SVR12 Higher than 97% in GT3 Cirrhotic Patients with Evidence of Portal Hypertension Treated with SOF/VEL without Ribavirin: A Nation-Wide Cohort Study

In clinical trials, a sofosbuvir/velpatasvir (SOF/VEL) pangenotypic single-tablet regimen was associated with high sustained virological response (SVR) rates at 12 weeks (SVR12) after the end of treatment, regardless of genotype and fibrosis stage. No real-life data on genotype 3 (GT3) cirrhotic patients with portal hypertension are available. The aim of this study was to assess the effectiveness of SOF/VEL in GT3 cirrhotics with portal hypertension. Patients with GT3 and advanced cirrhosis were treated for 12 weeks with SOF/VEL without ribavirin at five different centers in Italy from June 2017 to August 2018 and their SVR12 was assessed. Of the 227 GT3 cirrhotics evaluated, 205 met the inclusion criteria and 111 had transient elastography results ≥20 KPa. SVR12 was 97.6% (95% CI 94.4–98.9), rates were 99.1% (95% CI 95.7–99.8) in patients with ≥20 KPa and 95.8% (95% CI 89.5–98.3) in those with <20 KPa (p = 0.18). Analyzed by presence of esophageal varices, the SVR12 rates were 98.4% (95% CI 91.4–99.7) and 97.1% (95% CI 92.9–98.9) in patients without and with varices, respectively (p = 1.0). In real life, SOF/VEL GT3 cirrhotic patients with evidence of portal hypertension can achieve SVR12 levels comparable to those of patients without portal hypertension. These SVR12 rates are similar to what is reported in compensated cirrhosis treated within clinical trials.

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“SPLEEN STIFFNESS MEASUREMENT IN LIVER CIRRHOSIS PATIENTS FOR NONINVASIVE ASSESSMENT OF ESOPHAGEAL VARICES USING FIBROSCAN”

10.36106/ijsr/8609582 ◽

2020 ◽

pp. 1-2

Author(s):

Revathy Marimuthu Shanmugam ◽

Vinay C ◽

Sathya Gopalasamy ◽

Chitra Shanmugam

Keyword(s):

Liver Cirrhosis ◽

Portal Hypertension ◽

Esophageal Varix ◽

Esophageal Varices ◽

Transient Elastography ◽

Liver Stiffness ◽

Surrogate Marker ◽

Stiffness Measurement ◽

Spleen Stiffness ◽

Cirrhotic Patients

BACKGROUND: Many noninvasive surrogate marker for Portal hypertension or for the presence or grade of esophageal varices were studied..Splenomegaly along with splenic congestion secondary to splenic hyperdynamic circulation is seen secondary to Portal hypertension in cirrhotic patients that can be quantified by elastography. AIM:The aim of this study was to investigate whether spleen stiffness, assessed by TE, useful tool for grading chronic liver diseases and to compare its performance in predicting the presence and size of esophageal varices in liver cirrhosis patients. METHODOLOGY:86 patients with cirrhosis and 80 controls underwent transient elastography of liver and spleen for the assessment of liver stiffness (LSM) and spleen stiffness (SSM) . Upper GI endoscopy done in all Cirrhotic patients. RESULTS: Spleen stiffness showed higher values in liver cirrhosis patients as compared with controls: 58.2 kpa vs14.8 kpa (P < 0.0001) and also found to be significantly higher in cirrhotic patients compared with varices and those without varices (69.01 vs 42.05 kpa, P < 0.0001). Liver stiffness was also found to be higher in cirrhotic patients with varices when compared to patients without varices (38.5vs 21.2 kpa). Using both liver and spleen stiffness measurement we can predicted the presence of esophageal varices correctly. CONCLUSION: Spleen stiffness can be assessed using transient elastography, higher value correlated well with liver cirrhosis and presence of esophageal varices although it couldn’t correlate with grade of Esophageal Varix. Combined assessment of spleen and liver stiffness had better prediction of presence of Esophageal Varix.

