Adipose Tissue Insulin Resistance Correlates with Disease Severity in Pediatric Metabolic Dysfunction-Associated Steatotic Liver Disease: A Prospective Cohort Study.

OBJECTIVES: To assess the role of adipose tissue insulin resistance (Adipo-IR) in the pathogenesis of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and to determine Adipo-IR evolution during a lifestyle intervention program. STUDY DESIGN: In this prospective cohort study, children and adolescents with severe obesity were recruited between July 2020 and December 2022 at an inpatient pediatric rehabilitation center. Treatment consisted of dietary intervention and physical activity. Liver steatosis and fibrosis were evaluated using ultrasound examination and transient elastography with controlled attenuation parameter and liver stiffness measurement. Every 4-6 months, anthropometric measurements, serum biochemical analysis, ultrasound examination, and elastography were repeated. Adipo-IR was estimated by the product of the fasting serum insulin times the fasting free fatty acid concentration, and hepatic IR by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), respectively. RESULTS: Of 200 patients with obesity, 56% had evidence of steatosis on ultrasound examination and 26% were diagnosed with fibrosis (≥F2). Adipo-IR increased progressively from lean controls to patients with obesity to patients with MASLD and MASLD with fibrosis. Adipo-IR was already increased in patients with only mild steatosis (P = .0403). Patients with more insulin-sensitive adipose tissue exhibited a lower liver fat content (P < .05) and serum alanine transaminase levels (P = .001). Adipo-IR correlated positively with visceral adipose tissue weight, waist circumference, and the visceral adipose tissue/gynoid adipose tissue ratio (P < .001), but not with total body fat percentage (P = .263). After 4-6 months of lifestyle management, both MASLD and Adipo-IR improved. CONCLUSIONS: Our data suggest that Adipo-IR is associated with the presence of pediatric MASLD, particularly steatosis.

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.

The Impact of a Sustained Virologic Response to Hepatitis C Virus Treatment on Liver Stiffness in the Puerto Rico Veterans Attending Liver Clinics in the Veterans Affairs Caribbean Healthcare System.

OBJECTIVE: To evaluate the impact of sustained virologic response (SVR) on liver stiffness, as measured by transient elastography (TE), in Hispanic patients treated with direct-acting antivirals (DAAs) in the outpatient clinics in the Veterans Affairs Caribbean Healthcare System. METHODS: We included hepatitis C virus (HCV) patients treated with DAA regimens from 11/2017 through 06/2019. Patient demographics and variables such as body mass index, HCV genotype, and treatment regimen were collected. The patients had a TE measurement before treatment initiation, and a repeat study 6 to 9 months after the achievement of SVR. A comparison between pre and post-treatment TE scores was performed via a paired t test. RESULTS: Forty-three subjects met all the inclusion criteria and completed a posttreatment TE. Most of the subjects were infected with genotypes 1a or 1b. Six to 9 months post SVR, we measured liver stiffness and found a statistically significant reduction in TE score (P value = .0003). The pretreatment median TE score was 10.2 kPa. On a repeat TE study at 6 to 9 months post-treatment, our subjects had a median score of 7.2 kPa. CONCLUSION: The eradication of HCV infection with DAAs is associated with improved TE scores. Fibrosis-stage reduction was more frequent in those who had stage 4 fibrosis prior to treatment. These results suggest that achieving SVR may spare patients from future clinical decompensation and complications. Adequate screening of this potentially deadly chronic infection can lead to early therapy with DAAs and the significant regression of fibrosis in this kind of patient.

Cohort study: Apparent redundancy of fibrosis assessment in young persons with HCV; development of realistic approaches to break the paradigm.

INTRODUCTION AND OBJECTIVES: Hepatitis C Virus (HCV) is a blood-borne, hepatotropic RNA virus causing both acute and chronic infection. Chronic HCV infection predisposes individuals to liver fibrosis, cirrhosis and hepatocellular carcinoma. Staging of fibrosis prior to treatment to determine either treatment choice or required follow up, is standard practice. However, this often acts as a barrier to treatment initiation. We sought to validate the hypothesis that those individuals; mono-infected with HCV, ≤35 years of age; with no additional hepatic insult were unlikely to have significant fibrosis. METHODS: We performed a retrospective analysis of a Hepatitis C Virus database; with collation of relevant basic demographics including age, sex and baseline Transient Elastography measurements pre-treatment. Additionally, we compared the reliability of biochemical fibrosis scores with corresponding transient elastography scores. RESULTS: Our results support the hypothesis that those individuals with chronic HCV ≤35 years old, with no additional risk for fibrogenesis did not have significant liver fibrosis within our cohort. CONCLUSION: Patients ≤35 years old likely do not necessitate fibrosis assessment prior to Direct Acting Antiviral (DAA) treatment in the absence of other significant risk factors for fibrosis. Given the emerging evidence that DAA treatment results in a significant decrease in all-cause mortality and hepatocellular carcinoma development, treatment of those with chronic HCV represents a global priority.

