Hepatic Encephalopathy in Cirrhotic Patients With Bacterial Infections: Frequency, Clinical Characteristics, and Prognostic Relevance.

Background/Objectives: Bacterial infections (BIs) are well-recognized precipitants of hepatic encephalopathy (HE). Nevertheless, there is a paucity of data in patients with HE associated with BI. Our aim was to describe clinical characteristics, recurrence, and prognosis of HE in patients with BI. Methods: A prospective study with inclusion of hospitalized cirrhotic patients with BI, followed until discharge, death, or liver transplantation. Results: 172 patients (age 57 ± 13, model of end-stage liver disease [MELD]-sodium 22 ± 8) were included. Infections were more commonly due to spontaneous bacterial peritonitis and cellulitis (22% and 23%), non-nosocomial (70%), and associated with systemic inflammatory response syndrome and septic shock in 40% and 9%, respectively. HE was diagnosed in 66 patients (grade ≥2 in 58%). In multivariate analysis, MELD-sodium, albumin, and prior HE were associated with HE at diagnosis of BI. Recurrence of HE was diagnosed in 30 patients (median 13 [interquartile range 5-22] days), more commonly manifested as overt HE (90% vs. 60% at first episode, P = 0.012) and more frequently in patients with hyponatremia (54% vs. 27% for patients without, P < 0.001). In-hospital mortality was 34% and was more common for patients with HE (51% vs. 22%, P < 0.001), irrespective of grade, and for those with recurrence (63% vs. 42%, P < 0.001). In multivariate analysis, HE at diagnosis of infection and MELD-sodium were predictors of mortality. Conclusions: HE is frequent in cirrhotic patients with BI and is associated with severity of liver disease, but not with infection. These patients are at increased risk of short-term HE recurrence, especially those with hyponatremia. The presence and recurrence of HE, independent of severity, are associated with in-hospital mortality.

Natural History of Hepatosplenic Schistosomiasis (HSS) Non-Cirrhotic Portal Hypertension (NCPH): Influence of Gastrointestinal Bleeding and Decompensation in Prognosis.

BACKGROUND: Hepatosplenic schistosomiasis (HSS) is a peculiar form of non-cirrhotic portal hypertension (NCPH). Although HSS patients present normal hepatic function, some evolve signs of hepatocellular failure and features of decompensated cirrhosis. The natural history of HSS-NCPH is unknown. METHODS: A retrospective study was conducted that evaluated patients who fulfilled clinical-laboratorial criteria for HSS. RESULTS: A total of 105 patients were included. Eleven patients already presented with decompensated disease and had lower transplant-free survival at 5 years than those without (61% vs. 95%, p = 0.015). Among 94 patients without prior decompensation, the median follow-up was 62 months and 44% of them had varicose bleeding (two or more episodes in 27%). Twenty-one patients presented at least one episode of decompensation (10-year probability 38%). Upon multivariate analysis, varicose bleeding and higher bilirubin levels were associated with decompensation. The 10-year probability of survival was 87%. Development of decompensation and age were predictive of mortality. CONCLUSION: HSS is characterized by multiple episodes of GI bleeding, a high probability of decompensation and reduced survival at the end of the first decade. Decompensation is more common in patients with varicose esophageal bleeding and is associated with lower survival.

Noninvasive predictors of esophageal varices in patients with hepatosplenic schistosomiasis mansoni.

