Disease Progression in Patients With Hepatitis C Virus Infection Treated With Direct-Acting Antiviral Agents.

BACKGROUND & AIMS: Little is known about how a sustained virologic response (SVR) to treatment of hepatitis C virus infection with direct-acting antivirals (DAAs) affects patient mortality and development of new liver-related events. We aimed to evaluate the incidence of disease progression in patients treated with DAAs. METHODS: We performed a prospective multicenter cohort study of 1760 patients who received DAA treatment at 23 hospitals in Latin America, from May 1, 2016, through November 21, 2019. We excluded patients with a history of liver decompensation, hepatocellular carcinoma (HCC), or solid-organ transplantation. Disease progression after initiation of DAA therapy included any of the following new events: liver decompensation, HCC, liver transplantation, or death. Evaluation of variables associated with the primary outcome was conducted using a time-dependent Cox proportional hazards models. RESULTS: During a median follow-up period of 26.2 months (interquartile range, 15.3-37.5 mo), the overall cumulative incidence of disease progression was 4.1% (95% CI, 3.2%-5.1%), and after SVR assessment was 3.6% (95% CI, 2.7%-4.7%). Baseline variables associated with disease progression were advanced liver fibrosis (hazard ratio [HR], 3.4; 95% CI, 1.2-9.6), clinically significant portal hypertension (HR, 2.1; 95% CI, 1.2-3.8), and level of albumin less than 3.5 mg/dL (HR, 4.1; 95% CI, 2.3-7.6), adjusted for SVR achievement as a time covariable. Attaining an SVR reduced the risk of liver decompensation (HR, 0.3; 95% CI, 0.1-0.8; P = .016) and de novo HCC (HR, 0.2; 95% CI, 0.1%-0.8%; P = .02) in the overall cohort. CONCLUSIONS: Treatment of hepatitis C virus infection with DAAs significantly reduces the risk of new liver-related complications and should be offered to all patients, regardless of disease stage. Clinicaltrials.gov: NCT03775798.

Decompensated cirrhosis and liver transplantation negatively impact in DAA treatment response: Real-world experience from HCV-LALREAN cohort.

INTRODUCTION: Although the effectiveness of direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) has been reported in real-world settings, predictive factors of treatment failure are lacking. Therefore, we sought to explore the baseline predictors of treatment response to DAAs. METHODS: This was a prospective multicenter cohort study from the Latin American Liver Research Educational and Awareness Network (LALREAN) including patients who received DAA treatment from May 2016 to April 2019. A multivariate logistic regression model was conducted to identify variables associated with unachieved sustained virological response (SVR), defined as treatment failure (odds ratios [OR] and 95% confidence intervals [CIs]). RESULTS: From 2167 patients (55.2% with cirrhosis) who initiated DAA therapy, 89.4% completed a full-course treatment (n = 1938). Median treatment duration was 12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance or other causes was observed in only 1.0% cases (n = 20). Overall non-SVR12 was 4.5% (95% CI, 3.5-5.7). There were no significant differences in treatment failure according to HCV genotypes and the degree of fibrosis. Independently associated variables with DAA failure were liver function impairment according to the Child-Pugh score B OR, 2.09 (P = .06), Child-Pugh C OR, 11.7 (P < .0001); and liver transplant (LT) recipient OR, 3.75 (P = .01). CONCLUSION: In this real-life setting, higher DAA treatment failure rates were observed in patients with decompensated cirrhosis and in LT recipients. These predictive baseline factors should be addressed to individualize the appropriate time-point of DAA treatment (NCT03775798; www. CLINICALTRIALS: gov).

A Latin American survey on demographic aspects of hospitalized, decompensated cirrhotic patients and the resources for their management.

