Review article: Recent advances in ascites and acute kidney injury management in cirrhosis.

BACKGROUND: Better understanding of disease pathophysiology has led to advances in managing ascites and its associated complications including hepatorenal syndrome-acute kidney Injury (HRS-AKI), especially medicinal and interventional advances. AIM: To review the latest changes in the management of ascites and HRS-AKI. METHODS: A literature search was conducted in Pubmed, using the keywords cirrhosis, ascites, renal dysfunction, acute kidney injury, hepatorenal syndrome, beta-blockers, albumin, TIPS and vasoconstrictors, including only publications in English. RESULTS: The medicinal advances include earlier treatment of clinically significant portal hypertension to delay the onset of ascites and the use of human albumin solution to attenuate systemic inflammation thus improving the haemodynamic changes associated with cirrhosis. Furthermore, new classes of drugs such as sodium glucose co-transporter 2 are being investigated for use in patients with cirrhosis and ascites. For HRS-AKI management, newer pharmacological agents such as vasopressin partial agonists and relaxin are being studied. Interventional advances include the refinement of TIPS technique and patient selection to improve outcomes in patients with refractory ascites. The development of the alfa pump system and the study of outcomes associated with the use of long-term palliative abdominal drain will also serve to improve the quality of life in patients with refractory ascites. CONCLUSIONS: New treatment strategies emerged from better understanding of the pathophysiology of ascites and HRS-AKI have shown improved prognosis in these patients. The future will see many of these approaches confirmed in large multi-centre clinical trials with the aim to benefit the patients with ascites and HRS-AKI.

Combined Spontaneous Portosystemic Shunt Embolization and Transjugular Intrahepatic Portosystemic Shunt Creation for Treatment of Hepatic Encephalopathy.

This retrospective case series assessed the early effectiveness of combined spontaneous portosystemic shunt (SPSS) embolization and preemptive transjugular intrahepatic portosystemic shunt (TIPS) creation for alleviation of medically refractory hepatic encephalopathy (HE) and prevention of portal hypertension complications in patients with liver cirrhosis. Eight patients with liver cirrhosis (5 men and 3 women; mean age, 61 years [SD ± 10]) and HE (overt [West-Haven Grade 2-4], n = 7; covert [West-Haven Grade 1], n = 1) refractory to lactulose and rifaximin therapy who underwent concurrent or staged SPSS embolization and TIPS creation between 2018 and 2022 were included in this study. The primary outcomes were 3-month improvement in HE and postprocedural HE-related hospitalizations. HE improvement was achieved in 7 (87.5%) of 8 cases. Among all patients, there was 1 HE-related hospitalization within 90 days that responded to repeat embolization with no further admissions. No patients developed new ascites, variceal hemorrhage, or other portal hypertension complications within 3 months.

Distinct structural and dynamic components of portal hypertension in different animal models and human liver disease etiologies.

BACKGROUND AND AIMS: Liver fibrosis is the static and main (70%-80%) component of portal hypertension (PH). We investigated dynamic components of PH by a three-dimensional analysis based on correlation of hepatic collagen proportionate area (CPA) with portal pressure (PP) in animals or HVPG in patients. APPROACH AND RESULTS: Different animal models (bile duct ligation: n = 31, carbon tetrachloride: n = 12, thioacetamide: n = 12, choline-deficient high-fat diet: n = 12) and patients with a confirmed single etiology of cholestatic (primary biliary cholangitis/primary sclerosing cholangitis: n = 16), alcohol-associated (n = 22), and metabolic (NASH: n = 19) liver disease underwent CPA quantification on liver specimens/biopsies. Based on CPA-to-PP/HVPG correlation, potential dynamic components were identified in subgroups of animals/patients with lower-than-expected and higher-than-expected PP/HVPG. Dynamic PH components were validated in a patient cohort (n = 245) using liver stiffness measurement (LSM) instead of CPA. CPA significantly correlated with PP in animal models (Rho = 0.531; p < 0.001) and HVPG in patients (Rho = 0.439; p < 0.001). Correlation of CPA with PP/HVPG varied across different animal models and etiologies in patients. In models, severity of hyperdynamic circulation and specific fibrosis pattern (portal fibrosis: p = 0.02; septa width: p = 0.03) were associated with PH severity. In patients, hyperdynamic circulation (p = 0.04), vascular dysfunction/angiogenesis (VWF-Ag: p = 0.03; soluble vascular endothelial growth factor receptor 1: p = 0.03), and bile acids (p = 0.04) were dynamic modulators of PH. The LSM-HVPG validation cohort confirmed these and also indicated IL-6 (p = 0.008) and hyaluronic acid (HA: p < 0.001) as dynamic PH components. CONCLUSIONS: The relative contribution of "static" fibrosis on PH severity varies by type of liver injury. Next to hyperdynamic circulation, increased bile acids, VWF-Ag, IL-6, and HA seem to indicate a pronounced dynamic component of PH in patients.

