Probiotic Supplementation, Hepatic Fibrosis, and the Microbiota Profile in Patients with Nonalcoholic Steatohepatitis: A Randomized Controlled Trial.

BACKGROUND: Promising results in improvement of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) have been identified following probiotic (PRO) treatment. OBJECTIVES: To evaluate PRO supplementation on hepatic fibrosis, inflammatory and metabolic markers, and gut microbiota in NASH patients. METHODS: In a double-blind, placebo-controlled clinical trial, 48 patients with NASH with a median age of 58 y and median BMI of 32.7 kg/m2 were randomly assigned to receive PROs (Lactobacillus acidophilus 1 × 109 colony forming units and Bifidobacterium lactis 1 × 109 colony forming units) or a placebo daily for 6 mo. Serum aminotransferases, total cholesterol and fractions, C-reactive protein, ferritin, interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, and leptin were assessed. To evaluate liver fibrosis, Fibromax was used. In addition, 16S rRNA gene-based analysis was performed to evaluate gut microbiota composition. All assessments were performed at baseline and after 6 mo. For the assessment of outcomes after treatment, mixed generalized linear models were used to evaluate the main effects of the group-moment interaction. For multiple comparisons, Bonferroni correction was applied (α = 0.05/4 = 0.0125). Results for the outcomes are presented as mean and SE. RESULTS: The AST to Platelet Ratio Index (APRI) score was the primary outcome that decreased over time in the PRO group. Aspartate aminotransferase presented a statistically significant result in the group-moment interaction analyses, but no statistical significance was found after the Bonferroni correction. Liver fibrosis, steatosis, and inflammatory activity presented no statistically significant differences between the groups. No major shifts in gut microbiota composition were identified between groups after PRO treatment. CONCLUSIONS: Patients with NASH who received PRO supplementation for 6 mo presented improvement in the APRI score after treatment. These results draw attention to clinical practice and suggest that supplementation with PROs alone is not sufficient to improve enzymatic liver markers, inflammatory parameters, and gut microbiota in patients with NASH. This trial was registered at clinicaltrials.gov as NCT02764047.

Validation and Performance of FibroScan®-AST (FAST) Score on a Brazilian Population with Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIM: FAST score has a good performance for diagnosing the composite of NASH + NAS ≥ 4 + F ≥ 2. However, it has not been evaluated in Latin American individuals with nonalcoholic fatty liver disease (NAFLD). We aimed to analyze the performance of the FAST score in a Brazilian NAFLD population. METHODS: Cross-sectional study was held in ≥ 18 years NAFLD patients diagnosed by ultrasonography and submitted to liver biopsy (LB). Liver stiffness (LSM) and CAP measurements were performed with FibroScan®, using M (BMI < 32 kg/m2) or XL probes. Area under receiver operating characteristic (AUROC) curves were calculated as well as sensitivity (S), specificity (Spe), positive predictive value (VPP) and negative predictive value (NPV) for the previously established FAST score cut-offs. RESULTS: Among 287 patients included (75% female; mean age 55 ± 10 years), NASH + NAS ≥ 4 + F ≥ 2 was reported in 30% of LB. For the FAST cut-off of 0.35, the S and NPV to rule out NASH + NAS ≥ 4 + F ≥ 2 were 78.8% and 87.8%, respectively. Regarding the cut-off of 0.67, the Spe and PPV to rule-in NASH + NAS ≥ 4 + F ≥ 2 were 89.1%, 61.8%, respectively. The AUROC of FAST for all included patients was 0.78 (95% CI 0.72-0.84) and for those with ≥ 32 kg/m2 was 0.81 (95% CI 0.74-0.88). CONCLUSION: FAST score has a good performance in a Brazilian NAFLD population, even in patients with higher BMI when the XL probe is adopted. Therefore, FAST can be used as a noninvasive screening tool mainly for excluding the diagnosis of progressive NASH, reducing the number of unnecessary liver biopsies.

Albumin in the management of hepatic encephalopathy: A systematic review and meta-analysis.

