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1.
J Hepatol ; 80(6): 904-912, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38428641

ABSTRACT

BACKGROUND & AIMS: Infections by multidrug-resistant bacteria (MDRB) are an increasing healthcare problem worldwide. This study analyzes the incidence, burden, and risk factors associated with MDRB infections after liver transplant(ation) (LT). METHODS: This retrospective, multicenter cohort study included adult patients who underwent LT between January 2017 and January 2020. Risk factors related to pre-LT disease, surgical procedure, and postoperative stay were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of MDRB infections within the first 90 days after LT. RESULTS: We included 1,045 LT procedures (960 patients) performed at nine centers across Spain. The mean age of our cohort was 56.8 ± 9.3 years; 75.4% (n = 782) were male. Alcohol-related liver disease was the most prevalent underlying etiology (43.2.%, n = 451). Bacterial infections occurred in 432 patients (41.3%) who presented with a total of 679 episodes of infection (respiratory infections, 19.3%; urinary tract infections, 18.5%; bacteremia, 13.2% and cholangitis 11%, among others). MDRB were isolated in 227 LT cases (21.7%) (348 episodes). Enterococcus faecium (22.1%), Escherichia coli (18.4%), and Pseudomonas aeruginosa (15.2%) were the most frequently isolated microorganisms. In multivariate analysis, previous intensive care unit admission (0-3 months before LT), previous MDRB infections (0-3 months before LT), and an increasing number of packed red blood cell units transfused during surgery were identified as independent predictors of MDRB infections. Mortality at 30, 90, 180, and 365 days was significantly higher in patients with MDRB isolates. CONCLUSION: MDRB infections are highly prevalent after LT and have a significant impact on prognosis. Enterococcus faecium is the most frequently isolated multi-resistant microorganism. New pharmacological and surveillance strategies aimed at preventing MDRB infections after LT should be considered for patients with risk factors. IMPACT AND IMPLICATIONS: Multidrug-resistant bacterial infections have a deep impact on morbidity and mortality after liver transplantation. Strategies aimed at improving prophylaxis, early identification, and empirical treatment are paramount. Our study unveiled the prevalence and main risk factors associated with these infections, and demonstrated that gram-positive bacteria, particularly Enterococcus faecium, are frequent in this clinical scenario. These findings provide valuable insights for the development of prophylactic and empirical antibiotic treatment protocols after liver transplantation.


Subject(s)
Bacterial Infections , Drug Resistance, Multiple, Bacterial , Liver Transplantation , Humans , Liver Transplantation/adverse effects , Male , Middle Aged , Female , Risk Factors , Retrospective Studies , Prevalence , Bacterial Infections/epidemiology , Bacterial Infections/etiology , Spain/epidemiology , Postoperative Complications/epidemiology , Postoperative Complications/microbiology , Enterococcus faecium/isolation & purification , Aged , Incidence , Anti-Bacterial Agents/therapeutic use , Urinary Tract Infections/epidemiology , Urinary Tract Infections/microbiology , Urinary Tract Infections/etiology
2.
Liver Transpl ; 30(2): 170-181, 2024 02 01.
Article in English | MEDLINE | ID: mdl-37589505

ABSTRACT

The long-term (>5 y) outcomes following liver transplantation (LT) have not been extensively reported. The aim was to evaluate outcomes of LT recipients who have survived the first 5 years. A multicenter retrospective analysis of prospectively collected data from 3 high volume LT centers (Dallas-USA, Birmingham-UK, and Barcelona-Spain) was undertaken. All adult patients, who underwent LT since the inception of the program to December 31, 2010, and survived at least 5 years since their LT were included. Patient survival was the primary outcome. A total of 3682 patients who survived at least 5 years following LT (long-term survivors) were included. Overall, median age at LT was 52 years (IQR 44-58); 53.1% were males; and 84.6% were Caucasians. A total of 49.4% (n=1820) died during a follow-up period of 36,828 person-years (mean follow-up 10 y). A total of 80.2% (n=1460) of all deaths were premature deaths. Age-standardized all-cause mortality as compared to general population was 3 times higher for males and 5 times higher for females. On adjusted analysis, besides older recipients and older donors, predictors of long-term mortality were malignancy, cardiovascular disease, and dialysis. Implementation of strategies such as noninvasive cancer screening, minimizing immunosuppression, and intensive primary/secondary cardiovascular prevention could further improve survival.


