Clinical evaluation and surgical intervention for diaphragmatic eventration mimicking peritoneopericardial hernia in a cat.

A 2-year-old spayed female British Shorthair cat presented with an increased frequency and duration of cough since infant period. Based on radiographic, ultrasonographic, and computed tomography findings, peritoneopericardial diaphragmatic hernia was considered so that repair surgery was planned. During celiotomy, lax diaphragm was identified instead of defect. Transabdominal diaphragmatic plication was performed to resolve lax diaphragm and to prevent recurrence by overlapping relatively normal part of diaphragm. Diagnosed with diaphragmatic eventration postoperatively, the cat showed improvement in clinical signs and imaging results. Transabdominal diaphragmatic plication is a suitable treatment; the patient maintained normally during a 14-month follow-up period.

Treatment outcome and long-term stability of orthognathic surgery for facial asymmetry: A systematic review and meta-analysis.

Objective: : This systematic review aimed to provide a comparative analysis of the treatment outcomes, including hard and soft tissues, postoperative stability, temporomandibular disorders (TMD), and quality of life (QoL), in patients with facial asymmetry who underwent orthognathic surgery. Methods: : The primary objective was to address the question, "How do different factors related to surgery affect the outcomes and stability of orthognathic surgery in the correction of facial asymmetry?" A meta-analysis was conducted on the outcome parameters, such as skeletal, dental, and soft tissue symmetry, TMD, QoL, and relapse, using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Subgroup analyses were conducted considering surgery-related factors such as surgical techniques (one-jaw vs. two-jaw), use of the surgery-first approach, utilization of computer simulation, and analytical methods employed to evaluate asymmetry (2D vs. 3D). Results: : Forty-nine articles met the inclusion criteria. The meta-analysis demonstrated a significant improvement in the symmetry of hard and soft tissues. The subgroup analysis indicated that the treatment outcomes showed significant improvement, regardless of the factors related to surgery. Changes in TMD signs and symptoms varied according to the surgical technique used. Quality of life improved in the facial, oral, and social domains. Skeletal relapse was observed during the follow-up. Conclusions: : Our findings support the positive outcomes of orthognathic surgery in the treatment of facial asymmetry in terms of skeletal and soft tissue improvements, stability, relief of TMD symptoms, and enhancement of QoL. However, most of the included studies showed a low certainty of evidence and high heterogeneity.

Current status of laparoscopic emergency surgery in Korea: multicenter restrospective cohort study.

Purpose: Laparoscopic surgery is a choice in several emergency settings. However, there has been no nationwide study or survey that has compared the clinical use of laparoscopic emergency surgery (LES) versus open abdominal emergency surgery (OES) in Korea. Therefore, we examined the state of LES across multiple centers in Korea and further compared this data with the global state based on published reports. Methods: Data of 2,122 patients who received abdominal emergency surgery between 2014 and 2019 in three hospitals in Korea were collected and retrospectively analyzed. Several clinical factors were investigated and analyzed. Results: Of the patients, 1,280 (60.3%) were in the OES group and 842 (39.7%) were in the LES group. The most commonly operated organ in OES was the small bowel (25.8%), whereas that for LES was the appendix. In appendectomy and cholecystectomy, 93.7% and 88.0% were in the LES group. In small bowel surgery, gastric surgery, and large bowel surgery, 89.4%, 92.0%, and 79.1% were in the OES group. The severity-related factors of patient status demonstrated statistically significant limiting factors of selection between LES and OES. Conclusion: Although our study has several limitations, compared to the LES data from other countries, the general LES state was similar in appendectomies, cholecystectomies, and small bowel surgeries. However, in gastric and colorectal surgeries, the LES state was different from those of other countries. This study demonstrated the LES state and limiting factors of selection between LES and OES in various operated organs. Further studies are required to analyze these differences and the various limiting factors.

Enhanced extraction of bioactive compounds from propolis (Apis mellifera L.) using subcritical water.

