Validation of the number connection test for identifying patients with minimal hepatic encephalopathy.

OBJECTIVES: Hepatic encephalopathy is a serious neuropsychiatric complication in advanced liver disease. The affected patients exhibit alterations in psychomotor and intellectual functions. The aims of this study were to identif the set ofnormal values for the number connection tests (NCT-A and NCT-B) in a population of volunteers without liver disease, to compare the values from this reference population with those from patients with cirrhosis without hepatic encephalopathy. MATERIALS AND METHODS: This study was performed in two referral hospitals in an urban setting from the city of La Plata. We evaluated the Number Connection Tests in 112 healthy subjects and 30 patients with cirrhosis without manifestations of hepatic encephalopathy. Time for performing the tests was measured in seconds. Results were compared according to age, gender, level of education and fine motor skills in both groups. RESULTS: Mean age in the control group was 45.3years; 56 (50%) were women. Mean age in the cirrhotic group was 54.5 years; 8 (27%) were women. In the control group, the mean time for completing NCT-A and NCT-B was 60 s +/- 36s and 140 s +/- 60 s, respectively. In the cirrhotic group, the mean time for completing NCT-A and NCT-B was 114 s +/- 64 y 232 s +/- 87 s, respectively (P = 0.00001 for both tests). 56.6% of cirrhotic patients took more than 2 SD to perform the NCT-A and 53.3%, more than 2 SD to perform the NCT-B. CONCLUSION: We have obtained reference values for NCT-A and NCT-B completing times in our healthy population. Cirrhotic patients without overt hepatic encephalopathy took double time than controls to complete NCT-A and NCT-B and over half of our patients would have minimal hepatic encephalopathy.

Etiology of hepatocellular carcinoma in Argentina: results of a multicenter retrospective study.

Incidence and etiology of hepatocellular carcinoma (HCC) are variable around the world, depending mainly on theprevalence ofchronic hepatitis B carriers in each region. No study has been published analyzing epidemiological features of patients with HCC in Argentina. The aim of this retrospective study was to describe demographical and etiological results in a series of 587 consecutive patients with HCC diagnosed in 15 Hepatology and Gastroenterology Units distributed all around our country. Seventy-two per cent of patients were male, the median age was 62 years (interquartile range 55-68 years), and 93% had cirrhosis. Regarding to etiological data (fully available in 551 cases), main etiologies were chronic alcoholism in 229 patients (41.6%) (the sole risk factor in 182, associated to HCVin 35 and to HBV in 12); hepatitis C in 223 patients (40.5%) (the sole risk factor in 181, associated to alcoholism in 35 and to HBV in 7); hepatitis B in 74 patients (13.4%) (the sole risk factor in 55, associated to alcoholism in 12 and to HCV in 7); cryptogenic cirrhosis in 51 patients (9.2%). There were significant differences in percentages of genders between main groups: males were highly predominant in alcoholic cirrhosis (93%), hepatitis B (87%) and HCV plus alcohol (94%), compared to 63% in cryp togenic cirrhosis and 49% in hepatitis C (p<0.01). There were no differences in age at presentation between the main etiologies. In conclusion, the main causes of HCC in Argentina are alcoholic cirrhosis and hepatitis C (76% of cases). A majority of patients with HCC in our country are cirrhotics, males, and in their 6th or -7th decades of life.

[Severe acute hepatitis associated with intake of Aloe vera tea]. / Hepatitis aguda grave asociada al consumo de té de Aloe vera.

We present a 26-year-old man who developed severe acute hepatitis after consumption of an Aloe vera tea. On admission, the patient showed characteristic biochemical and clinical features of acute hepatitis and liver failure. The patient reported that he had been drinking an Aloe vera tea 2-4 weeks before symptom onset. Other causes of acute hepatitis were excluded and the patient improved after withdrawal of the Aloe vera tea. Aloe vera should be considered as a possible cause in cases of acute hepatitis.

[The Dubin-Johnson syndrome: case report and review of literature]. / Síndrome de Dubin Johnson: presentación de un caso y revisión de la literatura.

