Liver decompensation is a frequent cause of treatment discontinuation and prognostic factor in intermediate-advanced HCC.

INTRODUCTION AND OBJECTIVES: With the advent of new therapeutic options for patients with hepatocellular carcinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real-world data regarding prognostic survival factors are of significant importance. PATIENTS AND METHODS: A multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic variables and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, estimating hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: Overall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enrollment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was independently associated with increased mortality [HR 3.22 (CI 1.64;6.33); P<.001]. Systemic treatment was initiated in 48.2% of the cohort (n=188), with a median survival of 15.7 months. Of these, 48.9% presented first-line treatment discontinuation (44.4% tumor progression, 29.3% liver decompensation, 18.5% symptomatic deterioration, and 7.8% intolerance), and only 28.7% received second-line systemic treatments. Liver decompensation [HR 2.9 (1.64;5.29); P<.0001], and symptomatic progression [HR 3.9 (1.53;9.78); P=0.004] were independently associated with mortality after first-line systemic treatment discontinuation. CONCLUSIONS: The complexity of these patients, with one-third presenting liver decompensation after systemic therapies, underlines the need for multidisciplinary team management and the central role of hepatologists.

Abnormal Liver Tests during Hospitalization Predict Mortality in Patients with COVID-19: A Multicenter Study from South America.

Background: The role of liver function tests (LFT) as prognostic factors in patients admitted with COVID-19 has not been fully investigated, particularly outside resource-rich countries. We aimed at evaluating the prognostic value of abnormal LFT on admission and during hospitalization of patients with COVID-19. Methods: We performed a retrospective study that included 298 adult patients hospitalized for COVID-19, between 05/2020 and 02/2021, in 6 hospitals from 5 countries in South America. We analyzed demographic and comorbid variables and laboratory tests on admission and during hospitalization. LFT over twice the upper limit of normal (ALEx2) were also evaluated in relation to a variety of factors on admission and during hospitalization. De novo-ALEx2 was defined as the presence of ALEx2 at one week of hospitalization in patients without ALEx2 on admission. Patients were followed until hospital discharge or death. Multivariable analysis was used to evaluate the association between ALEx2 on admission and during hospitalization and mortality. Results: Of the total of 298 patients, 60% were male, with a mean age of 60 years, and 74% of patients had at least one comorbidity. Of those, 137 (46%) patients were transferred to the intensive care unit and 66 (22.1%) patients died during hospitalization. ALEx2 on admission was present in 87 (29.2%) patients and was found to be independently associated with 1-week mortality (odds ratio (OR) = 3.55; 95% confidence interval (95%CI) 1.05-12.05). Moreover, 84 (39.8%) out of 211 patients without ALEx2 at admission developed de novo-ALEx2, which was independently associated with mortality during second week of hospitalization (OR = 6.09; 95%CI 1.28-29) and overall mortality (OR = 2.93, 95%CI 1.05-8.19). Conclusions: A moderate elevation of LFT during admission was associated with a poor short-term prognosis in patients hospitalized with COVID-19. In addition, moderate elevation of LFT at one week of hospitalization was an independent risk factor for overall mortality in these patients.

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.

Familial association in autoimmune liver disease.

The occurrence of autoimmune liver disease in members of the same family is hardly a frequent observation in clinical practice. In a group of 204 cases of primary biliary cirrhosis (PBC) (196 women) and 219 of type 1 autoimmune hepatitis (AIH) (183 women), seen from 1985 to 2000, family occurrence of autoimmune liver disease was investigated. Diagnosis of both entities was based on clinical criteria, immunological studies and liver biopsy. Six families were identified with 2 members each presenting with autoimmune liver disease. In 4 of them the index case had an AIH. This association was observed between mother and daughter in 3 instances. In the remaining AIH index case the association found was with a PBC in her sister. In the other two families the index cases were PBC. In one of them, PBC and AIH association were observed in sisters. Lastly, in another case, an antimitochondrial (AMA) negative variant of PBC was detected in mother and her daughter. The low frequency of family association observed in this cohort could be due to the fact that only symptomatic cases were included. Concurrent autoimmune manifestations were confirmed in 5 members of 6 families (42%). Our results, given the concurrence of both liver diseases in the same family, suggest a link among diverse entities of the autoimmune lineage. The frequency of AIH family association seems to be more prominent in this series than that of PBC. It is also shown that family association in the case of an AMA-negative variant of PBC is feasible, thus confirming that no substantial differences exist between the latter and AMA-positive PBC.

