Hipertransaminasemia, astenia, artralgias e hiperpigmentación cutánea / Hypertransaminasemia, asthenia, arthralgia and skin hyperpigmentation

RESUMEN La hemocromatosis hereditaria es una enfermedad metabólica infrecuente que afecta primariamente al hígado, y que se caracteriza por un incremento de la absorción intestinal de hierro. Se presentó un paciente de 49 años de edad, evaluado en consulta externa, desde alrededor de dos años atrás, por: astenia, anorexia, artralgias e hiperpigmentación cutánea, asociada a hipertransaminasemia y seronegatividad para virus B y C. Los niveles de saturación de transferrina y ferritina evidenciaron la sobrecarga de hierro, y el estado homocigoto para la mutación C282Y confirmó la sospecha diagnóstica; se descartaron otras condiciones como: hepatitis crónica por virus B y C, esteatohepatitis no alcohólica, anemia hemolítica crónica, anemia sideroblástica, talasemia mayor, u otras enfermedades metabólicas que afectan al hígado. La biopsia hepática mostró hallazgos típicos de esta condición. Las flebotomías semanales fueron bien toleradas y se logró una mejoría clínica del paciente y de los parámetros de laboratorio.

ABSTRACT Hereditary hemochromatosis is an uncommon metabolic disease, primarily affecting the liver in which increased intestinal absorption of iron is seen. We presented a 49- year -old patient who was evaluated in an outpatient clinic for suffering from asthenia, anorexia, arthralgia and skin hyperpigmentation associated with hypertransaminasemia and negative serology for B and C viruses from about two years ago. Serum ferritin, and transferrin saturation levels evidenced iron overload and homozygosity for the C282Y mutation confirmed the suspected diagnosis; other conditions were ruled out such as chronic hepatitis due to B and C viruses, non-alcoholic steatohepatitis, chronic hemolytic anemia, sideroblastic anemia, thalassemia major or some other metabolic diseases affecting the liver. Liver biopsy showed typical findings related to this condition. Weekly phlebotomies were well tolerated, as well as clinical improvement of the patient and laboratory parameters were achieved.

Serum biomarkers can predict a change in liver fibrosis 1 year after lifestyle intervention for biopsy-proven NASH.

BACKGROUND & AIMS: The dynamic response of serum fibrosis biomarkers to histological changes within the liver following lifestyle intervention (LI) is unknown. We explored relationships between changes in serum biomarkers and liver fibrosis in NASH patients undergoing LI. METHODS: Paired liver biopsies were performed in 261 NASH patients to assess fibrosis change after 1 year of LI. We explored the utility of serum fibrosis markers to predict changes in hepatic fibrosis and developed and internally validated a model for predicting fibrosis improvement in patients with baseline fibrosis. RESULTS: Regression, stabilization and worsening of fibrosis occurred in 51 (20%), 165 (63%) and 45 (17%) patients respectively. By multivariable analysis, change in HbA1c (OR, 0.39, P<.01), platelets (OR, 1.22, P<.01) and NFS (OR, 0.27, P<.01), as well as ALT normalization (OR, 9.7, P<.01) were independently associated with fibrosis improvement, whereas change in platelets (OR, 0.96, P<.01), and NFS (OR, 1.8, P<.01) as well as ALT normalization (OR, 0.21, P<.01) were linked to fibrosis progression. A model, including change in HbA1c, platelet and ALT normalization, was significantly more accurate (AUC of 0.96, 95% CI, l0.94-0.99) than NFS, FIB-4 and APRI for predicting fibrosis improvement. Using a threshold of ≥0.497, positive and negative predictive values were 94% (95% CI, 84-98) and 91% (95% CI, 81-96) respectively. CONCLUSIONS: Change in NFS, platelets and ALT normalization are associated with change in liver fibrosis after 1 year of LI. A model including change in HbA1c, platelet and ALT normalization discriminated patients with fibrosis improvement significantly better than other biomarkers.

Development and validation of a noninvasive prediction model for nonalcoholic steatohepatitis resolution after lifestyle intervention.

UNLABELLED: Liver biopsy is the gold standard method to assess nonalcoholic steatohepatitis (NASH) resolution after therapeutic interventions. We developed and validated a simple and noninvasive scoring system to predict NASH resolution without fibrosis worsening after 1 year of lifestyle intervention. This was a prospective cohort study conducted in 261 patients with histologically proven NASH who were treated with lifestyle changes for 52 weeks and underwent a second liver biopsy to confirm NASH resolution. We divided the data into development (140 subjects) and validation (121 individuals) sets. NASH resolution occurred in 28% (derivation group) and 27% (validation group). At the multivariable analysis, weight loss (odds ratio [OR] = 2.75, 95% confidence interval [CI] 1.65-4.58; P < 0.01), type 2 diabetes (OR = 0.04, 95% CI 0.005-0.49; P = 0.01), normal levels of alanine aminotransferase at the end of intervention (OR = 9.84, 95% CI 2.21-44.1; P < 0.01), age (OR = 0.89, 95% CI 0.83-0.97; P = 0.01), and a nonalcoholic fatty liver activity score ≥5 (OR = 0.08, 95% CI 0.01-0.43; P < 0.01) were independent predictors of NASH resolution. The area under the receiver operating characteristic curve of the selected model was 0.956 and 0.945 in the derivation and validation cohorts, respectively. Using a score threshold of ≤46.15, negative predictive values were 92% in the derivation and validation groups, respectively. By applying a cutoff ≥69.72, positive predictive values were 92% and 89% in the derivation and validation groups, respectively. Using both cutoffs, a liver biopsy would have been avoided in 229 (88%) of 261 patients, with a correct prediction in 209 (91%) CONCLUSIONS: A noninvasive prediction model including weight loss, type 2 diabetes, alanine aminotransferase normalization, age, and a nonalcoholic fatty liver activity score ≥5 may be useful to identify NASH resolution in patients under lifestyle intervention. (Hepatology 2016;63:1875-1887).

Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: It is not clear how weight loss affects histologic features of liver in patients with nonalcoholic steatohepatitis (NASH). We examined the association between the magnitude of weight loss through lifestyle modifications and changes in histologic features of NASH. METHODS: We conducted a prospective study of 293 patients with histologically proven NASH who were encouraged to adopt recommended lifestyle changes to reduce their weight over 52 weeks, from June 2009 through May 2013, at a tertiary medical center in Havana, Cuba. Liver biopsies were collected when the study began and at week 52 of the diet and were analyzed histologically. RESULTS: Paired liver biopsies were available from 261 patients. Among 293 patients who underwent lifestyle changes for 52 weeks, 72 (25%) achieved resolution of steatohepatitis, 138 (47%) had reductions in nonalcoholic fatty liver disease activity score (NAS), and 56 (19%) had regression of fibrosis. At week fifty-two, 88 subjects (30%) had lost ≥5% of their weight. Degree of weight loss was independently associated with improvements in all NASH-related histologic parameters (odds ratios = 1.1-2.0; P < .01). A higher proportion of subjects with ≥5% weight loss had NASH resolution (51 of 88 [58%]) and a 2-point reduction in NAS (72 of 88 [82%]) than subjects who lost <5% of their weight (P < .001). All patients who lost ≥10% of their weight had reductions NAS, 90% had resolution of NASH, and 45% had regression of fibrosis. All patients who lost 7%-10% of their weight and had few risk factors also had reduced NAS. In patients with baseline characteristics that included female sex, body mass index ≥35, fasting glucose >5.5 mmol/L, and many ballooned cells, NAS scores decreased significantly with weight reductions ≥10%. CONCLUSIONS: A greater extent of weight loss, induced by lifestyle changes, is associated with the level of improvement in histologic features of NASH. The highest rates of NAS reduction, NASH resolution, and fibrosis regression occurred in patients with weight losses ≥10%.

Interferón alfa 2b recombinante más ribavirina en el tratamiento de la hepatitis crónica C / Recombinant Interferon alfa-2b plus Ribavirin in treatment of chronic hepatitis C

El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: El presente estudio estuvo dirigido a determinar la evolución virológica, bioquímica e histológica de los pacientes con hepatitis crónica C bajo terapia combinada Interferón a 2b recombinante más ribavirina e identifica los principales factores asociados a las tasas obtenidas de respuesta virológica sostenida. MÉTODOS: Ensayo clínico-terapéutico fase IV, abierto, no controlado y multicéntrico rectorado por el Instituto de Gastroenterología y el Centro de Ingeniería Genética y Biotecnología en el período comprendido de mayo de 2001 a mayo de 2006. La muestra estuvo conformada por 122 pacientes con hepatitis crónica C que cumplieron con criterios de inclusión y exclusión predeterminados. Se utilizó interferón a 2b recombinante (3 millones de unidades 3 veces por semana) más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal) durante 48 sem. RESULTADOS: Se obtuvo una tasa de respuesta virológica y bioquímica sostenida a la semana 72 de 32,8 y 50,8 por ciento respectivamente. Un 41,3 por ciento del total de pacientes experimentó mejoría histológica a expensas de la reducción de la fibrosis y pocos cambios en la inflamación. CONCLUSIONES: Teniendo en cuenta la tasa de respuesta global obtenida, se consideró como tratamiento eficaz para la hepatitis crónica C y se recomendó profundizar en el conocimiento de las características de la infección en Cuba así como en opciones de tratamiento más eficaces para esta enfermedad

The hepatitis C virus becomes in leading cause of chronic hepatitis, hepatic cirrhosis, hepatocarcinoma and liver transplant at world level. OBJECTIVE: The aim of present study is to determine the virological, biochemical and histological course of patients presenting with Chronic hepatitis C under a combination of recombinant Interferon alfa-2b plus Ribavirin and to identify the main factors associated with the rates obtained of virological response. METHODS: A non-controlled and multicenter phase IV clinical-therapeutical trial was sponsored by the Institute of Gastroenterology and the Genetics and Biotechnology Engineering Center from May, 2002 to May, 2006. Sample included 122 patients diagnosed with chronic hepatitis C fulfilling the predetermined inclusion and exclusion criteria. Recombinant Interferon alfa-2b (3 millions of t.i.d units) was used plus Ribavirin (1000 or 1200 mg daily depending on the body weight) during 48 weeks. RESULTS: We achieved a sustained biochemical and virological response rate of 32,8 and 50,8 percent, respectively at week 72. A 41,3, percent from the total of patients had a histological improvement at the expense of reduction of fibrosis and a few changes in inflammation level. CONCLUSIONS: Raking into account the global response rate achieved this combined treatment was considered effectiveness for chronic hepatitis C and we recommended to deepen in the knowledge of infection in Cuba, as well as in more efficient treatment options for this disease