The bioactive compounds and antioxidant activities of propolis extracts were investigated using subcritical water extraction (SWE). SWE was performed by varying temperature (110-200 °C) and time (10-30 min). SWE using only water as solvent successfully to extracted bioactive compounds from propolis using high-purity glass thimbles. The concentrations of galangin (16.37 ± 0.61 mg/g), and chrysin (7.66 ± 0.64 mg/g) were maximal at 200 °C for 20 min, and 170 °C for 20 min, respectively. The antioxidative properties from propolis increased with the increasing extraction temperature and extraction time on SWE. The maximum yields of the total phenolics (226.37 ± 4.37 mg/g), flavonoids (70.28 ± 1.33 mg/g), and antioxidant activities (88.73 ± 0.58%, 98.86 ± 0.69%, and 858.89 ± 11.48 mg/g) were obtained at 200 °C for 20 min. Compared with using ethanol extraction (at 25 °C for 24 h, total phenolics = 176.28 ± 0.35, flavonoids = 56.41 ± 0.65, antioxidant activities = 72.74 ± 0.41%, 95.18 ± 0.11%, 619.51 ± 8.17 mg/g), all yields of SWE extracts obtained at 200 °C for 20 min were higher. SWE is suitable for a much faster and more efficient method extracting bioactive compounds from propolis compared to traditional extraction method.

Thermal conversion kinetics and solubility of soy isoflavones in subcritical water extraction.

The conversion of isoflavones during subcritical water extraction were studied using first-order reaction kinetics modeling. Isoflavones were extracted from soybean using temperatures from 100℃ to 180℃ for 3 to 30 min. It was found that malonylgenistin was the most thermally unstable, with little being detected above 100℃. The optimal extraction temperatures for acetylgenistin (AG), genistin (G), and genistein (GE) were 120℃, 150℃, and 180℃, respectively. A larger sum of the numbers of both hydroxyl groups and oxygen molecules was associated with a lower melting point and optimal extraction temperature. Kinetics modeling of reaction rate constant k and activation energy Ea showed that all of the reaction rates tended to increase with temperature, with the relationship fitted well by a first-order model in nonlinear regression. For temperatures between 100℃ and 150℃, AG â†’ G and AG â†’ GE conversions showed the highest rate constants, but G â†’ GE and G â†’ D3 (degraded G) conversions became dominant at 180℃. Chemical compounds studied in this article: genistein (PubChem CID: 5280961), genistin (PubChem CID: 5281377), 6″-O-malonylgenistin (PubChem CID: 15934091), 6″-O-acetylgenistin (PubChem CID: 5315831).

The Incidence and Care Cascade of the Hepatitis C Virus in Korea.

Background/Aims: The 2030 hepatitis C virus (HCV) elimination targets of the World Health Organization are an 80% reduction in incidence and 65% reduction in mortality compared to the 2015 rates. However, information on the nationwide incidence and treatment rates of HCV infection are limited. We aimed to investigate the nationwide incidence and status of the care cascade for HCV infection in Korea. Methods: This study used data from the Korea Disease Control and Prevention Agency linked with the data of the Korea National Health Insurance Service. Linkage to care was defined as visiting hospitals twice or more due to HCV infection within 1.5 years of the index date. The treatment rate was the number who had been prescribed antiviral medication within 1.5 years from the index date out of patients newly diagnosed with HCV. Results: The new HCV infection rate was 17.2 per 100,000 person-years (n=8,810) in 2019. The number of new HCV infections was the highest in patients aged 50 to 59 years (n=2,480), and the new HCV infection rate significantly increased with age (p<0.001). Among newly infected patients with HCV, the linkage to care rate was 78.2% (78.2% men, 78.2% women) and the treatment rate was 58.1% (56.8% men, 59.3% women) within 1.5 years. Conclusions: The new HCV infection rate was 17.2 per 100,000 person-years in Korea. It is necessary to continuously monitor the incidence and care cascade of HCV to establish proper strategies to reach the goal of HCV elimination by 2030.

Clinical effect and safety of thread embedding acupuncture on facial nerve palsy sequelae: A retrospective observational study.

