Browsing by Subject "Hepatocellular carcinoma"
Now showing 1 - 10 of 43
Results Per Page
Sort Options
Item A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers(Elsevier, 2022) Whitfield, John B.; Schwantes-An, Tae-Hwi; Darlay, Rebecca; Aithal, Guruprasad P.; Atkinson, Stephen R.; Bataller, Ramon; Botwin, Greg; Chalasani, Naga P.; Cordell, Heather J.; Daly, Ann K.; Day, Christopher P.; Eyer, Florian; Foroud, Tatiana; Gleeson, Dermot; Goldman, David; Haber, Paul S.; Jacquet, Jean-Marc; Liang, Tiebing; Liangpunsakul, Suthat; Masson, Steven; Mathurin, Philippe; Moirand, Romain; McQuillin, Andrew; Moreno, Christophe; Morgan, Marsha Y.; Mueller, Sebastian; Müllhaupt, Beat; Nagy, Laura E.; Nahon, Pierre; Nalpas, Bertrand; Naveau, Sylvie; Perney, Pascal; Pirmohamed, Munir; Seitz, Helmut K.; Soyka, Michael; Stickel, Felix; Thompson, Andrew; Thursz, Mark R.; Trépo, Eric; Morgan, Timothy R.; Seth, Devanshi; GenomALC Consortium; Medical and Molecular Genetics, School of MedicineBackground & aims: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. Methods: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). Results: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18-8.60) (GenomALC-1), 2.81 (2.03-3.89) (GenomALC-2), and 3.10 (2.32-4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 ± 0.06 vs. 0.61 ± 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. Conclusions: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions. Lay summary: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.Item A global evaluation of advanced dosimetry in transarterial radioembolization of hepatocellular carcinoma with Yttrium-90: the TARGET study(Springer, 2022) Lam, Marnix; Garin, Etienne; Maccauro, Marco; Kappadath, S. Cheenu; Sze, Daniel Y.; Turkmen, Cuneyt; Cantasdemir, Murat; Haste, Paul; Herrmann, Ken; Alsuhaibani, Hamad Saleh; Dreher, Matthew; Fowers, Kirk D.; Salem, Riad; Radiology and Imaging Sciences, School of MedicinePurpose: To investigate the relationships between tumor absorbed dose (TAD) or normal tissue absorbed dose (NTAD) and clinical outcomes in hepatocellular carcinoma (HCC) treated with yttrium-90 glass microspheres. Methods: TARGET was a retrospective investigation in 13 centers across eight countries. Key inclusion criteria: liver-dominant HCC with or without portal vein thrombosis, < 10 tumors per lobe (at least one ≥ 3 cm), Child-Pugh stage A/B7, BCLC stages A-C, and no prior intra-arterial treatment. Multi-compartment pre-treatment dosimetry was performed retrospectively. Primary endpoint was the relationship between ≥ grade 3 hyperbilirubinemia (such that > 15% of patients experienced an event) without disease progression and NTAD. Secondary endpoints included relationships between (1) objective response (OR) and TAD, (2) overall survival (OS) and TAD, and (3) alpha fetoprotein (AFP) and TAD. Results: No relationship was found between NTAD and ≥ grade 3 hyperbilirubinemia, which occurred in 4.8% of the 209 patients. The mRECIST OR rate over all lesions was 61.7%; for the target (largest) lesion, 70.8%. Responders and non-responders had geometric mean total perfused TADs of 225.5 Gy and 188.3 Gy (p = 0.048). Probability of OR was higher with increasing TAD (p = 0.044). Higher TAD was associated with longer OS (HR per 100 Gy increase = 0.83, 95% CI: 0.71-0.95; p = 0.009). Increased TAD was associated with higher probability of AFP response (p = 0.046 for baseline AFP ≥ 200 ng/mL). Conclusion: Real-world data confirmed a significant association between TAD and OR, TAD and OS, and TAD and AFP response. No association was found between ≥ grade 3 hyperbilirubinemia and NTAD.Item Advancements in Immunotherapeutic Treatments for Hepatocellular Carcinoma: Potential of Combination Therapies(MDPI, 2024-06-21) Zarlashat, Yusra; Mushtaq, Hassan; Pham, Linh; Abbas, Wasim; Sato, Keisaku; Medicine, School