Subject(s)
Cardiovascular Diseases , Liver Transplantation , Adult , Female , Humans , Male , Middle Aged , Cardiovascular Diseases/etiology , Immunosuppression Therapy , Liver Transplantation/adverse effects , Retrospective Studies , Spain/epidemiology , Treatment Outcome
3.
Liver Int ; 44(2): 279-285, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38100141

ABSTRACT

Recommended post-liver transplant (LT) prophylaxis in patients with hepatitis delta includes a nucleos(t)ide analogue (NA) and anti-hepatitis B immunoglobulin (HBIG) indefinitely. We analysed the use of HBIG in real-life clinical practice and its impact on HBV/HDV recurrence in 174 HDV-related LT patients from 10 Spanish liver transplant centres (1988-2018). Median post-LT follow-up was 7.8 (2.3-15.1) years and patient survival at 5 years was 90%. Most patients (97%) received HBIG in the immediate post-LT, but only 42% were on HBIG at the last control. Among those discontinuing HBIG, the median time on treatment was 18 (7-52) months. Post-LT HBsAg+ was detected in 16 (9%) patients and HBV-DNA in 12 (7%). Despite HBsAg positivity, HDV recurrence was reported only in three patients (1.7%), all of whom were not receiving NA and had discontinued HBIG. Our data suggest that a finite HBIG prophylaxis in HDV-LT is feasible, especially if high-barrier NAs are used.


Subject(s)
Liver Transplantation , Humans , Antiviral Agents/therapeutic use , Hepatitis B Surface Antigens , Treatment Outcome , Liver Cirrhosis/complications , Liver Cirrhosis/surgery , Liver Cirrhosis/drug therapy , Immunoglobulins/therapeutic use , Recurrence , Hepatitis B virus/genetics
4.
Ann Hepatol ; 29(5): 101515, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38851394

ABSTRACT

Frailty and sarcopenia are well-recognized factors related to worse outcomes in patients with cirrhosis, including liver transplant (LT) candidates. Implications of pre-LT functional and muscle deterioration also affect post-LT outcomes. Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have a lower survival rate, both before and after LT. There is a need to better identify those patients with ACLF who would benefit from LT. This review aims to present the available data about frailty and sarcopenia in patients with ACLF in the LT setting. An exhaustive review of the published literature was conducted. Data regarding frailty and sarcopenia in LT candidates with ACLF are scarce and heterogeneous. Studies evaluating frailty and sarcopenia in critically ill patients outside the liver literature are also presented in this review to enrich the knowledge of this field in expansion. Frailty and sarcopenia seem to contribute to worse outcomes in LT candidates with ACLF, both before and after LT. Sarcopenia evaluation may be the most prudent approach for those very sick patients. Skeletal muscle index assessed by computed tomography is recommended to evaluate sarcopenia. The role of muscle ultrasound and bioelectrical impedance analysis is to be determined. Frailty and sarcopenia are crucial factors to consider on a case-by-case basis in LT candidates with ACLF to improve patient outcomes.

5.
Clin Transplant ; 36(10): e14631, 2022 10.
Article in English | MEDLINE | ID: mdl-35257411

ABSTRACT

BACKGROUND: Antimicrobial prophylaxis is well-accepted in the liver transplant (LT) setting. Nevertheless, optimal regimens to prevent bacterial, viral, and fungal infections are not defined. OBJECTIVES: To identify the optimal antimicrobial prophylaxis to prevent post-LT bacterial, fungal, and cytomegalovirus (CMV) infections, to improve short-term outcomes, and to provide international expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. PROSPERO ID: CRD42021244976. RESULTS: Of 1853 studies screened, 34 were included for this review. Bacterial, CMV, and fungal antimicrobial prophylaxis were evaluated separately. Pneumocystis jiroveccii pneumonia (PJP) antimicrobial prophylaxis was analyzed separately from other fungal infections. Overall, eight randomized controlled trials, 21 comparative studies, and five observational noncomparative studies were included. CONCLUSIONS: Antimicrobial prophylaxis is recommended to prevent bacterial, CMV, and fungal infection to improve outcomes after LT. Universal antibiotic prophylaxis is recommended to prevent postoperative bacterial infections. The choice of antibiotics should be individualized and length of therapy should not exceed 24 hours (Quality of Evidence; Low | Grade of Recommendation; Strong). Both universal prophylaxis and preemptive therapy are strongly recommended for CMV prevention following LT. The choice of one or the other strategy will depend on individual program resources and experiences, as well as donor and recipient serostatus. (Quality of Evidence; Low | Grade of Recommendation; Strong). Antifungal prophylaxis is strongly recommended for LT recipients at high risk of developing invasive fungal infections. The drug of choice remains controversial. (Quality of Evidence; High | Grade of Recommendation; Strong). PJP prophylaxis is strongly recommended. Length of prophylaxis remains controversial. (Quality of Evidence; Very Low | Grade of Recommendation; Strong).