The Dubin-Johnson syndrome is a hereditary deficiency in the excretion ofconjugated bilirrubin by hepatocytes characterized by chronic hyperbilirubinemia, alteration in coproporphyrin metabolism, and intracellular deposition of a dark melanin-like pigment giving the liver a typical black cast. We report a 28-year-old male patient who presented conjunctival jaundice and conjugated-hyperbilirubinemia without no other alteration in hepatic biochemistry. The diagnosis of this syndrome was perfomed by using the low-risk methods of laparoscopy-facilitated hepatic biopsy and oral cholecystography In contrast, we avoided the classical Bromsulphalein test because of potential severe side effects. We stress here the current importance of these tests for confirming the diagnosis. By using this methodology, we were not able to quantify the isomeric profile of the urinary coproporphyrins nor 99mTc-HIDA cholescintigraphy. In conclusion, we confirm the utility of hepatic biopsy with the aid of laparoscopy and oral cholecystography for the diagnosis of the Dubin-Johnson syndrome on the basis of their effectiveness and relative lack of complications.

Alanine-aminotransferase: an early marker for insulin resistance?

In a population-based sample, after excluding alcohol consumption, hepatotoxic drugs and hepatitis B and C infected, we investigated if alanine-aminotransferase (ALT) was associated with metabolic syndrome and insulin resistance, and if this association was caused by non-alcoholic fatty liver disease (NAFLD). The sample (432 female and 119 male) was divided into two ALT thresholds corresponding to the 50th and 75th percentiles (P) (female > or = 15 and > or = 19 U/L; male > or = 17 and > or = 23 U/I, respectively). Blood pressure, body mass index, waist circumference, cholesterol, HDL cholesterol (HDLc), triglyceride (TG), TG/HDLc ratio, glycemia and homeostasis model assessment of insulin resistance (HOMA-IR) were compared between those above and below each ALT threshold. Female placed above the 50th P of ALT had higher levels of TG/HDLc ratio (p=0.029), glycemia (p=0.028), and homeostasis model assessment of insulin resistance, (p=0.045), and above the 75th P had higher SBP (p=0.036), DBP (p=0.018), TG (p=0.024), TG/HDLc ratio (p=0.028), glycemia (p=0.004) and HOMA-IR (p=0.0014). Male placed above the 50th P of ALT had higher BMI (p=0.017) and TG/HDLc ratio (p=0.048), and above the 75th P had lower values of HDLc (p=0.042). Only 16.5% of women and 14.5% of men, above the 75th P of ALT, showed an increase in liver brightness in the echography. This work shows in woman an early association of ALT with TG/HDLc ratio and HOMA-IR. Since the last two are independent predictors of cardiovascular risk, attention should be drawn to ALT values near the upper limit of the normal range even in the absence of NAFLD and obesity.

[Liver damage in workers exposed to hydrocarbons]. / Daño hepático en trabajadores expuestos a hidrocarburos.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the occurrence of hypertransaminasemia (hTAMSemia) as an indicator of liver damage and to establish the association of this hepatotoxicity with exposure to aromatic hydrocarbons (benzene, toluene, and xylene [BTX]) among workers in a petrochemical company. PATIENTS AND METHOD: The medical records of 167 industrial employees, 95 with hydrocarbon exposure (EHCs) and 72 without exposure (NEHCs) were reviewed. Age, sex, number of years employed, body mass index, and biochemical and hematological parameters were evaluated. Employees with previous liver disease, diabetes mellitus, or alcohol intake (> 50 g/day) were excluded. In employees with hTAMSemia, we performed a proteinogram and hepatic ultrasonography and tested blood samples for prothrombin and hepatitis B and C markers. Within this subgroup, 3 workers were excluded (due to serum markers of hepatitis B virus in 2 and refusal to participate in 1), leaving a total of 92 in the EHC group. Finally, the working environment was screened for volatile contaminants. RESULTS: Twenty-seven employees from the EHC group (29.4%) and 1 from the NEHC group (1.4%) had hTAMSemia (p = 0.001). The remaining biochemical tests and parameters measured showed no significant differences between the two groups. Comparison between the EHC subgroup of 27 workers showing hTAMSemia and the remainder of the EHC group with normal values (65 workers) revealed no differences in the other parameters measured. Of the 27 workers of the former subgroup, 14 (51.9%) showed ultrasonographic images compatible with a fatty liver. One worker (1.4%) in the NEHC group showed hTAMSemia and ultrasonography compatible with fatty liver. The environmental levels of BTX during the 9 months of the study remained below the maximum values permitted by law in Argentina (benzene, 1.5 ppm., toluene 10 ppm and xylene 18.5 ppm). The odds ratio of developing hTAMSemia in the EHC group was 27.7 (p = 0.002). CONCLUSIONS: Occupational exposure to aromatic hydrocarbons may cause liver damage. The liver is more vulnerable to these hydrocarbons than bone marrow. These conclusions would argue for a modification of the environmental regulations currently in force within the petroleum refineries in Argentina.