The purpose of this study was to investigate the clinical effect and safety of thread embedding acupuncture (TEA) in patients with facial nerve palsy sequelae. This was a retrospective observational study on 82 patients treated with TEA from January 2021 to May 2022. The Facial Disability Index (FDI) reported by patients and Sunnybrook Facial Grading System scores assessed by clinical practitioners were used to evaluate the intensity of facial movements, functional problems, and psychosocial status. One-way repeated measure analysis of variance showed that the Sunnybrook Facial Grading System scores improved significantly following the 2nd to 6th TEA treatments (Txs). FDI scores also showed significant increases except for the 4th Tx. Additionally, the physical scores improved significantly among the subscales of FDI, but the social/well-being scores did not. There were no reported serious adverse events or adverse events requiring medical Tx. TEA is a safe Tx that has a clinically cumulative effect, in terms of patient-oriented self-assessment of functional problems and objective facial movements, for treating facial nerve palsy sequelae.

Direct-Acting Antivirals and the Risk of Hepatitis B Reactivation in Hepatitis B and C Co-Infected Patients: A Systematic Review and Meta-Analysis.

Hepatitis B (HBV) reactivation was observed to be more than 10% in patients receiving interferon-based therapy for hepatitis C (HCV) co-infection. At present, when direct-acting antiviral (DAA) has become the main treatment for HCV, there are few large-scale studies on the reactivation of HBV in these population. We studied HBV reactivation risk and prophylactic HBV treatment efficacy in HBV/HCV co-infected patients receiving DAA therapy. Relevant studies were selected from the Ovid-Medline, Ovid-EMBASE, Cochrane Central Register of Controlled Trials, KoreaMed, KMbase, and RISS databases through 4 September 2020. Data pooling was carried out using the random-effects method. We identified 39 articles with 119,484 patients with chronic (n = 1673) or resolved (n = 13,497) HBV infection under DAA therapy. When the studies were pooled, the HBV reactivation rate was 12% (95% confidence interval (CI) 6-19, I2 = 87%), indicating that this population needs careful attention. When stratified by baseline HBV DNA, the undetectable HBV DNA group showed a significantly lower risk of reactivation than the detectable HBV DNA group (odds ratio (OR) 0.30, 95% CI 0.11-0.86, I2 = 0%). Prophylactic HBV therapy reduced HBV reactivation risk (OR 0.25, 95% CI 0.07-0.92, I2 = 0%). Patients with a resolved HBV infection showed a negligible rate (0.4%) of HBV reactivation. In conclusion, patients with detectable HBV DNA levels warrant careful monitoring for HBV reactivation and may benefit from preventive anti-HBV treatment.

Direct-Acting Antivirals for HCV Treatment in Decompensated Liver Cirrhosis Patients: A Systematic Review and Meta-Analysis.

DAA therapy is known to clear hepatitis C virus infection in patients with decompensated cirrhosis (DC). However, the safety and benefits of DAA in DC remain unclear, especially with the use of protease inhibitors (PI). Therefore, we evaluated the efficacy and clinical safety of DAA in DC patients and observed whether there was a discrepancy between PI-based and non-PI-based treatment. We searched Ovid-Medline, Ovid-EMBASE, Cochrane Library, and three local medical databases through October 2021 to identify relevant studies on the clinical safety and effectiveness of DAA in DC patients. The outcomes were sustained virologic response (SVR), overall mortality, the incidence rate of hepatocellular carcinoma (HCC), adverse events, improvement or deterioration of liver function, and delisting from liver transplantation (LT). Two independent reviewers extracted the data from each study using a standardized form. The pooled event rate in DC patients and relative effect (odds ratio (OR)) of PI-treated versus non-PI-based DAA in DC patients were calculated using a random-effects model. In patients with DC, the SVR rate was 86% (95% CI 83-88%), the development of HCC 7% (95% CI 5-9%), and mortality 6% (95% CI 4-8%). Improvement in liver function was observed in 51% (95% CI 44-58%) of patients, and 16% (95% CI 5-40%) were delisted from LT. PI-based treatment showed a similar rate of serious adverse events (23% vs. 18%), HCC occurrence (5% vs. 7%), and mortality (5% vs. 6%) to that of non-PI-based DAA treatment in DC patients. HCC occurrence and mortality rates were low in patients with DC following DAA treatment. PI-based treatment in DC patients was relatively safe when compared to non-PI-based treatment. Overall, DAA improved liver function, which may have allowed for delisting from LT.

