Mitochondrial Dysfunction by FADDosome Promotes Gastric Mucosal Injury in Portal Hypertensive Gastropathy.

Mucosal epithelial death is an essential pathological characteristic of portal hypertensive gastropathy (PHG). FADDosome can regulate mucosal homeostasis by controlling mitochondrial status and cell death. However, it remains ill-defined whether and how the FADDosome is involved in the epithelial death of PHG. The FADDosome formation, mitochondrial dysfunction, glycolysis process and NLRP3 inflammasome activation in PHG from both human sections and mouse models were investigated. NLRP3 wild-type (NLRP3-WT) and NLRP3 knockout (NLRP3-KO) littermate models, critical element inhibitors and cell experiments were utilized. The mechanism underlying FADDosome-regulated mitochondrial dysfunction and epithelial death in PHG was explored. Here, we found that FADD recruited caspase-8 and receptor-interacting serine/threonine-protein kinase 1 (RIPK1) to form the FADDosome to promote Drp1-dependent mitochondrial fission and dysfunction in PHG. Also, FADDosome modulated NOX2 signaling to strengthen Drp1-dependent mitochondrial fission and alter glycolysis as well as enhance mitochondrial reactive oxygen species (mtROS) production. Moreover, due to the dysfunction of electron transport chain (ETC) and alteration of antioxidant enzymes activity, this altered glycolysis also contributed to mtROS production. Subsequently, the enhanced mtROS production induced NLRP3 inflammasome activation to result in the epithelial pyroptosis and mucosal injury in PHG. Thus, the FADDosome-regulated pathways may provide a potential therapeutic target for PHG.

Obliteration of portal venules contributes to portal hypertension in biliary cirrhosis.

The effects of the obliteration of portal venules (OPV) in cirrhotic portal hypertension are poorly understood. To investigate its contribution to portal hypertension in biliary cirrhosis and its underlying mechanism, we evaluated OPV using two-dimensional (2D) histopathology in liver explants from patients with biliary atresia (BA, n = 63), primary biliary cholangitis (PBC, n = 18), and hepatitis B-related cirrhosis (Hep-B-cirrhosis, n = 35). Then, three-dimensional (3D) OPV was measured by X-ray phase-contrast CT in two parallel models in rats following bile duct ligation (BDL) or carbon tetrachloride (CCl4) administration, representing biliary cirrhosis and post-necrotic cirrhosis, respectively. The portal pressure was also measured in the two models. Finally, the effects of proliferative bile ducts on OPV were investigated. We found that OPV was significantly more frequent in patients with biliary cirrhosis, including BA (78.57 ± 16.45%) and PBC (60.00 ± 17.15%), than that in Hep-B-cirrhotic patients (29.43 ± 14.94%, p < 0.001). OPV occurred earlier, evidenced by the paired liver biopsy at a Kasai procedure (KP), and was irreversible even after a successful KP in the patients with BA. OPV was also significantly more frequent in the BDL models than in the CCl4 models, as shown by 2D and 3D quantitative analysis. Portal pressure was significantly higher in the BDL model than that in the CCl4 model. With the proliferation of bile ducts, portal venules were compressed and irreversibly occluded, contributing to the earlier and higher portal pressure in biliary cirrhosis. OPV, as a pre-sinusoidal component, plays a key role in the pathogenesis of portal hypertension in biliary cirrhosis. The proliferated bile ducts and ductules gradually take up the 'territory' originally attributed to portal venules and compress the portal venules, which may lead to OPV in biliary cirrhosis. © 2024 The Pathological Society of Great Britain and Ireland.

Possible use of 2D shear wave liver elastography in new-onset ascites evaluation.

