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Background Patient heterogeneity poses significant challenges for managing individuals and designing clinical trials, especially in complex diseases. Existing classifications rely on outcome-predicting scores, potentially overlooking crucial elements contributing to heterogeneity without necessarily impacting prognosis. Methods To address patient heterogeneity, we developed ClustALL, a computational pipeline that simultaneously faces diverse clinical data challenges like mixed types, missing values, and collinearity. ClustALL enables the unsupervised identification of patient stratifications while filtering for stratifications that are robust against minor variations in the population (population-based) and against limited adjustments in the algorithm’s parameters (parameter-based). Results Applied to a European cohort of patients with acutely decompensated cirrhosis ( n  = 766), ClustALL identified five robust stratifications, using only data at hospital admission. All stratifications included markers of impaired liver function and number of organ dysfunction or failure, and most included precipitating events. When focusing on one of these stratifications, patients were categorized into three clusters characterized by typical clinical features; notably, the 3-cluster stratification showed a prognostic value. Re-assessment of patient stratification during follow-up delineated patients’ outcomes, with further improvement of the prognostic value of the stratification. We validated these findings in an independent prospective multicentre cohort of patients from Latin America ( n  = 580). Conclusions By applying ClustALL to patients with acutely decompensated cirrhosis, we identified three patient clusters. Following these clusters over time offers insights that could guide future clinical trial design. ClustALL is a novel and robust stratification method capable of addressing the multiple challenges of patient stratification in most complex diseases.

Hepatorenal syndrome (HRS) is a severe and progressive functional renal failure occurring in patients with cirrhosis and ascites. Terlipressin is recognized as an effective treatment of HRS, but it is expensive and not widely available. Norepinephrine could be an effective alternative. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of norepinephrine compared to terlipressin in the management of HRS. We searched the Medline, Embase, Scopus, CENTRAL, Lilacs and Scielo databases for randomized trials of norepinephrine and terlipressin in the treatment of HRS up to January 2014. Two reviewers collected data and assessed the outcomes and risk of bias. The primary outcome was the reversal of HRS. Secondary outcomes were mortality, recurrence of HRS and adverse events. Four studies comprising 154 patients were included. All trials were considered to be at overall high risk of bias. There was no difference in the reversal of HRS (RR = 0.97, 95% CI = 0.76 to 1.23), mortality at 30 days (RR = 0.89, 95% CI = 0.68 to 1.17) and recurrence of HRS (RR = 0.72; 95% CI = 0.36 to 1.45) between norepinephrine and terlipressin. Adverse events were less common with norepinephrine (RR = 0.36, 95% CI = 0.15 to 0.83). Norepinephrine seems to be an attractive alternative to terlipressin in the treatment of HRS and is associated with less adverse events. However, these findings are based on data extracted from only four small studies.

Background Despite adequate treatment, a subgroup of patients with inflammatory bowel disease (IBD), including Crohn`s disease and ulcerative colitis, have persistent gastrointestinal symptoms that are not always related to mucosal damage. Recently, two autoantibodies, anti-CdtB and anti-vinculin, were validated as post-infectious IBS (PI-IBS) markers, however there is limited evidence of its diagnostic role in IBD population. Methods Patients with more than 3 bowel movements/day and indication of colonoscopy were enrolled. Samples were collected at the time of colonoscopy for assessment of serum levels of anti-CdtB and anti-vinculin antibodies. Results A total of 160 subjects were included in 4 groups: active IBD ( n  = 44); quiescent IBD and chronic diarrhea IBD-IBS ( n  = 25); predominant-diarrhea IBS ( n  = 45) and controls ( n  = 46). The mean value of the optical density for anti-CdtB was 1.2 ± 0.65 in group 1, 1.27 ± 0.64 in group 2, 1.49 ± 0.47 in the group 3 and 1.6 ± 0.68 in group 4, p  = 0.012. For anti-vinculin, optical densities were: 1.34 ± 0.78 in group 1, 1.46 ± 0.92 in group 2, 1.31 ± 0.79 in group 3 and 1.41 ± 0.86 for controls ( p  = 0.875). Using a cut-off of 1.56 for anti-CdtB, the positivity between groups was n  = 10 (22.7%) in group 1, n  = 9 (34.6%) in group 2, 19 (43.2%) in group 3, 21 (45.7%) in group 4 ( p  = 0.106). The positivity of anti-vinculin using a cut-off of 1.6 was n  = 18 (40.9%) in group 1, n  = 11 (42.3%), n  = 15 (34.1%), n  = 22 (47.8%) ( p  = 0.622). Conclusions Our findings show that anti-CdtB and anti-vinculin could not identify IBD-IBS patients or discriminate IBS-D from healthy controls.

