Nodal infiltration in endometrial cancer: a prediction model using best subset regression.

OBJECTIVES: To build preoperative prediction models with and without MRI for regional lymph node metastasis (r-LNM, pelvic and/or para-aortic LNM (PENM/PANM)) and for PANM in endometrial cancer using established risk factors. METHODS: In this retrospective two-center study, 364 patients with endometrial cancer were included: 253 in the model development and 111 in the external validation. For r-LNM and PANM, respectively, best subset regression with ten-time fivefold cross validation was conducted using ten established risk factors (4 clinical and 6 imaging factors). Models with the top 10 percentile of area under the curve (AUC) and with the fewest variables in the model development were subjected to the external validation (11 and 4 candidates, respectively, for r-LNM and PANM). Then, the models with the highest AUC were selected as the final models. Models without MRI findings were developed similarly, assuming the cases where MRI was not available. RESULTS: The final r-LNM model consisted of pelvic lymph node (PEN) ≥ 6 mm, deep myometrial invasion (DMI) on MRI, CA125, para-aortic lymph node (PAN) ≥ 6 mm, and biopsy; PANM model consisted of DMI, PAN, PEN, and CA125 (in order of correlation coefficient ß values). The AUCs were 0.85 (95%CI: 0.77-0.92) and 0.86 (0.75-0.94) for the external validation, respectively. The model without MRI for r-LNM and PANM showed AUC of 0.79 (0.68-0.89) and 0.87 (0.76-0.96), respectively. CONCLUSIONS: The prediction models created by best subset regression with cross validation showed high diagnostic performance for predicting LNM in endometrial cancer, which may avoid unnecessary lymphadenectomies. CLINICAL RELEVANCE STATEMENT: The prediction risks of lymph node metastasis (LNM) and para-aortic LNM can be easily obtained for all patients with endometrial cancer by inputting the conventional clinical information into our models. They help in the decision-making for optimal lymphadenectomy and personalized treatment. KEY POINTS: •Diagnostic performance of lymph node metastases (LNM) in endometrial cancer is low based on size criteria and can be improved by combining with other clinical information. •The optimized logistic regression model for regional LNM consists of lymph node ≥ 6 mm, deep myometrial invasion, cancer antigen-125, and biopsy, showing high diagnostic performance. •Our model predicts the preoperative risk of LNM, which may avoid unnecessary lymphadenectomies.

Potential of an artificial nerve graft containing Schwann cells for the treatment of a 20-mm nerve defect in rats.

OBJECTIVE: In a previous study, the authors showed that the migration of Schwann cells (SCs) through end-to-side (ETS) neurorrhaphy promotes axonal regrowth within an acellular nerve graft. In the present study, the authors investigated whether a similar strategy using an artificial nerve (AN) would allow reconstruction of a long nerve gap (20 mm) in rats. METHODS: Forty-eight 8- to 12-week-old Sprague Dawley rats were divided into control (AN) and experimental (SC migration-induced AN [SCiAN]) groups. Prior to the experiment, the ANs used in the SCiAN group were populated in vivo with SCs over a 4-week period by ETS neurorrhaphy onto the sciatic nerve. In both groups, a 20-mm sciatic nerve defect was reconstructed in an end-to-end fashion using 20-mm ANs. Sections from the nerve graft and distal sciatic nerve in both groups underwent assessments at 4 weeks for SC migration by immunohistochemical analysis and quantitative reverse transcription-polymerase chain reaction. At 16 weeks, axonal elongation was assessed by immunohistochemical analysis, histomorphometry, and electron microscopy. The number of myelinated fibers was counted, the g-ratio was calculated, and myelin sheath thickness and axon diameter were measured. Furthermore, functional recovery was evaluated at 16 weeks using the Von Frey filament test for sensory recovery and by calculating the muscle fiber area for motor recovery. RESULTS: The area occupied by SCs at 4 weeks and by axons at 16 weeks was significantly larger in the SCiAN group than in the AN group. Histomorphometric evaluation of the distal sciatic nerve revealed a significantly greater number of axons. At 16 weeks, plantar perception in the SCiAN group was significantly better, demonstrating improvement in sensory function. However, no tibialis anterior muscle motor improvement was observed in either group. CONCLUSIONS: The induction of SC migration into an AN by ETS neurorrhaphy is a useful technique for repairing 20-mm nerve defects in rats, with better nerve regeneration and sensory recovery. No motor recovery was observed in either group; however, motor recovery might require a longer period of time than the lifespan of the AN used in this study. Future studies should investigate whether structural and material reinforcement of the AN, to lower its decomposition rate, can improve functional recovery.

