Improvement in liver histology due to lifestyle modification is independently associated with improved kidney function in patients with non-alcoholic steatohepatitis.

BACKGROUND: Several recent studies have shown a strong association between non-alcoholic steatohepatitis (NASH) and chronic kidney disease. AIM: To examine the relationship between changes in liver histology and renal function in patients with NASH. METHODS: The present analysis represents a post hoc analysis of a recently published trial that included 261 patients with NASH who were treated with lifestyle modifications during 52 weeks. Kidney function was evaluated through Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rates (eGFR, mL/min/1.73 m2 ) overtime. We explored correlations between the kidney function and improvement in histological outcomes at 52 weeks. RESULTS: Interestingly, a one-stage reduction in fibrosis (r = 0.20, P < 0.01) and resolution of NASH (r = 0.17, P < 0.01) were significantly correlated with an improvement in the kidney function. The eGFR values significantly increased in patients with fibrosis improvement (+7.6 ± 6.5 mL/min/1.73 m2 ), compared to those without fibrosis improvement (-1.98 ± 6.4 mL/min/1.73 m2 ) (P < 0.01) at end of treatment (EOT). Likewise, NASH resolution was associated with an increase in eGFR compared with patients without NASH resolution (2.32 ± 7.8 mL/min/1.73 m2 vs. -1.04 ± 5.9 mL/min/1.73 m2 , P = 0.04) at EOT. After controlling for the confounders, the association between fibrosis improvement, NASH resolution and eGFR change remained significant (P < 0.05 for both). CONCLUSIONS: Improvement in liver histology due to lifestyle modification is independently associated with improved kidney function in NASH. As new drugs for NASH emerge, studies should address whether improvement in histology in response to pharmacotherapies yield the same improvement in kidney function as weight loss.

Clinical trial: a nutritional supplement Viusid, in combination with diet and exercise, in patients with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a significant health problem for which there is no universally accepted pharmacological treatment. The combination of weight loss and antioxidant drugs to ameliorate insulin resistance and improve steatosis, inflammation and fibrosis provides the rational for therapeutic trials. AIM: To evaluate the efficacy and safety of a nutritional supplement Viusid in association with diet and exercise for NAFLD. METHODS: A randomized, controlled and parallel-group trial was conducted at a tertiary care academic centre (National Institute of Gastroenterology, Havana, Cuba). We randomly assigned 60 patients with liver biopsy-proven NAFLD to 6 months of treatment with a hypocaloric diet plus aerobic exercise daily and three Viusid sachets daily or a hypocaloric diet and exercise. Endpoints were improvement in the NAFLD activity score (NAS), fibrosis and normalization of serum aminotransferase levels. RESULTS: A significant improvement in steatosis, necroinflammation and fibrosis was seen in each group of treatment (P < 0.01 for each feature). The Viusid group, as compared with the control group, significantly reduced the mean of NAS [from 4.18 to 0.54 points in the Viusid group vs. 4.45 to 2.2 points in the control group (P < 0.001)]. On between-group comparison, Viusid was found to be associated with a significantly greater improvement in steatosis (P < 0.001), ballooning (P = 0.002) and lobular inflammation (P = 0.025), but not in fibrosis (P = 0.07). Viusid was well tolerated. CONCLUSIONS: Our results indicate that treatment with diet and exercise leads to a notable improvement in the histological features of NAFLD; however, the administration of Viusid intensifies the improvements of histological findings, especially of steatosis and inflammation.

Efficacy of ribavirin in patients with chronic hepatitis B.

This study aimed to evaluate the efficacy and safety of a 6-month course of ribavirin (Rb) (1200 mg/day) in the treatment of chronic hepatitis B (CHB). Sixty patients with CHB were randomly assigned in a double-blind placebo (Pl) controlled study; 30 patients received oral Rb (1200 mg/day) and 30 received Pl for 24 weeks. Patients were hepatitis B surface antigen (HBsAg); hepatitis B envelope antigen (HBeAg); and hepatitis B virus (HBV)-DNA-positive, with alanine aminotransferase (ALT) levels 1.5 times higher than normal values. Clinical evaluations and laboratory tests were carried out at regular intervals; tests included total blood cell count, liver function tests, and HBV serum markers. Baseline and control liver biopsies were carried out. HBeAg seroconversion occurred in 50.0% of the patients in the Rb group (vs 6.6% in the Pl group; P = 0.00019); HBV DNA negativization occurred in 33.3% in the Rb group (vs 6.6% in the Pl group; P = 0.009); and improvement in the necroinflammatory index occurred in 53.3% in the Rb group (vs 23.3% in the Pl group; P = 0.02). The drug was well tolerated; the most important side effect in the Rb group was hemoglobin reduction, which was reversible once the treatment was stopped. Ribavirin was an effective treatment, demonstrated by decreased ALT levels, alleviation of histological damage, seroconversion of HBeAg, and HBV-DNA negativization; Rb may be an alternative agent in the treatment of CHB, without significant side effects.

