Incidence Rate Of Hepatocellular Carcinoma Research Articles

Comparison of Cholangiocarcinoma and Hepatocellular Carcinoma Incidence Trends from 1993 to 2012 in Lampang, Thailand.

Liver cancer is the most common cancer in Northern Thailand, mainly due to the dietary preference for raw fish, which can lead to infection by the parasite, O. viverrini, a causal agent of cholangiocarcinoma. We conducted a temporal trend analysis of cross-sectional incidence rates of liver cancer in Lampang, Northern Thailand. Liver cancer data from 1993–2012 were extracted from Lampang Cancer Registry. The multiple imputation by chained equations method was used to impute missing histology data. Imputed data were analyzed using Joinpoint and age-period-cohort (APC) models to characterize the incidence rates by gender, region, and histology, considering hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). We observed a significant annual increase in CCA incidence and a considerable decrease in HCC incidence for both genders in Lampang. The APC analysis suggested that CCA incidence rates were higher in older ages, younger cohorts, and later years of diagnosis. In contrast, HCC incidence rates were higher in older generations and earlier years of diagnosis. Further studies of potential risk factors of CCA are needed to better understand and address the increasing burden of CCA in Lampang. Our findings may help to draw public attention to cholangiocarcinoma prevention and control in Northern Thailand.

Risk of hepatocellular carcinoma after sustained virologic response in hepatitis C virus patients without advanced liver fibrosis.

Hepatocellular carcinoma (HCC) after sustained virologic response (SVR) has been observed even in hepatitis C virus (HCV) patients without advanced liver fibrosis. Identifying predictors for HCC incidence in patients without advanced liver fibrosis will enable efficient post-SVR HCC surveillance. This study aimed to develop a scoring system to predict the incidence of HCC after SVR in HCV patients without advanced liver fibrosis. A total of 1682 HCV patients without advanced liver fibrosis (defined as Fibrosis-4 index <3.25) with no history of HCC who initiated direct-acting antiviral treatment between September 2014 and October 2020 at 26 institutions, and achieved SVR24, were included. We divided 1682 patients into training (1122) and validation (560) cohorts. In the multivariate analysis, baseline age ≥65years (p=0.030), alanine aminotransferase (ALT) levels at SVR24≥30 U/l (p=0.001), and α-fetoprotein (AFP) levels at SVR24≥5.0ng/ml (p=0.001) were independent predictors for HCC incidence in the training cohort. We developed a scoring system to predict HCC incidence after SVR24 using these three factors (1 point was added for each factor). The cumulative HCC incidence rates at 5years were 7.1% in patients who scored 2 or 3, and no patients developed HCC in those who scored 0 in the validation cohort. Our scoring system using the three factors of baseline age, ALT levels at SVR, and AFP levels at SVR is useful for post-SVR HCC surveillance of patients without advanced liver fibrosis.

Evaluation of the aMAP score for hepatocellular carcinoma surveillance: a realistic opportunity to risk stratify

Background and aimsThe aMAP score is a model that predicts risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis. Its performance in a ‘real world’ surveillance setting has not yet been ascertained.Patients and methodsWe had access to a cohort of 3473 individuals enrolled in a rigorously implemented and prospectively accrued surveillance programme (patients undergoing regular ultrasound and biomarker examination between 1998 and 2021). During this period 445 had HCC detected. Of these, 77.8% had early stage disease (within Milan criteria), permitting potentially curative therapy to be implemented in nearly 70% of cases. We applied the recently developed aMAP score to classify patients according to their initial aMAP score in to low, medium and high-risk groups as proposed in the original publication. The performance of the aMAP score was assessed according to the concordance-index and calibration (i.e. agreement between observed and predicted risk). Allowance was made for competing causes of death.ResultsThe aMAP score achieved an overall C-index of 0.81 (95% CI: 0.79–0.82) consistent with the initial report and was unaffected by allowance for competing causes of death. Sub-group analysis showed that the results did not change significantly according to gender, or aetiology. However, aMAP discrimination was greater for younger individuals (versus older individuals), and also for individuals without cirrhosis. The HCC incidence rate was 0.98, 7.05 and 29.1 events per 1000 person-years in the low-, moderate- and high-risk aMAP groups, respectively.ConclusionsThe results from this ‘real-world’ cohort demonstrate that risk stratification is a realistic prospect and that identification of a subgroup of chronic liver disease patients who have a very low risk of HCC is feasible.