BACKGROUND: No previous study have evaluated transient elastography for predicting esophageal varices in hepatosplenic schistosomiasis. AIM: To investigate noninvasive methods of predicting esophageal varices in patients with hepatosplenic schistosomiasis mansoni. METHODS: Cross-sectional multicentric study included 51 patients with hepatosplenic schistosomiasis. Patients underwent ultrasonography-dopplerfluxometry, upper endoscopy, complete blood cell count and transient elastography (Fibroscan®) for liver and spleen stiffness measurement (LSM and SSM). Noninvasive scores previously established for cirrhotic population were studied: platelet count to spleen diameter ratio (PSR), LSM-spleen diameter to platelet ratio score (LSPS) and varices risk score (VRS). We proposed a version of LSPS and VRS by replacing LSM with SSM and named them SSPS and modified-VRS, respectively. RESULTS: Esophageal varices were detected in 42 (82.4%) subjects. Individuals with varices presented higher SSM (73.5 vs 36.3 Kpa, p = 0.001), splenic vein diameter (10.8 vs 8.0 mm, p = 0.017), SSPS (18.7 vs 6.7, p = 0.003) and modified-VRS (4.0 vs 1.4, p = 0.013), besides lower PSR (332 vs 542, p = 0.038), than those without varices. SSPS was independently associated with varices presence (OR=1.19, 95%CI 1.03-1.37, p = 0.020) after multivariate analysis. In a model excluding noninvasive scores, SSM was independently associated with varices diagnosis (OR=1.09, 95%CI 1.03-1.16, p = 0.004). AUROC was 0.856 (95%CI 0.752-0.961, p = 0.001) for SSM and 0.816 (95%CI 0.699-0.932, p = 0.003) for SSPS (p = 0.551). CONCLUSIONS: Spleen-related variables were predictors of esophageal varices: SSM, splenic vein diameter, SSPS, modified-VRS and PSR. Multivariate models indicated that SSM and SSPS are useful tools for predicting varices in non-cirrhotic portal hypertension by hepatosplenic schistosomiasis and may be used in clinical practice.

Frequency and predictive factors of minimal hepatic encephalopathy before and after sustained virological response in HCV cirrhosis.

Introduction: Data of minimal hepatic encephalopathy (MHE) before and after hepatitis C virus (HCV) treatment remain scarce. We aimed to describe the prevalence, evolution and predictive factors of MHE before and after a sustained virological response (SVR). Material and methods: It was a prospective study that included adults with cirrhosis due to HCV treated by direct-acting agents (DAA). MHE was assessed using the Psychometric Hepatic Encephalopathy Score (PHES). Results: 104 patients (65% female, age 60 ±10 years; 69% with diabetes, 47% with hypertension; 82% Child-Pugh A) were included. MHE was assessed just before therapy and 12 (IQR 7-15) months after SVR. Prevalence of MHE before HCV treatment and after SVR were 16% and 22%, respectively (p = 0.18). Resolution of MHE after SVR occurred in a few patients (n = 4/17) and 10 of 87 patients (11.5%) without MHE before treatment developed this condition after SVR. MHE after SVR was more common in patients with MHE before treatment (57% vs. 5%, p < 0.001). In multivariate analysis, older age, hypertension and hypoalbuminemia after treat-ment were predictors of MHE after SVR. In the absence of all these variables, none of the patients had MHE. In contrast, the prevalence of MHE was 42% and 70% in the case of presence of any 2 of these factors and all these conditions, respectively. Conclusions: MHE is frequent in patients with cirrhosis who achieved SVR after DAA. SVR is associated with low probability of resolution of MHE and may not entirely protect patients from developing de novo MHE. Presence of MHE before DAA, older age, hypertension and hypoalbuminemia after SVR were independently associated with this condition.

CLIF-C AD Score Predicts Development of Acute Decompensations and Survival in Hospitalized Cirrhotic Patients.