Cystic fibrosis-related liver disease: Clinical presentations, diagnostic and monitoring approaches in the era of CFTR modulator therapies.

Cystic fibrosis (CF) is the most common autosomal recessive disease in the Caucasian population. Cystic fibrosis-related liver disease (CFLD) is defined as the pathogenesis related to the underlying CFTR defect in biliary epithelial cells. CFLD needs to be distinguished from other liver manifestations that may not have any pathological significance. The clinical/histological presentation and severity of CFLD vary. The main histological presentation of CFLD is focal biliary fibrosis, which is usually asymptomatic. Portal hypertension develops in a minority of cases (about 10%) and may require specific management including liver transplantation for end-stage liver disease. Portal hypertension is usually the result of the progression of focal biliary fibrosis to multilobular cirrhosis during childhood. Nevertheless, non-cirrhotic portal hypertension as a result of porto-sinusoidal vascular disease is now identified increasingly more frequently, mainly in young adults. To evaluate the effect of new CFTR modulator therapies on the liver, the spectrum of hepatobiliary involvement must first be precisely classified. This paper discusses the phenotypic features of CFLD, its underlying physiopathology and relevant diagnostic and follow-up approaches, with a special focus on imaging.

Overlooked subclinical portal hypertension in non-cirrhotic NAFLD: Is it real and how to measure it?

Clinical and experimental advances related to the detection, magnitude and pathobiology of subclinical portal hypertension in non-alcoholic fatty liver disease (NAFLD), primarily observed in the presence of non-alcoholic steatohepatitis (NASH), prompt us to revisit current disease paradigms. Hepatic venous pressure gradient (HVPG) has been reported to underestimate portal pressure in NASH-related cirrhosis, while inaccuracy is more likely in non-cirrhotic livers, indicating a potential need for new and preferably non-invasive methods of measurement. Although clinically significant portal hypertension (HVPG ≥10 mmHg) retains its prognostic significance in NASH, subclinical portal hypertension (HVPG 6.0-9.5 mmHg) has been repeatedly detected in patients with NAFLD in the absence of cirrhosis or even significant fibrosis whereas the impact of these findings on disease outcomes remains unclear. Mechanocrine signalling pathways in various types of liver cell reveal a molecular basis for the adverse effects of subclinical portal hypertension and suggest a bidirectional relationship between portal pressure and fibrosis. These findings may guide efforts to improve risk assessment and identify novel therapeutic targets in NAFLD.

Splenic Arteriovenous Fistula Accompanied by Splenic Artery Aneurysm Associated with Acute-onset Portal Hypertension and Gastrointestinal Bleeding: Case Report and Literature Review.

Splenic arteriovenous fistula is an uncommon aetiology of portal hypertension, which has definitive treatment effectiveness and good prognosis. We report a case of portal hypertension and gastrointestinal bleeding in the absence of hepatic parenchymal disease in a 50 year-old woman with multiple pregnancies. Abdominal computed tomography and transabdominal arteriography recorded the presence of tortuous and aneurysmal splenic arteries and the premature filling of enlarged splenic veins, which are highly suggestive of splenic arteriovenous fistula. The above vascular abnormalities were successfully treated by transcatheter embolization. No recurrence or other complications were observed. In addition, a literature review concerning splenic arteriovenous fistula published in recent 30 years was performed to further our understanding of the management strategy on this entity.

To the Editor: Pathophysiology of Splenic Arteriovenous Fistula.

