Hepatocellular Cancer In Patients Research Articles

Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis

BackgroundInflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive...

Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis.

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide but is often diagnosed at an advanced incurable stage. Yet, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify risk-stratifying biomarkers. We address this gap using the TGF-β pathway because of its biological role in liver disease and cancer, established through rigorous animal models and human studies. Using machine learning methods with blood levels of 108 proteomic markers in the TGF-β family, we found a pattern that differentiates HCC from non-HCC in a cohort of 216 patients with cirrhosis, which we refer to as TGF-β based Protein Markers for Early Detection of HCC (TPEARLE) comprising 31 markers. Notably, 20 of the patients with cirrhosis alone presented an HCC-like pattern, suggesting that they may be a group with as yet undetected HCC or at high risk for developing HCC. In addition, we found two other biologically relevant markers, Myostatin and Pyruvate Kinase M2 (PKM2), which were significantly associated with HCC. We tested these for risk stratification of HCC in multivariable models adjusted for demographic and clinical variables, as well as batch and site. These markers reflect ongoing biology in the liver. They potentially indicate the presence of HCC early in its evolution and before it is manifest as a detectable lesion, thereby providing a set of markers that may be able to stratify risk for HCC.

The role of calcineurin inhibitors in the progression of hepatocellular carcinoma after liver transplantation

Introduction. Orthotopic liver transplantation is the most radical method of treatment of hepatocellular carcinoma. The high recurrence rate limits the use of transplantation in patients with hepatocellular cancer. Immunosuppressive therapy may affect the frequency of oncoprogression after liver transplantationAim. To evaluate the role of immunosuppressive therapy in the postoperative progression of hepatocellular cancer in patients after liver transplantationMaterial and methods. The recurrence rate of hepatocellular cancer and tumor free survival in 104 patients after liver transplantation were analyzed. To evaluate the effect of the immunosuppression main component concentration on the postoperative progression of hepatocellular carcinoma, we studied the mean baseline concentration (C0) for the entire follow-up period for patients with a tumor-free period and the mean baseline concentration for patients with hepatocellular carcinoma progression, in whom only the duration of the tumor-free period was studied. According to the degree of tumor lesion, patients were distributed in accordance with the Milan criteria (based on the results of a pathologic and morphological examination of the recipient's explanted liver.Results. The values of the baseline blood level of tacrolimus>6.0 ng/ml and cyclosporine A>100 ng/ml is associated with a high rate of progression of hepatocellular cancer. Reducing the load of calcineurin inhibitors can reduce the incidence of cancer progression by at least 2 times. The values of 1-, 3- and 5-year relapse-free survival in patients with advanced cancer and low figures of the baseline blood level of calcineurin inhibitor are 82%, 70% and 70%, respectively.Conclusion. Minimization of immunosuppression is of crucial importance in the prevention of posttransplant progression of hepatocellular cancer, especially among patients with its common form.

Discriminatory Changes in Circulating Metabolites as a Predictor of Hepatocellular Cancer in Patients with Metabolic (Dysfunction) Associated Fatty Liver Disease

Introduction: The burden of metabolic (dysfunction) associated fatty liver disease (MAFLD) is rising mirrored by an increase in hepatocellular cancer (HCC). MAFLD and its sequelae are characterized by perturbations in lipid handling, inflammation, and mitochondrial damage. The profile of circulating lipid and small molecule metabolites with the development of HCC is poorly characterized in MAFLD and could be used in future studies as a biomarker for HCC. Methods: We assessed the profile of 273 lipid and small molecule metabolites by ultra-performance liquid chromatography coupled to high-resolution mass spectrometry in serum from patients with MAFLD (n = 113) and MAFLD-associated HCC (n = 144) from six different centers. Regression models were used to identify a predictive model of HCC. Results: Twenty lipid species and one metabolite, reflecting changes in mitochondrial function and sphingolipid metabolism, were associated with the presence of cancer on a background of MAFLD with high accuracy (AUC 0.789, 95% CI: 0.721–0.858), which was enhanced with the addition of cirrhosis to the model (AUC 0.855, 95% CI: 0.793–0.917). In particular, the presence of these metabolites was associated with cirrhosis in the MAFLD subgroup (p < 0.001). When considering the HCC cohort alone, the metabolic signature was an independent predictor of overall survival (HR 1.42, 95% CI: 1.09–1.83, p < 0.01). Conclusion: These exploratory findings reveal a metabolic signature in serum which is capable of accurately detecting the presence of HCC on a background of MAFLD. This unique serum signature will be taken forward for further investigation of diagnostic performance as biomarker of early stage HCC in patients with MAFLD in the future.