Liver stiffness is able to differentiate hepatosplenic Schistosomiasis mansoni from liver cirrhosis and spleen stiffness may be a predictor of variceal bleeding in hepatosplenic schistosomiasis.

BACKGROUND: Ultrasonography is limited for differentiating portal hypertension due to liver cirrhosis from that secondary to hepatosplenic schistosomiasis (HSS). We aimed to investigate the role of transient elastography (TE) in differentiating HSS mansoni from cirrhosis and the factors associated with liver and spleen stiffness (LS and SS) in HSS. METHOD: A cross-sectional study was conducted including patients with HSS mansoni (n=29) and liver cirrhosis due to non-alcoholic steatohepatitis (n=23). All patients underwent TE and those with HSS were assessed by the Niamey protocol. RESULTS: HSS subjects presented lower median LS (9.6 vs 21.3 Kpa, p<0.001) and liver controlled attenuation parameter (229 vs 274 dB/m, p=0.010) than cirrhosis subjects, in addition to higher SS (73.5 vs 42.2 Kpa, p=0.002). The area under the receiver operating characteristic curve for detecting cirrhosis by LS was 0.947 (95% CI 0.89 to 1.00, p<0.001), with an optimal cut-off of 11.75 Kpa. In HSS subjects, higher SS was associated with the presence of the following: diabetes mellitus (p=0.036), metabolic syndrome (p=0.043), esophageal varices (p=0.001), portal vein thrombosis (p=0.047) and previous variceal bleeding (p=0.011). In HSS patients without portal vein thrombosis, variceal bleeding was associated with higher SS (p=0.018). Niamey categories were not associated with LS (p=0.676) or SS (p=0.504). CONCLUSION: TE can play a role in differentiating HSS from cirrhosis, especially by LS. SS may be further investigated for predicting complications in HSS.

Prognostic impact of liver fibrosis and steatosis by transient elastography for cardiovascular and mortality outcomes in individuals with nonalcoholic fatty liver disease and type 2 diabetes: the Rio de Janeiro Cohort Study.

BACKGROUND: Liver stiffness measurement (LSM, which reflects fibrosis) and controlled attenuation parameter (CAP, which reflects steatosis), two parameters derived from hepatic transient elastography (TE), have scarcely been evaluated as predictors of cardiovascular complications and mortality in individuals with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). METHODS: Four hundred type 2 diabetic patients with NAFLD had TE examination (by Fibroscan®) performed at baseline. Multivariate Cox analyses evaluated the associations between TE parameters and the occurrence of cardiovascular events (CVEs) and mortality. TE parameters were assessed as continuous variables and dichotomized at low/high values reflecting advanced liver fibrosis (LSM > 9.6 kPa) and severe steatosis (CAP > 296 or > 330 dB/m). Improvements in risk discrimination were assessed by C-statistic and by the relative Integrated Discrimination Improvement (IDI) index. RESULTS: During a median follow-up of 5.5 years, 85 patients died (40 from cardiovascular causes), and 69 had a CVE. As continuous variables, an increasing LSM was a risk marker for total CVEs (hazard ratio [HR]: 1.05; 95% CI: 1.01-1.08) and all-cause mortality (HR: 1.04; 95% CI: 1.01-1.07); whereas an increasing CAP was a protective factor for both outcomes (HR: 0.93; 95% CI: 0.89-0.98; and HR: 0.92; 95% CI: 0.88-0.97; respectively). As dichotomized variables, a high LSM remained a risk marker of adverse outcomes (with HRs ranging from 2.5 to 3.0) and a high CAP was protective (with HRs from 0.3 to 0.5). The subgroup of individuals with low-LSM/high-CAP had the lowest risks while the opposite subgroup with high-LSM/low-CAP had the highest risks. Both LSM and CAP improved risk discrimination, with increases in C-statistics up to 0.037 and IDIs up to 52%. CONCLUSIONS: Measured by hepatic TE, advanced liver fibrosis is a risk marker and severe steatosis is a protective factor for cardiovascular complications and mortality in individuals with type 2 diabetes and NAFLD.

Serum leptin as a mediator of the influence of insulin resistance on hepatic steatosis in youths with excess adiposity.