INTRODUCTION & OBJECTIVES: Liver cirrhosis is a major cause of mortality worldwide. Adequate diagnosis and treatment of decompensating events requires of both medical skills and updated technical resources. The objectives of this study were to search the demographic profile of hospitalized cirrhotic patients in a group of Latin American hospitals and the availability of expertise/facilities for the diagnosis and therapy of decompensation episodes. METHODS: A cross sectional, multicenter survey of hospitalized cirrhotic patients. RESULTS: 377 patients, (62% males; 58±11 years) (BMI>25, 57%; diabetes 32%) were hospitalized at 65 centers (63 urbans; 57 academically affiliated) in 13 countries on the survey date. Main admission causes were ascites, gastrointestinal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis/other infections. Most prevalent etiologies were alcohol-related (AR) (40%); non-alcoholic-steatohepatitis (NASH) (23%), hepatitis C virus infection (HCV) (7%) and autoimmune hepatitis (AIH) (6%). The most frequent concurrent etiologies were AR+NASH. Expertise and resources in every analyzed issue were highly available among participating centers, mostly accomplishing valid guidelines. However, availability of these facilities was significantly higher at institutions located in areas with population>500,000 (n=45) and in those having a higher complexity level (Gastrointestinal, Liver and Internal Medicine Departments at the same hospital (n=22). CONCLUSIONS: The epidemiological etiologic profile in hospitalized, decompensated cirrhotic patients in Latin America is similar to main contemporary emergent agents worldwide. Medical and technical resources are highly available, mostly at great population urban areas and high complexity medical centers. Main diagnostic and therapeutic approaches accomplish current guidelines recommendations.

The ECHO model proved to be a useful tool to increase clinicians' self-effectiveness for care of patients with Hepatitis C in Argentina.

The ECHO model was developed to expand access to medical care for populations with HCV infection in underserved areas. We aimed to compare HCV treatment outcomes in community-based clinics with the Austral University Hospital (AUH) and to assess improvement in physician knowledge and skills. In October 2015, we established an HCV ECHO clinic at the AUH in Buenos Aires. To evaluate the impact of this programme, we conducted a prospective cohort study comparing treatment for HCV infection at the AUH with healthcare providers from different Argentinean provinces. A survey evaluating skills and competence in HCV care was administered, and results were compared. The primary endpoint was sustained virologic response (SVR) and under direct-acting antivirals. Since the implementation of ECHO clinics, a total of 25 physicians participated in at least one session (median 10.0; IQR 3.0-18.0). SVR rates (n = 437 patients) were 94.2% (95% CI 90.4-96.8) in patients treated at AUH clinic (n = 227/242) and 96.4% (95% CI 92.7-98.5) in those treated at ECHO sites (n = 188/195), with a nonsignificant difference between sites, 2.2% SVR difference (95% CI -0.24-0.06; P = 0.4). We also found a significant improvement in all the evaluated skills and abilities. Replicating the ECHO model helped to improve participants' skills in the management of HCV achieving similar SVR rates. ECHO model was demonstrated to be an effective intervention able to multiply and expand HCV treatment, a critical barrier to access to care that needs to be solved if we are committed with WHO goals to eliminate HCV by 2030.

Treatment with direct-acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma.

BACKGROUND & AIMS: Data from Europe and North America have been published regarding the risk of developing hepatocellular carcinoma (HCC) after treatment with direct antiviral agents (DAA). We proposed to evaluate cumulative incidence and associated risk factors for de novo HCC. METHODS: This was a prospective multicentre cohort study from Latin America including 1400 F1-F4-treated patients with DAAs (F3-F4 n = 1017). Cox proportional regression models (hazard ratios, HR and 95% CI) were used to evaluate independent associated variables with HCC. Further adjustment with competing risk regression and propensity score matching was carried out. RESULTS: During a median follow-up of 16 months (IQR 8.9-23.4 months) since DAAs initiation, overall cumulative incidence of HCC was 0.02 (CI 0.01; 0.03) at 12 months and 0.04 (CI 0.03; 0.06) at 24 months. Cumulative incidence of HCC in cirrhotic patients (n = 784) was 0.03 (CI 0.02-0.05) at 12 months and 0.06 (CI 0.04-0.08) at 24 months of follow-up. Failure to achieve SVR was independently associated with de novo HCC with a HR of 4.9 (CI 1.44; 17.32), after adjusting for diabetes mellitus, previous interferon non-responder, Child-Pugh and clinically significant portal hypertension. SVR presented an overall relative risk reduction for de novo HCC of 73% (CI 15%-91%), 17 patients were needed to be treated to prevent one case of de novo HCC in this cohort. CONCLUSIONS: Achieving SVR with DAA regimens was associated with a significant risk reduction in HCC. However, this risk remained high in patients with advanced fibrosis, thus demanding continuous surveillance strategies in this population.