Enhanced delivery to brain using sonosensitive liposome and microbubble with focused ultrasound.

Glioblastoma is considered one of the most aggressive and dangerous brain tumors. However, treatment of GBM has been still challenged due to blood-brain barrier (BBB). BBB prevents that the chemotherapeutic molecules are extravasated to brain. In this study, sonosensitive liposome encapsulating doxorubicin (DOX) was developed for enhancement of GBM penetration in combination with focused ultrasound (FUS) and microbubbles. Upon ultrasound (US) irradiation, microbubbles induce cavitation resulting in the tight junction of BBB endothelium to temporarily open. In addition, the composition of sonosensitive liposome was optimized by comparison of sonosensitivity and intracellular uptake to U87MG cells. The optimal sonosensitive liposome, IMP301-DC, resulted 123.9 ± 38.2 nm in size distribution and 98.2 % in loading efficiency. Related to sonosensitivity of IMP301-DC, US-triggered release ratio of doxorubicin was 69.2 ± 12.3 % at 92 W/cm2 of US intensity for 1 min. In the in vivo experiments, the accumulation of DiD fluorescence probe labeled IMP301-DC-shell in the brain through the BBB opening was increased more than two-fold compared to that of Doxil-shell, non-sonosensitive liposome. US exposure significantly increased GBM cytotoxicity of IMP301-DC. In conclusion, this study demonstrated that IMP301-DC could serve as an alternative solution to enhance the penetration to GBM treatment via BBB opening by non-invasive FUS combined with microbubbles.

Ultrasound-Responsive Liposomes for Targeted Drug Delivery Combined with Focused Ultrasound.

Chemotherapeutic drugs are traditionally used for the treatment of cancer. However, chemodrugs generally induce side effects and decrease anticancer effects due to indiscriminate diffusion and poor drug delivery. To overcome these limitations of chemotherapy, in this study, ultrasound-responsive liposomes were fabricated and used as drug carriers for delivering the anticancer drug doxorubicin, which was able to induce cancer cell death. The ultrasound-sensitive liposome demonstrated a size distribution of 81.94 nm, and the entrapment efficiency of doxorubicin was 97.1 ± 1.44%. The release of doxorubicin under the ultrasound irradiation was 60% on continuous wave and 50% by optimizing the focused ultrasound conditions. In vivo fluorescence live imaging was used to visualize the doxorubicin release in the MDA-MB-231 xenografted mouse, and it was demonstrated that liposomal drugs were released in response to ultrasound irradiation of the tissue. The combination of ultrasound and liposomes suppressed tumor growth over 56% more than liposomes without ultrasound exposure and 98% more than the control group. In conclusion, this study provides a potential alternative for overcoming the previous limitations of chemotherapeutics.

Application of Pulsed Electric Field as a Pre-Treatment for Subcritical Water Extraction of Quercetin from Onion Skin.

Pulsed electric field (PEF) treatment promotes the electroporation of biological membranes, and if included as a pre-treatment, could improve the extraction of certain constituents therefrom. The aim of this study was to determine the optimal extraction conditions for extracting the flavonoid quercetin from dried onion skin and to establish whether the yield could be enhanced by combining PEF pre-treatment with an eco-friendly extraction method that uses subcritical water extraction (SWE). Samples of onion skin were treated with PEF under conditions of varying electric field strength (0.5-2.5 kV/cm) and duration (5-120 s). SWE was then performed with an extraction time of 15 min and at temperatures ranging from 105 °C to 185 °C. Among the conditions tested, the yield of total quercetin was the highest after pretreatment with PEF at 2.5 kV/cm for 15 s, followed by SWE at 145 °C for 15 min (yield 19.25 ± 0.77 mg/g dried onion skin, mean ± standard deviation). Pretreatment with PEF improved the yield of total quercetin extracted by 33.22% compared with the PEF-untreated samples. These findings demonstrate that pretreatment of onion skin with PEF has the potential to improve flavonoid extraction.

