Prevalence of non-alcoholic fatty liver disease and liver fibrosis in a general population cohort from Argentina.

INTRODUCTION AND OBJECTIVES: South America is one of the regions with the highest rates of non-alcoholic fatty liver disease (NAFLD). This study aimed to assess the prevalence and severity of NAFLD in suburban Argentina. PATIENTS AND METHODS: The study involved a general community cohort of 993 subjects evaluated sequentially with a comprehensive lifestyle questionnaire, laboratory testing, abdominal ultrasound (US) and transient elastography with XL probe. NAFLD was diagnosed according to standard criteria. RESULTS: The prevalence of NAFLD by the US was 37.2% (326/875) overall, 50.3% in subjects with overweight/obesity, 58.6% with hypertriglyceridemia, 62.3% with diabetes/hyperglycemia and 72.1% with all three risk factors. Male gender (OR 1.42, 95% CI 1.03-1.47, p = 0.029), age (50-59 years: OR 1.98, 95 CI 1.16-3.39, p = 0.013 and ≥60 years: OR 1.86, 95% CI 1.13-3.09, p = 0.015), BMI (25-29: OR 2.87, 95% CI 1.86-4.51, p<0.001 and ≥30: OR 9.57, 95% CI 6.14-15.20, p<0.001), diabetes/hyperglycemia (OR 1.65, 95% CI 1.05-2.61, p = 0.029) and hypertriglyceridemia (OR 1.73, 95% CI 1.20-2.48, p = 0.002) were independent predictors of NAFLD. Among patients with steatosis, 22.2% (69/311) had ≥F2 fibrosis (overweight 25%, hypertriglyceridemia 32%, diabetes/hyperglycemia 34%). BMI (OR 5.22, 95% CI 2.64-11.74, p<0.001), diabetes/hyperglycemia (OR 2.12, 95% CI 1.05-4.29, p = 0.04) and hypertriglyceridemia (OR 1.94, 95% CI 1.03-3.68, p = 0.040) were independent predictors of liver fibrosis. CONCLUSIONS: This general population study from Argentina showed a high prevalence of NAFLD. Significant liver fibrosis was present in 22% of subjects with NAFLD. This information adds to the existing knowledge of NAFLD epidemiology in Latin America.

Twenty-year follow-up of an outbreak of hepatitis C in a small rural town of Argentina: The O'Brien Project.

INTRODUCTION AND OBJECTIVES: In 1999, a population-based survey showed a 5.6 % (102/1832) prevalence of HCV infection in O'Brien, a small rural town of Argentina. The aim of this study was to assess the impact of screening, clinical evaluation and antiviral therapy on elimination of HCV after 20 years of follow-up. PATIENTS AND METHODS: HCV+ subjects (n=102) underwent clinical, biochemical and histological evaluation to assess the presence and severity of liver disease. Antiviral therapy included pegylated interferon + ribavirin in 2005 and direct antiviral agents from 2017. RESULTS: All viremic subjects (n=84) had genotype 1b with 90%-97.5% sequence homology scores, suggesting the existence of a common source of infection (use of unsafe injections administered by the same health professional). Liver biopsy (n=55) showed chronic hepatitis in all patients. The prevalence of cirrhosis was 28% overall (29/102) and 34.5% among viremic patients. Sustained virological response (SVR) was obtained in 20/34 (59%) patients treated with interferon. From 2005 to 2017, when oral antivirals became available 37/50 untreated patients died. Median age of this group in 2005 was 67 years. Six interferon non-responders and five naive subjects received direct antiviral agents and all developed SVR. Only 1/31 patient (3.2%) with SVR died and none developed decompensated cirrhosis or HCC. In 2019, a new population-based study showed that the prevalence of HCV in O'Brien decreased 20-fold, from 5.6% to 0.28% (3/1070). CONCLUSIONS: Despite the high mortality rate precluding timely access to direct antiviral agents, the O'Brien Project is a good example of HCV micro-elimination studies.

Simeprevir versus telaprevir with peginterferon and ribavirin in previous null or partial responders with chronic hepatitis C virus genotype 1 infection (ATTAIN): a randomised, double-blind, non-inferiority phase 3 trial.

