Hepatitis: Espinosa M

Barril G, González Parra E, Alcázar R, Arenas D, Campistol JM, Caramelo C, Carrasco M, Carreño V, Espinosa M, García Valdecasas J, Górriz JL, López MD, Martín L, Ruiz P, Terruel JL, Anonymous00170. · Nefrólogo Hosp. Universitario de La Princesa, Madrid. · Nefrologia. · Pubmed #15085792 No free full text.

Abstract: The viric infections influence morbi-mortality in Chronic kidney Disease patients in hemodialysis therapy and can affect to the Staff of the Units. The guides considered the most relevant virus at the present moment: C Virus, B Virus and HIV. To prevent horizontal nosocomial transmission is necessary the observance always the universal precautions in the HD units, although sometimes can appeared seroconversions and epidemic bud when exist a break of these. Is analyzed different situations with special focus in units for acute patients. The following steps under the suspicious of the epidemic bud appeared in one of the annexes together with legislation according to this case. Respect to the staff in every one of the virus is shown prevention patterns, serologic markers to perform when an accident with infected blood occur, also is considered when treatment is indicated. The guides considered too the conditions necessary for include these patients on waiting list for kidney transplantation.

Barril G, Castillo I, Arenas MD, Espinosa M, Garcia-Valdecasas J, Garcia-Fernández N, González-Parra E, Alcazar JM, Sánchez C, Diez-Baylón JC, Martinez P, Bartolomé J, Carreño V. · Department of Nephrology, Hospital de Princesa, Madrid, Spain. · J Am Soc Nephrol. · Pubmed #18684893 No free full text.

Abstract: Occult hepatitis C virus (HCV) infection (i.e., detectable HCV-RNA in the liver or peripheral blood mononuclear cells) in the absence of both serum HCV-RNA and anti-HCV antibodies has not been investigated in hemodialysis patients. In this study, real-time PCR and in situ hybridization was used to test for the presence of genomic and antigenomic HCV-RNA in peripheral blood mononuclear cells of 109 hemodialysis patients with abnormal levels of liver enzymes. Occult HCV infection, determined by the presence of genomic HCV-RNA, was found in 45% of the patients; 53% of these patients had ongoing HCV replication, indicated by the presence of antigenomic HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on hemodialysis and had significantly higher mean alanine aminotransferase levels during the 6 mo before study entry. Logistic regression analysis revealed that mortality was associated with age >60 yr (odds ratio 3.30; 95% confidence interval 1.05 to 10.33) and the presence of occult HCV infection (odds ratio 3.84; 95% confidence interval 1.29 to 11.43). In conclusion, the prevalence of occult HCV infection is high among hemodialysis patients with persistently abnormal values of liver enzymes of unknown cause. The clinical significance of occult HCV infection in these patients requires further study.

Espinosa M, Arenas MD, Aumente MD, Barril G, Buades JM, Aviles B, Carretero D, Alvarez-Lara MA, Carnicer F, Martin-Malo A, Aljama P. · Servicio de Nefrología, Hospital Universitario Reina Sofia, Cordoba, Spain. · Clin Nephrol. · Pubmed #17598372 No free full text.