Direct-acting antivirals for hepatitis C virus-infected patients with hepatocellular carcinoma.

BACKGROUNDHepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients has a high risk of recurrence. Although eradication of HCV is expected to reduce this risk, the risk in patients with a history of HCC may be high after treatment with direct-acting antivirals (DAAs).AIMTo determine the risk factors for HCC recurrence in patients with HCV and a history of HCC.METHODSThe risk of HCC recurrence in patients with a history of HCC and/or of HCC occurrence in patients without a history of HCC after DAA therapy was retrospectively analyzed in 311 HCV patients treated at our institution and several neighboring hospitals. The frequency and predictors of HCC recurrence/ occurrence after DAA treatment were included in these analyses. The clinical course of HCC before and after DAA treatment was also evaluated.RESULTSHCV patients with a history of HCC were older and had greater progression of liver fibrosis and diabetes than patients without a history of HCC. Median recurrence-free survival (RFS) was 1092 d in patients with a history of HCC, and post-DAA HCC recurrence/occurrence was observed in 29 patients (53.7%) with and 5 (1.9%) without a history of HCC over 6 years (P < 0.001). RFS in patients with a history of HCC did not differ significantly before and after DAA treatment. The frequency of HCC recurrence/occurrence in patients with a history of HCC was lower after than before DAA treatment. Multivariate analysis showed that the incidence rate of HCC recurrence/occurrence before DAA treatment was the only independent predictor of HCC recurrence/occurrence after DAA treatment. Liver function was well preserved and clinical course was good in patients with HCC recurrence/occurrence after DAA therapy.CONCLUSIONDAA therapy in patients infected with HCV is also effective in patients with a history of HCC. Curative treatment for HCC is desirable before DAA therapy. The frequency of HCC recurrence/occurrence before DAA therapy was associated with a significantly increased risk of HCC recurrence after DAA therapy. Careful observation after DAA therapy is required in patients with a history of HCC.

EPH4 Incidence and Survival of Patients with Hepatocellular Carcinoma in the United States from 2008 to 2018

Hepatocellular Carcinoma (HCC) is the most prevalent primary liver cancer in adults, and it is one of the fastest-rising causes of cancer-related deaths in the US. This study examined the incidence and survival rates for HCC in recent years.

Association of statin treatment with hepatocellular carcinoma risk in end-stage kidney disease patients with chronic viral hepatitis

Statin use in end-stage kidney disease (ESKD) patients are not encouraged due to low cardioprotective effects. Although the risk of hepatocellular carcinoma (HCC), a frequently occurring cancer in East Asia, is elevated in ESKD patients, the relationship between statins and HCC is not known despite its possible chemopreventive effect. The relationship between statin use and HCC development in ESKD patients with chronic hepatitis was evaluated. In total, 6165 dialysis patients with chronic hepatitis B or C were selected from a national health insurance database. Patients prescribed with ≥ 28 cumulative defined daily doses of statins during the first 3 months after dialysis commencement were defined as statin users, while those not prescribed with statins were considered as non-users. Primary outcome was the first diagnosis of HCC. Sub-distribution hazard model with inverse probability of treatment weighting was used to estimate HCC risk considering death as competing risk. During a median follow-up of 2.8 years, HCC occurred in 114 (3.2%) statin non-users and 33 (1.2%) statin users. The HCC risk was 41% lower in statin users than in non-users (sub-distribution hazard ratio, 0.59; 95% confidence interval [CI], 0.42–0.81). The weighted incidence rate of HCC was lower in statin users than in statin non-users (incidence rate difference, − 3.7; 95% CI − 5.7 to − 1.7; P < 0.001). Incidence rate ratio (IRR) was also consistent with other analyses (IRR, 0.56; 95% CI, 0.41 to 0.78; P < 0.001). Statin use was associated with a lower risk of incident HCC in dialysis patients with chronic hepatitis B or C infection.

Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease.

