Cumulative Incidence Rates Of Hepatocellular Carcinoma Research Articles

A novel formula used for predicting hepatocellular carcinoma after the achievement of sustained virologic response by direct-acting antivirals in patients with chronic hepatitis C.

Although eliminating HCV can prevent hepatocellular carcinoma (HCC), some patients develop HCC even after obtaining sustained virologic response (SVR). Previously, we developed a new formula to predict advanced liver fibrosis. This study aimed to clarify the usefulness of this formula for predicting HCC after achieving SVR. Among 351 consecutive patients who had been treated with direct-acting antivirals, 299 were included in this study. New formula scores were used as a marker for predicting liver fibrosis and as a predictive model for HCC incidence. The participants were 172 men and 127 women with a median age of 68 years. The median new formula score was -1.291. The cumulative HCC incidence rates were 4.3%, 9.7%, and 12.5% at 1, 3, and 5 years, respectively. The cumulative incidence of HCC was significantly higher in patients with a history of HCC than in those without treatment history of HCC (P = 2.52×10-26). Multivariate analysis revealed that male (HR = 6.584, 95% CI = 1.291-33.573, P = 0.023) and new formula score (HR = 1.741, 95% CI = 1.041-2.911, P = 0.035) were independent factors associated with the development of HCC in patients without a treatment history of HCC. The optimal cutoff value for predicting the development of HCC was -0.214. The cumulative incidence rates of HCC in patients with new formula scores ≥-0.214 were 5.4%, 15.3%, and 15.3% at 1, 3, and 5 years, respectively, whereas the incidence rates of HCC in patients with new formula scores <-0.214 were 0.0%, 0.6%, and 4.8%, respectively (P = 2.12×10-4). In conclusion, this study demonstrated the usefulness of new formula scores as a predictor of HCC after achieving SVR, especially in patients without past treatment history of treatment for HCC.

Simple new clinical score to predict hepatocellular carcinoma after sustained viral response with direct-acting antivirals

The time point of the most precise predictor of hepatocellular carcinoma (HCC) development after viral eradication with direct-acting antiviral (DAA) therapy is unclear. In this study we developed a scoring system that can accurately predict the occurrence of HCC using data from the optimal time point. A total of 1683 chronic hepatitis C patients without HCC who achieved sustained virological response (SVR) with DAA therapy were split into a training set (999 patients) and a validation set (684 patients). The most accurate predictive scoring system to estimate HCC incidence was developed using each of the factors at baseline, end of treatment, and SVR at 12 weeks (SVR12). Multivariate analysis identified diabetes, the fibrosis-4 (FIB-4) index, and the α-fetoprotein level as independent factors at SVR12 that contributed to HCC development. A prediction model was constructed with these factors that ranged from 0 to 6 points. No HCC was observed in the low-risk group. Five-year cumulative incidence rates of HCC were 1.9% in the intermediate-risk group and 15.3% in the high-risk group. The prediction model at SVR12 most accurately predicted HCC development compared with other time points. This simple scoring system combining factors at SVR12 can accurately evaluate HCC risk after DAA treatment.

Comparison of acknowledged hepatocellular carcinoma risk scores in high-risk hepatitis C patients with sustained virological response.

Hepatitis C patients with advanced fibrosis or cirrhosis are at high risk of developing hepatocellular carcinoma (HCC) even after sustained virological response (SVR). Several HCC risk scores have been developed but which one is most suitable for this population is unclear. In this study, we compared the prediction ability of the aMAP model, THRI model, PAGE-B model and Models of HCV in a prospective hepatitis C cohort in order to propose better model(s) to clinical practice. Adult hepatitis C patients with baseline advanced fibrosis (141 cases), compensated cirrhosis (330 cases) and decompensated cirrhosis (80 cases) were included and followed up every 6 months for about 7 years or until HCC development. Demographic data, medical history and laboratory results were recorded. HCCs were diagnosed by radiography, AFP or liver histology. The median follow-up period was 69.93(60.99-74.93) months, during which 53 (9.62%) patients developed HCC. The areas under the receiver operating characteristic curve of aMAP, THRI, PAGE-B and Models of HCV scores were 0.74, 0.72, 0.70 and 0.63 respectively. The predictive power of the aMAP model score was comparable to that of THRI, PAGE-Band higher than that of Models of HCV (p < 0.05). Dividing patients into non-high-risk and high-risk groups, the cumulative incidence rates of HCC based on aMAP, THRI, PAGE-B and Models of HCV was 5.57% vs. 24.17%, 1.10% vs. 13.90%, 5.80% vs. 15.90% and 6.41% vs. 13.81% (all p < 0.05). The AUC of the four models were all below 0.7 in male while all were higher than 0.7 in female. The performance of all the models was not influenced by fibrosis stage. aMAP, THRI model and PAGE-B model were all performed well while THRI model and PAGE-B model were easier to calculate. There was no need to select score according to fibrosis stage but should be caution when explain the results in male patients.

