Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

[Tuberculosis in patients with HIV infection]. / Tuberculosis en pacientes infectados por el VIH.

Tuberculosis is a clear example of infection that requires cellular immunity for its control. The spread throughout the world of the Human Immunodeficiency Virus (HIV) resulted in its interaction with tuberculosis altering the descending curve of the latter disease in some developed countries, and brought an aggravation of the problem in other countries with few economic and health resources and where tuberculosis was endemic. HIV increases the risk of reactivation of latent tuberculosis infection and accelerates progression after infection or reinfection; on the other hand, TB aggravates the prognosis of patients infected with HIV. This article sets out the differential aspects in the clinical manifestations of TB amongst populations with and without HIV infection; we also comment on some special characteristics in the treatment of tuberculosis in HIV patients. With the exception of primary cutaneous infections produced by accidental inoculation and infantile lymphadenitis, the majority of the cases of disease due to non-tuberculosis mycobacteria (NTM) affect patients with certain predisposing factors. In the case of patients with AIDS, the deep immunological disorder provoked by HIV brings a particular susceptibility to suffering invasive disease due to certain NTM, principally M. avium complex and M. kansasii.

[Fever, pleural effusion and osteolytic lesion in a patient with HIV infection]. / Fiebre, derrame pleural y lesión osteolítica en paciente con infección por VIH.

We present the case of a 28 year old patient who came for consultation on a fever of up to 40.8 degrees C, pleuritic pain on the right side and the appearance of a painful mass in the lower left extremity of four days evolution. Computerised axial tomography (CAT) showed the existence of a condensation in the middle lobe of the right lung with associated pleural effusion and bilateral miliary pattern. The echographic study of the lower left extremity showed a mass of soft parts with a cystic aspect with destruction of the cortical of the fibula and osseous destruction. Magnetic resonance confirmed the presence of osteomyelitis in the left fibula and of an abscess; Mycobacterium tuberculosis was also isolated in three samples of sputum that led to a diagnosis of disseminated tuberculosis with miliary lung affectation, peroneous osteomyelitis and tuberculous abscess of the soft parts. Anti-tuberculosis treatment was started (riphampicine, isoniacide and pirazinamide) followed, two weeks later, with antiretroviral treatment (AZT, 3TC and NVP). The patient developed a clinical picture of generalised cutaneous eruption that disappeared following the replacement of the riphampicine by etambutol. Due to the persistence of the mass of soft parts following five weeks of anti-tuberculosis treatment, we proceeded to surgical draining of the abscess. The subsequent evolution was favourable, with the patient remaining asymptomatic one month after hospital discharge.

[Natural history of hepatitis C virus infection]. / Historia natural de la infección por el VHC.

The generally indolent, slow and protracted course of hepatitis C virus infection has limited the realisation of studies that evaluate its natural history. The aim of such studies has been the probability of death through hepatic disease, hepatic cirrhosis (compensated or decompensated), and/or hepatocarcinoma, or the development of a significant hepatic fibrosis (essential anatamopathological substrate for the development of the complications of hepatic cirrhosis). In spite of their possible limitations, the results of these studies show that chronic hepatitis C virus infection generally follows a benign evolutionary course, above all if this occurs in young patients (<50 years of age), without other aggravating factors of a possible hepatopathy (alcohol, coinfection by other viruses, immunosuppression) and if this is evaluated in the first 10-20 years of infection. At present, it is not possible to identify with precision those patients with HCV infection with a greater risk of developing a clinically relevant hepatic disease. However, it is likely that those subjects with high transaminases (> 2 times the normal value) and significant necroinflammatory activity (periportal necrosis) and fibrosis in the hepatic biopsy will show a more aggressive evolutionary course than those with normal transaminases and an almost normal hepatic biopsy.

Sublethal effects of contamination on the Mediterranean sponge Crambe crambe: metal accumulation and biological responses.

