Further decompensation in cirrhosis: Results of a large multicenter cohort study supporting Baveno VII statements.

BACKGROUND AND AIMS: The prognostic weight of further decompensation in cirrhosis is still unclear. We investigated the incidence of further decompensation and its effect on mortality in patients with cirrhosis. APPROACH AND RESULTS: Multicenter cohort study. The cumulative incidence of further decompensation (development of a second event or complication of a decompensating event) was assessed using competing risks analysis in 2028 patients. A 4-state model was built: first decompensation, further decompensation, liver transplant, and death. A cause-specific Cox model was used to assess the adjusted effect of further decompensation on mortality. Sensitivity analyses were performed for patients included before or after 1999. In a mean follow-up of 43 months, 1192 patients developed further decompensation and 649 died. Corresponding 5-year cumulative incidences were 52% and 35%, respectively. The cumulative incidences of death and liver transplant after further decompensation were 55% and 9.7%, respectively. The most common further decompensating event was ascites/complications of ascites. Five-year probabilities of state occupation were 24% alive with first decompensation, 21% alive with further decompensation, 7% alive with a liver transplant, 16% dead after first decompensation without further decompensation, 31% dead after further decompensation, and <1% dead after liver transplant. The HR for death after further decompensation, adjusted for known prognostic indicators, was 1.46 (95% CI: 1.23-1.71) ( p <0.001). The significant impact of further decompensation on survival was confirmed in patients included before or after 1999. CONCLUSIONS: In cirrhosis, further decompensation occurs in ~60% of patients, significantly increases mortality, and should be considered a more advanced stage of decompensated cirrhosis.

MultiCOVID: a multi modal deep learning approach for COVID-19 diagnosis.

The rapid spread of the severe acute respiratory syndrome coronavirus 2 led to a global overextension of healthcare. Both Chest X-rays (CXR) and blood test have been demonstrated to have predictive value on Coronavirus Disease 2019 (COVID-19) diagnosis on different prevalence scenarios. With the objective of improving and accelerating the diagnosis of COVID-19, a multi modal prediction algorithm (MultiCOVID) based on CXR and blood test was developed, to discriminate between COVID-19, Heart Failure and Non-COVID Pneumonia and healthy (Control) patients. This retrospective single-center study includes CXR and blood test obtained between January 2017 and May 2020. Multi modal prediction models were generated using opensource DL algorithms. Performance of the MultiCOVID algorithm was compared with interpretations from five experienced thoracic radiologists on 300 random test images using the McNemar-Bowker test. A total of 8578 samples from 6123 patients (mean age 66 ± 18 years of standard deviation, 3523 men) were evaluated across datasets. For the entire test set, the overall accuracy of MultiCOVID was 84%, with a mean AUC of 0.92 (0.89-0.94). For 300 random test images, overall accuracy of MultiCOVID was significantly higher (69.6%) compared with individual radiologists (range, 43.7-58.7%) and the consensus of all five radiologists (59.3%, P < .001). Overall, we have developed a multimodal deep learning algorithm, MultiCOVID, that discriminates among COVID-19, heart failure, non-COVID pneumonia and healthy patients using both CXR and blood test with a significantly better performance than experienced thoracic radiologists.

[Revisit after discharge from the emergency department in a cohort of patients with COVID-19 pneumonia and analysis based on the healthcare resource used for follow-up. RESALSEVID study]. / Análisis de la evolucion tras el alta de urgencias en pacientes con neumonía por COVID-19 en función del recurso sanitario utilizado para el seguimiento: estudio RESALSEVID.