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Validation of the Combined Model Based on Platelet Count and Albumin to Rule out High-Risk Varices in Liver Cirrhosis

BioMed Research International ◽

10.1155/2020/5783748 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Zhihui Duan ◽

Li Li ◽

Jinlong Li ◽

Shengyun Zhou

Keyword(s):

Platelet Count ◽

High Risk ◽

Transient Elastography ◽

Liver Stiffness ◽

Hepatitis B Infection ◽

Combined Model ◽

Blood Tests ◽

Compensated Cirrhosis ◽

Cirrhotic Patients ◽

Rule Out

Background. The Baveno VI criteria based on platelet count and liver stiffness, measured by transient elastography (TE), have been proposed to rule out high-risk varices (HRV) defined as medium or large-sized varices or the presence of high-risk stigmata (cherry red spots and red wale marks). However, TE is not available in all hospitals. Recently, the Rete Sicilia Selezione Terapia hepatitis C virus (RESIST-HCV) criteria recommended that cirrhotic patients with a platelet count>120000/μL and serum albumin>36 g/L could avoid esophagogastroduodenoscopy (EGD) screening for HRV. Aim. We aimed to validate the performance of the RESIST-HCV criteria in two cohorts predominantly characterized with hepatitis B infection. Methods. Patients with compensated cirrhosis who had blood tests within three months of performing EGD and TE were enrolled retrospectively from two centers. RESIST-HCV criteria were applied to identify patients who did not require EGD screening. Results. This study included 188 patients from the Xingtai cohort (28 (14.9%) with HRV) and 104 patients from the Beijing cohort (19 (18.3%) with HRV). Of the patients who met the RESIST-HCV criteria (83 in the Xingtai cohort and 26 in the Beijing cohort), 0 and 1 had HRV, respectively, accounting for 44.1% (Xingtai cohort) and 25% (Beijing cohort) of endoscopies that were unnecessary. In the combined cohort, 109 (37.3%) patients met the RESIST-HCV criteria, only 1 (0.9%) HRV was missed, and the negative predictive value was 99.1%. Baveno VI and Expanded Baveno VI criteria spared 15.6% and 23.3% of EGDs, respectively, while missing 0% and 4.8% of HRV, respectively. Conclusions. In our population, the combined criteria based on platelet count and serum albumin performed well, saving 30-40% of EGDs and correctly identifying 99.1% of patients who could safely avoid screening endoscopies for high-risk varices in compensated cirrhotic patients.

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Safety and Pharmacokinetics of Glecaprevir/Pibrentasvir in Adults With Chronic Genotype 1–6 Hepatitis C Virus Infections and Compensated Liver Disease

Clinical Infectious Diseases ◽

10.1093/cid/ciz022 ◽

2019 ◽

Vol 69 (10) ◽

pp. 1657-1664 ◽

Cited By ~ 5

Author(s):

Edward Gane ◽

Fred Poordad ◽

Neddie Zadeikis ◽

Joaquin Valdes ◽

Chih-Wei Lin ◽

...

Keyword(s):