Subject(s)
Anti-Infective Agents , Communicable Diseases , Cytomegalovirus Infections , Liver Transplantation , Mycoses , Pneumonia, Pneumocystis , Humans , Liver Transplantation/adverse effects , Cytomegalovirus Infections/prevention & control , Antibiotic Prophylaxis , Anti-Infective Agents/therapeutic use , Postoperative Complications/prevention & control , Postoperative Complications/drug therapy , Communicable Diseases/drug therapy , Mycoses/drug therapy , Anti-Bacterial Agents/therapeutic use
6.
Infection ; 50(2): 371-380, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34331263

ABSTRACT

PURPOSE: We aim to assess risk factors related to early readmission in previous hospitalized patients with COVID-19. METHODS: We analyzed a retrospective cohort of patients with laboratory-confirmed COVID-19 admitted to Vall d'Hebron University Hospital, Barcelona, Spain. Early readmission was defined as the need for hospitalization within a period of 60 days after discharge. A descriptive analysis of the readmission was performed, including hospitalization outcome. We also performed a multivariate logistic regression to define risk factors for readmission RESULTS: A total of 629 patients were followed up during 60 days with a readmission cumulative incidence of 5.4% (34 out of 629) and an incidence rate of 0.034 person-years. Main reasons for readmission were respiratory worsening (13, 38.2%), decompensation of previous disease (12, 35.3%) or infectious complications (6, 17.6%). Median time to readmission was 12 days (interquartile range 7-33 days). Prior diagnosis of heart failure (OR 4.09; 95% CI 1.35-12.46; p = 0.013), length of stay during index admission greater than 13 days (OR 2.72; 95% CI 1.21-6.12; p = 0.015), treatment with corticosteroids (OR 2.39; 95% CI 1.01-5.70; p = 0.049) and developing pulmonary thromboembolism (OR 11.59; 95% CI 2.89-46.48; p = 0.001) were the risk factors statistically associated with early readmission. CONCLUSION: Readmission cumulative incidence was 5.4%. Those patients with prior diagnosis of heart failure, length of stay greater than 13 days, treated with corticosteroids or who developed pulmonary thromboembolism might benefit from close monitoring after being discharged.


Subject(s)
COVID-19 , COVID-19/epidemiology , Cohort Studies , Hospitalization , Humans , Incidence , Patient Readmission , Retrospective Studies , Risk Factors , SARS-CoV-2
7.
Ann Hepatol ; 27(3): 100687, 2022.
Article in English | MEDLINE | ID: mdl-35192963

ABSTRACT

INTRODUCTION AND OBJECTIVES: Spontaneous portosystemic shunts (SPSS) are a common cause of recurrent hepatic encephalopathy (HE). Shunt occlusion is an effective and safe procedure when performed in patients with cirrhosis and preserved liver function. We aimed to describe our experience with SPSS embolization after liver transplantation (LT). PATIENTS: We identified five patients who underwent SPSS embolization after LT. Clinical, biochemical and technical procedure data were collected. RESULTS: At presentation, all patients had developed graft cirrhosis and HE after LT. Median Model for End-stage Liver Disease (MELD) at embolization was 9 (range 7-12), median Child-Pugh was 8 (range 7-9). Splenorenal and mesocaval shunt were the most frequent types of SPSS found. Three patients have been completely free of HE. Of the two patients who had HE recurrence after embolization, one patient had two episodes of HE which was controlled well with medications. The other patient required three embolizations because of recurrent HE. Median follow-up was 4.4 years (range 1.0-5.0) and MELD score at last follow up was 13 (range 10-18) and median Child-Pugh score B, 7 points (range 5-12). CONCLUSIONS: SPSS can be considered as a cause of HE after LT. SPSS embolization is feasible and safe in LT recipients.


