Efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for hepatitis C in Korea: a Phase 3b study

Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.

Current status of ultrasonography in national cancer surveillance program for hepatocellular carcinoma in South Korea: a large-scale multicenter study

Background@#/Aim: Abdominal ultrasonography (USG) is recommended as a surveillance test for high-risk groups for hepatocellular carcinoma (HCC). This study aimed to analyze the current status of the national cancer surveillance program for HCC in South Korea and investigate the effects of patient-, physician-, and machine-related factors on HCC detection sensitivity. @*Methods@#This multicenter retrospective cohort study collected surveillance USG data from the high-risk group for HCC (liver cirrhosis or chronic hepatitis B or C >40 years of age) at eight South Korean tertiary hospitals in 2017. @*Results@#In 2017, 45 experienced hepatologists or radiologists performed 8,512 USG examinations. The physicians had a mean 15.0±8.3 years of experience; more hepatologists (61.4%) than radiologists (38.6%) participated. Each USG scan took a mean 12.2±3.4 minutes. The HCC detection rate by surveillance USG was 0.3% (n=23). Over 27 months of follow-up, an additional 135 patients (0.7%) developed new HCC. The patients were classified into three groups based on timing of HCC diagnosis since the 1st surveillance USG, and no significant intergroup difference in HCC characteristics was noted. HCC detection was significantly associated with patient-related factors, such as old age and advanced fibrosis, but not with physician- or machine-related factors. @*Conclusions@#This is the first study of the current status of USG as a surveillance method for HCC at tertiary hospitals in South Korea. It is necessary to develop quality indicators and quality assessment procedures for USG to improve the detection rate of HCC.

Surgery versus radiofrequency ablation in patients with Child- Pugh class-A/single small (≤3 cm) hepatocellular carcinoma

Background/Aims@#We compared the post-treatment overall survival (OS) and recurrence-free survival (RFS) between patients with Child-Turcotte-Pugh (CTP) class-A and single small (≤3 cm) hepatocellular carcinoma (HCC) treated by surgical resection (SR) and radiofrequency ablation (RFA). @*Methods@#We retrospectively analyzed 391 HCC patients with CTP class-A who underwent SR (n=232) or RFA (n=159) as first-line therapy for single small (≤3 cm) HCC. Survival was compared according to the tumor size (≤2 cm/2–3 cm) and the presence of cirrhosis. Inverse probability of treatment weighting (IPW) method was used to estimate the average causal effect of treatment. @*Results@#The median follow-up period was 64.8 months (interquartile range, 0.1–162.6). After IPW, the estimated OS was similar in the SR and RFA groups (P=0.215), and even in patients with HCC of ≤2 cm (P=0.816) and without cirrhosis (P=0.195). The estimated RFS was better in the SR group than in the RFA groups (P=0.005), also in patients without cirrhosis (P<0.001), but not in those with HCC of ≤2 cm (P=0.234). The weighted Cox proportional hazards model with IPW provided adjusted hazard ratios (95% confidence interval) for OS, and the RFS after RFA versus SR were 0.698 (0.396–1.232) (P=0.215) and 1.698 (1.777–2.448) (P=0.005), respectively. @*Conclusions@#SR was similar for OS compared to RFA, but was better for RFS in patients with CTP class-A and single small (≤3 cm) HCC. The RFS was determined by the presence or absence of cirrhosis. Hence, SR rather than RFA should be considered in patients without cirrhosis to prolong the RFS, although there is no OS difference.

Outcome prediction of pediatric drowning

Purpose@#Despite the well-known mortality of pediatric drowning, there is a paucity of evidence on the implications of an initial evaluation on the relevant outcome of drowning. This study aimed to investigate the association of initial clinical findings with outcome of children undergoing drowning. @*Methods@#This retrospective study was conducted using the medical records of 56 children undergoing drowning who visited 3 Korean academic hospitals from January 2000 through May 2020. We analyzed information regarding the prehospital resuscitation, drowning time, a 4-tiered chest radiographic grade, and the baseline characteristics. The grade was defined based on the findings of initial chest radiographs. The poor outcomes were defined as the need for intensive care unit care or death aftercare. We analyzed the association of the prehospital resuscitation, submersion time, and the radiographic grade with the poor outcomes using binary logistic regression. @*Results@#Among the 56 children, 31 (55.4%) were aged 1-4 years. Prehospital resuscitation and 1-5 minutes of submersion time were noted in the 25 (44.6%) and 30 children (53.6%), respectively. The chest radiographic grades 1 through 4 accounted for 17 (30.4%), 20 (35.7%), 12 (21.4%), and 3 children (5.4%), respectively. Poor outcomes occurred in 17 children (30.4%), including 3 deaths (5.4%). The association with the poor outcomes was noted in the submersion time of longer than 5 minutes (adjusted odds ratio, 21.49; 95% confidence interval, 1.11-415.73; compared with < 1 minute) while not in the submersion time and chest radiographic grade. @*Conclusion@#This study confirms that submersion time is an outcome predictor of drowning.

