Filipe S. Cardoso

Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure

Hyperammonemia has been associated with intracranial hypertension and mortality in patients with acute liver failure (ALF). We evaluated the effect of renal replacement therapy (RRT) on serum ammonia level and outcomes in ALF. This was a multicenter cohort study of consecutive ALF patients from the United States ALF Study Group registry between January 1998 and December 2016. First, we studied the association of ammonia with hepatic encephalopathy (HE) and 21‐day transplant‐free survival (TFS; n = 1,186). Second, we studied the effect of RRT on ammonia for the first 3 days post study admission (n = 340) and on 21‐day TFS (n = 1,186). Higher admission (n = 1,186) median ammonia level was associated with grade 3‐4 HE (116 vs. 83 μmol/L) and mortality at day 21 attributed to neurological (181 vs. 90 μmol/L) and all causes (114 vs. 83 μmol/L; P < 0.001 for all). Among 340 patients with serial ammonia levels, 61 (18%) were on continuous RRT (CRRT), 59 (17%) were on intermittent RRT (IRRT), and 220 (65%) received no RRT for the first 2 days. From days 1 to 3, median ammonia decreased by 38%, 23%, and 19% with CRRT, IRRT, and no RRT, respectively. Comparing to no RRT use, whereas ammonia reduction with CRRT was significant (P = 0.007), with IRRT it was not (P = 0.75). After adjusting for year of enrollment, age, etiology, and disease severity, whereas CRRT (odds ratio [OR], 0.47 [95% confidence interval {CI}, 0.26‐0.82]) was associated with reduction in 21‐day transplant‐free all‐cause mortality, IRRT (OR, 1.68 [95% CI, 1.04‐2.72]) was associated with an increase. Conclusion: In a large cohort of ALF patients, hyperammonemia was associated with high‐grade HE and worse 21‐day TFS. CRRT was associated with a reduction in serum ammonia level and improvement of 21‐day TFS. (Hepatology 2018;67:711‐720).

Incidence and outcomes of acute kidney injury following orthotopic lung transplantation: a population-based cohort study

BACKGROUND Acute kidney injury (AKI) is a serious complication following lung transplantation (LTx). We aimed to describe the incidence and outcomes associated with AKI following LTx. METHODS A retrospective population-based cohort study of all adult recipients of LTx at the University of Alberta between 1990 and 2011. The primary outcome was AKI, defined and classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, in the first 7 post-operative days. Secondary outcomes included risk factors, utilization of renal replacement therapy (RRT), occurrence of post-operative complications, mortality and kidney recovery. RESULTS Of 445 LTx recipients included, AKI occurred in 306 (68.8%), with severity classified as Stage I in 38.9% (n = 173), Stage II in 17.5% (n = 78) and Stage III in 12.4% (n = 55). RRT was received by 36 (8.1%). Factors associated with AKI included longer duration of cardiopulmonary bypass [per minute, odds ratio (OR) 1.003; 95% confidence interval (CI), 1.001-1.006; P = 0.02], and mechanical ventilation [per hour (log-transformed), OR 5.30; 95% CI, 3.04-9.24; P < 0.001], and use of cyclosporine (OR 2.03; 95% CI, 1.13-3.64; P = 0.02). In-hospital and 1-year mortality were significantly higher in those with AKI compared with no AKI (7.2 versus 0%; adjusted P = 0.001; 14.4 versus 5.0%; adjusted P = 0.02, respectively). At 3 months, those with AKI had greater sustained loss of kidney function compared with no AKI [estimated glomerular filtration rate, mean (SD): 68.9 (25.7) versus 75.3 (22.1) mL/min/1.73 m(2), P = 0.01]. CONCLUSIONS By the KDIGO definition, AKI occurred in two-thirds of patients following LTx. AKI portended greater risk of death and loss of kidney function.

Association between transient acute kidney injury and morbidity and mortality after lung transplantation: a retrospective cohort study.

