Altered phenotype and functionality of circulating immune cells characterize adult patients with nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a chronic inflammatory liver disease associated with insulin resistance and its metabolic consequences. Leukocyte mobilization, intrahepatic activation, and an exacerbated production of reactive oxygen species (ROS) and cytokines contribute to the development of NASH. Though alterations in peripheral blood (PB) T cell proportions and functionality remain unidentified, they might play a main role in NASH progression. We have compared the phenotype and Th1/Th2 commitment of peripheral immune cell reservoirs in adult patients and controls as well as the ability of neutrophils and monocytes to handle an ex vivo challenge. Also, we correlated those parameters with the main histological characteristics in NASH. Compared with controls, patients showed increased numbers of CD4(+) cells and both CD4(+) and CD8(+) CD45RO subsets together with a higher frequency of IFN-γ-producing CD4(+) and CD8(+) T cells. We also found a decreased number of CD4(+) and CD8(+) CD45RA subsets. The distinctive production of IFN-γ highlights the significance of the observed skewed frequencies of PB T cells. Whereas ROS production by monocytes from NASH patients did not differ from controls, circulating neutrophils displayed a particularly higher phorbol myristate acetate-induced production of ROS. A negative correlation between oxidative burst and fibrosis grade was observed. This study reveals the presence of a characteristic profile of peripheral immune cells in NASH. We also discuss the probable influence of obesity on some of our present findings.

Serum creatinine and bilirubin predict renal failure and mortality in patients with spontaneous bacterial peritonitis: a retrospective study.

BACKGROUND: Patients with spontaneous bacterial peritonitis (SBP) are at a high risk for renal failure and death despite successful treatment of infection. Intravenous (IV) albumin administration combined with antibiotic treatment has been shown to significantly decrease these risks. Clinical evidence is lacking on which patients are appropriate candidates for albumin treatment. AIM: To retrospectively analyse the usefulness of serum creatinine and bilirubin levels in predicting renal failure and mortality of patients hospitalized for SBP. METHODS: Between March 1995 and September 1998, 127 cirrhotic patients with SBP who had not received plasma expansion were evaluated. Eighty-one patients (64%) were classified as having a high risk for renal failure and mortality (serum bilirubin >4 mg/dl or serum creatinine >1 mg/dl) and 46 (36%) as having a low risk. RESULTS: At admission, 36.3% of all patients presented renal failure. Mortality during their hospitalization was 23% among those with a high risk and 6.5% among those with a low risk (P=0.01). Renal failure occurred in 23% of the high-risk patients, compared with 2.6% of the low-risk patients (P=0.006). The presence of hyponatraemia was significantly associated with higher mortality and renal failure in the high-risk group. CONCLUSIONS: Our retrospective review of patients with SBP suggests that serum bilirubin levels >4 mg and serum creatinine levels >1 mg/dl at the time of diagnosis represent significant risk factors for the clinical outcomes of patients with SBP. Patients without these risk factors may have a very low likelihood of death or renal failure.

Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis and the risk of developing malignancies. A large prospective study.

BACKGROUND/AIM: primary sclerosing cholangitis (PSC) is associated with ulcerative colitis (UC) and seems to be a risk factor for colon cancer. However, taking into account that no data are available in South American population, we analyzed the prevalence of PSC in 1,333 patients with UC and the risk for developing colon cancer. MATERIAL: patients with persistent increases of alkaline phosphatase were studied by cholangiography and liver biopsy. To assess the risk of colon cancer, each patient with PSC and UC was matched with two control patients with UC without PSC of the same age, gender, extent and duration of UC. RESULTS: the whole prevalence of PSC was 2.9% (39 patients) reaching 6.2% in extensive colitis. Seven (18%) out of 39 patients with PSC developed colorectal carcinoma compared with 2 out of 78 (2.6%) in the control group (p=0.006). The cumulative risk of colorectal carcinoma was 11% and 18% after 10 and 20 years in the PSC group compared with 2% and 7% in the control group, respectively (p=0.002). CONCLUSION: this is the first prospective study performed in Latin America showing that the prevalence of PSC in patients with UC is similar to that reported in the Anglo-Saxon population. Patients with UC and PSC have a high risk of colorectal cancer.