MRI in liver cirrhosis

AbstractLiver magnetic resonance imaging (MRI) has seen a massive increase in its use over the last decades. Since its first description in the early 1980s, contrast‐enhanced MRI is now the gold standard for the diagnosis of hepatocellular cancer in patients with liver cirrhosis. Techniques like magnetic resonance (MR) elastography and combinations of multiple MR parameters in single scanning protocols are now available and these are opening new possibilities for the assessment of multiple aspects of disease in patients with liver cirrhosis. In this narrative review, we provide an overview of the use of MRI in patients with cirrhosis for the diagnosis of and screening for liver cancer, for the diagnosis of cirrhosis and prediction of long‐term outcomes, and for the evaluation of portal hypertension. With the multitude of techniques now available and the number of cirrhosis aspects that can be assessed by single scans make the study and application of MRI an attractive target in the search for a technique for use in this group of patients that often have to attend for multiple appointments and multiple tests, including invasive investigations.

To study the risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease in central India

common cancer and the third leading cause of cancer-related deaths. A known risk factor for HCC is non-alcoholic fatty liver disease (NAFLD), a continuum of hepatic disorders related to obesity and the metabolic syndrome. AIM: We conducted an observational study to identify risk factors for hepatocellular cancer in patients with non-alcoholic fatty liver disease who came to SMHRC Nagpur for a routine visit. MATERIAL AND METHODS: The study included 300 people aged 35 to 85 years old who visited Shalinitai Meghe hospital in Nagpur for a health check-up. We were able to keep the two groups apart here. The control group is made up of alcoholics with fatty liver, while the study group is made up of non-alcoholics with fatty liver. Each community consists of 150 patients. A quantitative diagnostic kit was used to analyse liver function and lipid profile analyses, which were then examined using a photometric process. The enzyme related immunosorbant assay was used to detect glutathione s transferase pi. RESULTS: Non-alcoholic fatty liver had greater LFT than alcoholic fatty liver in the control group, according to the report.

Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease.

In patients with NAFLD, those with type 2 diabetes mellitus (DM) have a high risk of progression to HCC. However, the determinants of HCC risk in these patients remain unclear. We assembled a retrospective cohort of patients with NAFLD and DM diagnosed at 130 facilities in the Veterans Administration between 1/1/2004 and 12/31/2008. We followed patients from the date of NAFLD diagnosis to HCC, death, or 12/31/2018. We used landmark Cox proportional hazards models to determine the effects of anti-DM medications (metformin, insulin, sulfonylureas) and glycemic control (percent of follow-up time with hemoglobin A1c < 7%) on the risk of HCC while adjusting for demographics and other metabolic traits (hypertension, obesity, dyslipidemia). We identified 85,963 patients with NAFLD and DM. In total, 524 patients developed HCC during a mean of 10.3 years of follow-up. Most common treatments were metformin monotherapy (19.7%), metformin-sulfonylureas (19.6%), insulin (9.3%), and sulfonylureas monotherapy (13.6%). Compared with no medication, metformin was associated with 20% lower risk of HCC (HR, 0.80; 95% CI, 0.93-0.98). Insulin had no effect on HCC risk (HR, 1.02; 95% CI, 0.85-1.22; p = 0.85). Insulin in combination with other oral medications was associated with a 1.6 to 1.7-fold higher risk of HCC. Adequate glycemic control was associated with a 31% lower risk of HCC (HR, 0.69; 95% CI, 0.62-0.78). In this large cohort of patients with NAFLD and DM, use of metformin was associated with a reduced risk of HCC, whereas use of combination therapy was associated with increased risk. Glycemic control can serve as a biomarker for HCC risk stratification in patients with NAFLD and diabetes.