Interferón alfa 2b recombinante más ribavirina en el tratamiento de la hepatitis crónica C / Recombinant Interferon alfa-2b plus Ribavirin in treatment of chronic hepatitis C

El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: El presente estudio estuvo dirigido a determinar la evolución virológica, bioquímica e histológica de los pacientes con hepatitis crónica C bajo terapia combinada Interferón a 2b recombinante más ribavirina e identifica los principales factores asociados a las tasas obtenidas de respuesta virológica sostenida. MÉTODOS: Ensayo clínico-terapéutico fase IV, abierto, no controlado y multicéntrico rectorado por el Instituto de Gastroenterología y el Centro de Ingeniería Genética y Biotecnología en el período comprendido de mayo de 2001 a mayo de 2006. La muestra estuvo conformada por 122 pacientes con hepatitis crónica C que cumplieron con criterios de inclusión y exclusión predeterminados. Se utilizó interferón a 2b recombinante (3 millones de unidades 3 veces por semana) más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal) durante 48 sem. RESULTADOS: Se obtuvo una tasa de respuesta virológica y bioquímica sostenida a la semana 72 de 32,8 y 50,8 por ciento respectivamente. Un 41,3 por ciento del total de pacientes experimentó mejoría histológica a expensas de la reducción de la fibrosis y pocos cambios en la inflamación. CONCLUSIONES: Teniendo en cuenta la tasa de respuesta global obtenida, se consideró como tratamiento eficaz para la hepatitis crónica C y se recomendó profundizar en el conocimiento de las características de la infección en Cuba así como en opciones de tratamiento más eficaces para esta enfermedad(AU)

The hepatitis C virus becomes in leading cause of chronic hepatitis, hepatic cirrhosis, hepatocarcinoma and liver transplant at world level. OBJECTIVE: The aim of present study is to determine the virological, biochemical and histological course of patients presenting with Chronic hepatitis C under a combination of recombinant Interferon alfa-2b plus Ribavirin and to identify the main factors associated with the rates obtained of virological response. METHODS: A non-controlled and multicenter phase IV clinical-therapeutical trial was sponsored by the Institute of Gastroenterology and the Genetics and Biotechnology Engineering Center from May, 2002 to May, 2006. Sample included 122 patients diagnosed with chronic hepatitis C fulfilling the predetermined inclusion and exclusion criteria. Recombinant Interferon alfa-2b (3 millions of t.i.d units) was used plus Ribavirin (1000 or 1200 mg daily depending on the body weight) during 48 weeks. RESULTS: We achieved a sustained biochemical and virological response rate of 32,8 and 50,8 percent, respectively at week 72. A 41,3, percent from the total of patients had a histological improvement at the expense of reduction of fibrosis and a few changes in inflammation level. CONCLUSIONS: Raking into account the global response rate achieved this combined treatment was considered effectiveness for chronic hepatitis C and we recommended to deepen in the knowledge of infection in Cuba, as well as in more efficient treatment options for this disease(AU)

Tumor de células granulares de esófago / Tumor of granular cells of esophagus

Los tumores de células granulares son lesiones raras y asintomáticas, generalmente un hallazgo incidental en la endoscopia alta o baja. Fueron descritos por primera vez en 1926 por Abrikossoff. Las localizaciones más frecuentes son la mucosa bucal, la dermis y el tejido celular subcutáneo, la mayor parte de estos tumores tienen una naturaleza benigna. Presentamos el caso clínico de una mujer, de 44 años con historia de pirosis desde hace aproximadamente 1 año, se observa por endoscopia superior lesión elevada de 8 mm en tercio distal de esófago y se confirma por estudio histológico el diagnóstico de tumor de celulas granulares. El tratamiento de elección de esta lesión es la polipectomía endoscópica. A pesar de que el potencial maligno es escaso se sugiere seguimiento estrecho clínico y endoscópico

Granular cells tumors are rare and asymptomatic lesions and by general, it is an incidental finding en high or low endoscopy. They were described for the first time by Abrikossoff in 1926. The more frequent locations are the buccal mucosa, dermis and subcutaneous cellular tissue, most of these tumors has a benign origin. This is the case of a woman aged 44 with a pyrosis history from a year ago; by high endoscopy it is noted a 8mm lesion distal to esophagus and confirmed by histological study of granular cells tumor. Elective treatment of this lesion is the endoscopic polypectomy. Despite that the malign potential is low; we suggested a close clinical and endoscopic follow-up

Metaplasia intestinal en pacientes con reflujo duodenogástrico y ácidos biliares totales elevados / Intestinal metaplasia en patients with duodenogastric reflux and high total bile acids