INTRODUCTION: COVID-19 pneumonia is a manifestation of SARS-CoV-2 infection and in most cases involves hospital admission. There are recommendations according to which these patients can be discharged without hospital admission, but there is no evidence regarding the revisit and the most appropriate type of follow-up. The objective of the RESALSEVID study was to investigate the variables associated with the 30-day revisit (Rev30d) in a group of patients discharged directly from 4 emergency departments (ED) with COVID-19 pneumonia, and analyze whether there were differences based on 4 different tracking devices. METHOD: Analysis of a prospective cohort of patients discharged directly from the ED with COVID-19 pneumonia in 4 hospital with different models of follow-up at discharge (primary care, hospitalization at home [HaH] phone and in person, HaH phone, hospital phone). RESULTS: Five hundred twenty patients were included, with a mean age of 50.1 years and 51% men. Rev30d was 18.3% and was related only to immunosuppression, odds ratio 4.49 (95% confidence interval 1.10-18.24); p=0.022. There was no difference in Rev30d based on the follow-up model used at discharge from the ED. CONCLUSIONS: There are some recommendations that allow the safe discharge of patients with COVID-19 pneumonia, with no differences in Rev30d depending on the type of follow-up.

Impact of COVID-19 on Hospital Admissions and Healthcare Quality Indicators in Non-COVID Patients: A Retrospective Study of the First COVID-19 Year in a University Hospital in Spain.

Few studies have assessed the impact of the COVID-19 pandemic on non-COVID diseases and healthcare quality. We aimed to evaluate changes in rates of hospitalisations, complications, in-hospital mortality, and readmissions among patients with non-COVID diseases during a one-year period after the pandemic onset. From March 2018 to February 2021 a retrospective observational study of hospital admissions in a university hospital in Spain was conducted. Non-COVID hospitalisations admitted through the emergency department were compared between the pre-COVID period (n = 28,622) and the COVID period (n = 11,904). We assessed rate ratios (RaR), comparing the weekly number of admissions and risk ratios (RR) to examine rates of complications, in-hospital mortality, readmissions, and severity. Statistical significance was set at p < 0.05. The weekly admission rate dropped by 20.8% during the complete lockdown. We observed significant reductions in admissions related to diseases of the respiratory system and circulatory system. Admissions for endocrine and metabolic diseases increased. The complication rates increased (RR = 1.21, 95% CI: 1.05;1.4), while in-hospital mortality rates held steady during the COVID period (RR = 1.09, 95% CI: 0.98;1.2). Hospital efforts to maintain quality and safety standards despite disruptions translated into a moderate increase in complications but not in in-hospital mortality. Reduced hospitalisations for conditions requiring timely treatment may have significant public health consequences.

Effect of rifaximin on infections, acute-on-chronic liver failure and mortality in alcoholic hepatitis: A pilot study (RIFA-AH).

BACKGROUND & AIMS: Alcoholic hepatitis (AH) is associated with a high incidence of infection and mortality. Rifaximin reduces bacterial overgrowth and translocation. We aimed to study whether the administration of rifaximin as an adjuvant treatment to corticosteroids decreases the number of bacterial infections at 90 days in patients with severe AH compared to a control cohort. METHODS: This was a multicentre, open, comparative pilot study of the addition of rifaximin (1200 mg/day/90 days) to the standard treatment for severe AH. The results were compared with a carefully matched historical cohort of patients treated with standard therapy and matching by age and model of end-stage liver disease (MELD). We evaluated bacterial infections, liver-related complications, mortality and liver function tests after 90 days. RESULTS: Twenty-one and 42 patients were included in the rifaximin and control groups respectively. No significant baseline differences were found between groups. The mean number of infections per patient was 0.29 and 0.62 in the rifaximin and control groups, respectively (p = .049), with a lower incidence of acute-on-chronic liver failure (ACLF) linked to infections within the treatment group. Liver-related complications were lower within the rifaximin group (0.43 vs. 1.26 complications/patient respectively) (p = .01). Mortality was lower in the treated versus the control groups (14.2% vs. 30.9, p = .15) without significant differences. No serious adverse events were associated with rifaximin treatment. CONCLUSIONS: Rifaximin is safe in severe AH with a significant reduction in clinical complications. A lower number of infections and a trend towards a lower ACLF and mortality favours its use in these patients.

Sociodemographic characteristics, functional status, and health resource use of older patients treated in Spanish emergency departments: a description of the EDEN cohort. / Características sociodemográficas, funcionales y consumo de recursos de la población mayor atendida en los servicios de urgencias españoles: una aproximación desde la cohorte EDEN.

