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.

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.

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.

High reproducibility of spleen stiffness measurement by vibration-controlled transient elastography with a spleen-dedicated module.

Spleen stiffness measurement (SSM) by vibration-controlled transient elastography (VCTE) is a noninvasive technique for estimating portal hypertension in patients with chronic liver disease (CLD), with its reproducibility yet to be established and its feasibility still unknown beyond CLD. We have studied 420 participants from two tertiary referral centers for liver diseases (Novara, Milan): 297 patients with CLD (32% with cirrhosis) of different etiology (Group A), 63 Philadelphia-negative myeloproliferative neoplasms (Group B), and 60 heathy volunteers (Group C). All underwent SSM by VCTE with a spleen-dedicated module (SSM@100 Hz) and liver stiffness measurement (LSM), blindly performed by 2 different operators. In total, 1680 VCTE examinations for SSM were performed (1000 in Novara, 680 in Milan), with an overall 3.2% failure rate. Median SSM was 26.5 kPa (interquartile range [IQR] 20.0-42.3) in Group A, 26.3 kPa (IQR 22.3-33.6) in Group B, and 16.1 kPa (IQR 14.6-18.7) in Group C. In Group A, the median LSM was 6.8 kPa (IQR 4.9-11.3) in Novara and 8.3 kPa (IQR 7.1-10.8) in Milan, the proportion of patients with cirrhosis being 34% in Novara and 31% in Milan. The Group A interobserver agreement ICC was 0.90 (0.88-0.92), significantly lower in the absence of splenomegaly (ICC 0.87 vs. 0.91) and in absence of cirrhosis (ICC 0.84 vs. 0.90); overweight slightly, but not significantly reduced the interobserveragreement. The intra-observer agreement ICC ranged from 0.91 to 0.96 for the four operators. The Group B interobserver agreement ICC was 0.90 (0.83-0.94). In conclusion, SSM measured by the new spleen-dedicated VCTE module is a feasible, reliable, and highly reproducible tool in patients with CLD and hematological disorders, and in healthy volunteers.

Imaging of fibropolycystic liver disease.

Fibropolycystic liver diseases (FLDs) make up a rare spectrum of heritable hepatobiliary diseases resulting from congenital ductal plate malformations (DPMs) due to the dysfunction of proteins expressed on the primary cilia of cholangiocytes. The embryonic development of the ductal plate is key to understanding this spectrum of diseases. In particular, DPMs can result in various degrees of intrahepatic duct involvement and a wide spectrum of cholangiopathies, including congenital hepatic fibrosis, Caroli disease, polycystic liver disease, and Von Meyenberg complexes. The most common clinical manifestations of FLDs are portal hypertension, cholestasis, cholangitis, and (in rare cases) cholangiocarcinoma. This article reviews recent updates in the pathophysiology, imaging, and clinical management of FLDs.

Comparison of sequential CT arterioportography-arteriosplenography with standard cross-sectional imaging and endoscopy in children with portal hypertension.

In this study the diagnostic capability and additional value of sequential CT arterioportography-arteriosplenography (CT AP-AS) in comparison to standard cross-sectional imaging and upper gastrointestinal endoscopy (UGE) in pediatric portal hypertension (PH) was analyzed. Patients with clinical signs of PH who underwent CT AP-AS in combination with additional contrast-enhanced magnetic resonance imaging (CE-MR) and/or contrast-enhanced computed tomography (CE-CT) were included. Two radiologists reviewed independently imaging regarding the capability to prove patency of (1) extrahepatic and intrahepatic main stem portal vein (PV), (2) intrahepatic PV system and (3) splenomesenteric venous axis. Imaging was reviewed for detection of abdominal varices and results were compared to UGE. Main venous supply of varices (PV and/or splenic vein system) and splenorenal shunting were evaluated. 47 imaging studies (20 CT AP-AS, 16 CE-MR, 11 CE-CT) and 12 UGE records of 20 patients were analyzed. CT AP-AS detected significantly more splenorenal shunts (p = 0.008) and allowed more confident characterization of the extra-/intrahepatic PV-system and splenomesenteric veins in comparison to CE-MR (p < 0.001). Extra- and intrahepatic PV-system were significantly more confidently assessed in CT AP-AS than in CE-CT (p = 0.008 and < 0.001 respectively). CT AP-AS was the only modality that detected supply of varices and additional gastric/duodenal varices. In this retrospective study CT AP-AS was superior to standard cross-sectional imaging concerning confident assessment of the venous portosplenomesenteric axis in pediatric patients. CT AP-AS detected additional varices, splenorenal shunting and supply of varices.

