Decision tree algorithm predicts hepatocellular carcinoma among chronic hepatitis C patients following viral eradication.

Successful eradication of the hepatitis C virus (HCV) cannot eliminate the risk of hepatocellular carcinoma (HCC). Next-generation RNA sequencing provides comprehensive genomic insights into the pathogenesis of HCC. Artificial intelligence has opened a new era in precision medicine. This study integrated clinical features and genetic biomarkers to establish a machine learning-based HCC model following viral eradication. A prospective cohort of 55 HCV patients with advanced fibrosis, who achieved a sustained virologic response after antiviral therapy, was enrolled. The primary outcome was the occurrence of HCC. The genomic signatures of peripheral blood mononuclear cells (PBMC) were determined by RNA sequencing at baseline and 24 weeks after end-of-treatment. Machine learning algorithms were implemented to extract the predictors of HCC. HCC occurred in 8 of the 55 patients, with an annual incidence of 2.7%. Pretreatment PBMC DEFA1B, HBG2, ADCY4, and posttreatment TAS1R3, ABCA3, and FOSL1 genes were significantly downregulated, while the pretreatment ANGPTL6 gene was significantly upregulated in the HCC group compared to that in the non-HCC group. A gene score derived from the result of the decision tree algorithm can identify HCC with an accuracy of 95.7%. Gene score = TAS1R3 (≥0.63 FPKM, yes/no = 0/1) + FOSL1 (≥0.27 FPKM, yes/no = 0/1) + ABCA3 (≥2.40 FPKM, yes/no = 0/1). Multivariate Cox regression analysis showed that this gene score was the most important predictor of HCC (hazard ratio = 2.38, 95% confidence interval [CI] = 1.06-5.36, P = 0.036). Combining the gene score and fibrosis-4 index, a nomogram was constructed to predict the probability of HCC with an area under the receiver operating characteristic curve up to 0.950 (95% CI = 0.888-1.000, P = 7.0 × 10-5). Decision curve analysis revealed that the nomogram had a net benefit in HCC detection. The calibration curve showed that the nomogram had optimal concordance between the predicted and actual HCC probabilities. In conclusion, down-regulated posttreatment PBMC TAS1R3, ABCA3, and FOSL1 expression were significantly correlated with HCC development after HCV eradication. Decision-tree-based algorithms can refine the assessment of HCC risk for personalized HCC surveillance.

Hepatitis B-related outcomes following direct-acting antiviral therapy in Taiwanese patients with chronic HBV/HCV co-infection.

BACKGROUND & AIMS: The outcome of HBV infection, including the dynamics of HBsAg and HBV virological reactivation, among patients coinfected with HCV receiving direct-acting antivirals (DAAs) remains unclear. Thus, we aimed to analyze HBV-related outcomes in these patients. METHODS: Serial HBsAg and HBV DNA levels were measured in 79 HBV/HCV-coinfected patients receiving DAAs (13 receiving anti-HBV nucleot(s)ide analog [NUC] therapy simultaneously). The endpoints included HBsAg dynamics and seroclearance, HBV reactivation (HBV DNA >1 log increase or >100 IU/ml if undetectable at baseline) and HBV-related clinical reactivation. RESULTS: HBsAg levels declined from a median of 73.3 IU/ml at baseline to 16.2 IU/ml at the end-of-DAA treatment and increased to 94.1 IU/ml at 12 months post-treatment. During a mean 11.1-months of follow-up, 8 (10.1%) patients experienced HBsAg seroclearance and 30 (38.0%) HBV reactivation (12-month cumulative incidence, 10.3% and 40.4%, respectively). Patients with pre-treatment HBsAg ≤10 IU/ml had a significantly higher rate of HBsAg seroclearance (hazard ratio [HR] 8.52; 95% CI 1.048-69.312) and lower risk of HBV reactivation than those with pre-treatment HBsAg >10 IU/ml (HR 2.88; 95% CI 1.057-7.844) in multivariate analyses. Six patients (4 cirrhotics) not receiving NUC therapy experienced HBV-related clinical reactivation; 3 of the 4 cirrhotics developed liver failure and 2 died despite immediate NUC therapy. Compared to untreated HBV-monoinfected patients, HBV/HCV-coinfected patients without NUC prophylaxis had a similar rate of HBsAg seroclearance, but a significantly higher risk of HBV reactivation following DAA therapy (HR 6.59; 95% CI 2.488-17.432). CONCLUSIONS: DAA-treated HBV/HCV-coinfected patients had significantly higher rates of HBV seroclearance, particularly among those with low pre-treatment HBsAg titer, but were at higher risk of HBV reactivation, particularly among those with higher pre-treatment HBsAg titer. Prophylactic anti-HBV therapy is essential for cirrhotic patients, irrespective of baseline HBV DNA levels. LAY SUMMARY: We studied outcomes relating to hepatitis B virus (HBV) in patients coinfected with both hepatitis B and C. Patients receiving direct-acting antiviral treatment for hepatitis C were more likely to experience seroclearance (or functional cure of HBV), but were also more likely to experience HBV reactivation, which can lead to hepatitis, liver failure and death. In coinfected cirrhotic patients being treated for HCV, prophylactic treatment for HBV is mandatory.