OBJECTIVES: To describe the sociodemographic characteristics of and the health care resources used to treat patients aged 65 years or older who come to hospital emergency departments (EDs) in Spain, according to age groups. MATERIAL AND METHODS: We studied the phase-1 data for the EDEN cohort (Emergency Department and Elder Needs). Forty Spanish EDs collected data on all patients aged 65 years or older who were treated on the first 7 days in April 2019. We registered information on 6 sociodemographic and 5 function variables for all patients. For health resource use we used 6 diagnostic, 13 therapeutic, and 5 physical structural variables, for a total of 24 variables. Differences were analyzed according to age in blocks of 5 years. RESULTS: A total of 18 374 patients with a median age of 78 years were included; 55% were women. Twenty-seven percent arrived by ambulance, 71% had not previously been seen by a physician, and 13% lived alone without assistance. Ten percent had a high level of functional dependence, and 14% had serious comorbidity. Resources used most often were blood analysis (in 60%) and radiology (59%), analgesics (25%), intravenous fluids (21%), antibiotics (14%), oxygen (13%), and bronchodilators (11%). Twenty-six percent were kept under observation in the ED, 26% were admitted to wards, and 2% were admitted to intensive care units (ICUs). The median stay in the ED was 3.5 hours, and the median hospital stay was 7 days. Sociodemographic characteristics changed according to age. Functional dependence worsened with age, and resource requirements increased in general. However, benzodiazepine use was unaffected, while the use of nonsteroidal anti-inflammatory drugs and ICU admission decreased. CONCLUSION: The functional dependence of older patients coming to EDs increases with age and is associated with a high level of health care resource use, which also increases with age. Planners should take into consideration the characteristics of the older patients and the proportion of the caseload they represent when arranging physical spaces and designing processes for a specific ED.

OBJETIVO: Investigar las características sociodemográficas y consumo de recursos de los pacientes de 65 o más años que consultan en servicios de urgencias hospitalarios (SUH) en España, y su modificación por grupos etarios. METODO: Se utilizaron datos de la cohorte EDEN obtenidos en fase 1 (Emergency Department and Elder Needs). Cuarenta SUH españoles incluyeron todos los pacientes de $ 65 años atendidos del 1-4-2019 al 7-4-2019 (7 días). Se analizaron 6 características sociodemográficas, 5 funcionales y 24 referidas a consumo de recursos (6 diagnósticos, 13 terapéuticos, 5 estructurales) y sus cambios a medida que avanza la edad (agrupada en bloques de 5 años). RESULTADOS: Se analizaron 18.374 pacientes (mediana edad: 78 años; 55% mujeres). El 27% acude a urgencias en ambulancia, el 71% sin consulta médica previa y el 13% vive solo sin cuidadores. Funcionalmente, el 10% tiene dependencia grave y el 14% comorbilidad grave. La solicitud de analítica sanguínea (60% de casos) y radiología (59%) destaca entre el consumo de recursos diagnósticos, y el uso de analgésicos (25%), sueroterapia (21%), antibioticoterapia (14%), oxigenoterapia (13%) y broncodilatadores (11%), entre los terapéuticos. El 26% requiere observación en urgencias, el 26% hospitalización y el 2% cuidados intensivos. La mediana de estancia en urgencias es de 3:30 horas y la de hospitalización es de 7 días. Las características sociodemográficas se modifican con la edad, las funcionales empeoran y el consumo de recursos aumenta (excepto benzodiacepinas, que no se modifica, y antinflamatorios no esteroideos y cuidados intensivos, que disminuye). CONCLUSIONES: Las características funcionales de la población mayor que consulta en los SUH empeora a medida que su edad avanza, y se asocia a un consumo de recursos alto que también se incrementa con la edad. Las características de esta población y su proporción en un determinado SUH deben tenerse en cuenta en su planificación estructural y funcional.

The prognostic role of hepatic venous pressure gradient in cirrhotic patients undergoing elective extrahepatic surgery.