BACKGROUND: We did a phase 3 study in previous non-responders with chronic hepatitis C virus (HCV) genotype 1 infection and compensated liver disease that related to the standard of care for these patients at the time this study was initiated. We investigated whether simeprevir is non-inferior in terms of efficacy to telaprevir, each in combination with peginterferon alfa-2a and ribavirin. METHODS: We did this randomised, double-blind, phase 3 trial at 169 investigational sites in 24 countries. We enrolled adults (≥18 years) with chronic HCV genotype 1 infection, compensated liver disease, and plasma HCV RNA higher than 10 000 IU/mL who were null or partial responders during at least one previous course of peginterferon alfa-2a and ribavirin treatment. We randomly assigned (1:1) patients (stratified by HCV genotype 1 subtype [1a plus other/1b] and previous treatment response [partial or null]) to receive simeprevir (150 mg once a day) plus telaprevir placebo (three times a day 7-9 h apart) or telaprevir (750 mg three times a day) plus simeprevir placebo (once a day) in combination with peginterferon alfa-2a and ribavirin for 12 weeks followed by 36 weeks of peginterferon alfa-2a and ribavirin alone. The primary efficacy endpoint was sustained virological response 12 weeks after end of treatment (SVR12) in the intention-to-treat and the per-protocol population. We compared groups with the Cochran-Mantel-Haenszel test. We established a non-inferiority margin of 12%. Adverse events were reported descriptively. This trial is registered with ClinicalTrials.gov, number NCT01485991. FINDINGS: Patient screening began on Jan 19, 2012, and the last visit was on April 7, 2014. We included 763 patients (472 previous null responders [62%]). Simeprevir and peginterferon alfa-2a and ribavirin was non-inferior to telaprevir and peginterferon alfa-2a and ribavirin for SVR12 (54% [203/379] vs 55% [210/384]; difference -1·1%, 95% CI -7·8 to 5·5; p=0·0007). SVR12 was achieved in 70% (101/145) versus 68% (100/146) of previous partial responders and 44% (102/234) versus 46% (110/238) of previous null responders with simeprevir and peginterferon alfa-2a and ribavirin and telaprevir and peginterferon alfa-2a and ribavirin treatment, respectively. We recorded differences between treatment groups in simeprevir or telaprevir-related adverse events (69% [261/379] in the simeprevir group vs 86% [330/384] in the telaprevir group), serious adverse events (2% [8/379] vs 9% [33/384]), and adverse events leading to simeprevir or telaprevir discontinuation (2% [7/379] vs 8% [32/384]). INTERPRETATION: Simeprevir once a day with peginterferon alfa-2a and ribavirin was well tolerated in HCV genotype 1-infected previous non-responders and was non-inferior to telaprevir, thus providing an alternative treatment in areas of the world where all-oral HCV regimens are not available or accessible. FUNDING: Janssen.

Cuantificación de hierro hepático por espectrometría de absorción atómica con vaporización electrotérmica / Iron liver quantification using electrothermal atomic absorption spectrometry / Quantificação de ferro hepático por espectrometria de absorção atômica com vaporização eletrotérmica

Se estudió el depósito de hierro (Fe) en tejido hepático de individuos sanos y de individuos con enfermedades crónicas del hígado, siendo todos adultos entre 46 y 70 años. La cuantificación de hierro se realizó mediante la técnica de Espectrometría de Absorción Atómica con Vaporización Electrotérmica (ET AAS). Las muestras de hígado obtenidas por biopsia hepática fueron pesadas y sometidas a digestión ácida. Simultáneamente se realizaron ensayos de recuperación del analito fortificando las muestras y el blanco de reactivo con el agregado de un estándar de Fe. La cuantificación se realizó mediante una curva de calibración (con estándares entre 10 y 50 µg/L). Se midieron áreas de pico a 248,3 nm usando como fuente una lámpara de cátodo hueco. Los resultados obtenidos de las muestras correspondientes a individuos sanos fueron inferiores a 1.000 µg/g de tejido seco, mientras que los valores correspondientes a individuos con enfermedades crónicas del hígado resultaron superiores, entre 1.800 y 7.835 µg/g de tejido seco. Se observó una relación directa entre la concentración de hierro en tejido hepático y el grado de depósito de este metal, por lo que el desarrollo de la metodología ET AAS permitió cuantificar la sobrecarga de hierro y estimar los valores obtenidos asociados a diferentes hepatopatías.

The iron (Fe) deposit was studied in the liver tissue of healthy and chronic liver disease subjects, all of them adults aged 46 to 70. The iron quantification was made by electrothermal atomic absorption spectrometry (ET AAS). Biopsy liver samples were weighed, measured, and put under acid digestion. Simultaneously a test was performed to analyze recovery in both strong samples and bound reagents with the addition of a standard of iron. Quantification was carried out using a calibration curve (from 10 to 50 mg/L): Peak areas of 248.3 nm were measured through a hollow cathode lamp. The results of the samples for healthy individuals were less than 1,000 µg/g of dry tissue, while the range in subjects with chronic liver disease was higher, (range from 800 to 7,835 µg/g dry tissue). There is a direct relationship between concentrations of iron in liver tissue and the range of the metal deposit for which reason development of the ET AAS methodology made it possible to quantify the iron overload and estimate the values associated to the different hepatopathies.