Ciprofloxacin in primary prophylaxis of spontaneous bacterial peritonitis: a randomized, placebo-controlled study.

BACKGROUND/AIMS: Low protein concentration in ascitic fluid has been identified as a risk factor for spontaneous bacterial peritonitis (SBP). Until now, primary prophylaxis has not been recommended in these patients. The aim was to investigate the efficacy of long-term administration of ciprofloxacin to prevent SBP. METHODS: One hundred cirrhotic patients with <1.5 g/dl of total protein in ascitic fluid were randomized prospectively, in a double blind fashion to receive ciprofloxacin 500 mg/day (n=50) or placebo (n=50) for 12 months. RESULTS: Baseline data were similar in both groups. In the ciprofloxacin group, SBP occurred almost four times less frequently than in the placebo group but it was not statistically significant. The probability of survival at 12 months was significantly higher in patients receiving ciprofloxacin (86% versus 66%) (p<0.04). SBP and sepsis were the most frequent causes of death in the placebo group whereas gastrointestinal bleeding was responsible for the most deaths in the ciprofloxacin group. The probability of remaining free of bacterial infections was higher in patients receiving ciprofloxacin (80% versus 55%) (p=0.05). CONCLUSIONS: Patients with cirrhosis and low protein concentration in ascitic fluid are candidates to receive long-term prophylaxis to reduce the risk of infections and improve survival.

Nadolol plus spironolactone in the prophylaxis of first variceal bleed in nonascitic cirrhotic patients: A preliminary study.

Treatment with beta-blockers fails to decrease portal pressure in nearly 40% of cirrhotic patients. Recent studies have suggested that treatment with spironolactone reduces pressure and flow in the portal and variceal systems. This trial was designed to assess if nadolol plus spironolactone is more effective than nadolol alone to prevent the first variceal bleeding. One hundred patients with medium and large varices who had never bled and were without ascites were included in a prospective, randomized, multicenter, double-blind, placebo-controlled trial. The patients were randomized into 2 groups: 51 received nadolol plus placebo (N + P) and 49 received nadolol plus spironolactone 100 mg/d (N + S). Hepatic venous pressure gradient (HVPG) and activity of the renin-aldosterone system (plasma renin activity/plasma aldosterone levels) were measured in 24 patients. There were no significant differences in the appearance of variceal bleeding and ascites between groups at a mean follow-up of 22 +/- 16 months. However, analyzing both complications together, the incidence was significantly higher in the N + P group than in the N + S group (39% vs. 20%; P <.04). Clinical ascites was also higher in patients in the N + P group than in the N + S group (21% vs. 6%; P <.04). Significant increases in plasma renin activity and plasma aldosterone levels were only observed in patients in the N + S group (P <.01). The cumulative probabilities of remaining free of bleeding and ascites were similar in both groups after 70 months of follow-up. In conclusion, these results suggest that nadolol plus spironolactone does not increase the efficacy of nadolol alone in the prophylaxis of the first variceal bleeding. However, when bleeding and ascites were considered together, the combined therapy effectively reduced the incidence of both portal-hypertensive complications.

Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis and the risk of developing malignancies: a large prospective study / Prevalencia de colangitis esclerosante primaria en pacientes con colitis ulcerosa y el riesgo de desarrollar malignidades: un extenso estudio prospectivo

Background/aim: primary sclerosing cholangitis (PSC) is associated with ulcerative colitis (UC) and seems to be a risk factor for colon cancer. However, taking into account that no data are available in South American population, we analyzed the prevalence of PSC in 1.333 patients with UC and the risk for developing colon cancer. Material: patients with persistent increases of alkaline phosphatase were studied by cholangiography and liver biopsy. To assess the risk of colon cancer, each patient with PSC and UC was matched with two control patients with UC without PSC of the same age, gender, extent and duration of UC. Results: the whole prevalence of PSC was 2.9% (39 patients) reaching 6.2% in extensive colitis. Seven (18 %) out of 39 patients with PSC developed colorectal carcinoma compared with 2 out of 78 (2.6%) in the control group (p=0.006). The cumulative risk of colorectal carcinoma was 11% and 18% after 10 and 20 years in the PSC group compared with 2% and 7% in the control group, respectively (p=0.002). Conclusion: this is the first prospective study performed in Latin America showing that the prevalence of PSC in patients with UC is similar to that reported in the Anglo-Saxon population. Patients with UC and PSC have a high risk of colorectal cancer.