Clinical Trials ◽

Hepatitis C Virus ◽

Liver Disease ◽

Hepatitis C ◽

Transient Elastography ◽

Fixed Dose ◽

Integrated Analysis ◽

Genotype 1 ◽

Hepatic Decompensation ◽

Compensated Cirrhosis

Abstract Background Untreated, chronic hepatitis C virus (HCV) infection may lead to progressive liver damage, which can be mitigated by successful treatment. This integrated analysis reports the safety, efficacy, and pharmacokinetics (PK) of the ribavirin-free, direct-acting, antiviral, fixed-dose combination of glecaprevir/pibrentasvir (G/P) in patients with chronic HCV genotype 1–6 infections and compensated liver disease, including patients with chronic kidney disease stages 4 or 5 (CKD 4/5). Methods Data from 9 Phase II and III clinical trials, assessing the efficacy and safety of G/P treatment for 8–16 weeks, were included. The presence of cirrhosis was determined at screening using a liver biopsy, transient elastography, or serum biomarkers. The objectives were to evaluate safety, the rate of sustained virologic response at post-treatment week 12 (SVR12), and steady-state PK by cirrhosis status. Results Among 2369 patients, 308 (13%) were Child-Pugh Class A, including 20 with CKD 4/5. Overall, <1% of patients experienced an adverse event (AE) that led to G/P discontinuation or G/P-related serious AEs (SAEs). The most common AEs were headache and fatigue, occurring at similar frequencies with and without cirrhosis. SAEs were more common in patients with CKD 4/5, but all were unrelated to G/P. There were no cases of drug-induced liver injury or clinically relevant hepatic decompensation. SVR12 rates were 96.4% (297/308) with compensated cirrhosis and 97.5% (2010/2061) without cirrhosis. PK analysis demonstrated a 2.2-fold increase in glecaprevir exposure, but not pibrentasvir exposure, in patients with compensated cirrhosis. Conclusions G/P was safe and efficacious in patients with compensated liver disease, including those with CKD 4/5. Clinical Trials Registration NCT02243280, NCT02243293, NCT02604017, NCT02640482, NCT02640157, NCT02636595, NCT02642432, NCT02651194, and NCT02446717

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Effectiveness, Safety, and Costs of Dolutegravir/Abacavir/Lamivudine Single-Tablet Regimen in a Real-Life Cohort of HIV-1 Adult Infected Patients

Annals of Pharmacotherapy ◽

10.1177/1060028019896638 ◽

2020 ◽

Vol 54 (7) ◽

pp. 633-643

Author(s):

Carmen Guadalupe Rodriguez-Gonzalez ◽

Esther Chamorro-de-Vega ◽

Cristina Ortega-Navarro ◽

Roberto Alonso ◽

Ana Herranz-Alonso ◽

...

Keyword(s):

Cox Regression ◽

Real Life ◽

Pill Burden ◽

Intention To Treat ◽

Real Life Data ◽

Single Tablet Regimen ◽

Study Population ◽

The Impact ◽

Hiv 1 ◽

Treat Analysis

Background: Real-life data on single-tablet regimen (STR) dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) is scarce, and concerns about DTG neuropsychiatric adverse events (NP-AEs) have recently arisen. Objective: To explore the effectiveness and safety, in particular NP-AEs, of DTG/ABC/3TC in a cohort of HIV-1 adult infected patients. Pill burden, adherence to this STR, and the impact of switching on costs were also evaluated. Methods: This was an observational, retrospective study. The study population included antiretroviral therapy (ART)-naive and treatment-experienced (TE) patients who started DTG/ABC/3TC between February 1, 2016, and October 31, 2016. Effectiveness and safety were analyzed at week 48 (W48) by intention-to-treat analysis. The Cox regression model was used to investigate predictors of DTG/ABC/3TC discontinuation. Results: A total of 253 patients were included (44 ART naïve, 209 TE). At W48, the proportion of patients with virological suppression was 72.7% (95% CI = 58.4-87.0) in ART-naive patients, 85.6% (95% CI = 80.3-90.9) in previously suppressed TE patients, and 86.4% (95% CI = 65.1-97.1) in previously not suppressed TE patients. The rate of protocol-defined virological failure was 4.3%. The incidence of AEs was higher in the subgroup of ART-naive patients (56.1% vs 39.0%), with a rate of interruptions for this reason of 13.6% and 7.6%, respectively. The incidence of NP-AEs was 20.6%, with 3.9% of patients requiring discontinuation. Patients who had switched from a raltegravir-containing regimen discontinued DTG/ABC/3TC because of AEs more frequently (relative risk = 2.83; 95% CI = 1.04-7.72; P = 0.041) in the multivariate analysis. After switching to DTG/ABC/3TC, the median pill burden was reduced from 3 to 1 and the proportion of patients with an adherence <90%, from 20.1% to 12.0%. The annual per-patient ART costs increased by €48 (0.6% increase). Conclusion and Relevance: DTG/ABC/3TC is an effective strategy as first-line and switching ART. Our data suggest a worse tolerance in ART-naive patients, although the rate of discontinuation resulting from NP-AEs was relatively low. In the short-term, the adherence was slightly improved without significant changes in costs.