Comparison of clinical practice guidelines for the management of chronic hepatitis B: When to start, when to change, and when to stop

Clinical practice guidelines are important for guiding the management of specific diseases by medical practitioners, trainees, and nurses. In some cases, the guidelines are utilized as a reference for health policymakers in controlling diseases with a large public impact. With this in mind, practice guidelines for the management of chronic hepatitis B (CHB) have been developed in the United States, Europe, and Asian-Pacific regions to suggest the best-fit recommendations for each social and medical circumstance. Recently, the Korean Association for the Study of the Liver published a revised version of its clinical practice guidelines for the management of CHB. The guidelines included updated information based on newly available antiviral agents, the most recent opinion on the initiation and cessation of treatment, and updates for the management of drug resistance, partial virological response, and side effects. Additionally, CHB management in specific situations was comprehensively revised. This review compares the similarities and differences among the various practice guidelines to identify unmet needs and improve future recommendations.

Clinical characteristics of allergic rhinitis and nonallergic rhinitis in Korean children

PURPOSE: Recently, the prevalence of allergic rhinitis (AR) in Korean children has been increased. The aim of this study was to investigate the clinical characteristics of rhinitis and to compare clinical parameters between AR and nonallergic rhinitis (NAR) in children.METHODS: We retrospectively reviewed the medical records of 1,034 children under 18 years of age who visited Korea University Anam Hospital for rhinitis symptoms from January 2008 to December 2017. Clinical data, including clinical features, comorbidities, blood test results, allergen sensitization profile, and pulmonary function test parameters, were collected.RESULTS: Among the 1,034 children with rhinitis, 737 (71.3%) were AR and 297 (28.7%) were NAR. The prevalence of AR gradually increased with age. The median levels of eosinophil count (4.1%), serum total IgE (204.4 IU/L), eosinophil cationic protein (ECP) concentration (17.9 µg/L), and fractional exhaled nitric oxide (FeNO) (22.0 ppb) were significantly higher in children with AR than in those with NAR. The sensitization rate to the inhalant allergens increased with age; however, food allergen sensitization rate tended to decrease. Median levels of eosinophil count, total IgE, ECP, and FeNO were significantly higher in the poly-sensitized group than in the mono-sensitized and nonsensitized groups.CONCLUSION: More than 70% of Korean children who have rhinitis symptoms are AR. Children with AR more likely to have higher levels of FeNO and bronchial asthma. Poly-sensitized children showed increased rates of atopic dermatitis and bronchial asthma.

New Potential Therapies for Chronic Hepatitis B / 대한소화기학회지

A HBV infection is a dynamic disease and long-term liver inflammation contributes to the development of liver cirrhosis and hepatocellular carcinoma. Currently available nucleos(t)ide analogues and pegylated interferon are effective in inhibiting HBV replication but rarely achieve HBsAg clearance. The present article introduces a new definition of HBV cure and several emerging therapies for HBV cure, including direct acting antivirals and immune modulatory antivirals.

Efficacy and Safety of Daclatasvir and Asunaprevir in Patients with Hepatitis C Virus Genotype 1b Infection on Hemodialysis

BACKGROUND/AIMS: We evaluated the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) in patients with chronic hepatitis C virus (HCV) infection on hemodialysis. METHODS: We performed a single-arm, multicenter prospective study. Twenty-one chronic hemodialysis patients with HCV infection were prospectively enrolled from February 2016 to April 2017. We evaluated the virological responses at weeks 4, 12, and 24 (end of treatment [EOT]) and the sustained virological response at 12 weeks after the EOT (SVR12). The tolerability and safety of the drugs were also assessed. RESULTS: None of the 20 patients had the NS5A resistance-associated variant (NS5A RAV), and one patient was indeterminate for the NS5A RAV. Seventeen patients (80%) completed the 24 weeks of treatment with DCV and ASV. Four patients discontinued the study prior to week 12. In an intention-to-treat analysis, the SVR12 was 76.1%. In a per-protocol analysis, patients who completed DCV and ASV treatment achieved an SVR12 of 100%. DCV and ASV were well tolerated by the majority of patients. Three patients discontinued treatment due to adverse events (AEs) including dizziness, dyspnea, and neutropenia. The patient with indeterminate NS5A RAV showed viral breakthrough and discontinued treatment. CONCLUSIONS: DCV and ASV combination therapy in chronic hemodialysis patients with HCV infection achieved a high SVR12 rate with few AEs. To maximize the SVR12 rate, it is important to identify candidates by baseline RAV testing. Close monitoring of the safety and tolerability of DCV and ASV may be necessary in HCV-infected patients on hemodialysis. (ClinicalTrials.gov ID NCT02580474)