[Liver dysfunction in recipients of hematopoietic stem cells. Impact on mortality]. / Disfunción hepática en el trasplante de celulas progenitoras hematopoyéticas. Impacto sobre la mortalidad.

Liver disease is a well-known cause of early morbidity and mortality affecting 80% of patients receiving allogeneic bone-marrow transplantation (BMT). Drug toxicity, veno-occlusive disease (VOD), acute graft-versus-host disease (GVHD), and fungal, bacterial, and viral infections are the most frequent hepatic complications during this period. The aim of this retrospective study was to determine the prevalence and etiology of liver disease and its impact on mortality as well as to assess the predictive value of pre BMT hepatic biochemical tests on the subsequent occurrence of acute and/or chronic GVHD and patient mortality. Of a total of 236 patients who underwent allogeneic BMT, 82 were analysed. Liver dysfunction was found in 88%. The causes of liver disease were: acute GVHD, 40.2%; chronic GVHD, 15.9%; unknown, 9.8%; sepsis, 7.3%; hepatotoxicity, 6.1%; VOD, 3.7%; acute hepatitis and disease recurrence, 2.4%. The mortality rate was 37%. We found acute liver failure (ALF) in 10% of the deaths (8 patients). The causes of ALF in these cases were acute GVHD progression in 5, herpetic hepatitis in 1, disease recurrence in 1, and VOD in 1. The correlation coefficients indicating positive predictive values of pre BMT hepatic biochemical tests for the subsequent occurrence of acute GVHD, chronic GVHD, and mortality were 0.27, 0.14, and 0.43, respectively. There was no significant difference between patients with abnormal or normal pre BMT liver function tests in the frequency of acute and chronic GVHD or mortality.

Propafenone hepatotoxicity: report of two new cases.

Two patients developed acute cholestatic hepatitis during treatment with propafenone. Viral infections, alcohol abuse, hepatotoxicity by other drugs, and biliary obstruction were excluded as causes. In one patient, liver biopsy showed changes consistent with a drug-associated injury. Another patient had autoimmune antibodies (ANA) in the serum. Following propafenone withdrawal, the clinical and biochemical profiles of both patients improved. Hepatic toxicity from the antiarrhythmic drug propafenone is highly uncommon. Moreover, the drug produces hepatocellular injury by an unknown mechanism. Most of the seven cases reported here had acute cholestatic hepatitis after a latency period of two to four weeks.

Alanine-aminotransferase: an early marker for insulin resistance? / Alanino-aminotransferasa: un marcador temprano de resistencia a la insulina?

In a population-based sample, after excluding alcohol consumption, hepatotoxic drugs and hepatitis Band C infected, we investigated if alanine-aminotransferase (ALT) was associated with metabolic syndrome and insulin resistance, and if this association was caused by non-alcoholic fatty liver disease (NAFLD). The sample (432 female and 119 male) was divided into two ALT thresholds corresponding to the 50th and 75th percentiles (P) (female < or = 15 and < or = 19 U/L; male < or = 17 and < or = 23 U/l, respectively). Blood pressure, body mass index, waist circumference, cholesterol, HDL cholesterol (HDLc), triglyceride (TG), TG/HDLc ratio, glycemia and homeostasis model assessment of insulin resistance (HOMA-IR) were compared between those above and below each ALT threshold. Female placed above the 50th P of ALT had higher levels of TG/HDLc ratio (p=0.029), glycemia (p=0.028), and homeostasis model assessment of insulin resistance, (p=0.045), and above the 75th P had higher SBP (p=0.036), DBP (p=0.018), TG (p=0.024), TG/HDLc ratio (p=0.028), glycemia (p=0.004) and HOMA-IR (p=0.0014). Male placed above the 50th P of ALT had higher BMI (p=0.017) and TG/HDLc ratio (p=0.048), and above the 75th P had lower values of HDLc (p=0.042). Only 16.5 percent of women and 14.5 percent of men, above the 75th P of ALT, showed an increase in liver brightness in the echography. This work shows in woman an early association of ALT with TG/HDLc ratio and HOMA-IR. Since the last two are independent predictors of cardiovascular risk, attention should be drawn to ALT values near the upper limit of the normal range even in the absence of NAFLD and obesity.