Familial association in autoimmune liver disease

The occurrence of autoimmune liver disease in members of the same family is hardly a frequent observation in clinical practice. In a group of 204 cases of primary biliary cirrhosis (PBC) (196 women) and 219 of type 1 autoimmune hepatitis (AIH) (183 women), seen from 1985 to 2000, family occurrence of autoimmune liver disease was investigated. Diagnosis of both entities was based on clinical criteria, immunological studies and liver biopsy. Six families were identified with 2 members each presenting with autoimmune liver disease. In 4 of them the index case had an AIH. This association was observed between mother and daughter in 3 instances. In the remaining AIH index case the association found was with a PBC in her sister. In the other two families the index cases were PBC. In one of them, PBC and AIH association were observed in sisters. Lastly, in another case, an antimitochondrial (AMA) negative variant of PBC was detected in mother and her daughter. The low frequency of family association observed in this cohort could be due to the fact that only symptomatic cases were included. Concurrent autoimmune manifestations were confirmed in 5 members of 6 families (42). Our results, given the concurrence of both liver diseases in the same family, suggest a link among diverse entities of the autoimmune lineage. The frequency of AIH family association seems to be more prominent in this series than that of PBC. It is also shown that family association in the case of an AMA-negative variant of PBC is feasible, thus confirming that no substantial differences exist between the latter and AMA-positive PBC.

Familial association in autoimmune liver disease.

The occurrence of autoimmune liver disease in members of the same family is hardly a frequent observation in clinical practice. In a group of 204 cases of primary biliary cirrhosis (PBC) (196 women) and 219 of type 1 autoimmune hepatitis (AIH) (183 women), seen from 1985 to 2000, family occurrence of autoimmune liver disease was investigated. Diagnosis of both entities was based on clinical criteria, immunological studies and liver biopsy. Six families were identified with 2 members each presenting with autoimmune liver disease. In 4 of them the index case had an AIH. This association was observed between mother and daughter in 3 instances. In the remaining AIH index case the association found was with a PBC in her sister. In the other two families the index cases were PBC. In one of them, PBC and AIH association were observed in sisters. Lastly, in another case, an antimitochondrial (AMA) negative variant of PBC was detected in mother and her daughter. The low frequency of family association observed in this cohort could be due to the fact that only symptomatic cases were included. Concurrent autoimmune manifestations were confirmed in 5 members of 6 families (42

). Our results, given the concurrence of both liver diseases in the same family, suggest a link among diverse entities of the autoimmune lineage. The frequency of AIH family association seems to be more prominent in this series than that of PBC. It is also shown that family association in the case of an AMA-negative variant of PBC is feasible, thus confirming that no substantial differences exist between the latter and AMA-positive PBC.

Familial association in autoimmune liver disease

The occurrence of autoimmune liver disease in members of the same family is hardly a frequent observation in clinical practice. In a group of 204 cases of primary biliary cirrhosis (PBC) (196 women) and 219 of type 1 autoimmune hepatitis (AIH) (183 women), seen from 1985 to 2000, family occurrence of autoimmune liver disease was investigated. Diagnosis of both entities was based on clinical criteria, immunological studies and liver biopsy. Six families were identified with 2 members each presenting with autoimmune liver disease. In 4 of them the index case had an AIH. This association was observed between mother and daughter in 3 instances. In the remaining AIH index case the association found was with a PBC in her sister. In the other two families the index cases were PBC. In one of them, PBC and AIH association were observed in sisters. Lastly, in another case, an antimitochondrial (AMA) negative variant of PBC was detected in mother and her daughter. The low frequency of family association observed in this cohort could be due to the fact that only symptomatic cases were included. Concurrent autoimmune manifestations were confirmed in 5 members of 6 families (42). Our results, given the concurrence of both liver diseases in the same family, suggest a link among diverse entities of the autoimmune lineage. The frequency of AIH family association seems to be more prominent in this series than that of PBC. It is also shown that family association in the case of an AMA-negative variant of PBC is feasible, thus confirming that no substantial differences exist between the latter and AMA-positive PBC. (AU)

