Liver stiffness predicts clinical outcome in human immunodeficiency virus/hepatitis C virus-coinfected patients with compensated liver cirrhosis.

UNLABELLED: Our aim was to assess the predictive value of liver stiffness (LS), measured by transient elastography (TE), for clinical outcome in human immunodeficiency virus / hepatitis C virus (HIV/HCV)-coinfected patients with compensated liver cirrhosis. This was a prospective cohort study of 239 consecutive HIV/HCV-coinfected patients with a new diagnosis of cirrhosis, done by TE, and no previous decompensation of liver disease. The time from diagnosis to the first liver decompensation and death from liver disease, as well as the predictors of these outcomes, were evaluated. After a median (Q1-Q3) follow-up of 20 (9-34) months, 31 (13%, 95% confidence interval [CI]: 9%-17%) patients developed a decompensation. The incidence of decompensation was 6.7 cases per 100 person-years (95% CI, 4.7-9-6). Fourteen (8%) out of 181 patients with a baseline LS < 40 kPa developed a decompensation versus 17 (29%) out of 58 with LS ≥ 40 kPa (P = 0.001). Factors independently associated with decompensation were Child-Turcotte-Pugh (CTP) class B versus A (hazard ratio [HR] 7.7; 95% CI 3.3-18.5; P < 0.0001), log-plasma HCV RNA load (HR 2.1; 95% CI 1.2-3.6; P = 0.01), hepatitis B virus coinfection (HR, 10.3; 95% CI, 2.1-50.4; P = 0.004) and baseline LS (HR 1.03; 95% CI 1.01-1.05; P = 0.02). Fifteen (6%, 95% CI: 3.5%-9.9%) patients died, 10 of them due to liver disease, and one underwent liver transplantation. CTP class B (HR 16.5; 95% CI 3.4-68.2; P < 0.0001) and previous exposure to HCV therapy (HR 7.4; 95% CI 1.7-32.4, P = 0.007) were independently associated with liver-related death; baseline LS (HR 1.03; 95% CI 0.98-1.07; P = 0.08) was of borderline significance. CONCLUSION: LS predicts the development of hepatic decompensations and liver-related mortality in HIV/HCV-coinfection with compensated cirrhosis and provides additional prognostic information to that provided by the CTP score.

Sustained virological response to pegylated interferon plus ribavirin leads to normalization of liver stiffness in hepatitis C virus-infected patients.

INTRODUCTION: Pegylated interferon plus ribavirin (Peg-IFN/RBV) therapy leads to improvements in liver stiffness measurements (LSM) in hepatitis C virus (HCV)-infected patients. However, the rate of LSM return to normal values in response to Peg-IFN/RBV is unclear. Thus, our aim was to assess the probability and factors associated with LSM normalization in HCV-infected patients receiving Peg-IFN/RBV. METHODS: This prospective observational longitudinal study included 160 HCV-infected patients, 111 (69%) with human immunodeficiency virus and receiving Peg-IFN/RBV, with baseline LSM ≥ 7kPa. The outcome variable was LSM normalization, i.e. a stable decrease in LSM below 7kPa after starting Peg-IFN/RBV. RESULTS: After starting Peg-IFN/RBV, 56 [35%, 95% confidence interval (95% CI): 28-42%] patients showed LSM normalization. The probability of LSM normalization was 21% (95% CI: 13.2-32.4%) at 12 months, and 51.3% (95% CI: 39.9-63.9%) at 24 months after Peg-INF/RBV initiation for individuals with sustained virological response (SVR), and 8.3% (95% CI: 4-16.6%) at 12 months and 11.3% (95% CI: 6-20.7%) at 24 months for those without SVR (p<0.001). For individuals with LSM ≥ 7kPa 24 weeks after the pre-planned end of treatment, LSM normalizations were only observed among those with SVR. Achievement of SVR [Hazard ratio (HR, 95% CI): 6.84 (3.39-13.81)] and lack of baseline cirrhosis [HR (95% CI): 4.17 (1.69-10)] were independently associated with LSM normalization after starting Peg-IFN/RBV. CONCLUSIONS: LSM normalizations during Peg-IFN/RBV treatment are more likely, and occur earlier among patients with SVR. In addition, LSM normalizations continue 24 weeks after the scheduled end of therapy, but only among individuals who reach SVR.