Extraction characteristics and hydrolysis of flavoring compounds of cinnamon (Cinnamomum zeylanicum) under subcritical-water conditions.

Subcritical water extraction (SWE) of four flavoring compounds from cinnamon was performed at various temperatures and for various extraction times. The extraction temperature (°C) and time (min) corresponding to the maximum content of flavoring compounds were 190 °C and 5 min for cinnamyl alcohol, 200 °C and 20 min for cinnamic acid, 130 °C and 10 min for cinnamaldehyde, and 170 °C and 20 min for coumarin, respectively. Cinnamaldehyde underwent structural conversion to benzaldehyde via hydrolysis at high temperatures, and the rate of conversion rapidly increased above 150 °C. The extraction efficiency using subcritical water was slightly higher or comparable to that using conventional extractants. SWE is a potential and highly selectivity technology for extracting flavoring compounds from cinnamon.

Efficacy and safety of direct-acting antiviral therapy for hepatitis C virus in elderly patients (≥65 years old): A systematic review and meta-analysis.

Direct-acting agents (DAAs) have launched a new era of hepatitis C virus (HCV) treatment. As aged individuals comprise a large percentage of HCV-infected patients, the effectiveness and safety of DAAs in the elderly have come under scrutiny. This meta-analysis aimed to evaluate the efficacy and safety of DAAs in elderly patients. After a systematic search in PubMed (MEDLINE), Embase, OVID MEDLINE, the Cochrane Library and other databases, two investigators reviewed relevant abstracts and selected manuscripts for examination. The sustained virologic response (SVR) and adverse event (AE) rates were calculated with a random-effects model. Ninety studies evaluating SVR rates of elderly patients (≥65 years old) receiving DAAs were selected. DAAs in elderly patients exhibited a notable SVR rate of 96% (95% confidence interval [CI]: 95%-97%), accompanied by comparable rates in subgroup analyses. The comparison of SVR rates in elderly and non-elderly patients indicated no significant discrepancy (odds ratio [OR] 1.01, 95% CI: 1.00-1.01). The overall event rate of AEs was 45% (95% CI: 31%-60%), though AE rates varied by subgroups. Furthermore, AEs were comparatively more frequent (OR 1.15, 95% CI: 1.04-1.28) in the elderly than non-elderly, especially in subgroups such as SAE (OR 1.89, 95% CI: 1.52-2.36) and dose reduction in ribavirin (OR 1.90, 95% CI: 1.53-2.36). However, in the ribavirin (RBV)-free regimen, there was no significant difference in the incidence of AEs between the elderly and non-elderly groups. DAAs have high efficacy in elderly patients. Considering the possibility of AE, the RBV-free regimen should be given prior consideration for the treatment of elderly patients with HCV.

Selective extraction of oxygenated terpene in caraway (Carum carvi L.) using subcritical water extraction (SWE) technique.

Caraway contains terpenes such as carvone, limonene and carveol, that have antibacterial and antifungal properties. Subcritical-water extraction (SWE) can be used to extract terpenes by changing temperature under high pressure. This study evaluated the SWE of terpenes from caraway when varying the extraction conditions of temperature (110 °C-190 °C), time (5-15 min), and particle size (>1000, 850-1000, 425-850, and < 425 µm). The optimal conditions for the extraction of carvone, which determines the quality of caraway, were found to be 170 °C, 15 min, and a particle size of < 425 µm. Also, the carvone yield was much higher when using SWE (28.5 mg/g caraway) than for solvent extraction (20.2 mg/g caraway) and hydrodistillation (19.8 mg/g caraway). The overall results showed that oxygenated terpene like carvone has a high solubility in subcritical water, and nonoxygenated terpene like limonene can partially be converted to carvone via a process of SWE.

