Background/Aims: A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events. Results: The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p=0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well tolerated. Conclusions HK-660S is well tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis (cris.nih.go.kr, Number KCT0006590).

Background/Aims: A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events. Results: The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p=0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well tolerated. Conclusions HK-660S is well tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis (cris.nih.go.kr, Number KCT0006590).

Background/Aims: A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events. Results: The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p=0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well tolerated. Conclusions HK-660S is well tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis (cris.nih.go.kr, Number KCT0006590).

Background/Aims: Chronic hepatitis B (CHB) is related to an increased risk of extrahepatic malignancy (EHM), and antiviral treatment is associated with an incidence of EHM comparable to controls. We compared the risks of EHM and intrahepatic malignancy (IHM) between entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment. Methods: Using data from the National Health Insurance Service of Korea, this nationwide cohort study included treatment-naïve CHB patients who initiated ETV (n=24,287) or TDF (n=29,199) therapy between 2012 and 2014. The primary outcome was the development of any primary EHM. Secondary outcomes included overall IHM development. E-value was calculated to assess the robustness of results to unmeasured confounders. Results: The median follow-up duration was 5.9 years, and all baseline characteristics were well balanced after propensity score matching. EHM incidence rate differed significantly between within versus beyond 3 years in both groups (P<0.01, Davies test). During the first 3 years, EHM risk was comparable in the propensity score-matched cohort (5.88 versus 5.84/1,000 person-years; subdistribution hazard ratio [SHR]=1.01, 95% confidence interval [CI]=0.88–1.17, P=0.84). After year 3, however, TDF was associated with a significantly lower EHM incidence compared to ETV (4.92 versus 6.91/1,000 person-years; SHR=0.70, 95% CI=0.60–0.81, P<0.01; E-value for SHR=2.21). Regarding IHM, the superiority of TDF over ETV was maintained both within (17.58 versus 20.19/1,000 person-years; SHR=0.88, 95% CI=0.81–0.95, P<0.01) and after year 3 (11.45 versus 16.20/1,000 person-years; SHR=0.68, 95% CI=0.62–0.75, P<0.01; E-value for SHR=2.30). Conclusions TDF was associated with approximately 30% lower risks of both EHM and IHM than ETV in CHB patients after 3 years of antiviral therapy.

Purpose: Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. Materials and Methods: Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. Results: Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). Conclusion High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

Background/Aims: The controlled attenuation parameter (CAP), based on transient elastography, is widely used for noninvasive assessment of the degree of hepatic steatosis (HS). We investigated the correlation of the degree HS between CAP and ultrasound (US) in patients with HS. Methods: In total, 986 patients with US-based HS who underwent transient elastography within 1 month were evaluated. The US-based grade of HS was categorized as mild (grade 1), moderate (grade 2), or severe (grade 3). Results: The CAP was significantly correlated with the US-based grade of HS (r = 0.458, p < 0.001). The median CAP value of each US-based HS grade showed a positive correlation with grade (271.1, 303.7, and 326.7 dB/m for grades 1, 2, and 3). In a multivariate analysis, the US-based HS grade, body mass index, serum albumin, alanine aminotransferase, and total cholesterol, and liver stiffness were all significantly correlated with the CAP value (all p < 0.05). The areas under the receiver operating characteristic curves for grade 2 to 3 and grade 3 HS were 0.749 (95% confidence interval [CI], 0.714 to 0.784) and 0.738 (95% CI, 0.704 to 0.772). The optimal cut-off CAP values to maximize the sum of the sensitivity and specificity for grade 2 to 3 and grade 3 HS were 284.5 dB/m (sensitivity 78.6%, specificity 61.7%) and 298.5 dB/m (sensitivity 84.6%, specificity 55.6%). Conclusions The correlation of the degree of HS between CAP and US was significantly high in patients with HS, and the optimal cut-off CAP values for grade 2 to 3 and grade 3 HS were 284.5 and 298.5 dB/m.

BACKGROUND/AIMS: It remains to be determined whether switching from adefovir (ADV) to tenofovir (TDF) provides better virological outcomes in patients exhibiting suboptimal responses to ADV plus nucleoside analogue (ADV+NA) therapy for NA-resistant chronic hepatitis B (CHB). METHODS: In this prospective trial, patients who showed partial responses (defined as serum hepatitis B virus [HBV] DNA >60 IU/mL) to ADV+NA therapy for NA resistance were randomly allocated to receive TDF plus NA (TDF+NA group, n=16) or to continue their current therapy (ADV+NA group, n=16). The primary end point was the proportion of patients with complete virological response (CVR, defined as serum HBV DNA <60 IU/mL) at 48 weeks. RESULTS: The median age was 52 years (16 men), and 28 were positive for hepatitis B e antigen (HBeAg). The baseline characteristics did not differ significantly between the two groups. The proportion with CVR was significantly higher in the TDF+NA group than in the ADV+NA group at 24 weeks (81.3% vs. 25.0%, P=0.001) and 48 weeks (87.5% vs. 37.5%, P=0.002). Furthermore, a decrease in the serum HBV DNA level of >2log10 IU/mL was more likely in the TDF+NA group at both 24 and 48 weeks (68.8% vs. 56.3%, P=0.014 vs. 81.3% vs. 56.3%, P=0.001, respectively). During the follow-up, the rate of HBeAg seroconversion was higher in the TDF+NA group than the ADV+NA group (12.5% vs. 6.25%, P=0.640), as was that for the hepatitis B surface antigen (6.25% vs. 0%, P=0.080). No serious adverse events due to antiviral agents occurred. CONCLUSIONS: In patients exhibiting suboptimal responses to ADV+NA therapy for NA-resistant CHB, switching from ADV to TDF might provide better virological outcomes.
Adenine/*analogs & derivatives/therapeutic use ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Genotype ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy ; Humans ; Lamivudine/therapeutic use ; Male ; Middle Aged ; Organophosphonates/*therapeutic use ; Prospective Studies ; Tenofovir/*therapeutic use ; Treatment Outcome