Existen evidencias que tanto los ácidos biliares como el Helicobacter pylori en la mucosa gástrica son capaces de desencadenar un proceso inflamatorio que según su intensidad y persistencia favorecen la aparición de fallas y mutaciones en la replicación celular que se expresan desde una metaplasia, displasia hasta un cáncer. Se realizó un estudio epidemiológico observacional, descriptivo, prospectivo de corte transversal en el Instituto de Gastroenterología, en pacientes con reflujo duodenogástrico y ácidos biliares totales elevados, con el objetivo de conocer la asociación entre la metaplasia intestinal y la presencia o no de Helicobacter pylori. Al concluir la investigación se observó que la metaplasia estuvo presente en 48,7 por ciento de los 39 pacientes estudiados, que existió una asociación estadísticamente significativa (p<0,05) en la distribución de la bacteria en los pacientes con y sin metaplasia intestinal, que los pacientes con reflujo duodenogástrico, a pesar de tener una lesión histológica, presentaron resultados negativos en cuanto a la presencia de Helicobacter pylori. En las muestras con diagnóstico histológico de gastritis crónica severa y atrófica, el 75 por ciento presentaban Helicobacter pylori. La localización de la metaplasia intestinal fue mayor en la región antral (84,3 por ciento). En los pacientes con reflujo duodenogástrico la presencia de Helicobacter pylori no parece estar asociada a grados intensos de metaplasia, aunque el microorganismo se encuentre en todas las categorías, mientras que cuando no hay, la metaplasia tiende a ser menos severa. En el 100 por ciento de los casos la densidad de la bacteria fue ligera

The cytotoxic and cancerous action of bile acids on gastric mucosa is a very interesting subject within the gastroduodenal diseases due to they are able to alter the membrane, the cellular metabolism, to give rise to a inflammatory process, to increase the proliferation, the cell apoptosis and the DNA damage, that according to its intensity and persistence, favor the appearance of failures and mutations in cell replication. With the discovery and characterization of Helicobacter pylori it is considered that according to its intensity and the time of persistence in gastric mucosa provokes damages with failures and cellular mutations. In this sense, a prospective and descriptive study was conducted in the Institute of Gastroenterology in patients presenting with duodenogastric and high total bile acids to know the association between the intestinal metaplasia and the presence or not of Helicobacter pylori. Metaplasia was present in the 48.7 percent of the 39 study patients, that there was a statistically significant association (p< 0.05) in Helicobacter pylori distribution in patients with and without intestinal metaplasia; that patients with duodenogastric reflux, despite of a histological lesion also had a greater frequency of negative results as regards the presence of Helicobacter pylori. In samples with histological diagnosis of severe and atrophic chronic gastritis, 75 percent, respectively, had Helicobacter pylori and in consequence, there was a significant association between presence or not of microorganism and the chronic gastritis intensity. Intestinal metaplasia location was higher in antral region (84.3 percent) and also with a higher ratio of microorganism positivity. In patients with duodenogastric reflux, presence of Helicobacter pylori don't seems to be associated with intense degrees of intestinal metaplasia, although the microorganism is present in all categories, but when there is not Helicobacter pylori, intestinal metaplasia to tend to ...

Tumor de células granulares de esófago / Tumor of granular cells of esophagus

Los tumores de células granulares son lesiones raras y asintomáticas, generalmente un hallazgo incidental en la endoscopia alta o baja. Fueron descritos por primera vez en 1926 por Abrikossoff. Las localizaciones más frecuentes son la mucosa bucal, la dermis y el tejido celular subcutáneo, la mayor parte de estos tumores tienen una naturaleza benigna. Presentamos el caso clínico de una mujer, de 44 años con historia de pirosis desde hace aproximadamente 1 año, se observa por endoscopia superior lesión elevada de 8 mm en tercio distal de esófago y se confirma por estudio histológico el diagnóstico de tumor de celulas granulares. El tratamiento de elección de esta lesión es la polipectomía endoscópica. A pesar de que el potencial maligno es escaso se sugiere seguimiento estrecho clínico y endoscópico(AU)

Granular cells tumors are rare and asymptomatic lesions and by general, it is an incidental finding en high or low endoscopy. They were described for the first time by Abrikossoff in 1926. The more frequent locations are the buccal mucosa, dermis and subcutaneous cellular tissue, most of these tumors has a benign origin. This is the case of a woman aged 44 with a pyrosis history from a year ago; by high endoscopy it is noted a 8mm lesion distal to esophagus and confirmed by histological study of granular cells tumor. Elective treatment of this lesion is the endoscopic polypectomy. Despite that the malign potential is low; we suggested a close clinical and endoscopic follow-up(AU)

Metaplasia intestinal en pacientes con reflujo duodenogástrico y ácidos biliares totales elevados / Intestinal metaplasia en patients with duodenogastric reflux and high total bile acids

Existen evidencias que tanto los ácidos biliares como el Helicobacter pylori en la mucosa gástrica son capaces de desencadenar un proceso inflamatorio que según su intensidad y persistencia favorecen la aparición de fallas y mutaciones en la replicación celular que se expresan desde una metaplasia, displasia hasta un cáncer. Se realizó un estudio epidemiológico observacional, descriptivo, prospectivo de corte transversal en el Instituto de Gastroenterología, en pacientes con reflujo duodenogástrico y ácidos biliares totales elevados, con el objetivo de conocer la asociación entre la metaplasia intestinal y la presencia o no de Helicobacter pylori. Al concluir la investigación se observó que la metaplasia estuvo presente en 48,7 por ciento de los 39 pacientes estudiados, que existió una asociación estadísticamente significativa (p<0,05) en la distribución de la bacteria en los pacientes con y sin metaplasia intestinal, que los pacientes con reflujo duodenogástrico, a pesar de tener una lesión histológica, presentaron resultados negativos en cuanto a la presencia de Helicobacter pylori. En las muestras con diagnóstico histológico de gastritis crónica severa y atrófica, el 75 por ciento presentaban Helicobacter pylori. La localización de la metaplasia intestinal fue mayor en la región antral (84,3 por ciento). En los pacientes con reflujo duodenogástrico la presencia de Helicobacter pylori no parece estar asociada a grados intensos de metaplasia, aunque el microorganismo se encuentre en todas las categorías, mientras que cuando no hay, la metaplasia tiende a ser menos severa. En el 100 por ciento de los casos la densidad de la bacteria fue ligera(AU)