Subject(s)
End Stage Liver Disease , Hepatic Encephalopathy , Hypertension, Portal , Liver Transplantation , Portasystemic Shunt, Transjugular Intrahepatic , End Stage Liver Disease/diagnosis , End Stage Liver Disease/surgery , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/therapy , Humans , Hypertension, Portal/etiology , Liver Cirrhosis/complications , Liver Transplantation/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Severity of Illness Index
8.
Am J Transplant ; 21(9): 3148-3156, 2021 09.
Article in English | MEDLINE | ID: mdl-33749113

ABSTRACT

We evaluated whether indications for liver transplantation (LT) have changed among people with/without human immunodeficiency virus (HIV) infection and compared LT outcomes and trends by HIV serostatus. LT recipients (2008-2018) from the United Network for Organ Sharing and Organ Procurement and Transplantation Network (UNOS/OPTN) were identifed. Among 62 195 LT recipients, 352 (0.6%) were HIV-infected. The proportion of HIV-infected patients increased over time (P trend = .001), as did the number of transplant centers performing LT for HIV-infected recipients; average annual percentage change of 9.2% (p < .001). Nonviral causes became the leading indication in 2015 for HIV-uninfected and in 2018 for HIV-infected (P trend < .001). Three-year cumulative patient survival rates were 77.5%, for HIV-infected and 84.6%, for HIV-uninfected (p = .15). Over time, graft and patient survival rates improved for both HIV-infected and uninfected (p < .001). Among HCV-infected LT recipients, 3-year patient survival rates were 72.5% for HIV-infected and 81.8% for HIV-uninfected (p = .02). However, in a subanalysis restricted to 2014-2018, differences in graft and patient survival by HIV serostatus were no longer observed (3-year patient survival rates were 81.2% for HIV-infected and 86.4% for HIV-uninfected, p = .34). In conclusion, in the United States, nonviral liver disease is now the leading indication for LT in HIV-infected patients, and posttransplant outcomes have improved over time.


Subject(s)
HIV Infections , Liver Diseases , Liver Transplantation , Graft Survival , HIV , HIV Infections/complications , HIV Infections/epidemiology , Humans , Liver Diseases/surgery , Retrospective Studies , Treatment Outcome , United States/epidemiology
9.
J Hepatol ; 75(2): 275-283, 2021 08.
Article in English | MEDLINE | ID: mdl-33746085

ABSTRACT

BACKGROUND & AIMS: To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). METHODS: We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. RESULTS: One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. CONCLUSIONS: A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. LAY SUMMARY: Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable.


Subject(s)
Liver Cirrhosis, Alcoholic/therapy , Liver Transplantation/classification , Waiting Lists , Adult , Antiviral Agents/therapeutic use , Female , Humans , Liver Transplantation/methods , Liver Transplantation/statistics & numerical data , Male , Middle Aged , Spain
10.
Transpl Int ; 34(10): 1908-1913, 2021 10.
Article in English | MEDLINE | ID: mdl-34121244

ABSTRACT

Solid organ transplant recipients might be at greater risk for acquisition and mortality because of SARS-CoV-2. There are no data regarding SARS-CoV-2 seroprevalence among liver transplant (LT) recipients, and whether it is different from that of the general population or other immunosuppressed groups. We evaluated the prevalence of IgG SARS-CoV-2 antibodies among LT recipients to estimate the frequency of asymptomatic SARS-CoV-2 infection using serological assays in our outpatient clinic. We conducted a cross-sectional analysis from 10 May to 26 October 2020 of all adult (>18 years) LT recipients that underwent a routine laboratory test for the outpatient clinic follow-up at the Hospital Universitari Vall d'Hebron (Barcelona) in which we included serological testing for SARS-CoV-2. Nine out of 294 LT recipients (3.1%) tested positive for anti-SARS-CoV-2 IgG antibodies. Five of them (55.5%) had suffered clinically symptomatic SARS-CoV-2 infection confirmed by RT-PCR, four (44.4%) had presented compatible symptoms but without microbiological confirmation and only one patient (1/9, 11.1%) tested positive without any previous symptom. SARS-CoV-2 seroprevalence among LT recipients in an area highly affected by the pandemic is lower than in the general population in the same area. These results render the possibility of asymptomatic infection in LT recipients very unlikely.