Prediction of hepatocellular carcinoma (HCC) risk is an urgent unmet need in patients with nonalcoholic fatty liver disease (NAFLD). In cohorts of 409 patients with NAFLD from multiple global regions, we defined and validated hepatic transcriptome and serum secretome signatures predictive of long-term HCC risk in patients with NAFLD. A 133-gene signature, prognostic liver signature (PLS)-NAFLD, predicted incident HCC over up to 15 years of longitudinal observation. High-risk PLS-NAFLD was associated with IDO1+ dendritic cells and dysfunctional CD8+ T cells in fibrotic portal tracts along with impaired metabolic regulators. PLS-NAFLD was validated in independent cohorts of patients with NAFLD who were HCC naïve (HCC incidence rates at 15 years were 22.7 and 0% in high- and low-risk patients, respectively) or HCC experienced (de novo HCC recurrence rates at 5 years were 71.8 and 42.9% in high- and low-risk patients, respectively). PLS-NAFLD was bioinformatically translated into a four-protein secretome signature, PLSec-NAFLD, which was validated in an independent cohort of HCC-naïve patients with NAFLD and cirrhosis (HCC incidence rates at 15 years were 37.6 and 0% in high- and low-risk patients, respectively). Combination of PLSec-NAFLD with our previously defined etiology-agnostic PLSec-AFP yielded improved HCC risk stratification. PLS-NAFLD was modified by bariatric surgery, lipophilic statin, and IDO1 inhibitor, suggesting that the signature can be used for drug discovery and as a surrogate end point in HCC chemoprevention clinical trials. Collectively, PLS/PLSec-NAFLD may enable NAFLD-specific HCC risk prediction and facilitate clinical translation of NAFLD-directed HCC chemoprevention.

Abstract 2258: Predictors of hepatocellular carcinoma development in nonalcoholic fatty liver disease

Abstract Background: The incidence of nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is predicted to increase with increasing worldwide prevalence. We aimed to identify predictors of HCC risk in patients with NAFLD, an unmet clinical need. Methods: We identified all patients diagnosed with NAFLD in the electronic health records (EHR) of a large US-based health system from 2004 to 2018. Information on demographics, body mass index (BMI), smoking status, serum biochemistries, comorbidities, albumin-bilirubin (ALBI) score, AST/√ALT ratio, fibrosis-4 index (FIB-4), and cirrhosis status were extracted from the EHR. Over an average 5.5 year at risk from date of first recorded NAFLD to the last contact with the healthcare system, date of HCC diagnosis or death, whichever occurred first, we identified 371 patients diagnosed with HCC. Cox proportional regression method with a stepwise approach was employed to identify independent predictors of HCC incidence. A Poisson regression method was used to estimate the incidence rate of HCC in NAFLD patients with a specified set of identified risk factors in the stepwise Cox regression analysis. Results. Among the 39,424 NAFLD patients, 57.8% were women, 44.5% were ever smokers, 27.3% had diabetes, 39.9% had dyslipidemia, 4.7% had Fibrosis-4 index (FIB-4)&amp;gt;2.67 (advanced fibrosis), and 3.7% had cirrhosis. The mean (standard deviation) age and BMI at first recorded diagnosis of NAFLD were 57.0 (11.4) years and 33.7 (7.4) kg/m2, respectively. The corresponding figures in 371 incident HCC cases were 65.1 (10.6) years of age, 31.9 (6.9) kg/m2 of BMI, 47.7% women, 52.8% ever smokers, 38.3% diabetes, 39.6% dyslipidemia, 17.8% FIB-4 &amp;gt;2.67, and 11.6% cirrhosis. All of these were independent factors for HCC risk. The estimated incidence rate of HCC for a male patient with NAFLD who was 65 years old, ever smoked, had BMI 30 kg/m3 and a history of diabetes and dyslipidemia, but had neither advanced fibrosis nor cirrhosis, was 3.02 (95% confidence interval [CI], 2.37-3.84) per 1000 person-years. The corresponding figures were 8.20 (95% CI, 5.78-11.62) for a male with advanced fibrosis but no cirrhosis and the same other characteristics as described above, and 18.05 (95% CI, 12.19-26.72) for the same patient with cirrhosis. On the other hand, the incidence of HCC for a male cirrhotic patient without a history of smoking or diabetes was 9.53 per 1000 person-years, a 47% reduction in risk. Conclusion. In this large cohort of NAFLD patients, we identified age, sex, BMI, smoking, diabetes, dyslipidemia, advanced fibrosis and cirrhosis as independent risk predictors for HCC. Although the effect of smoking and diabetes was relatively small in low-risk patients, their impact on high-risk NAFLD, especially those with advanced fibrosis or cirrhosis is discernable. Smoking cessation and treatment of diabetes may be potential strategies for reducing HCC risk in high-risk NAFLD patients. Citation Format: Jian-Min Yuan, Renwei Wang, Hung N. Luu, Jaideep Behari. Predictors of hepatocellular carcinoma development in nonalcoholic fatty liver disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2258.