The clinical effect of antiviral therapy in patients with hepatitis B virus-related decompensated cirrhosis and undetectable DNA.

Antiviral therapy (AVT) is the mainstay of hepatitis B virus (HBV) management. We investigated whether AVT improves the outcomes of HBV-related decompensated cirrhosis and undetectable HBV-DNA. Between 2000 and 2017, treatment-naïve patients with HBV-related decompensated cirrhosis and undetectable HBV-DNA were recruited from two tertiary hospitals. The endpoints included death and hepatocellular carcinoma (HCC). A total of 429 patients were analyzed (50 and 379 patients in the AVT and non-AVT groups, respectively). Patients in the AVT group were significantly younger and had higher alanine aminotransferase and alpha-fetoprotein levels than those in the non-AVT group (all P<0.05). During follow-up (median 49.6months), 98 patients died and 105 developed HCC. The cumulative incidence rates of death (2.0%, 4.1%, and 6.4%, and 4.9%, 7.2%, and 10.2% at 6months, 1year, and 2years, respectively) and HCC (8.6%, 15.8%, and 26.4% vs 1.6%, 7.7%, and 24.4% at 1, 2, and 5years, respectively) were statistically comparable between the AVT and non-AVT groups (all P>0.05). Using Cox regression analysis, AVT was not significantly associated with death nor HCC (all P>0.05). Similar results were observed after balancing baseline characteristics with inverse probability of treatment weighting. In the non-AVT group, the cumulative incidence rates of HBV-DNA detection at 6months, 1year, and 2years were 2.0%, 3.1%, and 6.4%, respectively. Antiviral therapy did not attenuate the risk of death nor HCC in patients with HBV-related decompensated cirrhosis and undetectable HBV-DNA.

Imaging features of hepatobiliary MRI and the risk of hepatocellular carcinoma development

Objective This study aimed to determine whether hepatocellular carcinoma (HCC) risk and time to HCC development differ according to hepatobiliary magnetic resonance imaging (MRI) findings among people at risk for developing HCC. Materials and methods A total of 199 patients aged 40 years or older with liver cirrhosis or chronic liver disease who underwent gadoxetic acid-enhanced hepatobiliary MRI between 2011 and 2015 were analyzed. An independent radiologist retrospectively reviewed MRI findings, blinded to clinical information, and categorized them into low-risk features, high-risk features and high-risk nodules. High-risk features were defined as liver cirrhosis diagnosed by imaging. High-risk nodules were defined as LR-3 or LR-4 nodules based on LI-RADS version 2018. The primary outcome was development of HCC within 5-year of MRI evaluation. Results HCC was diagnosed in 28 patients (14.1%). HCC development was null for those with low-risk features (n = 84). The cumulative incidence rates of HCC were 0%, 2.3%, 13.4% and 22.1% at 1-, 2-, 3- and 5-year for those with high-risk features (n= 64), and were 19.1%, 31.8%, 37.3% and 46.7% at 1-, 2-, 3- and 5-year for those with high-risk nodules (n= 51). Among 28 patients developed HCC, the median time from baseline MRI to HCC diagnosis was 33.1 months (interquartile range: 25.9–46.7 months) for high-risk feature group, and 17.3 months (interquartile range: 6.2–26.5 months) for high-risk nodule group. Conclusions HCC risk and time to HCC development differ according to baseline hepatobiliary MRI findings, indicating that hepatobiliary MRI findings can be used as biomarkers to differentiate HCC risk.

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.

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.

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.