Nodular Regenerative Hyperplasia of the liver in Juvenile Dermatomyositis.

BACKGROUND: We present two cases of Nodular Regenerative Hyperplasia (NRH) associated with Juvenile Dermatomyositis (JDM). CASE PRESENTATION: Case 1: A nine-year-old Caucasian male with refractory JDM and anti-NXP2 autoantibodies was diagnosed at age two. Over seven years, he developed arthritis, dysphagia, dysphonia, severe calcinosis, and colitis. Complications included recurrent cellulitis, infections, and hepatosplenomegaly. Multiple medications were chronically used, including prednisone, methotrexate, azathioprine, cyclophosphamide, mycophenolate mofetil, rituximab, tacrolimus, etanercept, abatacept, infliximab, and tocilizumab. Case 2: A 19-year-old Asian female with chronically active JDM and anti-MDA5 autoantibodies was diagnosed at age 15. Symptomatology included ulcerative skin lesions, Raynaud's phenomenon with digital ulcers, arthritis, interstitial lung disease with pulmonary hypertension, and calcinosis. Medications included chronic use of prednisone, methotrexate, abatacept, cyclophosphamide, mycophenolate mofetil, rituximab, tofacitinib, and sildenafil. In both patients, clinical symptomatology was not suggestive of liver disease or portal hypertension, but laboratory studies revealed elevated serum transaminases with progressive thrombocytopenia and no active liver-associated infections. The first patient's liver ultrasound showed coarse hepatic texture with mild echogenicity, splenomegaly, and portal hypertension. The second patient's liver ultrasound was normal, but elastography indicated increased stiffness. Liver biopsy confirmed NRH in both patients. CONCLUSIONS: It is difficult to recognize NRH in JDM, as it often presents with elevated transaminases which may be mistaken for JDM muscle flare, corticosteroid-related fatty liver, or medication-related transaminitis. NRH has been associated with several medications used to treat JDM, including methotrexate, azathioprine, and cyclophosphamide, which should be discontinued if NRH develops. Providers should consider NRH in JDM patients with severe, refractory disease who have persistently elevated transaminases and persistent thrombocytopenia.

Application of ultrasound for the diagnosis of cirrhosis/portal hypertension.

With advances in technologic approaches in patients with cirrhosis, including the improvement of management, a simple, one-step approach for advanced fibrotic state of the liver is clinically useful. Although refining the diagnosis of cirrhosis to reflect disease heterogeneity is essential, current diagnostic tests have not kept pace with the progression of this new paradigm. There are unmet needs in primary care centers with respect to patients with cirrhosis. Liver biopsy and measurement of hepatic venous pressure gradient in patients with cirrhosis are the gold standards for the estimation of hepatic fibrosis, and they have diagnostic and prognostic value. However, both approaches are invasive and cannot be used repeatedly in clinical practice. Ultrasonography (US) is safe, easy to perform, inexpensive, and yields numerical and accurate results. Conventionally, the size of the liver and spleen, bluntness of the liver edge, nodularity of the liver surface, and coarseness of the liver parenchyma have been known as useful parameters for hepatic fibrosis or portal hypertension (PHT) in chronic liver disease. Additionally, some functional US indices including Doppler and CEUS-based examination have been suggested as promising markers for diagnosing cirrhosis and PHT. Identification of the reproducibility and long-term prognostic value through further investigations can demonstrate the clinical usefulness of functional US indices, which are characterized as quantitative parameters for hepatic fibrosis and PHT.

Conventional and artificial intelligence-based imaging for biomarker discovery in chronic liver disease.