Characteristics of hepatocellular carcinoma in patients with hepatitis C virus who received direct-acting antiviral therapy and achieved sustained virological response: The impact of a hepatologist on surveillance.

Background and AimThe relationship between the characteristics of hepatocellular carcinoma (HCC) diagnosed after sustained virological response (SVR) with direct‐acting antiviral (DAA) therapy and surveillance status has not been sufficiently investigated. This study investigated the clinical risk factors for HCC development and HCC characteristics according to which type of physician performed follow‐up after SVR.MethodsA total of 1070 patients in whom hepatitis C virus (HCV) was eradicated with DAA therapy were evaluated.ResultsThere were 458 patients followed by hepatologists (specialist group) and 612 followed by non‐hepatologists (non‐specialist group) after SVR. During the follow‐up period, 54 patients developed HCC. The 1‐, 2‐, 3‐, 4‐, and 5‐year cumulative incidence rates of HCC were 1.8, 4.1, 6.9, 10.5, and 17.2%, respectively. Multivariate Cox proportional hazards analysis showed that male sex (hazard ratio [HR], 3.139; 95% confidence interval [CI], 1.732–5.690), α‐fetoprotein level (HR, 1.056; 95% CI, 1.035–1.077), and fibrosis‐4 (FIB‐4) index (HR, 1.051; 95% CI, 1.017–1.085) were significantly associated with HCC development, while the follow‐up physician type after SVR was not. There were 25 patients with stage I HCC, 17 with stage II, 9 with stage III, and 3 with stage IV. Multivariate ordinal logistic regression showed that follow‐up physician type (non‐specialist) (HR, 39.100; 95% CI, 9.350–224.00) was independently associated with HCC stage, while α‐fetoprotein level and FIB‐4 index were not.ConclusionWhen patients have more risk factors for HCC development after SVR (i.e., male sex, elevated α‐fetoprotein, or elevated FIB‐4 index), they should be followed by a hepatologist for HCC surveillance.

Prevalence of underlying cirrhosis etiologies in hepatocellular carcinoma patients of Hispanic versus non-Hispanic ethnicity.

e16163 Background: While the incidence and rates of mortality are in decline for the vast majority of cancers, those of hepatocellular carcinoma (HCC) continue to increase. Forecasts from the Surveillance, Epidemiology, and End Results (SEER) database suggest that the Hispanic population will have the highest incidence rate of HCC in the United States by the end of this decade. As a result, further studies are needed to identify specific risk factors for the development of HCC in this ethnic group. Methods: This was a retrospective, single center study conducted in Southern California to identify the prevalence of underlying cirrhosis etiologies in HCC patients of Hispanic versus non-Hispanic ethnicity. Causes of cirrhosis included nonalcoholic fatty liver disease (NAFLD), viral hepatitis, alcohol, and other chronic liver disease. The designation of NAFLD cirrhosis was assigned to patients in whom there was an exclusion of viral hepatitis B, viral hepatitis C, significant alcohol consumption, other etiology of chronic liver disease, and who had the presence of fatty liver on imaging or were diagnosed with cirrhosis with a concomitant metabolic risk factor (diabetes mellitus, hypertension, hyperlipidemia, or obesity). Results: A total of 165 patients were included in this study. There were 57 patients of Hispanic ethnicity and 108 patients of non-Hispanic ethnicity. No significant differences in age or gender were found between the two groups. When analyzing the prevalence of cirrhosis etiologies, 17 patients (29.8%) of Hispanic background were found to have underlying NAFLD cirrhosis compared to 10 patients (9.3%) of non-Hispanic background (p = 0.001). In contrast, 67 patients (62%) in the non-Hispanic group had diagnoses of cirrhosis associated with viral hepatitis B or C compared to 22 patients (38.6%) in the Hispanic group (p = 0.005). There was no significant difference in the prevalence of alcoholic cirrhosis (24.6% vs 13%, p = 0.08), cirrhosis due to other chronic liver disease (1.8% vs 2.8%, p = 1), or HCC without cirrhosis (5.3% vs 13%, p = 0.178) between Hispanic and non-Hispanic patients, respectively (Table). Conclusions: There were significantly higher rates of NAFLD cirrhosis identified in HCC patients of Hispanic ethnicity compared to those of non-Hispanic ethnicity. With the continually rising incidence rate of HCC in this patient group, it is important for providers to be aware of this association so that appropriate surveillance and prevention strategies may be pursued.[Table: see text]

