003 ◽  
Vol 125 (5) ◽  
pp. 1559-1560 ◽  
Author(s):  
Gianguglielmo Zehender ◽  
Chiara De Maddalena ◽  
Laura Milazzo ◽  
Manuela Piazza ◽  
Massimo Galli ◽  
...  

2014 ◽  
Vol 30 (S1) ◽  
pp. A280-A280
Author(s):  
Dismas C.O. Oketch ◽  
Eunice Kaguiri ◽  
Nereo Murgor ◽  
Cosmas Apaka ◽  
Paul Ayuo ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Yuka Miyake ◽  
Aki Hasebe ◽  
Tetsuya Tanihira ◽  
Akiko Shiraishi ◽  
Yusuke Imai ◽  
...  

A 47-year-old man diagnosed with Crohn’s disease was treated with infliximab. He tested negative for hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) but positive for anti-HB core antibody (anti-HBc). He tested positive for hepatitis B virus (HBV-) DNA 3 months after treatment and was administered entecavir. HBV-DNA test showed negative results 1 month later. ALT was persistently within the normal range, and HBV-DNA was persistently negative thereafter despite the continuation of infliximab every 8 weeks. In our hospital, 14 patients with inflammatory bowel disease, who tested negative for HBsAg, were treated with infliximab; 2 of them tested positive for anti-HBs and/or anti-HBc, and HBV reactivation was observed in 1 patient (the present patient). The present case and these findings highlight that careful follow-up is needed in patients with inflammatory bowel disease treated with infliximab who test positive for anti-HBc and/or anti-HBs.


2016 ◽  
Vol 10 ◽  
Author(s):  
Elena Garlatti Costa ◽  
Michela Ghersetti ◽  
Silvia Grazioli ◽  
Pietro Casarin

Acute hepatitis A is generally a self-limited disease in healthy subjects within few weeks, but an uncommon type of prolonged and biphasic acute course of hepatitis A infection has been also described. This type of presentation is observed in about 6-10% of patients, but a small number of reports, concerning this topic, are available in literature. In addition hepatitis A virus (HAV) infection in hepatitis B virus (HBV) carriers has rarely been discussed. A 41-year-old Italian man, already known to our Department for HBV infection as an inactive carrier HBsAg(+)ve, experienced a prolonged and biphasic course of acute hepatitis A, lasting about 7 months. In this patient possible factors, causing the second flare of transaminases, were excluded (in particular autoimmunity). Liver biopsy as well HAV RNA search in blood/stools were not performed. In conclusion, the hepatologist should take into account this type of atypical course in patients with HAV-related hepatitis and should promote HAV vaccination in subjects with HBV-chronic hepatitis, to prevent possible life-threatening acute exacerbation of hepatic damage, mainly in HBV-carriers with more severe forms of liver diseases.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1801-1801
Author(s):  
Blanca Sanchez-Gonzalez ◽  
Montserrat Garcia-Retortillo ◽  
Teresa Murcia ◽  
Mariana Ferraro ◽  
Francesc Garcia-Pallarols ◽  
...  