Abstract: AIMS: Anemia is a well-known side effect of interferon therapy since interferons are potent inhibitors of erythropoiesis. The aim of this study was to compare the anemia associated with pegylated interferon (PEG-IFN) (alpha2a versus alpha2b therapy in hemodialysis patients (HD) with chronic hepatitis C. METHODS: In order to study the anemia, doses of erythropoietic growth factors (EGF), hemoglobin (Hb) and erythropoietin resistance index (ERI) were compared at baseline and after PEG-IFN-alpha2a or alpha2b therapy in 16 HD patients with chronic C hepatitis. Pharmacokinetic studies were performed in 4 of those treated with PEG-IFN-alpha2b and 2 patients treated with PEG-IFN-alpha2a. Secondary end-points were viral response and serious adverse events. RESULTS: At 4-6 months after the beginning of therapy, both PEG-IFN-alpha induced a significant increment in the erythropoietin resistance index. This increment was significantly higher in patients treated with PEG-IFN-alpha2a when compared with alpha2b (45 vs 9.9, p = 0.012). The pharmacokinetics of PEG-IFN-alpha2a and alpha2b in HD patients were different, the C(max), C(min) and the area under the serum concentration time curve, were all higher in patients treated with PEG-IFN-alpha2a compared with PEG-INF-alpha2b. Discontinuation of therapy occurred in 2 (28.5%) of the 7 patients in the PEG-IFN-alpha2a group and in 4 (44%) of the 9 patients in the PEG-IFN-alpha2b group. Three (42%) subjects in the alpha2a group and 5 (55%) in the alpha2b group had a response at the end of the 48 weeks of therapy. In 4 (44.4%) of the 9 patients treated with alpha2b the viral response was sustained. CONCLUSIONS: In summary, patients treated with PEG-IFN-alpha2a have a major inhibitory effect on erythropoiesis. This could be explained by the different pharmacokinetic properties of PEG-IFN-alpha2a and alpha2b. Further studies are needed to clarify how these findings influence the efficacy, safety and cost-effectiveness of the PEG-IFN-alpha2.

Arenas MD, Sánchez-Payá J, Barril G, García-Valdecasas J, Gorriz JL, Soriano A, Antolin A, Lacueva J, García S, Sirvent A, Espinosa M, Angoso M. · Hospital Perpetuo Socorro, Alicante, Spain. · Nephrol Dial Transplant. · Pubmed #15769816 links to  free full text

Abstract: BACKGROUND: This study intended to investigate the degree of compliance with hand hygiene and use of gloves by health workers in haemodialysis (HD) units, and the factors that influenced adherence to hand hygiene protocols. METHODS: During the month of November 2003, one person observed the health care staff in each of nine different dialysis units, during 495 randomly distributed 30 min observation periods that covered all steps of a haemodialysis session (connection, dialysis and disconnection). The observers noted the number of potential opportunities to implement standard precautions and the number of occasions on which the precautions were actually taken. Adherence to standard precautions was evaluated, analysing the influence of the following variables: the patient-to-nurse ratio, the number of HD shifts scheduled per day, acute HD units vs chronic, whether or not infectious patients were isolated and in-house vs contract cleaning personnel. RESULTS: There were a total of 977 opportunities to wear gloves for, and to wash the hands following, a patient-oriented activity, and 1902 opportunities to wash hands before such an activity. Gloves were actually used on 92.9% of these occasions. Hands were washed only 35.6% of the time after patient contact, and only 13.8% of the time before patient contact. Poor adherence to hand washing was associated with the number of shifts per HD unit per day and with higher patient-to-nurse ratios. In the acute HD units, there was greater adherence to standard precautions than in the chronic units, although there too it was substandard. The personnel's knowledge of patients' infectious status did not modify their adherence to hand hygiene practices. A higher patient-to-nurse ratio independently influenced hand washing both before and after patient contact. CONCLUSIONS: The overall adherence of health care workers to recommended hand washing practices is low. Whether or not programmes promoting higher hand hygiene standards and the potential use of alcohol-based hand cleansers will improve hand hygiene practices in HD units requires further investigation.

Espinosa M, Martn-Malo A, Ojeda R, Santamara R, Soriano S, Aguera M, Aljama P. · Servicio de Nefrologa, Hospital Universitario Reina Sofia, Cordoba, Spain. · Am J Kidney Dis. · Pubmed #15042545 No free full text.