Low-dose cisplatin exposure and SNAIL, Vimentin, E-cadherin expression in HEPG2 cell line

Cisplatin, the first platinum compound approved for cancer treatment, is widely used in the treatment of various cancers including hepatocellular carcinoma (HCC). HCC incidence rates rise globally. Epithelial mesenchymal transition (EMT) is implicated in cancer invasion and metastasis, which are associated with increased mortality. Cisplatin dose might influence cancer invasion and metastatic behavior of the cells. The aim of the study was to investigate the effect of low-dose cisplatin treatment on EMT- related changes in HepG2 cells. Following treatment with 4 µM cisplatin, HepG2 cells were evaluated morphologically. Gene expression of E-cadherin, Vimentin, Snail1 was assessed by quantitative PCR. Immunofluorescence analyses of NA-K ATPase were performed. Although the low-dose cisplatin treated cells exhibited a more stretched morphology, no statistical difference was detected in gene expression of E-cadherin, Vimentin, Snail1 and immunofluorescence of NA-K ATPase. Findings on low-dose cisplatin effects in HepG2 might contribute to the knowledge of antineoplastic inefficacy by further understanding the molecular mechanisms of drug action.

Increasing on-treatment hepatocellular carcinoma risk with decreasing baseline viral load in HBeAg-positive chronic hepatitis B.

BACKGROUNDIt is unclear whether the level of serum hepatitis B virus (HBV) DNA at baseline affects the on-treatment risk of hepatocellular carcinoma (HCC) in hepatitis B e antigen–positive (HBeAg-positive), noncirrhotic patients with chronic hepatitis B (CHB).METHODSWe conducted a multicenter cohort study including 2073 entecavir- or tenofovir-treated, HBeAg-positive, noncirrhotic adult CHB patients with baseline HBV DNA levels of 5.00 log10 IU/mL or higher at 3 centers in South Korea between January 2007 and December 2016. We evaluated the on-treatment incidence rate of HCC according to baseline HBV DNA levels.RESULTSDuring a median 5.7 years of continuous antiviral treatment, 47 patients developed HCC (0.39 per 100 person-years). By Kaplan-Meier analysis, the risk of HCC was lowest in patients with baseline HBV DNA levels of 8.00 log10 IU/mL or higher, increased incrementally with decreasing viral load, and was highest in those with HBV DNA levels of 5.00–5.99 log10 IU/mL (P < 0.001). By multivariable analysis, the baseline HBV DNA level was an independent factor that was inversely associated with HCC risk. Compared with HBV DNA levels of 8.00 log10 IU/mL or higher, the adjusted HRs for HCC risk with HBV DNA levels of 7.00–7.99 log10 IU/mL, 6.00–6.99 log10 IU/mL, or 5.00–5.99 log10 IU/mL were 2.48 (P = 0.03), 3.69 (P = 0.002), and 6.10 (P < 0.001), respectively.CONCLUSIONOn-treatment HCC risk increased incrementally with decreasing baseline HBV DNA levels in the range of 5.00 log10 IU/mL or higher in HBeAg-positive, noncirrhotic adult patients with CHB. Early initiation of antiviral treatment when the viral load is high (≥8.00 log10 IU/mL) may maintain the lowest risk of HCC for those patients.FUNDINGPatient-Centered Clinical Research Coordinating Center (PACEN) (grant no. HC20C0062) of the National Evidence-based Healthcare Collaborating Agency; National R&D Program for Cancer Control through the National Cancer Center (grant no. HA21C0110), Ministry of Health and Welfare, South Korea.

