DataSheet1_Neuropsychiatric disorders in chronic hepatitis C patients after receiving interferon or direct-acting antivirals: a nationwide cohort study.docx

Background: Data on the neuropsychological outcomes after receiving direct-acting antivirals (DAAs) among chronic hepatitis C (CHC) patients have not been well-documented.Aim: This study aimed to evaluate the difference in incidence of neuropsychological disorders (NPDs) after treatment completion between CHC patients receiving interferon (IFN) therapy and DAA therapy.Methods: A nationwide retrospective cohort study was performed using Taiwan’s National Health Insurance Research Database (NHIRD) between 2010 and 2018. CHC patients without pre-existing mental disorders were included and divided into the treatment (Tx)-naïve DAA group, retreatment (re-Tx) DAA group, and Tx-naïve IFN group based on their HCV therapy. Propensity score matching was used to balance baseline differences between groups. The primary outcome was the incidence of NPDs during 6 months after completion of therapy.Results: After one-to-one matching, there were 6,461 pairs of patients selected from the Tx-naïve DAA group and Tx-naïve IFN group and 3,792 pairs from the re-Tx DAA group and Tx-naïve IFN group. A lower incidence of NPDs was observed in the Tx-naïve DAA group than in the Tx-naïve IFN group (HR = 0.72, 95% CI = 0.55–0.94, and p = 0.017). The risk of NPDs did not differ between the re-Tx DAA group and the Tx-naïve IFN group (HR = 0.74, 95% CI: 0.52–1.05, and p = 0.092).Conclusion: DAA therapy was associated with lower risk of NPDs when compared with IFN therapy among Tx-naïve CHC patients in a 6-month period after treatment completion, especially among the patients less than 65 years, male gender, and cirrhosis.</p

Risk of Severe Acute Exacerbation of Chronic HBV Infection Cancer Patients Who Underwent Chemotherapy and Did Not Receive Anti-Viral Prophylaxis

<div><p>Background</p><p>Reactivation of HBV replication with an increase in serum HBV DNA and alanine aminotransferase (ALT) activity has been reported in 20–50% of hepatitis B carriers undergoing cytotoxic chemotherapy for cancer treatment. Manifestation of HBV reactivation ranges from asymptomatic self-limiting hepatitis to severe progressive hepatic failure and fatal consequences.</p><p>Aim</p><p>To investigate the risk of severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients with solid tumors or hematological malignancies who underwent chemotherapy without antiviral prophylaxis.</p><p>Methods</p><p>A retrospective review of charts was conducted for HBsAg-positive cancer patients in our institution who underwent chemotherapy and did not receive anti-viral prophylaxis between the periods of July 2007 to January 2013. We investigate the incidence of severe acute exacerbation of chronic HBV infection if these patients with a variety of solid tumors and hematological malignancies.</p><p>Results</p><p>A total of 156 patients (hematological malignancies: 16; solid tumors: 140) were included. The incidence of severe acute HBV exacerbation in the patients with hematological malignancy was higher than that in solid tumors (25.0% [4/16] <i>vs</i> 4.3% [6/140]); <i>P</i> = 0.005). Additionally, patients receiving rituximab-based chemotherapy had higher acute exacerbation rate than those with non-rituximab-based chemotherapy (40.0% <i>vs</i> 4.1%, <i>P</i> = 0.001). Among the patients with solid tumors, the incidences of severe acute exacerbation of chronic HBV in hepatocellular carcinoma, colorectal cancer, lung cancer, breast cancer, gynecological cancer, urological tract cancer, head/neck cancer and other solid malignancies were 2.3%, 4.0%, 7.1%, 9.0%, 16.7%, 6.7%, 0% and 0%, respectively.</p><p>Conclusion</p><p>Severe acute exacerbation of chronic HBV infection may occur in HBsAg-positive patients with a variety of solid tumors who received chemotherapy without adequate anti-viral prophylaxis. Hematological malignancy and rituximab-based chemotherapy are the risk factors related to severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients undergoing chemotherapy.</p></div

Severe acute exacerbation of HBV infection in HBsAg-positive cancer patients who received chemotherapy without antiviral prophylaxis.

<p>Severe acute exacerbation of HBV infection in HBsAg-positive cancer patients who received chemotherapy without antiviral prophylaxis.</p

Characteristics of the 156 HBsAg-positive cancer patients who received chemotherapy without antiviral prophylaxis.

<p>Characteristics of the 156 HBsAg-positive cancer patients who received chemotherapy without antiviral prophylaxis.</p

Patient disposition and clinical outcomes.

<p>A total of 156 patients were included for HBsAg-positive cancer patients in our institution who underwent chemotherapy and did not receive anti-viral prophylaxis between the periods of July 2007 to January 2013.</p

Flow chart of patients with or without screening for hepatitis B surface antigen (HBsAg), antiviral prophylaxis and hepatitis B virus reactivation in overall (n = 1053) by way of the computer－assisted reminding system.

<p>Flow chart of patients with or without screening for hepatitis B surface antigen (HBsAg), antiviral prophylaxis and hepatitis B virus reactivation in overall (n = 1053) by way of the computer－assisted reminding system.</p

Demographic data of solid tumor patients undergoing systemic cytotoxic chemotherapy and using prophylactic entecavir or lamivudine.

<p>^<i>a</i>Entecavir group included 6 head and neck cancers, 4 gynecologic cancers, and 7 genitourinary cancers. Lamivudine group included 31 head and neck cancers, 15 gynecologic cancers, and 11 genitourinary cancers.</p><p>^<i>b</i>SCC: systemic cytotoxic chemotherapy</p><p>^<i>c</i>ALT: alanine aminotransferase.</p><p>^<i>d</i>INR: international normalized ratio.</p><p>Demographic data of solid tumor patients undergoing systemic cytotoxic chemotherapy and using prophylactic entecavir or lamivudine.</p

Flow chart of the strategy of computer-assisted system for reminding the doctors in charge before prescribing chemotherapy.

<p>Flow chart of the strategy of computer-assisted system for reminding the doctors in charge before prescribing chemotherapy.</p

The rates of reactivation of hepatitis B and related events in patients (n = 134) with and without antiviral prophylaxis before prescribing chemotherapy.

<p>The rates of reactivation of hepatitis B and related events in patients (n = 134) with and without antiviral prophylaxis before prescribing chemotherapy.</p

Clinical data of 11 patients with hepatitis B reactivation without antiviral prophylaxis before chemotherapy.

<p>ALT, alanine aminotransferase; HCC, hepatocellular carcinoma; NA, not available; C/T, chemotherapy; ETV, entecavir; LdT, telbivudine; LAM, lamivudine; TDF, tenofovir.</p><p>All patients were hepatitis B e antigen-negative.</p><p>Case 5, Case 7, Case 10 reported themselves to be inactive HBV carriers in other medical institutions.</p><p>Case 11 died within 2 days after admission without virological data and antiviral treatment.</p><p>Clinical data of 11 patients with hepatitis B reactivation without antiviral prophylaxis before chemotherapy.</p