The absence of warfarin treatment and situs inversus are associated with the occurrence of hepatocellular carcinoma after Fontan surgery.

Hepatocellular carcinoma (HCC) is a long-term complication of Fontan-associated liver disease (FALD). However, risk factors for HCC in patients with FALD remain unclear. This study aimed to identify factors associated with HCC development post-Fontan procedure. We retrospectively examined 103 post-Fontan patients who underwent hepatic imaging at our institution. HCC incidence and patient characteristics were analyzed. A Cox proportional hazards model was used to identify risk factors for HCC. The median interval between Fontan surgery and final hepatic imaging was 19.6 (1.0-37.7) years. Among 103 patients, nine developed HCC. The cumulative incidence rates of HCC at 10, 20, and 30years postoperatively were 0%, 7%, and 13%, respectively. In the univariate analysis, age at Fontan surgery, situs inversus, and warfarin absence were associated with HCC occurrence. The multivariate analysis identified the warfarin absence (adjusted hazard ratio [aHR], 22.71; 95% confidence interval: 3.29-507.1; p = 0.0005) and situs inversus (aHR, 14.36; 95% confidence interval: 2.75-105.5; p = 0.002) as risk factors. The prevalence of situs inversus and the warfarin absence was 12% and 50%, respectively. The 20- and 30-year incidence rates of HCC among patients who received warfarin were 0% and 7%, respectively, while those among patients who did not receive warfarin were 14% and 21%, respectively. HCC incidence was significantly higher in the non-warfarin group than in the warfarin group (p = 0.006) and among patients with situs inversus than among those with situs solitus (p = 0.004). Warfarin absence and situs inversus were associated with HCC development post-Fontan procedure.

Predicting the risk of hepatocellular carcinoma in chronic hepatitis B patients receiving antiviral therapy: Validating the CAMD and AASL scores in China.

We aimed to validate the predictive value of the cirrhosis, age, male sex, and diabetes (CAMD) score and age, albumin, sex, and liver cirrhosis (AASL) score for chronic hepatitis B (CHB) patients, treated with nucleos(t)ide analogues (NUCs) in Northeast China. From January 2009 to June 2020, 945 patients diagnosed with CHB who received NUC therapy at China-Japan Union Hospital of Jilin University were included. Comprehensive medical records were retrospectively analyzed, and the predictive values of the CAMD score and AASL score for hepatocellular carcinoma (HCC) were evaluated. A total of 58 patients (5.94%) were diagnosed with HCC. Multivariate analysis revealed that age [odds ratio (OR) = 1.041, 95% confidence interval (CI) 1.009-1.073, P < 0.011] and cirrhosis (OR = 3.297, 95% CI 1.383-7.861, P < 0.007) were independent predictors of HCC. Either the CAMD or AASL score was significantly higher in the HCC group compared to the non-HCC group. The area under the receiver operating characteristic (ROC) curve (AUC) of CAMD and AASL was 0.721 (95% CI 0.663-0.780) and 0.718 (95% CI 0.662-0.774), respectively. Risk stratification using either CAMD or AASL revealed significant differences in the one-, three-, and five-year cumulative incidence rates of HCC between the low-, intermediate-, and high-risk groups (all P < 0.001, log-rank test). Both CAMD and AASL scores have predictive value for HCC risk of CHB patients in Northeast China. In future, the optimal monitoring frequency and methods should be personalized.

Tenofovir is superior to entecavir in reducing HCC for patients with HBV-related compensated cirrhosis at high HCC risk scores.