Automatic segmentation of bladder cancer on MRI using a convolutional neural network and reproducibility of radiomics features: a two-center study.

This study aimed to develop a versatile automatic segmentation model of bladder cancer (BC) on MRI using a convolutional neural network and investigate the robustness of radiomics features automatically extracted from apparent diffusion coefficient (ADC) maps. This two-center retrospective study used multi-vendor MR units and included 170 patients with BC, of whom 140 were assigned to training datasets for the modified U-net model with five-fold cross-validation and 30 to test datasets for assessment of segmentation performance and reproducibility of automatically extracted radiomics features. For model input data, diffusion-weighted images with b = 0 and 1000 s/mm2, ADC maps, and multi-sequence images (b0-b1000-ADC maps) were used. Segmentation accuracy was compared between ours and existing models. The reproducibility of radiomics features on ADC maps was evaluated using intraclass correlation coefficient. The model with multi-sequence images achieved the highest Dice similarity coefficient (DSC) with five-fold cross-validation (mean DSC = 0.83 and 0.79 for the training and validation datasets, respectively). The median (interquartile range) DSC of the test dataset model was 0.81 (0.70-0.88). Radiomics features extracted from manually and automatically segmented BC exhibited good reproducibility. Thus, our U-net model performed highly accurate segmentation of BC, and radiomics features extracted from the automatic segmentation results exhibited high reproducibility.

Risk Stratification for Pregnancies Diagnosed With Fetal Growth Restriction Based on Placental MRI.

BACKGROUND: Diagnosis of fetal growth restriction (FGR) entails difficulties with differentiating fetuses not fulfilling their growth potential because of pathologic conditions, such as placental insufficiency, from constitutionally small fetuses. The feasibility of placental MRI for risk stratification among pregnancies diagnosed with FGR remains unexplored. PURPOSE: To explore quantitative MRI features useful to identify pregnancies with unfavorable outcomes and to assess the diagnostic performance of visual analysis of MRI to detect pregnancies with unfavorable outcomes, among pregnancies diagnosed with FGR. STUDY TYPE: Retrospective. POPULATION: Thirteen pregnancies with unfavorable outcomes (preterm emergency cesarean section or intrauterine fetal death) and 11 pregnancies with favorable outcomes performed MRI at gestational weeks 21-36. FIELD STRENGTH/SEQUENCE: A 5-T, half-Fourier-acquired single-shot turbo spin echo (HASTE), spin-echo echo-planar imaging (SE-EPI) and T2 map derived from SE-EPI. ASSESSMENT: Placental size on HASTE sequences and T2 mapping-based histogram features were extracted. Three radiologists qualitatively evaluated the visibility of maternal cotyledon on HASTE and SE-EPI sequences with echo times (TEs) = 60, 90, and 120 msec using 3-point Likert scales: 0, absent; 1, equivocal; and 2, present. STATISTICAL TESTS: Welch's t-test or Mann-Whitney U test for quantitative features between the favorable and unfavorable outcome groups. Areas under the receiver operating curves (AUCs) of the three readers' visual analyses to detect pregnancies with unfavorable outcomes. A P value of <0.05 was inferred as statistically significant. RESULTS: Placental size (major and minor axis, estimated area of placental bed, and volume of placenta) and T2 mapping-based histogram features (mean, skewness, and kurtosis) were statistically significantly different between the two groups. Visual analysis of HASTE and SE-EPI with TE = 60 msec showed AUCs of 0.80-0.86 to detect pregnancies with unfavorable outcomes. DATA CONCLUSION: Placental size, histogram features, and visual analysis of placental MRI may allow for risk stratification regarding outcomes among pregnancies diagnosed with FGR. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