Abstract INTRODUCTION Chemotherapy-induced hepatitis B virus (HBV) reactivation is a well-recognized complication and is a potentially life-threatening condition in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg]-positive). Rituximab has been associated with an increase in HBV reactivation in chronic HBV patients (45%) and even in patients with resolved infection (HBsAg negative and hepatitis B core antibody [anti-HBc]-positive (22%); however, the reported frequency varies among different studies. Current guidelines for management of chronic HBV recommend routine antiviral HBV prophylaxis with lymphoma before starting chemotherapy. In contrast, there is little evidence-based consensus regarding patients with resolved HBV infection. Aim: To analyze the incidence of HBV reactivation and the role of antiviral HBV prophylaxis in lymphoma patients with chronic HBV or resolved HBV treated with chemotherapy, immunotherapy or immunochemotherapy managed according to our institutional HBV guidelines. Secondary endpoints were to analyze the incidence of HBV in this population and HBV guidelines adherence. PATIENTS AND METHODS Lymphoma patients with chronic HBV or resolved HBV in a single center. HBV viral status definitions: Active Chronic HBV infection: HBsAg positive, anti-HBc positive and HBV DNA >2000 IU/mL; Inactive Carriers: HBsAg positive, Anti-HBc positive, HBV DNA undetectable or <2000 IU/mL with normal transaminases; Resolved HBV: HBsAg negative, anti-HBc positive, HBV DNA undetectable. HBV reactivation was defined as increased serum HBV DNA (≥1 log10), regardless of liver biochemistry or HBsAg status. Institutional HBV guidelines: serum samples were collected at baseline for HBsAg and anti-HBc testing in all lymphoma patients. Patients were evaluated by a hepatologist if any of them fulfilled HBV viral status definition. Baseline at screening and monitoring every 3 months during therapy and up to 24 months after completing therapy (assessment of liver biochemistry, serum HBV DNA, HBsAg and anti-HBs levels). Specific prophylaxis strategies according to HBV status: Group A (Active chronic HBV): treatment for HBV; Group B (Inactive carriers): antiviral HBV prophylaxis; Group C (Resolved HBV): antiviral HBV prophylaxis if rituximab containing-therapy or follow-up only if rituximab-free therapy. HBV antiviral prophylaxis was started before therapy and finished 12 months after completing therapy. RESULTS From January 2012 to January 2015, 227 lymphoma patients received chemotherapy or immunochemotherapy. 142 (63%) patients received rituximab-containing therapy. 43 (19%) patients were anti-HBc positive. Group A: 2 (1%) patients; Group B: 2 (1%) patients; Group C: 39 (17%) patients. 14 (6%) patients have coinfection with hepatitis C virus and 12 (5%) patients co-infection with human immunodeficiency virus (HIV). Adherence to HBV guidelines was 90%. Patients in Group A (n=2) and B (n=2) received antiviral treatment/prophylaxis before starting therapy. In the Group C, 16 (41%) patients underwent only follow-up and 23 (59%) patients received HBV antiviral prophylaxis (lamivudine in 4, entecavir in 8 and tenofovir in 11). Median duration of HBV prophylaxis was 18 months (95% CI: 16-19 months). After a median follow-up of 21 months, 2 patients developed HBV reactivation during lymphoma treatment: 1 from group B (reactivation rate of 50%) and 1 from group C (reactivation rate of 3%). Both patients had received rituximab-containing treatment and both developed HBV reactivation (without hepatitis flare) within the first 6 months after finishing antiviral HBV prophylaxis (delayed HBV reactivation). Outcome was favorable in both patients. Characteristics of HBV reactivation patients are shown in table I. Cumulative incidence of HBV reactivation at 12 and 24 months were 0% and 8%, respectively. CONCLUSION Our strategy of close monitoring patients with chronic HBV or resolved HBV that receive chemotherapy and adding antiviral HBV prophylaxis only in selected patients clearly decrease HBV reactivation. Nevertheless, this strategy may not fully protect patients from late HBV reactivations. Larger validation studies are needed to confirm our data and to establish the best cost-effective strategy in this lymphoma population, especially in the new era of inmunomodulatory drugs of their real involvement in HBV reactivation is unknown. Table 1 Table 1. Disclosures No relevant conflicts of interest to declare.


Author(s):  
V. U. Obisike ◽  
C. M. Uke ◽  
E. U. Amuta

Hepatitis B is a life threatening infectious liver disease caused by hepatitis B virus (HBV). The aim of this study was to determine the prevalence of HBV among food vendors in Wurukum, a highly commercial section of metropolitan Makurdi in Benue State. The test was carried out with the use of an immunochromatographic  micropoint HBsAg test strips and a HBsAg  buffer screen for the virus. Out of the 250 non-vaccinated food vendors sampled, 27(10.8%) had HBV infection, with more in males (21.7%) than in females (6.6%). No significant difference (p>0.05) was found among age groups in spite of the observed highest prevalence of 14.3% among the 20-29 year olds. Therefore, the need for routine screening cannot be overemphasized in spite of known risk factors among food vendors.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7481 ◽  
Author(s):  
Yu-Fen Tsai ◽  
Ching-I Yang ◽  
Jeng-Shiun Du ◽  
Ming-Hui Lin ◽  
Shih-Hao Tang ◽  
...  

