gs-5816 and Liver-Neoplasms

Topics: Antiviral Agents; Carcinoma, Hepatocellular; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Liver Neoplasms; Ribavirin; Sofosbuvir; Sustained Virologic Response; Treatment Outcome

Topics: Aminoisobutyric Acids; Antiviral Agents; Carbamates; Carcinoma, Hepatocellular; Cyclopropanes; Guanine; Hepatitis B, Chronic; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Lactams, Macrocyclic; Leucine; Liver Neoplasms; Liver Transplantation; Macrocyclic Compounds; Proline; Quinoxalines; Salvage Therapy; Sofosbuvir; Sulfonamides; Tenofovir; Transplants

The sofosbuvir (SOF) / velpatasvir (VEL) / voxilaprevir (VOX) combination has been evaluated in more than 800 patients enrolled in phase II and phase III studies, where it demonstrated excellent safety and efficacy, achieving overall sustained viral response (SVR) rates of more than 95%. We aimed to assess the efficacy and safety of SOF/VEL/VOX in a real-world study, including patients previously treated for genotype 1b hepatitis C virus (HCV) infection that did not obtain a sustained viral response with previous direct-acting antivirals (DAAs) therapy.. In Romania, through a nationwide government-funded program in 2019-2020, 213 patients with chronic hepatitis C non-responders to previous DAAs therapy, received treatment with SOF/VEL/ VOX 400/100/100 mg/day for 12 weeks. We performed a retrospective longitudinal study that included 143 individuals who were treated in Bucharest, Iași, Craiova and Constanța clinics, all with genotype 1b HCV infection. Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). Serious adverse events (SAE) were registered.. Our cohort comprised 53% males with a median age of 60 years (27÷77); 47% were pre-treated with ombitasvir/paritaprevir/ritonavir+dasabuvir ± ribavirin, 40% with ledipasvir/SOF, 13% with elbasvir/ grazoprevir. 42% of patients associated co-morbidities, 45% had compensated liver cirrhosis, 2% had treated hepatocellular carcinoma (HCC) and 1% had hepatitis B virus co-infection. SVR by intention to treat was reported in 139/143 (97.2%) and per protocol in 141/143 (98.6%). No predictive factors for SVR were identified. Rate of liver decompensation in patients with cirrhosis was 6% and was statistically associated in multivariate analysis with Child-Pugh score (p<0.01) and with severe steatosis (p=0.004). Occurrence of new HCC was reported in 3.6% of all patients with cirrhosis and was associated with poor liver function [higher Child-Pugh score (p=0.001) and low albumin levels (p=0.02)]. Serious adverse events related to therapy were reported in 1/143(0.7%).. SOF/VEL/VOX was highly efficient in our population of patients with a 97.2% SVR. Liver decompensation occurred in 6% of cirrhotic patients at SVR, related to hepatic dysfunction.

Topics: Antiviral Agents; Carcinoma, Hepatocellular; Drug Therapy, Combination; Female; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Liver Neoplasms; Longitudinal Studies; Male; Middle Aged; Retrospective Studies; Romania; Sofosbuvir; Sustained Virologic Response; Treatment Outcome

Current literature indicates that direct-acting antivirals (DAAs) are cost-effective to treat compensated cirrhotic patients with hepatitis C. Although already funded by public payers, it is unknown whether it is economical to reimburse DAAs within the more advanced decompensated cirrhosis population.. A state-transition model was developed to conduct a cost-utility analysis of sofosbuvir-velpatasvir (SOF/VEL) plus ribavirin regimen for 12 weeks. The evaluated cohort had a mean age of 58 years and Child-Turcotte-Pugh (CTP) class B cirrhosis with decompensated symptoms. A scenario analysis was performed on CTP C patients. We used a payer perspective, a lifetime time horizon and a 1.5% annual discount rate.. While SOF/VEL plus ribavirin treatment for 12 weeks increased costs by $156 676, it provided an extra 4.00 quality-adjusted life years (QALYs) compared to best supportive care (no DAA therapy). With an incremental cost-effectiveness ratio of $39 169 per QALY, SOF/VEL plus ribavirin was determined to be cost-effective at a willingness to pay of $50 000 per QALY. SOF/VEL reduced liver-related deaths and reduced progression to CTP C cirrhosis by 20.4% and 21.9%, respectively. On the contrary, SOF/VEL regimen resulted in increases in liver transplants and hepatocellular carcinoma (HCC) by 54.0% and 42.5%, respectively. Similar results were found for CTP C patients.. This analysis informs payers that SOF/VEL should continue to be reimbursed in decompensated hepatitis C patients. It also supports the recommendations by the American Association for the Study of Liver Diseases to continue screening for HCC in decompensated cirrhotic patients who have achieved sustained virologic response.

