Longitudinal liver stiffness assessment in patients with chronic hepatitis C undergoing antiviral therapy.

BACKGROUND/AIMS: Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). METHODS: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. RESULTS: 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥ 9.5 and ≥ 7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. CONCLUSIONS: LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage.

ARFI, FibroScan, ELF, and their combinations in the assessment of liver fibrosis: a prospective study.

BACKGROUND & AIMS: Our aim was to evaluate a serologic marker (ELF) and two ultrasound-based methods (FibroScan and ARFI), as well as their combinations, in the assessment of liver fibrosis. METHODS: One-hundred and forty-six patients (87 liver transplant recipients, 59 non-transplant patients) who underwent liver biopsy were prospectively included. We evaluated the diagnostic accuracy of FibroScan, ARFI, ELF and the combination of ELF with either ARFI or FibroScan. After analyzing in separate transplant and non-transplant patients, the whole cohort was divided into a training set and a validation set. RESULTS: ARFI imaging was successfully performed across the whole cohort, while FibroScan failed in 16 (11%) patients. The three methods showed similar AUROCs and best cut-off values in transplant and non-transplant patients. In the training set, differences between the AUROCs of ARFI, FibroScan and ELF to diagnose F⩾2 (0.879, 0.861, and 0.764, respectively) and cirrhosis (0.936, 0.918, and 0.841) were not statistically significant, although both ultrasound-based methods showed higher accuracy than ELF. The combination of ELF with ARFI or FibroScan increased the negative and positive predictive values of single tests for the diagnosis of F ≥ 2 and cirrhosis. Similar results were obtained when the methods were tested in the validation set. CONCLUSIONS: ARFI is as effective as either FibroScan or ELF in the non-invasive assessment of liver fibrosis, and its inclusion in an ultrasound device could facilitate its incorporation into routine clinical practice. The combination of ARFI or FibroScan with ELF may help better identify patients with or without significant fibrosis or cirrhosis.

Noninvasive assessment of liver fibrosis.

Liver biopsy has long been an important tool for assessing the degree of liver fibrosis. Information on the presence and degree of liver fibrosis is useful before making therapeutic decisions or predicting disease outcomes. The need to stage liver fibrosis, however, should decrease as treatment options become more successful (as has occurred with viral hepatitis). In recent years, noninvasive tests have demonstrated a reasonable ability to identify significant fibrosis, cirrhosis in particular, nor is it surprising that liver disease specialists and patients favor a noninvasive approach. However, only those tests with the highest diagnostic accuracy, cost-effectiveness, and availability should be implemented. Apart from their diagnostic accuracy, the potential ability of these tests to predict disease outcomes (a more relevant endpoint) should be compared with that of liver biopsy. Indeed, the use of a standardized system to evaluate the utility of biomarkers would facilitate their implementation in clinical practice.

Peginterferon plus ribavirin and sustained virological response in HCV-related cirrhosis: outcomes and factors predicting response.

OBJECTIVES: Patients with hepatitis C virus (HCV) cirrhosis are difficult to treat and have a high risk of liver decompensation or hepatocellular carcinoma. We sought to identify factors that could predict treatment response. METHODS: Collaborating centers (n=26) provided data for patients (n=568) with HCV cirrhosis undergoing treatment with peginterferon-α plus ribavirin (RBV). Univariate and multivariate analyses were used to evaluate factors predicting treatment outcomes. RESULTS: Sustained viral response (SVR) in naive patients was 30.7%, with no significant differences between centers. Median follow-up was 35 months (range: 1-81). Factors predicting SVR were: non-genotype 1 (odds ratio (OR)=4.183; 95% confidence interval (CI): 2.353-7.438) overall dose and ≥80% of the scheduled time of treatment (OR=3.177; 95% CI: 1.752-5.760); serum γ-glutamyl transpeptidase (GGT) <76 IU per ml (OR=4.092; 95% CI: 2.418-6.927); baseline viral load <6 × 10(5) (OR=2.597; 95% CI: 1.583-4.262); absence of ultrasound signs of portal hypertension (OR=2.067; 95% CI: 1.26-3.39). No patient with a HCV-RNA decline <1 log(10) at week 4 achieved SVR. Event-free survival at 5 years was 91% in patients with SVR vs. 59% in non-responders (P<0.001). Overall survival in patients with SVR was 98% vs. 86% in non-responders (P=0.005). Independent factors predicting events were absence of SVR (hazard ratio (HR)=2.66; 95% CI: 1.32-5.54), baseline serum albumin <3.9 g per 100 ml (HR=3.06; 95% CI: 1.81-5.15), presence of esophageal varices on endoscopy (HR=2.489; 95% CI: 1.546-4). Improved outcome was more evident in responders with less advanced disease at baseline. CONCLUSIONS: SVR can be achieved in approximately one-third of patients with HCV-related cirrhosis. SVR independently reduces the likelihood of clinical decompensation and improves survival.

The eSS rat, a nonobese model of disordered glucose and lipid metabolism and fatty liver.

