Tenofovir Disoproxil Fumarate Reduces the Severity of COVID-19 in Patients with Chronic Hepatitis B.

BACKGROUND AND AIMS: HIV-positive patients on tenofovir hydroxyl fumarate (TDF)/emtricitabine have a lower risk of COVID-19 and hospitalization than those given other treatments. Our aim was to analyze the severity of COVID-19 in patients with chronic hepatitis B (CHB) on TDF or entecavir (ETV). METHODS: Spanish hospital databases (n = 28) including information regarding adult CHB patients on TDF or ETV for the period February 1st to November 30th 2020 were searched for COVID-19, defined as a positive SARS-CoV-2 polymerase chain reaction, and for severe COVID-19. RESULTS: Of 4736 patients, 117 had COVID-19 (2.5%), 67 on TDF and 50 on ETV. Compared to patients on TDF, those on ETV showed (p < 0.05) greater rates of obesity, diabetes, ischemic cardiopathy, and hypertension. COVID-19 incidence was similar in both groups (2.3 vs. 2.6%). Compared to TDF, patients on ETV more often (p < 0.01) had severe COVID-19 (36 vs. 6%), required intensive care unit (ICU) (10% vs. 0) or ventilatory support (20 vs. 3%), were hospitalized for longer (10.8 ± 19 vs. 3.1 ± 7 days) or died (10 vs. 1.5%, p = 0.08). In an IPTW propensity score analysis adjusted for age, sex, obesity, comorbidities, and fibrosis stage, TDF was associated with a sixfold reduction in severe COVID-19 risk (adjusted-IPTW-OR 0.17, 95%CI 0.04-0.67, p = 0.01). CONCLUSION: Compared to ETV, TDF seems to play a protective role in CHB patients with SARS-CoV-2 whereby the risk of severe COVID-19 is lowered.

Factors associated with diagnosis delay in head and neck cancer.

INTRODUCTION AND OBJECTIVES: Tumour stage is an important prognostic factor in head and neck tumours. Many tumours are diagnosed in advanced stages despite almost universal healthcare and their being symptomatic. This paper seeks to determine the diagnostic delay in head and neck tumours in our health department, to analyse factors associated with delay and if it is associated with diagnosis in advanced stages. METHODS: Retrospective study of 137 patients with head and neck cancer diagnosed from 2016-2018. Patient delay, delay in primary health care, delay in secondary health care, diagnostic delay and possible associated factors (smoking, location, stage, …) were evaluated. RESULTS: Many patients (44.5%) were diagnosed in advanced stages. The median patient delay was 30 days. The median referral to otorhinolaryngology was 3.5 days. If the referral was made by another specialist (p = .008), the patients were under previous treatment (P=.000) and the tumours were in initial stages (P=.038) this delay was greater. The median from the first visit to otorhinolaryngology was 15 days, higher in regular referrals (43%) (P=.000). The median diagnostic delay was 12 days, higher in surgical biopsies (P=.000). The median professional delay was 58.5 days and total delay was 118.5 days. CONCLUSIONS: Many head and neck tumours are diagnosed in advanced stages. A relationship was not found between diagnosis in advanced stages and diagnostic delay. However, steps must be taken to reduce these excessive delays.

Are Steroids Still Useful in Immunosuppressed Patients With Inflammatory Bowel Disease? A Retrospective, Population-Based Study.