[Prevalence of liver diseases in a small rural community isolated in the mountain heights: clinical, biochemical and ultrasonographic study]. / Prevalencia de enfermedades hepáticas en una población rural de alta montaña: estudio clínico, bioquímico y ecográfico.

The goal of this population-based clinical, biochemical and ultrasonographic study was to assess the prevalence of liver diseases in Lara, a small rural community isolated in the mountain heights of Tucumán, a Province of Argentina with the highest reported rates of HAV infection in children. Inhabitants of Lara lack electricity, potable water and a sewer system. The study included 102 individuals representing 41% of the total population. Anti-HBc and anti-HCV were negative in all cases. No children showed clinical, biochemical or ecographic abnormalities. Among adults, 41% referred alcohol consumption and 12% blood transfusions. Only 3 adults (6%) had mildly elevated ALT. Ultrasound showed steatosis in 8 individuals (16%), gallstones in 7 (14%), parenchymal micro-calcifications in 5 (10%) and parasitic cysts in 4 (8%). Prevalence of HAV infection in Lara was 89% in adults and 35% in children, being significantly lower than that of children of medium/high (53%, p = 0.05) and low (74%, p = 0.0006) socioeconomic level from the city of Tucumán (control groups). These differences were more marked in children aged < 5 years (anti-HAV in 0%, 53% and 75% respectively). Serologic tests for echinoccocal disease were positive in 3/4 individuals with parasitic cysts, 2/5 with micro-calcifications and 17/85 (20%) with normal ultrasound, thus suggesting a high rate of false-positive results of the Elisa test utilized. This study showed that in Lara there is a high prevalence of steatosis, gallstones and equinoccocal disease in adults, absence of HBVand HCV infection and low exposure to HAV in children especially in those aged < 5 years.

Prevalencia de enfermedades hepáticas en una población rural de alta montaña: estudio clínico, bioquímico y ecográfico / Prevalence of liver diseases in a small rural community isolated in tne mountain heights: clinical, biochemical and ultrasonographic study

En este estudio clínico, bioquímico y ecográfico se evaluó la prevalencia de hepatopatías en Lara, una comunidad rural aislada de alta montaña en Tucumán, provincia con la máxima prevalencia de infección por HAV en niños de Argentina. Lara carece de agua potable, electricidad y cloacas. Se estudiaron 102 habitantes, lo que representa el 41% de la población. El anti-HBc y anti-HCV fueron negativos en todos los casos. Ningún niño presentó anormalidades hepáticas. El 41% de los adultos refirió ingesta alcohólica y el 12% transfusiones. Se observó incremento leve de ALT en 3 casos (6%). La ecografía demostró esteatosis en 8 individuos (16%), litiasis vesicular en 7 (14%), microcalcificaciones en 5 (10%) y quistes de aspecto parasitario en 4 (8%). La prevalencia de infección por HAV en Lara fue de 89% en adultos y 35% en niños, siendo significativamente menor que la de los niños de la ciudad de Tucumán con nivel socioeconómico medio / alto (53%, p = 0.05) o bajo (74%, p = 0.0006). La diferencia fue más evidente en niños menores de 5 años (0%, 53% y 75% respectivamente). La serología para hidatidosis fue positiva en 3/4 individuos con quistes, 2/5 con microcalcificaciones y 17/85 (20%) con ecografía normal, lo que sugiere que la técnica de Elisa utilizada se asocia a frecuentes resultados falsos positivos. El estudio poblacional de Lara demostró una elevada prevalencia de esteatosis, litiasis vesicular e hidatidosis en adultos, ausencia de infección por HBV y HCV, y una baja exposición al HAV en niños, especialmente en menores de 5 años.(AU)

