Browsing by Subject "Portal hypertension"

Now showing 1 - 7 of 7
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    Changing epidemiology and outcomes of acute kidney injury in hospitalized patients with cirrhosis - a US population-based study
    (Elsevier, 2020-11) Desai, Archita P.; Knapp, Shannon M.; Orman, Eric S.; Ghabril, Marwan S.; Nephew, Lauren D.; Anderson, Melissa; Ginès, Pere; Chalasani, Naga P.; Patidar, Kavish R.; Medicine, School of Medicine
    Background & aims: Acute kidney injury (AKI) is a significant clinical event in cirrhosis yet contemporary population-based studies on the impact of AKI on hospitalized cirrhotics are lacking. We aimed to characterize longitudinal trends in incidence, healthcare burden and outcomes of hospitalized cirrhotics with and without AKI using a nationally representative dataset. Methods: Using the 2004-2016 National Inpatient Sample (NIS), admissions for cirrhosis with and without AKI were identified using ICD-9 and ICD-10 codes. Regression analysis was used to analyze the trends in hospitalizations, costs, length of stay and inpatient mortality. Descriptive statistics, simple and multivariable logistic regression were used to assess associations between individual characteristics, comorbidities, and cirrhosis complications with AKI and death. Results: In over 3.6 million admissions for cirrhosis, 22% had AKI. AKI admissions were more costly (median $13,127 [IQR $7,367-$24,891] vs. $8,079 [IQR $4,956-$13,693]) and longer (median 6 [IQR 3-11] days vs. 4 [IQR 2-7] days). Over time, AKI prevalence doubled from 15% in 2004 to 30% in 2016. CKD was independently and strongly associated with AKI (adjusted odds ratio 3.75; 95% CI 3.72-3.77). Importantly, AKI admissions were 3.75 times more likely to result in death (adjusted odds ratio 3.75; 95% CI 3.71-3.79) and presence of AKI increased risk of mortality in key subgroups of cirrhosis, such as those with infections and portal hypertension-related complications. Conclusions: The prevalence of AKI is significantly increased among hospitalized cirrhotics. AKI substantially increases the healthcare burden associated with cirrhosis. Despite advances in cirrhosis care, a significant gap remains in outcomes between cirrhotics with and without AKI, suggesting that AKI continues to represent a major clinical challenge.
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    Interobserver study on histologic features of idiopathic non-cirrhotic portal hypertension
    (BMC, 2020-10-23) Kmeid, Michel; Zuo, Chunlai; Lagana, Stephen M.; Choi, Won-Tak; Lin, Jingmei; Yang, Zhaohai; Liu, Xiuli; Westerhoff, Maria; Fiel, M. Isabel; Affolter, Kajsa; Choi, Eun-Young K.; Lee, Hwajeong; Pathology and Laboratory Medicine, School of Medicine
    Background Histologic features of idiopathic non-cirrhotic portal hypertension (INCPH) may overlap with those without INCPH. Recently, these features have been recognized as part of the larger spectrum of porto-sinusoidal vascular disease (PSVD). We assessed interobserver agreement on histologic features that are commonly associated with INCPH and studied whether a provision of relevant clinical history improves interobserver agreement. Methods The examined histologic features include lobular (such as anisocytosis, nodular regeneration, sinusoidal dilatation, increased parenchymal draining veins, and incomplete fibrous septa) and portal tract changes (such as paraportal shunting vessel(s), portal tract remnant, increased number of portal vessels, and obliterative portal venopathy). Thirty-four archived liver samples from patients with (group A) and without (group B) INCPH were retrieved. A total of 90 representative images of lobules (L) and portal tracts (P) were distributed among 9 liver pathologists blinded to true clinical history. Each pathologist answered multiple choice questions based on the absence (Q1) or presence (Q2) of clinical history of portal hypertension. Fleiss’ kappa coefficient analysis (unweighted) was performed to assess interobserver agreement on normal versus abnormal diagnosis, in L and P, based on Q1 and Q2. Results The kappa values regarding normal versus abnormal diagnosis were 0.24, 0.24, 0.18 and 0.18 for L-Q1, L-Q2, P-Q1, and P-Q2, respectively. With true clinical history provided, the kappa values were L- 0.32, P-0.17 for group A and L-0.12, P-0.14 for group B. Four pathologists changed their assessments based on the provided history. Interobserver agreement on the interpretation of L and P as normal versus abnormal was slight to fair regardless of provision of clinical history. Conclusions Our findings indicate that the histologic features of INCPH/PSVD are not limited to patients with portal hypertension and are subject to significant interobserver variation. Supplementary information The online version contains supplementary material available at 10.1186/s13000-020-01049-0.