Automated fibrosis phenotyping of liver tissue from non-tumor lesions of patients with and without hepatocellular carcinoma after liver transplantation for non-alcoholic fatty liver disease.

Fibrosis is the most important pathological feature in predicting development of Hepatocellular carcinoma (HCC). However, the incidence rate of HCC in patients with non-alcoholic fatty liver disease (NAFLD) is relatively low. We evaluated phenotypic histological features to differentiate HCC from non-HCC in patients with non-tumor lesions of cirrhotic livers. Seventeen patients with NAFLD who underwent liver transplantation were enrolled. FibroNest was used to quantify histological phenotypes of non-tumor fibrosis lesions. Quantification included collagen content and structure traits, fiber morphometric traits, and fibrosis architecture traits. Each trait was described by up to seven quantitative fibrosis traits (qFTs). Among the qFTs measured in each specimen, those that described most of the variability between consecutive groups were automatically detected and combined into a normalized Phenotypic Composite Fibrosis Score (Ph-CFS). We trained FibroNest to identify the principal traits that differentiate HCC from non-HCC. HCC was found in 8 cases and non-HCC in 9 cases. The Ph-CFS significantly differentiated HCC from non-HCC (4.6 vs. 5.9, p < 0.05). Individual qFTs for morphometric features including collagen fiber length, width, perimeter, and area denoted significant differences between HCC and non-HCC. The Ph-CFS could be used to distinguish HCC (Ph-FCS < 5.0) from non-HCC (Ph-FCS ≥ 5.0) with 75% sensitivity and 100% specificity. In patients who underwent liver transplantation, fibrotic histological phenotypes in non-tumor lesions appeared to be different between HCC and non-HCC. Phenotypic analysis of collagen in non-tumor lesions might be an effective and automated method to distinguish HCC from non-HCC on histopathology imaging.

Prognostic Value of Computed Tomography Texture Features in Patients with Hepatocellular Carcinoma Following Stereotactic Ablative Radiotherapy

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide. Cases of HCC in Africa and East Asia account for 80% of all HCC cases around the world. China is one of the countries with a high incidence rate of HCC. Objectives: This case-control study aimed to explore the prognostic value of computed tomography (CT) texture features in patients with HCC following stereotactic ablative radiotherapy (SABR). Patients and Methods: A total of 100 HCC patients, treated with SABR from January 2019 to January 2021, were divided into good prognosis (n = 57) and poor prognosis (n = 43) groups. The patients’ general data and CT texture features were then compared. Factors associated with a poor prognosis were investigated in a multivariate logistic regression analysis. A clinical feature model, a CT texture feature model, and a joint model of clinical features and CT texture features were established, and their prognostic values were evaluated by plotting the receiver operating characteristic (ROC) curves. Moreover, a nomogram prediction model was developed according to the multivariate analysis results, and its prediction efficiency was assessed. Results: Age ≤ 40 years, serum alpha-fetoprotein level &gt; 9 ng/mL, gamma-glutamyl transpeptidase &gt; 60 U/L, aspartate aminotransferase &gt; 40 U/L, lesion size &gt; 5 cm, unsmooth tumor margins, no tumor capsule or incomplete capsule, multiple tumors, portal phase CT value of cancer &gt; 135%, and a relative washout ratio &gt; -24% in the portal phase of cancer were risk factors for a poor prognosis in HCC patients after SABR. The area under the ROC curve and sensitivity and specificity of the joint model were 0.817 (95% confidence interval [CI]: 0.773 - 0.861, P &lt; 0.001), 80.47%, and 91.05%, respectively, which significantly exceeded those of the other two models. The nomogram prediction model showed high accuracy and validity. Conclusion: The texture features of CT images before SABR are of a high prognostic value for HCC patients and contribute to the selection of appropriate treatment protocols.

The risk of hepatocellular carcinoma in cirrhosis differs by etiology, age and sex: A Swedish nationwide population-based cohort study.