Background:Both tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are known to reduce the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to compare the difference in HCC risk reduction between TDF and ETV in treatment-naïve patients with CHB-related compensated cirrhosis.Methods:Patients with compensated cirrhosis initially treated with TDF or ETV at nine Chinese hospitals between June 2014 and March 2021 were enrolled in this retrospective study. The cumulative HCC incidence rates for the two drugs were compared for the entire cohort, and a subgroup analysis was performed according to the HCC risk scores. Propensity score matching (PSM) was used to control confounding biases.Results:The analysis included 1453 patients (TDF group, n = 188; ETV group, n = 1265). Ninety-five patients developed HCC, with a median follow-up period of 26.1 months. The 3-year HCC incidence was 2.0% in the TDF group and 7.5% in the ETV group (log-rank p = 0.005). TDF treatment was associated with a lower risk of HCC than ETV treatment [hazard ratio (HR) = 0.222, 95% confidence interval (CI), 0.070–0.702, p = 0.010] but was similar after PSM (HR = 0.483, 95% CI, 0.144–1.626, p = 0.240; log-rank p = 0.230). However, subgroup analysis showed that the cumulative HCC incidence was lower in the TDF group than in the ETV group among patients with a modified PAGE-B score (mPAGE-B) ⩾9, either before or after PSM (log-rank p = 0.048 and p = 0.023, respectively).Conclusion:Among patients with an mPAGE-B score ⩾9, TDF is associated with a lower HCC incidence than ETV in patients with CHB-related compensated cirrhosis.

A validation study of after direct-acting antivirals recommendation for surveillance score for the development of hepatocellular carcinoma in patients with hepatitis C virus infection who had received direct-acting antiviral therapy and achieved sustained virological response.

Background and AimThe pathogenic process underlying the development of hepatocellular carcinoma (HCC) is not yet clear in patients with hepatitis C virus (HCV) who have received direct‐acting antiviral (DAA) therapy and achieved sustained virological response (SVR). This study validated a composite predictive model for HCC in these patients.MethodsThis study included 3058 patients in whom HCV was eradicated with DAA therapy. After DAAs recommendation for surveillance (ADRES) score, which is based on sex, FIB‐4 index, and α‐fetoprotein, was used as a composite predictive model for HCC development.ResultsThe 1‐, 3‐, and 5‐year cumulative incidence rates of HCC were 0.9, 4.5, and 15.2%, respectively. Multivariate analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 2.646; 95% confidence interval [CI], 1.790–3.911), FIB‐4 index >3.25 (HR, 2.891; 95% CI, 1.947–4.293), and α‐fetoprotein >5 ng/mL (HR, 2.835; 95% CI, 1.914–4.200) are independently associated with HCC development. The incidence of HCC differed significantly by ADRES score (P < 0.001). Cox proportional hazards models showed that compared to the ADRES score 0 group, the HR for HCC development was 2.947 (95% CI, 1.367–6.354) in the ADRES score 1 group, 9.171 (95% CI, 4.339–19.380) in the ADRES score 2 group, and 20.630 (95% CI, 8.641–49.230) in the ADRES score 3 group. ADRES score had superior predictive power for HCC development compared with the FIB‐4 index and α‐fetoprotein according to time‐dependent receiver operating characteristic analysis.ConclusionThe ADRES score is useful for predicting HCC development after SVR.

Risk assessment of hepatocellular carcinoma and liver-related events using ultrasonography and transient elastography in patients with chronic hepatitis B.

Cirrhosis has prognostic value. We investigated whether the combined use of ultrasonography (US) and transient elastography (TE) to diagnose cirrhosis is beneficial for the risk assessment of hepatocellular carcinoma (HCC) and liver-related events in patients with chronic hepatitis B (CHB). A total of 9300 patients with CHB who underwent US and TE in two institutions between 2006 and 2018 were enrolled. TE value ≥13kPa was set to indicate cirrhosis. Patients were divided into four groups: US(+)TE(+) (cirrhosis by US and TE), US(+)TE(-) (cirrhosis by US, but not by TE), US(-)TE(+) (cirrhosis by TE, but not by US) and US(-)TE(-) (non-cirrhosis by US and TE).The patients were predominantly male (n=5474, 58.9%) with a mean age of 47.5years. The proportions of patients with cirrhosis diagnosed by US and TE were 17.2% (n=1595) and 13.2% (n=1225), respectively. The proportion of patients with discordant results in diagnosing cirrhosis by US and TE was 18.7% (n=1740). During follow-up (median: 60.0months), HCC and liver-related events developed in 481 (5.2%) and 759 (8.2%) patients, respectively. The cumulative incidence rates of HCC and liver-related events were highest in the US(+)TE(+) group, intermediate-high in the US(-)TE(+) group, intermediate-low in the US(+)TE(-) group and lowest in the US(-)TE(-) group (overall p<.001). Cirrhosis assessed using US and TE was a major predictor of HCC and liver-related event development in patients with CHB. Cirrhosis assessed using TE seemed better in predicting HCC or liver-related events than using US, when cirrhosis diagnosis was discordant by US and TE.