BACKGROUND & AIMS: Surgery in cirrhosis is associated with a high morbidity and mortality. Retrospectively reported prognostic factors include emergency procedures, liver function (MELD/Child-Pugh scores) and portal hypertension (assessed by indirect markers). This study assessed the prognostic role of hepatic venous pressure gradient (HVPG) and other variables in elective extrahepatic surgery in patients with cirrhosis. METHODS: A total of 140 patients with cirrhosis (Child-Pugh A/B/C: 59/37/4%), who were due to have elective extrahepatic surgery (121 abdominal; 9 cardiovascular/thoracic; 10 orthopedic and others), were prospectively included in 4 centers (2002-2011). Hepatic and systemic hemodynamics (HVPG, indocyanine green clearance, pulmonary artery catheterization) were assessed prior to surgery, and clinical and laboratory data were collected. Patients were followed-up for 1 year and mortality, transplantation, morbidity and post-surgical decompensation were studied. RESULTS: Ninety-day and 1-year mortality rates were 8% and 17%, respectively. Variables independently associated with 1-year mortality were ASA class (American Society of Anesthesiologists), high-risk surgery (defined as open abdominal and cardiovascular/thoracic) and HVPG. These variables closely predicted 90-, 180- and 365-day mortality (C-statistic >0.8). HVPG values >16 mmHg were independently associated with mortality and values ≥20 mmHg identified a subgroup at very high risk of death (44%). Twenty-four patients presented persistent or de novo decompensation at 3 months. Low body mass index, Child-Pugh class and high-risk surgery were associated with death or decompensation. No patient with HVPG <10 mmHg or indocyanine green clearance >0.63 developed decompensation. CONCLUSIONS: ASA class, HVPG and high-risk surgery were prognostic factors of 1-year mortality in cirrhotic patients undergoing elective extrahepatic surgery. HVPG values >16 mmHg, especially ≥20 mmHg, were associated with a high risk of post-surgical mortality. LAY SUMMARY: The hepatic venous pressure gradient is associated with outcomes in patients with cirrhosis undergoing elective extrahepatic surgery. It enables a better stratification of risk in these patients and provides the foundations for potential interventions to improve post-surgical outcomes.

Differences in clinical features of two immigrant populations with tuberculosis.

A study was performed to assess differences in the clinical presentation of tuberculosis between two groups of immigrants. Ninety-four patients seen in the emergency room for newly diagnosed tuberculosis between 2006 and 2012 were included. Forty-nine patients were from Asian countries and 45 from Latin America. Mean age [years (SD)] was 35.3 (13) in Asian patients and 33.9 (10) in Latin American patients. Asian subjects were predominantly male (40/49 vs 25/45; P=0.006). Patients from Latin American countries had a higher rate of pulmonary tuberculosis. A higher percentage of Asian patients lived in overcrowded conditions, whereas HIV infection was more frequent among Latin Americans. Most patients were treated with a quadruple regimen. Resistance to isoniazid was documented in two patients from Latin America.

Rebleeding prophylaxis improves outcomes in patients with hepatocellular carcinoma. A multicenter case-control study.

UNLABELLED: Outcome of variceal bleeding (VB) in patients with hepatocellular carcinoma (HCC) is unknown. We compared outcomes after VB in patients with and without HCC. All patients with HCC and esophageal VB admitted between 2007 and 2010 were included. Follow-up was prolonged until death, transplantation, or June 2011. For each patient with HCC, a patient without HCC matched by age and Child-Pugh class was selected. A total of 292 patients were included, 146 with HCC (Barcelona Classification of Liver Cancer class 0-3 patients, A [in 25], B [in 29], C [in 45], and D [in 41]) and 146 without HCC. No differences were observed regarding previous use of prophylaxis, clinical presentation, endoscopic findings, and initial endoscopic treatment. Five-day failure was similar (25% in HCC versus 18% in non-HCC; P = 0.257). HCC patients had greater 6-week rebleeding rate (16 versus 7%, respectively; P = 0.025) and 6-week mortality (30% versus 15%; P = 0.003). Fewer patients with HCC received secondary prophylaxis after bleeding (77% versus 89%; P = 0.009), and standard combination therapy was used less frequently (58% versus 70%; P = 0.079). Secondary prophylaxis failure was more frequent (50% versus 31%; P = 0.001) and survival significantly shorter in patients with HCC (median survival: 5 months versus greater than 38 months in patients without HCC; P < 0.001). Lack of prophylaxis increased rebleeding and mortality. On multivariate analysis Child-Pugh score, presence of HCC, portal vein thrombosis, and lack of secondary prophylaxis were predictors of death. CONCLUSIONS: Patients with HCC and VB have worse prognosis than patients with VB without HCC. Secondary prophylaxis offers survival benefit in HCC patients.