BACKGROUND AND AIMS: The relationship between insulin resistance (IR) and hepatic steatosis (fatty liver) is well known; however, the extent to which the satiety hormone leptin acts as a confounder or mediator in this relationship is uncertain. We examined whether the association between IR and hepatic steatosis is mediated by leptin in Colombian adolescents with excess adiposity. METHODS AND RESULTS: A total of 122 adolescents (mean age: 13.4 years; 68% girls) participated in the study. We assessed body composition, hepatic steatosis (as defined by the controlled attenuation parameter [CAP]), cardiometabolic risk factors (body mass index, waist circumference, body composition), biochemical variables (leptin, insulin, glucose, lipid profile, cardiometabolic Z-score, transaminases, etc.), and physical fitness (cardiorespiratory fitness and grip strength). Partial correlation, regression, and mediation analyses were conducted using the Barron and Kenny framework. RESULTS: Ninety-two youths (75.4%) had IR. Mediation analysis revealed a positive relationship between Homeostasis Model Assessment-IR (HOMA-IR) and CAP (ßdir = 3.414, 95% confidence interval [CI]: 1.012 to 5.816, p < 0.001), which was attenuated when leptin was included in the model, thus indicating that leptin mediates this relationship (ßind = 1.074, 95% CI: 0.349 to 2.686, p < 0.001). The percentage of the total effect mediated by leptin was 21%. Regarding sex, the mediation effect of leptin remains significant among boys (ßind = 0.962, 95% CI: 0.009 to 2.615, p < 0.001), but not in girls (ßind = 0.991, 95% CI: 1.263 to 5.483, p = 0.477). CONCLUSIONS: The findings are clinically relevant to consider leptin levels as a surrogate marker of insulin sensitivity when assessing youths with excess adiposity and/or suspected Nonalcoholic hepatic steatosis or nonalcoholic fatty liver disease (NAFLD).

Changes in Liver Stiffness and Noninvasive Fibrosis Scores in Egyptian Adolescents Successfully Treated with Ledipasvir-Sofosbuvir for Chronic Hepatitis C Virus Infection.

OBJECTIVE: To assess changes in noninvasive liver fibrosis measurements after chronic hepatitis C eradication by direct-acting antivirals in Egyptian adolescents. STUDY DESIGN: Liver stiffness measurement (LSM), by vibration-controlled transient elastography and noninvasive fibrosis scores (Firbosis-4, aspartate aminotransferase-platelet ratio index), was obtained before and 12 months after eradication with ledipasvir-sofosbuvir. The primary outcome was a more than 30% decrease in LSM with resulting fibrosis stage regression for initial fibrosis of F2 or higher and nonprogression of F0-F1, using the Ishak score (F0-F6). The secondary outcome was change in noninvasive fibrosis scores after treatment. RESULTS: Analyzing 85 patients, the median baseline LSM was 5.8 (IQR, 4.2-6.5) and at follow-up 5.1 kPa (IQR, 4-6 kPa) (P = .045); 62 (73%) met the primary outcome, 16 patients (19%) experienced regression, and 46 (54%) nonprogression of LSM. Of 18 with initial fibrosis of F2 0r higher, 13 regressed to F0-F1 and 2 from F6 to F5, 1 unchanged at F3, and 1 increased to F3 and 1 to F4. Among 67 patients with a baseline fibrosis of F0-F1, 62 were unchanged and 5 increased-4 to F2 and 1 to F3. Although 23 (27%) had a more than 30% LSM increase, only 7 (8%), with associated comorbidities (4 ß-thalassemia, 3 hepatic steatosis), had increased fibrosis stage. The median baseline FIB-4 and aspartate aminotransferase-platelet ratio index scores were 0.34 (IQR, 0.22-0.47) and 0.35 (0.24-0.57), and at follow-up 0.3 (IQR, 0.22-0.34) and 0.2 (0.18-2.8) (P < .001, <.001), respectively. CONCLUSIONS: Chronic hepatitis C eradication by direct-acting antiviral agents in Egyptian adolescents was associated with nonprogression or regression of liver fibrosis, by noninvasive fibrosis measurements, at 12 months after treatment in the majority of cases.

Bariatric surgery during the evolution of fatty liver-A randomized clinical trial comparing gastric bypass and sleeve gastrectomy based on transient elastography.

Nonalcoholic fatty liver disease (NAFLD) is closely related to patients with obesity. For patients with NAFLD, bariatric surgery is the best treatment. However, the best technique to patient with severe NAFLD is still unknown. Currently available, the imaging methods for assessing and monitoring NAFLD are of limited use for diagnosing. In contrast, compared with liver biopsy and transient hepatic elastography (THE) has shown good accuracy in individuals with obesity. To prospectively compare the evolution of THE parameters of NAFLD right after the procedures: gastric bypass vs sleeve gastrectomy. Patients with obesity were randomized into two groups: gastric bypass and sleeve gastrectomy in a previous study. Iin a previous study one week before and three months after surgery the patients underwent evaluation by THE. The patients were also analyzed with controlled attenuation parameter (CAP), which assesses the degree of hepatic steatosis using the same device. Sleeve gastrectomy group showed a greater decrease in THE values (from 8.13 to 5.53 kPa) compared to the gastric bypass group (from 9.25 to 8.81 kPa; P = .004). CAP also revealed a greater decrease in sleeve subjects (from 287 to 242 dB/m) compared to gastric bypass subjects (from 290 to 276 dB/m; P < .0001). The absolute values of these differences also had a largest decrease with both methods in sleeve gastrectomy group (P = .013 and P = .005 for THE and CAP, respectively).Sleeve gastrectomy showed a greater decrease in both parameters (THE and CAP) than gastric bypass in the first months.