[Role of ribavirin in the treatment of chronic hepatitis B]. / Papel de la ribavirina en el tratamiento de la hepatitis crónica B.

AIM: To evaluate the safety and efficacy of 1,200 mg/day of ribavirin for 6 months in the treatment of chronic hepatitis B. MATERIALS AND METHODS: An open study was carried out with 25 patients with chronic hepatitis B who had previously received placebo (first phase) as part of a randomized, double blind study and who remained HBeAg and HBV DNA positive. In the second phase they received oral ribavirin (1,200 mg/day) for 24 weeks and the results of the first phase were compared with those of the second. All the patients had a recent histological diagnosis and were anti-HCV and anti-HIV negative. In both phases clinical and laboratory evaluations were carried out at weeks, 0, 4, 8, 12, 16, 24, 32, 40 and 48 which included blood tests, liver function tests and serological markers of HBV, and HBV DNA when HBeAg became negative. Liver biopsy was performed at the beginning of the first phase, 6 months later and at the end of the second phase. RESULTS: Mean values of alanine aminotransferase (ALT) showed a clear downward trend and were reduced by 50% at the end of the study while during the first phase these values were similar to basal values (range 32.3-45.5 IU). In the second phase, seroconversion of HBeAg was 56.0% (p = 0.00001) and HBV DNA was negative in 36%. The number of patients who showed improvement in Knodell's index was 86.7% in the second phase vs. 13.3% in the first phase (p = 0.00001). The drug was well tolerated and the only significant adverse reactions were a reduction in hemoglobin levels greater than 10% of the basal value in 84% of the patients, gastric acidity in 40% and fatigue in 32%. CONCLUSIONS: Ribavirin therapy at a dose of 1,200 mg/day for 24 weeks was well tolerated and efficacious in returning serum ALT levels to normal, in the seroconversion of HBeAg and negativization of HBV DNA as well as in reducing liver necrosis and inflammation. This study confirms that ribavirin may be considered a therapeutic option in the treatment of chronic hepatitis B.

[Morphologic characterization with light and electron microscopy of "nonspecific elements" in biliary drainage]. / Caracterización morfológica al microscopio óptico y electrónico de "elementos inespecíficos" en el drenaje biliar.

Since some years ago in our country are reported "inspecific elements" in biliary drainage, name given to some round shaped structures of approximately 12 microns, which generally appear associated to trophozoites of Giardia lamblia, disappearing after an antigiardia treatment. Many gastroenterologists consider such elements as Giardia, but they are still unknown in nature. Our object was to study them at the optic and electronic microscope for their comparison with the biologic forms of G. lamblia. Samples of rich G. lamblia trophozoites and "inspecific elements" biliary drainage, culture trophozoites and G. lamblia cysts rich feces were used. The samples were processed by a routine technique for transmission electronic microscope, with some modifications. Our studies demonstrated that the morphologic characters of the "inspecific elements" correspond to macrophages.

[Distribution of the antigen of hepatitis B virus in liver tissue in healthy carriers and in patients with chronic active and acute hepatitis]. / Distribución del antígeno del virus de la hepatitis B en tejido hepático, en portadores sanos y en pacientes con hepatitis crónica activa y aguda.

We have studied 120 cases of B hepatitis. Sixty were healthy carriers of B virus, 40 had chronic active hepatitis (CAH) and 20 acute hepatitis (AH). The AgsHBV distribution was made in liver tissue by immunoperoxidase technic. In 73% of patients with CAH the AgsHBV was found around portal tracts. In contrast in patients with AH the AgsHBV was seen around central vein. Healthy carriers showed an disseminated pattern. All healthy carrier had AgSHBV in liver, in contrast only 65% of patients with CAH and 20% with AH exhibited AgSHBV in liver biopsy.