The effect of low levels of pollution on the growth, reproduction output, morphology and survival of adult sponges and settlers of the sponge Crambe crambe were examined. We transplanted sponges from a control area to a contaminated site and measured the main environmental variables (chemical and physical) of both sites during the study period. Except some punctual differences in particulate organic matter, silicates, nitrates, and water motion, most environmental variables in the water were similar at both sites during the study months. Mainly copper, lead and OM concentrations in the sediment, and water motion were significantly higher at the polluted site and may be implicated in the biological effects observed: decrease in the percentage of specimens with embryos, increase in shape irregularity and decrease in growth rate. Individuals naturally occurring at the polluted site and those transplanted there for four months accumulated ten times more copper than either untouched or transplant controls. Although lead concentration in sediment did not differ between sites, native specimens from the contaminated site accumulated this metal more than untouched controls. Vanadium concentration also tended to increase in the sponges living at or transplanted to the contaminated site but this difference was not significant. C. crambe is a reliable indicator of metal contamination since it accumulates copper, lead and vanadium in high amounts. At the contaminated site, sponge growth, fecundity and survival were inhibited, whereas sponge irregularity ending in sponge fission was promoted. All these effects may compromise the structure and dynamics of the sponge populations in sheltered, metal-contaminated habitats.

[Hospital admissions for varicella complications in children aged less than 15 years old]. / Hospitalizaciones por complicaciones de la varicela en niños menores de 15 años.

BACKGROUND: The complications of varicella are one of the arguments in favor of universal vaccination programs in children. OBJECTIVE: To describe the complications of varicella requiring hospital admission in a well-defined population (Gipuzkoa, Spain) and to compare the incidence of hospitalization with that reported in other series. MATERIAL AND METHODS: Observational, retrospective, multicenter study of admissions for varicella. The medical histories codified as varicella (minimum data set, CIE-0, codes 952.0-052.9) from 1 January 1993 to 31 December 2002 were reviewed. Calculation of hospitalization rates was based on emergency department visits and population data. The pediatric population of Gipuzkoa seeking medical attention at one of the four Basque Country Health Service hospitals in the area: Hondarribia, Mendaro, San Sebastian and Zumarraga. The mean coverage in Gipuzkoa is 54,999 children aged less than 15 years/year. All the children aged 0-15 years old admitted for more than 24 h with a discharge diagnosis of varicella complications. The variables studied are: age, gender, personal history, varicella immunization, immune status, fever, chest X-ray, complementary investigations, length of hospital stay, treatment, discharge diagnosis, clinical course, complications and sequelae at discharge. RESULTS: Seventy-one children were hospitalized. None had been vaccinated against the varicella-zoster virus. Eighty percent were aged less than 5 years and three were immunocompromised. Fifty-six percent had bacterial superinfection and invasive forms were found in seven patients. The mean length of admission was 6.5 days +/- 5.1. No deaths or sequelae were reported. CONCLUSIONS: The annual incidence rate of admissions longer than 24 hours due to varicella complications was 12.9 cases per 100,000 children aged less than 15 years, representing 0.31% of all annual admissions in this age group.

Isoinmunización Rh: evaluación de la utilidad del Doppler de arteria cerebral media en la predicción y manejo de anemia fetal / Rh isoimmunization: evaluation of the utility of Doppler cerebral artery average in the prediction and handling of fetal anemia

Se presenta la experiencia en el manejo de pacientes altamente sensibilizadas por incompatibilidad Rh, analizando la utilidad de la evaluación de la velocidad circulatoria fetal, por Doppler-color, a través de la medición de la velocidad máxima sistólica (VMS) de la arteria cerebral media (ACM). Se realizan 19 transfusiones intravasculares en 3 casos afectados por esta enfermedad. En 14 de ellas se encontró anemia fetal moderada o leve, la que fue diagnosticada correctamente en 13 oportunidades, (92,8 por ciento) por la medición anteriormente señalada. Se encuentra una adecuada correlación entre la velocidad máxima sistólica de la arteria cerebral media y el grado de anemia fetal moderada o severa, con un índice correlacional (r= (_) 0,78). Se destaca el beneficio de un método no invasivo en el manejo de la anemia fetal de causa inmunológica o asociada a otras condiciones mórbidas y se abre un campo para futuras investigaciones.