A splenic arteriovenous fistula causes a "prehepatic" hypertension in the portal venous system with the double mechanism of an increased blood amount and mainly its high pressure inflow. It aggravates for a secondary fibrosis of the portal vein branches and "capillarization" of the hepatic sinusoids, adding a further "intra-hepatic" component. The subsequent development of portosystemic collaterals induces the risk of gastrointestinal hemorrhages All this suggests to perform a close monitoring of every case of splanchnic aneurysm or pseudo-aneurysm, through the current cross-section imaging tools, for their possible evolution in an arteriovenous fistula, and to consider an early therapy, also endovascular, before any secondary damage of the liver parenchyma. In this case the treatment of the portal vein hypertension can be "ethiological" and resolutive.

Role of the posterior mucosal defense barrier in portal hypertensive gastropathy.

Portal hypertensive gastropathy (PHG) is a complication of cirrhotic or noncirrhotic portal hypertension. PHG is very important in the clinic because it can cause acute or even massive blood loss, and its treatment efficacy and prognosis are poor. Currently, the incidence of PHG in patients with cirrhosis is 20-80%, but its pathogenesis is complicated and poorly understood. Studies have shown that portal hypertension can cause changes in gastric mucosal microcirculation hemodynamics, leading to changes in gastric mucosal histology and function and thereby weakening the mucosal defense barrier. However, no specific drug treatment plans are currently available. This article reviews the current literature to further our understanding of the mechanism underlying PHG and the relationship between PHG and the posterior mucosal defense barrier and to explore new therapeutic targets.

Impact of lifestyle interventions targeting physical exercise and caloric intake on cirrhosis regression in rats.

In patients, advanced cirrhosis only regresses partially once the etiological agent is withdrawn. Animal models for advanced cirrhosis regression are missing. Lifestyle interventions (LIs) have been shown to improve steatosis, inflammation, fibrosis, and portal pressure (PP) in liver disease. We aimed at characterizing cirrhosis regression after etiological agent removal in experimental models of advanced cirrhosis and to study the impact of different LI on it. Advanced cirrhosis was induced in rats either by carbon tetrachloride (CCl4) or by thioacetamide (TAA) administration. Systemic and hepatic hemodynamics, liver fibrosis, hepatic stellate cell (HSC) activation, hepatic macrophage infiltration, and metabolic profile were evaluated after 48 h, 4 wk or 8 wk of etiological agent removal. The impact of LI consisting in caloric restriction (CR) or moderate endurance exercise (MEE) during the 8-wk regression process was analyzed. The effect of MEE was also evaluated in early cirrhotic and in healthy rats. A significant reduction in portal pressure (PP), liver fibrosis, and HSC activation was observed during regression. However, these parameters remained above those in healthy animals. During regression, animals markedly worsened their metabolic profile. CR although preventing those metabolic disturbances did not further reduce PP, hepatic fibrosis, or HSC activation. MEE also prevented metabolic disturbances, without enhancing, but even attenuating the reduction of PP, hepatic fibrosis, and HSC activation achieved by regression. MEE also worsened hepatic fibrosis in early-TAA cirrhosis and in healthy rats.NEW & NOTEWORTHY We have developed two advanced cirrhosis regression experimental models with persistent relevant fibrosis and portal hypertension and an associated deteriorated metabolism that mimic what happens in patients. LI, despite improving metabolism, did not enhance the regression process in our cirrhotic models. CR did not further reduce PP, hepatic fibrosis, or HSC activation. MEE exhibited a profibrogenic effect in the liver blunting cirrhosis regression. One of the potential explanations of this worsening could be ammonia accumulation.

Mild changes of hepatic nodular regenerative hyperplasia may cause portal hypertension and be visible on reticulin but not hematoxylin and eosin staining.