Introduction and objectives It has been suggested that albumin administration could alter the natural history of cirrhosis, and also, that long-term treatment with albumin might be associated with improvement in survival, control of ascites, reduction in the incidence bacterial infections, renal dysfunction, hepatic encephalopathy (HE) and hyponatremia, as well as reduction in length of hospitalization in patients with cirrhosis and ascites. The objective of the present study is to evaluate the role of albumin in the management of HE. Materiales and methods:: This is a systematic review of randomized controlled trials that evaluated the use of albumin in adult patients with cirrhosis and HE. The search for eligible studies was performed in MEDLINE, EMBASE, and Cochrane CENTRAL databases until June 2020. The outcomes of interest were the complete reversal of HE and mortality. Meta-analysis was performed using the random effects model, through the Mantel-Haenszel method. Results: This systematic review was registered at the PROSPERO platform (CRD42020194181). The search strategy retrieved 1,118 articles. After reviewing titles and abstracts, 24 studies were considered potentially eligible, but 22 were excluded after full-text analysis. Finally, 2 studies were included. In the meta-analysis, albumin was associated to significant lower risks of persistent HE (risk ratio - RR = 0.60; 95% confidence interval - CI = 0.38-0.95, p = 0.03) and mortality (RR = 0.54; 95% CI = 0.33-0.90, p = 0.02). Conclusion: Albumin administration improves HE and reduces mortality in patients with cirrhosis and HE.

Brazilian Society of Hepatology and Brazilian College of Radiology practice guidance for the use of elastography in liver diseases.

In 2015 the European Association for the Study of Liver Diseases (EASL) and the Asociación Latinoamericana para el Estudio del Hígado (ALEH) published a guideline for the use of non-invasive markers of liver disease. At that time, this guideline focused on the available data regarding ultrasonic-related elastography methods. Since then, much has been published, including new data about XL probe use in transient elastography, magnetic resonance elastography, and non-invasive liver steatosis evaluation. In order to draw evidence-based guidance concerning the use of elastography for non-invasive assessment of fibrosis and steatosis in different chronic liver diseases, the Brazilian Society of Hepatology (SBH) and the Brazilian College of Radiology (CBR) sponsored a single-topic meeting on October 4th, 2019, at São Paulo, Brazil. The aim was to establish specific recommendations regarding the use of imaging-related non-invasive technology to diagnose liver fibrosis and steatosis based on the discussion of evidence-based topics by an organizing committee of experts. It was submitted online to all SBH and CBR members. The present document is the final version of the manuscript that supports the use of this new technology as an alternative to liver biopsy.

Role of zinc supplementation in the management of chronic liver diseases: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Zinc deficiency has been associated with poor prognosis in chronic liver disease. This systematic review and meta-analysis aimed to evaluate the role of zinc supplementation in the management of chronic liver diseases. MATERIALS AND METHODS: We searched MEDLINE, LILACS, EMBASE, and Cochrane CENTRAL databases from inception to August 2018. We included randomized controlled trials evaluating adult patients with chronic liver disease of any etiology receiving zinc supplementation. Studies with other designs or evaluating chronic conditions other than liver disease were excluded. Two reviewers independently screened and extracted data from eligible studies. Study quality was assessed using the Cochrane Collaboration's tool for assessing risk of bias in randomized studies. RESULTS: Of 1315 studies screened, 13 were included. Six assessed chronic hepatitis C treatment, with a relative risk of 0.83 indicating no protective effect of zinc supplementation on the improvement of sustained virological response. Three evaluated response to hepatic encephalopathy treatment, with a relative risk of 0.66 indicating a favorable effect of zinc supplementation on clinical improvement of this condition. Of four studies evaluating the management of cirrhosis, two analyzed the effect of zinc supplementation on serum albumin levels, with no statistical difference between zinc and placebo groups. CONCLUSIONS: Clinical trials assessing zinc supplementation in liver diseases do not show benefits in terms of clinical improvement or disease halting. There are possible benefits of zinc supplementation on hepatic encephalopathy, however, this is based on limited evidence. This research question is still open for evaluation in larger, well-designed, clinical trials.

Evaluation of thrombocytopenia in patients with non-alcoholic fatty liver disease without cirrhosis.

INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries. It is often related to metabolic syndrome, presenting an increased risk of advanced liver disease and cardiovascular-related death. In some etiologies of chronic liver disease, thrombocytopenia has been associated not only with advanced stages of fibrosis but also with autoimmune disease. In NAFLD, however, its prevalence and related factors are still unknown. The aim of this study is to evaluate the prevalence of thrombocytopenia in NAFLD patients without cirrhosis and to investigate its related risk factors. PATIENTS AND METHODS: This was a retrospective study carried out in two tertiary hospitals in the South and Southeast regions of Brazil. Patients diagnosed with NAFLD by liver biopsy were included. Those with other causes of liver disease and/or cirrhosis were excluded. For analysis, patients were divided into two groups, with and without thrombocytopenia. Data was analyzed using a significance level of 5%. RESULTS: 441 non-cirrhotic patients with NAFLD (evaluated by liver biopsy) were included in the study. The prevalence of thrombocytopenia was 3.2% (14/441 patients). In the comparative analysis between groups, thrombocytopenia was associated with male sex (p=0.007) and level of hemoglobin (p=0.023). CONCLUSION: Thrombocytopenia is an infrequent event in NAFLD patients without cirrhosis and is related with male sex and higher hemoglobin levels.

Drug and herb-induced liver injury: A critical review of Brazilian cases with proposals for the improvement of causality assessment using RUCAM.

INTRODUCTION AND OBJECTIVES: Although hepatotoxicity accounts for 10% of adverse drug reactions, it remains poorly understood and underreported. This study aimed to summarize case reports of herb- and drug-induced liver injury in Brazil. METHODOLOGY: Systematic review in the following databases: PubMed, SciELO, Science Direct, CAPES, and gray literature. RESULTS: Twenty-seven studies reporting 32 cases were identified. Brazilian cases were primarily detected in hospitals, and occurred mainly in young males suffering from chronic diseases. Drugs (n=29) were a more frequent cause of liver injury than herbs (n=3). Almost a third of these drugs were anticonvulsants, and 15 appear in the Brazilian List of Essential Medicines. In 50% of the cases, clinical manifestations started within 30 days of drug ingestion. Regarding the decline of liver enzymes, 50% of the cases reached normality after drug withdrawal. However, 7 deaths and 2 liver transplantations were reported. Only one study assessed causality using RUCAM. CONCLUSION: Given the severe outcomes of DILI and HILI, early detection and management of hepatotoxicity to increase drug safety are necessary, as well as pharmacotherapeutic monitoring of patients with chronic diseases. Moreover, the application of the RUCAM algorithm in clinical practice has to be further disseminated.

Acute-on-chronic liver failure: A comparison of three different diagnostic criteria.

INTRODUCTION AND AIM: Different criteria are applied for the diagnosis of acute-on-chronic liver failure (ACLF). Our aim was to compare the performance of different ACLF diagnostic criteria for predicting mortality. MATERIALS AND METHODS: This was a prospective cohort study of adult cirrhotic patients admitted to a tertiary hospital for acute decompensation (AD) of cirrhosis. The evaluated outcome was mortality at 28 and 90 days, according to the different ACLF diagnostic criteria: Chronic Liver Failure Consortium (CLIF-C), Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC) and North American Consortium for the Study of End-Stage Liver Disease (NACSELD). Prognostic performance was evaluated using receiver operating characteristic (ROC) curves. RESULTS: 146 patients were included. 43 (29.5%) with ACLF according to CLIF-C definition, 14 (9.6%) with ACLF by AARC definition, and 6 (4.1%) by NACSELD definition. According to Kaplan-Meier survival analyses median survival of patients with ACLF by CLIF-C definition was 27.0 days, median survival of patients with ACLF by AARC definition was 27.0 days, and median survival of patients with ACLF by NACSELD definition was 4.0 days. The areas under the ROC curves for performance evaluation in predicting mortality at 28 days for CLIF-C, AARC and NACSELD criteria were, respectively, 0.710, 0.560 and 0.561 (p=0.002). Regarding 90-day mortality, the areas under the ROC curves were 0.760, 0.554 and 0.555 respectively (p<0.001). CONCLUSION: ACLF definition proposed by CLIF-C had better performance in predicting mortality at 28 and 90 days when compared to criteria proposed by AARC and NACSELD.

Evaluation of response to hepatitis B virus vaccine in adults with human immunodeficiency virus.