MR findings of polypoid endometriosis of female genital organs: report of three cases.

Polypoid endometriosis is a benign, rare variant of endometriosis that forms polypoid nodules mimicking malignant tumors. For three cases of polypoid endometriosis of female genital organs, this report presents characteristic MR imaging features reflecting the histopathological findings. The solid and microcystic pattern or the multilocular pattern both reflecting dilated endometrial glands, and characteristic morphology of the nodules, multilobulated or polypoid-shaped, were helpful diagnostic clues present in these three cases. Earlier reported MR findings were also recognized, including signal intensity similar to that of the endometrium on T2-weighted image and contrast enhanced T1-weighted image, hypointense rim on T2-weighted image, lack of diffusion restriction, and hyperintense foci on T1-weighted image. Two cases were diagnosed preoperatively based on MR imaging findings as polypoid endometriosis. Fertility-preserving treatment was administered for one patient. Preoperative inference of polypoid endometriosis from MR imaging can avoid overtreatment and lead to fertility preservation.

Radiomic machine learning for pretreatment assessment of prognostic risk factors for endometrial cancer and its effects on radiologists' decisions of deep myometrial invasion.

PURPOSE: To evaluate radiomic machine learning (ML) classifiers based on multiparametric magnetic resonance images (MRI) in pretreatment assessment of endometrial cancer (EC) risk factors and to examine effects on radiologists' interpretation of deep myometrial invasion (dMI). METHODS: This retrospective study examined 200 consecutive patients with EC during January 2004 -March 2017, divided randomly to Discovery (n = 150) and Test (n = 50) datasets. Radiomic features of tumors were extracted from T2-weighted images, apparent diffusion coefficient map, and contrast enhanced T1-weighed images. Using the Discovery dataset, feature selection and hyperparameter tuning for XGBoost were performed. Ten classifiers were built to predict dMI, histological grade, lymphovascular invasion (LVI), and pelvic/paraaortic lymph node metastasis (PLNM/PALNM), respectively. Using the Test dataset, the diagnostic performances of ten classifiers were assessed by the area under the receiver operator characteristic curve (AUC). Next, four radiologists assessed dMI independently using MRI with a Likert scale before and after referring to inference of the ML classifier for the Test dataset. Then, AUCs obtained before and after reference were compared. RESULTS: In the Test dataset, mean AUC of ML classifiers for dMI, histological grade, LVI, PLNM, and PALNM were 0.83, 0.77, 0.81, 0.72, and 0.82. AUCs of all radiologists for dMI (0.83-0.88) were better than or equal to mean AUC of the ML classifier, which showed no statistically significant difference before and after the reference. CONCLUSION: Radiomic classifiers showed promise for pretreatment assessment of EC risk factors. Radiologists' inferences outperformed the ML classifier for dMI and showed no improvement by review.

Diagnostic Value of DCE-MRI for Differentiating Malignant Adnexal Masses Compared with Contrast-enhanced-T1WI.