Baveno VI and Expanded Baveno VI criteria successfully predicts the absence of high-risk gastro-oesophageal varices in a Chilean cohort.

BACKGROUND: Baveno VI and expanded Baveno VI criteria have been recommended to circumvent the need for endoscopy screening in patients with a very low probability of varices needing treatment (VNT). AIM: To validate these criteria in a Latin American population. METHODS: The ability of Baveno VI criteria (liver stiffness measurement (LSM) <20 kPa and platelet count >150 × 103/µL) and expanded Baveno VI criteria (LSM < 25kPa and platelet count >110 × 103/µL) to exclude the presence of VNT was tested in a prospectively recruited cohort of patients with Child-Pugh A liver cirrhosis and with no previous variceal haemorrhage who attended the liver clinics of three major hospitals in Chile. RESULTS: Three hundred patients were included. The median (IQR) age was 61 [18-86] years, median MELD was 8.0 (6-17), median LSM was 17.2 (10.2-77) kPa and median platelet count was 137 (23-464) × 103 /µL. The main aetiology was non-alcoholic fatty liver disease (67.3%). VNT were present in 18% of patients. The Baveno VI criteria had a sensitivity of 98.1% and a specificity of 38.2%, potentially sparing 31.3% of upper endoscopies with a very low risk of missing VNT (1.1%). The expanded Baveno VI criteria had a sensitivity of 90.7% and a specificity of 61%, potentially sparing 51.3% of upper endoscopies with a risk of missing VNT of 3.6%. Both criteria were independently associated with the absence of VNT. CONCLUSION: We validated the Baveno VI and expanded Baveno VI criteria in Chilean population, potentially sparing 31.3% and 51.3% of endoscopies, respectively, with a very low risk of missing VNT. Fondecyt 1191183.

Fibroscan como diagnóstico de hipertensión portal en pacientes cirróticos / Fibroscan as a diagnosis of portal hypertension in cirrhotic patients / Fibroscan como diagnóstico de hipertensão portal em pacientes cirróticos

Resumen: Introducción: La hipertensión portal es un síndrome frecuente en las hepatopatías crónicas. Entre sus etiologías destaca la cirrosis hepática, responsable en la gran mayoría de los casos. Desde la incorporación de la Elastografía de Transición (Fibroscan) en Uruguay, no se han realizado estudios a nivel nacional que relacionen los resultados obtenidos mediante esta técnica con la presencia de hipertensión portal en pacientes cirróticos. Objetivo: Caracterizar la población cirrótica diagnosticada mediante Fibroscan, atendida en la policlínica de Hepatología del Hospital Pasteur. Material y Métodos: Se estudiaron los pacientes con diagnóstico de cirrosis hepática de cualquier etiología asistidos y controlados en la policlínica de Hepatología del Hospital Pasteur en el periodo de 2015 a 2018. Resultados: Se incluyeron 49 pacientes, de los cuales 34 presentaban hipertensión portal. Se encontró mayor prevalencia de cirrosis hepática en hombres con etiología alcohólica y por infección por virus de la hepatitis C. Se halló asociación entre valores de ET ≥ 15 kPa y la presencia de hipertensión portal. No fue posible demostrar asociación estadísticamente significativa entre valores de ET ≥ 15 kPa y la presencia de várices esófago gástricas y/o gastropatía por hipertensión portal. Conclusiones: El punto de corte utilizado en el Fibroscan es útil para diagnóstico de hipertensión portal. Es necesario continuar realizando fibrogastroscopía para el diagnóstico de la misma.

Abstract: Introduction: Portal hypertension is a syndrome that is frequently present in chronic liver diseases. Within the causes that results in portal hypertension, liver cirrhosis outstands, being responsible for most cases. Since the incorporation of transient elastography (Fibroscan) in Uruguay, no research has been conducted at a national level that correlates the results obtained by Fibroscan with the presence of portal hypertension in cirrhotic patients. Objectives: To characterize cirrhotic population diagnosed by Fibroscan who are assisted in the Hepatology polyclinic of Hospital Pasteur. Material and Methods: Patients with diagnosis of liver cirrhosis of any etiology were studied, who have been assisted and monitored in the Hepatology polyclinic of Hospital Pasteur in the period 2015 - 2018. Results: 49 patients were included, of which 34 presented elements of portal hypertension. A higher prevalence of cirrhosis was found in men with alcoholic etiology and infection with hepatitis C virus. An association was found between Fibroscan values ≥ 15 kPa and the presence of portal hypertension. It was not possible to demonstrate a statistically significant association between Fibroscan values ≥ 15 kPa and the presence of gastric esophageal varices and/or gastropathy due to portal hypertension. Conclusions: The cut-off point used in Fibroscan is useful for the diagnosis of portal hypertension. It is necessary to continue performing fibrogastroscopy for the diagnosis of portal hypertension.