Prediction of response to pegylated interferon plus ribavirin in HIV/hepatitis C virus (HCV)-coinfected patients using HCV genotype, IL28B variations, and HCV-RNA load.

BACKGROUND & AIMS: This study aimed at developing a predictive algorithm based on interleukin 28B (IL28B) genotype, hepatitis C virus (HCV) genotype, and plasma HCV-RNA load, which could accurately allow us to define the probability of response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy in HIV/HCV-coinfected patients. METHODS: Five hundred and twenty-one treatment-naive HIV-infected patients, who initiated HCV therapy with Peg-IFN/RBV, were analysed in an on-treatment basis. Patients were categorized as unlikely responders, uncertain responders, and anticipated responders (<20%, 20-60%, and >60% probability to achieve SVR, respectively). RESULTS: HCV genotype, baseline HCV-RNA load, and IL28B genotype were confirmed as independent predictors of SVR in a logistic regression analysis. A stepwise algorithm based on these three variables was created based on 321 patients and evaluated in the remaining 200 patients. Unlikely responders included patients with genotype 1 or 4, HCV-RNA load ≥600,000IU/ml, and rs12979860 non-CC (rate of SVR: 17.3%). Anticipated responders were those with HCV genotype 2-3, patients harboring HCV genotype 4 and IL28B CC, as well as those who simultaneously bore HCV genotype 1, HCV-RNA load <600,000IU/ml, and IL28B CC (rate of SVR 74.1%, 77.8%, and 64.4%, respectively). The area under the receiver operating characteristic curve of the model was 0.77 (0.733-0.814). CONCLUSIONS: The combined use of IL28B genotype, HCV genotype, and HCV-RNA load enables to easily identify patients with a high and very low likelihood of SVR. HCV therapy could be deferred in the latter patients, until more effective options are available, at least if they do not show advanced liver fibrosis.

[Prevalence and risk factors of methicillin-resistant Staphylococcus aureus colonization among residents living in long-term care facilities in southern Spain]. / Prevalencia y factores asociados a la colonización por Staphylococcus aureus resistente a meticilina en centros de larga estancia en el sur de España.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) has become the most important problem related to multiresistant microorganisms in the health care system. Long-term-care facilities (LTCFs) are one of the main reservoirs of this microorganism. The objective of our study was to determine the prevalence and factors associated with MRSA colonization among subjects living in LTCFs in southern Spain. METHODS: During the period from 1st April 2009 to 30th June 2010, all subjects living in 17 LTCFs of our area were included in a cross-sectional study. Patients were screened by using nasal swabs and these were cultured in a chromogenic media. Suspected S. aureus colonies were identified by the latex agglutination test. Testing for antimicrobial identification and susceptibility was performed by an automated system. A logistic regression model was built, in which to be colonized by MRSA was the dependent variable, and covariates were entered if a difference with P<.2 was detected in the bivariate analysis. Residents were classified as MRSA carriers, methicillin-susceptible S. aureus carriers and non-carriers. RESULTS: Seven hundreds and forty-four subjects were included. There were 481 (65%) females. The median (Q1-Q3) age was 81 (74-86) years. Seventy-nine (10.6%) and 67 (9%) were colonized by MRSA and methicillin-susceptible S. aureus, respectively. Significant risk factors for MRSA carriers were recent antibiotic use, previous hospital admission in the last three months, a high comorbidity measured by Charlson index and a history of colonization by MRSA. CONCLUSIONS: The prevalence of MRSA colonization in the LTCFs of our area is similar to that described in others European countries. In our institutions, subjects with recent antibiotic use, a high comorbidity, a history of MRSA colonization and a hospital admission in the last three months are more susceptible to be colonized by MRSA.

Incidence of and risk factors for insulin resistance in treatment-naive HIV-infected patients 48 weeks after starting highly active antiretroviral therapy.