of MedicineHepatocellular carcinoma (HCC) is the sixth most prevalent cancer and a significant global health burden, with increasing incidence rates and limited treatment options. Immunotherapy has become a promising approach due to its ability to affect the immune microenvironment and promote antitumor responses. The immune microenvironment performs an essential role in both the progression and the development of HCC, with different characteristics based on specific immune cells and etiological factors. Immune checkpoint inhibitors, including programmed death-1/programmed death-ligand 1 inhibitors (pembrolizumab, nivolumab, and durvalumab) and cytotoxic T lymphocyte antigen-4 inhibitors (tremelimumab and ipilimumab), have the potential to treat advanced HCC and overcome adverse effects, such as liver failure and chemoresistance. Phase II and phase III clinical trials highlight the efficacy of pembrolizumab and nivolumab, respectively, in advanced HCC patients, as demonstrated by their positive effects on overall survival and progression-free survival. Tremelimumab has exhibited modest response rates, though it does possess antiviral activity. Thus, it is still being investigated in ongoing clinical trials. Combination therapies with multiple drugs have demonstrated potential benefits in terms of survival and tumor response rates, improving patient outcomes compared to monotherapy, especially for advanced-stage HCC. This review addresses the clinical trials of immunotherapies for early-, intermediate-, and advanced-stage HCC. Additionally, it highlights how combination therapy can significantly enhance overall survival, progression-free survival, and objective response rate in advanced-stage HCC, where treatment options are limited.Item Assessment and management of comorbidities (including cardiovascular disease) in patients with nonalcoholic fatty liver disease(Wiley, 2012-09-25) Corey, Kathleen E.; Vuppalanchi, Raj; Medicine, School of MedicineNonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. Nonalcoholic steatohepatitis, the progressive form of NAFLD, can lead to end‐stage liver disease and hepatocellular carcinoma. However, the consequences of NAFLD are not confined to the liver. NAFLD is associated with an increased risk of cardiovascular disease (CVD) and is frequently associated with metabolic syndrome. Thus, there is a pressing need for the diagnosis and management of the comorbidities of NAFLD, including CVD. This review will guide clinicians in the assessment and management of metabolic disease and CVD in patients with NAFLD.Item Benefits of combination therapy with immune checkpoint inhibitors and predictive role of tumour mutation burden in hepatocellular carcinoma: A systematic review and meta-analysis(Elsevier, 2022-11) Zheng, Jiaxi; Shao, Minghai; Yang , Weifang; Ren , Justin; Chen, Xiaofeng; Yang, Haihua; Radiation Oncology, School of MedicineObjectives To investigate the clinical benefits of combination therapy with immune checkpoint inhibitors (ICIs) and best combination regimen for people with advanced hepatocellular carcinoma (HCC) and to explore the predictive performance of tumour mutation burden (TMB). Methods We conducted a systematic literature search to identify clinical trials. Meta-analysis and subgroup analyses were performed to estimate the benefits of combination regimens with PD-1/PD-L1 inhibitors for patients with advanced HCC and compare the effectiveness of PD-1/PD-L1 inhibitors and sorafenib as first-line therapy. Individualized analysis and Kaplan-Meier were used to assess the prognostic value of TMB. Results A total of 29 studies with 5396 patients were included. ICIs’ combination therapy had higher ORR (26 % vs 15 %) and DCR (73 % vs 55 %), longer PFS (5.5 vs 3.1 months) and OS (15.9 vs 12.6 