Risk of Cirrhosis and Hepatocellular Cancer in Patients With NAFLD and Normal Liver Enzymes.

The long-term risk of disease for patients with nonalcoholic fatty liver disease (NAFLD) in the absence of elevated enzymes is unclear. We conducted a retrospective cohort study using the Corporate Data Warehouse of the Veterans Health Administration. We classified patients into three groups: patients with steatosis/normal alanine aminotransferase (ALT), steatosis/elevated ALT, and no steatosis/normal ALT. We examined incidence rates for cirrhosis and hepatocellular carcinoma (HCC) and conducted cause-specific hazard models to evaluate the risk of cirrhosis and HCC. We identified 3,522 patients with steatosis/normal ALT, 15,419 patients with steatosis/elevated ALT, and 9,267 patients with no steatosis/normal ALT. The mean age in each group was 58.9, 54.7 and 59.3years, respectively; over 90% were men. Compared to patients with hepatic steatosis/normal ALT, those with steatosis/elevated ALT were younger and more likely to be obese (both P<0.01). In patients with steatosis/normal ALT, the incidence rates of cirrhosis and HCC were 1.22 (95% confidence interval [CI]: 0.83-1.74) and 0.20 (95% CI: 0.06-0.46) per 1,000 person-years, respectively; this was lower than in patients with steatosis/elevated ALT (cirrhosis: 3.85; 95% CI: 3.50-4.23, and HCC: 0.37; 95% CI: 0.26-0.49). Patients with steatosis/elevated ALT had a higher risk of developing cirrhosis (adjusted hazard ratio:3.37; 95% CI: 2.34-4.86; P<0.01) than patients with steatosis/normal ALT; they also had a higher risk of HCC, although it did not reach statistical significance (hazard ratio:2.07; 95% CI:0.82-5.28; P=0.13). The risk of cirrhosis and HCC in patients with steatosis/normal ALT and those without steatosis was not significantly different. Patients with hepatic steatosis with persistently normal ALT are at lower risk for cirrhosis compared to those with steatosis and elevated ALT and not different from the risk in a clinical cohort without hepatic steatosis.

Surveillance for Hepatocellular Carcinoma: Current Best Practice and Future Direction.

Hepatocellular cancer (HCC) is the fourth leading cause of cancer-related deaths worldwide and the fastest growing cause of cancer deaths in the United States. The overall prognosis of HCC remains dismal, except for the subset of patients who are diagnosed at early stage and receive potentially curative therapies, such as surgical resection and liver transplantation. Given this, expert society guidelines recommend HCC surveillance every 6 months in at-risk individuals. Despite these recommendations, the effectiveness of HCC surveillance remains a subject of debate. We discuss current best practices for HCC surveillance and the evidence that support these recommendations. We also describe several initiatives that are underway to improve HCC surveillance and outline areas that may serve as high-yield targets for future research. Overall, we believe these efforts will help the field move toward precision surveillance, where surveillance tests and intervals are tailored to individual HCC risk. Doing so can maximize surveillance benefits, minimize surveillance harms, and optimize overall value for all patients.

CME Exam 3: Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease

CME Exam 3: Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease

Covering the Cover

Covering the Cover

Effects of antiviral treatment on the risk of hepatocellular cancer in patients with chronic viral hepatitis.

Hepatocellular carcinoma (HCC) is a major complication of chronic hepatitis B (CHB) and chronic hepatitis C (CHC). Accumulating data suggest that antiviral treatment in both CHB and CHC reduces the incidence of HCC. Evidence is more consistent for interferon-based treatment in both CHB and CHC and for lamivudine in patients with CHB. However, more limited data suggest that other nucleos(t)ide analogues might also reduce the risk of HCC. In contrast, conflicting data have been reported on the effects of direct-acting antivirals on the incidence of HCC.

Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease

There are limited data on the risk of hepatocellular cancer (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to estimate the risk of incident HCC among patients with NAFLD. We conducted a retrospective cohort study from a total of 130 facilities in the Veterans Health Administration. Patients with NAFLD diagnosed between January 1, 2004 and December 31, 2008 were included and followed until HCC diagnosis, death, or December 31, 2015. We also identified a sex- and age-matched control cohort without NAFLD. We ascertained all new HCC cases from the Central Cancer Registry and manual chart reviews. We calculated incidence rates for HCC by NAFLD status, as well as in subgroups of NAFLD patients. We used competing risk models to compare the risk of HCC in patients with NAFLD vs those without NAFLD. We reviewed electronic medical records of all HCC cases that developed in NAFLD patients without cirrhosis. We compared 296,707 NAFLD patients with 296,707 matched controls. During 2,382,289 person-years [PYs] of follow-up, 490 NAFLD patients developed HCC (0.21/1000 PYs). HCC incidence was significantly higher among NAFLD patients vs controls (0.02/1000 PYs; hazard ratio, 7.62; 95% confidence interval, 5.76-10.09). Among patients with NAFLD, those with cirrhosis had the highest annual incidence of HCC (10.6/1000 PYs). Among patients with NAFLD cirrhosis, HCC risk ranged from 1.6 to 23.7 per 1000 PYs based on other demographic characteristics; risk of HCC was thehighest in older Hispanics with cirrhosis. In medical record reviews, 20% of NAFLD patients with HCC had no evidence of cirrhosis. Risk of HCC was higher in NAFLD patients than that observed in general clinical population. Most HCC cases in NAFLD developed in patients with cirrhosis. The absolute risk of HCC was higher than the accepted thresholds for HCC surveillance for most patients with NAFLD cirrhosis.

Predictors of intermediate-term survival with destination locoregional therapy of hepatocellular cancer in patients either ineligible or unwilling for liver transplantation.

Intra-arterial or percutaneous locoregional therapies (LRT) are often employed to maintain potential liver transplant (LT) recipients with hepatocellular carcinoma (HCC) within T2/Milan criteria. Predictors of survival when LRT is used as destination therapy in those who are either ineligible or unwilling for LT remain poorly defined. We evaluated predictors of 3-year survival with destination LRT in a population of cirrhotic patients diagnosed with HCC, presenting within T2 criteria, and either ineligible or unwilling for LT. The cohort surviving 3 years had a significantly lower model for end-stage liver disease (MELD) score at HCC diagnosis (9.7 vs. 11.4, P=0.037) and MELD following initial locoregional therapy (10.7 vs. 13.3, P=0.008) compared to those not surviving three years despite similar demographic, tumor, and treatment variables. LRT as destination therapy results in modest intermediate term survival, with liver function at presentation and immediately following initiation of LRT predicting intermediate survival with this approach.

Mo1511 Predictors of Survival With “Destination” Loco Regional Therapy of Hepatocellular Cancer in Patients Either Ineligible or Unwilling for Liver Transplantation: Score Yet Another One for MELD

Mo1511 Predictors of Survival With “Destination” Loco Regional Therapy of Hepatocellular Cancer in Patients Either Ineligible or Unwilling for Liver Transplantation: Score Yet Another One for MELD

Human vascular adhesion proteın-1 (VAP-1): Serum levels for hepatocellular carcinoma in non-alcoholic and alcoholic fatty liver disease

BackgroundThe incidence of hepatocellular cancer in complicated alcoholic and non-alcoholic fatty liver diseases is on the rise in western countries as well in our country. Vascular adhesion protein-1 (VAP-1) levels have been presented as new marker. In our study protocol, we assessed the value of this serum protein, as a newly postulant biomarker for hepatocellular cancer in patients with a history of alcoholic and non-alcoholic fatty liver diseases.MethodsPre-operative serum samples from 55 patients with hepatocellular cancer with a history of alcoholic and non-alcoholic fatty liver diseases and patients with cirrhosis were assessed by a quantitative sandwich ELISA using anti-VAP-1 mAbs. This technique is used to determine the levels of soluble VAP-1 (sVAP-1) in the serum.ResultssVAP-1 levels were evaluated in patients with hepatocellular cancer and liver cirrhosis. There was a significant difference in mean VAP-1 levels between groups. Serum VAP-1 levels were found higher in patients with hepatocellular cancer.ConclusionThese findings indicate that the serum level of sVAP-1 might be a beneficial marker of disease activity in chronic liver diseases.