A multidisciplinary support programme increases the efficiency of pegylated interferon alfa-2a and ribavirin in hepatitis C.

BACKGROUND & AIMS: Adherence to antiviral treatment is important to achieve sustained virological response (SVR) in chronic hepatitis C (CHC). We evaluated the efficiency of a multidisciplinary support programme (MSP), based on published HIV treatment experience, to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in CHC. METHODS: 447 patients receiving antiviral treatment were distributed into 3 groups: control group (2003-2004, n=147), MSP group (2005-2006, n=131), and MSP-validation group (2007-2009, n=169). The MSP group included two hepatologists, two nurses, one pharmacist, one psychologist, one administrative assistant, and one psychiatrist. Cost-effectiveness analysis was performed using a Markov model. RESULTS: Adherence and SVR rates were higher in the MSP (94.6% and 77.1%) and MSP-validation (91.7% and 74.6%) groups compared to controls (78.9% and 61.9%) (p<0.05 in all cases). SVR was higher in genotypes 1 or 4 followed by the MSP group vs. controls (67.7% vs. 48.9%, p=0.02) compared with genotypes 2 or 3 (87.7% vs. 81.4%, p=n.s.). The MSP was the main predictive factor of SVR in patients with genotype 1. The rate of adherence in patients with psychiatric disorders was higher in the MSP groups (n=95, 90.5%) compared to controls (n=28, 75.7%) (p=0.02). The cost per patient was € 13,319 in the MSP group and € 16,184 in the control group. The MSP group achieved more quality-adjusted life years (QALYs) (16.317 QALYs) than controls (15.814 QALYs) and was dominant in all genotypes. CONCLUSIONS: MSP improves patient compliance and increases the efficiency of antiviral treatment in CHC, being cost-effective.

Long-term clinical course of decompensated alcoholic cirrhosis: a prospective study of 165 patients.

BACKGROUND: Prognosis of decompensated alcoholic cirrhosis is based mainly on studies that included patients with different severities of liver disease and did not recognize either hepatitis C virus epidemic or changes in clinical management of cirrhosis. AIM: To define the long-term course after the first hepatic decompensation in alcoholic cirrhosis. METHODS: Prospective inclusion at the start point of decompensated cirrhosis of 165 consecutive patients with alcoholic cirrhosis without known hepatocellular carcinoma hospitalized from January 1998 to December 2001 was made. Follow-up was maintained until death or the end of the observation period (April 1, 2010). RESULTS: The patients were followed for 835.75 patient years. Median age was 56 years (95% confidence interval: 54-58). Baseline Child-Pugh score was 9 (95% CI: 8-9), and model for end-stage liver disease (MELD) was 13.8 (95% CI: 12.5-14.7). Ascites was the most frequent first decompensation (51%). During follow-up, 99 (60%) patients were abstinent, hepatocellular carcinoma developed in 18 (11%) patients, and 116 patients died (70%). Median overall survival was 61 months (95% CI: 48-74). Median survival probability after onset of hepatic encephalopathy (HE) was only 14 months (95% CI: 5-23). Age, baseline MELD, albumin, development of HE, and persistence of alcohol use were independently correlated with mortality. CONCLUSIONS: Patients with alcoholic cirrhosis show a high frequency of complications. The low mortality rate in our cohort of patients probably reflects the improvement in the management of patients with cirrhosis; it is mainly influenced by baseline MELD, age, HE development, and continued abstinence. Patients who develop HE should be considered for hepatic transplantation.

Incidence and prognosis of different types of functional renal failure in cirrhotic patients with ascites.

