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.

Accuracy and concordance of two-dimensional shear-wave elastography using transient elastography as the reference in chronic viral hepatitis and HIV infection in Rio de Janeiro, Brazil.

OBJECTIVES: Evaluate the accuracy and agreement of two-dimensional shear-wave elastography (2D-SWE) LOGIQ-S8 with transient elastography in patients from Rio de Janeiro, Brazil. METHOD: This retrospective study compared liver stiffness measurements (LSMs) using transient elastography (M and XL probes) and 2D-SWE GE-LOGIQ-S8 performed by a single experienced operator on the same day in 348 consecutive individuals with viral hepatitis or HIV infection. Suggestive and highly suggestive compensated-advanced chronic liver disease (c-ACLD) were defined by transient elastography-LSM ≥10 kPa and ≥15 kPa, respectively. Agreement between techniques and accuracy of 2D-SWE using transient elastography-M probe as the reference was assessed. Optimal cut-offs for 2D-SWE were identified using the maximal Youden index. RESULTS: Three hundred five patients [61.3% male, median age = 51 [interquartile range (IQR), 42-62] years, 24% with hepatitis C virus (HCV) ± HIV; 17% with hepatitis B virus (HBV) ± HIV; 31% were HIV mono-infected and 28% had HCV ± HIV post-sustained virological response] were included. The overall correlation (Spearman's ρ ) was moderate between 2D-SWE and transient elastography-M ( ρ = 0.639) and weak between 2D-SWE and transient elastography-XL ( ρ = 0.566). Agreements were strong ( ρ > 0.800) in people with HCV or HBV mono-infection, and poor in HIV mono-infected ( ρ > 0.400). Accuracy of 2D-SWE for transient elastography-M ≥ 10 kPa [area under the receiver operating characteristic (AUROC) = 0.91 (95% confidence interval [CI], 0.86-0.96); optimal cut-off = 6.4 kPa, sensitivity = 84% (95% CI, 72-92), specificity = 89% (95% CI, 84-92)] and for transient elastography-M ≥ 15 kPa [AUROC = 0.93 (95% CI, 0.88-0.98); optimal cut-off = 7.1 kPa; sensitivity = 91% (95% CI, 75-98), specificity = 89% (95% CI, 85-93)] were excellent. CONCLUSION: 2D-SWE LOGIQ-S8 system had a good agreement with transient elastography and an excellent accuracy to identify individuals at high risk for c-ACLD.

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.

Results of interferon-free treatment for HCV-infected patients with decompensated cirrhosis from a Brazilian real-life cohort.

Real-life data on the HCV treatment with direct-acting agents in patients with decompensated cirrhosis are scarce. Study to investigate the effectiveness and safety of sofosbuvir-containing regimens in a prospective cohort of patients with HCV decompensated cirrhosis. A total of 150 patients were enrolled (64% male, 84% genotype 1 with a mean age of 61 ± 9 years). The median MELD was 12, and 79% were Child-PughB. Most patients were treated with sofosbuvir and daclatasvir (98%) with ribavirin in 27%. The overall intention to treat SVR12 was 91% (137/150). The most frequent adverse event was anemia (17%), 73% associated with ribavirin. Twenty-one (14%) patients experienced renal dysfunction, 81% AKI I, and 1 discontinued treatment. Thirty-five (23%) patients presented at least 1 infectious episode, mainly respiratory tract infection (29%). Thirty-three patients (22%) had at least 1 episode of cirrhosis decompensation throughout treatment, particularly worsening of previous ascites in 19%. Nine patients died, and among those, 7 patients died from sepsis. The probability of decompensation in 28, 90 and 180 days was 4%, 19% and 25%. During treatment, infection (OR 2.24; 95 CI 1.09-4.61; P = .03) was a predictor of cirrhosis decompensation, and baseline MELD and CHILD ≥ B8 were both associated with infection. In decompensated cirrhosis, the overall virological response was high with mild adverse events. However, this population had a high frequency of liver-associated decompensation and infections.

Agreement and accuracy of shear-wave techniques (point shear-wave elastography and 2D-shear-wave elastography) using transient elastography as reference.