Real-World Outcomes of On- vs Off-pump Coronary Bypass Surgery: Result From Korean Nationwide Cohort.

BACKGROUND: Although several randomized trials have shown conflicting results regarding the comparative effectiveness of on- and off-pump coronary artery bypass grafting (CABG), research on long-term outcomes in large-scale, real-world clinical settings are limited. The study sought to examine the comparative effectiveness of on- and off-pump CABG in a real-world clinical setting. METHODS: Using the nationwide claims database of the Korean National Health Insurance Service, the study identified patients who underwent isolated CABG from 2004 to 2013. Propensity-score matching with multivariable adjustment was used to assemble a cohort of patients with similar baseline characteristics. RESULTS: Among 23 828 patients, 12 639 in the off-pump group (53.0%) and 11 189 in the on-pump group (47.0%) were enrolled. After matching, 6483 pairs were included in the final analysis. At 30 days, there was no significant difference in adjusted mortality between the off- and on-pump groups (hazard ratio [HR], 1.00; 95% CI, 0.87-1.16). During long-term follow-up (100% complete; median, 5.3 years; maximum, 13.2 years), however, off-pump CABG was associated with a higher risk of mortality than on-pump CABG (HR, 1.09; 95% CI, 1.03-1.15). The risks of myocardial infarction (HR, 1.3; 95% CI, 1.16-1.45) and repeat revascularization (HR, 1.50; 95% CI, 1.37-1.63) were also significantly higher in the off-pump CABG group than in the on-pump CABG group, whereas the stroke risk was similar between the groups (HR, 0.99; 95% CI, 0.87-1.13). CONCLUSIONS: In this contemporary, nationwide, clinical practice claim registry, off-pump CABG was associated with higher long-term risks of mortality, myocardial infarction, and repeat revascularization than on-pump CABG.

A risk scoring system to predict clinical events in chronic hepatitis B virus infection: A nationwide cohort study.

Many patients with chronic hepatitis B do not receive adequate follow-up. This study aimed to develop a risk score to predict clinical events in patients with chronic hepatitis B virus (HBV) infection at the population level for identifying patients at high risk to warrant regular follow-up. This study analysed population-based data from the nationwide claims database of South Korea obtained between 2005 and 2015. We identified 507,239 non-cirrhotic patients with chronic HBV infection who are not under antiviral treatment. A risk score for predicting clinical events (hepatocellular carcinoma, death or liver transplantation) was developed based on multivariable Cox proportional hazard model in a development cohort (n = 401,745) and validated in a validation cohort (n = 105,494). The cumulative incidence rates of clinical events at 5 years were 2.56% and 2.44% in the development and validation cohorts, respectively. Clinical events in asymptomatic patients with chronic HBV infection (CAP-B) score ranging from 0 to 7.5 points based on age, sex, socioeconomic status, chronic hepatitis C co-infection, diabetes mellitus, statin or antiplatelet exposure, smoking, alcohol consumption, alanine aminotransferase and gamma-glutamyltransferase had good discriminatory accuracy in both the development and validation cohorts (c-indices for 3-, 5- and 10-year risk prediction: all 0.786). The predicted and observed probabilities of clinical events were calibrated in both cohorts. A score of >3.5 points identified subjects at distinctly high risk. The CAP-B score using easily accessible variables can predict clinical events and may allow selection of patients with chronic HBV infection for priority of regular follow-up.

Thermal decomposition and oxidation of ß-caryophyllene in black pepper during subcritical water extraction.

Subcritical water extraction is an efficient technique for extracting components from various plants by changing the polarity of water. ß-caryophyllene is a natural bicyclic sesquiterpene with the highest content found among black pepper essential oils. In this study, the efficiency of extraction and yield of ß-caryophyllene from black pepper were investigated using a subcritical water extraction technique. The optimal conditions of ß-caryophyllene (1.19 ± 0.38 mg/g), and caryophyllene oxide (0.82 ± 0.38 mg/g) were obtained from black pepper under extraction conditions of 170 °C/10 min, and 200 °C/15 min, respectively. As the extraction temperature was increased, ß-caryophyllene oxidation proceeded and the extraction content of caryophyllene oxide increased. It is anticipated that both ß-caryophyllene and caryophyllene oxide with high biological activity can be used to selectively extract compounds using subcritical water extraction, which will be helpful in industrial applications.