BackgroundCurrent risk estimates for hepatocellular carcinoma (HCC) in individuals with cirrhosis vary between studies. The risk has mostly been evaluated for single etiologies separately.ObjectivesWe examined the risk of HCC in Swedish outpatients with a new diagnosis of cirrhosis, aiming to identify subgroups with a particularly high risk for incident HCC.MethodsAll patients with a first diagnosis of cirrhosis in the National Outpatient Register for whom the etiology of cirrhosis could be estimated were identified. Incident cases of HCC were ascertained until the end of 2016 using record linkage to national registers. The cumulative incidence of HCC across etiologies of cirrhosis, sex and age was calculated considering non‐HCC death as a competing risk.ResultsWe identified 15,215 individuals with cirrhosis. The incidence rate for HCC in cirrhosis was 23/1000 person‐years (95%CI = 22–24). Stratified on gender, it was 29/1000 person‐years (95%CI = 27–31) in men versus 14/1000 person‐years (95%CI = 13–16) in women. The cumulative incidence of HCC in cirrhosis was 8.3% (95%CI = 7.8–8.8) at 5 years and 12.2% (95%CI = 11.6–13.0) at 10 years. At 10 years, the lowest cumulative incidence was seen in women with alcohol‐related liver disease (4.3%) and the highest in men with viral hepatitis (26.6%). These figures also varied by age.ConclusionsThe risk of HCC differs extensively across subgroups of etiologies of cirrhosis, age and sex, suggesting that initiation of HCC surveillance could be individually tailored.

Real‐world long‐term analysis of daclatasvir plus asunaprevir in patients with hepatitis C virus infection

Background and AimThis study aimed to evaluate the long‐term clinical course of patients achieving a sustained virologic response (SVR) with daclatasvir plus asunaprevir (DCV/ASV) therapy.MethodsA total of 911 patients who achieved SVR with DCV/ASV were assessed. To evaluate pretreatment factors contributing to hepatocellular carcinoma (HCC) after SVR, univariate and multivariate analyses were performed in all patients, in those with preexisting HCC, and in those without preexisting HCC. We selected a low‐risk group of HCC cases after SVR. Finally, we evaluated liver function after achieving SVR.ResultsIn multivariable analyses, male sex, older age, patients with a history of HCC treatment, excess alcohol use, lower albumin, and low platelet count remained significant in the overall group; male sex and low albumin remained significant in patients with a history of HCC treatment; and male sex, older age, excess alcohol use, low platelet count, high alpha‐fetoprotein (AFP), and high des‐γ‐carboxy prothrombin (DCP) remained significant in those without a history of HCC treatment. Patients who had not received treatment for HCC, females, those under 70 years of age, and those with platelet count ≥13 (×104/μL), AFP <6 ng/mL, and DCP <23 mAU/mL were at low risk of HCC. The process of liver function improvement was different according to the factors.ConclusionsThe incidence rate of HCC, risk factors associated with HCC, group with very low risk of developing HCC, and the clinical course in a real‐world long‐term study were evaluated.

Targeting population groups with heavier burden of hepatocellular carcinoma incidence: A nationwide descriptive epidemiological study in Sweden

Contemporary European studies examining associations between socioeconomic status and hepatocellular carcinoma (HCC) incidence are scarce. We aimed to target population groups with a heavier burden of HCC by assessing associations of individual‐level sociodemographic variables and neighbourhood deprivation with all‐stage and stage‐specific HCC incidence rates (IR). Patient and population data stratified by calendar year (2012‐2018), sex, age (5‐year groups), household income (low, medium and high), country of birth (Nordic, non‐Nordic) and neighbourhood deprivation (national quintiles Q1‐Q5) were retrieved from Swedish registers. HCC stages were defined by Barcelona Clinic Liver Cancer stages 0 to A (early‐stage) and B to D (late‐stage). IR (per 100 000 person‐years) were estimated by Poisson regression models. Men had four times higher IR than women. IRs increased markedly with lower household income as well as with neighbourhood deprivation. Seven times higher IR was observed among people with a low household income living in the most deprived neighbourhoods (IR 3.90, 95% confidence interval [CI] 3.28‐4.64) compared to people with a high household income living in the least deprived neighbourhoods (IR 0.58, 95% CI 0.46‐0.74). The gradient across income categories was more pronounced for late‐stage than early‐stage HCC. IR reached 30 (per 100 000 person‐years) for people in the age span 60 to 79 years with low income and 20 for 60 to 79 year old people living in the most deprived neighbourhoods (regardless of income). Men with low household income and/or living in the most deprived neighbourhoods might be considered as primary targets in studies evaluating the cost‐effectiveness of screening for early‐stage HCC detection.

