Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B.

BACKGROUND AND AIM: Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD). METHODS: This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA < 20 IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021. RESULTS: This study included 309 patients with a median age of 59 years, and 42.1% were male. The mean duration of TDF and TAF administration were 54.0 and 37.5 months, respectively. All patients maintained VR after switching to TAF. Alanine aminotransferase (ALT) normalization rate significantly increased 6 months after switching (74.8%-83.5%; P = 0.008). Adjusted eGFR significantly improved at 6 months (+5.55 ± 10.52 mL/min/1.73 m2; P < 0.001) and 12 months (+6.02 ± 10.70 mL/min/1.73 m2; P < 0.001) after switching. In the subgroup of patients with renal impairment (eGFR < 60 mL/min/1.73 m2), significant improvement in renal function was observed at 6 months (+0.6 ± 10.5 mL/min/1.73 m2; P < 0.001) and 12 months (+1.0 ± 10.7 mL/min/1.73 m2; P < 0.001) after switching to TAF. In patients with osteoporosis (n = 182), switching to TAF resulted in significant improvement in spine and hip BMD at 12 months, with increases of 9.7% (95% CI: 7.0-12.5) and 9.4% (95% CI: 7.0-11.8), respectively. CONCLUSION: In this real-world study, switching to TAF was effective and safe in patients, with notable improvements in ALT levels, renal function, and BMD.

Prediction of Hepatocellular Carcinoma by On-Therapy Response of Noninvasive Fibrosis Markers in Chronic Hepatitis B.

INTRODUCTION: Antiviral therapy improves hepatic fibrosis and reduces hepatocellular carcinoma (HCC) incidence. This study aimed to evaluate whether on-therapy changes in scores for fibrosis index based on 4 factors and aspartate aminotransferase-to-platelet ratio index are associated with HCC development and establish an HCC risk score model incorporating noninvasive fibrosis marker (NFM) response. METHODS: This multicenter study recruited 5,147 patients with chronic hepatitis B (4,028 for derivation cohort and 1,119 for validation cohort) who were given entecavir/tenofovir for >12 months between 2007 and 2018. A risk prediction model for HCC was developed using predictors based on multivariable Cox models, and bootstrapping was performed for validation. RESULTS: The 10-year cumulative HCC incidence rates were 12.6% and 13.7% in the derivation and validation cohorts, respectively. The risk of HCC significantly differed with early NFM response, with a marked reduction in HCC risk in patients achieving a significant decrease in NFM by 12 months (P < 0.001). NFM response, sex, age, and cirrhosis were independently predictive of HCC. We developed the Fibrosis marker response, Sex, Age, and Cirrhosis (FSAC) score based on regression coefficients of each variable. For the 10-year prediction of HCC, FSAC showed higher C-index values than PAGE-B, modified PAGE-B, CU-HCC, and REACH-B (0.84 vs 0.77, 0.80, 0.77, and 0.67, respectively; all P < 0.005). The predictive performance of FSAC was corroborated in the validation cohort, with higher C-index than other models (all P < 0.050). DISCUSSION: On-therapy changes in NFM are an independent indicator of HCC risk. FSAC incorporating NFM response is a reliable risk score for risk estimation for HCC with better performance than other models.

Effectiveness of sorafenib dose modifications on treatment outcome of hepatocellular carcinoma: Analysis in real-life settings.

Controlling adverse events (AEs) through dose reduction can enhance drug adherence and treatment response. Currently, there is no guide for sorafenib dosing. The aim of this study was to evaluate whether sorafenib dosing could affect treatment outcomes. A total of 782 hepatocellular carcinoma (HCC) patients treated with sorafenib were evaluated for sorafenib dosing and its modifications via medical records at baseline and regular follow-up. Study outcomes included progression-free survival (PFS), overall survival (OS), sorafenib duration, cumulative dose, AEs and drug discontinuation. The median patient survival was 7.7 months. Overall, 242 (30.9%) patients underwent dose reduction and 121 (17.5%) discontinued sorafenib due to AEs. In multivariate analysis, dose reduction was identified to be independently predictive of PFS and OS. The 800-to-400 mg/day group provided significantly better PFS than the 800 mg/day-maintained group or the 800-to-600 mg/day group. Likewise, the 800-to-400 mg/day group resulted in a significantly better OS than other dosing. However, dose reduction to 200 mg/day led to significantly worse PFS and OS. Hand-foot skin reaction and drug discontinuation due to AEs were higher in the 800-to-600 mg/day group than the 800-to-400 mg/day group. The 800-to-400 mg/day group had significantly longer treatment duration and higher cumulative dose than the 800 mg/day-maintained group. Sorafenib dose reduction can improve HCC survival and increase patient tolerance and adherence coupled with longer duration and higher cumulative dose. Dose reduction from 800 to 400 mg/day than to 600 mg/day is recommended when clinically warranted. However, dose reduction to 200 mg/day is not recommendable.