Radiosurgery in the Treatment of Unresectable Hepatocellular Cancer and as a Bridge to Transplantation

Radiosurgery in the Treatment of Unresectable Hepatocellular Cancer and as a Bridge to Transplantation

Review: Interferon and nucleoside/tide analogues reduce risk for hepatocellular cancer in patients with chronic hepatitis B

ACP Journal Club21 April 2009Review: Interferon and nucleoside/tide analogues reduce risk for hepatocellular cancer in patients with chronic hepatitis BAverell H. Sherker, MD, FRCP(C)Averell H. Sherker, MD, FRCP(C)Washington Hospital Center and Georgetown University, Washington, DC, USA (A.H.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-8-200904210-02011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008;28:1067-77. https://pubmed.ncbi.nlm.nih.gov/18657133Clinical Impact RatingsGastroenterology: Infectious Disease: References1 Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315-41. [PMID: 18845489] Google Scholar2 Bruix J, Sherman M, Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208-36. [PMID: 16250051] Google Scholar Author, Article, and Disclosure InformationAuthors: Averell H. Sherker, MD, FRCP(C)Affiliations: Washington Hospital Center and Georgetown University, Washington, DC, USA (A.H.S.)This article was published at Annals.org on 7 April 2009. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 April 2009Volume 150, Issue 8Page: JC4-11KeywordsCancer preventionCancer treatmentChronic hepatitis BCirrhosisCohort studiesInfectious diseasesInfectious hepatitisInterferonsLiver transplantationTreatment guidelines ePublished: 21 April 2009 Issue Published: 21 April 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Standard Ultrasound Examination of the Liver Does Not Correlate with APRI Score or Histological Level of Fibrosis in a Population with Hepatitis C

Purpose: In the management of patients (pts) with liver disease, ultrasound (US) examinations of the liver are commonly ordered to estimate hepatic fibrosis as well as to monitor the development of hepatocellular cancer in patients with chronic hepatitis C (HCV). Our aim was to test the utility of US to detect fibrosis in a group of patients with chronic hepatitis C who have undergone determination of the aspartate aminotransferase/platelet ratio index (APRI) score and liver biopsy Methods: Out of the pool of pts examined at our institution within the last year, 195 have had an ultrasound examination within 6 months of a pretreatment staging liver biopsy. 9 patients with HIV co-infection, 1 patient with autoimmune hepatitis and 12 patients with Hepatitis B were excluded, because the APRI and histological fibrosis scores have not been validated in these groups. 54 pts had incomplete data. Thus, 119 patients were studied: APRI <0.4 = 17, 0.4–1.5 = 75, >1.5 = 27. The following ultrasound criteria were utilized: Liver size: small, normal, or enlarged; nodularity: + or -; echogenicity: normal, increased or coarse; spleen size: normal or >12 cm = enlarged; Liver biopsy fibrosis was scored 0–4 on the Batts-Ludwig scale. Data was analyzed using SAS 9.1® statistical software. Results: The correlation coefficient between fibrosis stage and APRI across all values was 0.505 (P < .0001). Limiting the APRI to the indeterminant range (0.4–1.5), the score was 0.460 (P < .0001). The correlation coefficient between fibrosis stage and ultrasound score was 0.167 (P= 0.069, ns) for all stages of fibrosis and 0.372 (P= 0.0278) when limited to stage 3 and 4 fibrosis on biopsy. Limiting to APRI between 0.4–1.5, the correlation between ultrasound score and fibrosis was 0.099 (P= 0.398). Conclusion: Confirming previous studies, The APRI score significantly correlates with fibrosis stage when all samples are compared or when the comparison is limited to APRI values in the indeterminant range (0.4–1.5). In contrast the ultrasound score correlates with fibrosis score only in patients with advanced fibrosis. The addition of ultrasound score to APRI does not improve correlation with fibrosis score. Examination of traditional criteria for evaluation of liver ultrasound studies does not add significantly to the detection of hepatic fibrosis over and above APRI, in patients with well compensated chronic hepatitis C.

Interferon therapy for prevention of hepatocellular cancer in patients with HCV related cirrhosis: A meta-analysis

Interferon therapy for prevention of hepatocellular cancer in patients with HCV related cirrhosis: A meta-analysis