Assessment of thermal necrosis risk regions for different bone qualities as a function of drilling parameters.

BACKGROUND AND OBJECTIVE: During bone drilling, the heat generated by friction depends directly on bone quality and surgical parameters. Excessive bone temperatures may cause thermal necrosis around the pilot hole, weaken the purchase of inserted screws, and in turn reduce the stability of screw fixation. A few studies have addressed the key parameters of drilling, such as the rotation speed of the drill-bit, feed force (axial force), feed rate, tool type, and tip geometry of drill-bits. Nevertheless, in the literature, information on the relationship between bone quality and thermally affected regions is still lacking. This study employed a three-dimensional dynamic elastoplastic finite element model to evaluate the influence of surgical parameters on the bone temperature elevation and assess the risk region of thermal necrosis for different bone qualities as a function of drilling parameters. METHODS: To ascertain the heat generation rate and the high-risk region of thermal necrosis, the effects of bone quality, feed rate, feed force, and drill-bit diameter on the bone temperature elevation were explained using a three-dimensional dynamic elastoplastic finite element model, which was validated through experimental measurements. RESULTS: The bone temperature was affected by the drilling parameters; the maximum temperature was attained at the junction of cancellous and cortical bones. The bone temperature increased with cortical bone thickness, bone density, and drill-bit diameter, and it decreased with the drilling speed and feed force. CONCLUSIONS: The present model could assess the risk region of thermal necrosis by accurately analyzing the bone temperature elevation for various bone qualities, feed forces, and feed rates. The bone temperature increased with the bone mineral density and cortical bone thickness. The highest bone temperature and maximum necrosis region were found near the junction of cortical and cancellous bones. Increasing the drilling speed or feed force can minimize the bone temperature elevation and the risk range of thermal necrosis.

Identification of treatment-experienced hepatitis C patients with poor cost-effectiveness of pegylated interferon plus ribavirin from a real-world cohort.

BACKGROUND/PURPOSE: Pegylated interferon (PegIFN) plus ribavirin (RBV) combination therapy has been the standard of care since 2002. Although a better viral response has been achieved among chronic hepatitis C (CHC) patients in Taiwan, approximately 25% of hepatitis C virus (HCV) genotype 1 (G1) patients and 15% of G2 patients failed to achieve a sustained virological response (SVR) at the first therapy. The actual cost-effectiveness of the retreatment remains elusive. The present study conducted a real-world cost-effectiveness analysis of a large cohort among different pre-specified subgroups of treatment-experienced CHC patients. METHODS: A total of 117 patients with CHC who failed to achieve SVR at the first IFN-based therapy and received a second IFN-based therapy were enrolled. The inpatient and outpatient costs were acquired from National Health Insurance Research Database of Taiwan. The related medical care costs per treatment and per SVR were calculated. RESULTS: We demonstrated that the average cost per SVR achieved was $13,722 in treatment-experienced CHC patients. Especially, patients with HCV G1 infection, baseline viral loads > 400,000 IU/mL, advanced hepatic fibrosis, not achieving a rapid viral response at week 4 or complete early viral response at week 12, had poorer cost-effectiveness for PegIFN/RBV retherapy, ranging from around $15,520 to as high as $72,546 per SVR achieved. CONCLUSION: In the current study, we explored the real-world cost-effectiveness data of PegIFN/RBV for different subgroups of treatment-experienced HCV patients. These findings provide information for policy-makers for making decisions on treatment strategies of costly direct-acting antiviral agents for retreating CHC patients.