Clinical outcomes after the introduction of direct antiviral agents for patients infected with genotype 1b hepatitis C virus depending on the regimens: A multicenter study in Korea.

BACKGROUND: A real-life study is essential outside clinical trials. The aim is to evaluate the clinical outcomes of direct acting agents (DAA) for patients with chronic hepatitis C (CHC) in real practice. METHODS: We analyzed 590 consecutively enrolled patients with CHC-1b who received DAAs since 2015, when DAAs were introduced in Korea. The patients were checked for resistance-associated variants (RAV) against nonstructural protein 5A inhibitors and then daclatasvir/asunaprevir or sofosbuvir based regimens were chosen. RESULTS: The frequency of patients with cirrhosis and prior hepatocellular carcinoma (HCC) was 29.2% and 4.7%, respectively. For the RAV test, 10% were positive and in 3.6% the result was "indeterminate." Overall, 518 patients were treated with a 24-week regimen of daclatasvir/asunaprevir, 72 patients (RAV positive 75%) were treated with 12 weeks regimen of ledipasvir/sofosbuvir or daclatasvir/sofosbuvir. The SVR12 was 94.0% in the daclatasvir/asunaprevir, 98.2% in the ledipasvir/sofosbuvir, and 100% in the daclatasvir/sofosbuvir group. A total of 93.3% of SVR12 in the RAV-"indeterminate" patients was not difference 95.0% in the RAV-negative patients. Up to 1 year, de novo HCC occurrence and recurrence developed in 2.6% and 17.8%, respectively. HCC was more frequent in cirrhotic patients than in noncirrhotic patients (P = 0.000). α Fetoprotein (AFP) level at the end of treatment was a predicting factor for de novo HCC. CONCLUSIONS: Optimizing the choice of DAAs according to RAV test resulted in high SVR among CHC-1b Korean patients. This real practice multicenter cohort study suggests the importance of AFP and HCC surveillance in cirrhotic patients even after successful HCV therapy.

Efficacy and Safety of Tenofovir Disoproxil Fumarate in Treatment-Naïve Patients with Chronic Hepatitis B in Korea.

AIMS: To evaluate the efficacy and safety of 144-week tenofovir disoproxil fumarate (TDF) therapy in treatment-naïve chronic hepatitis B (CHB) patients in Korean. METHODS: In total, 579 treatment-naïve CHB patients at 11 medical centers were enrolled retrospective and prospective from September 2015 to January 2016 by design (NCT02533544). We evaluated the complete virologic response (CVR) rate and the renal safety of TDF. RESULTS: The overall CVR rate was 69.4%, 87.0%, and 89.7% at weeks 48, 96, and 144, respectively. In the HBeAg-positive CHB patients, the CVR rate at weeks 48, 96, and 144 was 61.4%, 83.1%, and 89.6%, respectively. The rates of HBeAg loss and seroconversion at weeks 48, 96, and 144 were 16.6%, 23.5%, 34.1%, and 7.6%, 8.9%, 13.3%, respectively. In HBeAg-negative CHB patients, the CVR rate at weeks 48, 96, and 144 was 82.5%, 93.2%, and 90.0%, respectively. The rate of alanine aminotransferase normalization was 36.9%, 45.4%, and 46.8% at weeks 48, 96, and 144, respectively. Of the CHB patients, 0.9% showed an elevated creatinine (> 0.5 mg/dL from baseline). Age (≥ 60 years) was significantly associated with a decline in renal function at week 144 (P < 0.0001). Comorbidities (diabetes or hypertension) showed the tendency to reduce renal function (P = 0.0624). Hepatocellular carcinoma developed in 10 (1.7%) patients and was related to cirrhosis. CONCLUSIONS: TDF therapy induced sustained viral suppression and had a favorable safety profile over a 3-year period. However, close monitoring of renal function should be mandatory in treating CHB patients receiving TDF, particularly older patients.

Propensity-matched analysis to compare the therapeutic efficacies of cefuroxime versus cefotaxime as initial antimicrobial therapy for community-onset complicated nonobstructive acute pyelonephritis due to Enterobacteriaceae infection in women.