Renal failure after upper gastrointestinal bleeding in cirrhosis: incidence, clinical course, predictive factors, and short-term prognosis.

To assess the incidence, clinical course, predictive factors, and prognosis of renal failure in patients with cirrhosis and gastrointestinal bleeding, 175 consecutive episodes of gastrointestinal bleeding in 161 patients were analyzed. Renal failure occurred in 20 (11%) episodes and was transient in 8 episodes and nontransient in 12. Renal failure was more common in patients with cirrhosis than in a control population of bleeding patients without cirrhosis matched by age and severity of the bleeding episode. Among 39 clinical and laboratory variables obtained at admission or during hospitalization related with the bleeding episode or with liver and renal function, the presence of hypovolemic shock, number of packed red blood cells transfused, Child-Pugh class at admission, and baseline platelet count were independent predictors of renal failure. The development of renal failure and hypovolemic shock was the only independent predictors of in-hospital mortality. Mortality rate among the 20 episodes with renal failure was 55% (11 deaths) as compared with only 3% (5 deaths) in the 155 episodes without renal failure (P <.01). The development of nontransient renal failure entailed a much greater mortality as compared with transient renal failure (10 of 12 [83%] vs. 1 of 8 [12%]; P <.01). In conclusion, renal failure is a common event in patients with cirrhosis and gastrointestinal bleeding, the occurrence of which is mainly related to the severity of bleeding and baseline liver function. Renal failure is a strong predictor of mortality in patients with cirrhosis and gastrointestinal bleeding.

Evidence of serious graft damage induced by de novo hepatitis B virus infection after liver transplantation.

De novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) is commonly believed to be a relatively benign condition, in contrast to post-OLT infection recurrence, considered a very aggressive complication. We reviewed the charts of 569 non-HBV-related OLTs performed at our institution and identified 19 patients (3%) with de novo HBV infection (appearance of hepatitis B surface antigen [HBsAg] after OLT). After a median follow-up of 25 months beyond the detection of HBsAg, 12 patients (63%) had developed serious HBV-related graft damage (cirrhosis in 6 patients, bridging chronic hepatitis in 4 patients, and fulminant hepatitis in 2 patients); 7 patients (37%) had lost their grafts; and 4 patients (21%) had died. All graft losses and deaths were related to de novo HBV infection. Similar rates of severe graft damage (62%), graft loss (38%), and death (33%) related to HBV infection were found in a concomitant series of 21 patients with recurrent HBV infection after OLT. Responses to antiviral therapy (interferon or lamivudine) were also similar in the 2 groups of patients. In 12 patients with de novo HBV infection, evidence of past HBV infection (positive serum antibody to hepatitis B core antigen and/or serum or liver tissue HBV DNA) were detected in the donor (7 patients) or recipient (5 patients). No differences were observed in the clinical course after stratification according to the attributed origin of de novo HBV infection. We conclude that de novo HBV infection after OLT is associated with high rates of morbidity and mortality, similar to those described for post-OLT HBV infection recurrence.

A prognostic model for predicting survival in cirrhosis with ascites.

BACKGROUND/AIMS: Parameters evaluating renal function and systemic hemodynamics are of prognostic significance in cirrhosis with ascites but are rarely used in the evaluation of survival of these patients. The aim of the current study was to develop a prognostic model to estimate survival of patients with cirrhosis and ascites. METHODS: 216 Cirrhotic patients admitted to hospital for the treatment of ascites were evaluated. Thirty-two demographic, clinical and laboratory variables, including parameters assessing liver and renal function and systemic hemodynamics, were analyzed as predictive factors of survival by using a Cox regression model. RESULTS: Four variables had independent prognostic value: renal water excretion, as assessed by measuring diuresis after water load, mean arterial pressure, Child-Pugh class, and serum creatinine. According to these features a prognostic index was calculated that allows to estimate survival in patients with cirrhosis and ascites. The model accurately predicted survival in an independent series of 84 patients with cirrhosis and ascites. CONCLUSION: A prognostic model that uses four easily available variables and predicts prognosis in cirrhotic patients with ascites has been developed. This model may be useful in the evaluation of patients with ascites for liver transplantation.

Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome.

BACKGROUND/AIM: Ornipressin, a vasopressin analog with potent splanchnic vasoconstrictor action, has been shown to reverse hepatorenal syndrome. However, its usefulness in clinical practice is limited by frequent ischemic complications. The aim of this study was to assess the efficacy of terlipressin, an analog of vasopressin with a low profile of side effects, plus albumin in this condition. METHODS: Nine consecutive patients with cirrhosis and hepatorenal syndrome were included in a pilot study of terlipressin (0.5-2 mg/4 h i.v.) therapy associated with iv albumin. RESULTS: Treatment (9 days, range 5-15) was associated with a marked reduction of serum creatinine (3.9+/-0.7 to 1.3+/-0.1 mg/dl, p<0.001, mean+/-SE). Reversal of hepatorenal syndrome (reduction of creatinine below 1.5 mg/dl) was observed in seven of the nine patients. There was a remarkable improvement in circulatory function, with an increase in mean arterial pressure (68+/-2 to 80+/-4 mmHg, p<0.05) and suppression of vasoconstrictor systems activity (plasma renin activity and plasma norepinephrine decreased from 23+/-12 ng/ml x h and 1549+/-373 pg/ml to 3.5+/-2 ng/ml x h and 373+/-98 pg/ml, respectively, p<0.01 for both). No patient developed signs of intestinal, myocardial or distal ischemia. CONCLUSIONS: Terlipressin associated with albumin appears to be a safe and effective treatment of hepatorenal syndrome.

Pathophysiology, diagnosis and treatment of ascites in cirrhosis.

Ascites is the most common complication of patients with cirrhosis; its development constitutes the first and most important manifestation of the disease and is an indication for liver transplantation. During the last decade significant advances have been made in regard to the pathogenesis and treatment of ascites. The description of a new hypothesis, the identification of new vasoactive factors involved in the pathogenesis of arterial vasodilation and the introduction of different therapeutic modalities (therapeutic paracentesis, transjugular intrahepatic portosystemic shunt, aquaretics drugs and liver transplantation) are all proof of this. Similarly, the description of predictive factors for the survival of patients with cirrhosis has been of major importance for the identification of candidates for liver transplantation. This chapter reviews current knowledge on the pathophysiology, diagnosis and treatment of ascites in patients with cirrhosis.

[Bacterial infections in patients infected by HIV]. / Infecciones bacterianas en pacientes infectados por el VIH.

Individuals infected by the human immuno deficiency are more prone to suffering certain bacterial infections in the course of their clinical evolution. The agents involved in these infections are: Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, Salmonella spp and Campylobacter spp, which occasion an increase in morbidity and mortality. With a lower frequency, but with an equal morbidity and mortality, infections have been found caused by Rhodococcus equi, Nocardia spp and Bartonella spp. Even though all of them account for a selective impairment of immunodeficiency in one way or another, their incidence varies. Other factors such as degree of immuno suppression, habits, social and geographic living environment could be important. In general, there is a lack of chemoprophylactic strategies for their prevention. Early diagnosis and correct treatment could have important advantages for the quality of life and survival of these patients

Infection of a pacemaker by Brucella melitensis.

We report a case that, to the best of our knowledge, is the only published instance of infection of a pacemaker and its leads by Brucella melitensis. Furthermore, this case suggests that B. melitensis may be able to persist around pacemaker devices despite its having been eliminated from the rest of the body. The patient was a sheep shearer who had just undergone a 45-day course of antibiotic therapy for brucella and had been considered cured on the basis of negative blood cultures.