Association of aspirin and statin use with the risk of liver cancer in chronic hepatitis B: A nationwide population-based study.

BACKGROUND & AIMS: Aspirin and statins have been suggested to prevent hepatocellular carcinoma (HCC). However, the combined effects of aspirin and statins on HCC risk in patients with chronic hepatitis B (CHB) are not clear. METHODS: A nationwide nested case-control study was performed with data from the National Health Insurance Service gathered between 2005 and 2015 in Korea. In a cohort of 538,135 treatment-naïve, non-cirrhotic patients with CHB, 6,539 HCC cases were matched to 26,156 controls and were analysed by conditional logistic regression. Separate historical cohort studies for each drug were analysed by time-dependent Cox regression as a sensitivity analysis. RESULTS: In the nested case-control study, statins (OR 0.34; 95% CI 0.32-0.37) and aspirin (OR 0.92; 95% CI 0.85-0.99) were significantly associated with a HCC risk reduction. However, dose-dependent risk reduction was observed only with statins. By sensitivity analysis in the historical cohorts, statin users (n = 244,455; HR 0.67; 95% CI 0.66-0.68) and aspirin users (n = 288,777; HR 0.81; 95% CI 0.80-0.82) had significantly lower HCC risk. In the drug-stratified analyses, statins were associated with significantly reduced risk of HCC regardless of aspirin, whereas aspirin did not show such associations. CONCLUSIONS: In this nationwide population-based study of patients with CHB, statin use was consistently associated with a significant and dose-dependent reduction in HCC risk. In contrast, the association between aspirin use and HCC risk reduction was not dose-dependent and was suggested to be confounded by statins.

Tenofovir disoproxil fumarate on the risk of hepatocellular carcinoma in chronic hepatitis B patients with failure to preceding treatments: A nationwide cohort study.

Tenofovir disoproxil fumarate (TDF) monotherapy is recommended for the treatment of chronic hepatitis B (CHB) patients who are refractory to other drugs. Yet, little data are available for the effectiveness of TDF monotherapy compared with TDF-based combination therapy on the risk of hepatocellular carcinoma (HCC) and death/transplantation. This nationwide population-based cohort study included 11,289 CHB patients who initiated TDF rescue therapy after failure of preceding treatments between 2012 and 2014 in Korea. The risks of HCC and death/transplantation were compared between TDF combotherapy (n = 2,499) and TDF monotherapy (n = 8,790) groups. The findings were validated in a hospital cohort of 1,163 CHB patients. In the nationwide cohort, during 44.2 months of overall treatment duration, 529 patients developed HCC and 190 died or received transplantation. In the 2,499 propensity score-matched pairs, compared with TDF combotherapy, TDF monotherapy showed no significantly different risks of HCC (1.11/100 person-year [PY] vs. 1.32/100 PY; HR 1.23, 95% CI 0.95-1.60, p = .12) and death/transplant (0.43/100 PY vs. 0.42/100 PY; HR 1.04, 95% CI 0.67-1.60, p = .87). However, in the 469 propensity score-matched pairs of cirrhosis subcohort, TDF monotherapy was associated with a higher risk of HCC than TDF combotherapy (HR 1.46, 95% CI 1.002-2.12, p = .049). In the validation hospital cohort, TDF monotherapy was not associated with significantly different risks of HCC and death/transplant in the entire cohort and cirrhosis subcohort. In CHB patients with failure to preceding treatments, TDF monotherapy showed no higher risks of HCC and death/transplantation compared with TDF combotherapy. However, the comparative effectiveness of rescue TDF monotherapy should be further clarified in cirrhotic patients since the findings were not consistent in the nationwide and hospital cohorts.