Background: Effectiveness of corticosteroids in immunosuppressed patients with inflammatory bowel disease (IBD) has not been completely elucidated. Aims: To assess the effectiveness and examine the long-term follow-up of systemic or low-bioavailability oral steroid treatment for moderate flare-ups in patients treated with immunosuppressive drugs. Methods: Immunosuppressed patients with inflammatory bowel disease (IBD) from our population-data registry were analyzed. For statistical analysis, the chi-square test, Mann-Whitney U test, and Kaplan-Meier survival analysis were used as appropriate. Results: A total of 392 patients with IBD and a median of 82 (range, 6-271) months of immunosuppressive (IMM) treatment were identified. The mean follow-up was 87 months (range, 6-239 months). A total of 89 patients (23%) needed at least one steroid course during their follow-up. Average time from IMM to steroid treatment was 26 (range, 6-207) months. In patients with CD, fibrostenotic (B2) and fistulizing (B3) behaviors [p = 0.005; odds ratio (OR): 2.284] were risk factors for using steroids after IMM treatment. In patients with UC, no statistically significant variables were identified. Of the 89 patients who received one first steroid course, 49 (55%) stepped up to biological treatment or surgery after a median of 13 months (range, 0-178), 19 (21%) were treated with repeated steroid courses, and 31 (35%) required no further treatment. Patients with CD had a higher risk (p = 0.007; OR: 3.529) of receiving biological treatment or surgery than patients with UC. The longer the patients with UC (more months) spent using steroids, the greater the risk of requiring treatment with biological drugs or surgery (p = 0.009). Conclusion: A total of 23% of the immunosuppressed patients with IBD received at least one course of steroid treatment. In patients under immunosuppression treated with at least a course of steroids, CD patients were more likely stepped up to biologics and/or surgery than UC patients. In patients with CD, B2/B3 behavior pattern were significant risk factors. After one course of steroids only 35% of immunosuppressed IBD patients remained in remission without needing treatment scalation.

Factors associated with diagnosis delay in head and neck cancer. / Factores asociados a la demora diagnóstica en tumores de cabeza y cuello.

INTRODUCTION AND OBJECTIVES: Tumour stage is an important prognostic factor in head and neck tumours. Many tumours are diagnosed in advanced stages despite almost universal healthcare and their being symptomatic. This paper seeks to determine the diagnostic delay in head and neck tumours in our health department, to analyse factors associated with delay and if it is associated with diagnosis in advanced stages. METHODS: Retrospective study of 137 patients with head and neck cancer diagnosed from 2016-2018. Patient delay, delay in primary health care, delay in secondary health care, diagnostic delay and possible associated factors (smoking, location, stage, …) were evaluated. RESULTS: Many patients (44.5%) were diagnosed in advanced stages. The median patient delay was 30 days. The median referral to otorhinolaryngology was 3.5 days. If the referral was made by another specialist (p=.008), the patients were under previous treatment (P=.000) and the tumours were in initial stages (P=.038) this delay was greater. The median from the first visit to otorhinolaryngology was 15 days, higher in regular referrals (43%) (P=.000). The median diagnostic delay was 12 days, higher in surgical biopsies (P=.000). The median professional delay was 58.5 days and total delay was 118.5 days. CONCLUSIONS: Many head and neck tumours are diagnosed in advanced stages. A relationship was not found between diagnosis in advanced stages and diagnostic delay. However, steps must be taken to reduce these excessive delays.

Effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in patients with chronic hepatitis C previously treated with DAAs.