Chronic liver diseases, resulting from chronic injuries of various causes, lead to cirrhosis with life-threatening complications including liver failure, portal hypertension, hepatocellular carcinoma. A key unmet medical need is robust non-invasive biomarkers to predict patient outcome, stratify patients for risk of disease progression and monitor response to emerging therapies. Quantitative imaging biomarkers have already been developed, for instance, liver elastography for staging fibrosis or proton density fat fraction on magnetic resonance imaging for liver steatosis. Yet, major improvements, in the field of image acquisition and analysis, are still required to be able to accurately characterize the liver parenchyma, monitor its changes and predict any pejorative evolution across disease progression. Artificial intelligence has the potential to augment the exploitation of massive multi-parametric data to extract valuable information and achieve precision medicine. Machine learning algorithms have been developed to assess non-invasively certain histological characteristics of chronic liver diseases, including fibrosis and steatosis. Although still at an early stage of development, artificial intelligence-based imaging biomarkers provide novel opportunities to predict the risk of progression from early-stage chronic liver diseases toward cirrhosis-related complications, with the ultimate perspective of precision medicine. This review provides an overview of emerging quantitative imaging techniques and the application of artificial intelligence for biomarker discovery in chronic liver disease.

Validation of the New Diagnostic Criteria for Clinically Significant Portal Hypertension by Platelets and Elastography.

BACKGROUND AND AIMS: We aimed to validate newly proposed noninvasive criteria for diagnosing clinically significant portal hypertension (CSPH) using liver stiffness measurements (LSM) by transient elastography (TE) and platelet count. METHODS: Diagnostic performance of these new criteria for CSPH (LSM ≥ 25 kPa to rule in and Plt ≥ 150 × 109/L + LSM ≤ 15 kPa to rule out CSPH) were retrospectively tested in an independent cohort of consecutive patients who underwent hepatic venous pressure gradient (HVPG) measurements and liver biopsy due to suspicion of compensated advanced chronic liver disease. Suspicion of cACLD was based on LSM ≥ 10 kPa by TE or results of liver imaging, without overt signs of CSPH. Patients with conditions known to affect results of LSM (ALT > 5 × ULN, liver congestion, extrahepatic biliary obstruction, infiltrative liver neoplasms) were excluded. RESULTS: Seventy six (76) patients were included: 78.9% males, mean age 62 years, 36.8% suffered from alcoholic, 30.3% nonalcoholic fatty liver disease, 14.5% chronic viral hepatitis, 30.3% were obese, 52.6% had HVPG ≥ 10 mmHg, 56.6% had platelet count ≥ 150 × 109/L. LSM ≥ 25 kPa had 88.9% specificity (95% CI 73.9-96.9) to rule in, whereas Plt ≥ 150 + LSM ≤ 15 kPa had 100% sensitivity (95% CI 91.1-100) to rule out CSPH. CONCLUSION: By using these simple noninvasive criteria 49/76 (64.5%) patients could be classified correctly for the presence/absence of CSPH, thus obviating the need for HVPG measurements.

Hepatic stellate cells in the injured liver: Perspectives beyond hepatic fibrosis.

Over the last two decades, our understanding of the pathological role of hepatic stellate cells (HSCs) in fibrotic liver disease has increased dramatically. As HSCs are identified as the principal collagen-producing cells in the injured liver, several experimental and clinical studies have targeted HSCs to treat liver fibrosis. However, HSCs also play a critical role in developing nonfibrotic liver diseases such as cholestasis, portal hypertension, and hepatocellular carcinoma (HCC). Therefore, this review exclusively focuses on the role of activated HSCs beyond hepatic fibrosis. In cholestasis conditions, elevated bile salts and bile acids activate HSCs to secrete collagen and other extracellular matrix products, which cause biliary fibrosis and cholangitis. In the chronically injured liver, autocrine and paracrine signaling from liver sinusoidal endothelial cells activates HSCs to induce portal hypertension via endothelin-1 release. In the tumor microenvironment (TME), activated HSCs are the major source of cancer-associated fibroblasts (CAF). The crosstalk between activated HSC/CAF and tumor cells is associated with tumor cell proliferation, migration, metastasis, and chemoresistance. In TME, activated HSCs convert macrophages to tumor-associated macrophages and induce the differentiation of dendritic cells (DCs) and monocytes to regulatory DCs and myeloid-derived suppressor cells, respectively. This differentiation, in turn, increases T cells proliferation and induces their apoptosis leading to reduced immune surveillance in TME. Thus, HSCs activation in chronically injured liver is a critical process involved in the progression of cholestasis, portal hypertension, and liver cancer.