Nodular regenerative hyperplasia (NRH) can manifest as alternating parenchymal compression/expansion on hematoxylin and eosin (H&E) staining and as reticulin collapse/nodularity on reticulin staining. Histologic diagnosis can be challenging, especially when there is mild disease and on limited biopsy samples. We reviewed clinical and histologic parameters in a large series of NRH. We identified 60 liver specimens convincingly showing changes of NRH and reviewed them for clinical (age, sex, symptoms, lab values, portal hypertension [PHTN], NRH etiology) and histologic (inflammation, sinusoidal dilation, cholestasis, architectural change, portal vascular abnormalities, degree of changes on reticulin) parameters. The cases came from 28 women and 32 men (median age: 54 years). Most (55, 92%) were biopsies. Thirty patients were symptomatic. Forty-five cases showed mild NRH changes on reticulin; 24 of these (53%) showed them on H&E as well. Fifteen demonstrated well-developed changes on reticulin, which were always seen on H&E as well. Sinusoidal dilation was commonly observed in both of these subgroups (88% overall). Portal vascular abnormalities were seen in 33%. Well-developed NRH was diffuse more often than mild NRH (53% vs. 4%, P < 0.0001). Twenty-nine patients had clinically confirmed or likely PHTN. Of these, 21 showed mild and 8 showed well-developed NRH changes; only 3 had concomitant advanced fibrosis. Chemotherapy was the most frequent known cause of NRH; 30 patients lacked any definite etiology. NRH can be difficult to diagnose on biopsy, particularly since mild changes may be visible on reticulin but not H&E; even these patients can have PHTN. Additionally, NRH is often idiopathic, potentially lowering clinical and pathologic suspicion. Pathologists should have a low threshold for ordering reticulin stains, especially when a patient is known to have PHTN. Sinusoidal dilation, while nonspecific, commonly accompanies NRH.

DPP4 inhibitor reduces portal hypertension in cirrhotic rats by normalizing arterial hypocontractility.

AIMS: Dipeptidyl peptidase-4 inhibitor (DPP4i), a new antidiabetic agent, is reported to affect the progression of chronic liver diseases. The study aims to investigate the effects of DPP4i on contractile response, splanchnic hemodynamics, and portal pressure in cirrhotic rats. MATERIALS AND METHODS: A rat model of carbon tetrachloride-induced cirrhosis was used in this study. Sixteen rats with cirrhosis were treated with DDP4i sitagliptin for 5 consecutive days. Portal and systemic pressures and portal blood flow were measured. Mesenteric arterioles were isolated, and concentration-response curves to norepinephrine (NE) were evaluated. The expression of NADPH oxidase (Nox)1, Nox2, Nox4, and soluble epoxide hydrolase (sEH) were detected. Reactive oxygen species (ROS) and epoxyeicosatrienoic acid (EET) levels in mesenteric arteries were also measured. KEY FINDINGS: In cirrhotic rats, sitagliptin significantly reduced portal blood flow and portal pressure without effects on systemic pressure and reversed the decreased response of mesenteric arterioles to NE in an endothelium-dependent manner. Sitagliptin suppressed the increased Nox4 expression and ROS production. In vitro studies showed that Nox4 inhibitor enhanced arteriolar response to NE and reduced hydrogen peroxide (H2O2) level in cirrhotic rats. Sitagliptin also reduced EET levels and increased sEH expression of mesenteric vessels. Pre-incubation with sEH inhibitor in vitro reversed sitagliptin-induced augmentation of response to NE in cirrhotic rats. SIGNIFICANCE: DPP4 inhibition by sitagliptin in vivo has beneficial effects on portal hypertension in cirrhotic rats through normalizing arterial hypocontractility. DDP4 inhibitor may be a novel strategy in the treatment of patients with cirrhosis and portal hypertension.

Effects of transjugular intrahepatic portosystemic shunt treatment of patients with liver cirrhosis and portal hypertension: Case series.