BACKGROUND & AIMS: Around 5% of patients with chronic hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents do not achieve sustained virological response (SVR). The currently approved retreatment regimen for prior DAA failure is a combination of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX), although there is little data on its use in clinical practice. The aim of this study was to analyse the effectiveness and safety of SOF/VEL/VOX in the real-world setting. METHODS: This was a prospective multicentre study assessing the efficacy of retreatment with SOF/VEL/VOX in patients who had experienced a prior DAA treatment failure. The primary endpoint was SVR 12 weeks after the completion of treatment (SVR12). Data on safety and tolerability were also recorded. RESULTS: A total of 137 patients were included: 75% men, 35% with liver cirrhosis. Most were infected with HCV genotype (GT) 1 or 3. The most common prior DAA combinations were sofosbuvir plus an NS5A inhibitor or ombitasvir/paritaprevir/r+dasabuvir. A total of 136 (99%) patients achieved undetectable HCV RNA at the end of treatment. Overall SVR12 was 95% in the 135 patients reaching this point. SVR12 was lower in patients with cirrhosis (89%, p = 0.05) and those with GT3 infection (80%, p <0.001). Patients with GT3 infection and cirrhosis had the lowest SVR12 rate (69%). Of the patients who did not achieve SVR12, 1 was reinfected and 7 experienced treatment failure (6 GT3, 1 GT1a). The presence of resistance-associated substitutions did not impact SVR12. Adverse effects were mild and non-specific. CONCLUSION: Real-world data show that SOF/VEL/VOX is an effective, safe rescue therapy for patients with prior DAA treatment failure despite the presence of resistance-associated substitutions. However, patients with liver cirrhosis infected by GT3 remain the most-difficult-to-treat group. LAY SUMMARY: Treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks is the current recommendation for the 5% of patients infected with HCV who do not achieve eradication of the virus under treatment with direct-acting antivirals. In a Spanish cohort of 137 patients who failed a previous combination of direct-acting antivirals, a cure rate of 95% was achieved with SOF/VEL/VOX. Genotypic characteristics of the virus (genotype 3) and the presence of cirrhosis were factors that decreased the rate of cure. Treatment with SOF/VEL/VOX is an effective and safe rescue therapy due to its high efficacy and very good safety profile.

Eight weeks of Paritaprevir/r/Ombitasvir + Dasabuvir in HCV genotype 1b with mild-moderate fibrosis: Results from a real-world cohort.

BACKGROUND & AIMS: The interferon-free regimen paritaprevir/ritonavir, ombitasvir + dasabuvir (PTV/r/OBV/DSV) has shown high efficacy in patients with hepatitis C virus (HCV) genotype 1b infection when administered for 8 or 12 weeks, but data regarding the 8-week treatment are scarce. The aim of our study was to assess the efficacy and safety of the 8-week administration of PTV/r/OBV/DSV in a real-world cohort. METHODS: We performed a multicentre observational study from Spanish Hepa-C database including patients receiving 8 weeks of PTV/r/OBV/DSV (October 2016-November 2017). Those with advanced fibrosis, with non-genotype 1b or who were treatment-experienced were excluded. RESULTS: A total of 211 patients were registered from 23 Spanish centres; eleven were excluded. At baseline, 42.5% (n = 85) were male, median (range) age was 57 (23-86), ALT was 45 (11-494) IU/mL, viral load was 6.1 (3.3-8.2) log10 IU/mL, and 74.5% had mild liver fibrosis (F0-F1) and 25.5% moderate fibrosis (F2). At the end of treatment (EOT), HCV viral load was undetectable in 100% (200/200). Seven patients relapsed after treatment discontinuation. Sustained virological response (SVR12) rates by intention-to-treat analysis were 96% (192/200). Regarding treatment safety, 2 patients developed ALT elevation >5x ULN, but there were no treatment discontinuations. One patient died 7 weeks after EOT. CONCLUSION: Treatment with PTV/r/OBV/DSV in genotype 1b-infected treatment-naive patients with mild-moderate fibrosis shows excellent efficacy and safety in real life, similarly to clinical trials. Clinicaltrials.gov, number: NCT03122132.

Effectiveness and safety of elbasvir/grazoprevir therapy in patients with chronic HCV infection: Results from the Spanish HEPA-C real-world cohort.