Resumo. Introdução: A hipertensão portal é uma síndrome comum nas doenças hepáticas crônicas. Dentre suas etiologias, destaca-se a cirrose hepática, responsável na grande maioria dos casos. Desde a incorporação da Elastografia de Transição (Fibroscan) no Uruguai, não foram realizados estudos nacionais que relacionem os resultados obtidos por essa técnica com a presença de PHT em pacientes cirróticos. Objetivo: Caracterizar a população cirrótica diagnosticada por Fibroscan atendida na Policlínica de Hepatologia do Hospital Pasteur. Material e Métodos: Foram estudados pacientes com diagnóstico de cirrose hepática de qualquer etiologia assistida e controlada na Policlínica de Hepatologia do Hospital Pasteur no período de 2015 a 2018. Resultados: Foram incluídos no estudo 49 pacientes, dos quais 34 apresentavam elementos de hipertensão portal foi encontrada maior prevalência de cirrose hepática em homens com etiologia alcoólica e infecção pelo vírus da hepatite C. Foi encontrada associação entre valores de Fibroscan ≥ 15 kPa e presença de hipertensão portal. Não foi possível demonstrar associação estatisticamente significante entre valores de Fibroscan ≥ 15 kPa e presença de varizes esofágicas gástricas e / ou gastropatia por hipertensão portal. Conclusões: O ponto de corte utilizado no Fibroscan é útil para o diagnóstico da hipertensão portal. É necessário continuar realizando fibrogastroscopia para o diagnóstico de hipertensão portal.

PNPLA3 gene polymorphism in Brazilian patients with type 2 diabetes: A prognostic marker beyond liver disease?

BACKGROUND & AIMS: Genetic factors may impact nonalcoholic fatty liver disease (NAFLD) severity. We aimed to assess the prevalence of patatin-like phospholipase domain-containing 3 protein (PNPLA3) gene rs738409 C > G polymorphism in Brazilian individuals with type 2 diabetes and to investigate its association with liver disease severity, diabetic chronic degenerative complications, and metabolic control. METHODS AND RESULTS: PNPLA3 genotyping was performed and classified as CC, CG, and GG. Clinical and laboratory data were obtained, including chronic degenerative diabetes complications. Liver stiffness and steatosis were evaluated by transient hepatic elastography with CAP using FibroScan®. Multiple logistic regression was performed to investigate the association of PNPLA3 G allele with clinical and laboratory variables and with hepatic fibrosis/steatosis. Three hundred three patients were included (118 male, mean age 59 ± 9.5 years). The G allele frequency was 32.5% (CC 47%, CG 41%, and GG 12%). Significant liver fibrosis and severe steatosis were diagnosed in 26% and 43% of patients, respectively. The variables independently associated with the G allele were coronary artery disease (OR: 2.25; 95% CI: 1.03-4.88; p = 0.04), better glycemic control (OR for having an HbA1c ≥ 8% [64 mmol/mol]: 0.53; 95% CI: 0.31-0.89; p = 0.01), and significant liver fibrosis (OR: 1.82; 95% CI: 1.04-3.17; p = 0.03). CONCLUSION: In individuals with diabetes and NAFLD, PNPLA3 gene rs738409 C > G polymorphism is a marker for the risk of significant liver fibrosis and cardiovascular disease and may be associated with better glycemic control.

Transient Elastography and Controlled Attenuation Parameter (CAP) in the Assessment of Liver Steatosis in Severe Adult Growth Hormone Deficiency.

