ledipasvir and Hepatitis-B

Reactivation of occult or inactive Hepatitis B virus (HBV) infection during immunosuppressant treatments is well known and widely described in literature. The same observation has been made in Hepatitis C (HCV)-infected patients previously exposed to HBV and treated with interferon-free DAA treatments. Because of common transmission routes, persons may have been exposed to HCV, HBV and HIV, but few cases have been reported in this scenario to date. Frequency of HBV reactivation in HIV/HCV co-infected patients previously exposed to HBV and treated with DAA remains unclear. Herein, we report an episode of HBV reactivation in an HIV/HCV co-infected patient prescribed with sofosbuvir/ledipasvir for HCV.. This case-report highlights the risk of HBV reactivation with interferon-free DAA treatment in HIV/HCV co-infected patients previously exposed to HBV and who have contraindications for treatment with nucleoside/nucleotide reverse transcriptase Inhibitors because of comorbid conditions. In the setting of HIV infection, clinicians prescribing DAA should be aware of this risk, and HBV assessment at treatment start as well as virological monitoring during DAA treatment is recommended. Large epidemiological and virological studies are needed to investigate reactivation of occult HBV infection more in depth.

Topics: Antiviral Agents; Benzimidazoles; Coinfection; Female; Fluorenes; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis C; HIV Infections; Humans; Middle Aged; Sofosbuvir

Topics: Antiviral Agents; DNA, Viral; Fluorenes; Hepacivirus; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Pilot Projects; Retrospective Studies; Sofosbuvir; Symptom Flare Up

Postmarketing cases of hepatitis B virus (HBV) reactivation during hepatitis C treatment have been reported. We analyzed serum samples from patients in a clinical trial of ledipasvir-sofosbuvir in Taiwan and Korea. Of the 173 patients enrolled, 103 (60%) had been previously infected with HBV. None showed evidence of HBV reactivation.

Topics: Adult; Aged; Antiviral Agents; Benzimidazoles; Coinfection; Drug Therapy, Combination; Female; Fluorenes; Hepatitis B; Hepatitis B virus; Hepatitis C; Humans; Male; Middle Aged; Sofosbuvir; Virus Activation

For patients coinfected with hepatitis C virus (HCV) and hepatitis B virus (HBV), HCV treatment with direct-acting antivirals can lead to HBV reactivation. We evaluated HBV reactivation during ledipasvir/sofosbuvir treatment and 108-week follow-up.. In Taiwan, 111 patients with HCV genotype 1 or 2 and HBV received ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks. HBV virologic reactivation was defined as postbaseline increase in HBV DNA from either less than the lower limit of quantification (LLOQ, 20 IU/mL) to equal to or more than LLOQ or equal to or more than LLOQ to >1 log10 IU/mL. HBV clinical reactivation was HBV virologic reactivation with alanine aminotransferase (ALT) >2× upper limit of normal. Factors associated with development of HBV virologic or clinical reactivation were evaluated with logistic regression analysis.. All patients (100%, 111/111) maintained HCV suppression through 108 weeks after treatment. HBV virologic reactivation occurred in 73% of patients (81/111). Clinical reactivation occurred in 9% (10/111). The majority of HBV virologic reactivations (86%, 70/81) occurred by follow-up week 12, whereas clinical reactivation was generally more delayed. Eight (7%, 8/111) initiated HBV therapy. In regression analyses, baseline HBV DNA and hepatitis B surface antigen (HBsAg) levels were associated with HBV virologic reactivation and baseline ALT and HBV DNA, and HBsAg levels were associated with HBV clinical reactivation.. Among HCV/HBV coinfected patients treated with direct-acting antivirals for HCV, HBV virologic reactivation occurred in a majority of patients during treatment and follow-up. In most patients, HBV virologic reactivation was asymptomatic; only a small proportion initiated HBV treatment. Notably, clinical reactivation may still occur >3 months after end of therapy.. NCT02613871.

Topics: Antiviral Agents; Benzimidazoles; Coinfection; DNA, Viral; Fluorenes; Follow-Up Studies; Hepacivirus; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis C; Hepatitis C, Chronic; Humans; Sofosbuvir; Taiwan

Despite a known risk of hepatitis B virus (HBV) reactivation during direct-acting antiviral (DAA) treatment for patients with hepatitis C virus (HCV)-HBV coinfection, it remains unclear whether patients with past HBV infection are at risk for reactivation. This study evaluated the risk of HBV reactivation during treatment with sofosbuvir (SOF)-based regimens, focusing on patients with resolved HBV infection.. This study analyzes the data of 183 consecutive patients treated with SOF-based regimens. From these patients, 63 with resolved HBV infection (negative for hepatitis B surface antigen [HBsAg] and undetectable HBV DNA but positive for hepatitis B core antibody) were eligible for this study. HBV reactivation was defined as a quantifiable HBV DNA level >20 IU/mL.. Among the patients antibody to HBsAg (anti-HBs) positive (10-500 mIU/mL) (n = 30), the titre of anti-HBs was significantly decreased with time, as shown by the results of repeated-measures analysis of variance (P = .0029). Overall, four patients (6.3%) with resolved HBV infection came to have detectable HBV DNA during treatment, including one who had HBV reactivation at week 4 (HBV DNA 80 IU/mL). However, none developed hepatic failure. Among four patients who had detectable HBV DNA during treatment, all were negative or had very low-titre (<20 mIU/mL) anti-HBs at baseline.. The titre of anti-HBs was significantly decreased from the early stage of DAA treatment. Chronic hepatitis C patients with resolved HBV infection and negative or very low-titre anti-HBs at baseline are at risk for having detectable HBV DNA transiently during treatment.