Association of Physical Activity with the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B.

Simple SummaryAlthough viral replication in patients with a chronic hepatitis B (CHB) infection is effectively suppressed by potent antiviral therapy such as entecavir or tenofovir, the risk of hepatocellular carcinoma (HCC) development in CHB patients cannot be totally eliminated. Thus, control of modifiable risk factors for HCC development such as lifestyle modification is important to minimize the HCC risk. In this study, we analyzed a nationwide population-based cohort to evaluate whether there is a significant association between physical activity and development of HCC in CHB patients treated with entecavir or tenofovir. Results in this study suggest that physical activity was significantly associated with a lower risk of HCC development in CHB patients treated with potent antiviral therapy. Increasing physical activity can have beneficial outcomes on HCC development in CHB patients treated with entecavir or tenofovir.Background and Aims: In the general population, previous studies reported that physical activity was associated with risk of hepatocellular carcinoma (HCC) development. However, it is unclear whether physical activity is associated with risk of HCC development in patients with chronic hepatitis B (CHB). We aimed to elucidate the association between physical activity and risk of HCC development in CHB patients. Methods: This nationwide cohort study involved treatment-naive patients with CHB (n = 9727) who started treatment with entecavir or tenofovir and answered self-reported questionnaires between January 2012 and December 2017, using data from the Korean National Health Insurance Service database. The primary endpoint was development of HCC. Multivariable Cox regression and competing risk analyses were used. Results: During a median follow-up of 3.1 years, cumulative HCC incidence rates were 8.3%. There was an inverse association between physical activity and the risk of HCC (p < 0.001). Patients with 1000–1500 metabolic equivalent task (MET)-min/week, compared to those without physical activity, showed a significantly lower risk of HCC in both patients without cirrhosis (adjusted hazard ratio [aHR] 0.66, p = 0.02) and patients with cirrhosis (aHR 0.61, p = 0.02). In patients who were younger (<60), male, without diabetes, and with high BMI, amounts of physical activity of 1000–1500 MET-min/week showed an inverse association with the risk of HCC (aHR 0.65, 0.63, 0.65, and 0.64, respectively, all p < 0.05). Conclusion: Physical activity was significantly associated with a low risk of HCC in CHB patients treated with entecavir or tenofovir.

Association of liver stiffness and steatosis with hepatocellular carcinoma development in patients with hepatitisC virus infection who received direct-acting antiviral therapy and achieved sustained virological response.

The pathogenic process underlying the development of hepatocellular carcinoma (HCC) is not yet clear in patients with chronic hepatitisC virus who receive direct-acting antiviral therapy and achieve sustained virological response. This study investigated two risk factors for HCC in these patients; specifically, hepatic fibrosis and steatosis. A total of 355 patients in whom hepatitisC virus was eradicated by direct-acting antiviral were evaluated. Fibrosis and steatosis were assessed using transient elastography (TE) and the controlled attenuation parameter (CAP). Inverse probability weighting was applied to patient age, sex, albumin-bilirubin, α-fetoprotein, history of HCC, TE, or CAP. The 12-, 24-, and 36-month cumulative incidence rates of HCC were 0.9%, 2.4%, and 4.1%, respectively. Univariate analysis with the Cox proportional hazards model showed that whereas a high TE value (≥10kPa) was significantly associated with HCC development (HR 7.861, 95% CI 2.126-29.070; p=0.002), CAP was not. Additionally, univariate analysis with the Cox proportional hazards model adjusted by inverse probability weighting showed that a high TE value was significantly associated with HCC development (HR 3.980, 95% CI, 1.036-15.290; p=0.044), whereas CAP was not. The cumulative inverse probability weighting-adjusted incidence of HCC rates at 12, 24, and 36months were 0.0%, 0.5%, and 1.7%, respectively, in patients with a low TE value, and 2.5%, 5.1%, and 7.6%, respectively, in those with a high TE value. A high TE value was a risk factor for HCC in hepatitisC virus patients who received direct-acting antiviral therapy and achieved sustained virological response.