This study was performed to compare the therapeutic efficacy of cefuroxime with that of cefotaxime as initial antimicrobial therapies in women with complicated nonobstructive acute pyelonephritis (APN) caused by Enterobacteriaceae infections. The clinical characteristics and outcomes of a cefuroxime-treated group (n = 156) were compared with those of a cefotaxime-treated group (n = 166). Of these 322 women, 90 from each group were matched by propensity scores. The defervescence rates were not significantly different in the cefuroxime and cefotaxime groups at 72 h after the start of antimicrobial therapy (81.1% versus 78.9%, P = 0.709). The clinical and microbiological cure rates during the follow-up visits that were 4 to 14 days after the end of the antimicrobial therapies were not significantly different in the cefuroxime versus cefotaxime groups, which were 97.8% (87/89) versus 97.8% (87/89) (P > 0.999) and 89.5% (68/76) versus 90.7% (68/75) (P = 0.807), respectively. The median hospital stay duration and the median times to defervescence in the cefuroxime versus cefotaxime groups were 8 days (interquartile range [IQR], 7 to 10 days) versus 9 days (IQR, 7 to 11 days), respectively, and 55 h (IQR, 37 to 70 h) versus 55 h (IQR, 35 to 69 h), respectively. Bacteremia, extended-spectrum-ß-lactamase-producing Enterobacteriaceae, C-reactive protein levels of ≥ 15 mg/dl, and white blood cell counts of ≥ 15,000/mm(3) of blood had independent effects on the rates of early clinical failure. Our data suggest that the effects of cefuroxime are not different from those of cefotaxime when they are used as an initial antimicrobial treatments for community-onset complicated nonobstructive APN in women.

Risk factors for acute hepatitis A infection in Korea in 2007 and 2009: a case-control study.

This study aimed to identify the risk factors associated with acute hepatitis A virus (HAV) infection in the Korean population. Participants were recruited from five referral hospitals across the country in 2007 and from 11 hospitals in 2009. Patients with positive anti-HAV IgM antibody tests became the case group, while patients treated for non-contagious diseases at the same hospitals were recruited as controls. A total of 222 and 548 case-control pairs were studied in the 2007 and 2009 surveys, respectively. Data from the surveys were analyzed jointly. In a multivariate analysis, sharing the household with HAV-infected family members (OR, 6.32; 95% CI, 1.4-29.6), contact with other HAV-infected individuals (OR, 4.73; 95% CI, 2.4-9.4), overseas travel in 2007 (OR, 19.93; 95% CI, 2.3-174.4), consumption of raw shellfish (OR, 2.51; 95% CI, 1.8-3.5), drinking bottled water (OR, 1.64; 95% CI, 1.3-8.4), and occupation that involve handling food (OR, 3.30; 95% CI, 1.3-8.4) increased the risk of HAV infection. Avoiding contact with HAV-infected individuals and avoiding raw foods eating could help minimize the risk of hepatitis A infection. Immunization must be beneficial to individuals who handle food ingredients occupationally or travel overseas to HAV-endemic areas.

Change in skeletal muscle mass is associated with hepatic steatosis in nonalcoholic fatty liver disease.

The association between nonalcoholic fatty liver disease (NAFLD) and sarcopenia is known. We aimed to determine the association between skeletal muscle mass changes and NAFLD status. This retrospective single-center study analyzed patients who underwent health screening twice between November 2009 and December 2017, with a temporal gap of 6 ± 0.5 years. The degree of sarcopenia was assessed using appendicular skeletal muscle mass (ASM) adjusted for weight and body mass index (BMI). Changes in hepatic steatosis and fibrosis status were evaluated using noninvasive serum markers. Patients with a decrease in ASM/BMI (n = 353) had increased hepatic steatosis index (HSI) and fatty liver index (FLI) scores during 6 years (p < 0.05). The baseline sarcopenia group had a greater elevation in NAFLD fibrosis score (NFS) over 6 years than those without baseline sarcopenia. ASM changes over 6 years showed a negative correlation with variations in HSI (ß = - 0.96 in ASM/Weight and -28.93 in ASM/BMI) and FLI (ß = - 5.44 in ASM/Weight and - 167.12 in ASM/BMI). Subgroup analyses showed similar results according to sex and age. Sarcopenia may worsen steatosis and vice versa. Skeletal muscle status can be used to predict the course of NAFLD and establish individualized treatment strategies.

A Real-World Comparative Analysis of Atezolizumab Plus Bevacizumab and Transarterial Chemoembolization Plus Radiotherapy in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombosis.