BACKGROUND AND AIMS: Patients with decompensated cirrhosis are at increased risk of mortality, even in absence of ACLF. The CLIF-C AD score (CLIF-C ADs) was proposed as a prognostic score but lacks sufficient validation. Our aim was to describe clinical characteristics and hospital evolution according to score groups and evaluate prognostic capability of CLIF-C ADs alone or in combination with other scores. METHODS: Two hundred and sixty-six patients (55 ± 14 years, ascites in 63%, MELD 14 ± 5) were included, and classified as high, intermediate and low CLIF-C ADs in 13, 60 and 27% of cases. Development of new complications of cirrhosis during hospitalization and survival at 3 months were evaluated. RESULTS: Patients with high CLIF-C ADs had more severe systemic inflammation parameters and higher frequency of organ dysfunction. CLIF-C ADs ≥ 60, when compared to intermediate and low groups, was associated with higher incidence of complications of cirrhosis (90% vs 70% and 49%, p < 0.001) and lower survival (93%, 80% and 50%, p < 0.0001). In multivariate analysis, CLIF-C ADs, ascites and MELD were predictors of survival [(AUROC 0.76 (95% CI 0.69-0.83)]. Absence of ascites or MELD < 14 identified patients with intermediate CLIF-C ADs and good survival (89 and 84%, respectively). CONCLUSION: CLIF-C ADs predicts survival in cirrhotic patients with AD. High CLIF-C ADs is associated with higher frequency of organ dysfunction, increased risk of new complications of cirrhosis and high short-term mortality. On the contrary, individuals with low CLIF-C ADs, as well as those with intermediate score without ascites or with low MELD have excellent prognoses.

2-D Shear Wave Elastography for the Evaluation of Liver Fibrosis in Hepatosplenic Schistosomiasis: Reliability of a Single Measurement and Inter-Hepatic Lobe Variability.

Data on liver and spleen stiffness by 2-D shear wave elastography (2-D SWE) in hepatosplenic schistosomiasis (HES) remain scarce. We aimed to assess the correlation between single to multiple measurements of liver and spleen stiffness and to evaluate inter-hepatic lobe variability of liver stiffness measurement (LSM) using 2-D SWE in HES patients. Liver and spleen elastography were performed in HES patients in this cross-sectional study. A total of four stiffness measurements were performed in the right lobe (RL), left lobe (LL), and spleen. The correlation between the first measurement and the median of four measurements was assessed. Liver stiffness measurement of both hepatic lobes was compared. Twenty-six HES patients were included. Liver stiffness measurement was higher in the left than in the right hepatic lobe (17.9 kPa [11.3-92.0] versus 14.9 kPa [5.6-44.4]; P = 0.019). The first measurement was similar to the median of the four measurements for the RL (14.6 [5.6-60.8] versus 14.9 kPa [5.6-44.4]; P = 0.87), LL (17.4 [8.0-128.1] versus 17.9 kPa [11.3-92.0]; P = 0.54), and spleen (50.5 [10.0-157.0] versus 55.7 kPa [19.1-119.4]; P = 0.48). An excellent correlation between the first measurement and the median of four measurements for the RL (r = 0.93; P < 0.001), LL (r = 0.88; P < 0.001), and spleen (r = 0.89; P < 0.001) was observed. In HES, LSM of the LL seems to be higher than that of the right hepatic lobe. Considering the excellent correlation between the first measurement and the median of four measurements in both hepatic lobes and spleen, a single measurement would be sufficient to evaluate liver and splenic stiffness in patients with HES.

Combination and sequential evaluation of acute-on-chronic liver failure (ACLF) and hyponatremia and prognosis in cirrhotic patients.

BACKGROUND: Few studies have evaluated whether combination and sequential evaluation of ACLF (acute-on-chronic liver failure) and hyponatremia aids prognosis. AIMS: Describe clinical course and determine prognostic capability of assessing ACLF and hyponatremia at specific time-points. METHODS: Prospective study with inclusion of 376 patients. ACLF and hyponatremia were evaluated at days 1 and 7 and classified as persistent, transient, de novo or absent. Follow-up was 90 days. RESULTS: At inclusion, ACLF was diagnosed in 99 patients. Reversal was observed in 57 patients and was associated with lower creatinine and ACLF grade. De novo ACLF developed in 19 patients, and MELD (model of end-stage liver disease) score and lower albumin were predictive factors. Hyponatremia was present in 76 patients (persistent, transient and de novo in 27, 24 and 25 respectively). ACLF at D7 had the lowest survival compared to transient or no ACLF (21, 57 and 80%, p < 0.0001). Hyponatremia at admission was associated with low survival (35%) whereas survival was higher for de novo or absent cases (70%), p < 0.001. In multivariate analysis ACLF at D7 and hyponatremia at D1 were predictors of survival. CONCLUSION: ACLF and hyponatremia are dynamic and evaluation of both conditions at different time-points identifies patients at higher risk of short-term mortality.