Background Hepatitis B virus (HBV) reactivation with a hepatitis flare is a common complication in lymphoma patients treated with immunotherapy and/or chemotherapy. Anti-HBV prophylaxis is suggested for non-Hodgkin lymphoma (NHL) patients undergoing rituximab therapy, even those with resolved HBV infection. Since anti-HBV prophylaxis for patients with resolved HBV infection is not covered by national health insurance in Taiwan, a proportion of these patients receive no prophylaxis. In addition, late HBV reactivation has emerged as a new issue in recent reports, and no consensus has been reached for the optimal duration of antiviral prophylaxis. Thus, the aim of our study was to investigate the incidence and outcomes of HBV reactivation in NHL patients in a real-world setting and to study the frequency of late HBV reactivation. Materials Non-Hodgkin lymphoma patients who received rituximab and/or chemotherapy at our institute between January 2011 and December 2015 and who were hepatitis B surface antigen (HBsAg)- or hepatitis B core antibody (HBcAb)-positive were reviewed retrospectively. Results A total of 388 patients were screened between January 2011 and December 2015. In total, 196 patients were excluded because HBsAg was not assessed, HBcAb was negative or not assessed, or they were not treated with immunosuppressive therapy. Finally, the retrospective study included 62 HBsAg-positive NHL patients and 130 NHL patients with resolved HBV infection (HBsAg-negative and HBcAb-positive). During a median 30.5-month follow-up period, seven patients experienced HBV reactivation, five of whom had a hepatitis flare. The incidence of HBV reactivation did not significantly differ between the HBsAg-positive patients and the resolved HBV infection population without anti-HBV prophylaxis (4.8% vs. 3.1%, P = 0.683). All patients with HBV reactivation were exposed to rituximab. Notably, late HBV reactivation was not uncommon (two of seven patients with HBV reactivation events, 28.6%). Hepatitis B virus reactivation did not influence the patients’ overall survival. An age ≥65 years and an advanced disease stage were independent risk factors for poorer overall survival. Conclusion The incidence of HBV reactivation was similar between the HBsAg-positive patients with antiviral prophylaxis and the resolved HBV infection population without anti-HBV prophylaxis. All HBV reactivation events occurred in NHL patients exposed to rituximab. Late reactivation was not uncommon. The duration of regular liver function monitoring for more than 1 year after immunosuppressive therapy or after withdrawal of prophylactic antiviral therapy should be prolonged. Determining the exact optimal duration of anti-HBV prophylaxis is warranted in a future prospective study for NHL patients treated with rituximab-containing therapy.


2013 ◽  
Vol 31 (22) ◽  
pp. 2765-2772 ◽  
Author(s):  
Yi-Hsiang Huang ◽  
Liang-Tsai Hsiao ◽  
Ying-Chung Hong ◽  
Tzeon-Jye Chiou ◽  
Yuan-Bin Yu ◽  
...  

Purpose The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear. Patients and Methods Eighty patients with CD20+ lymphoma and resolved hepatitis B were randomly assigned to receive either prophylactic entecavir (ETV) before chemotherapy to 3 months after completing chemotherapy (ETV prophylactic group, n = 41) or to receive therapeutic ETV at the time of HBV reactivation and hepatitis B surface antigen (HBsAg) reverse seroconversion since chemotherapy (control group, n = 39). Results Fifty-eight patients (72.5%) were positive for hepatitis B surface antibody, and HBV DNA was undetectable in 50 patients (62.5%). During a mean 18-month follow-up period, one patient (2.4%) in the ETV prophylactic group and seven patients (17.9%) in the control group developed HBV reactivation (P = .027). The cumulative HBV reactivation rates at months 6, 12, and 18 after chemotherapy were 8%, 11.2%, and 25.9%, respectively, in the control group, and 0%, 0%, and 4.3% in the ETV prophylactic group (P = .019). Four patients (50%) in the control group had HBsAg reverse seroconversion after HBV reactivation. The cumulative HBsAg reverse seroconversion rates at months 6, 12, and 18 since chemotherapy were 0%, 6.4%, and 16.3% in the control group, respectively, which were significantly higher than those in the ETV prophylactic group (P = .032). Patients with detectable or undetectable viral load could develop HBV reactivation and HBsAg reverse seroconversion. Conclusion Undetectable HBV viral load before chemotherapy did not confer reactivation-free status. Antiviral prophylaxis can potentially prevent rituximab-associated HBV reactivation in patients with lymphoma and resolved hepatitis B.


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