OBJECTIVES: to assess the incidence and risk factors for insulin resistance (IR) in a cohort of naive HIV-infected patients 48 weeks after starting highly active antiretroviral therapy (HAART). DESIGN: prospective, two centre, observational, cohort study. METHODS: One-hundred and thirty-seven patients who started HAART and maintained the same regimen for 48 weeks were included. IR was determined by the homeostasis model assessment (HOMA-IR) method. Individuals with a HOMA-IR value >3.8 were defined as insulin resistant. Independent associations with the development of IR at 48 weeks were evaluated. RESULTS: Seventeen (12.4%) individuals showed a HOMA-IR value >3.8 at baseline and were excluded for incidence analyses. Fifteen patients developed IR at 48 weeks of HAART, giving an incidence of 13%. Independent predictors of the development or IR were indinavir exposure (beta-coefficient 5.45, 95% confidence interval [CI] 1.30-22.8; P=0.02), and hepatitis C virus (HCV) antibody positivity (beta-coefficient 5.22, 95% CI 1.34-20.33; P=0.01). The appearance of IR was associated with a higher BMI (beta-coefficient 1.72 for each 2 kg/m2 increase, 95% CI 1.54-1.94; P=0.02) and with the presence of lipodystrophy at 48 weeks (beta-coefficient 5.59, 95% CI 1.45-21.5; P=0.01). CONCLUSIONS: HAART induces the development of IR in previously naive non-insulin-resistant HIV-infected individuals, with an incidence of 13% in the first year of therapy. Indinavir exposure, and HCV coinfection are associated with an increased risk of developing IR.

Antiretroviral therapy based on protease inhibitors as a protective factor against liver fibrosis progression in patients with chronic hepatitis C.

Cohort studies have shown that highly active antiretroviral therapy (HAART) can improve liver-related mortality in HIV/hepatitis C virus (HCV)-coinfected patients. A reduction in the accelerated liver fibrosis progression observed in HIV infection induced by HAART could explain these findings. A few studies have assessed the impact of HAART on liver fibrosis, but with contradictory results. Therefore, we evaluated the associations between the use of different antiretroviral drug classes and HAART combinations, and liver fibrosis in HIV-infected patients with chronic hepatitis C. Six hundred and eighty-three HIV/HCV-coinfected patients, who underwent a liver biopsy and who had not received anti-HCV treatment were included. Age at HCV infection < 23years (adjusted odds ratio [AOR] = 0.7, 95% confidence interval [95% CI] = 0.3-0.9, P = 0.05) and protease inhibitor (PI)-based HAART versus no use of HAART (AOR = 0.5, 95% CI = 0.3-0.9, P = 0.01) were negatively associated with advanced fibrosis (> or = F3). PI-based HAART versus no use of HAART (AOR = 0.4, 95% CI = 0.2-0.7, P = 0.001) was negatively associated with fibrosis progression rate > or = 0.2 units/year and independently of age at HCV infection and CD4+ T-cell counts. Fifteen (17%) patients treated only with PIs and zidovudine plus lamivudine showed > or = F3, compared with 65 (37%) patients without HAART (P = 0.001). Forty (31%) patients on PI and stavudine plus lamivudine showed > or = F3 (P = 0.3, when compared with patients with no HAART). The use of PI-based HAART in HIV/HCV-coinfected patients is associated with less severe fibrosis and slower progression of fibrosis. The nucleoside analogue backbone in a HAART regimen may influence this association.

The PNPLA3 Genetic Variant rs738409 Influences the Progression to Cirrhosis in HIV/Hepatitis C Virus Coinfected Patients.

Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3 gene on liver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymorphisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hundred and thirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determinations without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients who underwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 G allele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.12-3.50). Also, 21 (30.4%) of 69 G allele carriers versus 16 (15.7%) of 102 CC patients showed significant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.23-6.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95% confidence interval = 1.01-11.70). Our results strongly suggest that the rs738409 polymorphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients.

Effect of antiretroviral drugs on liver fibrosis in HIV-infected patients with chronic hepatitis C: harmful impact of nevirapine.