In randomized controlled trials of patients with chronic HCV infection, elbasvir/grazoprevir (EBR/GZR) demonstrated high cure rates and a good safety profile. This study assessed the effectiveness and safety of EBR/GZR, with and without ribavirin, in a real-world HCV patient cohort. HEPA-C is a collaborative, monitored national registry of HCV patients directed by the Spanish Association for the Study of the Liver and the Networked Biomedical Research Centre for Hepatic and Digestive Diseases. Patients entered into HEPA-C between December 2016 and May 2017, and treated with EBR/GZR with at least end-of-treatment response data, were included. Demographic, clinical and virologic data were analysed, and adverse events (AEs) recorded. A total of 804 patients were included in the study. The majority were male (57.9%), with a mean age of 60 (range, 19-92) years. Genotype (GT) distribution was GT 1, 86.8% (1a, 14.3%; 1b, 72.5%); GT 4, 13.2% and 176 patients (21.9%) were cirrhotic. Overall, among 588 patients with available data, 570 (96.9%) achieved sustained virologic response at 12 weeks post-treatment (SVR12). SVR12 rates by genotype were GT 1a, 97.7%; GT 1b, 98.6%; and GT 4, 98.1%. No significant differences in SVR12 according to fibrosis stage were observed. Eighty patients experienced an AE, resulting in treatment discontinuation in three. In this large cohort of patients with chronic HCV managed in a real-world setting in Spain, EBR/GZR achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with a similarly good safety profile.

Interferon-free treatments in patients with hepatitis C genotype 1-4 infections in a real-world setting.

AIM: To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus (HCV). METHODS: We performed an observational study to analyze different antiviral treatments administered to 462 HCV-infected patients, of which 56.7% had liver cirrhosis. HCV RNA after 4 wk of treatment and at 12 wk after treatment sustained virologic response (SVR) as well as serious adverse events (SAEs) was analyzed first for the whole cohort and then separately in patients who met or did not meet the inclusion criteria of a clinical trial (CT-met and CT-unmet, respectively). RESULTS: The most frequently prescribed treatment was simeprevir/sofosbuvir (36.4%), followed by sofosbuvir/ledipasvir (24.9%) and ombitasvir/paritaprevir/ritonavir (r)/dasabuvir (19.9%). Ribavirin (RBV) was administered in 198 patients (42.9%). SVRs occurred in 437/462 patients (94.6%). The SVRs ranged between 93.3% and 100% for genotypes 1-4. SVRs were achieved in 96.2% patients in the CT-met group vs 91.9% patients in the CT-unmet group (P = 0.049). Undetectable HCV RNA at week 4 occurred in 72.9% of the patients. In the univariate analysis, the factors associated with SVRs were lower liver stiffness, absence of cirrhosis, higher platelet count, higher albumin levels, no RBV dose reduction, undetectable HCV RNA at week 4 and CT-met group. In the multivariate analysis, only albumin was an independent predictor of treatment failure (P = 0.04). Eleven patients (2.4%) developed SAEs; 5.2% and 0.7% of the patients in the CT-unmet and CT-met groups, respectively (P = 0.003). CONCLUSION: A high proportion of patients with HCV infection achieved SVRs. For patients who did not meet the CT criteria, treatment regimens must be optimized.

Treatment of hepatitis C virus infection in patients with cirrhosis and predictive value of model for end-stage liver disease: Analysis of data from the Hepa-C registry.

Direct-acting antiviral agents (DAAs) are highly effective and well tolerated in patients with chronic hepatitis C virus infection, including those with compensated cirrhosis. However, fewer data are available in patients with more advanced liver disease. Our retrospective, noninterventional, national, multicenter study in patients from the Spanish Hepa-C registry investigated the effectiveness and safety of interferon-free DAA regimens in patients with advanced liver disease, including those with decompensated cirrhosis, in routine practice (all currently approved regimens were registered). Patients transplanted during treatment or within 12 weeks of completing treatment were excluded. Among 843 patients with cirrhosis (Child-Turcotte-Pugh [CTP] class A, n = 564; CTP class B/C, n = 175), 90% achieved sustained virologic response 12 weeks after treatment (SVR12). Significant differences in SVR12 and relapse rates were observed between CTP class A and CTP class B/C patients (94% versus 78%, and 4% versus 14%, respectively; both P < 0.001). Serious adverse events (SAEs) were more common in CTP class B/C versus CTP class A patients (50% versus 12%, respectively; P < 0.001). Incident decompensation was the most common serious adverse event (7% overall). Death rate during the study period was 16/843 (2%), significantly higher among CTP class B/C versus CTP class A patients (6.4% versus 0.9%; P < 0.001). Baseline Model for End-Stage Liver Disease (MELD) score alone (cut-off 18) was the best predictor of survival. CONCLUSION: Patients with decompensated cirrhosis receiving DAAs present lower response rates and experience more SAEs. In this setting, a MELD score ≥18 may help clinicians to identify those patients with a higher risk of complications and to individualize treatment decisions. (Hepatology 2017;65:1810-1822).