months) compared to monotherapy. Anti-PD-1/PD-L1 agents provided improved ORR, DCR, PFS and OS compared to sorafenib. The overall ORs of ORR and DCR in subgroup analysis were 3.49 (95 % CI 2.36–5.17, p < 0.01) and 1.60 (95 % CI 1.15–2.21, p < 0.01). The overall HRs of PFS and OS were 0.68 (95 % CI 0.48–0.96, p = 0.03) and 0.73 (95 % CI 0.62–0.85, p < 0.01). PD-1/PD-L1 inhibitors plus anti-VEGF agents had an advantage in DCR (0.80 vs 0.48, meta-regression = − 0.32, P < 0.001), but an equal ORR (0.29 vs 0.26) compared to dual immune checkpoint inhibitors. The total OS in Dua-ICIs were 16.5 months (95 % CI 14.2–18.7), yet not reached in the major studies of ICI plus anti-VEGF regimen. In individualized analysis, the 1-year OS was superior for patients who had high-TMB (>10, mutations/Mb) than moderate-TMB (1–10, mutations/Mb; 28 % vs 15 %, P = 0.025). Conclusion Immune checkpoint inhibitors’ combination therapy improved clinical outcomes in the management of advanced hepatocellular carcinoma. However, the overall objective response rate still did not exceed 30%. PD-1/PD-L1 inhibitors plus anti-angiogenic agents and dual immunotherapy provided significantly increased survival over sorafenib, which also pose new challenges for future research, and more appropriate and guided control regimens are required. Also, TMB may be a promising prognostic biomarker for immunotherapy in HCC. However, the validation of prospective and large sample studies is needed.Item Changing Trends of Cirrhotic and Noncirrhotic Hepatocellular Carcinoma in the Era of Directly-Acting Antiviral Agents(Wolters Kluwer, 2021-11-03) Mathur, Karan; Mazhar, Areej; Patel, Milin; Dakhoul, Lara; Burney, Heather; Liu, Hao; Nephew, Lauren; Chalasani, Naga; deLemos, Andrew; Gawrieh, Samer; Medicine, School of MedicineIntroduction: The impact of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) on burden of cirrhotic and noncirrhotic hepatocellular carcinoma (HCC) has not been examined. We assessed recent trends in liver disease etiologies of HCC and proportion of noncirrhotic HCC since DAAs introduction. Methods: Clinical characteristics including presence or absence of underlying cirrhosis were collected from 2,623 patients diagnosed with HCC between 2009 and 2019 at 2 large US centers. Logistic regression was performed to investigate the annual trends of HCC due to different liver diseases and proportions of noncirrhotic cases. Results: In the DAA era (2014-2019), annual decline in HCV-HCC (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.88-0.99, P = 0.019), without change in trends of other liver diseases-related HCC, was observed. Annual increase in noncirrhotic HCC (OR 1.13, 95% CI 1.03-1.23, P = 0.009) and decline in cirrhotic HCC (OR 0.89, 95% CI 0.81-0.97, P = 0.009) along with similar trends for HCV-HCC-increase in noncirrhotic cases (OR 1.35, 95% CI 1.08-1.69, P = 0.009) and decrease in cirrhotic cases (OR 0.92, 95% CI 0.86-0.98, P = 0.012)-were observed during the DAA era. Compared with the pre-DAA era, HCC resection rate increased (10.7% vs 14.0%, P = 0.013) whereas liver transplantation rate decreased (15.1% vs 12.0%, P = 0.023) in the DAA era. Discussion: Since introduction of DAAs, proportions of cirrhotic HCC have decreased, whereas proportions of noncirrhotic HCC have increased. These new trends were associated with change in utilization of liver resection and transplantation for HCC. The impact of changing patterns of DAA use on these trends will require further study.Item Clinical, dosimetric, and reporting considerations for Y-90 glass microspheres in hepatocellular carcinoma: updated 2022 recommendations from an international multidisciplinary working group(Springer, 2023) Salem, Riad; Padia, Siddharth A.; Lam, Marnix; Chiesa, Carlo; Haste, Paul; Sangro, Bruno; Toskich, Beau; Fowers, Kirk; Herman, Joseph