BACKGROUND: No data on the use of 2D shear wave elastography exists regarding the evaluation of the new-onset ascites causality. AIMS: To determine whether 2D shear wave elastography can help in the non-invasive assessment of the new-onset ascites cause. To assess the applicability of liver stiffness measured by 2D shear wave elastography using Esaote MyLab Nine apparatus in patients with ascites. METHODS: In 52 consecutive patients with new-onset ascites (January 2020 to October 2021), liver stiffness using 2D shear wave elastography was prospectively measured. The reliable measurements were used for further analysis. Relevant clinical and laboratory data was collected. RESULTS: The calculated liver stiffness measurement cut-off value of 14.4 kPa held 94% accuracy, 100% sensitivity, and 83% specificity when determining ascites with serum ascites albumin gradient ≥11 g/L. Reliable 2D shear wave elastography success rate was 84%. CONCLUSIONS: 2D shear wave elastography may potentially be used to differentiate transudative from exudative ascites, especially in patients with portal hypertension and peritoneal carcinomatosis.

Budd-Chiari syndrome in children: Radiological intervention and role of shear wave elastography in monitoring response.

OBJECTIVES: Radiological intervention (RI) is the preferred treatment in children with Budd-Chiari syndrome (BCS). We studied the comparative long-term outcome of BCS children, with and without RI and utility of liver and splenic stiffness measurement (LSM, SSM) by 2-dimensional shear wave elastography (2D-SWE) in assessing response. METHODS: Sixty children (40 boys, median age 10.5 [6.5-15.25] years) with BCS (29 newly diagnosed, 31 follow-up) were evaluated. LSM and SSM by 2D-SWE and vascular patency were monitored pre- and postprocedure (≥ 6 months postprocedure) in those undergoing RI. Medical therapy without anticoagulation and monitoring was done in subjects without RI. The RI and no-RI groups were compared. RESULTS: Ascites (54,90%), hepatomegaly (56,93%) and prominent abdominal-veins (42,70%), were the commonest features. The majority (46,78%) had isolated hepatic vein block. 44 (73%) cases underwent RI, while 16 (27%) were managed conservatively. Both groups were similar at baseline. Post-RI subjects showed significant improvement in clinical findings, liver functions and portal hypertension. LSM [33 (32-34.5) to 19.2 (18-20.67) kPa] and SSM [54.5 (52.3-57.6) to 28.9 (27.6-30.25) kPa] showed a significant decline from baseline value over a follow-up of 12 (6-13) months. Gradual reduction occurred in the LSM and SSM over 1-5 years, with near-normal LSM [10.2 (9.2-11.5) kPa] and SSM [22.3 (20.5-24.3) kPa] values in patients (n-16) with > 5 years follow-up. Patients without RI showed worsening in LSM and SSM. Hepatopulmonary syndrome and hepatocellular carcinoma developed in 4 (8%) and 1 (1.7%) cases respectively. CONCLUSION: RI leads to clinical recovery and reduction with near normalization of LSM and SSM over long-term follow-up in children with BCS. 2D-SWE is a promising tool to monitor outcomes.

A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease: the ACCESS-ESLD study protocol.

BACKGROUND: Liver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients. METHODS: In this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations. DISCUSSION: The anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes. TRIAL REGISTRATION: Clinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05502198 .

The Portal Vein: A Comprehensive Review.

Radiologists are familiar with the appearances of a normal portal vein; variations in its anatomy are commonplace and require careful consideration due to the implications for surgery. These alterations in portal vein anatomy have characteristic appearances that are clearly depicted on CT, MR, and US images. Similarly, there are numerous congenital and acquired disorders of the portal vein that are deleterious to its function and can be diagnosed by using imaging alone. Some of these conditions have subtle imaging features, and some are conspicuous at imaging but poorly understood or underrecognized. The authors examine imaging appearances of the portal vein, first by outlining the classic and variant anatomy and then by describing each of the disorders that impact portal vein function. The imaging appearances of portal vein abnormalities discussed in this review include (a) occlusion from and differentiation between bland thrombus and tumor in vein and the changes associated with resultant hepatic artery buffer response changes, cavernous transformation of the portal vein, and portal biliopathy; (b) ascending thrombophlebitis of the portal vein (pylephlebitis); (c) portal hypertension and its causes and sequelae; (d) the newly described disease entity portosinusoidal vascular disorder; and (e) intra- and extrahepatic shunts of the portal system, both congenital and acquired (including Abernethy malformations), and the associated risks. Current understanding of the pathophysiologic processes of each of these disorders is considered to aid the approach to reporting. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

A high rate of post thrombotic complication in pediatric portal vein thrombosis.

