Evolving portal hypertension through Baveno VII recommendations.

The Baveno VII consensus workshop has provided several novel recommendations regarding the management of patients with clinically significant portal hypertension (CSPH). The expert panel summarized the existing data into simple clinical rules to aid clinicians in their clinical practice. The use of non-invasive tests (NITs), especially liver stiffness measurement (LSM), have gain an important role in daily practice. The use of LSM alone or in combination with platelet count can be used to rule-in and rule-out compensated advanced chronic liver disease (cACLD) and CSPH. Further decompensation events were defined as a prognostic stage associated with an even higher mortality than that associated with first decompensation. Moreover, the term hepatic recompensation was introduced in Baveno VII consensus implying a partial or complete regression of the functional and structural changes of cirrhosis after the removal of the underlying etiology. This review will summarize the reader main aspects of Baveno VII consensus regarding the use of NITs in cACLD, analyze further decompensation events, and evaluate recent recommendations for prophylaxis and management of liver decompensation events.

Prevalence and factors associated with liver fibrosis among first-degree relatives of Mexican Americans with hepatocellular carcinoma.

BACKGROUND AND AIMS: Whether hepatocellular carcinoma (HCC) increases the familial risk for hepatic fibrosis has not been thoroughly explored, particularly in Mexican Americans who are disproportionately affected by obesity and metabolic syndrome. We evaluated the risk of significant hepatic fibrosis in first-degree relatives of Mexican American adults with HCC. METHODS: We performed a cross-sectional analysis of a prospective cohort of Mexican American probands with HCC and first-degree relatives enrolled in the Hispanic Liver Cancer Cohort study. We evaluated the prevalence of hepatic fibrosis in first-degree relatives, defined by liver stiffness measurement (LSM) >= 7.0 kPa with transient elastography (TE). Secondary outcomes included the prevalence of definite hepatic steatosis, defined by controlled attenuation parameter >=288 dB/m. RESULTS: We identified 70 probands diagnosed with HCC; 47% were female and the mean age was 62 years (±13 years). Among 112 first-degree relatives with a mean age of 43 years (±14 years), 19 (17%) had significant fibrosis and 47 (42%) had definite hepatic steatosis, respectively. The prevalence of significant fibrosis was 20% in first-degree relatives 40 years of age or older. Regression analysis revealed that diabetes (OR 3.2, 95% CI: 1.1-9.2, p = 0.03) and aspartate aminotransferase >=30 units/L (OR 4.0, 95% CI: 1.4-11.7, p = 0.01) were predictors of significant fibrosis in first-degree relatives. CONCLUSIONS: Using a well-phenotyped familial cohort, we found that the prevalence of significant fibrosis and definite hepatic steatosis are high in first-degree relatives of Mexican Americans with HCC, particularly those with diabetes, suggesting that this population may benefit from screening for liver disease.

Current Medical Treatment for Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

Assessment of liver disease by non-invasive methods in perinatally infected Brazilian adolescents and young adults living with Human Immunodeficiency Virus (HIV).

INTRODUCTION: Effective and long-term combined antiretroviral therapy (cART) has decreased morbidity and mortality in HIV-infected individuals. Despite treatment advances, HIV-infected children continue to develop noninfectious conditions, including liver fibrosis. METHODS: Cross-sectional study designed to identify liver fibrosis in HIV-infected adolescents and young adults, in an outpatients clinic of Pediatric Infectious Diseases Division at Escola Paulista de Medicina/Universidade Federal de São Paulo (UNIFESP), diagnosed by noninvasive methods (liver elastography-FibroScan®, APRI and FIB4). Variables examined included demographics, clinical, laboratories, HIV treatment. All participants underwent FibroScan® to measure liver parenchyma elasticity. Values equal to above 7.0 kPa were interpreted as the presence of significant liver fibrosis. Two different biomarkers of liver fibrosis were employed: the AST-to-Platelet Ratio Index (APRI) and the Fibrosis-4 score (FIB-4). APRI values above 1.5 have been considered as levels of clinically significant liver fibrosis and FIB-4 values above 3.25 suggested the presence of advanced fibrosis. RESULTS: Between August 2014 and March 2017, the study enrolled 97 patients, age 10-27 years old, fourteen of 97 subjects (14.4%) presented liver stiffness (≥7 kPa) detected by the liver elastography. No patient had APRI> 1.5. No patient had FIB4 value > 3.25. The only isolated laboratory parameter that could be significantly associated with high liver stiffness was thrombocytopenia (p = 0.022, Fisher's exact test). CONCLUSION: Liver stiffness was identified in 14.4% (14/97) of this cohort by liver elastography. Liver disease in HIV-infected adolescents and young adults manifests itself silently, so should be routinely investigated.