M.; Kappadath, S. Cheenu; Leung, Thomas; Sze, Daniel Y.; Kim, Edward; Garin, Etienne; Radiology and Imaging Sciences, School of MedicinePurpose: In light of recently published clinical reports and trials, the TheraSphere Global Dosimetry Steering Committee (DSC) reconvened to review new data and to update previously published clinical and dosimetric recommendations for the treatment of hepatocellular carcinoma (HCC). Methods: The TheraSphere Global DSC is comprised of health care providers across multiple disciplines involved in the treatment of HCC with yttrium-90 (Y-90) glass microsphere-based transarterial radioembolization (TARE). Literature published between January 2019 and September 2021 was reviewed, discussed, and adjudicated by the Delphi method. Recommendations included in this updated document incorporate both the results of the literature review and the expert opinion and experience of members of the committee. Results: Committee discussion and consensus led to the expansion of recommendations to apply to five common clinical scenarios in patients with HCC to support more individualized efficacious treatment with Y-90 glass microspheres. Existing clinical scenarios were updated to reflect recent developments in dosimetry approaches and broader treatment paradigms evolving for patients presenting with HCC. Conclusion: Updated consensus recommendations are provided to guide clinical and dosimetric approaches for the use of Y-90 glass microsphere TARE in HCC, accounting for disease presentation, tumor biology, and treatment intent.Item Comparison of Dynamic Phase Enhancement of Hepatocellular Carcinoma using Gadoxetate Disodium versus Gadobenate Dimeglumine(Lippincott Williams & Wilkins, 2015-07) Tirkes, Temel; Mehta, Peter; Aisen, Alex M.; Lall, Chandana; Akisik, Fatih; Department of Radiology and Imaging Sciences, IU School of MedicineObjective: To determine the differences in enhancement of hepatocellular carcinoma during the first 5 minutes of postcontrast phases with gadoxetic acid (Gd-EOB-DTPA) vs gadobenate dimeglumine. Methods: Ninety-five cirrhotic patients with hepatocellular carcinoma were examined on a 1.5-T scanner: 74 patients with Gd-BOPTA and 21 patients with Gd-EOB-DTPA. Same magnetic resonance imaging parameters were used for both groups. Gadoxetate isodium was administered at a dose of 0.025 mmol/kg; and Gd-BOPTA, at a dose of 0.1 mmol/kg. Results: Mean contrast-to-noise ratios (CNR) were similar in arterial (P = 0.3), portal venous (P = 0.1), and 5-minute delayed phases (P = 0.73). The CNRs of lesions in the Gd-EOB-DTPA group were lower in arterial phase, although this did not reach statistical significance. The CNRs of Gd-EOB-DTPA during the equilibrium phase was higher (P = 0.006). Conclusions: Gadoxetate isodium resulted in lower CNR during the arterial phase and higher CNR during the portal venous, equilibrium, and 5-minute delayed phases compared with gadobenate dimeglumine using the Food and Drug Administration–approved doses; however, overall, there was no statistical significance (P = 0.077).Item Comparison of hepatic MDCT, MRI, and DSA to explant pathology for the detection and treatment planning of hepatocellular carcinoma(The Korean Association for the Study of the Liver, 2016-12) Ladd, Lauren M.; Tirkes, Temel; Tann, Mark; Agarwal, David M.; Johnson, Matthew S.; Tahir, Bilal; Sandrasegaran, Kumaresan; Department of Radiology and Imaging Sciences, IU School of MedicineBACKGROUND/AIMS: The diagnosis and treatment plan for hepatocellular carcinoma (HCC) can be made from radiologic imaging. However, lesion detection may vary depending on the imaging modality. This study aims to evaluate the sensitivities of hepatic multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) in the detection of HCC and the consequent