INTRODUCTION: Portal vein thrombosis (PVT) is a rare disease in children and may be complicated by portal hypertension (PH), hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHTN) but their incidence and risk factors are unknown. METHODS: An observational, retrospective cohort study of all consecutive children (≤18 years) with PVT treated at the Emma Children's Hospital Amsterdam University Medical Centers between January 1996 and January 2022 was conducted to identify the incidence and risk factors of these post thrombotic complications (PTC) in pediatric patients. RESULTS: In total 43/ 703 thrombosis patients had PVT (boys 72.1 %; mean age 1.3 ± 0.5 years). Overall, 51 % of patients developed PH (n = 22), complicated by PPHTN in one of them. In 16 of 22 patients, PVT presented with portal hypertension. Clinically relevant bleeding due to portal hypertension occurred in 13 (59.1 %) patients with PH. The mean age at the first clinically relevant bleeding was 5.1 ± 5.9 years. Risk factors for the development of PH were lack of complete thrombus resolution (OR 24.3, 95 % CI 1.2-7.0; p = 0.008) and unprovoked VTE (OR, 35.4; 95 % CI 1.4-6.3; p = 0.012). Median time from PVT to PH was 137 days (range: 0 days to 5.04 years). CONCLUSION: We demonstrated that half of the patients develop PH after PVT, with a lack of thrombus resolution and unprovoked VTE as independent risk factors. This high incidence underlines the importance of long-term standardized follow-up of patients after PVT and standard screening in patients at risk of PTC.

Transjugular liver biopsy: enlarge the indications for liver biopsy with reliable diagnostic quality.

BACKGROUND: Complications and diagnostic efficiency for liver biopsy are main concerns for clinicians. This study aimed to assess the safety and efficacy of transjugular liver biopsy (TJLB) compared with percutaneous liver biopsy (PLB) when patients had equal level of liver function and number of passes, using propensity score matching (PSM). METHODS: The clinical and pathological data of patients who received TJLB or PLB between January 2012 and October 2022 were collected. Matching factors included age, gender, cirrhosis, portal hypertension, liver function, creatinine, number of passes, hemodialysis, history of anti-coagulation and anti-platelet, and comorbidities. Coagulation indexes were not considered as matching factors due to different indications of the two techniques. RESULTS: 2711 PLBs and 30 TJLBs were evaluated. By PSM, 75 patients (50 PLBs, 25 TJLBs) were matched. The complication rates for TJLB and PLB were 4.0% (1/25) and 10.0% (5/50) (P > 0.05). Two PLBs had hepatic hemorrhage, one of which required only close monitoring (Grade 1) and the other needed hemostasis and rehydration therapy (Grade 2). The other 3 cases presented with mild abdominal pain (Grade 1). And only one TJLB presented with mild pain. The median number of complete portal tracts were 6.0 and 10.0 for TJLBs and PLBs (P < 0.05). Moreover, the median length of sample for TJLBs and PLBs were 10.0 and 16.5 mm (P < 0.05). The diagnostic efficiency of hepatopathy of unknown etiology of TJLB versus PLB groups before and after matching were 96.4% vs. 94.1% and 95.7% vs. 93.2%, respectively (P > 0.05). CONCLUSION: TJLB is an effective invasive diagnostic procedure that expands indications for liver biopsy with reliable diagnostic quality.

Lymphatic drainage dysfunction via narrowing of the lumen of cisterna chyli and thoracic duct after luminal dilation.