BACKGROUND & AIMS: Hepatorenal syndrome is a well-characterized type of terminal renal failure that occurs in patients with cirrhosis with ascites. Information about other types of functional renal failure in these patients is scarce. We assessed the incidence and prognosis of different types of functional renal failure in cirrhotic patients with ascites and investigated prognostic factors for these disorders. METHODS: Consecutive cirrhotic patients (n = 263) were followed for 41 +/- 3 months after their first incidence of ascites. Three types of functional renal failure were considered: pre-renal failure (when renal failure was associated with a depletion of intravascular volume), renal failure induced by infection that did not result in hepatorenal syndrome, and hepatorenal syndrome. RESULTS: During the follow-up period, 129 (49%) patients developed some type of functional renal failure. The most frequent was pre-renal failure (27.4%), followed by renal failure induced by infection (14.1%), and then hepatorenal syndrome (7.6%). The 1-year probability of developing the first episode of any functional renal failure was 23.6%. The independent predictors of functional renal failure development were baseline age, Child-Pugh score, and serum creatinine. Although the 1-year probability of survival was 91% in patients without renal failure, it decreased to 46.9% in those patients who developed any functional renal failure (P = .0001). CONCLUSIONS: Approximately 50% of the cirrhotic patients with ascites developed some type of functional renal failure during the follow-up period; renal failure was associated with worse prognosis. Efforts should be made to prevent renal failure in cirrhotic patients with ascites.

Serum and ascitic fluid bacterial DNA: a new independent prognostic factor in noninfected patients with cirrhosis.

UNLABELLED: We tested the hypothesis that the presence of bacterial DNA (bactDNA) in ascitic fluid and serum is associated with decreased survival in patients with cirrhosis. In a prospective, multicenter study, we analyzed the clinical evolution of 156 patients with cirrhosis and ascites (first or recurrence) with lower than 250 polymorphonuclear cells (PMN)/muL, negative ascites bacteriological culture, and absence of other bacterial infections being admitted for evaluation of large-volume paracentesis, according to the presence of bactDNA at admission. Survival, causes of death, and successive hospital admissions were determined during a 12-month follow-up period. BactDNA was detected in 48 patients. The most prevalent identified bactDNA corresponded to Escherichia coli (n = 32/48 patients, 66.6%). Patients were followed for 12 months after inclusion and in this period 34 patients died: 16 of 108 (15%) bactDNA negative versus 18 of 48 (38%) bactDNA positive (P = 0.003). The most frequent cause of death was acute-on-chronic liver failure in both groups (7/16 and 9/18 in patients without or with bactDNA, respectively), although more prevalent in the first month of follow-up in patients with presence of bactDNA (0 versus 4/7). When considering patients with model for end-stage liver disease (MELD) score less than 15, mortality was significantly higher in those with presence of bactDNA. Spontaneous bacterial peritonitis developed similarly in patients with or without bactDNA at admission. CONCLUSION: The presence of bactDNA in a patient with cirrhosis during an ascitic episode is an indicator of poor prognosis. This fact may be related to the development of acute-on-chronic liver failure at short term and does not predict the development of spontaneous bacterial peritonitis.

Differences in virological response to pegylated interferon and ribavirin between hepatitis C virus (HCV)-monoinfected and HCV-HIV-coinfected patients.

BACKGROUND: Suboptimal doses of ribavirin have been suggested to explain the diminished efficacy of pegylated interferon (PEG-IFN) plus ribavirin in hepatitis C virus (HCV)-HIV-coinfected patients. METHODS: A cohort of 104 coinfected patients and an age-, sex- and genotype-matched cohort of HCV-monoinfected patients (n = 104) were compared. All patients received PEG-IFN-alpha2a 180 microg/week plus ribavirin 800-1,200 mg daily (HCV genotype 2/3 patients received 800 mg daily and those with genotype 1/4 received 1,000-1,200 mg daily) for 48 weeks (24 weeks for monoinfected patients with genotypes 2/3). HCV RNA levels were determined qualitatively at weeks 4, 12, 24, 48 and 72 and quantified monthly until week 12. RESULTS: The coinfected cohort had more advanced liver disease and lower body weight. HCV genotype 1 patients coinfected with HIV showed higher levels of HCV RNA than monoinfected patients. A significantly higher proportion of coinfected patients interrupted the prescribed treatment period prematurely (84% versus 98%). During the first 12 weeks, smaller decreases in HCV RNA levels were observed in coinfected patients. Among patients with HCV genotype 1, coinfected patients achieved lower rates of early virological response (64% versus 87%), end-of-treatment response (47.3% versus 80%) and sustained virological response (SVR; 27.3% versus 56.4%), but not rapid virological response (RVR). HCV-HIV-coinfected patients with HCV genotype 2/3 achieved significantly lower rates of RVR (52% versus 88%). Multivariate analysis identified RVR, gender and liver fibrosis as independent predictors of SVR. CONCLUSIONS: Differences in efficacy of PEG-IFN-alpha2a plus ribavirin treatment between HCV-HIV-coinfected and HCV-monoinfected patients were maintained despite optimized ribavirin dose.