INTRODUCTION AND AIM: Viral hepatitis is a serious public health problem. The risk of progression to chronic hepatitis in hepatitis B virus (HBV) infection occurs in 5-10% of adults and is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Individuals infected with human immunodeficiency virus (HIV) may have coinfection with HBV. The existence of unvaccinated groups represents a significant risk not only individually but also at the community level. The aim of this study was to evaluate HBV vaccine response in adults with HIV infection. MATERIALS AND METHODS: A retrospective, descriptive study of the cross-sectional type was carried out in an outpatient HIV referral center in southern Brazil. All medical records of adult HIV patients seen during January 2006 to December 2015 were selected. In statistical analysis, a significance level of 5% was used. RESULTS: Of the 201 patients evaluated with a complete vaccination scheme, 55.72% were males, with a mean age of 43.86±12.68 years. Vaccine response occurred in 80.10% (161/201) of the patients, and it did not correlate with age, CD4+ cell count or viral load. CONCLUSION: HBV vaccine response in a HIV population was satisfactory, highlighting the importance of vaccination for prevention, cost reduction and better prognosis in preventing HBV/HIV coinfection.

Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD).

INTRODUCTION AND AIM: The gold-standard for fibrosis diagnosis in non-alcoholic fatty liver disease (NAFLD) is liver biopsy, despite its invasive approach, sampling limitations and variability among observers. The objective was to validate the performance of non-invasive methods (Fibroscan™; APRI, FIB4 and NAFLD score) comparing with liver biopsy in the evaluation of liver fibrosis in patients with NAFLD. MATERIAL AND METHODS: NAFLD patients ≥18 years of age who were submitted to liver biopsy were included and evaluated at two reference tertiary hospitals in Brazil with transient hepatic elastography (THE) assessment through Fibroscan™, APRI, FIB4 and NAFLD scores were determined. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for the diagnosis of advanced fibrosis were calculated to evaluate the performance of these non-invasive methods in NAFLD patients, adopting liver biopsy as the gold standard. RESULTS: A total of 104 patients were studied. At three different cutoff values (7.9, 8.7 and 9.6kPa) THE presented the highest sensitivity values (95%, 90% and 85% respectively), and the highest NPV (98%, 96.4% and 95.1% respectively) for the diagnosis of advanced fibrosis. It also presented the highest AUROC (0.87; CI 95% 0.78-0.97). CONCLUSION: When compared to the gold standard, transient hepatic elastography presented the best performance for the diagnosis and exclusion of advanced fibrosis in patients with NAFLD, overcoming APRI, FIB4 and NAFLD score.

Biochemical non-invasive assessment of liver fibrosis cannot replace biopsy in HIV-HCV coinfected patients.

BACKGROUND AND RATIONALE: The liver biopsy has been considered the gold standard for the diagnosis and quantification of fibrosis. However, this method presents limitations. In addition, the non-invasive evaluation of liver fibrosis is a challenge. The aim of this study was to validate the fibrosis cirrhosis index (FCI) index in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, and compare to AST/ALT ratio (AAR), AST to platelet ratio index (APRI) and FIB-4 scores, as a tool for the assessment of liver fibrosis in coinfected patients. MATERIAL AND METHODS: Retrospective cross sectional study including 92 HIV-HCV coinfected patients evaluated in two reference centers for HIV treatment in the Public Health System in Southern Brazil. Patients who underwent liver biopsy for any indication and had concomitant laboratory data in the 3 months prior to liver biopsy, to allow the calculation of studied noninvasive markers (AAR, APRI, FIB-4 and FCI) were included. RESULTS: APRI < 0.5 presents the higher specificity to detect no or minimal fibrosis, whereas APRI > 1.5 presents the best negative predictive value and FCI > 1.25 the best specificity to detect significant fibrosis. The values of noninvasive markers for each Metavir fibrosis stage showed statistically significant differences only for APRI. In conclusion, until better noninvasive markers for liver fibrosis are developed and validated for HIV-HCV coinfected patients, noninvasive serum markers should be used carefully in this population.

Efficacy of entecavir and tenofovir in chronic hepatitis B under treatment in the public health system in southern Brazil.