BACKGROUND: The chronological pattern of extrahepatic lymphatic vessel progression in the course of chronic liver disease has not been clarified. This study aimed to clarify the chronological changes in lymphatic vessels with liver disease progression. METHODS: This was a prospective cross-sectional study that enrolled a total of 199 patients. The maximum diameter of the cisterna chyli (CC) or terminal thoracic duct (tTD) was measured using computed tomography or ultrasonography, respectively. Changes in the maximum diameters of the CC and tTD were evaluated with patients with chronic liver disease as the pilot set (n = 138). Subsequently, we examined whether CC/tTD could be used to re-allocate unclassified patients by the Baveno-VII criteria to appropriately diagnose clinically significant portal hypertension (CSPH) in the pilot and validation sets. RESULTS: In the pilot set, a scatter-plot showed that both CC and tTD were narrowed as terminal features in chronic liver disease after dilation. Because there was a significant correlation between the CC diameter and hepatic venous pressure gradient (r = 0.724) in unclassified patients, the diagnostic value of CC and tTD for CSPH was good (AUC: 0.961 and 0.913, respectively). After re-allocation, 68 and 27 unclassified patients were reduced to 4 and 5 in the pilot and validation sets, respectively. CONCLUSION: Both the CC and tTD narrow in the course of liver disease after dilation. Moreover, the maximum diameter of the CC and tTD can be used to re-allocate patients who are unclassified according to the Baveno-VII criteria. CLINICAL TRIAL NUMBER: UMIN trial no. 000044857.

Use of Sound Touch Elastography and Sound Touch Quantification for the Noninvasive Evaluation of Portal Hypertension in a Rat Model.

OBJECTIVES: In this study, we used the recently developed ultrasound elastography techniques sound touch elastography (STE) and sound touch quantification (STQ) to quantify portal hypertension (PHT) severity in a rat model of carbon tetrachloride (CCl4 )-induced cirrhotic PHT. METHODS: In total, 60 rats were used. Various degrees of PHT were established. Liver and spleen stiffness were measured by STE (L-STE and S-STE, respectively) and STQ (L-STQ and S-STQ, respectively). We measured portal pressure (PP) after ultrasonographic examination. The performance of the STE and STQ parameters in the identification of PHT was evaluated using receiver operating characteristic (ROC) analyses. RESULTS: Liver and spleen stiffness measurements obtained with STE and STQ correlated positively with the PP (r = 0.566-0.882, all P < .001). The areas under ROC curves for L-STE, S-STE, L-STQ, and S-STQ values were 0.931 (95% confidence interval [CI], 0.847-1.000), 0.982 (95% CI, 0.956-1.000), 0.796 (95% CI, 0.680-0.912), and 0.925 (95% CI, 0.858-0.993), respectively, for PP ≥5 mmHg; 0.937 (95% CI, 0.865-1.000), 0.938 (95% CI, 0.864-1.000), 0.967 (95% CI, 0.923-1.000), and 0.960 (95% CI, 0.897-1.000), respectively, for PP ≥10 mmHg; and 0.954 (95% CI, 0.897-1.000), 0.790 (95% CI, 0.652-0.928), 0.808 (95% CI, 0.680-0.935), and 0.740 (95% CI, 0.595-0.885), respectively, for PP ≥12 mmHg. CONCLUSIONS: STE and STQ are reliable noninvasive tools for the assessment of PHT severity, especially for PP ≥10 mmHg, in a rat model of CCl4 -induced cirrhotic PHT.

PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study.