PURPOSE: To compare the diagnostic performance of dynamic contrast-enhanced-MR (DCE-MR) and delayed contrast-enhanced (CE)-MRI added to unenhanced MRI, including diffusion weighted image (DWI) for differentiating malignant adnexal tumors, conducting a retrospective blinded image interpretation study. METHODS: Data of 80 patients suspected of having adnexal tumors by ultrasonography between April 2008 and August 2018 were used for the study. All patients had undergone preoperative MRI and surgical resection at our institution. Four radiologists (two specialized in gynecological radiology and two non-specialized) were enrolled for blinded review of the MR images. A 3-point scale was used: 0 = benign, 1 = indeterminate, and 2 = malignant. Three imaging sets were reviewed: Set A, unenhanced MRI including DWI; Set B, Set A and delayed CE-T1WI; and Set C, Set A and DCE-MRI. Imaging criteria for benign and malignant tumors were given in earlier reports. The diagnostic performance of the three imaging sets of the four readers was calculated. Their areas under the curve (AUCs) were compared using the DeLong method. RESULTS: Accuracies of Set B were 81%-88%. Those of Set C were 81%-85%. The AUCs of Set B were 0.83 and 0.89. Those of Set C were 0.81-0.86. For two readers, Set A showed lower accuracy and AUC than Set B/Set C (less than 0.80), although those were equivalent in other readers. No significant difference in AUCs was found among the three sequence sets. Intrareader agreement was moderate to almost perfect in Sets A and B, and substantial to almost perfect in Set C. CONCLUSION: DCE-MR showed no superiority for differentiating malignant adnexal tumors from benign tumors compared to delayed CE-T1WI with conventional MR and DWI.

Diagnostic Accuracy of Magnetic Resonance Imaging for International Federation of Gynecology and Obstetrics 2018 IB to IIB Cervical Cancer Staging: Comparison Among Magnetic Resonance Sequences and Pathologies.

OBJECTIVE: This study aimed to investigate the most accurate magnetic resonance (MR) sequence for tumor detection, maximal tumor diameter, and parametrial invasion compared with histopathologic diagnoses. METHODS: Fifty-one patients with International Federation of Gynecology and Obstetrics 2018 IB1 to IIB cervical cancer underwent preoperative MR imaging and surgical resection. Two radiologists independently evaluated the tumor detection, parametrial invasion, and tumor size in each of T2-weighted image, diffusion-weighted image, and contrast-enhanced T1-weighted image. Results obtained for squamous cell carcinoma (SCC) and adenocarcinoma were also compared. RESULTS: Neither the tumor detection rate nor parametrial invasion was found to be significantly different among sequences. Tumor size assessment using MR imaging with pathology showed good correlation: r = 0.63-0.72. The adenocarcinoma size tended to be more underestimated than SCC in comparison with the pathologic specimen. CONCLUSIONS: Cervical cancer staging by MR images showed no significant difference among T2-weighted image, diffusion-weighted image, and contrast-enhanced T1-weighted image. Adenocarcinoma was prone to be measured as smaller than the pathologic specimen compared with SCC.

New Linked-Wire-Type External Fixator (the Ichi-Fixator System) for Metacarpal Fractures: Case Series and Literature Review.

Background: External fixator is an effective treatment option in the comminuted or unstable metacarpal fractures. The new linked-wire type of external fixator (the Ichi-Fixator System) developed for hand and wrist fractures enables fine adjustment of the fixation under fluoroscopic inspection through small screws inside the fixator fitted externally. This technique is designed to reinforce the stability and rigidity of conventional percutaneous Kirchner wire fixation. The aim of this study is to assess the effectiveness of the fixator for comminuted or unstable metacarpal fractures through the evaluation of short-term results in ten cases. Methods: Patients were fixated with fixator pins and metal clamps using the Ichi-Fixator System. All patients were then examined for post-operative complications, functional recovery, visual analogue scale (VAS) score, and the Quick Disabilities of the Arm, Shoulder, and Hand (Q-DASH) score at the end of the final follow-up consultation. Results: Operative treatment using the Ichi-Fixator System facilitates anatomical reduction and allows immediate full mobilization, producing good outcomes. No infections were observed in all cases, including those at pin insertion sites. There were no implant failure and nonunion. Patients could perform all routine activities with normal grip strength and retained a full range of hand motion without pain. This treatment method with improved postoperative comfort would allow immediate return to work, which would clearly boost patient satisfaction. Conclusions: Ichi-Fixator System is considered to be useful for the treatment of metacarpal fractures, and this will provide a new surgical option for all hand fractures.