An emerging role of radiation‑induced exosomes in hepatocellular carcinoma progression and radioresistance (Review).

The incidence rates of hepatocellular carcinoma (HCC) worldwide are increasing, and the role of radiotherapy is currently under discussion. Radioresistance is one of the most important challenges in the therapy of HCC compared with other local advanced, recurrent and metastatic cancers. The mechanisms of radioresistance are complex and remain to be fully understood; however, extracellular vesicles have been investigated in recent studies. Exosomes, which are 40- to 150-nm extracellular vesicles released by cancer cells, contain multiple pathogenic components, including proteins, nucleic acids and lipids, and play critical functions in cancer progression. Emerging data indicate a diagnosis potential for exosomes in HCC, since radiation-derived exosomes promote radioresistance. Radiation-based therapy alters the contents and components of exosomes, suggesting that exosomes and their components may serve as prognostic and predictive biomarkers to monitor radiation response. Therefore, understanding the roles and mechanisms of exosomes in HCC progression and radiation response during HCC therapy may increase our knowledge concerning the roles of exosomes in radioresistance, and may lead to novel approaches for HCC prognosis and treatment. The current review summarizes recent studies on exosome involvement in HCC and the molecular changes in exosome components during HCC progression. It also discusses the functions of exosomes in HCC therapy, and highlights the importance of exosomes in HCC progression and resistance for the development of novel therapies.

The Risk of Hepatocellular Carcinoma in Entecavir Versus Tenofovir Treated US Cohort With Chronic Hepatitis B Virus

The comparative effectiveness of tenofovir (TDF) vs entecavir (ETV) in reducing the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) remains unclear. Data from a retrospective Korean cohort study published by Choi etal1 initially suggested a lower-than-expected incidence of HCC in patients on long-term TDF. However, additional studies from Korea did not show a statistically significant difference in HCC incidence rate between TDF and ETV groups,2,3 and subsequent studies reported mixed results ranging from no association or a slight advantage for TDF.4 Most of these studies examined Asian patients from Korea, Taiwan, and China.

Low Incidence of Hepatocellular Carcinoma after Antiviral Therapy in Patients with Chronic Hepatitis C and Hemophilia.

Background: Hepatocellular carcinoma (HCC) rarely develops in patients with chronic hepatitis C (CHC) who achieve sustained virological response (SVR). We assessed the incidence of HCC in CHC patients with hemophilia after treatment with pegylated interferon plus ribavirin (PegIFN/RBV) and direct-acting antivirals (DAAs). Methods: Patients (n = 202) were enrolled between March 2007 and July 2019. A total of 139 patients were treated with PegIFN/RBV (genotype 1, n = 98; genotype 2, n = 41). Sixty-three patients were treated with DAAs (genotype 1, n = 44; genotype 2, n = 19). The cumulative incidence rates of HCC were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: For genotype 1, SVR was achieved in 78.6% (77/98) and 90.9% (40/44) of patients in the PegIFN/RBV and DAAs groups, respectively. For genotype 2, SVR was achieved in 95.1% (39/41) and 94.7% (18/19) of patients in the PegIFN/RBV and DAAs groups, respectively. Six HCC cases were identified. The cumulative incidence of HCC was 4.1% at 14 years in PegIFN/RBV and 1.7% at 5 years in DAAs. The 14-year cumulative incidence of HCC was 1.9% in the SVR group and 21.7% in the no-SVR group in the PegIFN/RBV group (p < 0.001). Conclusions: Treatment with PegIFN/RBV led to stable SVR and a low incidence of HCC. Although the follow-up period was short, DAAs led to more stable SVR than PegIFN/RBV and a low incidence of HCC in CHC patients with hemophilia.