Transient elastography evaluation of hepatic and spleen stiffness in patients with hepatosplenic schistosomiasis.

BACKGROUND: Hepatosplenic schistosomiasis (HES) has not been evaluated by transient elastography so far and its correlation with ultrasound variables remains to be defined. AIMS: The aim of this study was to describe the parameters of liver and spleen stiffness in HES assessed by transient elastography in comparison with cirrhotics and controls evaluating its correlation with ultrasonographic data. PATIENTS AND METHODS: HES, hepatitis C virus-cirrhotic, and control patients were included in this sectional study. Liver and spleen stiffness were compared among the three groups. The ultrasonographic parameters were compared with transient elastography in HES patients. RESULTS: Thirty HES, 30 hepatitis C virus-cirrhotic patients, and 17 controls were included. Those with HES presented liver stiffness that was significantly higher than the controls and lower than the cirrhotics: 9.7 (3.6-75.0) versus 3.7 (2.8-5.4) versus 27.0 (14.7-61.5) kPa (P<0.001). Spleen stiffness values were comparable between hepatosplenic and cirrhotics: 66.4 (25.7-75.0) versus 69.1 (18.0-75.0) kPa (P=0.78) and were significantly higher than the controls 16.5 kPa (6.3-34.3) (P<0.001). In patients with HES, high spleen stiffness was associated with right liver lobe diameter (P=0.015), splenic artery resistance index (P=0.002), portal vein diameter (P=0.021), portal vein area (P=0.008), portal vein congestion index (P=0.035), splenic vein diameter (P=0.013), and spleen diameter (P=0.021). CONCLUSION: Liver stiffness may be a useful tool to differentiate portal hypertension related to cirrhosis from that of HES. High spleen stiffness is a potential surrogate marker of portal hypertension in this population.

Métodos de imagem no diagnóstico de esquistossomose hepatoesplânica / Imaging techniques in the diagnosis of hepatosplenic schistosomiasis

A esquistossomose constitui grave problema de saúde pública, com mais de 200 milhões de infectados no mundo. Deste total, cerca de 10% desenvolvem a forma hepatoesplênica da doença caracterizada por fibrose periportal e hipertensão porta. No passado, o diagnóstico da esquistossomose hepatoesplênica (EHE) era realizado por métodos invasivos como esplenoportografia e biópsia hepática. O estudo das alterações no sistema porta e da morfologia hepática e esplênica com métodos de imagem representou um avanço significativo no diagnóstico da doença. Os métodos mais utilizados atualmente são a ultrassonografia abdominal, a ressonância nuclear magnética e a tomografia computadorizada de abdomen. O objetivo do presente artigo é abordar as principais contribuições de cada método no diagnóstico da EHE.

Schistosomiasis is a serious public health problem with over 200 million infected worldwide. Nearly 10% of infected individuals develop the hepatosplenic form of the disease characterized by periportal fi brosis and portal hypertension. In the past, the diagnosis of hepatosplenic schistosomiasis (HHS) was performed by invasive methods such as liver biopsy and splenoportography. The study of changes in portal system and morphological aspects of liver and spleen with imaging techniques represented a significant advance in the diagnosis of the disease. The most widely used techniques are abdominal ultrasonography, magnetic resonance imaging and computed tomography of the abdomen. The aim of this article is to discuss the main contribution of each technique in the diagnosis of HHS.