Introducción/objetivos: la colangitis esclerosante primaria (CEP) se asocia a colitis ulcerosa (CU) y parece ser un factor de riesgo para cáncer de colon. Sin embargo, teniendo en cuenta que no existen datos disponibles en población de Sudamérica, nosotros analizamos la prevalencia de CEP en 1.333 pacientes con CU y el riesgo de desarrollar cáncer de colon. Material: los pacientes con fosfatasa alcalina persistentemente elevada fueron estudiados con colangiografía y biopsia hepática. Para determinar el riesgo de cáncer de colon cada paciente con CEP y CU fueron apareados con dos pacientes controles con CU sin CEP de la misma edad, sexo, extensión y duración de la CU. Resultados: la prevalencia total de CEP fue de 2.9% (39 pacientes), alcanzando una prevalencia del 6.2% en colitis extensa. Siete (18%) de 39 pacientes con CEP desarrollaron cáncer colorectal comparado con 2 de 78 en el grupo control (p=0.006). El riesgo acumulado de cáncer colorectal fue 11 y 18% después de 10 y 20 años en el grupo con CEP comparado con 2 y 7% en el grupo control, respectivamente (p=0.002). Conclusión: este es el primer estudio prospectivo realizado en Latinoamérica mostrando que la prevalencia de CEP en pacientes con CU es similar a la reportada en población anglosajona. Los pacientes con CU y CEP tienen un alto riesgo de cáncer colorectal.

Acción de la SAMe en hepatopatía alcohólica / Effect of SAMe in alcoholic liver disease

Se presenta una experiencia en el tratamiento de la hepatopatia alcohólica con sulfo-adenosil-L-metionina (SAMe). La misma, se efectuó en un grupo de 20 pacientes durante 60 días y en una dosis de 200 mg/día de SAMe (i.m.) durante 30 días y 100 mg/día los 30 restantes. La respuesta clínica, valorada en forma subjetiva, evidenció una mejoría en el apetito, la astenia y la respuesta intelectual. Desde el punto de vista analítico se observaron mejorías significativas (p < .05 en adelante) en la gamaGT, TGP, TGO, bilirrubinemia, tiempo de Quick y colesterolemia. Los autores concluyen que la SAMe constituye un elemento terapéutico en la hepatopatía alcohólica, permitiendo una mejoría de la función hepática expresada mediante la clínica y las pruebas de síntesis proteica, de necrosis y de colestasis

Peritonitis espontanea en el cirrótico: nuestra experiencia / Spontaneus peritonitis in cirrhosis: our experience

Debido a la escasez de publicaciones en nuestro país, se analiza retrospectivamente la incidencia de peritonitis espontánea (PE) observados durante 2 años, en 76 episodios de ascitis provenientes de 63 pacientes con cirrosis hepática. Trece pacientes (17%) presentaron PE y la relación hombre-mujer fue de 5 a 1; el 70% de los gérmenes encontrados en el líquido ascítico fue de origen entérico, principalmente Escherichia Coli. En tres pacientes el diagnóstico se efectuó por el recuento de polinucleares y la clínica, a pesar del cultivo negativo. No hubo diferencias significativas en la presencia de complicaciones o alteraciones humorales al ingreso entre pacientes con ascitis estériles y con PE, pero sí con la mortalidad que fue de 7,9% (5/63) en los primeros y de 38% (5/13) en las ascitis infectadas. El 80% de los fallecidos presentaban falla renal en el final de la evolución y una vinculación con el uso de aminoglucósidos no puede ser descartado. La peritonitis espontánea en el cirrótico, buscada rutinariamente, parece tener la misma incidencia en nuestro medio que la descripta en la literatura