OBJECTIVE: We aimed to evaluate the agreement/accuracy of point shear-wave elastography (p-SWE) and 2D-shear-wave elastography (2D-SWE) for liver fibrosis staging using transient elastography (TE) as the reference. METHODS: This retrospective study analyzed data from people with chronic liver diseases submitted to TE, p-SWE, and 2D-SWE. Liver fibrosis stages were defined using the TE's 'rule of five': normal (<5 kPa); suggestive of compensated-advanced chronic liver disease (cACLD) (10-15 kPa); highly suggestive of cACLD (15-20 kPa); suggestive of clinically significant portal hypertension (>20 kPa). Agreement and accuracy of p-SWE and 2D-SWE were assessed. Optimal cutoffs for p-SWE and 2D-SWE were identified using the point nearest to the upper left corner of the ROC curves. RESULTS: A total of 289 participants were included. The correlation between TE and 2D-SWE (rho = 0.59; P < 0.001) or p-SWE (rho = 0.69; P < 0.001) was satisfactory. The AUROCs (95% CI) of 2D-SWE and p-SWE for TE ≥ 5 kPa; TE ≥ 10 kPa; TE ≥ 15 kPa and TE ≥ 20 kPa were 0.757 (0.685-0.829) and 0.741 (0.676-0.806); 0.819 (0.770-0.868) and 0.870 (0.825-0.915); 0.848 (0.803-0.893) and 0.952 (0.927-0.978); 0.851 (0.806-0.896) and 0.951 (0.920-0.982), respectively. AUROCs of 2D-SWE were significantly lower compared with p-SWE for detecting cACLD. Optimal thresholds of 2D-SWE and p-SWE for TE ≥ 15 kPa were 8.82 kPa (sensitivity = 86% and specificity = 79%) and 8.86 kPa (sensitivity = 90% and specificity = 92%), respectively. CONCLUSION: LSM by p-SWE and 2D-SWE techniques were correlated with TE. LSM by p-SWE seems to be more accurate than 2D-SWE to identify patients with more advanced fibrosis.

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.

Liver stiffness regression after sustained virological response by direct-acting antivirals reduces the risk of outcomes.

The role of liver stiffness measurement (LSM) after sustained virological response (SVR) in HCV patients treated by direct-acting antivirals (DAAs) remains unclear. We aimed to evaluate LSM regression value after SVR and to identify risk factors associated with liver related complications (LRC) or death. This retrospective study analyzed patients with LSM ≥ 10 kPa with LSM by transient elastography pre-DAAs and post-SVR. Patients with previous hepatic decompensation were excluded. Medical records were reviewed to identify primary outcomes. Kaplan-Meier curves and time-to-event Cox proportional-hazard models were performed. 456 patients [65% female, 62 years (IQR 57-68)] were included. During a follow-up of 2.3 years (IQR 1.6-2.7), 28 patients developed 37 outcomes [rate = 29.0 (95% CI 20.0-42.0) per 1000 person-years]. The cumulative incidence of outcomes was significantly lower in patients who regressed LSM ≥ 20% [3.4% (95% CI 1.8-7.0) vs. 9.0% (5.5-14.5), p = 0.028]. In a multivariate Cox-model [HR(95% CI)], male gender [HR = 3.00 (1.30-6.95), p = 0.010], baseline albumin < 3.5 mg/dL [HR = 4.49 (1.95-10.34), p < 0.001] and baseline unfavorable Baveno-VI [HR = 4.72 (1.32-16.83), p = 0.017] were independently associated and LSM regression ≥ 20% after SVR had a trend to reduce the risk of LRC or death [HR = 0.45 (0.21-1.02), p = 0.058]. The use of simple parameters before DAAs and repetition of LSM post-SVR can identify patients with different risks for severe outcome after HCV eradication.

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.

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.

COVID-19 in liver transplant recipients.

Coronavirus disease 2019 (COVID-19), an infection caused by severe acute respiratory syndrome coronavirus-type 2 (SARS-CoV-2), has emerged as a serious threat to public health. Liver transplant (LT) recipients may be at increased risk of acquisition of SARS-CoV-2 infection and higher morbidity and mortality due to constant contact with health-care services, the use of immunosuppressants and frequent comorbidities. In the first part of this review we discuss (1) the epidemiology and risk factors for SARS-CoV-2 infection in LT recipients; (2) the clinical and laboratory features of COVID-19 in this specific population, highlighting differences in presenting signs and symptoms with respect to general populations and (3) the natural history and prognostic factors in LT recipients hospitalized with COVID-19, with particular focus on the possible role of immunosuppression. Thereafter, we review the potential therapeutic options for COVID-19 treatment and prevention. Specifically, we give an overview of current practice in immunosuppressant regimen changes, showing the potential benefits of this strategy, and explore safety and efficacy issues of currently approved drugs in LT recipients. The last topic is dedicated to the potential benefits and pitfalls of vaccination.

Effectiveness of direct-acting agents for chronic hepatitis C treatment in South America: A systematic review and meta-analysis.