Subject(s)
COVID-19 , Liver Transplantation , Adult , Antibodies, Viral , Cross-Sectional Studies , Humans , SARS-CoV-2 , Seroepidemiologic Studies
11.
Clin Transplant ; 32(7): e13303, 2018 07.
Article in English | MEDLINE | ID: mdl-29851150

ABSTRACT

BACKGROUND: Clearance of hepatitis C virus (HCV) under antiviral therapy, including direct-acting antivirals (DAAs), has been associated with higher risk of rejection. Whether patients who are not on immunosuppression (IS) during DAA therapy are at higher risk of rejection is unknown. METHODS: Four transplant recipients who were off IS and treated with DAA therapy were identified. RESULTS: All patients were genotype 1 infection and treated for 12 weeks with sofosbuvir/ledipasvir/ribavirin. At the time of DAA therapy, patients were off IS for a median of 9.5 years. Time from liver transplant (LT) to treatment was 12.9 years. Median baseline ALT was 70 IU/L, at follow-up week 12 was 18 IU/L. No signs of rejection were observed during DAA therapy or follow-up after the end of therapy. All 4 patients obtained sustained virological response. CONCLUSION: Direct-acting antivirals therapy in HCV patients off IS post-LT can be successfully undertaken without the need to restart IS.


Subject(s)
Antiviral Agents/therapeutic use , Graft Rejection/drug therapy , Hepacivirus/isolation & purification , Hepatitis C, Chronic/surgery , Liver Transplantation/adverse effects , Postoperative Complications/drug therapy , Aged , Drug Therapy, Combination , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Rejection/pathology , Graft Survival , Humans , Immunosuppression Therapy , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/pathology , Retrospective Studies , Risk Factors , Survival Rate , Sustained Virologic Response , Transplant Recipients , Treatment Outcome
12.
Transpl Infect Dis ; 20(1)2018 Feb.
Article in English | MEDLINE | ID: mdl-29125670

ABSTRACT

The shortage of livers has led most transplant centers to use extended criteria donors. Hepatitis C virus (HCV) RNA-positive donor organs are typically not given to patients who have cleared HCV. A 64-year-old male with chronic hepatitis C, genotype 1b was listed for LT with hepatocellular carcinoma. While on the waiting list, the patient was treated with sofosbuvir, ledipasvir, and ribavirin and achieved an HCV RNA <15 IU/mL by week 10. At week 18 of a planned 24-week treatment course, the patient underwent deceased-donor LT and received an organ from an anti-HCV-positive donor. Treatment was stopped at LT. At week 3 post LT, HCV RNA was detectable and revealed a genotype 3 HCV infection, compatible with transplantation of an organ with established infection. With retreatment with sofosbuvir, daclatasvir, and ribavirin for 12 weeks, the patient achieved a sustained virologic response. This report highlights how antiviral therapies can be used to optimize the outcomes of HCV-infected transplant patients.


Subject(s)
Hepacivirus/genetics , Liver Transplantation , Liver/virology , RNA, Viral/drug effects , Antiviral Agents/therapeutic use , Benzimidazoles/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/virology , Drug Therapy, Combination , Fluorenes/therapeutic use , Genotype , Hepacivirus/drug effects , Hepatitis C/drug therapy , Hepatitis C/virology , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , RNA, Viral/blood , Ribavirin/therapeutic use , Sofosbuvir/therapeutic use , Sustained Virologic Response , Tissue Donors , Transplant Recipients , Viral Load/drug effects
16.
Ann Hepatol ; 16(1): 86-93, 2017.
Article in English | MEDLINE | ID: mdl-28051797

ABSTRACT

 Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. MATERIAL AND METHODS: We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program. RESULTS: Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion. CONCLUSION: The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.