Liver stiffness as measured by transient elastography is a predictor of outcomes in patients with chronic heart failure with reduced, mid-range, and recovered left-ventricular ejection fraction.

Background: Transient elastography is a noninvasive method for assessing liver stiffness (LS), which can reflect right-sided filling pressure associated with passive liver congestion in patients with HF. Methods: A prospective, single-center observational study in which LS was measured in consecutive ambulatory patients with heart failure with reduced, mid-range, and recovered left ventricular ejection fraction, between March 2018 and June 2019. Mean follow up was 219 ± 86 days. The primary endpoint was time to first event, which was defined as a composite of cardiovascular death or HF hospitalization. Results: Eighty-five patients were included in the final analysis. Mean age was 62 ± 10 and 68% were male. Mean ejection fraction and median NT-proBNP were, respectively, 38.7 ± 14.3% and 1140 pg/mL (interquartile range 224.3-2810.3). The median LS for the entire population was 6.3 (2.5-41.2) kPa. LS correlated with NT-proBNP (r = 0.46; p < 0.0001), total bilirubin (r = 0.47; p < 0.001), direct bilirubin (r = 0.43; p = 0.0001), gama-glutamyl-transpeptidase (r = 0.54; p < 0.0001), and alkaline phosphatase (r = 0.39; p = 0.0004). A Receiver Operating Characteristic (ROC) curve was performed and a cut point of 5.9 kPa showed sensitivity of 80% and specificity of 64.1% with area under the curve of 0.73. Using Cox proportional hazard model (independent variables: LS as a continuous variable, age, gender, NT-proBNP, LVEF, and creatinine), only LS was independently associated with the primary endpoint (hazard ratio 1.05, 95% confidence interval 1.01-1.09; for each increment of one unit of LS). Conclusion: LS correlates with biomarkers of myocardial stretch and several liver function tests and is an independent predictor of outcomes in ambulatory patients with HF.

Assessment of liver disease by non-invasive methods in perinatally infected Brazilian adolescents and young adults living with Human Immunodeficiency Virus (HIV)

ABSTRACT Introduction: Effective and long-term combined antiretroviral therapy (cART) has decreased morbidity and mortality in HIV-infected individuals. Despite treatment advances, HIV-infected children continue to develop noninfectious conditions, including liver fibrosis. Methods: Cross-sectional study designed to identify liver fibrosis in HIV-infected adolescents and young adults, in an outpatients clinic of Pediatric Infectious Diseases Division at Escola Paulista de Medicina/Universidade Federal de São Paulo (UNIFESP), diagnosed by noninvasive methods (liver elastography-FibroScan®, APRI and FIB4). Variables examined included demographics, clinical, laboratories, HIV treatment. All participants underwent FibroScan® to measure liver parenchyma elasticity. Values equal to above 7.0 kPa were interpreted as the presence of significant liver fibrosis. Two different biomarkers of liver fibrosis were employed: the AST-to-Platelet Ratio Index (APRI) and the Fibrosis-4 score (FIB-4). APRI values above 1.5 have been considered as levels of clinically significant liver fibrosis and FIB-4 values above 3.25 suggested the presence of advanced fibrosis. Results: Between August 2014 and March 2017, the study enrolled 97 patients, age 10-27 years old, fourteen of 97 subjects (14.4%) presented liver stiffness (≥7 kPa) detected by the liver elastography. No patient had APRI> 1.5. No patient had FIB4 value > 3.25. The only isolated laboratory parameter that could be significantly associated with high liver stiffness was thrombocytopenia (p= 0.022, Fisher's exact test). Conclusion: Liver stiffness was identified in 14.4% (14/97) of this cohort by liver elastography. Liver disease in HIV-infected adolescents and young adults manifests itself silently, so should be routinely investigated.