BACKGROUND: Patients with advanced cirrhosis are at high risk of developing clinically significant portal hypertension (CSPH). We analyzed the gene expression profile of peripheral blood mononuclear cells (PBMCs) from HIV/HCV coinfected patients to identify a gene expression signature of advanced cirrhosis with high risk for CSPH. METHODS: We conducted a cross-sectional study on 68 patients. Liver stiffness measurement (LSM) was used to stratify patients into < 12.5 kPa (no cirrhosis, n = 19), 12.5 - 24.9 kPa (cirrhosis, n = 20), and ≥ 25 kPa (advanced cirrhosis with high risk for CSPH, n = 29). Besides, we further evaluated LSM < 25 kPa (n = 39) vs. ≥ 25 kPa (n = 29). Total RNA was extracted from PBMCs, and poly(A) RNA sequencing was performed. Two significant differentially expressed (SDE) transcripts were validated by quantitative PCR in a different cohort (n = 46). RESULTS: We found 60 SDE transcripts between patients with LSM < 12.5 kPa and ≥ 25 kPa. Partial least squares discriminant analysis showed that those 60 SDE transcripts collectively discriminated LSM ≥ 25 kPa, with an area under the receiver operating characteristic curve (AUROC) of 0.84. Eight genes had an AUROC ≥ 0.75 for LSM ≥ 25 kPa: five were positively associated with LSM values (SCAMP1, ABHD17B, GPR146, GTF2A1, and TMEM64), while three were inversely associated (ZFHX2-AS1, MDK, and STAG3L2). We validated the two SDE transcripts with the highest discrimination capacity in a different cohort, finding significant differences between < 25 kPa and ≥ 25 kPa (MDK (p = 0.006) and STAG3L2 (p = 0.021)). CONCLUSIONS: A gene expression signature of 60 transcripts was associated with advanced cirrhosis with high risk for CSPH in HIV/HCV coinfected patients.

Diagnosis of Clinically Significant Portal Hypertension Using CT- and MRI-based Vascular Model.

Background Currently, the hepatic venous pressure gradient (HVPG) remains the reference standard for diagnosis of clinically significant portal hypertension (CSPH) but is limited by its invasiveness and availability. Purpose To investigate a vascular geometric model for noninvasive diagnosis of CSPH (HVPG ≥10 mm Hg) in patients with liver cirrhosis for both contrast-enhanced CT and MRI. Materials and Methods In this retrospective study, consecutive patients with liver cirrhosis who underwent HVPG measurement from August 2016 to April 2019 were included. Patients without hepatic diseases were included and marked as non-CSPH to balance the ratio of CSPH 1:1. A variety of vascular parameters were extracted from the portal vein, hepatic vein, aorta, and inferior vena cava and then entered into a vascular geometric model for identification of CSPH. Diagnostic performance was assessed with the area under the receiver operating characteristic curve (AUC). Results The model was developed and tested with retrospective data from 250 patients with liver cirrhosis and 273 patients without clinical evidence of hepatic disease at contrast-enhanced CT examination, including 213 patients with CSPH (mean age, 49 years ± 12 [SD]; 138 women) and 310 patients without CSPH (mean age, 50 years ± 9; 177 women). For external validation, an MRI data set with 224 patients with cirrhosis (mean age, 49 years ± 10; 158 women) and a CT data set with 106 patients with cirrhosis (mean age, 53 years ± 12; 71 women) were analyzed. Significant reductions in mean whole-vessel volumes were observed in the portal vein (ranging from 36.9 cm3 ± 16.0 to 29.6 cm3 ± 11.1; P < .05) and hepatic vein (ranging from 35.3 cm3 ± 21.5 to 22.4 cm3 ± 15.7; P < .05) when CSPH occurred. Similarly, the mean whole-vessel lengths were shorter in patients with CSPH (portal vein: 1.7 m ± 1.2 vs 3.0 m ± 2.4, P < .05; hepatic vein: 0.9 m ± 1.5 vs 1.8 m ± 1.5, P < .05) than in those without CSPH. The proposed vascular model performed well in the internal test set (mean AUC, 0.90 ± 0.02) and external test sets (mean AUCs, 0.84 ± 0.12 and 0.87 ± 0.11). Conclusion A contrast-enhanced CT- and MRI-based vascular model was proposed with good diagnostic consistency for hepatic venous pressure gradient measurement. ClinicalTrials.gov registration nos. NCT03138915 and NCT03766880 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Roldán-Alzate and Reeder in this issue.