BACKGROUND: The hepatotoxicity of highly active antiretroviral therapy (HAART) could enhance liver fibrosis in HIV/Hepatitis C virus (HCV)-coinfected patients. Moreover, HAART-related immune restoration could lessen HCV-associated liver damage. The data on the effect of protease inhibitors (PI) on liver fibrosis are scant and contradictory. No information is available on the relationship between non-nucleoside analogue therapy and liver fibrosis in co-infected patients. OBJECTIVE: To investigate the associations between the use of different antiretroviral drugs and the liver fibrosis in patients with HIV and HCV infections. DESIGN: Cross-sectional study. METHODS: All HIV/HCV co-infected patients with an available liver biopsy and known or estimated duration of HCV infection seen at a Infectious Diseases Unit were included in the study. The fibrosis stage and the fibrosis progression rate were evaluated. RESULTS: The inclusion criteria were fulfilled by 152 patients. Age at HCV infection < 20 years [adjusted odds ratio (AOR), 0.39; 95% confidence interval (CI), 0.19-0.82], PI-based HAART (AOR, 0.39; 95% CI, 0.19-0.78) and nevirapine-based HAART (AOR, 2.56; 95% CI, 1.02-6.58) were associated with fibrosis stage >or= F3. The variables associated with fibrosis progression rate > 0.2 units/year were age at HCV infection < 20 years (AOR, 0.23; 95% CI, 0.1-0.52), CD4 cell counts < or = 250 x 10/l at liver biopsy (AOR, 2.8; 95% CI, 1.1-7.1), PI-based HAART (AOR, 0.39; 95% CI, 0.2-0.8) and nevirapine-based HAART (AOR, 3.82; 95% CI, 1.9-7.6). CONCLUSIONS: HAART regimens including nevirapine are associated with faster liver fibrosis progression in HIV-infected patients with chronic hepatitis C. In contrast, patients on PI as the backbone of potent antiretroviral therapy are more likely to show less liver fibrosis.

Gynaecomastia in HIV-infected men on highly active antiretroviral therapy: association with efavirenz and didanosine treatment.

BACKGROUND: Gynaecomastia has been described in HIV-infected men undergoing highly active antiretroviral therapy (HAART). However, there are insufficient data on the relationship between gynaecomastia and any specific antiretroviral drug and hormone abnormality. OBJECTIVE: To assess the frequency of gynaecomastia in HIV-infected men receiving HAART and its association with antiretroviral drugs and hormone abnormalities. METHODS: We carried out a prospective study of 1304 HIV-infected men undergoing HAART. In addition, we included a case (with gynaecomastia)-control (without gynaecomastia) analysis in the second part of this study. Cases and controls were matched according to age, HIV infection CDC clinical category, HCV infection, the date of study and the physician responsible for the patient. Patients bearing known causes of gynaecomastia were excluded. We analysed epidemiological, clinical, haematological and immunological characteristics and the use and duration of the antiretroviral therapy. In 13 cases and 13 controls a sexual hormone profile was carried out. RESULTS: A total of 30 (2.3%) HIV-infected men presented with gynaecomastia of unexplained cause. In 22 (73%) of these individuals, gynaecomastia completely resolved after a median time of 9 months (range: 5-22 months). The percentage of individuals who were receiving efavirenz and didanosine at the time of the study was higher among patients with gynaecomastia [57% vs 17% (P=0.004) and 50% vs 13% (P=0.003), respectively]. Plasma total testosterone, free testosterone index and bioavailable testosterone levels were lower in patients with gynaecomastia, whereas plasma free testosterone levels were not significantly different in either population. CONCLUSIONS: Gynaecomastia is not uncommon in HIV-infected men undergoing HAART and it is usually transient. Efavirenz and didanosine treatment are associated with the emergence of gynaecomastia. An underlying hypoandrogenism seems to contribute to the emergence of this disorder in these patients.

Pharmacokinetic interactions between efavirenz and rifampicin in HIV-infected patients with tuberculosis.