What's new in portal hypertension?

Portal hypertension is defined as increased pressure in the portal venous system. The most common cause of portal hypertension is cirrhosis. In this setting, there is an increase in intrahepatic resistance leading to an increase in portal pressure. By increasing portal blood flow, splanchnic vasodilation further aggravates portal hypertension. New pathogenic pathways are being established which might result in new therapeutic strategies. The presence of varices at endoscopy and/or other abdominal portosystemic collaterals confirms the diagnosis of portal hypertension. The role of non-invasive and imaging tests in the diagnosis and prognosis of portal hypertension has been clarified. Non-selective beta-blockers decrease both the risk of variceal haemorrhage and hepatic decompensation. Terlipressin, somatostatin or octreotide, in combination with early endoscopic therapy, are recommended for the treatment of acute variceal haemorrhage. Early Transjugular intrahepatic portosystemic shunt (TIPS) is effective as salvage therapy in acute variceal bleeding in selected patients and prevents rebleeding more effectively than endoscopic and medical therapy resulting in an increased survival.

Spleen Stiffness Probability Index (SSPI): A simple and accurate method to detect esophageal varices in patients with compensated liver cirrhosis.

INTRODUCTION AND OBJECTIVES: Recent findings pointed out that even low-risk esophageal varices (EVs) are markers of severe prognosis. Accordingly, we analyzed spleen stiffness (SS) as a non-invasive method to predict EVs of any grade in a cohort of patients with compensated liver cirrhosis. METHOD: We measured SS and liver stiffness (LS) using point-Shear-Wave Elastography (pSWE) with Philips Affiniti 70 system in 210 cirrhotic patients who had undergone endoscopic screening for EVs. We compared SS and LS predictive capability for EVs of any grade. RESULTS: SS was higher in cirrhotic patients with EVs if compared to patients without EVs (p<0.001). The cut-off analysis detected 31kPa (100% sensitivity and negative predictive value) as the value to rule-out EVs and 69kPa (100% specificity and positive predictive value) to rule-in EVs. Besides, we developed the Spleen Stiffness Probability Index (SSPI), that can provide a probability of presence/absence of EVs. SSPI was the best model according to all discriminative and calibration metrics (AIC=120, BIC=127, AUROC=0.95, Pseudo-R2=0.74). SS demonstrated higher correlation with spleen bipolar diameter and spleen surface (r=0.52/0.55) if compared to LS (r=0.30/0.25) - and with platelet count as well (r=0.67 vs r=0.4). CONCLUSION: SS showed significantly higher performance than other parameters, proving to be the best non-invasive test in the screening of EVs: by directly applying SS cut-off of 31kPa, our department could have safely avoided endoscopy in 36% of patients. Despite cut-off analyses, it was possible to create a probability model that could further stratify low-risk from high-risk patients (for any grade of EVs).

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.

Assessment of Nonalcoholic Fatty Liver Disease Progression in Children Using Magnetic Resonance Imaging.