The aim of this study was to compare portal and splenic blood flows and the liver morphology in hepatosplenic (HS) and hepatointestinal (HI) schistosomiasis. Doppler ultrasound measurements were performed in 48 adult patients with schistosomiasis, according to the criteria of the World Health Organization, and compared with those performed in 20 healthy controls. Portal flow was significantly higher (P < 0.0001) in both HS and HI (2481 +/- 1467 and 2159 +/- 1446 ml/min, respectively) than in normal individuals (842 +/- 322 ml/min). There was no difference in splenic blood flow (822 +/- 685 and 458 +/- 292 ml/min, respectively) between HS and HI, but these values were significantly higher than those of normal controls (243 +/- 94 ml/min). Portal and splenic overflow are found in both the HS and the HI forms of schistosomiasis.

This study aimed to report the first case of a patient with hepatosplenic schistosomiasis mansoni, refractory ascites and portal vein thrombosis treated with a transjugular intrahepatic portosystemic shunt (TIPS), at the Instituto de Radiologia, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Brazil. After the procedure, the patient recovered favorably and progressed with portal pressure reduction and no deterioration of the liver function. Endovascular shunt modification is a conservative medical approach that often helps in reducing symptoms significantly, making it a less invasive and a safer alternative to liver transplantation for the treatment of schistosomiasis with portal hypertension.

Background Chronic hepatitis C virus (HCV) infection is associated with impairment of cognitive function and mood disorders. Our aim was to evaluate the impact of sustained virological response (SVR) on cognitive function and mood disorders. Method A prospective exploratory one arm study was conducted. Adult clinically compensated HVC patients were consecutively recruited before treatment with interferon and ribavirin for 24 to 48 weeks, according to HCV genotype. Clinical, neurocognitive and mood assessments using the PRIME-MD and BDI instruments were performed at baseline, right after half of the expected treatment has been reached and 6 months after the end of antiviral treatment. Exclusion criteria were the use of illicit psychotropic substances, mental confusion, hepatic encephalopathy, hepatocellular carcinoma, severe anemia, untreated hypothyroidism, Addison syndrome and major depression before treatment. Results Thirty six patients were enrolled and 21 completed HCV treatment ( n  = 16 with SVR and n  = 5 without). Regardless of the viral clearance at the end of treatment, there was a significant improvement in the immediate verbal episodic memory ( p  = 0.010), delayed verbal episodic memory ( p  = 0.007), selective attention ( p  < 0.001) and phonemic fluency ( p  = 0.043). Patients with SVR displayed significant improvement in immediate ( p  = 0.045) and delayed verbal episodic memory ( p  = 0.040) compared to baseline. The baseline frequency of depression was 9.5%, which rose to 52.4% during treatment, and returned to 9.5% 6 months after the end of treatment, without significant difference between patients with and without SVR. Depressive symptoms were observed in 19.1% before treatment, 62% during ( p  = 0.016) and 28.6% 6 months after the end of treatment ( p  = 0.719). Conclusions Eradication of HCV infection improved cognitive performance but did not affect the frequency of depressive symptoms at least in the short range.