Subject(s)
Antiviral Agents/administration & dosage , Coinfection , End Stage Liver Disease/surgery , HIV Infections/virology , Hepacivirus/drug effects , Hepatitis C/drug therapy , Imidazoles/administration & dosage , Liver Cirrhosis/drug therapy , Liver Transplantation/adverse effects , Sofosbuvir/administration & dosage , Virus Activation , Aged , Aged, 80 and over , Antiviral Agents/adverse effects , Carbamates , Compassionate Use Trials , Drug Administration Schedule , Drug Therapy, Combination , End Stage Liver Disease/diagnosis , End Stage Liver Disease/virology , Female , HIV Infections/diagnosis , Hepacivirus/genetics , Hepacivirus/pathogenicity , Hepatitis C/diagnosis , Hepatitis C/virology , Humans , Imidazoles/adverse effects , Immunosuppressive Agents/administration & dosage , Liver Cirrhosis/diagnosis , Liver Cirrhosis/virology , Male , Middle Aged , Pyrrolidines , RNA, Viral/genetics , Recurrence , Retrospective Studies , Sofosbuvir/adverse effects , Time Factors , Treatment Outcome , Valine/analogs & derivatives , Viral Load
17.
Clin Transplant ; 30(9): 1140-5, 2016 09.
Article in English | MEDLINE | ID: mdl-27411037

ABSTRACT

BACKGROUND: Human immunodeficiency virus (HIV)-infected liver transplant (LT) recipients have higher risk of graft loss than HIV-uninfected recipients. As the original donor risk index excluded HIV-positive patients, donor factors associated with graft loss in HIV-positive recipients are unknown. METHODS: Identifying all HIV-positive patients in the Scientific Registry of Transplant Recipients, supplemented by all HIV-infected patients in the solid organ transplantation in HIV: Multi-Site Study (HIV-TR), we evaluated donor factors associated with graft loss among HIV-positive recipients transplanted between March 2002 and August 2012. RESULTS: A total of 249 HIV-positive LT recipients were followed for median 2.4 (interquartile range [IQR]: 0.8-4.9) years. In univariate analysis, donor diabetes (HR=2.09; P=.002) and donor hypertension (HR=1.43; P=.048) were significantly associated with graft loss, and African-American (AA) recipient:non-AA donor race mismatch (HR=1.60; P=.07), other cause of donor death compared to trauma (HR=2.02; P=.09), and donor age 30 years or older (HR=1.53; P=.05) were of borderline significance. In multivariate analysis, donor diabetes (HR=2.12; 95% CI: 1.33-3.38; P=.002) was the only significant predictor of graft loss. CONCLUSION: In HIV-positive LT recipients, risk of graft loss is strongly influenced by donor diabetes. This information may be useful to transplant physicians seeking to optimize overall graft survival in their HIV-positive LT recipients.


Subject(s)
Graft Rejection/etiology , HIV Seropositivity/complications , HIV , Liver Transplantation , Risk Assessment , Tissue Donors , Transplant Recipients , Female , Graft Rejection/epidemiology , Graft Survival , HIV Seropositivity/epidemiology , Humans , Male , Middle Aged , Risk Factors , United States/epidemiology
18.
Clin Infect Dis ; 60(1): 108-16, 2015 Jan 01.
Article in English | MEDLINE | ID: mdl-25228702

ABSTRACT

Complications of cirrhosis due to hepatitis C virus (HCV) are increasing, and liver transplantation (LT) is the most effective treatment for those with liver decompensation or small hepatocellular carcinoma. However, for patients with human immunodeficiency virus (HIV) coinfection, barriers to LT exist. This is related to the poorer survival rates post-LT (55% at 5 years) and, up until this year, the limited options for treating those coinfected LT recipients with progressive recurrent HCV disease, the commonest reason for reduced survival. The newly approved antiviral therapies sofosbuvir and simeprevir, with significantly improved efficacy and markedly better safety and tolerability in HIV and transplant patients, offer the opportunity to transform the outcomes of HIV/HCV-coinfected patients with liver complications. Additional new therapies, anticipated within the year, are expected to further simplify the management of coinfected patients in the transplant setting.


Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Liver Transplantation , Drug Therapy, Combination/methods , Drug Therapy, Combination/trends , Heterocyclic Compounds, 3-Ring/therapeutic use , Humans , Simeprevir , Sofosbuvir , Sulfonamides/therapeutic use , Uridine Monophosphate/analogs & derivatives , Uridine Monophosphate/therapeutic use
19.
Intervirology ; 58(3): 160-5, 2015.
Article in English | MEDLINE | ID: mdl-26022419

ABSTRACT

AIMS: To investigate the influence of IL28B polymorphism in occult hepatitis B infection (OBI) and whether IL28B genetic variants are associated with hepatitis B virus (HBV)-specific T-cell responses. PATIENTS AND METHODS: The rs12979860 IL28B genotype was determined in 34 OBI blood donors, 22 spontaneous HBV resolvers, 36 inactive HBV carriers and 25 seronegative donors. T-cell responses to HBV recombinant proteins were assessed by interferon-γ enzyme-linked immunospot assay. RESULTS: The frequency of the IL28B CC genotype among OBI patients was similar to that of inactive carriers [41 vs. 39%, respectively, p = 0.961; odds ratio (OR) = 1.10; 95% confidence interval (CI) = 0.42-2.86; p = 0.845]. The IL28B CC genotype was found more frequently in spontaneous resolvers, although the differences were not significant (45 vs. 39%, spontaneous resolvers and inactive carriers, respectively; p = 0.828; OR = 1.31; 95% CI = 0.45-3.83; p = 0.622). HBV-specific T-cell responses were detected in OBIs, and significantly stronger T-cell responses towards hepatitis B envelope antigen were observed in those with the IL28B CC genotype. In spontaneous resolvers and inactive carriers, IL28B CC did not correlate with the magnitude of T-cell responses. CONCLUSIONS: In OBI donors, IL28B CC correlates with the intensity of HBV-specific T-cell responses. In this study, IL28B CC is not statistically associated with OBI or with HBV clearance, but a larger number of cases is needed before completely ruling out its role in HBV infection.


Subject(s)
Hepatitis B/genetics , Hepatitis B/immunology , Interleukins/genetics , Polymorphism, Single Nucleotide , T-Lymphocytes/immunology , Adult , Blood Donors , Enzyme-Linked Immunospot Assay , Female , Genotype , Hepatitis B/virology , Hepatitis B virus , Humans , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Interferons , Interleukins/immunology , Male , Middle Aged , Spain
20.
Liver Transpl ; 20(7): 856-63, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24723503

ABSTRACT

Spontaneous bacterial peritonitis (SBP) in liver transplantation (LT) recipients who progress to cirrhosis has received little attention. We investigated the adequacy of empirical treatment with third-generation cephalosporins for SBP in this population and the impact of transplantation on the evolution of the infection. We performed a cohort study with 138 SBP episodes: 19 in LT patients and 119 in non-LT patients. The etiology of SBP was identified for 73.7% of the episodes in LT patients and for 38.7% of the episodes in non-LT patients (P = 0.004). The main microorganisms in recipients were Escherichia coli (35.7%) and Streptococcus pneumoniae (21.4%). The etiologies did not differ in non-LT patients. The cephalosporin sensitivity was similar in the 2 groups (85.7% versus 78.4%, P = 0.7). LT recipients developed renal failure (57.9% versus 25.2%, P = 0.004) and encephalopathy (42.1% versus 22%, P = 0.08) more often than non-LT patients, and the mortality rates during episodes (52.6% versus 13.4%, P < 0.001) and at 6 months (70.6% versus 34.7%, P = 0.005) were higher. According to a multivariate analysis, the mortality-associated risk factors at diagnosis were a Model for End-Stage Liver Disease (MELD) score > 18 odds ratio (OR) = 6.1 and being an LT recipient (OR = 4.45). At 6 months, the risk factors for mortality were a MELD score > 18 (OR = 3.08), being an LT recipient (OR = 3.47), a known etiology (OR = 2.08), and the presence of hepatocellular carcinoma (OR = 3.73).


Subject(s)
Carcinoma, Hepatocellular/surgery , End Stage Liver Disease/complications , End Stage Liver Disease/surgery , Liver Neoplasms/surgery , Liver Transplantation/adverse effects , Peritonitis/microbiology , Adult , Aged , Carcinoma, Hepatocellular/microbiology , Cephalosporins/pharmacology , Cohort Studies , Escherichia coli , Female , Hepatic Encephalopathy , Humans , Liver Neoplasms/microbiology , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Peritonitis/etiology , Postoperative Period , Renal Insufficiency , Risk Factors , Streptococcus pneumoniae
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