Impact of total splenectomy on peripheral lymphocytes and their subsets in patients with hypersplenism associated with cirrhotic portal hypertension.

To study the impact of total splenectomy (TS) on peripheral lymphocytes and their subsets in patients with hypersplenism associated with cirrhotic portal hypertension (CPH). We studied 102 consecutive patients who received TS from January 2008 to January 2020 due to CPH-related hypersplenism. A similar number of healthy individuals are used as healthy controls (HC). The total lymphocyte counts and their percentages of B lymphocytes, total T lymphocytes (cluster of differentiation (CD)3+) and their subsets (CD4+, CD8+), and natural killer (NK) cells in preoperative peripheral blood samples in hypersplenism patients were significantly lower than that of the HCs (both P < 0.05). The total lymphocyte counts and percentages of B lymphocytes in peripheral blood were significantly increased 1 week and 1 month after TS when compared with the pre-TS values (P < 0.05). There was no significant difference in the percentages of NK cells before or after surgery (P > 0.05). However, the percentages of CD3+ cells was significantly higher 1 month after than before surgery (P < 0.001). The percentages of CD4+, and CD8+ T lymphocytes were significantly lower 1 week after surgery (P < 0.05), but they were significantly higher 1 month after surgery (P < 0.01). The CD4+:CD8+ ratio was not significantly different from those before surgery, and 1 week or 1 month after surgery (P > 0.05). Patients with hypersplenism associated with CPH were significantly immunosuppressed preoperatively. After TS, the total lymphocyte count and percentages of B lymphocytes, and total T lymphocytes and their subsets increased significantly, resulting in improved immune functions.

Three-dimensional MR Elastography Depicts Liver Inflammation, Fibrosis, and Portal Hypertension in Chronic Hepatitis B or C.

Background The value of measuring mechanical properties to categorize various pathophysiologic states of the liver is as yet undetermined in chronic hepatitis B (CHB) or C (CHC). Purpose To evaluate multiparametric three-dimensional (3D) MR elastography as a means of detecting early necroinflammation, distinguishing necroinflammation from fibrosis, and gauging the severity of portal hypertension (PH) in CHB or CHC. Materials and Methods From January 2015 to September 2019, participants with CHB or CHC were prospectively enrolled from a single institution and were divided into two groups: those with liver biopsy and no evidence of PH (group 1) and those with PH and a hepatic venous pressure gradient (HVPG) measurement (group 2). For group 3, healthy volunteers were separately recruited from a nearby community. Multiple viscoelastic parameters (shear stiffness [SS], storage modulus, loss modulus, and damping ratio [DR]) were determined at 3D MR elastography at 60 Hz, and multivariable logistic or linear regression analysis was used to assess associations of mechanical parameters with histologic scores and HVPG. Results A total of 155 participants (median age, 41 years [interquartile range, 32-48 years]; 85 women) were in group 1 (training set: n = 78, validation set: n = 77), 85 participants (median age, 57 years [interquartile range, 43-61 years]; 51 women) in group 2, and 60 healthy volunteers (median age, 49 years [interquartile range, 27-64 years]; 38 men) in group 3. The liver DR was higher in participants with necroinflammation (DR, 0.13 ± 0.03) versus those without (at liver fibrosis stage F0) (DR, 0.10 ± 0.02; P < .001). Liver DR and SS together performed well in the diagnosis of necroinflammation (area under the receiver operating characteristic curve [AUC], 0.88 [95% CI: 0.79, 0.96]) and the scoring of moderate to severe activity (AUC, 0.88 [95% CI: 0.81, 0.95]) in the validation data set. Liver DR (regression coefficient [ß] = -30.3 [95% CI: -58.0, -2.5]; P = .03) and splenic SS (ß = 2.3 [95% CI: 1.7, 2.9]; P < .001) were independently associated with HVPG. Conclusion Three-dimensional MR elastography may detect early necroinflammation, distinguish necroinflammation from liver fibrosis, and correlate with hepatic venous pressure gradient in chronic hepatitis B and C. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Reeder in this issue.