Non-alcoholic fatty liver disease (NAFLD) is common in patients with growth hormone deficiency (GHD). Some noninvasive techniques have been used to quantify liver fat, such as the controlled attenuation parameter (CAP). Objective: To evaluate CAP as a tool to identify liver steatosis and its relationship with different clinical and biochemical metabolic parameters in a group of patients with severe adult growth hormone deficiency (AGHD), and to compare the evolution of metabolic profiles after 6 months of human growth hormone (rhGH) replacement therapy in a subgroup of patients. Methods: Cross-sectional observational study at baseline of naive rhGH multiple pituitary hormonal deficiency (MPHD) hypopituitarism patients. A 6-month intervention clinical trial in a selected group of a non-randomized, non-controlled cohort was also applied. Results: Liver stiffness measurement (LSM) was normal in severe AGHD patients. CAP evaluation showed steatosis in 36.3% of baseline patients (8/22), associated with higher BMI, waist circumference, insulin, and alanine aminotransferase (ALT) levels. According to steatosis degree by CAP, child-onset growth hormone deficiency (CO-GHD) was graded as 68.75% (11/16) S0, 12.5% (2/16) S1, and 18.75% (3/16) S3, whereas AO-GHD was graded as 50% (3/6) S0, 16.66% (1/6) S2, and 33.33% S3. After 6 months of hrGH replacement, CAP measurements did not change significantly, neither on group without hepatic steatosis at baseline (194.4 ± 24.3 vs. 215.4 ± 51.3; p = 0.267) nor on the group with hepatic steatosis (297.2 ± 32.3 vs. 276.4 ± 27.8; p = 0.082). A significant improvement of body composition was observed only in the first group. Conclusions: We have demonstrated the importance of CAP as a non-invasive tool in the liver steatosis identification on hypopituitary patients. This method may be an important indicator of the severity of metabolic disorders in MPHD patients. In our study, no liver health modification in LSM at baseline or after 6 months of rhGH replacement was found. Longer studies can help to establish the potential repercussions of growth hormone replacement therapy on liver steatosis.

First detection of hepatitis E virus genotype 3 as a common infectious agent in patients with chronic liver damage in Mexico.

INTRODUCTION AND OBJECTIVES: To characterize the virological features of hepatitis E virus (HEV) in serum from patients exhibiting chronic liver damage. METHODS: A data-base of 513 unrelated individuals from West-Mexico with liver-disease determined by clinical and biochemical tests and transient elastography between 2011 and 2016 were retrospectively analyzed. According to infectious etiologies, patients were classified as hepatitis B virus (HBV)-, hepatitis C virus (HCV)-infected patients, and patients exhibiting chronic liver damage with non-identified infectious etiological agent (NIIEA). Available serum samples from NIIEA-patients were tested by RT-nPCR for the presence of HEV-RNA and partially sequenced for genotyping. RESULTS: Out of the 513 cases, 5.85% were patients infected with HBV, 67.64% with HCV, and 26.51% were NIIEA-patients. Among 76 available samples from NIIEA-cases, 30.26% tested positive for HEV-RNA. Twelve (15.79%) partial HEV sequences allowed phylogenetic analysis, revealing the classification of HEV as HEV-Gt3. Advanced fibrosis (F3-F4 stage) was found in a 26.1% of patients with HEV-active infection. CONCLUSION: Although HCV is the main infectious agent related to chronic liver disease in Mexico, liver damage without an infectious etiology is common. Our findings reveal that an elevated rate of chronic liver disease might be represented by autochthonous infection of HEV-Gt3, whose detection makes Mexico unique in Latin-America with the circulation of HEV strains belonging to three genotypes (Gt1, Gt2, and Gt3). Thus, HEV infection should be a matter of health concern, and mandates for HEV screening to properly handle this commonly undiagnosed disease.

Chronic Hepatitis C Patients with Obesity: Do we Need two Operators for Accurate Evaluation of Liver Stiffness?

INTRODUCTION AND AIM: Transient elastography is gaining popularity as a non-invasive method for predicting liver fibrosis, but inter observer agreement and factors influencing reproducibility have not been adequately assessed. MATERIAL AND METHODS: This cross-sectional study was conducted at Specialized Medical Hospital and the Egyptian Liver Foundation, Mansoura, Egypt. The inclusion criteria were: age older than 18 years and chronic infection by hepatitis C. The exclusion criteria were the presence of ascites, pacemaker or pregnancy. Three hundred and fifty-six patients participated in the study. Therefore, 356 pairs of exams were done by two operators on the same day. RESULTS: The overall inter observer agreement ICC was 0.921. The correlation the two operators was excellent (Spearman's value q = 0.808, p < 0.001). Inter-observer reliability values were κ = 0.557 (p < 0.001). A not negligible discordance of fibrosis staging between operators was observed (87 cases, 24.4%). Discordance of at least one stage and for two or more stages of fibrosis occurred in 60 (16.9%) and 27 cases (7.6%) respectively. Obesity (BMI ≥ 30 kg/m2) is the main factor associated with discordance (p = 0.002). CONCLUSION: Although liver stiffness measurement has had an excellent correlation between the two operators, TE presented an inter-observer variability that may not be negligible.

Early Detection of Liver Damage in Mexican Patients with Chronic Liver Disease.