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    Machine learning liver histology scores correlate with portal hypertension assessments in nonalcoholic steatohepatitis cirrhosi
    (Wiley, 2023) Noureddin, Mazen; Goodman, Zachary; Tai, Dean; Chng, Elaine L. K.; Ren, Yayun; Boudes, Pol; Shlevin, Harold; Garcia-Tsao, Guadalupe; Harrison, Stephen A.; Chalasani, Naga P.; Medicine, School of Medicine
    Background and aims: In cirrhotic nonalcoholic steatohepatitis (NASH) clinical trials, primary efficacy endpoints have been hepatic venous pressure gradient (HVPG), liver histology and clinical liver outcomes. Important histologic features, such as septa thickness, nodules features and fibrosis area have not been included in the histologic assessment and may have important clinical relevance. We assessed these features with a machine learning (ML) model. Methods: NASH patients with compensated cirrhosis and HVPG ≥6 mm Hg (n = 143) from the Belapectin phase 2b trial were studied. Liver biopsies, HVPG measurements and upper endoscopies were performed at baseline and at end of treatment (EOT). A second harmonic generation/two-photon excitation fluorescence provided an automated quantitative assessment of septa, nodules and fibrosis (SNOF). We created ML scores and tested their association with HVPG, clinically significant HVPG (≥10 mm Hg) and the presence of varices (SNOF-V). Results: We derived 448 histologic variables (243 related to septa, 21 related to nodules and 184 related to fibrosis). The SNOF score (≥11.78) reliably distinguished CSPH at baseline and in the validation cohort (baseline + EOT) [AUC = 0.85 and 0.74, respectively]. The SNOF-V score (≥0.57) distinguished the presence of varices at baseline and in the same validation cohort [AUC = 0.86 and 0.73, respectively]. Finally, the SNOF-C score differentiated those who had >20% change in HVPG against those who did not, with an AUROC of 0.89. Conclusion: The ML algorithm accurately predicted HVPG, CSPH, the development of varices and HVPG changes in patients with NASH cirrhosis. The use of ML histology model in NASH cirrhosis trials may improve the assessment of key outcome changes.
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    Murine study of portal hypertension associated endothelin-1 hypo-response
    (Baishideng Publishing Group, 2015-04-28) Theodorakis, Nicholas; Maluccio, Mary; Skill, Nicholas; Department of Medicine, IU School of Medicine
    AIM: To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes. METHODS: Wild type, eNOS(-/-) and iNOS(-/-) mice received partial portal vein ligation surgery to induce portal hypertension or sham surgery. Development of portal hypertension was determined by measuring the splenic pulp pressure, abdominal aortic flow and portal systemic shunting. To measure splenic pulp pressure, a microtip pressure transducer was inserted into the spleen pulp. Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery. Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds. Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration. In addition, thoracic aorta endothelin-1 contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph. RESULTS: In wild type and iNOS(-/-) mice splenic pulp pressure increased from 7.5 ± 1.1 mmHg and 7.2 ± 1 mmHg to 25.4 ± 3.1 mmHg and 22 ± 4 mmHg respectively. In eNOS(-/-) mice splenic pulp pressure was increased after 1 d (P = NS), after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls (6.9 ± 0.6 mmHg and 7.3 ± 0.8 mmHg respectively, P = 0.3). Abdominal aortic flow was increased by 80% and 73% in 7 d portal vein ligated wild type and iNOS when compared to shams, whereas there was no significant difference in 7 d portal vein ligated eNOS(-/-) mice when compared to shams. Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type, eNOS(-/-) and iNOS(-/-) sham mice (50% ± 8%, 73% ± 9% and 47% ± 9% respectively). Following portal vein ligation endothelin-1 reduction in blood flow was significantly diminished in each mouse group. Abdominal aortic flow was reduced by 19% ± 9%, 32% ± 10% and 9% ± 9% in wild type, eNOS(-/-) and iNOS(-/-) mice respectively. CONCLUSION: Aberrant endothelin-1 response in murine portal hypertension is NOS isoform independent. Moreover, portal hypertension in the portal vein ligation model is independent of ET-1 function.