Topics: Aged; Antiviral Agents; Benzimidazoles; DNA, Viral; Female; Fluorenes; Hepacivirus; Hepatitis B; Hepatitis B Antibodies; Hepatitis B virus; Hepatitis C, Chronic; Humans; Male; Middle Aged; Retrospective Studies; Ribavirin; Risk Assessment; Risk Factors; Sofosbuvir; Time Factors; Treatment Outcome; Virus Activation

Anti-PD-1 monoclonal antibodies have shown durable long-term survival benefit in patients with metastatic melanoma. Limited evidence exists on the safety and efficacy of PD-1 inhibitors in patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections as these patients have traditionally been excluded from clinical trials because of a theoretical risk of immune reconstitution inflammatory syndrome. We aim to determine the safety and efficacy of treatment with PD-1 inhibitors in seven patients with HBV/HCV infection and concurrent metastatic melanoma or non-small-cell lung cancer (NSCLC). We describe seven patients treated with PD-1 inhibitors nivolumab and pembrolizumab for either metastatic melanoma or metastatic NSCLC in the setting of chronic or past HBV/HCV infection. The safety and efficacy of treatment were analysed retrospectively by examining response to treatment, alanine transaminase (ALT) trends and viral load trends. One patient showed an increase in ALT of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 severity that returned to the normal range following treatment of his HCV infection with ledipasvir 90 mg/sofosbuvir 400 mg. An additional four patients showed an increase in ALT of CTCAE grade 1 severity. The remaining two patients experienced no hepatic toxicity, with stable disease continuing after more than 24 cycles of nivolumab. Efficacy was similar to the data of published trials. Our results indicate that patients with metastatic melanoma and NSCLC can be treated safely with PD-1 inhibitors in the context of HBV/HCV infection. However, we recommend that those with active viral hepatitis be monitored closely in consultation with a hepatologist and treated with antiviral therapy if indicated.

Topics: Aged; Antibodies, Monoclonal, Humanized; Benzimidazoles; Carcinoma, Non-Small-Cell Lung; Fluorenes; Hepatitis B; Hepatitis C; Humans; Interferons; Lung Neoplasms; Male; Melanoma; Middle Aged; Nivolumab; Programmed Cell Death 1 Receptor; Skin Neoplasms; Sofosbuvir

Hepatitis B reactivation in patients with resolved HBV can occur during hepatitis C treatment with direct-acting antivirals, but only a few cases have been described. It is not clear which patients are at risk for HBV reactivation and how to manage them.. Three patients (all hepatitis B surface antigen [HBsAg]-negative, antibody to hepatitis B core [anti-HBc] positive and HBV DNA negative) experienced a late HBV reactivation 12 weeks post-treatment but were able to control their viraemia. HCV RNA, HBV DNA, anti-HBc and anti-HBs were measured in these patients and in 37 HBsAg-negative, anti-HBc positive, HBV DNA negative control patients during direct-acting antiviral therapy for chronic hepatitis C.. Baseline anti-HBs do not differ between patients with and without HBV reactivation. Patients with HBV reactivation, however, significantly increased their anti-HBs at time of reactivation, while patients without HBV reactivation show stable anti-HBs during therapy (P=0.007).. Anti-HBs might be an important marker to delineate patients at risk for clinically significant HBV reactivation.

Topics: Antiviral Agents; Benzimidazoles; DNA, Viral; Female; Fluorenes; Hepacivirus; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Core Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis C, Chronic; Humans; Male; Middle Aged; Prospective Studies; Sofosbuvir; Viremia; Virus Activation

Topics: Benzimidazoles; Coinfection; Fluorenes; Hepatitis B; Hepatitis B virus; Hepatitis C, Chronic; HIV Infections; Humans; Sofosbuvir

Topics: Benzimidazoles; Coinfection; Fluorenes; Hepatitis B; Hepatitis B virus; Hepatitis C, Chronic; HIV Infections; Humans; Sofosbuvir

Topics: Antiviral Agents; Benzimidazoles; Drug Therapy, Combination; Fluorenes; Hepatitis B; Hepatitis C, Chronic; Humans; Recurrence; Sofosbuvir; Time Factors; Treatment Outcome

Currently there are no all-oral treatment regimens for HCV in patients coinfected with HBV. In this pilot study, we evaluated whether ledipasvir and sofosbuvir therapy can suppress HCV infection in patients coinfected with HBV.. Patients with HBV and genotype-1 HCV received 90 mg ledipasvir and 400 mg sofosbuvir daily for 12 weeks. The efficacy end point was sustained virological response (HCV RNA <15 IU/ml) 12 weeks after the end of treatment.. Of the eight patients enrolled, six (75%) were male, five (63%) were Polynesian, seven (88%) had the CC IL28B genotype and two (25%) had cirrhosis. All eight patients (100%; 95% CI 63%, 100%) reached the primary end point of HCV RNA <15 IU/ml 12 weeks after treatment. In seven of eight patients (88%), serum HBV DNA levels increased during treatment, but none of the increases were greater than 20,000 IU/ml, and none were associated with clinical HBV flares or required treatment. The most common adverse events were viral infection (63%), fatigue (25%) and upper respiratory tract infection (25%). No patients had serious adverse events and none discontinued treatment for any reason.. In this small sample, 12 weeks of ledipasvir/sofosbuvir was a safe and effective treatment for genotype-1 HCV infection in patients coinfected with HBV. Larger studies with longer follow-up are warranted.

Topics: Aged; Antiviral Agents; Benzimidazoles; Coinfection; DNA, Viral; Drug Therapy, Combination; Female; Fluorenes; Hepatitis B; Hepatitis C; Humans; Male; Middle Aged; Pilot Projects; Sofosbuvir