Automatic segmentation of uterine endometrial cancer on multi-sequence MRI using a convolutional neural network.

Endometrial cancer (EC) is the most common gynecological tumor in developed countries, and preoperative risk stratification is essential for personalized medicine. There have been several radiomics studies for noninvasive risk stratification of EC using MRI. Although tumor segmentation is usually necessary for these studies, manual segmentation is not only labor-intensive but may also be subjective. Therefore, our study aimed to perform the automatic segmentation of EC on MRI with a convolutional neural network. The effect of the input image sequence and batch size on the segmentation performance was also investigated. Of 200 patients with EC, 180 patients were used for training the modified U-net model; 20 patients for testing the segmentation performance and the robustness of automatically extracted radiomics features. Using multi-sequence images and larger batch size was effective for improving segmentation accuracy. The mean Dice similarity coefficient, sensitivity, and positive predictive value of our model for the test set were 0.806, 0.816, and 0.834, respectively. The robustness of automatically extracted first-order and shape-based features was high (median ICC = 0.86 and 0.96, respectively). Other high-order features presented moderate-high robustness (median ICC = 0.57-0.93). Our model could automatically segment EC on MRI and extract radiomics features with high reliability.

Diagnostic performance of preoperative MR imaging findings for differentiation of uterine leiomyoma with intraligamentous growth from subserosal leiomyoma.

PURPOSE: To evaluate the diagnostic performance of MRI findings for differentiating uterine leiomyoma with intraligamentous growth, or broad ligament fibroid, from subserosal leiomyoma. METHODS: This study included 37 patients with surgically confirmed uterine smooth muscle tumors (36 leiomyomas and one smooth muscle tumor of uncertain malignant potential) with intraligamentous growth (IL) and size-matched control of 37 patients with subserosal leiomyoma (SS). Two radiologists independently evaluated eight preoperative MRI findings: tumor shape, degeneration, attachment to uterus, ovary elevation, ureter displacement, bladder deformation, rectal displacement, and separation of round ligament (RL) and uterine artery (UA). The diagnostic values of these findings and interobserver agreement were assessed. Receiver-operating characteristic (ROC) analysis of the number of positive MRI findings for diagnosing IL was performed. Clinical outcomes including surgical method, operation time, intraoperative blood loss, perioperative complications, and postoperative hospital stay of the two groups were compared. RESULTS: Significant differences in tumor shape, attachment to uterus, ovary elevation, ureter displacement, and separation of RL and UA were found between IL and SS. Four of these findings, excluding ureter displacement, showed moderate to substantial interobserver agreement. When two or more of these four findings were positive, sensitivity, specificity, and area under the ROC curve were 91%, 77%, 0.90 in reader 1 and 82%, 89%, 0.91 in reader 2. The operation time was significantly longer for IL than for SS. CONCLUSION: Tumor shape, attachment to uterus, ovary elevation, and separation of RL and UA are useful MRI findings for differentiating intraligamentous leiomyoma from subserosal leiomyoma.

Effect of long-term clarithromycin therapy on prevention of pneumonia in older adults: A randomized, controlled trial.

