Long-term survival and clinical outcomes following direct-acting antiviral (DAA) treatment in HCV decompensated cirrhosis in Brazil: a real-world study.

INTRODUCTION: The outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario. PATIENTS AND METHODS: This was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method. RESULTS: One hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p < 0.001). CONCLUSIONS: Decompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.

Long-term survival and clinical outcomes following direct-acting antiviral (DAA) treatment in HCV decompensated cirrhosis in Brazil: a real-world study

Abstract Introduction The outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario. Patients and methods This was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method. Results One hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p< 0.001). Conclusions Decompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.

Systemic Inflammatory Response Syndrome in Patients Hospitalized for Acute Decompensation of Cirrhosis.

Background: Although recently challenged, systemic inflammatory response syndrome (SIRS) criteria are still commonly used in daily practice to define sepsis. However, several factors in liver cirrhosis may negatively impact its prognostic ability. Goals. To investigate the factors associated with the presence of SIRS, the characteristics of SIRS related to infection, and its prognostic value among patients hospitalized for acute decompensation of cirrhosis. Study. In this cohort study from two tertiary hospitals, 543 patients were followed up, up to 90 days. Data collection, including the prognostic models, was within 48 hours of admission. Results: SIRS was present in 42.7% of the sample and was independently associated with upper gastrointestinal bleeding (UGB), ACLF, infection, and negatively related to beta-blockers. SIRS was associated with mortality in univariate analysis, but not in multiple Cox regression analysis. The Kaplan-Meier survival probability of patients without SIRS was 73.0% and for those with SIRS was 64.7%. The presence of SIRS was not significantly associated with mortality when considering patients with or without infection, separately. Infection in SIRS patients was independently associated with Child-Pugh C and inversely related to UGB. Among subjects with SIRS, mortality was independently related to the presence of infection, ACLF, and Child-Pugh C. Conclusions: SIRS was common in hospitalized patients with cirrhosis and was of no prognostic value, even in the presence of infection.

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.

A class of residuals for outlier identification in zero adjusted regression models.

Zero adjusted regression models are used to fit variables that are discrete at zero and continuous at some interval of the positive real numbers. Diagnostic analysis in these models is usually performed using the randomized quantile residual, which is useful for checking the overall adequacy of a zero adjusted regression model. However, it may fail to identify some outliers. In this work, we introduce a class of residuals for outlier identification in zero adjusted regression models. Monte Carlo simulation studies and two applications suggest that one of the residuals of the class introduced here has good properties and detects outliers that are not identified by the randomized quantile residual.

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.

FUM Gene Expression Profile and Fumonisin Production by Fusarium verticillioides Inoculated in Bt and Non-Bt Maize.

This study aimed to determine the levels of fumonisins produced by Fusarium verticillioides and FUM gene expression on Bt (Bacillus thuringiensis) and non-Bt maize, post harvest, during different periods of incubation. Transgenic hybrids 30F35 YG, 2B710 Hx and their isogenic (30F35 and 2B710) were collected from the field and a subset of 30 samples selected for the experiments. Maize samples were sterilized by gamma radiation at a dose of 20 kGy. Samples were then inoculated with F. verticillioides and analyzed under controlled conditions of temperature and relative humidity for fumonisin B1 and B2 (FB1 and FB2) production and FUM1, FUM3, FUM6, FUM7, FUM8, FUM13, FUM14, FUM15, and FUM19 expression. 2B710 Hx and 30F35 YG kernel samples were virtually intact when compared to the non-Bt hybrids that came from the field. Statistical analysis showed that FB1 production was significantly lower in 30F35 YG and 2B710 Hx than in the 30F35 and 2B710 hybrids (P < 0.05). However, there was no statistical difference for FB2 production (P > 0.05). The kernel injuries observed in the non-Bt samples have possibly facilitated F. verticillioides penetration and promoted FB1 production under controlled conditions. FUM genes were expressed by F. verticillioides in all of the samples. However, there was indication of lower expression of a few FUM genes in the Bt hybrids; and a weak association between FB1 production and the relative expression of some of the FUM genes were observed in the 30F35 YG hybrid.