Topics: Antiviral Agents; Carbamates; Carcinoma, Hepatocellular; Cost-Benefit Analysis; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Infant, Newborn; Liver Cirrhosis; Liver Neoplasms; Ribavirin; Sofosbuvir; Treatment Outcome

Chronic hepatitis C (CHC) is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and mortality. Eliminating hepatitis C virus (HCV) can greatly improve long-term outcomes. Several direct-acting antiviral agents (DAAs), including sofosbuvir (SOF) plus different NS5A inhibitors, as well as non-SOF-based DAAs, including glecaprevir/pibrentasvir (GLE/PIB), have been approved for treating CHC genotype-2 (GT-2) patients in Taiwan. However, there is limited real-world effectiveness data regarding these different regimens. Thus, we aimed to evaluate the real-world efficacy in CHC GT-2 patients who underwent these DAA regimens. We retrospectively enrolled CHC GT-2 patients who were treated with SOF-based DAAs or GLE/PIB at a single medical center. A total of 704 enrolled patients were treated with either SOF + ribavirin (RBV), SOF/daclatasvir (DCV) ± RBV, SOF/ledipasvir (LDV) ± RBV, SOF/velpatasvir (VEL) ± RBV, or with GLE/PIB. The overall sustained virological response (SVR) rate was 97.9%. The SVR rate was significantly lower in the SOF + RBV group (95.6%) than in the non-SOF + RBV (98.9%) group, especially compared to the SOF/DCV (100%) and GLE/PIB groups (99.5%). Among patients treated with SOF + RBV, cirrhotic patients had significantly lower SVR rates than noncirrhotic patients (89.4% vs 98.2%). Multivariate analysis showed that patients with a younger age, hepatitis B virus coinfection, baseline cirrhosis, or those who received SOF + RBV were less likely to achieve SVR. In conclusion, for CHC GT-2 patients, SOF in combination with DCV, LDV, or VEL, as well as GLE/PIB, achieved similar high efficacies, regardless of cirrhosis, treatment experience, or chronic kidney disease status. Therefore, the use of DAA therapy to eradicate HCV should not be delayed in these populations.

Topics: Age Factors; Aged; Antiviral Agents; Benzimidazoles; Carbamates; Carcinoma, Hepatocellular; Drug Combinations; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Imidazoles; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Multivariate Analysis; Pyrrolidines; Quinoxalines; Retrospective Studies; Ribavirin; Sofosbuvir; Sulfonamides; Taiwan; Treatment Outcome; Valine

Topics: Adult; Antiviral Agents; Carbamates; Child; Fatty Liver; Female; Hepacivirus; Hepatectomy; Hepatitis C; Heterocyclic Compounds, 4 or More Rings; Humans; Liver Function Tests; Liver Neoplasms; Liver Transplantation; Living Donors; Monitoring, Physiologic; Sofosbuvir; Transplant Recipients; Treatment Outcome; Viral Load

In this study, the authors report the case of a patient diagnosed with hepatitis C virus who was treated with sofosbuvir-velpatasvir (400/100 mg). As the patient was unable to swallow whole tablets, therapeutic drug monitoring was performed to evaluate the effect of crushing sofosbuvir-velpatasvir tablets on drug absorption and global exposure.

Topics: Aged; Antiviral Agents; Benzimidazoles; Carbamates; Carcinoma, Hepatocellular; Drug Combinations; Drug Monitoring; Female; Half-Life; Hepatitis C; Heterocyclic Compounds, 4 or More Rings; Humans; Liver Neoplasms; Pyrrolidines; Quinoxalines; Sofosbuvir; Sulfonamides; Tablets

Topics: Aged; Antiviral Agents; Carbamates; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Liver Neoplasms; Lymphoma, Large B-Cell, Diffuse; Magnetic Resonance Imaging; Male; Radiography, Abdominal; Ribavirin; Sofosbuvir; Treatment Outcome

Data are sparse on treatment of chronic hepatitis C virus (HCV) in cancer patients. We evaluated the efficacy and safety of sofosbuvir-based therapy (SOFBT) in cancer patients.. Patients treated with SOFBT at our center during 2014-2017 were included in a prospective observational study. Efficacy [sustained virologic response at 12 weeks after the end of treatment (SVR12)], cancer-related outcomes and adverse events (AEs) were assessed.. We included 153 patients. Most were men (109; 71%), white (92; 60%), non-cirrhotic (105; 69%), and with HCV genotype 1 (110; 72%). The most common cancers were hepatocellular carcinoma (HCC) (27; 18%) and multiple myeloma (14; 9%). The overall SVR12 rate was 91% (128/141). SVR12 was 100% in patients treated with ledipasvir/sofosbuvir for 8 weeks. Of the 32 patients initially excluded from cancer clinical trials because of HCV, 27 (84%) were granted cancer therapy access after starting SOFBT. Six patients with indolent non-Hodgkin's lymphoma (NHL) received SOFBT without cancer treatment. Two achieved complete remission, one had partial remission, and two had stable cancer. Within 6 months after SOFBT, 5% (6/121) of patients in remission or with stable cancer, had progression or recurrence (two with HCC and one each with esophageal cancer, cholangiocarcinoma, NHL, and tonsillar cancer). No de novo HCCs occurred. AEs were most commonly grade 1-2 (90%).. SOFBT in HCV-infected cancer patients is effective and safe, may permit access to investigational cancer therapy expanding treatment options, may induce remission of NHL, and may be used for 8 weeks.

Topics: Aged; Antiviral Agents; Benzimidazoles; Breast Neoplasms; Carbamates; Carcinoma, Hepatocellular; Drug Therapy, Combination; Female; Fluorenes; Head and Neck Neoplasms; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Imidazoles; Interferons; Liver Neoplasms; Lymphoma, Non-Hodgkin; Male; Middle Aged; Multiple Myeloma; Neoplasms; Polyethylene Glycols; Prospective Studies; Pyrrolidines; Ribavirin; Simeprevir; Sofosbuvir; Sustained Virologic Response; Valine