RATIONALE: Transjugular intrahepatic portosystemic shunt (TIPS) is well established as an effective treatment tool for portal hypertension. However, the effects of TIPS in patients with liver cirrhosis and portal hypertension have not been adequately verified in clinical trials. PATIENT CONCERNS: To evaluate the effects of TIPS in patients with liver cirrhosis and portal hypertension with or without portal vein thrombosis (PVT). INTERVENTIONS: A total of 55 patients with liver cirrhosis and portal hypertension received TIPS treatment from December 2014 to April 2018 were enrolled. Clinical data, including portal pressure, Child-Pugh score, and relevant complications were recorded. OUTCOMES: TIPS was successfully performed in 54 patients. The overall technical success rate was 98.19% without serious technical complications. After TIPS treatment, portal pressure was significantly reduced from 38.13 ±â€Š4.00 cmH2O to 24.14 ±â€Š3.84 cmH2O (P < 0.05). In addition, symptoms including gastrointestinal bleeding and ascites were improved after TIPS treatment. During the 6 to 21-month follow up, hepatic encephalopathy in 15 patients (27.8%), shunt dysfunction in 5 patients (9.3%), rebleeding in 12 patients (22.2%) and deterioration of liver function in 2 patients (3.7%) were recorded. Moreover, there were no significant differences in the rates of rebleeding and hepatic encephalopathy between patients with PVT and the non-PVT group, whereas the occurrence rate of TIPS dysfunction was higher in the PVT group, but not statistically significant. LESSONS: TIPS treatment could alleviate the symptoms of liver cirrhosis and portal hypertension in individuals with or without PVT. However, complications during follow-up should be appropriately noted and addressed with corresponding treatments.

Portal hypertensive vasculopathy - An entity worth remembering with non-neoplastic gastrointestinal lesions.

Portal hypertensive vasculopathy (PHV) represents an increase in the pressure in the portal circulation. This increased pressure leads to changes in the mucosa that can be appreciated endoscopically as well as histopathologically. Lesions can be observed in the entire gastrointestinal tract (GIT) including stomach, duodenum, jejunum and colon. The histological changes are appreciated mainly in the mucosal and submucosal blood vessels. A knowledge of these lesions as well as the changes helps in separating them from other close differentials with specific treatment to be instituted. The pathogenesis of the hemodynamic changes is not well-understood. The underlying factor is increased portal pressure. Studies indicate, that besides increased portal pressure other factors in combination led to the observed changes. Portal hypertensive gastropathy (PHG) is seen in the gastric body and fundus, while varices are noted in the cardia and fundus. Changes may be seen in the small intestine and throughout the colon with anorectal varices. Histopathological changes include dilated, congested and ectatic capillaries and edema in the lamina propria besides a large spectrum of other histopathological changes. Mucosal capillaries with thick irregular wall show absence of red blood cells in the lumen. Thickening of the vessel wall serves as a better marker than the vascular diameter when portal hypertension (PHT) is considered. Long standing cases may show fibrosis in lamina propria. At times, these changes may lead to occult gastrointestinal bleeding. Important differentials need to be ruled out in all the cases as the treatment and the outcome of all differs. Endoscopically or histopathologically if the mucosal changes are observed they should not be overlooked and a detailed work-up must be carried out.

Test-Retest Reliability and Consistency of HVPG and Impact on Trial Design: A Study in 289 Patients from 20 Randomized Controlled Trials.

BACKGROUND AND AIMS: Portal hypertension (PH) is a major driver for cirrhosis complications. Portal pressure is estimated in practice by the HVPG. The assessment of HVPG changes has been used for drug development in PH. This study aimed at quantifying the test-retest reliability and consistency of HVPG in the specific context of randomized controlled trials (RCTs) for the treatment of PH in cirrhosis and its impact on power calculations for trial design. APPROACH AND RESULTS: We conducted a search of published RCTs in patients with cirrhosis reporting individual patient-level data of HVPG at baseline and after an intervention, which included a placebo or an untreated control arm. Baseline and follow-up HVPGs in the control groups were extracted after digitizing the plots. We assessed reliability and consistency and the potential impact of study characteristics. We retrieved a total of 289 before and after HVPG measurements in the placebo/untreated groups from 20 RCTs. The time span between the two HVPG measurements ranged between 20 minutes and 730 days. Pre-/post-HVPG variability was lower in studies including only compensated patients; therefore, modeled sample size calculations for trials in compensated cirrhosis were lower than for decompensated cirrhosis. A higher proportion of alcohol-associated cirrhosis and unicentric trials was associated with lower differences between baseline and follow-up measurements. The smallest detectable difference in an individual was 26% and 30% in compensated and decompensated patients, respectively. CONCLUSIONS: The test-retest reliability of HVPG is overall excellent. Within-individual variance was higher in studies including higher proportions of decompensated patients. These findings should be taken into account when performing power analysis for trials based on the effects on HVPG or when considering HVPG as a tool to guide therapy of PH.