BACKGROUND AND OBJECTIVE: Liver cirrhosis is usually detected at the later stages of disease. This study is aimed to detect liver damage in patients with chronic liver disease using transitional elastography (TE) and to assess the biochemical parameters associated with liver damage. METHODS: In 578 patients, chronic liver disease based on etiology was diagnosed by clinical and laboratory tests. Liver damage was evaluated with TE (FibroScan®), while its association with biochemical parameters was performed using the logistic regression tests. RESULTS: Overall, the main etiologies of liver damage were hepatitis C virus (HCV) (37%), alcoholic liver disease (ALD) (33%) and non-alcoholic steatohepatitis (NASH) (26%). Patients were 40 to 50 years of age. ALD and hepatitis B prevailed in men, whereas HCV and NASH in women. The stages of fibrosis were F0 (n = 121, 21%), F1 (n = 122, 21%), F2 (n = 58, 10%), F3 (n = 46, 8%) and F4 (n = 87, 15%). In patients with liver cirrhosis, ALD (n = 96/217, 45%), HCV (n = 94/217, 43%) and NASH (n = 21/217, 10%) were the leading etiologies. Platelets count (OR=3.31, 95%CI 1.61-6.78), glucose (OR=3.07, 95%CI 1.50-6.26), gamma-glutamyl-transferase (OR=3.60, 95%CI 1.79-7.25), albumin (OR=3.89, 95%CI 1.61-9.36), and total bilirubin (OR=3.93, 95%CI 1.41-10.91) were associated to advanced stages of fibrosis (F3-F4) regardless of etiology. The concordance and positive predictive values of these parameters were higher as compared to other scores. CONCLUSION: Asymptomatic liver disease due to HCV, ALD and NASH prevailed in young adults. Advanced liver damage assessed by TE was associated with five biochemical parameters. In conjunction, both methodologies may be useful for the early detection of fibrosis and cirrhosis in Latin America.

Diagnostic Accuracy of Transient Elastography for Detecting Liver Fibrosis After Liver Trannsplantation: A Specific Cut-Off Value Is Really Needed?

INTRODUCTION: Liver transplant recipients often perform liver biopsy (LB), specially in the context of potentially recurring diseases, such as hepatitis C infection. However, the LB has risks of complications, despite being the gold standard. Transient elastography (TE) is a noninvasive method comparable to the LB to evaluate liver fibrosis in various settings, but its accuracy among transplant recipients is not fully understood. OBJECTIVE: To determine the accuracy of TE in liver transplant recipients compared with LB to successfully predict liver fibrosis. PATIENTS AND METHODS: Patients who underwent liver transplantation at Hospital Israelita Albert Einstein from 2010 to 2012 and presented with LB indication were also subjected to TE at the time of LB. The medium value of ten successful measurements was kept as a representative of the liver stiffness. The definition of cut-off points was made to ensure specificity of ≥90 % for all fibrosis stages (F0-F4). RESULTS: LB was performed in 267 patients. TE was not analyzed in only 8 (3 %) due to an elevated body mass index. The optimal liver stiffness cut-off value and diagnostic performance were 8.1 kPa for F ≥ 1, 12.3 kPa for F ≥ 2, 15.1 for F ≥ 3, and 16.7 for F = 4 for all patients and were 8.1 kPa for F ≥ 1, 12.3 kPa for F ≥ 2, 16.5 for F ≥ 3, and 17.6 for F = 4 for patients with hepatitis C. CONCLUSIONS: TE demonstrated good performance in defining cut-off points for fibrosis on liver histology observed in transplant recipients. The TE can be considered an alternative to LB in post-liver transplantation.

Relación entre el factor de crecimiento hepático y el estadio de la cirrosis / Relationship between Hepatocyte Growth Factor (Hgf) and Stage of Cirrosis

Introducción: en el hígado, el factor de crecimiento hepático (FCH) es conocido por ser un potente agente mitogénico tanto in vivo como in vitro. Sin embargo, el papel del FCH en la cirrosis no está completamente claro y algunos estudios lo señalan como un marcador de severidad en la cirrosis, en la insuficiencia hepática aguda y en la hepatitis crónica. Objetivos: determinar la relación entre el FCH y el estadio de la cirrosis hepática e identificar los factores asociados con los niveles de FCH en esta población. Metodología: se evaluaron todos los pacientes con cirrosis hepática atendidos desde enero a marzo de 2014. La elastografía transitoria (ET), la recopilación de la información clínica y la extracción de la muestra para la determinación del FCH se realizó de forma simultánea en el momento de la inclusión. Resultados: no se encontró relación entre los niveles de FCH y la clasificación de Child-Pugh; sin embargo, se observaron niveles más elevados en pacientes con enfermedad descompensada. Se determinó una asociación lineal positiva entre el FCH y la dureza hepática estimada por elastografía (b = 0,53; r2 = 0,26; p = 0,002) y una asociación lineal negativa con la albúmina (b = -0,62; r2 = 0,39; p <0,001). Únicamente la albúmina conservó esta asociación en el análisis multivariante. Conclusión: el FCH es un marcador de severidad en la cirrosis hepática. La albúmina y el grado de fibrosis determinada por ET se asociaron con niveles de FCH