This study aimed to compare the treatment outcomes of atezolizumab-plus-bevacizumab (Ate/Bev) therapy with those of transarterial chemoembolization plus radiotherapy (TACE + RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and without metastasis. Between June 2016 and October 2022, we consecutively enrolled 855 HCC patients with PVTT. After excluding 758 patients, 97 patients (n = 37 in the Ate/Bev group; n = 60 in the TACE + RT group) were analyzed. The two groups showed no significant differences in baseline characteristics and had similar objective response and disease control rates. However, the Ate/Bev group showed a significantly higher one-year survival rate (p = 0.041) compared to the TACE + RT group, which was constantly displayed in patients with extensive HCC burden. Meanwhile, the clinical outcomes were comparable between the two groups in patients with unilobar intrahepatic HCC. In Cox-regression analysis, Ate/Bev treatment emerged as a significant factor for better one-year survival (p = 0.049). Finally, in propensity-score matching, the Ate/Bev group demonstrated a better one-year survival (p = 0.02) and PFS (p = 0.01) than the TACE + RT group. In conclusion, Ate/Bev treatment demonstrated superior clinical outcomes compared to TACE + RT treatment in HCC patients with PVTT. Meanwhile, in patients with unilobar intrahepatic HCC, TACE + RT could also be considered as an alternative treatment option alongside Ate/Bev therapy.

Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinoma.

BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is a widely used treatment for hepatocellular carcinoma. In order to maximize its therapeutic efficacy, doxorubicin-loaded drug-eluting beads have been developed to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. The purpose of this study was to evaluate the efficacy and safety of drug-eluting bead (DC bead®) TACE in comparison with conventional TACE (cTACE). METHODS: A total of 129 patients who underwent TACE between August 2008 and February 2011 were enrolled. We compared HCC patients who underwent TACE with DC bead® (n=60) to controls who received cTACE (n=69). The primary end points were treatment response and treatment-related adverse events. The secondary end point was time to progression. RESULTS: The treatment response in the DC bead® group was significantly higher than that of the cTACE group (p<0.001). The time to progression was significantly better in the DC bead® group than in the cTACE group (11.7 and 7.6months, respectively, p=0.018). Subgroup analysis showed that in intermediate-stage HCC, DC bead® treatment resulted in a significantly better treatment response and longer time to progression than cTACE (p<0.001 and 0.038, respectively). However, there was no statistically significant difference in liver toxicity between the DC bead® and cTACE group (p>0.05). CONCLUSIONS: TACE with DC bead® showed better treatment response and delayed tumor progression compared with cTACE. There was no significant difference in hepatic treatment-related toxicities. DC bead® TACE thus appears to be a feasible and promising approach to the treatment of HCC.

Association between serum tumor necrosis factor-α and sarcopenia in liver cirrhosis.

BACKGROUND/AIMS: Sarcopenia is an independent prognostic factor of liver cirrhosis (LC). However, the association between LC-related systemic inflammation and sarcopenia is unclear. METHODS: Sprague-Dawley rats were treated with thioacetamide (TAA) or saline as a control. Rifaximin was administered to TAA-induced LC rats. Enzyme-linked immunosorbent assay was performed to measure inflammatory mediators in rat serum. RT-PCR was performed to measure the molecular expression in tissues. Hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to investigate tissue pathology. Serum tumor necrosis factor-α levels, liver stiffness (LS), and the L3 skeletal muscle index (L3SMI) were measured in 60 patients with chronic liver disease. RESULTS: LC and sarcopenia were successfully induced by TAA. Serum TNF-α levels were increased in LC rats and correlated with myostatin expression, muscle weight, and myofiber diameter. The expression of intestinal occludin and zona occludens-1 was reduced in LC rats and associated with serum TNF-α levels and sarcopenia. In patients with LS ≥7 kPa or sarcopenia, serum TNF-α levels were significantly increased, which was also confirmed when we raised the LS cutoff to 10 kPa. The L3SMI was inversely correlated with serum TNF-α levels in patients with LS ≥7 kPa. TNF-α was reduced by rifaximin, which might have resulted in reduced expression of muscular MuRF1 and myostatin and improvements in myofiber diameters within muscle tissues. CONCLUSION: These results suggest that serum TNF-α is associated with LC-related sarcopenia. Rifaximin might be effective in reducing serum TNF-α levels and improving sarcopenia in LC, but these results need to be validated in future studies.

Real-life experience of ledipasvir and sofosbuvir for HCV infected Korean patients: a multicenter cohort study.