Intraoperative radiofrequency ablation and distilled water peritoneal lavage for spontaneously ruptured hepatocellular carcinoma

PURPOSE: Spontaneously ruptured hepatocellular carcinoma (srHCC) is known to be a life-threatening complication with poor prognosis. Although there are various treatment modalities, there is no definite treatment guideline. The purpose of this study was to review the surgical outcome and prognosis of srHCC treated with intraoperative radiofrequency ablation (RFA) and distilled water peritoneal lavage (DWPL). METHODS: From March 2012 to October 2018, 9 patients with srHCC who underwent emergent surgery were reviewed. After hematoma removal, intraoperative RFA and DWPL were applied to all patients. Hepatectomy was performed if necessary. Patients with multiple tumors, distant metastasis, and vascular tumor involvement in radiologic imaging were excluded. RESULTS: Six of 9 patients with diameters less than 7 cm were able to obtain hemostasis using RFA alone (RFA group). However, 3 patients with a tumor size of more than 10 cm underwent liver resection because they could not obtain hemostasis with RFA (hepatectomy only group). The RFA group had shorter operation time (148.3 ± 31.7 minutes vs. 251.7 ± 20.2 minutes, P < 0.05) and less red blood cell transfusion (5.8 ± 2.5 packs vs. 24.0 ± 11.5 packs, P < 0.05) than the hepatectomy only group. There was no peritoneal metastasis at long-term follow-up in the RFA group. Five-year recurrence-free survival rate was 0% in both groups. However, 5-year overall survival rate was better in the RFA group (83.3% vs. 0%, P < 0.05). CONCLUSION: Intraoperative RFA and DWPL are easy to perform and theoretically the best methods for managing relatively small srHCC.

Brachial Artery Thrombosis in an 8-year-old Boy with Antiphospholipid Antibodies Induced by Mycoplasma pneumoniae Infection: a Case Report

Antiphospholipid antibodies may be produced in cases involving autoimmune diseases and can sometimes be caused by infections, such as Mycoplasma pneumoniae infection. However, antiphospholipid antibodies causing thrombosis associated with M. pneumoniae pneumonia in children have rarely been reported. We report a case of an 8-year-old boy with M. pneumoniae pneumonia with antiphospholipid antibodies, complicated by brachial artery thrombosis. He was found to have antiphospholipid antibodies and low protein S levels. The brachial artery thrombus was removed via thrombectomy. The titers of antiphospholipid antibodies turned normal within 5 months. This is a rare case of M. pneumoniae infection with brachial artery thrombosis associated with transient antiphospholipid antibodies.

New Potential Therapies for Chronic Hepatitis B / 대한소화기병학회잡지

A HBV infection is a dynamic disease and long-term liver inflammation contributes to the development of liver cirrhosis and hepatocellular carcinoma. Currently available nucleos(t)ide analogues and pegylated interferon are effective in inhibiting HBV replication but rarely achieve HBsAg clearance. The present article introduces a new definition of HBV cure and several emerging therapies for HBV cure, including direct acting antivirals and immune modulatory antivirals.

Diagnosis of Liver Fibrosis With Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein (WFA-M2BP) Among Chronic Hepatitis B Patients

BACKGROUND: Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA-M2BP) is a protein with altered glycosylation that reacts with lectin, and was recently identified as a useful non-invasive biomarker for the diagnosis of liver fibrosis in patients with hepatitis C virus infection.This study aimed to evaluate the diagnostic efficacy of WFA-M2BP for liver fibrosis in the context of hepatitis B virus (HBV). METHODS: We enrolled 151 patients infected with HBV. Liver biopsy and elastography (Fibroscan) were performed during the initial visit. Fibrosis was graded according to the Knodell histologic activity index (F0–3). WFA-M2BP levels were determined with an automated immunoassay analyzer (M2BPGi, HISCL-5000, Sysmex, Japan). The diagnostic efficacy of WFA-M2BP was compared with those of various conventional or composite biomarkers, including enhanced liver fibrosis (ELF) score, Fibroscan, aspartate transaminase (AST)-to-platelet ratio index (APRI), and FIB-4, based on the area under the ROC curve (AUC) value. RESULTS: The majority of patients were at fibrosis stages F1 and F2. The F2 and F3 AUC values for WFA-M2BP were similar to those for FIB-4, APRI, ELF, and Fibroscan, although the latter showed the best diagnostic efficacy. The diagnostic accuracy of all tested biomarkers for F2 and F3 was 60–70%. In multivariate analysis, WFA-M2BP, ELF, and platelet count significantly predicted stage ≥F2, whereas only platelet count significantly predicted F3. CONCLUSIONS: WFA-M2BP can support a diagnosis of liver fibrosis with similar diagnostic efficacy to other biomarkers, and predicted liver fibrosis stage ≥2 among patients with chronic hepatitis B.