En una muestra poblacional, luego de excluir a quienes consumían alcohol y drogas hepatotóxicas y a los infectados con virus B y C de la hepatitis, investigamos si la alanino-aminotransferasa (ALT), o transaminasa glutámico pirúvica (TGP), se asociaba con el síndrome metabólico y con resistencia a la insulina y si esta asociación se explicaba por enfermedad hepática grasa no alcohólica (NAFLD). La muestra (432 mujeres y 119 varones) se dividió por los percentilos (P) 50 y 75 de la distribución de ALT (mujeres < o = 15 y < o = 19 U/l; varones < o = 17 y < o = 23 U/l, respectivamente). Las mujeres a partir del P50 de ALT tuvieron valores más altos de índice triglicéridos (TG)/HDLc (p=0.029), glucemia (p=0.028) y de la valoración del modelo homeostático de insulino-resistencia (HOMA-IR) (p=0.045); a partir del P75 tuvieron valores más altos de presión arterial sistólica (PAS) (p=0.036), presión arterial diastólica (PAD) (p=0.018), TG (p=0.024), índice TG/HDLc (p=0.028), glucemia (p=0.004) y HOMA-IR (p=0.001). Los varones a partir del P50 de ALT tuvieron valores más altos del índice de masa corporal (p=0.017) y del índice (TG/HDLc (p=0.048); a partir del P75 mostraron valores más bajos de HDLc (p=0,042). Sólo 16.5 porciento de las mujeres y 14.5 porciento de los varones, a partir del P75 de ALT, mostraron aumento del brillo hepático en la ecografía. Este trabajo muestra, en mujeres, asociación temprana de ALT con el índice TG/HDLc y el HOMA-IR. Dado que estos dos últimos son predictores independientes del riesgo cardiovascular se debería prestar atención a los valores de ALT cercanos al límite superior aun en ausencia de NAFLD y de obesidad.

Armónica-inversión de pulsos y agente de contraste US: caracterización de lesiones focales hepáticas / Pulse inversion harmonic US imaging after levovist injection: patterns in hepatic focal lesions

Propósito: Evaluar con armónica-inversión de pulsos (AIP) y agente de contraste ultrasonográfico el realce a nivel de la microcirculación hepática y establecer diferencias en el comportamiento de lesiones focales sólidas (LFS). Material y Métodos: Se incluyeron 31 pacientes con 37 LFS: 13/37 hepatocarcinomas (HC), 14/37 hemangiomas (HG) y 10/37 metástasis (MTS). El diagnóstico de MTS y de HC se definió histológicamente y el de HG con TC o RNM y seguimiento. Ecorrealzador: Se utilizó Levovist, inyectándose en bolo rápido 12 ml de solución (400 mgs/ml). Técnica US: Se utilizó un equipo ATL HDI 5000 con transductor convex 2-5 Mhz. Procedimiento: 1. Se configuró para evaluación con AIP y alto índice mecánico (1,3). 2. Se obtuvo un registro basal. 3. Se administró el ecorrealzador. 4. Transcurridos 30 se barrió la lesión. El procedimiento se repitió cada 30, durante 5, guardándose en cine-loops para su evaluación ulterior con un programa de investigación (HDI LAB; ATL Ultrasound). Análisis cualitativo: se definió el realce parenquimatoso como presente o ausente. El realce lesional se agrupó en: ausente (AU), periférico globular (PG), periférico anular (PA), intralesional (IL). Análisis cuantitativo: se cuantificó en dB el realce lesional y el parenquimatoso. Análisis estadístico: se utilizó media ñ DS y X2. Resultados: Análisis cualitativo: Realce parenquimatoso presente en todos los casos. Realce lesional AU: 0/13 HC, 8/14 HG y 5/10 MTS (p<0.05). Realce PG: 6/14 HG y en ningún HC ni MTS (p<0.05). Realce PA: 5/10 MTS y en ningún HC ni HG (p<0.05). Realce IL: 13/13 HC y en ningún HG ni MTS (p<0.05). Análisis cuantitativo: La media de la intensidad del realce fue: parénquima hepático, 17 ñ 4 dB; HC, 25 ñ 7 dB; HG con realce PG, 23 ñ 5 dB; MTS con realce PA de 20 ñ 3 dB; lesiones con realce AU 4 ñ 3 dB. Conclusiones: utilizando AIP y ecorrealzador es posible lograr realce a nivel de la microcirculación hepática. Las LFS mostraron diferencias en su comportamiento, sugeriendo que éste procedimiento puede ser de utilidad en su caracterización