BACKGROUND: eSS is a rat model of type 2 diabetes characterized by fasting hyperglycemia, glucose intolerance, hyperinsulinemia and early hypertriglyceridemia. Diabetic symptoms worsen during the second year of life as insulin release decreases. In 12-month-old males a diffuse hepatic steatosis was detected. We report the disturbances of lipid metabolism of the model with regard to the diabetic syndrome. METHODS: The study was conducted in eight 12-month-old eSS male rats and seven age/weight matched eumetabolic Wistar rats fed with a complete commercial diet al libitum. Fasting plasmatic glucose, insulin, triglycerides, total cholesterol, low-density and high-density lipoprotein, and nonesterified fatty acids levels were measured. Very low density and intermediate-density lipoproteins were analyzed and hepatic lipase activity was determined. RESULTS: eSS rats developed hyperglycemia and hyperinsulinemia, indicating insulin resistance. Compared with controls, diabetic rats exhibited high plasmatic levels of NEFA, triglycerides (TG), total cholesterol (Chol) and LDL-Chol while high-density lipoprotein (HDL) cholesterol values were reduced. eSS rats also displayed TG-rich VLDL and IDL particles without changes in hepatic lipase activity. CONCLUSION: The nonobese eSS rats develop a syndrome characterized by glucose and lipid disorders and hepatic steatosis that may provide new opportunities for studying the pathogenesis of human type 2 diabetes.

Quantification of pancreatic zinc output as pancreatic function test: making the secretin-caerulein test applicable to clinical practice.

BACKGROUND/AIM: The secretin-caerulein test (SCT) is generally considered the gold standard for evaluation of the exocrine pancreatic function. Problems related to enzyme inactivation in the aspirated duodenal juice limit the clinical applicability of the test. Pancreatic zinc, which is mainly secreted as constituent of metalloenzymes, is stable in duodenal juice and easy to quantify. The aim of this study was to analyze the accuracy of the secretin-caerulein-stimulated pancreatic zinc output as pancreatic function test in comparison with the standard SCT. METHODS: Forty consecutive patients with suspected chronic pancreatitis and 28 healthy subjects were studied. A SCT was performed after overnight fast by infusing intravenously secretin (1 U/kg/h) and caerulein (100 ng/kg/h) over 90 min. The duodenal content was continuously aspirated and separated at 15-min intervals and immediately analyzed for pH, bicarbonate, amylase, lipase, elastase, carboxypeptidase A, and zinc. Correlation and concordance between standard SCT and quantification of zinc output and the accuracy of the latter for diagnosing and grading the exocrine pancreatic dysfunction were calculated. RESULTS: The pancreatic zinc output correlated significantly with enzyme and bicarbonate output (r ranging from 0.670 to 0.855; p < 0.001). A highly significant concordance was found between the degree of exocrine pancreatic dysfunction based on the standard SCT (bicarbonate and enzymes output) and that based only on zinc output (k = 0.831; p < 0.001). Quantification of the stimulated pancreatic zinc output has a sensitivity of 97% and a specificity of 91% in the diagnosis of exocrine pancreatic dysfunction. CONCLUSIONS: The determination of pancreatic zinc output during secretin and caerulein stimulation is a simple and accurate method for evaluation of the exocrine pancreatic function. Zinc is stable in duodenal juice, and its determination as a single parameter simplifies the clinical applicability of the SCT.

Hepatic delta9, delta6, and delta5 desaturations in non-insulin-dependent diabetes mellitus eSS rats.

Both diabetes mellitus type 1 and diabetes mellitus type 2 are widespread diseases that alter carbohydrate and lipid metabolism. e Stilmann-Salgado (eSS) rats are experimental animals that spontaneously evolve to a state similar to that of young people affected by non-insulin-dependent diabetes mellitus (NIDDM; type 2). Using 6-mon-old eSS rats that, according to the literature [Martinez, S.M., Tarrés, M.C., Montenegro, S., Milo, R., Picena, J.C., Figueroa, N., and Rabasa, S.R. (1988) Spontaneous Diabetes in eSS Rats, Acta Diabetol. Lat. 25, 303-313], had already developed insulin resistance, we investigated the changes evoked on delta9, delta6, and delta5 liver desaturases. The abundance of mRNA and enzymatic activities were measured, as well as the FA composition of liver microsomal lipids. Compared to control rats, the mRNA content and activity of SCD-1 (stearoyl CoA-desaturase, isoform of the delta9 desaturase) were significantly higher, whereas the mRNA and activities of delta6 and delta5 desaturases were not significantly modified. Correspondingly, the proportion of 18:1n-9 and the ratios of 18:1n-9/18:0 and 16:1/16:0 in lipids were significantly increased, whereas the proportion of 20:4n-6 was unaltered. These effects were found while glycemia was constant or increased. The results are completely opposite those described in insulin-dependent diabetes mellitus (type 1), in which a depression of all the desaturases is found. They suggest that in eSS rats, the activities of the desaturases were not modified by an insulin-resistance effect. Moreover, we suggest that the enhancement of SCD-1 activity might be considered as another typical sign of the NIDDM syndrome, because it has also been found in other animal models of NIDDM, for example, the ones evoked by the sucrose-rich diet and in the Zucker rat.