management impact on potential liver transplant patients. METHODS: One hundred and sixteen HCC lesions were analyzed in 41 patients who received an orthotopic liver transplant (OLT). All of the patients underwent pretransplantation hepatic DSA, MDCT, and/or MRI. The imaging results were independently reviewed retrospectively in a blinded fashion by two interventional and two abdominal radiologists. The liver explant pathology was used as the gold standard for assessing each imaging modality. RESULTS: The sensitivity for overall HCC detection was higher for cross-sectional imaging using MRI (51.5%, 95% confidence interval [CI]=36.2-58.4%) and MDCT (49.8%, 95% CI=43.7-55.9%) than for DSA (41.7%, 95% CI=36.2-47.3%) (P=0.05). The difference in false-positive rate was not statistically significant between MRI (22%), MDCT (29%), and DSA (29%) (P=0.67). The sensitivity was significantly higher for detecting right lobe lesions than left lobe lesions for all modalities (MRI: 56.1% vs. 43.1%, MDCT: 55.0% vs. 42.0%, and DSA: 46.9% vs. 33.9%; all P<0.01). The sensitivities of the three imaging modalities were also higher for lesions ≥2 cm vs. <2 cm (MRI: 73.4% vs. 32.7%, MDCT: 66.9% vs. 33.8%, and DSA: 62.2% vs. 24.1%; all P<0.01). The interobserver correlation was rated as very good to excellent. CONCLUSION: The sensitivity for detecting HCC is higher for MRI and MDCT than for DSA, and so cross-sectional imaging modalities should be used to evaluate OLT candidacy.Item Core implementation strategies for improving cirrhosis care in the Veterans Health Administration(Wolters Kluwer, 2022) Yakovchenko, Vera; Morgan, Timothy R.; Miech, Edward J.; Neely, Brittney; Lamorte, Carolyn; Gibson, Sandra; Beste, Lauren A.; McCurdy, Heather; Scott, Dawn; Gonzalez, Rachel; Park, Angela; Powell, Byron J.; Bajaj, Jasmohan S.; Dominitz, Jason A.; Chartier, Maggie; Ross, David; Chinman, Matthew J.; Rogal, Shari S.; Emergency Medicine, School of MedicineBackground and aims: The Veterans Health Administration (VHA) provides care for more than 80,000 veterans with cirrhosis. This longitudinal, multimethod evaluation of a cirrhosis care quality improvement program aimed to (1) identify implementation strategies associated with evidence-based, guideline-concordant cirrhosis care over time, and (2) use qualitative interviews to operationalize strategies for a manualized intervention. Approach and results: VHA providers were surveyed annually about the use of 73 implementation strategies to improve cirrhosis care in fiscal years 2018 (FY18) and 2019 (FY19). Implementation strategies linked to guideline-concordant cirrhosis care were identified using bivariate statistics and comparative configurational methods. Semistructured interviews were conducted with 12 facilities in the highest quartile of cirrhosis care to specify the successful implementation strategies and their mechanisms of change. A total of 106 VHA facilities (82%) responded at least once over the 2-year period (FY18, n = 63; FY19, n = 100). Facilities reported using a median of 12 (interquartile range [IQR] 20) implementation strategies in FY18 and 10 (IQR 19) in FY19. Of the 73 strategies, 35 (48%) were positively correlated with provision of evidence-based cirrhosis care. Configurational analysis identified multiple strategy pathways directly linked to more guideline-concordant cirrhosis care. Across both methods, a subset of eight strategies was determined to be core to cirrhosis care improvement and specified using qualitative interviews. Conclusions: In a national cirrhosis care improvement initiative, a multimethod approach identified a core subset of successful implementation strategy combinations. This process of empirically identifying and specifying implementation strategies may be applicable to other implementation challenges in hepatology.