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Rapid Development of Bleeding Esophageal Varices after Placement of Continuous Flow Left Ventricular Assist Device

Case Reports in Hepatology ◽

10.1155/2019/8410420 ◽

2019 ◽

Vol 2019 ◽

pp. 1-3

Author(s):

Kaushal Majmudar ◽

Michael Northcutt ◽

Robert Gordon ◽

Claus J. Fimmel

Keyword(s):

Portal Hypertension ◽

Esophageal Varices ◽

Continuous Flow ◽

Rapid Development ◽

Fatal Outcome ◽

Left Ventricular ◽

Ventricular Assist ◽

Compensated Cirrhosis ◽

Bleeding Esophageal Varices ◽

Cirrhotic Patients

We describe a patient with compensated cirrhosis and portal hypertension who underwent continuous flow LVAD implantation. Shortly after LVAD implantation, the patient developed new onset bleeding esophageal varices and ultimately had a fatal outcome. Our experience suggests that even well-compensated cirrhotic patients with significant portal hypertension are at risk of variceal bleeding after LVAD placement.

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OC-062 Real Life Data on Sofosbuvir/Ledipasvir for 8 Weeks in Genotype 1 Treatment Naive, Non Cirrhotic Patients in the North East of Scotland: Abstract OC-062 Table 1

Gut ◽

10.1136/gutjnl-2016-312388.61 ◽

2016 ◽

Vol 65 (Suppl 1) ◽

pp. A37.1-A37

Author(s):

P Dundas ◽

A Fraser ◽

S English ◽

L McLeman ◽

Keyword(s):

Real Life ◽

Genotype 1 ◽

Life Data ◽

North East ◽

The North ◽

Real Life Data ◽

Treatment Naïve ◽

Cirrhotic Patients

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PTH-109 Real Life Data on Sofosbuvir/Ledipasvir + Ribavirin for 12 Weeks in Genotype 3 Patients in The North East of Scotland

Gut ◽

10.1136/gutjnl-2016-312388.512 ◽

2016 ◽

Vol 65 (Suppl 1) ◽

pp. A272.1-A272

Author(s):

P Dundas ◽

A Fraser ◽

S English ◽

L McLeman

Keyword(s):

Real Life ◽

Genotype 3 ◽

Life Data ◽

North East ◽

The North ◽

Real Life Data

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Treatment of 320 genotype 3 cirrhotic patients with 12 weeks Sofosbuvir/Velpatasvir with or without ribavirin: real life experience from Italy

Digestive and Liver Disease ◽

10.1016/j.dld.2018.11.065 ◽

2019 ◽

Vol 51 ◽

pp. e16-e17

Author(s):

L. Pasulo ◽

M. Gambato ◽

A. Spinetti ◽

R. D’Ambrosio ◽

M. Puoti ◽

...

Keyword(s):

Life Experience ◽

Real Life ◽

Genotype 3 ◽

Cirrhotic Patients

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Clinical, Virological Characteristics, and Outcomes of Treatment with Sofosbuvir/Ledipasvir in Two Pediatric Patients Infected by HCV Genotype 4

Cells ◽

10.3390/cells8050416 ◽

2019 ◽

Vol 8 (5) ◽

pp. 416

Author(s):

Nadia Marascio ◽

Maria Mazzitelli ◽

Grazia Pavia ◽

Aida Giancotti ◽

Giorgio Settimo Barreca ◽

...

Keyword(s):

Clinical Trials ◽

Pediatric Patients ◽

Real Life ◽

Fixed Dose ◽

Genotype 4 ◽

Direct Acting Antiviral ◽

Life Data ◽

Real Life Data ◽

Dose Combination ◽

Direct Acting

Direct-acting antiviral drugs to cure infections with Hepatitis C virus (HCV) achieve a sustained virological response (SVR) in more than 90% of adult patients. At present, clinical trials are ongoing and real-life data are still limited in children. Herein, we report two cases of pediatric patients treated with fixed-dose combination of sofosbuvir/ledipasvir, already approved to treat HCV4 genotype. Both young girls achieved SVR even though HCV4 isolates carried L28M and M31L NS5A resistance-associated substitutions (RASs). Therefore, possible effects of these RASs merit further study, especially in children.

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