OBJECTIVE: To assess liver disease progression using paired magnetic resonance imaging (MRI) measurements of liver fat fraction (FF) and stiffness. STUDY DESIGN: Retrospective cohort study including patients with nonalcoholic fatty liver disease who had undergone repeat MRI studies. Descriptive statistics were used, as well as Pearson or Spearman correlation when appropriate. Mixed model analyses were used to determine relationships between liver FF/stiffness and predictor variables. RESULTS: Sixty-five patients (80% non-Hispanic, mean age 14 ± 3 years) were included. Time from first to last MRI was 27 ± 14 months. Over time, body mass index z score remained stable, and there were no significant differences in mean serum aminotransferases, insulin, glucose, triglycerides, low-density lipoprotein, and high-density lipoprotein (HDL) levels. However, the proportion of patients with alanine aminotransferase (ALT) < 50 U/L increased. MRI FF and stiffness decreased in 29% and 20% of patients, respectively, and increased in 25% and 22% of patients, respectively. There was a weak positive correlation between FF change and ALT change (r = 0.41, P = .053) and a moderate negative correlation between change in FF and change in serum HDL levels (r = -0.58, P = .004). After adjusting for HDL, increase in serum insulin was the only variable predictive of increase in FF (P = .061). There was no correlation between change in liver stiffness and change in ALT (r = .02, P = .910). CONCLUSIONS: MRI-determined hepatic FF and stiffness improved in a minority of patients overtime. ALT levels were not reflective of the change in FF or stiffness. MRI-based imaging is complementary in the assessment of NAFLD progression.

The Diagnostic Value of FibroScan in Assessing Significant Liver Fibrosis in Patients with Chronic Hepatitis B.

OBJECTIVE: Significant liver fibrosis is recognized as the key link of therapy and prognosis in patients with chronic hepatitis B infection (CHB). The present study is designed to estimate the benefits of FibroScan (FS) in diagnosing significant fibrosis in patients with CHB. METHODS: Two hundred and eight consecutive CHB patients, who underwent liver biopsy, FS and laboratory tests, were recruited. The receiver operating characteristic (ROC) curves were generated to assess the performance of non-invasive models. RESULTS: Liver stiffness measurement (LSM) and aspartate transaminase (AST) to platelet (PLT) ratio index (APRI), but not age-platelet index (API) or AST to alanine aminotransferase (ALT) ratio (AAR), were closely correlated with significant fibrosis; areas under ROC curves (AUROC) were 0.817 (p < 0.001), 0.705 (p = 0.003), 0.626 (p = 0.065) and 0.631 (p = 0.055), respectively. When combining LSM with APRI, the AUROC was 0.813, p < 0.001. CONCLUSION: FibroScan can predict the presence of significant liver fibrosis, so as to avoid liver biopsy. It seems that the combination of FS and APRI does not significantly improve the ability to predict significant fibrosis.

Elastography and Contrast-enhanced Ultrasonography in the Early Detection of Hepatocellular Carcinoma in an Experimental Model of Nonalcoholic Steatohepatitis.

BACKGROUND/OBJECTIVE: The early detection of focal hepatic lesions using ultrasound scanning is challenging, and this challenge becomes even greater in the presence of diffuse parenchymal disease. This study aimed to evaluate the diagnostic performance of elastography and contrast-enhanced ultrasonography (CEUS) in the early detection of hepatocellular lesions in an experimental rat model of nonalcoholic steatohepatitis (NASH). METHODS: B-mode and Doppler ultrasonography was performed weekly in 30 rats divided into a NASH group (n = 20) and a group without liver disease (n = 10). The animals underwent elastography and CEUS and were then euthanized. Liver nodules were assessed by histopathology. RESULTS: Doppler mapping results of lesions with vascularization were considered indicative of malignancy, with a sensitivity of 29% before and 71% after contrast injection. The specificity was 71% before and 96% after CEUS. Elastograms of positive lesions showed areas of high stiffness, which were indicative of malignancy. This malignancy was confirmed by the histologic evaluation, with a sensitivity of 90% and a specificity of 60%. After CEUS analysis, 4 nodules were identified that were not observed on B-mode ultrasonography. Early wash-in was significantly associated with malignancy (sensitivity of 88% and specificity of 67%). CONCLUSIONS: Both techniques allow for the correct diagnosis of well-differentiated to moderately differentiated hepatocellular carcinomas with good accuracy in an experimental rat model of NASH.