Ascitis / Ascites

La ascitis puede ocurrir como una manifestación clinica de ciertas enfermedades hepáticas como una complicación de la hipertensión portal, o bien obedecer a otras causas. Aproximadamente el 85 por ciento de las ascitis son secundarias a hipertensión portal, 10 por ciento a neoplasias, 2 por ciento a tuberculosis, 1 por ciento a enfermedades pancreáticas y el 2 por ciento restante a causas poco frecuentes. La paracentesis confirma la ascitis y posibilita el análisis bioquímico y citológico del líquido, lo cual resulta de extraordinaria importancia para el diagnóstico etiológico diferencial y a su vez permite establecer o excluir la presencia de "peritonitis bacteriana expontanea" y eventualmente instaurar el tratamiento para prevenirla. El gradiente sero-ascitico de albumina > de 1.1 g/dl identifica las ascitis por hipertensión portal con una exactitud del 96,7 por ciento. Para una manejo terapeutico racional de los pacientes cirróticos con ascitis, se debe recordar que en ellos siempre hay disminución de la resistencia vascular sistemica, oliguria, retención renal de sodio y agua y expansión del volúmen plasmático. Esta aumentada la secreción de hormona antidiuretica y tienen dificultad para excretar agua libre. El filtrado glomerular depende de la producción renal de prostaglandinas que intentan compensar la vasoconstricción de la microcirculación renal.

Cáncer gástrico intermedio / Intermediate gastric cancer

Se presenta un caso de cáncer gástrico que penetra la pared del estómago hasta la capa muscular (C.G.P.M.) en un paciente de cincuenta y tres años que consultó por dolor abdominal y pérdida de peso, y que en la actualidad lleva dos años y medio de sobrevida libre de síntomas. Se analizan las características radiológicas, endoscópicas y anatompatológicas de esta enfermedad. Se enfatiza la trascendencia del diagnóstico de cáncer gástrico en este estadío

Hepatitis no A - no B: significación epidemiológica en hepatitis viral aguda y hepatitis crónica activa de consulta hepatológica / Hepatitis non-A, non-B: epidemiological significance in acute viral hepatitis and chronic active hepatitis of hepatological consultation

1- La hepatitis aguda NANB representa en nuestro medio 31.2% de las hepatitis virales agudas; si bien estos porcentajes no son directamente transpolables a la población general, el especialista gastroenterólogo o hepatólogo, debe esperar que casi 1 de cada 3 pacientes de su consulta presente una hepatopatía con multitud de aspectos aun desconocidos, etiológicos, evolutivos, vinculación con el cáncer hepático, etc. 2- El predominio de la hepatitis aguda a HAV es neto en la infancia (0-9 años: 72.2%) y excepcional después de los 40 años, mientras que el HBV es etiología predominante por encima de los 50; los NANBV se presentan en todas las edades, con 77,6% de los casos entre 20-49. 3- Al no incluirse casos sub-clínicos post-transfusionales, generalmente provenientes de estudios de seguimiento, el porcentaje de forma agudas NANB presuntamente esporádicas es elevado (71.5%), aunque no debiera descartarse la posibilidad de acción en nuestro medio de formas de transmisión no-parenteral. 4- 25% de nuestra serie de hapatitis crónicas activas, es atribuido por exclusión a la etiología NANB, englobando posiblemente a otras causas aun no conocidas. 5- Estos aspectos epidemiológicos, así como otros clínico-evolutivos, variarán seguramente en los próximos años gracias a los esfuerzos realizados por investigadores de todo el mundo en la identificación etiológica y la puesta a punto de marcadores serológicos específicos de los hoy denominados virus de la hepatiti No A- No B