AIM: Pneumonia in older adults is increasingly recognized as a healthcare issue in countries with an aging population. Long-term macrolide therapy reduces exacerbations of chronic respiratory diseases, but its effects on the prevention of pneumonia have not been determined. METHODS: We carried out a randomized, controlled trial to test the effect of long-term clarithromycin therapy on the prevention of pneumonia among older adults. People aged ≥65 years who had recovered from pneumonia within the previous 3 months were recruited and randomly allocated to a long-term, low-dose clarithromycin (CAM) therapy group (n = 13) or a control group (n = 15). RESULTS: Both groups were followed up until recurrence of pneumonia. The median follow-up period was 251 days (95% CI 171-330) in the CAM group and 132 days (95% CI 67-196) in the control group (P = 0.627). The recurrence rate of pneumonia was two out of 13 (15%) in the CAM group and five out of 15 (33%) in the control group (P = 0.268). The median time to recurrence of pneumonia was 315 days (95% CI 249-382) in the CAM group and 260 days (95% CI 184-335) in the control group (P = 0.260). None of the differences between groups were statistically significant. CONCLUSIONS: No statistically significant suppressive effects of long-term, low-dose macrolide therapy on the development of pneumonia among older people were found in this small sample. A large-scale, randomized, controlled study is required. Geriatr Gerontol Int 2019; 19: 1006-1009.

MR findings of uterine PEComa in patients with tuberous sclerosis: report of two cases.

Tuberous sclerosis complex (TSC), a rare autosomal dominant neurocutaneous disorder, is characterized by the presence of benign congenital tumors in multiple organs. Neoplasms with perivascular epithelioid cell differentiation (PEComas), including angiomyolipoma (AML) and lymphangioleiomyomatosis (LAM), can occur in association with TSC. This report describes two cases of uterine PEComas presenting characteristic MR imaging features reflecting pathological findings. From MR images, both cases showed single or multiple large, irregularly shaped or lobulated hemorrhagic lesions within the myometrium. They differed from typical adenomyotic cysts in their large size and irregular margins. Histopathologic analysis revealed that the hemorrhage was caused by adenomyosis and tumor cells that proliferated in surrounding stroma of the hemorrhagic lesions, compatible with PEComas. Microscopic observation revealed an infiltrative growth pattern of PEComas, with small nodules formed. The tumor lesions, however, were difficult to detect on MR images. The myometrium showed normal appearance on both T1-weighted and T2-weighted images in both cases. We speculate that PEComas may infiltrate extensively into the myometrium even when the myometrium shows almost normal radiologic appearance.

The number of CD34+CD133+ hematopoietic stem cells residing in umbilical cord blood (UCB) units is not correlated with the numbers of total nucleated cells and CD34+ cells: a possible new indicator for quality evaluation of UCB units.

Umbilical cord blood transplantation (UCBT) is often associated with delayed neutrophil and platelet recovery. Engraftment failure is another major obstacle. Several factors influence these serious complications, including the numbers of total nucleated cells (TNCs) and CD34+ cells which have been used as reliable factors for selecting UCB units for transplantation. However, whether both factors are reliable indices of the hematopoietic stem cell (HSC) activity of UCB units remains unknown. To evaluate the quality of UCB units, we quantified the actual number of transplantable CD34+CD133+ HSCs (tHSCs) residing in UCB units. The number of tHSCs was not correlated with the numbers of TNCs or CD34+ cells. These results strongly suggest that neither factor reflects the numbers of tHSCs residing in UCB units. To validate the significance of the number of tHSCs, further analysis is required to determine whether the number of tHSCs residing in UCB units is useful as a new indicator for the quality assessment of UCB units.

Sub-minimum inhibitory concentrations of ceftazidime inhibit Pseudomonas aeruginosa biofilm formation.