The cytotoxic and cancerous action of bile acids on gastric mucosa is a very interesting subject within the gastroduodenal diseases due to they are able to alter the membrane, the cellular metabolism, to give rise to a inflammatory process, to increase the proliferation, the cell apoptosis and the DNA damage, that according to its intensity and persistence, favor the appearance of failures and mutations in cell replication. With the discovery and characterization of Helicobacter pylori it is considered that according to its intensity and the time of persistence in gastric mucosa provokes damages with failures and cellular mutations. In this sense, a prospective and descriptive study was conducted in the Institute of Gastroenterology in patients presenting with duodenogastric and high total bile acids to know the association between the intestinal metaplasia and the presence or not of Helicobacter pylori. Metaplasia was present in the 48.7 percent of the 39 study patients, that there was a statistically significant association (p< 0.05) in Helicobacter pylori distribution in patients with and without intestinal metaplasia; that patients with duodenogastric reflux, despite of a histological lesion also had a greater frequency of negative results as regards the presence of Helicobacter pylori. In samples with histological diagnosis of severe and atrophic chronic gastritis, 75 percent, respectively, had Helicobacter pylori and in consequence, there was a significant association between presence or not of microorganism and the chronic gastritis intensity. Intestinal metaplasia location was higher in antral region (84.3 percent) and also with a higher ratio of microorganism positivity. In patients with duodenogastric reflux, presence of Helicobacter pylori don't seems to be associated with intense degrees of intestinal metaplasia, although the microorganism is present in all categories, but when there is not Helicobacter pylori, intestinal metaplasia to tend to ...(AU)

Application of a biochemical and clinical model to predict individual survival in patients with end-stage liver disease

AIM: To investigate the capability of a biochemical and clinical model, BioCliM, in predicting the survival of cirrhotic patients. METHODS: We prospectively evaluated the survival of 172 cirrhotic patients. The model was constructed using clinical (ascites, encephalopathy and variceal bleeding) and biochemical (serum creatinine and serum total bilirubin) variables that were selected from a Cox proportional hazards model. It was applied to estimate 12-, 52- and 104-wk survival. The model¡¯s calibration using the Hosmer-Lemeshow statistic was computed at 104 wk in a validation dataset. Finally, the model¡¯s validity was tested among an independent set of 85 patients who were stratified into 2 risk groups (low risk ¡Ü 8 and high risk > 8). RESULTS: In the validation cohort, all measures of fit, discrimination and calibration were improved when the biochemical and clinical model was used. The proposed model had better predictive values (c-statistic: 0.90, 0.91, 0.91) than the Model for End-stage Liver Disease (MELD) and Child-Pugh (CP) scores for 12-, 52- and 104-wk mortality, respectively. In addition, the Hosmer-Lemeshow (H-L) statistic revealed that the biochemical and clinical model (H-L, 4.69) is better calibrated than MELD (H-L, 17.06) and CP (H-L, 14.23). There were no significant differences between the observed and expected survival curves in the stratified risk groups (low risk, P = 0.61; high risk, P = 0.77). CONCLUSION: Our data suggest that the proposed model is able to accurately predict survival in cirrhotic patients(AU)

Helicobacter pylori y lesiones endoscópicas e histológicas en mucosa gástrica de pacientes de 50 años y más / Helicobacter pylori and the endoscopic and histological lesions in the gastric mucosa of patients aged 50 and over

Mundialmente es aceptado que la infección por Helicobacter pylori se incrementa con la edad y alcanza niveles entre 40 y 60 por ciento en sujetos asintomáticos y 70 por ciento en pacientes sintomáticos mayores de 50 años con enfermedades gastroduodenales. Teniendo en cuenta la relación entre la infección por Helicobacter pylori y las enfermedades gastroduodenales se cifran prevalencias e incidencias en aumento sostenido con la edad (50-70 por ciento en mayores de 50 años) y se considera el significado aumento de la población cubana por encima de esa edad. Se realizó un estudio prospectivo, descriptivo en el Instituto de Gastroenterología, para conocer la frecuencia de este microorganismo, así como la presencia de lesiones en la mucosa gástrica en pacientes de 50 y más años de edad. Se concluyó que el 69,6 por ciento de los pacientes tuvieron resultados positivos al Helicobacter pylori por test de ureasa; de los 132 fragmentos de muestras tomados para biopsias de la mucosa gástrica, el 37,8 por ciento fueron positivas para Helicobacter pylori, de ellas, el 25,7 por ciento se localizó en la región antral. Se realizaron 68 diagnósticos endoscópicos en los pacientes con Helicobacter pylori positivos por test de ureasa; 64,7 por ciento correspondió a gastritis crónica agudizada al nivel antral, seguido en orden de frecuencia por pangastritis, gastritis crónica agudizada al nivel del cuerpo, úlcera gástrica y úlcera duodenal. No se presentó lesión endoscópica de aspecto maligno en ningún paciente. Al estudiar la densidad de colonización de Helicobacter pylori en los 84 diagnósticos histológicos realizados, 69,0 por ciento presentó densidad ligera; 29,9 por ciento, moderada y 1,1 por ciento, severa. Se observó una tendencia hacia la densidad de colonización ligera a medida que progresaba la lesión histológica...