Portal hypertension is the main driver of liver stiffness in advanced liver cirrhosis.

Liver stiffness (LS) is a novel non-invasive parameter widely used in clinical hepatology. LS correlates with liver fibrosis stage in non-cirrhotic patients. In cirrhotic patients it also shows good correlation with Hepatic Venous Pressure Gradient (HVPG). Our aim was to assess the contribution of liver fibrosis and portal hypertension to LS in patients with advanced liver cirrhosis. Eighty-one liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG and LS measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France). Liver collagen content was assessed in the explanted liver as collagen proportionate area (CPA) and hydroxyproline content (HP). The studied cohort included predominantly patients with Child-Pugh class B and C (63/81, 77.8%), minority of patients were Child-Pugh A (18/81, 22.2%). LS showed the best correlation with HVPG (r=0.719, p< 0.001), correlation of LS with CPA (r=0.441, p< 0.001) and HP/Amino Acids (r=0.414, p< 0.001) was weaker. Both variables expressing liver collagen content showed good correlation with each other (r=0.574, p<0.001). Multiple linear regression identified the strongest association between LS and HVPG (p < 0.0001) and weaker association of LS with CPA (p = 0.01883). Stepwise modelling showed minimal increase in r2 after addition of CPA to HVPG (0.5073 vs. 0.5513). The derived formula expressing LS value formation is: LS = 2.48 + (1.29 x HVPG) + (0.26 x CPA). We conclude that LS is determined predominantly by HVPG in patients with advanced liver cirrhosis whereas contribution of liver collagen content is relatively low.

Hepatic venous-portal gradient (HVPG) measurement: pearls and pitfalls.

Hepatic venous pressure gradient (HVPG) is the gold-standard for measurement of portal hypertension, a common cause for life-threatening conditions such as variceal bleeding and hepatic encephalopathy. HVPG also plays a crucial role in risk stratification, treatment selection and assessment of treatment response. Thus recognition of common pitfalls and unusual hepatic venous conditions is crucial. This article aims to provide a radiographical and clinical guide to HVPG with representative clinical cases.

Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study.

BACKGROUND AND AIMS: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.

Noninvasive Diagnosis of Portal Hypertension in Patients With Compensated Advanced Chronic Liver Disease.

INTRODUCTION: We aimed to explore the prevalence of portal hypertension in the most common etiologies of patients with compensated advanced chronic liver disease (cACLD) and develop classification rules, based on liver stiffness measurement (LSM), that could be readily used to diagnose or exclude clinically significant portal hypertension (CSPH) in clinical practice. METHODS: This is an international cohort study including patients with paired LSM/hepatic venous pressure gradient (HVPG), LSM ≥10 kPa, and no previous decompensation. Portal hypertension was defined by an HVPG >5 mm Hg. A positive predictive value ≥90% was considered to validate LSM cutoffs for CSPH (HVPG ≥10 mm Hg), whereas a negative predictive value ≥90% ruled out CSPH. RESULTS: A total of 836 patients with hepatitis C (n = 358), nonalcoholic steatohepatitis (NASH, n = 248), alcohol use (n = 203), and hepatitis B (n = 27) were evaluated. Portal hypertension prevalence was >90% in all cACLD etiologies, except for patients with NASH (60.9%), being even lower in obese patients with NASH (53.3%); these lower prevalences of portal hypertension in patients with NASH were maintained across different strata of LSM values. LSM ≥25 kPa was the best cutoff to rule in CSPH in alcoholic liver disease, chronic hepatitis B, chronic hepatitis C, and nonobese patients with NASH, whereas in obese NASH patients, the positive predictive value was only 62.8%. A new model for patients with NASH (ANTICIPATE-NASH model) to predict CSPH considering body mass index, LSM, and platelet count was developed, and a nomogram was constructed. LSM ≤15 kPa plus platelets ≥150 × 10/L ruled out CSPH in most etiologies. DISCUSSION: Patients with cACLD of NASH etiology, especially obese patients with NASH, present lower prevalences of portal hypertension compared with other cACLD etiologies. LSM ≥25 kPa is sufficient to rule in CSPH in most etiologies, including nonobese patients with NASH, but not in obese patients with NASH.