Evaluation of advanced fibrosis measured by transient elastography after hepatitis C virus protease inhibitor-based triple therapy.

AIM: Few studies have investigated the course of liver stiffness after treatment with protease inhibitors. We evaluated the impact of this therapy on liver fibrosis measured by transient elastography. METHODS: This multicenter observational, cohort, prospective study included 90 patients with hepatitis C genotype 1 treated with telaprevir or boceprevir who had advanced fibrosis evidenced by liver stiffness (≥9.5 kPa). Liver stiffness was measured at baseline and 24 weeks after treatment ended, and was compared with virological responses at week 12. RESULTS: Liver stiffness decreased in 89% of patients who achieved sustained virological response. The median intrapatient liver stiffness value at the end of follow-up decreased by 5.1 kPa (35%) from baseline compared with 0.1 kPa (0.5%) in those who did not achieve a sustained virological response (P<0.001). The liver stiffness level fell below 9.5 kPa in 58% of patients with sustained virological response, and 71% of those with sustained virological response and cirrhosis evidenced by liver stiffness at baseline achieved regression below 12.5 kPa by the end of follow-up. Sustained virological response was the only variable associated with improved liver stiffness in multivariate analysis (odds ratio: 17.3; 95% confidence interval: 4.4-67.6; P<0.001). CONCLUSION: In patients with advanced fibrosis measured by transient elastography at the beginning of protease inhibitor-based therapy with sustained virological response, liver stiffness was significantly reduced 24 weeks after treatment. This suggests the possibility of liver cirrhosis evidenced by liver stiffness regression after sustained virological response in a significant proportion of patients.

[Prosthetic joint infection: a prospective study in five Catalonian hospitals]. / Infección de prótesis articulares: estudio prospectivo en 5 hospitales de Cataluña.

BACKGROUND: Prosthetic joint infections are a cause of increasing morbidity and medical expenditure. OBJECTIVES: To determine the incidence and the clinical and the epidemiological characteristics of knee and hip prosthetic infections (PI) in patients undergoing elective surgery in five Catalonian hospitals. To determine the predictive factors of PI. METHODS: A total of 425 patients operated on between 8 January and 8 July 2001 were prospectively followed for a period of two years. The cumulative incidence, incidence rate and effect measures were determined. Logistic regression was used to identify variables associated with PI. RESULTS: Average age was 71 years and 63.1% were women. Antibiotic prophylaxis with cefazolin was given to 44.7% of the patients, with a mean duration of two days. Prophylaxis was administered during anesthesia induction in 75.6% of the patients. Among the total, 63.4% of the patients were ASA 2. Microbiological confirmation was obtained in all the infected patients; Staphylococcus epidermidis was found in 58%. Fourteen PI were diagnosed, 71% during the first 3 months, with a cumulative incidence of 3.29% and a 3-month incidence rate of 63 patients/10,000 patients/month. Diabetes mellitus was the only variable related to PI in the multivariate analysis: 3.18, 95% CI (1.1-9.9). CONCLUSIONS: The cumulative incidence of PI was slightly higher than that seen in other studies. Variations were observed in the antibiotic used for prophylaxis, and the place where it was administered. PI occurred 3.18 times more frequently in diabetic patients.