It is accepted all over the world that Helicobacter pylori infection increases with age and reaches levels between 40 and 60 percent in asymptomatic individuals, and of 70 percent in symptomatic patients over 50 with gastroduodenal diseases. Taking into account the relation existing between Helicobacter pylori infection and the gastroduodenal diseases, prevalences and incidences showing a sustained increase with age (50-70 percent in patients over 50) are ciphered, and the significant growth of the Cuban population above this age is considered. A prospective and descriptive study was undertaken at the Institute of Gastroenterology to know the frequency of this microorganism, as well as the presence of lesions in the gastric mucosa in patients aged 50 and over. It was concluded that 69.6 percent of the patients had positive results to Helicobacter pylori in the urease test. Of the 132 fragments of samples taken for biopsies of the gastric mucosa, 37.8 percent yielded positive to Helicobacter pylori, of them, 25.7 percent were located in the antral region. 68 endoscopic diagnoses were made in those patients positive to Helicobacter pylori by urease test, 64.7 percent corresponded to more acute gastritis at the antral level; followed in frequency by pangastritis, more serious chronic gastritis at the body level, gastric ulcer and duodenal ulcer. No endoscopic lesion of malignant aspect was observed. On studying the colonization density of Helicobacter pylori in 84 histological diagnoses made, 69.0 percent presented mild density; 29.9 percent, moderate; and 1.1 percent, severe. It was observed a tendency towards the colonization density as the histological lesion progressed. It was suggested to continue the study with more patients to characterize the behavior of the infection in patients aged 50 and over in order to take preventive measures to eradicate the bacteria and to improve the quality of life.

Helicobacter pylori y lesiones endoscópicas e histológicas en mucosa gástrica de pacientes de 50 años y más / Helicobacter pylori and the endoscopic and histological lesions in the gastric mucosa of patients aged 50 and over

Mundialmente es aceptado que la infección por Helicobacter pylori se incrementa con la edad y alcanza niveles entre 40 y 60 por ciento en sujetos asintomáticos y 70 por ciento en pacientes sintomáticos mayores de 50 años con enfermedades gastroduodenales. Teniendo en cuenta la relación entre la infección por Helicobacter pylori y las enfermedades gastroduodenales se cifran prevalencias e incidencias en aumento sostenido con la edad (50-70 por ciento en mayores de 50 años) y se considera el significado aumento de la población cubana por encima de esa edad. Se realizó un estudio prospectivo, descriptivo en el Instituto de Gastroenterología, para conocer la frecuencia de este microorganismo, así como la presencia de lesiones en la mucosa gástrica en pacientes de 50 y más años de edad. Se concluyó que el 69,6 por ciento de los pacientes tuvieron resultados positivos al Helicobacter pylori por test de ureasa; de los 132 fragmentos de muestras tomados para biopsias de la mucosa gástrica, el 37,8 por ciento fueron positivas para Helicobacter pylori, de ellas, el 25,7 por ciento se localizó en la región antral. Se realizaron 68 diagnósticos endoscópicos en los pacientes con Helicobacter pylori positivos por test de ureasa; 64,7 por ciento correspondió a gastritis crónica agudizada al nivel antral, seguido en orden de frecuencia por pangastritis, gastritis crónica agudizada al nivel del cuerpo, úlcera gástrica y úlcera duodenal. No se presentó lesión endoscópica de aspecto maligno en ningún paciente. Al estudiar la densidad de colonización de Helicobacter pylori en los 84 diagnósticos histológicos realizados, 69,0 por ciento presentó densidad ligera; 29,9 por ciento, moderada y 1,1 por ciento, severa. Se observó una tendencia hacia la densidad de colonización ligera a medida que progresaba la lesión histológica......(AU)

It is accepted all over the world that Helicobacter pylori infection increases with age and reaches levels between 40 and 60 percent in asymptomatic individuals, and of 70 percent in symptomatic patients over 50 with gastroduodenal diseases. Taking into account the relation existing between Helicobacter pylori infection and the gastroduodenal diseases, prevalences and incidences showing a sustained increase with age (50-70 percent in patients over 50) are ciphered, and the significant growth of the Cuban population above this age is considered. A prospective and descriptive study was undertaken at the Institute of Gastroenterology to know the frequency of this microorganism, as well as the presence of lesions in the gastric mucosa in patients aged 50 and over. It was concluded that 69.6 percent of the patients had positive results to Helicobacter pylori in the urease test. Of the 132 fragments of samples taken for biopsies of the gastric mucosa, 37.8 percent yielded positive to Helicobacter pylori, of them, 25.7 percent were located in the antral region. 68 endoscopic diagnoses were made in those patients positive to Helicobacter pylori by urease test, 64.7 percent corresponded to more acute gastritis at the antral level; followed in frequency by pangastritis, more serious chronic gastritis at the body level, gastric ulcer and duodenal ulcer. No endoscopic lesion of malignant aspect was observed. On studying the colonization density of Helicobacter pylori in 84 histological diagnoses made, 69.0 percent presented mild density; 29.9 percent, moderate; and 1.1 percent, severe. It was observed a tendency towards the colonization density as the histological lesion progressed. It was suggested to continue the study with more patients to characterize the behavior of the infection in patients aged 50 and over in order to take preventive measures to eradicate the bacteria and to improve the quality of life(AU)