Identification of groups with poor cost-effectiveness of peginterferon plus ribavirin for naïve hepatitis C patients with a real-world cohort and database.

BACKGROUND: For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. METHODS: A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. RESULTS: The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P < .001). Treatment-naïve G1 patients of old ages, those with advanced fibrosis, high viral loads, or interleukin-28B unfavorable genotypes, or those without a rapid virological response (RVR: undetectable HCV RNA at week 4), or those with complete early virological response (cEVR: undetectable HCV RNA at week 12). Treatment-naïve G2 patients with high viral loads or without RVR or cEVR incurred significantly higher costs per SVR than their counterparts. The cost/SVR was extremely high among patients without RVR and in patients without cEVR. CONCLUSION: We investigated the real-world cost effectiveness data for different subgroups of treatment-naïve HCV patients with PegIFN/RBV therapies, which could provide useful, informative evidence for making decisions regarding future therapeutic strategies comprising costly direct-acting antivirals.

Quantitative assessment of iron in heart and liver phantoms using dual-energy computed tomography.

The aim of the present study was to determine the correlation between dual-energy computed tomography (DECT) Hounsfield units (HU) and iron concentration, as well as the correlation between HU and magnetic resonance imaging (MRI)-derived R2* values, in phantoms of the heart and liver tissue. Phantoms were constructed containing pig heart or liver tissue and varying concentrations of iron (0.1, 5, 10, 15, 20 and 25 mg/ml). The phantoms were then examined by DECT and MRI. Linear regression analysis was used to determine the correlations between HU and iron concentration and HU and R2* values. The HU value of DECT increased with increasing iron concentrations in the liver and heart phantoms in a linear manner. The slope of the HU value change against iron concentration revealed that ΔH80-140 provided a better discernment of iron concentration as compared with ΔH100-140. The derived R2 values were all >0.9 for the associations of DECT and MRI measurements with iron concentrations. Therefore, DECT may be used for the determination of iron concentration in the liver and heart tissue, with the results correlating with those obtained with MRI.

Nitroglycerine use in transcatheter arterial (chemo)embolization in patients with hepatocellular carcinoma and dual-energy CT assessment of Lipiodol retention.

OBJECTIVES: To investigate whether the addition of nitroglycerine to transcatheter arterial (chemo)embolization (TAE/TACE) can increase the delivery and effectiveness of TAE/TACE in patients with hepatocellular carcinoma (HCC) by dual-energy CT. METHODS: HCC patients (BCLC stage A or B) were randomized to (n = 51) or not to (n = 50) receive nitroglycerine and an emulsion of Lipiodol with or without doxorubicin, followed by embolization with Gelfoam pledgets. Dual-energy CT was performed pre- and 1 to 3 months post-embolization to assess changes in tumour diameter and Lipiodol levels in tumours. RESULTS: Median tumour diameter decreased from baseline in both groups with and without nitroglycerine (7.11 % vs. 12.5 %, respectively), and was statistically significant in the group receiving nitroglycerine (P = 0.023). There was no difference between the two groups in disease response (P = 0.237). The concentration and percentage of Lipiodol retained in tumours were significantly greater in patients treated with nitroglycerine compared to those without (median concentration 15.05 mg/mL vs. 4.40 mg/mL, respectively, P < 0.001; median percentage 82.01 % vs. 36.75 %, respectively, P < 0.001). CONCLUSIONS: Nitroglycerine increased delivery of the Lipiodol emulsion via TAE/TACE to HCC tumours with significant tumour reduction. Dual-energy CT can accurately quantify the amount of Lipiodol deposited in tumours. KEY POINTS: • Nitroglycerine improves delivery of tumour-targeted therapy via enhanced permeability and retention. • In hepatocellular carcinoma, nitroglycerine added to TAE/TACE showed greater tumour reduction. • Dual-energy CT can reliably quantify the amount of Lipiodol in TAE/TACE.