Introduction: Hepatocyte growth factor (HGF) is known to be a potent mitogenic agent both in vivo and in vitro. The role of HGF in cirrhosis is not completely clear, but some studies point to it as a marker of severity in cirrhosis, acute liver failure and chronic hepatitis. Objective: The objective of this study was to determine the relationship between HGF and the stage of hepatic cirrhosis and to identify factors associated with HGF levels in this population. Methodology: All patients with hepatic cirrhosis treated from January to March 2014 were evaluated. At the time patients were enrolled in the study their clinical histories were taken and they underwent transient elastography and extraction of samples for measurement of HGF. Results: No relationships were found between HGF levels and Child-Pugh classifications, however, higher levels of HGF were observed in patients with decompensated disease. A positive linear relations was found between HGF and hepatic hardness estimated by elastography (b = 0.53, r2 = 0.26, p = 0.002) and a negative linear relation was found between HGF and albumin (b = -0.62, r2 = 0.39, p <0.001). Only albumin retained this association in the multivariate analysis. Conclusion: HGF is a marker of severity in liver cirrhosis. Albumin and the degree of fibrosis determined by transient elastography were associated with HGF levels.

The Correlation Between Obesity-Related Diseases and Non-alcoholic Fatty Liver Disease in Women in the Pre-operative Evaluation for Bariatric Surgery Assessed by Transient Hepatic Elastography.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common, severe disease in obese patients. However, NAFLD is usually underestimated by ultrasonography. Liver biopsy is not routinely done in bariatric surgery or during the follow-up. This study therefore examined the correlation between metabolic syndrome and NAFLD in morbidly obese patients based on an assessment using transient hepatic elastography (THE). MATERIAL AND METHODS: This study involved 50 female patients in the pre-operative phase for bariatric surgery. Before surgery, we collected clinical, laboratory, and anthropometric variables. THE measurements were obtained using a FibroScan® device (Echosens, Paris, France), and steatosis was quantified using Controlled Attenuation Parameter software (CAP). Statistical analyses were done using linear correlation and the Kruskal-Wallis test. RESULTS: The mean of THE and CAP values were 7.56 ± 4.78 kPa and 279.94 ± 45.69 dB/m, respectively, and there was a significant linear correlation between the two measurements (r = 0.651; p < 0.001). The numbers of metabolic syndrome parameters did not influence the THE (p = 0.436) or CAP (p = 0.422) values. HbA1c and HOMA-IR showed a strong linear correlation with CAP (r = 0.643, p = 0.013 and r = 0.668, p = 0.009, respectively) and a tendency to some linear correlation with THE (r = 0.500, p = 0.05 and r = 0.500, p = 0.002, respectively). CONCLUSION: Morbidly obese women submitted to FibroScan® presented a high prevalence of severe steatosis and advanced fibrosis in our sample. Insulin resistance parameters were correlated with steatosis, but less with fibrosis.

Increasing aortic stiffness is predictive of advanced liver fibrosis in patients with type 2 diabetes: the Rio-T2DM cohort study.

BACKGROUND & AIMS: Type 2 diabetes mellitus (T2DM) is a risk factor for cardiovascular disease (CVD) and advanced stages of non-alcoholic fatty liver disease (NAFLD). The aim was to evaluate the association between aortic stiffness, a preclinical CVD marker, with advanced liver fibrosis identified by transient elastography (TE) in T2DM outpatients with NAFLD. METHODS: This longitudinal study included 291 T2DM patients with NAFLD detected by ultrasonography, who had two carotid-femoral pulse wave velocity (cf-PWV) measurements and a TE examination (Fibroscan(®) ) performed over a median follow-up of 7 years. Advanced liver fibrosis (corresponding to ≥ F3 stage) was considered as median values >7.9 kPa (M probe) or >7.2 kPa (XL probe). Increased aortic stiffness was defined as cf-PWV >10 m/s. RESULTS: Eighty patients (27.5%) had advanced liver fibrosis. Overall, there was an increase in cf-PWV of 0.1 m/s/year (1% per year). Both a high aortic stiffness at the 2nd cf-PWV examination [odds ratios (OR): 3.0; 95% CI: 1.3-7.2; P = 0.011] and a serial increase in aortic stiffness (OR: 2.1; 95% CI: 1.0-4.3; P = 0.046) were associated with increased odds of having advanced liver fibrosis. Patients who presented either an increase in aortic stiffness or persisted with high values had significantly higher mean liver stiffness than those who either decreased aortic stiffness or persisted with normal cf-PWV values (mean difference: 2.1 kPa, 95% CI: 0.5-3.7 kPa, P = 0.012), after adjustments for anthropometric-demographic and clinical laboratory covariates. CONCLUSIONS: In T2DM patients with NAFLD, a high or increasing aortic stiffness predicted development of advanced liver fibrosis on TE.