OBJECTIVE: To evaluate the pharmacokinetic interactions between efavirenz and rifampicin (rifampin) in patients with HIV infection and tuberculosis. DESIGN: Nonblind, randomised, pharmacokinetic study. PATIENTS: 24 patients (21 male, 3 female; mean age 37 years) with HIV infection and tuberculosis. INTERVENTIONS: Patients were randomised to one of the following treatments: group A (n = 16) received antituberculosis drugs without rifampicin, plus highly active antiretroviral therapy (HAART) including efavirenz 600 mg once daily, on days 1 to 7. Patients were then switched to rifampicin in bodyweight-adjusted fixed-dose combination plus HAART including efavirenz 600 mg once daily (group A-1; n = 8) or efavirenz 800 mg once daily (group A-2; n = 8). Group B (n = 8) received rifampicin in bodyweight-adjusted fixed-dose combination on days 1 to 7; on day 8, HAART including efavirenz 800 mg once daily was added. Blood samples were obtained on days 7 and 14. METHODS: Plasma concentrations of efavirenz and rifampicin were quantified by using validated high performance liquid chromatography assays, and pharmacokinetic parameter values were determined by noncompartmental methods. The differences between pharmacokinetic parameters on days 7 and 14 were used to assess interactions. RESULTS: There was a correlation between the pharmacokinetic parameters of efavirenz and the dose/kg administered. For efavirenz, mean (median) peak concentration, trough concentration and area under the concentration-time curve over the administration interval decreased 24% (24%), 25% (18%) and 22% (10%), respectively, in the presence of rifampicin. Large interpatient variability was observed, suggesting that plasma concentration monitoring of efavirenz may be advisable. Overall, the pharmacokinetics of efavirenz 800 mg plus rifampicin were similar to those of efavirenz 600 mg without rifampicin. The pharmacokinetics of rifampicin did not change substantially in the presence of efavirenz. Differences in patients' bodyweight appeared to cause further differences in exposure to efavirenz. Plasma concentrations of efavirenz in patients weighing <50 kg were similar to those previously described in HIV-infected patients without concomitant tuberculosis. However, plasma concentrations in patients weighing >or=50 kg were almost halved compared with those in patients weighing <50 kg. CONCLUSIONS: Although the minimal effective efavirenz plasma concentration that assures virological success is not currently known, it may be advisable to increase the dosage of efavirenz to 800 mg once daily when it is coadministered with rifampicin. Rifampicin can be used with efavirenz without dosage modification.

Frequency of visceral leishmaniasis relapses in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy.

There are contradictory data about whether highly active antiretroviral therapy (HAART) prevents visceral leishmaniasis (VL) relapses in human immunodeficiency virus type 1 (HIV-1)-infected patients. The aim of this study was to assess the frequency of VL relapses in individuals receiving HAART. Thirty-one patients who received HAART after developing VL were included in a retrospective cohort study. Ten of them received secondary chemoprophylaxis and the rest did not. Eight (38%) patients without secondary chemoprophylaxis showed a VL relapse. None of the seven subjects with VL relapses and 6 of 11 without recurrence (P = 0.038), in whom all scheduled data were available, showed an increase of more than 100 CD4+ cells/mm(3) during the follow-up. Patients with relapse showed higher levels of HIV RNA viral load at their last visit (P = 0.047). The frequency of VL relapses in patients receiving HAART is high. Relapses of VL are observed only in individuals with uncontrolled HIV replication and/or poor immunologic responses.

Low-density lipoprotein receptor genotyping enhances the predictive value of IL28B genotype in HIV/hepatitis C virus-coinfected patients.

OBJECTIVE: The aims of this study were to appraise the predictive value of variations in a single-nucleotide polymorphism (SNP) in the low-density lipoprotein receptor (LDLR) gene for sustained virological response (SVR) to pegylated interferon (Peg-IFN) and ribavirin (RBV), as well as to analyze the relationship between LDLR genotype and other predictors of SVR, particularly IL28B genotype, in patients coinfected with HIV and hepatitis C virus (HCV). METHODS: One hundred and eighty-four HIV/HCV-coinfected, treatment-naive patients with chronic HCV infection, who received Peg-IFN and RBV, were included. Variations in the SNP rs14158 and rs12979860 were tested by Taqman PCR assay. RESULTS: Twenty-eight (38%) patients with rs14158 TT/TC and 61 (55%) with CC (P = 0.028) achieved SVR. The rates of SVR in patients with rs14158 TT/TC and with CC harboring HCV 1-4 were 20 and 41% (P = 0.020), respectively, and, in those with HCV genotype 2-3, 75 and 84% (P = 0.513), respectively. Patients with rs14158 CC showed less commonly plasma HCV-RNA load at least 600000 IU/ml (57 vs. 71%, P = 0.047) and lower likelihood of relapse (13 vs. 30%, P = 0.023). In patients with HCV genotype 1-4, the rates of SVR according to the combination of IL28B/LDLR genotypes were: CC/CC = 69%; CC/non-CC: 30%; non-CC/CC: 25%; non-CC/non-CC: 14% (P < 0.001). CONCLUSION: Variations in rs14158 are associated with SVR to Peg-IFN and RBV in HIV/HCV-coinfected patients harboring HCV genotype 1-4. LDLR and IL28B genotypes seem to have a synergistic effect on SVR. The combined use of LDLR and IL28B genotypes in routine clinical practice could enhance the predictive value of IL28B genotype alone.