There are about 350 million hepatitis B virus (HBV) carriers worldwide and chronic HBV is considered a major public health problem. The objective of the present study was to assess the effectiveness of the nucleos(t)ide analogues tenofovir (TDF) and entecavir (ETV) in the treatment of chronic HBV. A cross-sectional study was carried out from March-December 2013, including all patients with chronic HBV, over 18 years of age, undergoing therapy through the public health system in southern Brazil. Only the data relating to the first treatments performed with TDF or ETV were considered. Retreatment, co-infection, transplanted or immunosuppressed patients were excluded. Six hundred and forty patients were evaluated, of which 336 (52.5%) received TDF and 165 (25.8%) ETV. The other 139 (21.7%) used various combinations of nucleos(t)ide analogues and were excluded. The negativation of viral load was observed in 87.3% and 78.8% and the negativation of hepatitis B e antigen was achieved in 79% and 72% of those treated with ETV or TDF, respectively. Negativation of hepatitis B surface antigen was not observed. There was no occurrence of adverse effects. This is a real-life study demonstrating that long-term treatment with ETV and TDF is both safe and effective.

Non-Alcoholic Steatohepatitis (NASH): Risk Factors in Morbidly Obese Patients.

The aim was to investigate the prevalence of non-alcoholic steatohepatitis (NASH) and risk factors for hepatic fibrosis in morbidly obese patients submitted to bariatric surgery. This retrospective study recruited all patients submitted to bariatric surgery from January 2007 to December 2012 at a reference attendance center of Southern Brazil. Clinical and biochemical data were studied as a function of the histological findings of liver biopsies done during the surgery. Steatosis was present in 226 (90.4%) and NASH in 176 (70.4%) cases. The diagnosis of cirrhosis was established in four cases (1.6%) and fibrosis in 108 (43.2%). Risk factors associated with NASH at multivariate analysis were alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN); glucose ≥ 126 mg/dL and triglycerides ≥ 150 mg/dL. All patients with ALT ≥1.5 times the ULN had NASH. When the presence of fibrosis was analyzed, ALT > 1.5 times the ULN and triglycerides ≥ 150 mg/dL were risk factors, furthermore, there was an increase of 1% in the prevalence of fibrosis for each year of age increase. Not only steatosis, but NASH is a frequent finding in MO patients. In the present study, ALT ≥ 1.5 times the ULN identifies all patients with NASH, this finding needs to be further validated in other studies. Moreover, the presence of fibrosis was associated with ALT, triglycerides and age, identifying a subset of patients with more severe disease.

Probiotics and synbiotics may improve liver aminotransferases levels in non-alcoholic fatty liver disease patients.

Non-alcoholic fatty liver disease (NAFLD) is defined as a spectrum of liver diseases ranging from simple steatosis to steatohepatitis (NASH). Alterations in intestinal microbiota and inflammatory response may play a key role in disease progression and development of complications in liver diseases, mainly in cirrhosis and NASH. The aim of this study was to perform a systematic review on randomized clinical trials (RCTs) testing probiotics, prebiotics or both (synbiotics) in the treatment of NAFLD in adult patients. After the screening process, 9 full-text articles were included in the review and 6 studies were excluded. Three randomized controlled trials were finally included in the qualitative synthesis. All patients in all the 3 studies were randomized to receive different formulations of probiotics, synbiotics or placebo. Reductions in aminotransferases were observed in the treated group in 2 of the studies. However, in one study reductions were also detected in the control group. In conclusion, the available evidence precludes, for the moment, recommendations on the use of pre and probiotics in clinical practice.

SPONTANEOUS REGRESSION OF HEPATOCELLULAR CARCINOMA: FOCUSING IN THE ASSOCIATED RISK FACTORS.