The Role of Serum HBV-RNA Levels as a Marker of Intrahepatic Viral and Histologic Activity / 대한소화기학회지

No abstract available.

Effect of antiviral therapy in reducing perinatal transmission of hepatitis B virus and maternal outcomes after discontinuing them

BACKGROUND/AIMS: There have been numerous efforts to reduce mother-to-child transmission (MTCT) of hepatitis B virus (HBV) with antiviral agents during pregnancy. However, there are limited data regarding the outcomes of pregnant women after delivery. This study was performed to evaluate the efficacy of antiviral agents in preventing MTCT of HBV and maternal long-term outcomes. METHODS: The HBV-infected pregnant women treated with antiviral agents to prevent MTCT were retrospectively reviewed. Forty-one pregnant women who received telbivudine or tenofovir during late pregnancy (28-34 week) were analyzed. Hepatitis B virus surface antibody (HBsAb) positivity was tested in 43 infants after 7 months of birth. Eleven mothers were followed >1 year after delivery. RESULTS: The mean HBV DNA titer before antiviral therapy was 8.67 (6.60–9.49) log copies/mL, and the median age at delivery was 32 years (range, 22–40). Eleven patients were treated with tenofovir and 30 with telbivudine. The median duration was 57 days (range, 23–100), and the median HBV DNA titer at birth was 5.06 log copies/mL (range, 2.06–6.50). Antiviral treatments were associated with significant HBV DNA reduction (P 12 months, and an antiviral agent was administered. CONCLUSIONS: Antiviral treatment during late pregnancy effectively reduced MTCT. Long-term follow-up should be required in such cases. In addition, given that maternal biochemical flare occurred in 18% of mothers, re-administration of antiviral agents might be required.

Favorable effect of corticosteroids in treating acute-on-chronic liver failure underlying chronic hepatitis B

Acute-on-chronic liver failure (ACLF) occurs in the presence of a chronic liver disease or cirrhosis, and often results from exacerbation of chronic hepatitis B (CHB). The efficacy of corticosteroid treatment in ACLF patients with underlying CHB remains unclear. We report the case of a 50-year-old woman who experienced ACLF due to CHB exacerbation and was treated with a combination of corticosteroids and nucleot(s)ide analogue (NUC). The patient showed rapid decompensation due to CHB exacerbation. Three months of antiviral therapy produced no improvement in liver function. Combination therapy with corticosteroids and NUC was started, which did result in improvement of liver function. This case shows that the combined therapy of corticosteroids and NUC can be effective in treating ACLF due to CHB exacerbation.

The Role of Tenofovir on the Prevention of Hepatitis B Transmission in Mothers with High Viral Load / 대한소화기학회지

No abstract available.

Clinical characteristics of respiratory viral coinfection in pediatric Mycoplasma pneumoniae pneumonia

PURPOSE: Bacterial/viral coinfection is not uncommon in children with community acquired pneumonia. However, the data about viral coinfection in Mycoplasma pneumoniae pneumonia is limited. The aim of this study was to investigate the frequency and clinical characteristics of respiratory viral coinfection in pediatric M. pneumoniae pneumonia. METHODS: A retrospective cross sectional study was performed in 432 children hospitalized with M. pneumoniae pneumonia in a tertiary teaching hospital between June 2015 and May 2016. RESULTS: One hundred forty patients (32.4%) were coinfected with M. pneumoniae and respiratory viruses. Among coinfected viruses, rhinovirus (44.4%) was most commonly detected. Viral coinfection was more likely to occur under the age of 5 years in winter and spring. As compared with patients infected with M. pneumoniae monoinfection, patients coinfected with respiratory viruses showed a lower mean age and shorter total febrile days. Although total leukocyte count was higher, relative proportion of neutrophils and C-reactive protein level were significantly lower in these patients. CONCLUSION: Viral coinfection was common in pediatric M. pneumoniae pneumonia, especially in patients under the age of 5 years, and this was associated with shorter total febrile days and lower level of acute phase response as compared with M. pneumoniae monoinfection.