Distribucion de los genotipos del virus de la hepatitis C en una poblacion argentina de drogadictos endovenosos / Distribution of the genotypes of Hepatitis C virus in a Argentine population of intravenous drug addicts

El antecedente de drogadicción endovenosa constituye un factor de riesgo poco frecuente en pacientes (pts) con infección crónica por el virus C (HCV) en la Argentina, representando en nuestro servicio menos del 10 por ciento. Nos propusimos determinar la prevalencia de los diferentes genotipos (Gt) del HCV en un grupo de pts con hepatitis crónica por HCV con antecedentes de drogadicción endovenosa. Un total de 68 pts con antecedentes de drogadicción endovenosa y hepatitis crónica HCV fueron comparados con 68 pts de igual edad y sexo pero sin el antecedente de drogadicción. La biopsia hepática fue realizada en todos los pts. La genotipificación del HCV fue efectuada por INNO LiPA (Innogenetics). Para el análisis estadístico se empleó el test de Student. La edad media en ambos grupos fue de 35 + 7.8 años correspondiendo 50 pts al sexo masculino. No se observaron diferencias entre ambos grupos en la prevalencia de los GT 1a, 2a/c e infecciones mixtas. El Gt 1b fue más frecuente en el grupo control 26/68 (38,2 por ciento) que en el de drogadictos 13/68 (19.1 por ciento) (p = 0.0228). También fue observada una diferente prevalencia en el GT3, presente en 29/68 (42.6 por ciento) de los drogadictos y en 8/68 (11.8 por ciento) del grupo control (p = 0.0001). El Gt1a fue el segundo más frecuente en el grupo con antecedentes de drogadicción 18/68 (26.5 por ciento). La infección simultánea con el HIV fue observada en 8 pts con antecedentes de drogadicción y en ninguno del grupo control. La biopsia hepática mostró una mayor prevalencia de lesiones leves en el grupo control 39/68 (57.3 por ciento) que en los pts con antecedentes de drogadicción 22/68 (32.4 por ciento) (p = 0.0058). En los pts infectados con el Gt3 la hepatitis crónica severa y cirrosis fueron más frecuentes en los pts con antecedentes de drogadicción. Se concluye que en nuestro medio el Gt 3 es el más prevalente en los pts con antecedentes de drogadicción endovenosa. Las formas de hepatitis leves son menos frecuentes en los pts con antecedentes de drogadicción. A pesar del pequeño número de pts coinfectados con el HIV es importante notar que el 25 por ciento de ellos presentaron hepatitis crónica severa o cirrosis.

Distribucion de los genotipos del virus de la hepatitis C en una poblacion argentina de drogadictos endovenosos / Distribution of the genotypes of Hepatitis C virus in a Argentine population of intravenous drug addicts