Citologia aspirativa nueno metodo en el diagnostico del cancer del colon / Aspirative citology: a new method in the diagnosis of cancer of the colon

El método de toma citológica por punción aspirativa se ha usado con éxito en las lesiones accesibles con agujas corrientes. Las lesiones del tractus digestivo son de más dificil acceso, lo que ha hecho que no conozcamos antecedentes ninguno en la literatura con este método. Hemos ideado, desde 1978 la forma de tomar la muestra através de los aparatos de fibra óptica en las exploraciones endoscópicas, adaptando a un tubo de polietileno de tamaño suficiente para sobrepasar el colonoscopio, en su extremo distal un pequeño trócar y en su extremo proximal a la parte ajustable del trócar para adaptar la jeringuilla que va a efectuar la aspiración. Se pasa a través del canal de la biopsia del colonoscopio, puncionando la lesión y extrayendo por aspiración el material para el extendido citológico que se hace en ese momento fijándose para su posterior coloración y observacion microscópica. Se presenta el resultado de la citología aspirativa en 100 casos de lesiones tumorales o elevadas detectadas en el curso de las colonoscopias haciendo un estudio comparativo con la citología exfoliativa y la biopsia de los mismos casos, de forma de poder comparar el índice de positividad diagnóstica entre los tres métodos. Se estudiaron 77 adenocarciocomas, 9 adenomas vellosos, 6 polipos, 5 lesiones elevadas en el curso de colitis ulcerativa idiopática de larga evolución y 3 lesiones inflamatorias. La citología aspirativa tuvo mayor positividad que la exfoliativa complementando los fallos de los estudios biópsicos en los casos de neoplasis malignas con gran componente necrótico. Se resalta la utilida del método de la citología aspirativa por su sencillez, inocuidad y seguridad diagnóstica

Citologia aspirativa nueno metodo en el diagnostico del cancer del colon / Aspirative citology: a new method in the diagnosis of cancer of the colon

El método de toma citológica por punción aspirativa se ha usado con éxito en las lesiones accesibles con agujas corrientes. Las lesiones del tractus digestivo son de más dificil acceso, lo que ha hecho que no conozcamos antecedentes ninguno en la literatura con este método. Hemos ideado, desde 1978 la forma de tomar la muestra através de los aparatos de fibra óptica en las exploraciones endoscópicas, adaptando a un tubo de polietileno de tamaño suficiente para sobrepasar el colonoscopio, en su extremo distal un pequeño trócar y en su extremo proximal a la parte ajustable del trócar para adaptar la jeringuilla que va a efectuar la aspiración. Se pasa a través del canal de la biopsia del colonoscopio, puncionando la lesión y extrayendo por aspiración el material para el extendido citológico que se hace en ese momento fijándose para su posterior coloración y observacion microscópica. Se presenta el resultado de la citología aspirativa en 100 casos de lesiones tumorales o elevadas detectadas en el curso de las colonoscopias haciendo un estudio comparativo con la citología exfoliativa y la biopsia de los mismos casos, de forma de poder comparar el índice de positividad diagnóstica entre los tres métodos. Se estudiaron 77 adenocarciocomas, 9 adenomas vellosos, 6 polipos, 5 lesiones elevadas en el curso de colitis ulcerativa idiopática de larga evolución y 3 lesiones inflamatorias. La citología aspirativa tuvo mayor positividad que la exfoliativa complementando los fallos de los estudios biópsicos en los casos de neoplasis malignas con gran componente necrótico. Se resalta la utilida del método de la citología aspirativa por su sencillez, inocuidad y seguridad diagnóstica (AU)

[Aspiration cytology. New method in the diagnosis of cancer of the colon]. / Citología aspirativa. Nuevo método en el diagnóstico de cáncer del colon.

The method of cytologic samples by aspirative punction was successfully used in lesions that are accessible with common needles. The digestive tract's lesions are of more difficult access, and that is the reason why we do not known any antecedent with this method in the literature. Since 1978 we have thought about some way of taking the sample by fiberoptic devices in endoscopic explorations, adjusting to a polyethylene tube of suitable measure, as to exceed the colonoscopy, in the distal extreme, a little trocar and on its proximal extreme the adjustable part of the trocar for the adaptation of the syringe that makes the aspiration. It crosses through the biopsy channel of the colonoscope, puncturing the lesion and extracting the material by aspiration to prepare the cytologic smear, and fixing it for its further coloration and microscopic observation. We present the result of the aspirative cytology in 100 cases of tumoral or elevated lesions detected in the course of a colonoscopy, performing a comparative study with the exfoliative cytology and biopsy of the same cases, to compare the diagnostic positivity index between all the tree methods. We have studied 77 adenocarcinomas, 9 villous adenomas or polyps, 5 elevated lesions in long-evolution idiopathic ulcerative colitis and 3 inflammatory lesions. The aspirative cytology had greater positivity than the exfoliative one, complementing the judgement of biopsy studies in cases of malign neoplasia with great necrotic component. It must be underlined the utility of aspirative cytology method due to its simplicity, innocuousness and diagnostic security.