Effects of Adrenal Androgen Levels on Bone Age Advancement in Prepubertal Children: Using the Ewha Birth and Growth Cohort Study

Bone age (BA) advancement in prepubertal children may be associated with earlier onset of puberty and obesity. This study aimed to define the effects of adrenal androgen levels on the advancement of BA in prepubertal children, independent of obesity. During July and August 2011, we examined BA in 200 prepubertal children aged 7–9 years who were part of the Ewha Birth & Growth Cohort Study. BA was assessed by the Greulich-Pyle method. An index of BA advancement was calculated as the ratio of BA to chronological age (CA) (BA/CA), and this ratio was classified into 3 tertiles. We analyzed the relationship between BA advancement and anthropometric characteristics and adrenal hormone levels. The number of overweight children increased from the first group to the third group (P(Trend) = 0.03). The levels of adrenal androgens showed a significant positive correlation with the tertile groups after adjusting for age and sex (testosterone: r = 0.26, P < 0.001; dehydroepiandrosterone: r = 0.21, P < 0.001; androstenedione: r = 0.20, P < 0.001). Further, after controlling for body mass index (BMI), sex, and age, the BA/CA was found to be positively correlated with androstenedione (β = 0.04, R² = 3.7%) and testosterone levels (β = 0.05, R² = 4.7%). Based on our results, it is suggested that adrenal androgen levels are associated with BA advancement independent of BMI.

Quantitative assessment of liver fibrosis using shore durometer

PURPOSE: The purpose of the present study was to investigate whether hardness of liver surface correlated with degree of liver fibrosis, and its association with posthepatectomy liver failure (PHLF). METHODS: A shore durometer was used to measure hepatic hardness in 41 patients with hepatocellular carcinoma (HCC) and in 10 patients with normal liver. We investigated how hepatic hardness correlates with various values indicating the degree of liver fibrosis, and how it correlates with PHLF. RESULTS: In the normal liver group, the surface shore units (SU) was 15.06 ± 2.64. In the HCC group, there was a correlation between surface SU and preoperative results indicating liver fibrosis. Among patients with PHLF after resecting over 3 segments, the surface SU of patients with grade A PHLF was 21.85 ± 5.63, and the surface SU of patients with grade C PHLF was 35.75 ± 9.26. In patients with PHLF after resecting 2 or less segments, the surface SU of patients with PHLF grade A was 20.95 ± 5.18, and the surface SU of patients with PHLF grade B was 31.60 ± 5.57. In predicting PHLF, surface SU was more effective than preoperative platelet count, spleen volume, or liver fibrosis index. CONCLUSION: Hepatic hardness measured by the shore durometer was correlated with the degree of liver fibrosis. Liver surface SU was a more effective parameter for predicting PHLF, as compared to other indicators evaluated before hepatectomy. The decision to perform major hepatectomy should be reconsidered in cases with a liver surface SU of >30.

Quantitative assessment of liver fibrosis using shore durometer

PURPOSE: The purpose of the present study was to investigate whether hardness of liver surface correlated with degree of liver fibrosis, and its association with posthepatectomy liver failure (PHLF). METHODS: A shore durometer was used to measure hepatic hardness in 41 patients with hepatocellular carcinoma (HCC) and in 10 patients with normal liver. We investigated how hepatic hardness correlates with various values indicating the degree of liver fibrosis, and how it correlates with PHLF. RESULTS: In the normal liver group, the surface shore units (SU) was 15.06 ± 2.64. In the HCC group, there was a correlation between surface SU and preoperative results indicating liver fibrosis. Among patients with PHLF after resecting over 3 segments, the surface SU of patients with grade A PHLF was 21.85 ± 5.63, and the surface SU of patients with grade C PHLF was 35.75 ± 9.26. In patients with PHLF after resecting 2 or less segments, the surface SU of patients with PHLF grade A was 20.95 ± 5.18, and the surface SU of patients with PHLF grade B was 31.60 ± 5.57. In predicting PHLF, surface SU was more effective than preoperative platelet count, spleen volume, or liver fibrosis index. CONCLUSION: Hepatic hardness measured by the shore durometer was correlated with the degree of liver fibrosis. Liver surface SU was a more effective parameter for predicting PHLF, as compared to other indicators evaluated before hepatectomy. The decision to perform major hepatectomy should be reconsidered in cases with a liver surface SU of >30.