Cardiac involvement in non-cirrhotic portal hypertension: MRI detects myocardial fibrosis and oedema similar to compensated cirrhosis.

AIMS: The exact role of portal hypertension in cirrhotic cardiomyopathy remains unclear, and it is uncertain whether cardiac abnormalities also occur in non-cirrhotic portal hypertension (NCPH). This magnetic resonance imaging (MRI) study aimed to evaluate the presence of subclinical myocardial dysfunction, oedema, and fibrosis in NCPH. METHODS AND RESULTS: In this prospective study (2018-2022), participants underwent multiparametric abdominal and cardiac MRI including assessment of cardiac function, myocardial oedema, late gadolinium enhancement (LGE), and abdominal and cardiac mapping [T1 and T2 relaxation times, extracellular volume fraction (ECV)]. A total of 111 participants were included [44 participants with NCPH (48 ± 15 years; 23 women), 47 cirrhotic controls, and 20 healthy controls]. The cirrhotic group was dichotomized (Child A vs. Child B/C). NCPH participants demonstrated a more hyperdynamic circulation compared with healthy controls (cardiac index: 3.7 ± 0.6 vs. 3.2 ± 0.8 L/min/m², P = 0.004; global longitudinal strain: -27.3 ± 4.6 vs. -24.6 ± 3.5%, P = 0.022). The extent of abnormalities indicating myocardial fibrosis and oedema in NCPH was comparable with Child A cirrhosis (e.g. LGE presence: 32 vs. 33 vs. 69%, P = 0.004; combined T1 and T2 elevations: 46 vs. 27 vs. 69%, P = 0.017; NCPH vs. Child A vs. Child B/C). Correlations between splenic T1 and myocardial T1 values were found (r = 0.41; P = 0.007). Splenic T1 values were associated with the presence of LGE (odds ratio, 1.010; 95% CI: 1.002, 1.019; P = 0.013). CONCLUSION: MRI parameters of myocardial fibrosis and oedema were altered in participants with NCPH to a similar extent as in compensated cirrhosis and were associated with splenic markers of portal hypertension, indicating specific portal hypertensive cardiomyopathy.

Derivation and Validation of a Model to Predict Clinically Significant Portal Hypertension Using Transient Elastography and FIB-4.

BACKGROUND: Liver biopsy and hepatic venous pressure gradient (HVPG), the gold standard for assessing advanced fibrosis (AF) and clinically significant portal hypertension (CSPH), are invasive, costly, and time-consuming. GOAL: We investigated if the combination of fibrosis index based on 4 factors (FIB-4) and liver stiffness measure (LSM) can identify AF and more importantly, CSPH. PATIENTS AND METHODS: Patients with chronic liver disease referred for transjugular liver biopsy were analyzed retrospectively. FIB-4 and LSM were compared with liver histology for diagnosing AF. FIB-4, LSM, and platelet count were compared with HVPG for diagnosing CSPH. Optimal cutoffs for predicting CSPH were determined by grid search. A composite log-odds to predict CSPH was derived from logistic regression using LSM, FIB-4, and gender. Internal bootstrap validation and external validation were performed. RESULTS: A total of 142 patients were included in the derivation; 42.3% had AF, and 11.3% had CSPH using the current gold standards. The area under the receiver operating characteristic curve (AUROC) for LSM, FIB-4, and their combination to predict AF were 0.7550, 0.7049, and 0.7768, respectively. LSM, FIB-4, and platelet count predicted CSPH with AUROC 0.6818, 0.7532, and 0.7240, respectively. LSM plus FIB-4 showed the best performance in predicting CSPH with AUROC 0.8155. Based on LSM, FIB-4, and gender, a novel model-the Portal Hypertension Assessment Tool (PHAT)-was developed to predict CSPH. PHAT score ≥-2.76 predicted CSPH with sensitivity 94%, specificity 67%, positive predictive value 27%, negative predictive value 99%, and accuracy 70%. In internal and external validation, AUROCs for the model were 0.8293 and 0.7899, respectively. CONCLUSION: A model consisting of FIB-4, LSM, and gender can identify CSPH among patients with chronic liver disease.