El antecedente de drogadicción endovenosa constituye un factor de riesgo poco frecuente en pacientes (pts) con infección crónica por el virus C (HCV) en la Argentina, representando en nuestro servicio menos del 10 por ciento. Nos propusimos determinar la prevalencia de los diferentes genotipos (Gt) del HCV en un grupo de pts con hepatitis crónica por HCV con antecedentes de drogadicción endovenosa. Un total de 68 pts con antecedentes de drogadicción endovenosa y hepatitis crónica HCV fueron comparados con 68 pts de igual edad y sexo pero sin el antecedente de drogadicción. La biopsia hepática fue realizada en todos los pts. La genotipificación del HCV fue efectuada por INNO LiPA (Innogenetics). Para el análisis estadístico se empleó el test de Student. La edad media en ambos grupos fue de 35 + 7.8 años correspondiendo 50 pts al sexo masculino. No se observaron diferencias entre ambos grupos en la prevalencia de los GT 1a, 2a/c e infecciones mixtas. El Gt 1b fue más frecuente en el grupo control 26/68 (38,2 por ciento) que en el de drogadictos 13/68 (19.1 por ciento) (p = 0.0228). También fue observada una diferente prevalencia en el GT3, presente en 29/68 (42.6 por ciento) de los drogadictos y en 8/68 (11.8 por ciento) del grupo control (p = 0.0001). El Gt1a fue el segundo más frecuente en el grupo con antecedentes de drogadicción 18/68 (26.5 por ciento). La infección simultánea con el HIV fue observada en 8 pts con antecedentes de drogadicción y en ninguno del grupo control. La biopsia hepática mostró una mayor prevalencia de lesiones leves en el grupo control 39/68 (57.3 por ciento) que en los pts con antecedentes de drogadicción 22/68 (32.4 por ciento) (p = 0.0058). En los pts infectados con el Gt3 la hepatitis crónica severa y cirrosis fueron más frecuentes en los pts con antecedentes de drogadicción. Se concluye que en nuestro medio el Gt 3 es el más prevalente en los pts con antecedentes de drogadicción endovenosa. Las formas de hepatitis leves son menos frecuentes en los pts con antecedentes de drogadicción. A pesar del pequeño número de pts coinfectados con el HIV es importante notar que el 25 por ciento de ellos presentaron hepatitis crónica severa o cirrosis. (AU)

Esteatohepatitis no alcoholica / Non alcoholic steatohepatitis

Se estudiaron prospectivamente 21 pacientes con el diagnóstico de esteato-hepatitis no alcohólica (EHNA). Clínicamente todos los pacientes tenían hepatomegalia y 10 (48 por ciento) tenían estudios por imágenes compatibles con esteatosis o fibrosis. Bioquímicamente se comprobó aumento de AST, ALT e hipercolesterolemia en el 48 por cento, de GGT en el 52 por ciento y de FA en el 38 por ciento. Dieciocho pacientes eran obesos, 2 de ellos diabéticos, 2 con antecedentes de tóxicos y el restante hipotiroideo. Morfológicamente las biopsias fueron evaluadas semicuantitativamente para evaluar el grado de esteatosis, infiltración inflamatoria y fibrosis en una escala de 1 a 3. Se obtuvo un puntaje medio de 2,6 para esteatosis, 1,5 para la inflamación y 1,8 para la fibrosis. Cuatro pacientes presentaban una cirrosis ya constituida y se halló hialina de Mallory en 11 casos (52 por ciento). La EHNA es una enfermedad oligosintomática que puede hallarse en diferentes condiciones clínicas siendo más frecuente en la obesidad, con mayor prevalencia en mujeres e histologicamente indeferenciable de la estatohepatitis alcohólica

Esteatohepatitis no alcoholica / Non alcoholic steatohepatitis

Se estudiaron prospectivamente 21 pacientes con el diagnóstico de esteato-hepatitis no alcohólica (EHNA). Clínicamente todos los pacientes tenían hepatomegalia y 10 (48 por ciento) tenían estudios por imágenes compatibles con esteatosis o fibrosis. Bioquímicamente se comprobó aumento de AST, ALT e hipercolesterolemia en el 48 por cento, de GGT en el 52 por ciento y de FA en el 38 por ciento. Dieciocho pacientes eran obesos, 2 de ellos diabéticos, 2 con antecedentes de tóxicos y el restante hipotiroideo. Morfológicamente las biopsias fueron evaluadas semicuantitativamente para evaluar el grado de esteatosis, infiltración inflamatoria y fibrosis en una escala de 1 a 3. Se obtuvo un puntaje medio de 2,6 para esteatosis, 1,5 para la inflamación y 1,8 para la fibrosis. Cuatro pacientes presentaban una cirrosis ya constituida y se halló hialina de Mallory en 11 casos (52 por ciento). La EHNA es una enfermedad oligosintomática que puede hallarse en diferentes condiciones clínicas siendo más frecuente en la obesidad, con mayor prevalencia en mujeres e histologicamente indeferenciable de la estatohepatitis alcohólica (AU)