Abstract: BACKGROUND: The prevalence of hepatitis C virus (HCV) infection in hemodialysis (HD) patients has decreased significantly in the course of the past decade in most HD units. The objective of this study is to analyze the causes of this reduction and obtain additional information for the near future that could be of use for health services planning. METHODS: All patients who underwent HD in the Province of Cordoba, Spain, between January 1992 and December 2002 were studied. We analyzed annual exclusions from the HD program of HCV-positive patients (deaths and kidney transplantations) and inclusions (predialysis patients, patients with chronic graft rejection, and HD patients with acute HCV infection). The trend in the time series of measurements was calculated by means of exponential smoothing with 2 parameters. RESULTS: In December 1992, the prevalence of antibody to HCV (anti-HCV) was 24% (N = 54), whereas by December 2002, it had decreased to 9.2% (N = 35). Of 657 predialysis patients included in the maintenance HD program, 2.8% (n = 19) were positive for anti-HCV. Annual mean incidence of acute HCV infection was 0.5%, and the median was 0.32%. Mean crude annual mortality rates were 12.2% for anti-HCV-positive patients versus 9.9% for anti-HCV-negative patients. The trend in this time series suggests that by 2006, the prevalence of anti-HCV in HD patients will be approximately 2.5%. CONCLUSION: Causes implicated in the reduction in prevalence of HCV infection in HD patients are a greater mortality rate, stabilization of the incidence of acute HCV infection, and a low percentage of HCV infection in predialysis patients. By the end of 2006, the rate of HCV infection in HD patients will be very close to that of the predialysis population.

Espinosa M, Martin-Malo A, Alvarez de Lara MA, Gonzalez R, Rodriguez M, Aljama P. · Servicios de Nefrologia, Hospital Universitario Reina Sofia, Cordoba, Spain. · Clin Nephrol. · Pubmed #12227687 No free full text.

Abstract: AIMS: Chronic liver disease develops in the majority of non-uremic patients with hepatitis C virus (HCV) infection. The aim of this study was to analyze the evolution towards chronic hepatopathy in 19 cases of acute hepatitis C observed in hemodialysis patients from 1990 to 2001. METHODS: A prospective follow-up study on HCV infection was conducted in 3 HD units from April 1990 to June 2001 to study clinical outcomes after acute hepatitis C. A total of 781 patients were tested monthly for alanine aminotransferase and anti-HCV in serum. In this period, 19 patients suffered from acute hepatitis C. Evolution to chronic liver disease in the follow-up was evaluated by means of biochemical (increased ALT) and virological criteria (HCV-RNA+). The transmission mechanism, the apparition of anti-HCV, clinical manifestations and mortality were also investigated. RESULTS: In 15 (78.9%) of the 19 patients, the viremia remained positive (chronic viremia) and 11 patients (57.8%) evolved to chronic liver disease (chronic viremia and high transaminase levels) with a median follow-up of 3 years (range 1 - 6). Five of them who underwent liver biopsies had histologic signs of chronic active hepatitis. One of them (5.2%) evolved to liver cirrhosis in the follow-up. In 4 out of 19 patients (21%) the HCV infection resolved. Although 7 (36.8%) of them died in the follow-up, acute hepatitis C infection was not a short-term independent risk factor of death. CONCLUSIONS: Three years after acute hepatitis C, 87.5% of the hemodialysis patients remained HCV-RNA positive and 56.2% evolved to chronic liver disease. It is important to stress that HCV infection spontaneously cleared in 4 out of 19 patients (21%).

Espinosa M, Martin-Malo A, Alvarez de Lara MA, Navarro MD, Aljama P. · Servicio de Nefrologia, Hospital Universitario Reina Sofia, Córdoba, Spain. · Clin Nephrol. · Pubmed #11758008 No free full text.