BACKGROUND: Spontaneous regression (SR) is defined as the partial or complete disappearance of a tumor, in the absence of a specific treatment. Evidence of the SR in hepatocellular carcinoma (HCC) is rare. OBJECTIVE: The authors aimed to review all the cases of SR of HCC in two reference centers of Southern Brazil, highlighting the main characteristics. METHODS: Data of all patients with HCC were retrospectively reviewed looking for the occurrence of SR in patients from two tertiary centers in Southern Brazil, in the last five years. The diagnosis of cirrhosis was established according to clinical, laboratory and imaging data, as well as upper endoscopy or histopathological examination when necessary. The diagnosis of HCC was based on typical findings according to radiologic criteria (LIRADS) or histopathological examination. Spontaneous regression was defined as a partial or complete involution of a HCC in the absence of a specific therapy. RESULTS: From all cases of HCC in the last 5 years (n=433), there were five cases of SR. Three (60%) were men, the mean age was 62.6 (50.0-76.0) years, and the etiology was HCV in 3 (60%). Complete regression was observed in three patients (60%), one patient (20%) presented partial regression, and one (20%) relapesed and died. The time of follow-up varied between 12 and 21 months. In this presentation, it was highlighted one case of SR observed after COVID-19 infection in a patient with cirrhosis. The possible mechanisms involved in this situation were reviewed, emphasizing the most common like hypoxia and immunological. There were also one patient submitted to a surgical procedure as a possible fator involved and three patients without obvious risk factors. CONCLUSION: This phenomenon will possibly contribute to a better understanding of the pathophysiological mechanisms of HCC.

Percutaneous liver biopsy--2 decades of experience in a public hospital in the South of Brazil.

INTRODUCTION: Liver biopsy is a complementary method for diagnosis, staging and therapeutic guidance in liver diseases, where chronic viral hepatitis are the most acknowledged causes for the indication of histopathological study. The objective is to assess the patients' profile as well as the indication and results of percutaneous liver biopsies in a tertiary hospital. MATERIAL AND METHODS: A descriptive, cross-section study was carried out through the review of medical charts (retrospective cohort) of patients submitted to blind percutaneous liver biopsies (PLB) at a hospital in Porto Alegre, South Brazil, from October 1993 to December 2011. RESULTS: 1,955 PLB were carried out, the mean patients' age was 44.8 years old, and 1,127 (57.65%) were men. Chronic hepatitis C was the main indication (60.5%), followed by HCV-HIV coinfection (12.2%) and chronic hepatitis B (3.5%). Seven cases (0.3%) had complications, without deaths. CONCLUSION: PLB is a safe method and continues to be an important option to assist patients with chronic liver disease.

THE ROLE OF ELASTOGRAPHY IN CLINICALLY SIGNIFICANT PORTAL HYPERTENSION.

• In compensated cirrhosis, using non-invasive methods would exempt the patient from the need of an endoscopy. • The Baveno VII presented the "rule of 5" for Vibration-Controlled Transient Elastography; liver stiffness measurement ≤15 kPa and platelets >150.000/mm3 exclude clinically significant portal hypertension (CSPH), while when ≥25 kPa is highly suggestive of CSPH. • Spleen stiffness measurement has been proposed as a more specific technique to predict the presence of CSPH. • Elastography has gained prestige in the non-invasive evaluation of patients with advanced chronic liver disease by allowing prophylactic measures to be taken when suggesting the presence of CSPH. This is a narrative review that aims to discuss the importance of elastographic methods in the evaluation of clinically significant portal hypertension (CSPH) in cirrhotic patients, where the authors propose an algorithm for evaluating these patients. In compensated advanced chronic liver disease, the goal is to prevent the development of CSPH and, in those already with CSPH, prevent the appearance of gastroesophageal varices (GEV) and other complications of portal hypertension. In compensated cirrhosis, the prevalence of GEV is 30-40%, of which 10-20% are at risk of bleeding. Therefore, using non-invasive methods would exempt the patient from the need of an endoscopy. Hepatic Elastography is a non-invasive, safe, reproducible method, available through many techniques: Vibration-Controlled Transient Elastography (VCTE), Shear Wave Elastography (SWE) and Magnetic Resonance Elastography (MRE). The Baveno VII presented the "rule of 5" for VCTE: liver stiffness measurement (LSM) ≤15 kPa and platelets >150.000/mm3 exclude CSPH, while an LSM ≥25 kPa is highly suggestive of CSPH. Also, the "rule of 4" for SWE has been proposed: patients with ≥17 kPa could be considered as having CSPH. At last, spleen stiffness measurement (SSM) has been proposed as a more specific technique to predict the presence of CSPH. In conclusion, elastography has gained prestige in the non-invasive evaluation of patients with advanced chronic liver disease by allowing prophylactic measures to be taken when suggesting the presence of CSPH.