Citología aspirativa. Nuevo método en el diagnóstico de cáncer del colon. / [Aspiration cytology. New method in the diagnosis of cancer of the colon]

The method of cytologic samples by aspirative punction was successfully used in lesions that are accessible with common needles. The digestive tracts lesions are of more difficult access, and that is the reason why we do not known any antecedent with this method in the literature. Since 1978 we have thought about some way of taking the sample by fiberoptic devices in endoscopic explorations, adjusting to a polyethylene tube of suitable measure, as to exceed the colonoscopy, in the distal extreme, a little trocar and on its proximal extreme the adjustable part of the trocar for the adaptation of the syringe that makes the aspiration. It crosses through the biopsy channel of the colonoscope, puncturing the lesion and extracting the material by aspiration to prepare the cytologic smear, and fixing it for its further coloration and microscopic observation. We present the result of the aspirative cytology in 100 cases of tumoral or elevated lesions detected in the course of a colonoscopy, performing a comparative study with the exfoliative cytology and biopsy of the same cases, to compare the diagnostic positivity index between all the tree methods. We have studied 77 adenocarcinomas, 9 villous adenomas or polyps, 5 elevated lesions in long-evolution idiopathic ulcerative colitis and 3 inflammatory lesions. The aspirative cytology had greater positivity than the exfoliative one, complementing the judgement of biopsy studies in cases of malign neoplasia with great necrotic component. It must be underlined the utility of aspirative cytology method due to its simplicity, innocuousness and diagnostic security.

[A proposal for the classification of intestinal complications in giardiasis]. / Propuesta de clasificación de la repercusión intestinal en giardiasis.

Two hundred children hospitalized in the National Institute of Gastroenterology were studied during the 1972-1980 period. The children, whose ages ranged between six months and ten years, presented chronic diarrhea in which Giardia lamblia was considered the causative agent. The diagnosis of parasitism was made with the detection of Giardia lamblia in the feces and/or duodenal content. A serum D-Xylose and jejunal biopsy were performed on all the patients and the histology of the mucosa was classified in keeping with the degree of atrophy according to Metayer and Laumonier. In our study we divided the patients into three groups: Group 1, parasitism due to Giardia lamblia in patients with a normal D-xylose and different degrees of atrophy of the jejunal mucosa, but with normal D-Xylose and Group 3, malabsorption due to Giardia lamblia, with a pathological D-Xylose and alterations in the intestinal mucosa. There were 35 cases in Group 1 (17.5%), 91 cases in Group 2 (45.5%) and 74 cases in Group 3 (37%). The predominant intestinal lesion was partial atrophy of the villi (143), 20 with subtotal atrophy of the villi and two with complete atrophy of the villi. It was shown that the host's response to infection by Giardia lamblia varies with differing effects on the structures and functioning of the jejunal mucosa. It is important to group patients with chronic diarrhea due to Giardia lamblia in this way since it allows for and individualized clinical approach and provides a prognosis in terms nutritional consequences resulting from possible persistence of the diarrhea and possible associated lactose intolerance.

Propuesta de clasificación de la repercusión intestinal en giardiasis. / [A proposal for the classification of intestinal complications in giardiasis]

Two hundred children hospitalized in the National Institute of Gastroenterology were studied during the 1972-1980 period. The children, whose ages ranged between six months and ten years, presented chronic diarrhea in which Giardia lamblia was considered the causative agent. The diagnosis of parasitism was made with the detection of Giardia lamblia in the feces and/or duodenal content. A serum D-Xylose and jejunal biopsy were performed on all the patients and the histology of the mucosa was classified in keeping with the degree of atrophy according to Metayer and Laumonier. In our study we divided the patients into three groups: Group 1, parasitism due to Giardia lamblia in patients with a normal D-xylose and different degrees of atrophy of the jejunal mucosa, but with normal D-Xylose and Group 3, malabsorption due to Giardia lamblia, with a pathological D-Xylose and alterations in the intestinal mucosa. There were 35 cases in Group 1 (17.5

), 91 cases in Group 2 (45.5

) and 74 cases in Group 3 (37

). The predominant intestinal lesion was partial atrophy of the villi (143), 20 with subtotal atrophy of the villi and two with complete atrophy of the villi. It was shown that the hosts response to infection by Giardia lamblia varies with differing effects on the structures and functioning of the jejunal mucosa. It is important to group patients with chronic diarrhea due to Giardia lamblia in this way since it allows for and individualized clinical approach and provides a prognosis in terms nutritional consequences resulting from possible persistence of the diarrhea and possible associated lactose intolerance.