Natural history of patients hospitalized for management of cirrhotic ascites.

BACKGROUND & AIMS: Since the International Ascites Club published the diagnostic criteria of refractory ascites (RA) and hepatorenal syndrome (HRS), there have been few studies assessing the natural history of ascites. The aims of this study were to define the natural history of cirrhotic ascites and to identify prognostic factors for dilutional hyponatremia (DH), RA, HRS, and survival. METHODS: Two hundred sixty-three consecutive cirrhotic patients were followed for 40.9 +/- 2.6 months after their first significant ascites. RESULTS: During follow-up 74 (28.1%) patients developed DH, 30 (11.4%) RA (diuretic-resistant in 2 cases and diuretic-intractable because of the development of diuretic-induced complications in 28 cases), and 20 (7.6%) HRS (type 1, 7; type 2, 13). The 5-year probability of DH, RA, and HRS development was 37.1%, 11.4%, and 11.4%, respectively. The probability of survival at 1 and 5 years was 85% and 56.5%, respectively. The independent predictors for survival were baseline age, baseline Child-Pugh score, and DH development. The 1-year probability of survival after developing DH, RA, and type 2 HRS was 25.6%, 31.6%, and 38.5%, respectively. In contrast, the mean survival was only 7 +/- 2 days in those patients developing type 1 HRS. CONCLUSIONS: (1) The survival of cirrhotic patients with first episode of ascites is relatively high, and it is mainly influenced by age and Child-Pugh score at the time of ascites decompensation, as well as by DH development. (2) The probability of RA and HRS development is relatively low, but they are associated with a poor prognosis.

Sequential determination of pharmacokinetics and pharmacodynamics of mycophenolic acid in liver transplant patients treated with mycophenolate mofetil.

BACKGROUND: In liver transplantation, mycophenolate mofetil (MMF) is habitually administered using fixed doses. We assessed whether mycophenolic acid (MPA) monitoring could be advisable in liver transplant patients. METHODS: In 15 liver transplant patients receiving tacrolimus, daclizumab and MMF (1 g bid, orally), we determined the 12-hour plasma MPA pharmacokinetic profile after one dose of MMF at days 6, 10, and 16, and months 3 and 6. The inhibitory capacity of serum MPA on proliferation of CEM cells, a cell line insensitive to other immunosuppressants, was also determined. RESULTS: A large interindividual variability in MPA profiles was observed at any time. Regardless of a gradual increase in individual MPA AUC and C(0) over time following transplantation, a substantial proportion of patients had these parameters below the ranges recommended in other organ transplantations throughout the study. When MPA AUC and C(0) were within the recommended ranges, CEM proliferation was inhibited by almost all serum samples, but when these pharmacokinetic parameters were below the recommended ranges, CEM proliferation was very variable and, therefore, unpredictable. No relationship between MPA pharmacokinetics and the efficacy of MMF could be established (only one patient developed rejection), probably due to the concomitant administration of tacrolimus and daclizumab. Gastrointestinal symptoms were the only adverse events with a significant relationship with MPA levels. CONCLUSIONS: During the first postoperative months, exposure to MPA is low in a considerable proportion of liver transplant patients receiving MMF at a fixed dose of 1 g bid. MPA monitoring appears necessary in these patients.