Prediction of Hepatocellular Carcinoma by On-Therapy Response of Noninvasive Fibrosis Markers in Chronic Hepatitis B.

Antiviral therapy improves hepatic fibrosis and reduces hepatocellular carcinoma (HCC) incidence. This study aimed to evaluate whether on-therapy changes in scores for fibrosis index based on 4 factors and aspartate aminotransferase-to-platelet ratio index are associated with HCC development and establish an HCC risk score model incorporating noninvasive fibrosis marker (NFM) response. This multicenter study recruited 5,147 patients with chronic hepatitis B (4,028 for derivation cohort and 1,119 for validation cohort) who were given entecavir/tenofovir for >12 months between 2007 and 2018. A risk prediction model for HCC was developed using predictors based on multivariable Cox models, and bootstrapping was performed for validation. The 10-year cumulative HCC incidence rates were 12.6% and 13.7% in the derivation and validation cohorts, respectively. The risk of HCC significantly differed with early NFM response, with a marked reduction in HCC risk in patients achieving a significant decrease in NFM by 12 months (P < 0.001). NFM response, sex, age, and cirrhosis were independently predictive of HCC. We developed the Fibrosis marker response, Sex, Age, and Cirrhosis (FSAC) score based on regression coefficients of each variable. For the 10-year prediction of HCC, FSAC showed higher C-index values than PAGE-B, modified PAGE-B, CU-HCC, and REACH-B (0.84 vs 0.77, 0.80, 0.77, and 0.67, respectively; all P < 0.005). The predictive performance of FSAC was corroborated in the validation cohort, with higher C-index than other models (all P < 0.050). On-therapy changes in NFM are an independent indicator of HCC risk. FSAC incorporating NFM response is a reliable risk score for risk estimation for HCC with better performance than other models.

Factors associated with hepatocellular carcinoma occurrence after HCV eradication in patients without cirrhosis or with compensated cirrhosis.

The present study aimed to investigate the incidence of hepatocellular carcinoma (HCC) and factors related to HCC occurrence after direct-acting antiviral (DAA) treatment in the Fukushima Liver Academic Group (FLAG). We conducted a multicenter retrospective cohort study of 1068 patients without cirrhosis (NC) or with compensated liver cirrhosis (LC) who achieved a sustained virologic response (SVR). First, we compared the cumulative HCC incidence and survival rates in NC (n = 880) and LC (n = 188) patients without a history of HCC treatment. Second, we performed multivariate analysis of factors related to HCC occurrence after DAA treatment. Overall, the average age was 65 years, and the male/female ratio was 511/557. Thirty-nine (4%) patients developed HCC. The cumulative 4-year HCC incidence and survival rates were 3.0% and 99.8% in NC patients and 11.5% and 98.5% in LC patients, respectively. The independent factors affecting HCC occurrence identified by multivariate analysis were the serum albumin (ALB) level before SVR for NC patients and the ALBI score, platelet count, and diabetes before SVR for LC patients. The factors related to HCC occurrence differed between NC and LC patients. Careful surveillance of post-SVR patients with these risk factors is needed.

Prognosis of late elderly patients with chronic hepatitis C after achieving a sustained viral response by direct-acting antivirals.

Background and AimWe investigated the prognosis of late elderly patients (≥75 years old) after the achievement of a sustained viral response (SVR) by direct‐acting antivirals (DAAs).MethodsOne hundred and four late elderly patients and 251 young patients (≤74 years old) who had achieved an SVR were included. We compared the cumulative hepatocellular carcinoma (HCC) incidence rates and survival rates after DAA administration. Furthermore, the factors associated with HCC incidence and the causes of death after DAA administration were also investigated.ResultsThe cumulative HCC incidence rates for 1 and 3 years were 2.9% and 11.7% in the late elderly patients and 2.4% and 5.4% in the young patients, respectively. The cumulative survival rates for 1 and 3 years were 100% and 95.6% in the late elderly patients and 100% and 96.4% in the young patients, respectively, with no significant differences in those rates noted (P = 0.133, P = 0.322, respectively). In the late elderly patients, only a history of HCC was a significant factor associated with HCC incidence after DAA administration. Five late elderly patients died after achieving an SVR, and malignant liver tumor was the cause of death in three of those patients.ConclusionsThe prognosis did not differ markedly between late elderly patients and young patients. The factor most strongly influencing the prognosis of late elderly patients was likely liver disease, including HCC. DAAs should be introduced even in late elderly patients who can be expected to have a relative long‐term survival.