The goal of this population-based clinical, biochemical and ultrasonographic study was to assess the prevalence of liver diseases in Lara, a small rural community isolated in the mountain heights of Tucumán, a Province of Argentina with the highest reported rates of HAV infection in children. Inhabitants of Lara lack electricity, potable water and a sewer system. The study included 102 individuals representing 41% of the total population. Anti-HBc and anti-HCV were negative in all cases. No children showed clinical, biochemical or ecographic abnormalities. Among adults, 41% referred alcohol consumption and 12% blood transfusions. Only 3 adults (6%) had mildly elevated ALT. Ultrasound showed steatosis in 8 individuals (16%), gallstones in 7 (14%), parenchymal micro-calcifications in 5 (10%) and parasitic cysts in 4 (8%). Prevalence of HAV infection in Lara was 89% in adults and 35% in children, being significantly lower than that of children of medium/high (53%, p=0.05) and low (74%, p=0.0006) socioeconomic level from the city of Tucumán (control groups). These differences were more marked in children aged <5 years (anti-HAV in 0%, 53% y 75% respectively). Serologic tests for echinoccocal disease were positive in 3/4 individuals with parasitic cysts, 2/5 with micro-calcifications and 17/85 (20%) with normal ultrasound, thus suggesting a high rate of false-positive results of the Elisa test utilized. This study showed that in Lara there is a high prevalence of steatosis, gallstones and equinoccocal disease in adults, absenceof HBV and HCV infection and low exposure to HAV in children especially in those aged <5 years. (AU)

Prevalencia de enfermedades hepáticas en una población rural de alta montaña: estudio clínico, bioquímico y ecográfico / Prevalence of liver diseases in a small rural community isolated in tne mountain heights: clinical, biochemical and ultrasonographic study

En este estudio clínico, bioquímico y ecográfico se evaluó la prevalencia de hepatopatías en Lara, una comunidad rural aislada de alta montaña en Tucumán, provincia con la máxima prevalencia de infección por HAV en niños de Argentina. Lara carece de agua potable, electricidad y cloacas. Se estudiaron 102 habitantes, lo que representa el 41% de la población. El anti-HBc y anti-HCV fueron negativos en todos los casos. Ningún niño presentó anormalidades hepáticas. El 41% de los adultos refirió ingesta alcohólica y el 12% transfusiones. Se observó incremento leve de ALT en 3 casos (6%). La ecografía demostró esteatosis en 8 individuos (16%), litiasis vesicular en 7 (14%), microcalcificaciones en 5 (10%) y quistes de aspecto parasitario en 4 (8%). La prevalencia de infección por HAV en Lara fue de 89% en adultos y 35% en niños, siendo significativamente menor que la de los niños de la ciudad de Tucumán con nivel socioeconómico medio / alto (53%, p = 0.05) o bajo (74%, p = 0.0006). La diferencia fue más evidente en niños menores de 5 años (0%, 53% y 75% respectivamente). La serología para hidatidosis fue positiva en 3/4 individuos con quistes, 2/5 con microcalcificaciones y 17/85 (20%) con ecografía normal, lo que sugiere que la técnica de Elisa utilizada se asocia a frecuentes resultados falsos positivos. El estudio poblacional de Lara demostró una elevada prevalencia de esteatosis, litiasis vesicular e hidatidosis en adultos, ausencia de infección por HBV y HCV, y una baja exposición al HAV en niños, especialmente en menores de 5 años.

The goal of this population-based clinical, biochemical and ultrasonographic study was to assess the prevalence of liver diseases in Lara, a small rural community isolated in the mountain heights of Tucumán, a Province of Argentina with the highest reported rates of HAV infection in children. Inhabitants of Lara lack electricity, potable water and a sewer system. The study included 102 individuals representing 41% of the total population. Anti-HBc and anti-HCV were negative in all cases. No children showed clinical, biochemical or ecographic abnormalities. Among adults, 41% referred alcohol consumption and 12% blood transfusions. Only 3 adults (6%) had mildly elevated ALT. Ultrasound showed steatosis in 8 individuals (16%), gallstones in 7 (14%), parenchymal micro-calcifications in 5 (10%) and parasitic cysts in 4 (8%). Prevalence of HAV infection in Lara was 89% in adults and 35% in children, being significantly lower than that of children of medium/high (53%, p=0.05) and low (74%, p=0.0006) socioeconomic level from the city of Tucumán (control groups). These differences were more marked in children aged <5 years (anti-HAV in 0%, 53% y 75% respectively). Serologic tests for echinoccocal disease were positive in 3/4 individuals with parasitic cysts, 2/5 with micro-calcifications and 17/85 (20%) with normal ultrasound, thus suggesting a high rate of false-positive results of the Elisa test utilized. This study showed that in Lara there is a high prevalence of steatosis, gallstones and equinoccocal disease in adults, absenceof HBV and HCV infection and low exposure to HAV in children especially in those aged <5 years.