Prevalence and risk factors for abnormal liver stiffness in HIV-infected patients without viral hepatitis coinfection: role of didanosine.

BACKGROUND: Unexpected cases of severe liver disease in HIV-infected patients have been reported and an association with didanosine (ddI) has been suggested. Transient elastography (TE) might detect patients harbouring such a condition. Our objective was to search for the presence of abnormal liver stiffness (LS) in a cohort of HIV-infected patients without HBV or HCV coinfection and to assess the related factors. METHODS: A cross-sectional prospective study was conducted. LS was assessed by TE in 258 HIV-infected patients without HBV or HCV coinfection and with no evidence of acute hepatotoxicity or other origins of liver disease. LS values > or =7.2 kPa were considered abnormal. Multivariate analyses were performed to identify factors associated with abnormal LS. RESULTS: Abnormal LS was observed in 29 (11.2%) patients. A total of 18 (16.4%) patients previously treated with ddI and 11 (7.4%) of those who never received ddI had LS values > or =7.2 kPa (P=0.02). The prevalence of abnormal LS was higher in patients previously treated with abacavir than in those who had never received abacavir (15 [21.7%] versus 14 [7.4%]; P=0.001). After multivariate analyses, age (adjusted odds ratio [AOR] 1.05, 95% confidence interval [CI] 1.002-1.1; P=0.004) alcohol intake >50 g/day (AOR 7.2, 95% CI 2.6-19.7; P<0.0001), CD4(+) T-cell count <200 cells/ml (AOR 3.4, 95% CI 1.06-11.007; P=0.03), time on ddI treatment (AOR 1.31, 95% CI 1.12-1.52; P=0.001) and previous abacavir exposure (AOR 3.01, 95% CI 1.18-7.67; P=0.02) were independently associated with abnormal LS. CONCLUSIONS: The prevalence of abnormal LS in HIV-infected patients without HBV or HCV coinfection is substantial. Long-term exposure to ddI is a major cause of liver damage in these patients.

Changes in liver-related hospital admissions and hospital mortality among HIV-infected patients (1998 to 2005).

Liver-related disease has increased as a cause of hospitalization and in-hospital death in HIV-infected patients since the introduction of highly active antiretroviral therapy (HAART). Better clinical management of these diseases may contribute to decreasing their incidence. Admissions due to liver-related disease in HIV-infected patients in our institution increased from 2.9% in 1998-1999 to 11.3% in 2004-2005 (P = 0.001). In-hospital deaths due to this cause increased from 2.7% in 1998-1999 to 26% in 2002-2003 (P = 0.02), with a subsequent decrease to 22% in 2004-2005. Hospitalization of HIV-infected patients for liver-related disease continues to increase, whereas the rate of in-hospital deaths from this cause appears to have changed since 2003.

[History of the infectious disease specialty in Spain]. / Relato histórico de la infectología española.

This paper includes a brief summary of the clinical history of the diagnosis and treatment of infectious diseases in Spain. Firstly, the origins of a specialty arising from the need for specialists to attend to, in a practical and modern form, the different health problems of patients affected by infectious diseases, are described. Secondly, the appearance of AIDS, at the beginning of the 1980's, prompted the creation of specific units dedicated to the care of problems associated with human immunodeficiency virus (HIV) infection and the concomitant opportunistic infections arising from the immunodeficiency arising from the HIV infection. Thirdly, in the last decades and even today, nosocomial infections have appeared as an alarming problem, needing the presence of specialist physicians in this field. Finally, emigration and international travel require specialists in infectious diseases with specific expertise in international health, once more highlighting the importance of the specialty of Infectious Diseases.

Low-level liver enzyme elevations during HAART are not associated with liver fibrosis progression among HIV/HCV-coinfected patients.