Abstract Ascites is a common complication of several conditions, but it is rare in cases of Chlamydia trachomatis infection. We report a 36-year-old patient presenting with abdominal swelling for a week prior to hospitalization. An extensive workup excluded liver or heart disease and malignancy. A computed tomography scan demonstrated massive ascites and severe thickening of peritoneal reflections. Laboratory tests showed low serum-ascites albumin gradient, high total protein, and low adenosine. Diagnostic laparoscopy revealed inflammatory signs of both fallopian tubes. The histopathological results from peritoneal biopsy were consistent with lymphoid proliferation with reactive lymphoplasmacytic infiltrate. A gynecological investigation showed a positive DNA for C. trachomatis in the cervical swab. After treatment with doxycycline, there was a complete resolution of ascites.

Background: Lysosomal acid lipase deficiency (LAL-D) is a rare genetic disease associated with the deregulation of lipid metabolism, leading to atherosclerosis, dyslipidemia, and hepatic steatosis, with potential progression to cirrhosis. Our study aims to assess the role of LAL-D in the setting of cryptogenic liver disease. Methods: A large multicenter cross-sectional study was conducted, which included 135 patients with cryptogenic liver disease from four liver centers in Brazil. All patients were submitted to the investigation of LAL enzyme activity on dried blood spots. Results: Three patients (two female) presented levels of LAL below the reference limit, compatible with LAL-D (2.2%). They had a mean age of 43.9 ± 10.1 years and a mean body-mass index (BMI) of 23.1 ± 1.7 kg/m2. The mean serum levels of glucose, HDL-cholesterol, and triglycerides were 89.7 ± 3.2, 21.7 ± 3.2, and 206.7 ± 25.5 mg/dL, respectively. All patients had duodenal polyposis with xanthomatous macrophages. LAL-D investigation should be considered for individuals with chronic liver disease of an unknown etiology, especially with a normal BMI, high triglycerides, and low-HDL-cholesterol levels. The identification of LAL-D patients is extremely important since enzyme replacement therapy with Sebelipase Alfa significantly increases their survival.

Patients with cirrhosis have high risk of bacterial infections and cirrhosis decompensation, resulting in admission to emergency department (ED). However, there are no criteria developed in the ED to identify patients with cirrhosis with bacterial infection and with high mortality risk. The objective of the study is to identify variables from ED arrival associated with bacterial infections and inhospital mortality. This is a retrospective single-center study using a tertiary hospital's database to identify consecutive ED patients with decompensated cirrhosis. Clinical variables and laboratory results were obtained by chart review. Logistic regression models were built to determine variables independently associated with bacterial infection and mortality. Scores using these variables were designed. One hundred forty-nine patients were enrolled, most of them males (77.9%) with alcoholic cirrhosis (53%) and advanced liver disease (Child-Pugh C, 47.2%). Bacterial infections were diagnosed in 72 patients (48.3%), and 36 (24.2%) died during hospital stay. Variables independently associated with bacterial infection were lymphocytes less than or equal to 900/mm3 (odds ratio [OR], 3.85 [95% confidence interval {CI}, 1.47-10]; P = .006) and C-reactive protein greater than 59.4 mg/L (OR, 5.05 [95% CI, 1.93-13.2]; P = .001). Variables independently associated with mortality were creatinine greater than 1.5 mg/dL (OR, 4.35 [95% CI, 1.87-10.1]; P = .001) and international normalized ratio greater than 1.65 (OR, 3.71 [95% CI, 1.6-8.61]; P = .002). Scores designed to predict bacterial infection and mortality (Mortality in Cirrhosis Emergency Department Score) had an area under the receiver operating characteristic curve of 0.82 and 0.801, respectively. The Mortality in Cirrhosis Emergency Department Score performed better than Model for End-Stage Liver Disease score. In this cohort of ED patients with decompensated cirrhosis, lymphopenia and elevated C-reactive protein were related to bacterial infections, and elevated creatinine and international normalized ratio were related to mortality. Scores built with these variables should be prospectively validated.