PURPOSE Acute kidney injury (AKI) is a common occurrence after lung transplantation (LTx). Whether transient AKI or early recovery is associated with improved outcome is uncertain. Our aim was to describe the incidence, factors, and outcomes associated with transient AKI after LTx. MATERIALS AND METHODS We performed a retrospective cohort study of all adult recipients of LTx at the University of Alberta between 1990 and 2011. Our primary outcome transient AKI was defined as return of serum creatinine below Kidney Disease-Improving Global Outcome AKI stage I within 7days after LTx. Secondary outcomes included occurrence of postoperative complications, mortality, and long-term kidney function. RESULTS Of 445 LTx patients enrolled, AKI occurred in 306 (68.8%) within the first week after LTx. Of these, transient AKI (or early recovery) occurred in 157 (51.3%). Transient AKI was associated with fewer complications including tracheostomy (17.2% vs 38.3%; P<.001), reintubation (16.4% vs 41.9%; P<.001), decreased duration of mechanical ventilation (median [interquartile range], 69 [41-142] vs 189 [63-403] hours; P<.001), and lower rates of chronic kidney disease at 3 months (28.5% vs 51.1%, P<.001) and 1 year (49.6% vs 66.7%, P=.01) compared with persistent AKI. Factors independently associated with persistent AKI were higher body mass index (per unit; odds ratio [OR], 0.91; 95% confidence interval, 0.85-0.98; P=.01), cyclosporine use (OR, 0.29; 0.12-0.67; P=.01), longer duration of mechanical ventilation (per hour [log transformed]; OR, 0.42; 0.21-0.81; P=.01), and AKI stages II to III (OR, 0.16; 0.08-0.29; P<.001). Persistent AKI was associated with higher adjusted hazard of death (hazard ratio, 1.77 [1.08-2.93]; P=.02) when compared with transient AKI (1.44 [0.93-2.19], P=.09) and no AKI (reference category), respectively. CONCLUSIONS Transient AKI after LTx is associated with fewer complications and improved survival. Among survivors, persistent AKI portends an increased risk for long-term chronic kidney disease.

Clinical Impact of Portal Vein Thrombosis Prior to Liver Transplantation: A Retrospective Cohort Study

BACKGROUND The prevalence of two functional polymorphisms (rs1127354 and rs7270101) of the inosine triphosphatase (ITPA) gene associated with ribavirin-induced hemolytic anemia (RIHA) during antiviral therapy for hepatitis C virus (HCV) infection varies by ethnicity. In Mexico, the distribution of these polymorphisms among Native Amerindians (NA) and admixed population (Mestizos) is unknown. This study aimed to determine the prevalence of the ITPA polymorphisms among healthy NA and Mestizos, as well as in HCV patients from West Mexico. MATERIAL AND METHODS In a cross-sectional study, 600 unrelated subjects (322 Mestizos, 100 NA, and 178 treatment-naïve, HCV-infected Mestizos patients) were enrolled. A medical history was registered. ITPA genotype was determined by Real-Time PCR. Fst-values and genetic relatedness between study and reference populations were assessed. RESULTS The frequency of the risk genotypes rs1127354CC and rs7270101AA was higher among NA (98-100%) than in Mestizos (87-92.9%), (p < 0.05). The NA presented the highest prevalence of the rs1127354CC genotype reported worldwide. The Fst-values revealed a genetic relatedness among Mexican NA, South Americans and African populations (p > 0.05). The frequency of the predicted risk for RIHA was higher among NA (98%) than in Mestizos (80.5%) and HCV-infected patients (81.5%) (p < 0 .01). The CC/AA alleles were associated with lower values of total bilirubin, aspartate/alanine aminotransferases, and aspartate-to-plate-let-ratio-index score among HCV-patients. CONCLUSION A high prevalence of the ITPA polymorphisms associated with RIHA was found in Mexican NA. These polymorphisms could be a useful tool for evaluating potential adverse effects and the risk or benefit of antiviral therapy in Mexicans and other admixed populations.INTRODUCTION To identify the impact of portal vein thrombosis (PVT) and associated medical and surgical factors on outcomes post liver transplant (LT). MATERIAL AND METHODS Two analyses were performed. Analysis One: cohort study of 505 consecutive patients who underwent LT (Alberta) between 01/2002-12/2012. PVT was identified in 61 (14%) patients. Analysis Two: cohort study of 144 consecutive PVT patients from two sites (Alberta and London) during the same period. Cox multivariable survival analysis was used to identify independent associations with post-LT mortality. RESULTS In Analysis One (Alberta), PVT was not associated with post-LT mortality (log rank p = 0.99). On adjusted analysis, complete/occlusive PVT was associated with increased mortality (Hazard Ratio (HR) 8.4, p < 0.001). In Analysis Two (Alberta and London), complete/occlusive PVT was associated with increased mortality only on unadjusted analysis (HR 3.7, p = 0.02). On adjusted analysis, Hepatitis C (HR 2.1, p = 0.03) and post-LT portal vein re-occlusion (HR 3.2, p = 0.01) were independently associated with increased mortality. CONCLUSION Well-selected LT patients who had PVT prior to LT had similar post-LT outcomes to non-PVT LT recipients. Subgroups of PVT patients who did worse post-LT (complete/occlusive thrombosis pre-LT, Hepatitis C or post-LT portal vein re-occlusion) warrant closer evaluation in listing and management post-LT.