Empleo del interferón leucocitario en la hepatitis crónica activa: estudio clínico-humoral e histológico / Use of leukocyte IFN in active chronic hepatitis: clinical humoral and histologic study

Doce pacientes con diagnóstico clínico, humoral, laparoscópico e histológico de hepatitis crónica activa, once de ellos portadores de antígeno de superficie de la hepatitis B y el restante con sospechas de infección crónica con el virus, no A no B, fueron tratados durante seis meses con interferón leucocitario por vía intramuscular recibiendo un total de 400 x 10 a la seis u. Con anterioridad, durante el proceso y al final del tratamiento, se realizó el estudio de transaminasa glutámico-pirúvica (TGP) gamma glutamil transpeptidasa (GGT), ácidos biliares séricos en ayunas, antígeno de superficie de la hepatitis B y conteo de linfocitos T y B. La biopsia hepática se repitió al final del tratamiento. Los resultados se compararon con un grupo similar de pacientes que recibió otro tipo de terapéutica (cloroquina, levamisol e inmunosupresores). Los niveles de TGP disminuyeron significativamente (p < 0,01) en los casos tratados con interferón, y en 10 de ellos las cifras de estas enzimas se normalizaron. Los ácidos biliares y la GGT también disminuyeron (p < 0,05) en dicho grupo. La antigenemia s desapareció en tres casos y los títulos de dicho antígeno disminuyero en los restantes al final del estudio. Las poblaciones linfocitarias T y B no mostraron diferencias significativas antes y después del tratamiento. Las biopsias hepáticas de los casos tratados mostraron una mejoría histológica en nueve de ellos, otro evolucionó a una hepatitis crónica persistente y en los dos restantes se constató un aumento de la fibrosis. En los pacientes que recibieron otro tipo de terapéutica solo en tres de ellos se normalizó la TGP, en dos se apreció mejoría del cuadro histológico, dos evolucionaron a una cirrosis y en los restantes no hubo cambios ostensibles

Empleo del interferón leucocitario en la hepatitis crónica activa: estudio clínico-humoral e histológico / Use of leukocyte IFN in active chronic hepatitis: clinical humoral and histologic study

Doce pacientes con diagnóstico clínico, humoral, laparoscópico e histológico de hepatitis crónica activa, once de ellos portadores de antígeno de superficie de la hepatitis B y el restante con sospechas de infección crónica con el virus, no A no B, fueron tratados durante seis meses con interferón leucocitario por vía intramuscular recibiendo un total de 400 x 10 a la seis u. Con anterioridad, durante el proceso y al final del tratamiento, se realizó el estudio de transaminasa glutámico-pirúvica (TGP) gamma glutamil transpeptidasa (GGT), ácidos biliares séricos en ayunas, antígeno de superficie de la hepatitis B y conteo de linfocitos T y B. La biopsia hepática se repitió al final del tratamiento. Los resultados se compararon con un grupo similar de pacientes que recibió otro tipo de terapéutica (cloroquina, levamisol e inmunosupresores). Los niveles de TGP disminuyeron significativamente (p < 0,01) en los casos tratados con interferón, y en 10 de ellos las cifras de estas enzimas se normalizaron. Los ácidos biliares y la GGT también disminuyeron (p < 0,05) en dicho grupo. La antigenemia s desapareció en tres casos y los títulos de dicho antígeno disminuyero en los restantes al final del estudio. Las poblaciones linfocitarias T y B no mostraron diferencias significativas antes y después del tratamiento. Las biopsias hepáticas de los casos tratados mostraron una mejoría histológica en nueve de ellos, otro evolucionó a una hepatitis crónica persistente y en los dos restantes se constató un aumento de la fibrosis. En los pacientes que recibieron otro tipo de terapéutica solo en tres de ellos se normalizó la TGP, en dos se apreció mejoría del cuadro histológico, dos evolucionaron a una cirrosis y en los restantes no hubo cambios ostensibles