OBJECTIVES: To assess the association between non-severe liver enzyme elevations (LEEs) during antiretroviral treatment and liver fibrosis in HIV/HCV-coinfected patients. METHODS: All co-infected patients from an Infectious Disease Unit who had received treatment with highly active antiretroviral therapy (HAART) for at least 12 months before undergoing a liver biopsy were included in the study. RESULTS: One-hundred and sixteen patients met the inclusion criteria of the study. Advanced liver fibrosis was observed in 32 (38%) of 84 patients who developed non-severe LEEs and in 11 (34%) of 32 subjects who developed severe (grade > or = 3) LEEs, (P = 0.7). Seven (6%) of 116 patients showed grade 3 or 4 LEEs for at least 30% of the follow-up. Advanced liver fibrosis was observed in five (71%) of these patients and in 38 (35%) of the 109 subjects who did not develop long-term severe LEEs (P = 0.05). Eight (10%) of 84 patients showed grade 2 LEEs for at least 30% of the follow-up. Advanced liver fibrosis was observed in 28 (37%) of 76 subjects who did not develop long-term grade 2 LEEs and in three (38%) of eight patients who developed them (P = 0.9). CONCLUSIONS: In HIV/HCV-coinfected patients, non-severe LEEs, whether persistent or not, are not associated with advanced liver fibrosis. On the other hand, long-term severe LEEs are associated with more severe liver fibrosis in this population.

Clinical progression of hepatitis C virus-related chronic liver disease in human immunodeficiency virus-infected patients undergoing highly active antiretroviral therapy.

UNLABELLED: Little is known about the natural history of liver disease in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected subjects under highly active antiretroviral therapy (HAART). The objectives of this study were to obtain information about the mortality, the incidence of hepatic decompensations, and the predictors thereof in this population. In a multicenter cohort study, the time to the first hepatic decompensation and the survival of 1,011 antiretroviral naïve, HIV/HCV-coinfected patients who started HAART and who were followed prospectively were analyzed. After a median (Q1-Q3) follow-up of 5.3 (2.9-7.1) years, 59(5.83%) patients developed a hepatic decompensation and 69 (6.82%) died, 30 (43%) of them because of liver disease. The factors independently associated [HR (95% CI)] with the occurrence of hepatic decompensations were age older than 33 years [2.11 (1.18-3.78)], female sex [2.11 (1.07-4.15)], Centers for Disease Control stage C [2.14 (1.24-3.70)], a diagnosis of cirrhosis at baseline [10.86 (6.02-19.6)], CD4 cell gain lower than 100/mm3 [4.10 (2.18-7.69)] and less than 60% of the follow-up with undetectable HIV viral load [5.23 (2.5-10.93)]. Older age [2.97 (1.18-7.50)], lack of HCV therapy [11.32 (1.44-89.05)], hepatitis D virus coinfection [16.15 (2.45-106.48)], a diagnosis of cirrhosis at recruitment [13.69 (5.55-34.48)], hepatic encephalopathy [62.5 (21.27-200)] and lower CD4 cell gain [3.63 (1.45-9.09)] were associated with mortality due to liver failure. CONCLUSION: End-stage liver disease is the primary cause of death in HIV/HCV-coinfected patients under HAART. Higher increase of CD4 cell counts, lack of markers of serious liver disease and therapy against HCV are factors associated with better hepatic outcome.

Influence of concomitant antiretroviral therapy on the rate of sustained virological response to pegylated interferon plus ribavirin in hepatitis C virus/HIV-coinfected patients.

OBJECTIVES: To investigate whether concomitant antiretroviral therapy (ART) is a predictor of sustained virological response (SVR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with pegylated interferon plus ribavirin. METHODS: Three hundred and ten HIV/HCV-coinfected patients on pegylated interferon plus ribavirin treatment, 258 of them with concurrent ART, were included in this retrospective multicentre study. The predictors of SVR were evaluated. RESULTS: SVR was shown by 114 (37%) subjects. HCV genotype 2 or 3, plasma HCV-RNA load lower than 600 000 IU/mL, an exposure to the therapy against HCV infection > or =80% of the planned dose and baseline CD4 cell counts higher than or equal to 300/mm(3) were predictors of SVR. Likewise, patients without ART and those receiving a combination including tenofovir or stavudine plus lamivudine plus a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) showed a higher SVR rate than the subjects who were on other ART strategies at baseline [44%, 44% and 29%, respectively; adjusted odd ratio (95% CI) for no ART = 1.96 (1.07-4.76), P = 0.025, and for ART including tenofovir or stavudine plus lamivudine plus a PI or a NNRTI = 2.08 (1.16-3.70), P = 0.014]. CONCLUSIONS: The ART strategy on starting therapy with pegylated interferon plus ribavirin is a predictor of SVR in HIV/HCV-coinfected patients. Subjects without ART and those receiving combinations of a PI or a NNRTI with a nucleos(t)ide backbone of tenofovir or stavudine plus lamivudine respond better than those who receive other regimens.