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    Nonalcoholic Fatty Liver Disease and Diabetes Mellitus Are Associated With Post-Transjugular Intrahepatic Portosystemic Shunt Renal Dysfunction: An Advancing Liver Therapeutic Approaches Group Study
    (Wolters Kluwer, 2021) Ge, Jin; Lai, Jennifer C.; Boike, Justin Richard; German, Margarita; Jest, Nathaniel; Morelli, Giuseppe; Spengler, Erin; Said, Adnan; Lee, Alexander; Hristov, Alexander; Desai, Archita P.; Junna, Shilpa; Pokhrel, Bhupesh; Couri, Thomas; Paul, Sonali; Frenette, Catherine; Christian-Miller, Nathaniel; Laurito, Marcela; Verna, Elizabeth C.; Rahim, Usman; Goel, Aparna; Das, Arighno; Pine, Stewart; Gregory, Dyanna; VanWagner, Lisa B.; Kolli, Kanti Pallav; Advancing Liver Therapeutic Approaches (ALTA) Study Group; Medicine, School of Medicine
    Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well characterized. Here we describe renal function and characteristics associated with renal dysfunction at 30 days post-TIPS. Adults with cirrhosis who underwent TIPS at 9 hospitals in the United States from 2010 to 2015 were included. We defined "post-TIPS renal dysfunction" as a change in estimated glomerular filtration rate (ΔeGFR) ≤-15 and eGFR ≤ 60 mL/min/1.73 m2 or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post-TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions. Of the 673 patients, the median age was 57 years, 38% of the patients were female, 26% had diabetes mellitus, and the median MELD-Na was 17. After 30 days post-TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post-TIPS renal dysfunction, compared with those with stable renal function, were more likely to have nonalcoholic fatty liver disease (NAFLD; 33% versus 17%; P = 0.01) and comorbid diabetes mellitus (42% versus 24%; P = 0.001). Multivariate logistic regressions showed NAFLD (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.00-4.17; P = 0.05), serum sodium (Na; OR, 1.06 per mEq/L; 95% CI, 1.01-1.12; P = 0.03), and diabetes mellitus (OR, 2.04; 95% CI, 1.16-3.61; P = 0.01) were associated with post-TIPS renal dysfunction. Competing risk regressions showed that those with post-TIPS renal dysfunction were at a higher subhazard of death (subhazard ratio, 1.74; 95% CI, 1.18-2.56; P = 0.01). In this large, multicenter cohort, we found NAFLD, diabetes mellitus, and baseline Na associated with post-TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes mellitus undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities before proceeding with the procedure.
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    Portal vein thrombosis, mortality and hepatic decompensation in patients with cirrhosis: A meta-analysis
    (Baishideng Publishing Group Co (World Journal of Hepatology), 2015-11-28) Stine, Jonathan G.; Shah, Puja M.; Cornella, Scott L.; Rudnick, Sean R.; Ghabril, Marwan S.; Stukenborg, George J.; Northup, Patrick G.; Department of Medicine, IU School of Medicine
    AIM: To determine the clinical impact of portal vein thrombosis in terms of both mortality and hepatic decompensations (variceal hemorrhage, ascites, portosystemic encephalopathy) in adult patients with cirrhosis. METHODS: We identified original articles reported through February 2015 in MEDLINE, Scopus, Science Citation Index, AMED, the Cochrane Library, and relevant examples available in the grey literature. Two independent reviewers screened all citations for inclusion criteria and extracted summary data. Random effects odds ratios were calculated to obtain aggregate estimates of effect size across included studies, with 95%CI. RESULTS: A total of 226 citations were identified and reviewed, and 3 studies with 2436 participants were included in the meta-analysis of summary effect. Patients with portal vein thrombosis had an increased risk of mortality (OR = 1.62, 95%CI: 1.11-2.36, P = 0.01). Portal vein thrombosis was associated with an increased risk of ascites (OR = 2.52, 95%CI: 1.63-3.89, P < 0.001). There was insufficient data available to determine the pooled effect on other markers of decompensation including gastroesophageal variceal bleeding or hepatic encephalopathy. CONCLUSION: Portal vein thrombosis appears to increase mortality and ascites, however, the relatively small number of included studies limits more generalizable conclusions. More trials with a direct comparison group are needed.
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    Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure
    (Baishideng Publishing Group, 2015-04-14) Theodorakis, Nicholas G.; Wang, Yining N.; Korshunov, Vyacheslav A.; Maluccio, Mary A.; Skill, Nicholas J.; Department of Medicine, IU School of Medicine
    AIM: Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity. Previous reports have suggested that the compound thalidomide attenuates portal hypertension (PHT). However, the mechanism for this action is not fully elucidated. One hypothesis is that thalidomide destabilizes tumor necrosis factor α (TNFα) mRNA and therefore diminishes TNFα induction of nitric oxide synthase (NOS) and the production of nitric oxide (NO). To examine this hypothesis, we utilized the murine partial portal vein ligation (PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice. METHODS: Wild type, inducible nitric oxide synthase (iNOS)-/- and endothelial nitric oxide synthase (eNOS)-/- mice received either PVL or sham surgery and were given either thalidomide or vehicle. Serum nitrate (total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis. Serum TNFα level was quantified by enzyme-linked immunosorbent assay. TNFα mRNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction. PHT was determined by recording splenic pulp pressure (SPP) and abdominal aortic flow after 0-7 d. Response to thalidomide was determined by measurement of SPP and mean arterial pressure (MAP). RESULTS: SPP, abdominal aortic flow (Qao) and plasma NOx were increased in wild type and iNOS-/- PVL mice when compared to sham operated control mice. In contrast, SPP, Qao and plasma NOx were not increased in eNOS-/- PVL mice when compared to sham controls. Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used. Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, eNOS-/- or iNOS-/- mice. Thalidomide acutely increased plasma NOx in wild type and eNOS-/- mice but not iNOS-/- mice. Moreover, thalidomide temporarily (0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, eNOS-/- and iNOS-/- PVL mice, after which time levels returned to the respective baseline. CONCLUSION: Thalidomide does not reduce portal pressure in the murine PVL model by modulation of NO biosynthesis. Rather, thalidomide reduces PHT by decreasing MAP by an undetermined mechanism.