El ketazolam administrado como medicación preanestésica la noche anterior a la cirugía / Ketazolam administered as an anaesthesic premedication the night before surgery

Se estudió la capacidad protectora del Ketazolam respecto del estrés preoperatório. Una 1,4 benzodiazepina con propiedades ansiolíticas utilizado en clínica médica y psiquitatría, en dosis de 30 mg (n = 20) y de 60 mg (n = 20), administrado en dosis única por vía oral la noche anterior a la cirugía. 16 pacientes que no habían recibido medicación preanestésica constituyeron el grupo testigo. Se midió la frecuencia cardíaca (FC) y la presión arterial (PA) y se calculó su producto (FC x PA) la noche anterior a la cirugía (A), 30 minutos antes de la misma (B) y al ingresar al quirófano (C). Simultáneamente, se evaluó el miedo de los pcacientes consignando la manifestación de 13 signos y síntomas que constituyen la escala valorativa del miedo (EVM). Se comprobó que la FC aumenta en C respecto de A en el grupo testigo, mientras que los grupos tratados permanecen sin cambio significativo. La PA disminuyó en B en los grupos medicados mientras que el grupo que recibió 60 mg de ketazolam no aumentó significativamente su PA en C respecto de A. En los pacientes medicados disminuyó FC x PA en B y permaneció constante en C respecto de A. Los valores de la EVM descendieron en B en los pacientes tratados, mientras que en C no aumentó su valor respecto de A el grupo de pacientes que recibió la dosis mayor. Se concluye que existiría un efecto favorable del ketazolam utilizado como medicación preanestésica y un efecto dosis detectable a través de su acción sobre la PA y los valores de la EVM

El ketazolam administrado como medicación preanestésica la noche anterior a la cirugía / Ketazolam administered as an anaesthesic premedication the night before surgery

Se estudió la capacidad protectora del Ketazolam respecto del estrés preoperatório. Una 1,4 benzodiazepina con propiedades ansiolíticas utilizado en clínica médica y psiquitatría, en dosis de 30 mg (n = 20) y de 60 mg (n = 20), administrado en dosis única por vía oral la noche anterior a la cirugía. 16 pacientes que no habían recibido medicación preanestésica constituyeron el grupo testigo. Se midió la frecuencia cardíaca (FC) y la presión arterial (PA) y se calculó su producto (FC x PA) la noche anterior a la cirugía (A), 30 minutos antes de la misma (B) y al ingresar al quirófano (C). Simultáneamente, se evaluó el miedo de los pcacientes consignando la manifestación de 13 signos y síntomas que constituyen la escala valorativa del miedo (EVM). Se comprobó que la FC aumenta en C respecto de A en el grupo testigo, mientras que los grupos tratados permanecen sin cambio significativo. La PA disminuyó en B en los grupos medicados mientras que el grupo que recibió 60 mg de ketazolam no aumentó significativamente su PA en C respecto de A. En los pacientes medicados disminuyó FC x PA en B y permaneció constante en C respecto de A. Los valores de la EVM descendieron en B en los pacientes tratados, mientras que en C no aumentó su valor respecto de A el grupo de pacientes que recibió la dosis mayor. Se concluye que existiría un efecto favorable del ketazolam utilizado como medicación preanestésica y un efecto dosis detectable a través de su acción sobre la PA y los valores de la EVM (AU)

Modificación del estres preoperatorio mediante el empleo de lorazepam / Modification of preoperative stress by the use of lorazepam

Se estudió la capacidad del lorazepam para proteger al paciente del estrés preoperatorio a través de la valoración del producto de la frecuencia cardíaca por la presión arterial sistólica (FC x PA). Se evaluaron 87 pacientes medicados y 16 no medicados con lorazepam y se comprobó una respuesta favorable al mismo consistente en el descenso del producto frecuencia-presión 30 minutos antes de la cirugía respecto de la noche anterior y en una menor proporción de pacientes con valores de dicho producto >- 12000 (valor riesgo). Por el contrario, en el grupo no medicado, el producto aumentó en forma progresiva hasta alcanzar los valores más altos en la evaluación realizada en el quirófano. También aumentó la proporción de pacientes con valores >- 12000. No se verificaron diferencias entre las dosis y vías empleadas

Modificación del estres preoperatorio mediante el empleo de lorazepam / Modification of preoperative stress by the use of lorazepam

Se estudió la capacidad del lorazepam para proteger al paciente del estrés preoperatorio a través de la valoración del producto de la frecuencia cardíaca por la presión arterial sistólica (FC x PA). Se evaluaron 87 pacientes medicados y 16 no medicados con lorazepam y se comprobó una respuesta favorable al mismo consistente en el descenso del producto frecuencia-presión 30 minutos antes de la cirugía respecto de la noche anterior y en una menor proporción de pacientes con valores de dicho producto >- 12000 (valor riesgo). Por el contrario, en el grupo no medicado, el producto aumentó en forma progresiva hasta alcanzar los valores más altos en la evaluación realizada en el quirófano. También aumentó la proporción de pacientes con valores >- 12000. No se verificaron diferencias entre las dosis y vías empleadas (AU)