Serum Myostatin Predicts the Risk of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Multicenter Study

Simple SummarySarcopenia is prevalent in patients with liver cirrhosis. It has been well-known that cirrhotic patients with sarcopenia had poorer survival as compared to those without it, and expression of serum myostatin is associated with sarcopenia. In this study, we aimed to evaluate whether serum myostatin is associated with hepatocellular carcinoma development in patients with alcoholic cirrhosis or not. We found that serum myostatin is associated with hepatocellular carcinoma development in a large cohort of patients with alcoholic cirrhosis. Among patients with similar residual liver function or similar risk of developing hepatocellular carcinoma using other models, higher serum myostatin was significantly associated with a higher risk of developing hepatocellular carcinoma. In addition, patients with more advanced hepatic fibrosis had significantly higher serum myostatin than those with less advanced hepatic fibrosis. Thus, serum myostatin as a prognostic marker can be useful to identify high-risk patients who need stringent surveillance for hepatocellular carcinoma.Background and Aim: Previous studies reported that serum myostatin is associated with sarcopenia. We aimed to elucidate the association between serum myostatin levels and hepatocellular carcinoma (HCC) development in patients with alcoholic liver cirrhosis (ALC). Methods: This retrospective, multicenter study assessed 1077 Asian ALC patients enrolled from 2007 to 2017. The primary endpoint was the development of HCC within 5 years. Cox proportional hazards model analyses were used to assess the association of serum myostatin levels and HCC development. The time-dependent areas under the receiver operating characteristic curve (AUROC) of serum myostatin for 5-year HCC development were calculated. Serum myostatin levels were measured using an enzyme-linked immunosorbent assay with samples collected on the index date. Results: During a median follow-up of 2.5 years, 5-year cumulative HCC incidence rates were 6.7% in the total population. The median level of serum myostatin was 3.3 ng/mL (interquartile, 2.1–5.2 ng/mL). The AUROC of serum myostatin for 5-year HCC development was 0.78 (95% confidence interval [CI], 0.76–0.81). In Cox proportional hazards model analyses, age, gender, platelet counts, and serum myostatin levels were independent risk factors for HCC development (adjusted hazard ratios [HRs] of age, male gender, platelet counts, and serum myostatin: 1.03, 2.79, 0.996, 1.18, respectively; all p < 0.05). Patients with high myostatin levels had a significantly higher risk of 5-year HCC development than those with low myostatin levels (HR 7.53, p < 0.001). Conclusion: Higher serum myostatin levels were significantly associated with a higher risk of developing HCC in ALC patients, which could identify high-risk patients who need stringent surveillance.

Age and fibrosis index for the prediction of hepatocellular carcinoma risk in patients with high hepatitis B virus DNA but normal alanine aminotransferase.

Chronic hepatitis B patients positive for hepatitis B e antigen (HBeAg) with high serum hepatitis B virus (HBV) DNA levels but normal alanine aminotransferase (ALT) levels may develop hepatocellular carcinoma (HCC). However, ways to risk stratify are limited. A retrospective cohort of 651 HBeAg positive, adult patients with high serum HBV DNA levels (>7 log IU/ml) but normal or mildly elevated ALT levels (<80 U/L) were analyzed. Age and FIB-4 index were independent factors associated with HCC development. When stratified, 5- and 10-year cumulative HCC incidence rates were 0 and 2.0% for patients aged <40 years with FIB-4 index <1.45, and were 5.9 and 32.7% for patients aged ≥40 years with FIB-4 index ≥1.45, respectively (P < 0.001). In patients with normal ALT levels (n = 301), the 10-year HCC incidence rate was 0% for patients aged <40 years with FIB-4 index <1.45, while 5- and 10-years HCC incidence rate was 4.5 and 27.1% for patients aged ≥40 years with FIB-4 index ≥1.45, respectively (P < 0.001). In patients with high HBV DNA but normal ALT levels, age and FIB-4 index could effectively stratify HCC risk, indicating that these parameters may guide management plans for this population.