Splenomegaly is a marker of advanced chronic liver disease and portal hypertension in HIV infection.

OBJECTIVES: To evaluate the clinical significance of splenomegaly as a marker of underlying liver disease in people with HIV (PWH). METHODS: We included consecutive PWH from a prospective cohort from 2010 to 2020 with available liver stiffness measurement (LSM) and liver imaging to define splenomegaly (> 13 cm) within 1 year. Cut-offs of LSM > 10 kPa and > 21 kPa were used to identify advanced chronic liver disease (ACLD) and portal hypertension, respectively. Logistic regression multivariable analysis was employed to identify independent predictors of ACLD. RESULTS: In all, 331 PWH were included, 76% of them men, with a median (interquartile range) age of 51.3 (45-58) years, all receiving antiretroviral treatment, and 53% were HIV monoinfected. The PWH with splenomegaly exhibited a higher prevalence of ACLD compared with those with normal spleen size, as per LSM (26% vs. 9%; p = 0.009). Portal hypertension diagnosed by LSM was also more prevalent in PWH with splenomegaly than in those without (15% vs. 2%; p < 0.001). Independent predictors of ACLD were viral hepatitis coinfection [adjusted odds ratio (aOR) = 3.15, 95% confidence interval (CI): 1.65-6.0], lower platelets (aOR = 0.99, 95% CI: 0.99-0.99) and splenomegaly (aOR = 2.41, 95% CI: 1.17-4.99). In patients with available oesophagogastroduodenoscopy, splenomegaly was also associated with higher prevalence of oesophageal varices and other endoscopic findings of portal hypertension (38% vs. 17%; p = 0.027). CONCLUSIONS: Splenomegaly identified on routine imaging may have utility as a marker of ACLD and portal hypertension, prompting further investigations.

Non-cirrhotic portal hypertension (obliterative portal venopathy) is the predominant form of chronic liver disease in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF)-associated liver disease commonly manifests as portal hypertension and its complications. We investigated the proposal that the pathophysiology is of non-cirrhotic rather than cirrhotic portal hypertension. This distinction may have important implications for treatment. METHODS: We compared liver transplant explants from cystic fibrosis patients with explants from patients with classical cholestatic diseases, primary biliary cholangitis and primary sclerosing cholangitis. Presence of cirrhosis, fibrosis, nodular regenerative hyperplasia, biliary and portal venous pathology were recorded. Quantitation of portal venules in representative section was performed. RESULTS: Nine patients with cystic fibrosis liver disease, 7 primary biliary cholangitis (PBC) and 7 primary sclerosing cholangitis (PSC) were evaluated. Cirrhosis was present in 0/9 of CF patients and 11/14 of the PBC and PSC controls (p < 0.01). Nodular regenerative hyperplasia was present in 8/9 of the CF patients but none of the controls (p < 0.01). Portal venule numbers per 15 mm2 section were significantly lower in the CF patients 52 (20-72) compared to the primary biliary cholangitis 78 (47-110) and primary sclerosing cholangitis patients, 79 (41-134) (p < 0.05). Portal sclerotic nodules were found in all the CF patients but in only one of the controls (9/9 vs 1/14 p < 0.01). CONCLUSIONS: This study demonstrates that non-cirrhotic portal hypertension or obliterative portal venopathy is the predominant hepatic pathophysiology in adult CF patients requiring liver transplantation. It suggests that treatments directed at the hepatic portal venous system may be more effective than current treatment directed at the biliary system in cystic fibrosis.