There have been no long-term complications or life-threatening adverse effects related to botulinum toxin treatment for any cosmetic indications. Nevertheless, there are well-known, mild side effects of botulinum toxin treatment on the upper face, though most of them are self limited with time. However, excluding brow ptosis, reports about site specific side effects are few and anecdotal. We experienced cases of exaggeration of wrinkles after botulinum toxin injection for forehead horizontal lines, and report them here. In our cases, new appearance of a noticeable glabellar protrusion following botulinum toxin injection on the forehead was observed in 2 patients. Also, a new deep wrinkle on one side of the forehead just above the eyebrow appeared in another 2 patients. The exaggerated wrinkles nearly disappeared without treatment by week 4 in all subjects. These exaggerations of wrinkles may be caused by hyperactivity and overcompensation of untreated muscles. With the increasing availability of diverse botulinum toxin for cosmetic purposes, physicians and patients should be aware of this temporary change after therapeutic injections. We recommend explaining this possible effect prior to injection, for better understanding of treatment for cosmetic indications.
Botulinum Toxins ; Cosmetics ; Eyebrows ; Forehead ; Humans ; Muscles

BACKGROUND/AIMS: Interferon beta (IFN-beta) has been shown to have antiviral activity, and thus could be useful in treating viral infections. Therefore, we compared the efficacy and safety of recombinant IFN-beta(IFN-beta-1a) plus oral ribavirin versus interferon alpha (IFN-alpha) plus ribavirin therapy for the treatment of chronic hepatitis C (HCV). METHODS: Twenty treatment-naive patients were randomized into two equal-sized treatment groups. Both IFN-beta-1a (44microgram) and IFN-alpha (3 MIU) were given subcutaneously three times a week, while ribavirin was given orally at 1,000-1,200 mg/day. Patients were treated for 24 weeks and followed for an additional 24 weeks. RESULTS: After 24 weeks of treatment, six (60%) and four patients (40%) in the IFN-beta-1a group and IFN-alpha groups, respectively, achieved viral clearance. The sustained virological response (SVR) at the end of the observation period was similar in both groups (40%). However, the baseline viral load was significantly higher (p=0.034) in the IFN-beta-1a group than in the IFN-alpha group, and there were more HCV genotype 1 patients in the IFN-beta-1a group (eight versus seven). The IFN-beta-1a group was associated with similar adverse events in terms of frequency and severity. CONCLUSIONS: The SVR rate and safety profile were similar for the combination of IFN-beta-1a and ribavirin and that of IFN-alpha and ribavirin.
Genotype ; Hepatitis C ; Hepatitis C, Chronic ; Humans ; Interferon-alpha ; Interferon-beta ; Interferons ; Pilot Projects ; Prospective Studies ; Ribavirin ; Treatment Outcome ; Viral Load

BACKGROUND: Transient elastography (FibroScan(R)) is a rapid and non-invasive method to measure liver stiffness and this allow the assessment of liver fibrosis. The aim of this study was to assess the diagnostic accuracy of measuring the liver stiffness in addition to measuring the other biochemical markers such as the aspartate transaminase to platelet ratio index [APRI] and the AST/ALT ratio. METHODS: We enrolled 228 HBsAg positive patients whose liver stiffness was measured by FibroScan(R) between March 2005 and September 2005. Liver biopsy examinations were performed in 34 patients. The fibrosis (F) was staged on a 0-4 scale according to the Ludwig classification. RESULTS: According to the clinical diagnosis, the median values of liver stiffness were 7.0+/-2.7 kPa for inactive carriers (n=29), 8.3+/-5.3 kPa for chronic hepatitis patients (n=106), 15.9+/-8.3 kPa for compensated cirrhosis patients (n=63), 31.8+/-20.3 kPa for decompensated cirrhosis patients (n=26), and 45.1+/-34.5 kPa for HCC patients (n=4). The degree of liver stiffness was significantly different between the different disease groups (p<0.001). Liver stiffness was well correlated with the fibrosis stages (r=0.726; p<0.001). The AUROC of FibroScan(R), the APRI and the AST/ALT ratio values were of the same order; 0.72, 0.61 and 0.58, respectively, for F> or =2; 0.92, 0.73, and 0.56, respectively, for F> or =3; and 0.97, 0.79, and 0.55, respectively, for F=4. FibroScan(R) offered the best diagnostic performance both for significant fibrosis (F> or =2) and severe fibrosis-cirrhosis (F3-F4). CONCLUSIONS: FibroScan(R) is a reliable, rapid non-invasive method to diagnose the severity of chronic liver disease and to predict fibrosis in patients with chronic hepatitis B, in addition to using the APRI and AST/ALT ratio.
Aspartate Aminotransferases ; Biomarkers* ; Biopsy ; Blood Platelets ; Classification ; Diagnosis ; Elasticity Imaging Techniques ; Fibrosis ; Hepatitis B ; Hepatitis B Surface Antigens ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Liver Cirrhosis* ; Liver Diseases ; Liver*