Foi estudado o depósito de ferro (Fe) em tecido hepático de indivíduos saudáveis e de indivíduos com doenças crônicas do fígado, sendo todos adultos entre 46 e 70 anos. A quantificação de ferro foi realizada através da Técnica de Espectrometria de Absorção Atômica com Vaporização Eletrotérmica (ET AAS). As amostras de fígado obtidas por biópsia hepática foram pesadas e submetidas à digestão ácida. Simultaneamente foram realizados testes de recuperação do analito fortificando as amostras e o branco de reagente com o acréscimo de um padrão de Fe. A quantificação foi realizada através de uma curva de calibragem (com padrões entre 10 e 50 mg/L). Mediram-se áreas de pico a 248,3 nm usando como fonte uma lâmpada de cátodo oco. Os resultados obtidos das amostras correspondentes a indivíduos sadios foram inferiores a 1.000 µg/g de tecido seco, e os valores correspondentes a indivíduos com doenças crônicas do fígado resultaram superiores, entre 1.800 a 7.835 µg/g de tecido seco. Foi observada uma relação direta entre a concentração de ferro em tecido hepático com o grau de depósito deste metal, pelo qual o desenvolvimento da metodologia ET AAS permitiu quantificar a sobrecarga de ferro e calcular os valores obtidos associados a diferentes hepatopatias.

Cuantificación de hierro hepático por espectrometría de absorción atómica con vaporización electrotérmica / Iron liver quantification using electrothermal atomic absorption spectrometry / QuantificaþÒo de ferro hepático por espectrometria de absorþÒo at¶mica com vaporizaþÒo eletrotérmica

Se estudió el depósito de hierro (Fe) en tejido hepático de individuos sanos y de individuos con enfermedades crónicas del hígado, siendo todos adultos entre 46 y 70 años. La cuantificación de hierro se realizó mediante la técnica de Espectrometría de Absorción Atómica con Vaporización Electrotérmica (ET AAS). Las muestras de hígado obtenidas por biopsia hepática fueron pesadas y sometidas a digestión ácida. Simultáneamente se realizaron ensayos de recuperación del analito fortificando las muestras y el blanco de reactivo con el agregado de un estándar de Fe. La cuantificación se realizó mediante una curva de calibración (con estándares entre 10 y 50 Ag/L). Se midieron áreas de pico a 248,3 nm usando como fuente una lámpara de cátodo hueco. Los resultados obtenidos de las muestras correspondientes a individuos sanos fueron inferiores a 1.000 Ag/g de tejido seco, mientras que los valores correspondientes a individuos con enfermedades crónicas del hígado resultaron superiores, entre 1.800 y 7.835 Ag/g de tejido seco. Se observó una relación directa entre la concentración de hierro en tejido hepático y el grado de depósito de este metal, por lo que el desarrollo de la metodología ET AAS permitió cuantificar la sobrecarga de hierro y estimar los valores obtenidos asociados a diferentes hepatopatías.(AU)

The iron (Fe) deposit was studied in the liver tissue of healthy and chronic liver disease subjects, all of them adults aged 46 to 70. The iron quantification was made by electrothermal atomic absorption spectrometry (ET AAS). Biopsy liver samples were weighed, measured, and put under acid digestion. Simultaneously a test was performed to analyze recovery in both strong samples and bound reagents with the addition of a standard of iron. Quantification was carried out using a calibration curve (from 10 to 50 mg/L): Peak areas of 248.3 nm were measured through a hollow cathode lamp. The results of the samples for healthy individuals were less than 1,000 Ag/g of dry tissue, while the range in subjects with chronic liver disease was higher, (range from 800 to 7,835 Ag/g dry tissue). There is a direct relationship between concentrations of iron in liver tissue and the range of the metal deposit for which reason development of the ET AAS methodology made it possible to quantify the iron overload and estimate the values associated to the different hepatopathies.(AU)

Foi estudado o depósito de ferro (Fe) em tecido hepático de indivíduos saudáveis e de indivíduos com doenþas cr¶nicas do fígado, sendo todos adultos entre 46 e 70 anos. A quantificaþÒo de ferro foi realizada através da Técnica de Espectrometria de AbsorþÒo At¶mica com VaporizaþÒo Eletrotérmica (ET AAS). As amostras de fígado obtidas por biópsia hepática foram pesadas e submetidas O digestÒo ácida. Simultaneamente foram realizados testes de recuperaþÒo do analito fortificando as amostras e o branco de reagente com o acréscimo de um padrÒo de Fe. A quantificaþÒo foi realizada através de uma curva de calibragem (com padr§es entre 10 e 50 mg/L). Mediram-se áreas de pico a 248,3 nm usando como fonte uma lÔmpada de cátodo oco. Os resultados obtidos das amostras correspondentes a indivíduos sadios foram inferiores a 1.000 Ag/g de tecido seco, e os valores correspondentes a indivíduos com doenþas cr¶nicas do fígado resultaram superiores, entre 1.800 a 7.835 Ag/g de tecido seco. Foi observada uma relaþÒo direta entre a concentraþÒo de ferro em tecido hepático com o grau de depósito deste metal, pelo qual o desenvolvimento da metodologia ET AAS permitiu quantificar a sobrecarga de ferro e calcular os valores obtidos associados a diferentes hepatopatias.(AU)