Tratamiento prolongado con interferón alfa-2b más lamivudina en pacientes con hepatitis crónica B y antígeno e positivo / Prolonged treatment with alpha-2b interferon plus lamivudine in patients with e antigen positive chronic hepatitis B

Las tasas de seroconversión del antígeno e alcanzadas con los antivirales actuales no sobrepasan el 35 por ciento. La combinación de inmunomodulador y antiviviral ha sido teóricamente la estrategia más aceptada en los últimos años; sin embargo, los resultados en la práctica clínica han sido contradictorios. Se realizó el presente trabajo para evaluar la eficacia y seguridad de un esquema de tratamiento prolongado durante 52 sem con interferón alfa-2b más lamivudina en pacientes con hepatitis crónica B y antígeno e positivo. Se estudiaron 46 pacientes asignados aleatoriamente: 23 recibieron 150 mg diarios de lamivudina por 4 sem, lamivudina más interferón alfa-2b (10 MU en días alternos) por 24 sem, seguido de lamivudina en la misma dosis y frecuencia hasta completar las 52 sem. Otros 23 recibieron 150 mg diarios de lamivudina por 4 sem y lamivudina más interferón alfa-2b (5 MU en días alternos) durante 52 sem. Se encontró que las tasas de seroconversión del antígeno fueron similares en ambos grupos. Una proporción significativa de pacientes con tratamiento combinado prolongado logró negativizar el ADN viral (52 por ciento frente al 26 por ciento, p=0,06) y el antígeno de superficie (48 por ciento frente al 26 por ciento, p=0,11), comparado con los controles. La mejoría en el índice de actividad histológica fue observada en el 48 por ciento de los pacientes tratados con tratamiento combinado prolongado frente al 22 por ciento de los controles (p=0,06). Se concluyó que el tratamiento prolongado de erferón y lamivudina durante 52 sem puede brindar beneficios clínicos en las tasas de pérdida sostenida del ADN viral, el antígeno de superficie y en el índice de actividad histológica.

The seroconversion rates of e antigen attained with the current antivirals do not exceed 35 percent. The combination of immunomodulator and antiviral has been theoretically the most accepted strategy in the last five years; however, the results in clinical practice have been contradictory. This paper is aimed at evaluating the efficacy and security of a treatment scheme prolonged for 52 weeks with alpha-2b interferon plus lamivudine in patients with e antigen positive chronic hepatitis B. 46 patients selected at random were studied: 23 received 150 mg of lamivudine daily during 4 weeks, lamivudine plus alpha-2b (10 MU every other day) for 24 weeks, followed by lamivudine in the same dose and frequency until completing the 52 weeks. Other 23 were administered 150 mg of lamivudine daily for 4 weeks plus alpha 2b interferon (5 MU every other day) during 52 weeks. It was found that the antigen seroconversion rates were similar in both groups. A marked proportion of patients with combined prolonged treatment proved to be negative to the viral DNA (52 percent vs. 26 p = 0.06) and the surface antigen (48 percent vs. 26 percent, p = 0.11) compared with the controls. The improvement in the histological activity rate was observed in 48 percent of the patients treated with combined prolonged treatment against 22 percent of the controls (p = 0.06) It was concluded that the prolonged treatment of interferon and lamivudine during 52 weeks may have clinical benefits on the rates of sustained viral DNA loss, surface antigen and the histological activity index.

Tratamiento prolongado con interferón alfa-2b más lamivudina en pacientes con hepatitis crónica B y antígeno e positivo / Prolonged treatment with alpha-2b interferon plus lamivudine in patients with e antigen positive chronic hepatitis B

Las tasas de seroconversión del antígeno e alcanzadas con los antivirales actuales no sobrepasan el 35 por ciento. La combinación de inmunomodulador y antiviviral ha sido teóricamente la estrategia más aceptada en los últimos años; sin embargo, los resultados en la práctica clínica han sido contradictorios. Se realizó el presente trabajo para evaluar la eficacia y seguridad de un esquema de tratamiento prolongado durante 52 sem con interferón alfa-2b más lamivudina en pacientes con hepatitis crónica B y antígeno e positivo. Se estudiaron 46 pacientes asignados aleatoriamente: 23 recibieron 150 mg diarios de lamivudina por 4 sem, lamivudina más interferón alfa-2b (10 MU en días alternos) por 24 sem, seguido de lamivudina en la misma dosis y frecuencia hasta completar las 52 sem. Otros 23 recibieron 150 mg diarios de lamivudina por 4 sem y lamivudina más interferón alfa-2b (5 MU en días alternos) durante 52 sem. Se encontró que las tasas de seroconversión del antígeno fueron similares en ambos grupos. Una proporción significativa de pacientes con tratamiento combinado prolongado logró negativizar el ADN viral (52 por ciento frente al 26 por ciento, p=0,06) y el antígeno de superficie (48 por ciento frente al 26 por ciento, p=0,11), comparado con los controles. La mejoría en el índice de actividad histológica fue observada en el 48 por ciento de los pacientes tratados con tratamiento combinado prolongado frente al 22 por ciento de los controles (p=0,06). Se concluyó que el tratamiento prolongado de erferón y lamivudina durante 52 sem puede brindar beneficios clínicos en las tasas de pérdida sostenida del ADN viral, el antígeno de superficie y en el índice de actividad histológica (AU)