Pseudomonas aeruginosa exhibits the biofilm mode of growth and causes chronic as well as acute infections in humans. Several reports have shown that the treatments with sub-minimum inhibitory concentrations (sub-MICs) of antimicrobial agents influence biofilm formation by P. aeruginosa. The antibiotic ceftazidime (CAZ) is used to treat P. aeruginosa infections, but few studies have examined the effects of ß-lactams on biofilm formation by P. aeruginosa. In this study, we investigated the role of sub-MICs of CAZ in the formation of P. aeruginosa biofilms. 1/4 × MIC CAZ reduced the biofilm volume of P. aeruginosa PAO1, as quantified by crystal violet staining. The formation of P. aeruginosa PAO1 biofilms treated with 1/4 × MIC CAZ were observed by confocal laser scanning microscopy. They were more heterogeneous than the PAO1 biofilms without CAZ treatment. Furthermore, sub-MICs of CAZ inhibited the twitching motility, which played an important role in mature biofilm formation. 1/4 × MIC CAZ also reduced the gene expressions of lecA, lecB, pel and psl, which mediate the adhesion and polysaccharide matrix synthesis of P. aeruginosa. These effects suggest that sub-MICs of CAZ may affect a number of stages of biofilm formation. Investigating the effects of sub-MIC antibiotics on targeted bacterial biofilm may lead to the development of future antibiotic treatment modalities.

Effect of interferon-based and -free therapy on early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C.

BACKGROUND AND AIMS: Although treatment for hepatitis C virus has been dramatically improved by the development of direct-acting antiviral agents (DAAs), whether interferon (IFN)-free therapy reduces hepatocarcinogenesis in an equivalent manner to IFN-based therapy remains controversial. The aims of this study were to evaluate the occurrence and recurrence of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients treated with DAAs and to identify biomarkers of HCC development after antiviral treatment. METHODS: A restrospective review of a prospective database of 1,897 CHC patients who were treated with IFN-based (1,145) or IFN-free therapies (752) was carried out. Cumulative HCC occurrence and recurrence rates were compared using propensity score-matched analysis. Predictors of HCC development after viral eradication were identified by multivariate analysis. RESULTS: Propensity score-matched analysis showed no significant difference in HCC occurrence (p=0.49) and recurrence rates (p=0.54) between groups treated with IFN-based or IFN-free therapies. In multivariate analysis, higher levels of post-treatment α-fetoprotein (AFP) or Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA+M2BP) were independently associated with HCC occurrence and recurrence after viral eradication. Only post-treatment WFA+M2BP level was significantly associated with HCC occurrence and recurrence among patients without severe fibrosis. The area under the receiver operating characteristic (ROC) curve for WFA+M2BP levels was greater than that for AFP levels in ROC analysis. CONCLUSION: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy. Patients with high WFA+M2BP levels after antiviral treatment, even without severe fibrosis, must be followed up carefully for HCC development. Lay summary: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy.

ITPA gene variation and ribavirin-induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin.

AIM: Sofosbuvir (SOF) and ribavirin (RBV) combination therapy produces a sustained response in many patients with genotype 2 chronic hepatitis C. However, RBV-induced anemia is a troublesome side-effect that may limit this treatment. Genetic variation leading to inosine triphosphatase (ITPA) deficiency is known to protect against RBV-induced hemolytic anemia. This study aimed to evaluate the relationships between the efficacy and safety of SOF/RBV treatment and ITPA gene variants. METHODS: Ninety patients with genotype 2 chronic hepatitis C treated with SOF/RBV were studied. The relationships among genetic polymorphisms of ITPA and the decline in hemoglobin levels from baseline, RBV dose reduction, and sustained virological response (SVR) rates were analyzed. RESULTS: Overall SVR at 12 weeks was 94.4% (85/90). Patients with the ITPA CA/AA genotypes had a lower degree of anemia throughout the therapy than those with the ITPA CC genotype. The percentage of patients requiring RBV dose reduction was significantly lower for those with the ITPA CA/AA variation, a difference even more apparent when the pretreatment hemoglobin level was <12 g/dL. The dose reduction of RBV and serum albumin level were significantly associated with SVR. CONCLUSIONS: Patients with the ITPA CA/AA genotype were less likely to develop anemia than those with the ITPA CC genotype and were more likely to complete SOF/RBV therapy. These results may provide a valuable pharmacogenetic diagnostic tool to predict drug-induced adverse events, particularly in patients with pre-existing anemia.