The effectiveness of direct-acting agents (DAAs) for hepatitis C treatment in limited-resource settings remains unclear. We estimated the pooled sustained virological response rates of DAA therapy in South America. We searched online databases for studies that reported 12-week sustained virological response (SVR12) to hepatitis C virus (HCV) treatment in individuals living in South America. Pooled SVR12 in intention-to-treat (ITT) and per-protocol were estimated. Additionally, using all studies with available data, the pooled relative risk (RR) of SVR12 using a random-effects model (DerSimonian-Laird) was estimated to compare effectiveness of DAAs in patients with or without cirrhosis, HIV co-infection or previous HCV therapy. Heterogeneity was assessed using the I2 statistics. We identified 20 studies [14 manuscripts and 6 conference abstracts] comprising 7393 individuals from five countries [Brazil (n = 11), Argentina (n = 4), Chile (n = 1), Colombia (n = 1) and Peru (n = 1)] and two South-American collaborations. The pooled overall SVR12 rates [95% confidence interval (CI)] were 92.6% [90.2-94.7] and 95.5% [94.3-96.6] by ITT (11 studies; n = 4,153; I2  = 84.2%) and per-protocol analysis (15 studies; n = 4,833; I2  = 64.5%), respectively. The RR of SVR12 was similar in patients with or without HIV co-infection [4 studies; RR = 1.03 (0.99-1.07)] and those naive compared with treatment experimented-individuals [9 studies; RR = 1.01 (1.00-1.03)], but significantly higher in patients without cirrhosis compared with those with cirrhosis [11 studies; RR = 1.04 (1.02-1.05), P < .001]. DAAs are highly effective for HCV treatment in South America. The use of DAAs should be considered in limited-resource settings to decrease the burden of liver disease in HCV-infected patients. PROSPERO[CRD 42019134603].

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.

Effectiveness of direct-acting agents for hepatitis C and liver stiffness changing after sustained virological response.

BACKGROUND AND AIM: Few studies have evaluated sustained virological response (SVR) rates by direct-acting agents (DAAs) and liver stiffness measurement (LSM) changing post-SVR in limited-resource settings. We aimed to describe the effectiveness of DAAs for hepatitis C virus treatment and to assess the changing of LSM post-SVR. METHODS: This retrospective study analyzed data of consecutive hepatitis C virus-infected patients treated by DAAs from 2015 to 2017 in two tertiary centers in Brazil. SVR rates were reported by intention-to-treat and per-protocol analyses. LSM by transient elastography performed before treatment and post-SVR was compared, and logistic regression models were performed. RESULTS: Six hundred seventy-one patients (63% female, 62 years [55-68], 89% genotype 1, 8% HIV co-infected, and 64% with cirrhosis) were included. Most patients were treated by sofosbuvir/daclatasvir ± ribavirin (74%) and sofosbuvir/simeprevir ± ribavirin (21%). SVR rates (95% confidence interval [CI]) were 94.6% (92.7-96.1) and 97.8% (96.4-98.7) for intention-to-treat and per-protocol analyses, respectively. The leading adverse event was anemia (9.6% [95% CI 7.6-12.1]). Pretreatment and post-SVR12 LSM were available in 400 patients. LSM had significantly decreased after SVR (13.6 kPa [interquartile range, 10.0-21.6] vs 10.2 kPa [7.0-17.6], P < 0.001). A total of 167 patients (42%) decreased at least 30% of LSM post-SVR. The absence of type 2 diabetes (odds ratio = 1.52 [95% CI 1.05-2.21], P = 0.028) and presence of platelet count ≥ 150 × 109 /mm3 (odds ratio = 1.75 [1.23-2.50], P = 0.002) were independently associated with a significant LSM regression (≥ 30%) post-SVR. CONCLUSION: DAAs were highly effective and safe, and LSM significantly decreased after SVR in a real-life cohort in Brazil. The absence of type 2 diabetes and presence of high platelet count were independently associated with LSM decrease post-SVR.

IRRADIAÇÃO DE ARROZ E ALTERAÇÕES NAS SUAS PROPRIEDADES FÍSICO-QUÍMICAS E SENSORIAIS / IRRADIATION OF RICE AND CHANGES IN THEIR PHYSICOCHEMICAL AND SENSORY PROPERTIES

O objetivo do presente trabalho foi avaliar as propriedades físico-químicas e a aceitação sensorial do arroz submetido à radiação gama. As amostras de arroz comercial (IRGA 417), exceto o controle, foram submetidas às doses de radiação gama de 1, 2 e 5 kGy, na taxa de dose de 0,5 kGy/h. A irradiação promoveu redução no teor de amido e amarelecimento dos grãos. Quanto às propriedades de cocção, o arroz apresentou menor absorção de água e volume de expansão e maior perda de sólidos na água de cocção, conforme o aumento nas doses de radiação. A análise sensorial revelou boa aceitabilidade do arroz pelos julgadores, exceto para a dose de 5 kGy. A dose de 1 kGy destacou-se como a melhor para irradiação de arroz, pois não apresentou diferença do controle em nenhum parâmetro estudado.