The seroconversion rates of e antigen attained with the current antivirals do not exceed 35 percent. The combination of immunomodulator and antiviral has been theoretically the most accepted strategy in the last five years; however, the results in clinical practice have been contradictory. This paper is aimed at evaluating the efficacy and security of a treatment scheme prolonged for 52 weeks with alpha-2b interferon plus lamivudine in patients with e antigen positive chronic hepatitis B. 46 patients selected at random were studied: 23 received 150 mg of lamivudine daily during 4 weeks, lamivudine plus alpha-2b (10 MU every other day) for 24 weeks, followed by lamivudine in the same dose and frequency until completing the 52 weeks. Other 23 were administered 150 mg of lamivudine daily for 4 weeks plus alpha 2b interferon (5 MU every other day) during 52 weeks. It was found that the antigen seroconversion rates were similar in both groups. A marked proportion of patients with combined prolonged treatment proved to be negative to the viral DNA (52 percent vs. 26 p = 0.06) and the surface antigen (48 percent vs. 26 percent, p = 0.11) compared with the controls. The improvement in the histological activity rate was observed in 48 percent of the patients treated with combined prolonged treatment against 22 percent of the controls (p = 0.06) It was concluded that the prolonged treatment of interferon and lamivudine during 52 weeks may have clinical benefits on the rates of sustained viral DNA loss, surface antigen and the histological activity index (AU)

Viusid, a nutritional supplement, in combination with interferon alpha-2b and ribavirin in patients with chronic hepatitis C.

BACKGROUND: The pathogenesis of chronic hepatitis C (CHC) is associated to severe oxidative stress that leads to necro-inflammation and progression of fibrosis. Previous trials suggested that antioxidative therapy may have a beneficial effect. We evaluated the efficacy and safety of Viusid in combination with interferon alpha-2b (IFN alpha-2b) and ribavirin in patients with CHC. METHODS: We randomly assigned 100 patients, between October 2002 and December 2004, in two arms: IFN alpha-2b (5 MU on alternate days), ribavirin at a dose of 13 mg/kg daily and Viusid (three sachets daily) vs. IFN alpha-2b (5 MU on alternate days) and ribavirin at a dose of 13 mg/kg daily. Subjects were treated for 48 weeks and then followed for an additional 24 weeks. The primary end point was the histologic response (reduction of at least two points without fibrosis worsening in the total score on the Histological Activity Index). RESULTS: A significantly high proportion of patients who received combined therapy plus Viusid had a histologic response better than those patients who received IFN alpha-2b and ribavirin (57% vs. 37%, P=0.03). The patients with virologic response achieved the highest percentages of histologic response, irrespective of assigned treatment. Among non-responders, the highest reduction in the mean change from baseline score for necro-inflammatory activity (NA) and fibrosis (F) was reported in patients treated with Viusid [NA, -1.50 (Viusid), -1.20 (without Viusid); F, -0.31 (Viusid), 0.00 (without Viusid)]. Sustained normalization of serum alanine aminotransferase concentration was highest in the Viusid group compared with standard therapy (67% vs. 41%, P=0.009). The overall safety profile was similar in both groups, but interestingly, the anemia was less intense in the group with Viusid (P=0.04). CONCLUSIONS: Our results suggest that triple therapy with Viusid, IFN alpha-2b and ribavirin was well tolerated and may have a beneficial effect on histologic and biochemical variables. The intensity of anemia is reduced in patients treated with Viusid.

[Sequential combination therapy with prednisone, lamivudine and interferon alfa-2b for HBeAg-positive chronic hepatitis B]. / Terapia de combinación secuencial con prednisona, lamivudina e interferón alfa-2b en pacientes con hepatitis crónica B y antígeno e positivo.

INTRODUCTION: Despite the development of potent, new antiviral drugs, the percentage of HBeAg seroconversion is approximately 35%. Immunosuppression before antiviral administration has recently been investigated with contradictory results. We evaluated the safety and efficacy of lamivudine and interferon alfa-2b with prior immunosuppression with prednisone in patients with HBeAg-positive chronic hepatitis B (CHB). METHODS: A randomized controlled study was conducted in a sample of 44 patients with HBeAg-positive CHB and persistently elevated alanine transferase (ALT) levels. The patients were distributed into two groups: 22 patients received prednisone 40 mg daily for 4 weeks, followed by 2 weeks without treatment, and lamivudine 150 mg daily for 4 weeks; lamivudine plus interferon alfa 2b (10 MIU every other day) was then administered for 24 weeks followed by continuous lamivudine 150 mg daily to complete 58 weeks. A further 22 patients received the same treatment regimen and duration, but without prednisone. RESULTS: Virologic response defined as HBeAg seroconversion plus a decrease of serum HBV DNA < 105 copies/ml 24 weeks after concluding the treatment was observed in 68% of the patients receiving previous immunosuppression compared with 54% of the control group (p = 0.26). Forty-five percent of patients with prednisone priming showed histologic improvement compared with 23% of the control group (p = 0.10). A significant proportion of patient with previous immunosuppression showed improvement in necroinflammatory activity (45% vs 23%) and fibrosis (50 vs 23%) compared with the control group. CONCLUSIONS: Virologic response was clinically, but not statistically, superior in the group with prednisone priming. Histologic improvement was notable in the group with previous immunosuppression.