Clinical and microbiological characteristics associated with mortality in spontaneous bacterial peritonitis: a multicenter cohort study.

Objectives Spontaneous bacterial peritonitis (SBP) is a prevalent and high mortality complication of cirrhosis. We aimed to describe these patients’ clinical and microbiological characteristics and evaluate their impact on outcomes. Methods This was a retrospective cohort study including 139 consecutive patients with positive culture SBP from three Portuguese centers diagnosed between 2009 and 2014. Multivariate logistic regression was used to study associations with 30-day mortality. Results The mean age of the patients was 62 years and 81% of patients were men. The mean model for end-stage liver disease score was 19. Hepatic encephalopathy, hepatorenal syndrome, and variceal bleeding developed in 47, 30, and 21% of patients, respectively. Gram-positive bacteria were isolated in the ascitic fluid of 42% of patients. Resistance to quinolones and multiresistance were found in 33 and 17% of patients, respectively. C-reactive protein level (adjusted odds ratio, 1.16 per 1 mg/l increment) and development of hepatorenal syndrome (adjusted odds ratio, 2.86) were associated independently with 30-day mortality (model’s area under the curve, 0.78). Conclusion In this cohort, SBP portended high early mortality. Gram-positive bacteria, bacteria resistant to quinolones, and multiresistant bacteria were identified in considerable proportions of patients. In the setting of the high early mortality and changing microbiological profile, SBP management strategies need to be improved.

Futility of care in patients with acute‐on‐chronic liver failure

In their article on the clinical course of acute-onchronic liver failure (ACLF), Gustot et al. proposed that organ support in the intensive care unit (ICU) should be discontinued for patients with four or more organ failures or Chronic Liver Failure Consortium (CLIF-C) ACLF score >64 at days 3-7 postinclusion, in the absence of liver transplantation, due to futility. In our ICU, 50 consecutive patients with ACLF were admitted between April 2013 and March 2016; 40 (80%) were male, and median (interquartile range) age was 59 (50-63) years. The precipitant event of ACLF was infection in 32 (64%) patients. Median (interquartile range) Model for End-Stage Liver Disease score at ICU admission was 29 (22-32). ACLF grade 3 was present in 23 (46%) patients at days 3-7 post–ICU admission, with a median (interquartile range) CLIF-C ACLF score of 55 (48-68). All-cause death occurred in 29 (58%) and 32 (64%) patients at days 28 and 90 post–ICU admission, respectively (Fig. 1). Liver transplantation was performed in 13 (26%) patients during follow-up (3 of these patients died within 90 days post–ICU admission). The number of organ failures at days 3-7 post ICU admission was associated with 28-day mortality with an odds ratio of 2.7 (95% confidence interval 1.5-4.8, P 5 0.001). Among 11 patients with four or more organ failures at days 3-7 post–ICU admission, without liver transplantation, 1 (9%) was alive at day 90 post–ICU admission (0% in Gustot et al.) (Table 1). Nevertheless, all 7 patients with five or more organ failures at days 3-7 post–ICU admission were dead at day 28 post–ICU admission. Median CLIF-C ACLF score at days 3-7 post– ICU admission was greater among nonsurvivors at day 28 post–ICU admission (62 versus 46, P < 0.001). CLIF-C ACLF score at days 3-7 post–ICU admission predicted 28-day mortality with an area under the curve of 0.79 (95% confidence interval 0.66-0.92). Among 14 patients with a CLIF-C ACLF score >64 at days 3-7 post–ICU admission, without liver FIG. 1. Overall cumulative survival following intensive care unit admission for patients with acute-on-chronic liver failure at Curry Cabral Hospital, Lisbon, Portugal (April 2013-March 2016).

HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death

BACKGROUND & AIMS: Acute liver failure (ALF) caused by hepatitis B virus (HBV) infection can occur after immunosuppressive treatment and be fatal, although it might be preventable. We aimed to characterize the causes, clinical course, and short‐term outcomes of HBV‐associated ALF after immune‐suppressive therapy, compared with patients with HBV‐associated ALF without immunosuppression (control subjects). METHODS: We performed a retrospective multicenter study of 156 consecutive patients diagnosed with HBV‐associated ALF (22 with a solid or blood malignancy) enrolled in the Acute Liver Failure Study Group registry from January 1998 through April 2015. We collected data on results of serologic and hepatic biochemistry analyses, grade of hepatic encephalopathy, Model for End‐Stage Liver Disease score, and Kings College criteria. We also collected data on clinical features, medical therapies, and complications in the first 7 days following study enrollment. Logistic regression was used to identify factors associated with transplant‐free survival at 21 days in HBV‐associated ALF (the primary outcome). RESULTS: Among patients with HBV‐associated ALF, 28 cases (18%) occurred after immunosuppressive therapy (15 patients received systemic corticosteroids and 21 received chemotherapy); and 128 cases did not (control subjects, 82%). Significantly greater proportions of patients with HBV‐associated ALF after immunosuppression were nonwhite persons, and had anemia or thrombocytopenia than controls (P < .02 for all). The serologic profile of HBV infection, severity of liver failure (based on MELD score), and complications (hepatic encephalopathy or need for mechanical ventilation, vasopressors, or renal replacement therapy) were similar between the groups (P > .17 for all). Factors associated with 21 day transplant‐free survival were increased MELD score (odds ratio ˜OR, 0.894 (95% confidence interval 0.842‐0.949 per increment), requirement for mechanical ventilation (OR 0.111(0.041‐0.300), and immunosuppressive therapy (OR 0.274(0.082‐0.923)). CONCLUSIONS: Within a cohort study of patients with HBV‐associated ALF, 18% had received immunosuppressive therapy. Significantly smaller proportions of patients with HBV‐associated ALF after immunosuppression survive beyond 21 days than patients with HBV‐associated ALF who did not receive immunosuppression. Patients undergoing chemotherapy should be screened for HBV infection and given appropriate antiviral therapies to reduce preventable mortality.

Can Red Cell Distribution Width Be Used as a Marker of Crohn's Disease Activity?

Introduction Recently, it has been suggested an association between red cell distribution width (RDW) and Crohns disease activity index (CDAI), but its use is not yet performed in daily clinical practice. Objectives To determine whether RDW can be used as a marker of Crohns disease (CD) activity. Methods This was a cross-sectional study including patients with CD, observed consecutively in an outpatient setting between January 1st and September 30th 2013. Blood cell indices, erythrocyte sedimentation rate (ESR), and C-reactive protein were measured. CD activity was determined by CDAI (active disease if CDAI ≥ 150). Associations were analyzed using logistic regression (SPSS version 20). Results 119 patients (56% female) were included in the study with a mean age of 47 years (SD 15.2). Twenty patients (17%) had active disease. The median RDW was 14.0 (13–15). There was an association between RDW and disease activity (p = 0.044). After adjustment for age and gender, this association remained consistent (OR 1.20, 95% CI 1.03–1.39, p = 0.016). It was also found that the association between RDW and disease activity was independent of hemoglobin and ESR (OR 1.36, 95% CI 1.08–1.72, p = 0.01) and of biologic therapy (OR 1.19, 95% CI 1.03–1.37, p = 0.017). A RDW cutoff of 16% had a specificity and negative predictive value for CDAI ≥ 150 of 88% and 86%, respectively. Conclusion In this study, RDW proved to be an independent and relatively specific marker of CD activity. These results may contribute to the implementation of this simple parameter, in clinical practice, aiming to help therapeutic decisions.

Respiratory Complications Before and After Liver Transplant

Respiratory complications before and after liver transplant are common, diverse, and potentially have a negative impact on patient outcomes. In this review, we discuss the most frequent respiratory conditions that patients may develop in the perioperative period. Their prevention and/or treatment may help to maximize the benefit these patients may derive from liver transplant. This review examines diagnostic and therapeutic approaches to these complications for hepatologists, surgeons, and critical care physicians.

Epidemiology of Acute Liver Failure from a Regional Liver Transplant Center in Portugal

Background and Aims: Acute liver failure (ALF) is a rare disease with potentially high mortality rates. We aimed to study the recent epidemiology of ALF in one of the Portuguese liver transplant (LT) regions. Methods: We assessed a retrospective cohort including 34 consecutive patients with ALF admitted to the intensive care unit (ICU) of Curry Cabral Hospital (Lisbon, Portugal) between October 2013 and December 2016. Results: The median age (IQR) was 49 (31–67) years, and 21 (62%) of the cohort were female. Non-paracetamol etiologies were found in 29 patients (85%). On ICU admission, grade 3–4 hepatic encephalopathy developed in 10 patients (29%); invasive mechanical ventilation, vasopressors, and renal replacement therapy were required for 8 (24%), 7 (21%), and 5 (15%) of the patients, respectively; the King’s College criteria (KCC) were fulfilled by 16 patients (47%). Of the 15 (44%) nontransplanted patients, 11 (73%) died during their hospital stay. Of the 19 (56%) transplanted patients, 4 (21%) died during their hospital stay. KCC were not associated with hospital mortality (p = 0.97), but they were significantly associated with LT (p = 0.008). Conclusions: In a Portuguese cohort of patients with ALF, non-paracetamol etiologies were predominant. Hospital mortality was much lower amongst transplanted patients.