Abstract: BACKGROUND/AIMS: Beta2-microglobulin is the main component of dialysis-associated amyloid. Interferons (IFNs) have the ability to induce an increase in the formation and release of this protein. The aim of this study was to evaluate serum beta2-microglobulin levels in 11 hemodialysis patients with chronic hepatitis C treated with IFNalpha. METHODS: Eleven hemodialysis patients with chronic hepatitis C that received IFNalpha treatment were included in this study. No patient had residual renal function. High-flux membranes were used in 5 patients, and low-flux membranes in the remaining 6 patients. Beta2-microglobulin was analyzed at baseline, during IFNalpha treatment and after IFNalpha was stopped. RESULTS: Serum beta2-microglobulin concentration rose in all patients during the IFNalpha therapy. Compared with baseline values (43 mg/l, range 22-59) the median beta2-microglobulin levels increased significantly at one month (65 mg/l, range 37-142, p = 0.008) and at 12 months (59 mg/l, range 42-137, p = 0.003) after the beginning of IFN therapy. One month after IFNalpha was discontinued, beta2-microglobulin decreased significantly (median 48, range 34-75 mg/l, p = 0.05) in comparison with that obtained at the end of the therapy. The increase observed during IFN therapy was lower in patients treated with high-flux membranes than in those with low-flux membranes, although it was not statistically different. CONCLUSION: Our results show that IFNalpha therapy increases serum beta2-microglobulin levels in hemodialysis patients. Further studies are needed to clarify whether the use of high-flux membranes should be recommended in hemodialysis patients requiring IFN treatment.

Espinosa M, Martin-Malo A, Alvarez de Lara MA, Aljama P. · Servicio de Nefrologia, Hospital Universitario Reina Sofia, Cordoba, Spain. · Nephrol Dial Transplant. · Pubmed #11477172 links to  free full text

Abstract: BACKGROUND: Hepatitis C virus (HCV) infection is the most common cause of chronic liver disease in haemodialysis patients. The aim of this study was to assess the impact of HCV infection on patient survival in a cohort of long-term haemodialysis patients and to evaluate the percentage of anti-HCV-positive patients that evolve to liver cirrhosis. METHODS: In 1992, 175 patients who had been on intermittent haemodialysis therapy for at least 6 months were included in the study (57 anti-HCV-positive and 118 anti-HCV-negative patients). Evaluation of patient outcome included date and cause of death, kidney transplantation, and the diagnosis of liver cirrhosis. Patient survival was estimated by the Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazards model was used to estimate the risk of death among dialysis patients who were anti-HCV positive. Other prognostic variables studied included age, gender, diabetes mellitus as cause of end-stage renal disease (ESRD), history of previous transplant, transplantation during follow-up, and time on haemodialysis treatment. The diagnosis of liver cirrhosis was made based on clinical and/or histological criteria. RESULTS: Eight-year patient survival in anti-HCV-positive subjects was lower (32%) than in anti-HCV-negative patients (52%) (log-rank, P=0.03). Four variables were found to be independent prognostic factors in patient survival: age (relative risk (RR) 1.04); diabetes as cause of ESRD (RR 3.6); transplantation during follow-up (RR 0.66) and presence of HCV antibodies (RR 1.62). The causes of death did not differ significantly between groups, except that four anti-HCV-positive patients died from liver disease. Ten (17.5%) of the 57 anti-HCV-positive patients were diagnosed to have liver cirrhosis at a median of 10 years after renal replacement therapy initiation and a median of 7 years after the first ALT level increase. CONCLUSION: In conclusion, our study shows an increased risk of death among long-term haemodialysis patients infected with HCV compared with non-infected patients. This might be partly explained by the high proportion of these patients that evolve to liver cirrhosis.

Espinosa M, Rodriguez M, Martin-Malo A, Alvarez de Lara MA, Gonzalez R, Lopez-Rubio F, de la Mata M, Aljama P. · Servicios de Nefrologia, Hospital Universitario Reina Sofia, Cordoba, Spain. · Clin Nephrol. · Pubmed #11316242 No free full text.

