Vincent L. Chen

Poor adherence and low persistency rates for hepatocellular carcinoma surveillance in patients with chronic hepatitis B.

AbstractOur goal was to examine rates and predictors for hepatocellular carcinoma (HCC) surveillance adherence and persistency, since studies of such adherence and persistency in patients with chronic hepatitis (CHB) are currently limited.Consecutive CHB patients (N = 1329) monitored for ≥1 year at 4 US clinics from January 1996 to July 2013 were retrospectively studied. Surveillance adherence was evaluated based on the American Association for the Study of Liver Diseases guidelines. Kaplan–Meier method was used to analyze surveillance persistency of 510 patients who had initially fair adherence (having at least annual surveillance imaging with further follow-up).Mean age was 48, with the majority being male (58%), Asian (92%), foreign-born (95%), and medically insured (97%). Patients with cirrhosis and those seen at university liver clinics were more likely to have optimal HCC surveillance than those without cirrhosis and those seen at community clinics (38.4% vs 21.6%, P <0.001 and 33.5% vs 14.4%, P < 0.001, respectively). HCC diagnosed in optimally adherent patients trended toward smaller tumor size (P < 0.08). On multivariate analysis also inclusive of age, sex, clinical visits, cirrhosis, clinic setting and antiviral therapy use, strong independent predictors for having at least annual imaging were a history of more frequent clinical visits (odds ratio [OR] = 2.5, P < 0.001) and university-based care (OR = 5.2, P < 0.001). Even for those with initially fair adherence, persistency dropped to 70% at 5 years.Adherence and persistency to HCC surveillance in CHB patients is generally poor. More frequent clinic visits and university-based settings were significant and strong predictors of at least annual HCC surveillance adherence.

Poor adherence to hepatocellular carcinoma surveillance: a systematic review and meta-analysis of a complex issue

Hepatocellular carcinoma (HCC) surveillance is associated with improved outcomes and long‐term survival. Our goal is to evaluate adherence rates to HCC surveillance.

More advanced disease and worse survival in cryptogenic compared to viral hepatocellular carcinoma.

Although hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major risk factors for hepatocellular carcinoma (HCC), non‐viral causes of HCC, particularly non‐alcoholic fatty liver disease (NAFLD), are becoming increasingly prevalent. The aim of this study was to compare the clinical characteristics and survival of cryptogenic and viral HCC.

Soluble intercellular adhesion molecule-1 is associated with hepatocellular carcinoma risk: multiplex analysis of serum markers

Individualized assessment of hepatocellular carcinoma (HCC) risk in chronic liver disease remains challenging. Serum biomarkers including cytokines may offer helpful adjuncts to standard parameters for risk prediction. Our aim was to identify markers associated with increased HCC incidence. This was a prospective cohort study of 282 patients with both viral or non-viral chronic liver disease. Baseline serum cytokines and other markers were measured in multiplex with a commercially-available Luminex-based system. Patients were followed until death or HCC diagnosis. We performed Lasso-based survival analysis to determine parameters associated with HCC development. Cytokine mean florescence intensity (MFI) was the primary predictor and HCC development the primary outcome. 25 patients developed HCC with total follow-up of 1,363 person-years. Parameters associated with increased HCC incidence were cirrhosis, hepatic decompensation, and soluble serum intercellular adhesion molecule 1 (sICAM-1) MFI. No other molecules increased predictive power for HCC incidence. On univariate analysis, the parameters associated with HCC incidence in patients with cirrhosis were age, antiviral treatment, and high sICAM-1 MFI; on multivariate analysis, sICAM-1 remained associated with HCC development (adjusted HR = 2.75). On unbiased screening of serum cytokines and other markers in a diverse cohort, baseline sICAM-1 MFI is associated with HCC incidence.

Increased Prevalence of Metabolic Risk Factors in Asian Americans With Hepatocellular Carcinoma.

Background: We used metabolic risk factors to estimate the prevalence and clinical significance of nonalcoholic fatty liver disease in Asian Americans with hepatocellular carcinoma (HCC). Methods: This is a retrospective cohort study of 824 consecutive Asian HCC patients at Stanford University Medical Center from 1998 to 2015. Patients were subdivided as: Chinese, other East Asian (Japanese and Korean), South East Asian (Vietnamese, Thai, and Laotian), Maritime South East Asian (MSEA: Malaysian, Indonesian, Filipino, and Singaporean), and South West Asian (Indian, Pakistani, and Middle Eastern). Metabolic risk factors studied were body mass index, hypertension, type II diabetes, and hyperlipidemia. Results: Most patients were male (76%) with mean age 63 years. Metabolic risk factors were highly prevalent on presentation and increased over time (P<0.001), as did the prevalence of cryptogenic HCC (P<0.004). Compared with other Asian subgroups, MSEAs had the highest body mass index (26.3) and higher rates of type II diabetes (44% vs. 23% to 35%, P=0.004), hypertension (59% vs. 38% to 55%, P=0.04), and cryptogenic HCC (15% vs. 4% to 10%, P=0.01). They were more likely to be symptomatic on presentation (44% vs. 32% to 58%, P=0.07), less likely to present within Milan criteria (34% vs. 35% to 63%, P<0.0001), and trended toward decreased 10-year survival rates compared with other ethnic subgroups (9% vs. 25% to 32%, P=0.07). Conclusions: Metabolic risk factors were increasingly prevalent among Asian Americans with HCC. MSEAs, who had the highest incidence of these risk factors, had more advanced tumor stage and trended toward worse survival.

Differential Serum Cytokine Profiles in Patients with Chronic Hepatitis B, C, and Hepatocellular Carcinoma

Cytokines play an important role in the pathogenesis of cirrhosis and hepatocellular carcinoma (HCC), most cases of which are related to either hepatitis B virus (HBV) or hepatitis C virus (HCV). Prior studies have examined differences in individual cytokine levels in patients with chronic liver disease, but comprehensive cytokine profiling data across different clinical characteristics are lacking. We examined serum cytokine profiles of 411 patients with HCC (n = 102: 32% HBV, 54% HCV, 14% non-viral) and without HCC (n = 309: 39% HBV, 39% HCV, 22% non-viral). Multiplex analysis (Luminex 200 IS) was used to measure serum levels of 51 common cytokines. Random forest machine learning was used to obtain receiver operator characteristic curves and to determine individual cytokine importance using Z scores of mean fluorescence intensity for individual cytokines. Among HCC and non-HCC patients, cytokine profiles differed between HBV and HCV patients (area under curve (AUC) 0.82 for HCC, 0.90 for non-HCC). Cytokine profiles did not distinguish cirrhotic HBV patients with and without HCC (AUC 0.503) or HCV patients with and without HCC (AUC 0.63). In conclusion, patients with HBV or HCV infection, with or without HCC, have distinctly different cytokine profiles, suggesting potential differences in disease pathogenesis and/or disease characteristics.

Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience

Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti‐viral therapy affects survival after HCC diagnosis.