Abstract: AIM: The aim of the present study was to analyze the efficacy and tolerance of interferon (IFN) therapy in hemodialysis (HD) patients with chronic hepatitis C virus (HCV) infection. Specifically, we assessed whether the "normalization" of serum ALT levels was associated with the disappearance of the HCV-RNA. METHODS: Thirteen hemodialysis patients with chronic hepatitis C were treated for one year with 3 MU of alpha-IFN. The primary end point was a sustained virological response defined as the absence of HCV-RNA in the last follow-up; the secondary end points were normalization of the serum ALT levels and histological improvement. ALT was considered "normal" below 27 IU/l. RESULTS: Ten patients completed the treatment, which was discontinued in the other 3 (23%). By the end of the treatment a virological response was observed in 8 of the 10 patients (80%) who completed the one-year IFN therapy. Biochemical response was associated with a virological response in 8 of the 9 patients in whom ALT levels became normal. Three patients had a biochemical and virological relapse in the follow-up. Two of them received a further year of IFN therapy, which resulted in a sustained biochemical and virological response. In all patients who underwent a liver biopsy (n = 5), the inflammation score improved. After a median follow-up of 5 years (range 2 - 7), a sustained response was observed in 6 (46%) of the 13 patients enrolled. Two patients with a sustained response received a kidney transplant and after more than 6 years still maintain a biochemical and virological response. Side effects included flu-like syndrome (n = 8), hemoglobin decrease (n = 8), thrombocytopenia (n = 3), depression (n = 1) and seizures (n = 1). CONCLUSION: IFN treatment over a one-year period produces a high rate of long-term virological response in HD patients, associated to a biochemical response in all cases.

Espinosa M, Martin-Malo A, Alvarez de Lara MA, Soriano S, Aljama P. · Servicio de Nefrologia, Hospital Universitario Reina Sofia, Cordoba, Spain. · Clin Nephrol. · Pubmed #10968693 No free full text.

Abstract: AIMS: Some studies have reported that ALT determination is of little value in the study of chronic hepatitis C in hemodialysis (HD) patients. This could be due to the fact that ALT values are lower in HD patients than in healthy individuals; ALT in HCV infection follows a fluctuating pattern and the HCV viremia may be intermittent. The aim of this study was to establish the reference ALT values in a large group of hepatitis-free HD patients, and to determine their role in predicting viremia in anti-HCV-positive HD patients. METHODS: Four subject groups were studied: group I, patients with normal renal function (n = 88); group II, hepatitis-free HD patients (n = 218); group III, non-viremic anti-HCV+ HD patients (n = 9); and group IV, viremic anti-HCV+ HD patients (n = 24). The ALT used for calculation purposes was the mean value of the twelve previous months for each individual patient. PCR screening for HCV-RNA was performed at least twice for anti-HCV+ patients; these were deemed viremic (HCV-RNA+) if at least one screening was positive, and non-viremic (HCV-RNA) if all PCR results were negative. RESULTS: Mean ALT in group II was lower than in subjects with normal renal function (15.6 +/- 12 vs. 22.7 +/- 18 IU/l, p < 0.05). No significant differences were observed between group III and group II (17.7 +/- 6 vs. 15.6 +/- 6 IU/l, ns). ALT levels in group IV patients were higher than those of groups II and III (38.5 +/- 39 IU/l, p < 0.05). The upper limit (mean + 2 SD and 95th percentile) for ALT in hepatitis-free HD patients was 27 IU/l. Sensitivity of a mean ALT value > or = 27 IU/l in the diagnosis of HCV viremia was 50%, and specificity was 100%. The positive predictive value of this test in the diagnosis of hepatitis C viremia was 100%. CONCLUSIONS: ALT values are lower in HD patients and a high ALT level can constitute an excellent tool in predicting viremia in anti-HCV-positive HD patients once other causes of liver disease have been excluded.

Espinosa M, Martín-Malo A, Aljama P. · No affiliation provided · Kidney Int. · Pubmed #10886596 links to  free full text

This publication has no abstract.