BACKGROUND/AIMS: To evaluate the efficacy and safety of ledipasvir/sofosbuvir (LDV/SOF) therapy in hepatitis C virus (HCV)-infected Korean patients in a real clinical setting. METHODS: A total of 273 patients who received LDV/SOF therapy between May 2016 and February 2021 were consecutively enrolled and analyzed. A per-protocol analysis was performed to evaluate the virologic response. RESULTS: Seventy-five percent were infected with genotype 1, and 25% were infected with genotype 2. A hundred eightyone (66.3%) patients had chronic hepatitis, 74 (27.1%) had compensated cirrhosis, eight (2.9%) had decompensated cirrhosis, and 10 (3.7%) had undergone liver transplantation. Undetectable HCV RNA at week 4 was achieved in 90.2% (231/256) of patients, 99.2% (250/252) achieved the end of treatment response, and 98.1% (202/206) achieved sustained virologic response at 12 weeks post-treatment (SVR12). According to liver function, the SVR12 rates were 99.3% (135/136) in chronic hepatitis, 96.4% (53/55) in compensated cirrhosis, and 100% (6/6) in decompensated cirrhosis. The SVR12 rates according to the genotype were 98.2% (167/170) for genotype 1 and 97.2% (35/36) for genotype 2. An 8-week LDV/SOF treatment in treatment-naïve chronic hepatitis patients with HCV RNA < 6,000,000 IU/mL at baseline resulted in 100% (23/23) SVR12 rates. Overall, LDV/SOF was tolerated well, with a 0.7% (2/273) discontinuation rate due to adverse events that were unrelated to LDV/SOF. CONCLUSION: LDV/SOF is effective and safe for treating HCV-infected Korean patients with high SVR12 rates.

Safety and effectiveness of direct-acting antivirals in patients with chronic hepatitis C and chronic kidney disease.

BACKGROUND/AIMS: To evaluate the effectiveness and safety of direct acting antivirals (DAAs) available in chronic kidney disease (CKD) patients with hepatitis C virus (HCV) infection in Korea. METHODS: In a retrospective, multicenter cohort study, 362 patients were enrolled from 2015 to 2019. The effectiveness and safety of DAAs including glecaprevir/pibrentasvir, sofosubvir/ribavirin, ledipasvir/sofosbuvir, and daclatasvir/asunaprevir were analyzed for patients according to CKD stage. We evaluated sustained virologic response at week 12 after treatment (SVR12) as primary endpoint. The effectiveness and safety were also evaluated according to CKD stage. RESULTS: Among 362 patients, 307 patients completed DAAs treatment and follow-up period after end of treatment. The subjects comprised 87 patients (62 with CKD stage 3 and 25 with CKD stage (4-5), of whom 22 were undergoing hemodialysis). HCV patients with CKD stage 1 and 2 (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2) showed SVR12 of 97.2% and 95.4% respectively. SVR12 of CKD stage 3 and 4-5 (eGFR < 60 mL/min/1.73 m2) patients was 91.9% and 91.6% respectively. Patients undergoing hemodialysis achieved SVR12 (90.9%). Treatment failure of DAAs in stage 1, 2, 3, and 4-5 was 2.8%, 2.7%, 1.6%, and 4%. DAAs showed good safety profile and did not affect deterioration of renal function. CONCLUSION: DAAs shows comparable SVR12 and safety in CKD patients (stage 3, 4, and 5) with HCV compared with patients with stage 1 and 2. The effectiveness and safety of DAAs may be related to the treatment duration. Therefore, it is important to select adequate regimens of DAAs and to increase treatment adherence.

Definition of Sarcopenia in Chronic Liver Disease.

Sarcopenia, which is characterized by decline in muscle mass, muscle strength, and physical performance, is common in patients with chronic liver disease (CLD) and is associated with poor clinical outcomes. Several consensus definitions for community-dwelling elderly people have been proposed, and these recommend the use of various tools and tests to assess muscle properties and performance. These measurement tools have also been applied in patients with CLD and have been useful for predicting prognosis. However, sarcopenia and its diagnostic criteria specific to patients with CLD have not yet been clearly defined. In addition, fluid retention and body composition should be considered when sarcopenia is assessed in patients with CLD. This review aims to introduce definitions of sarcopenia and diagnostic tools used in patients with CLD.

Clinical significance of colonic diverticulosis associated with bowel symptoms and colon polyp.

This study was done to evaluate prospectively the clinical significance of colonic diverticulosis. In the 1,030 consecutive outpatients undergoing colonoscopy, the information on the demographics, the patterns of bowel symptoms, and the prevalence of colon polyp were analyzed according to the presence of colonic diverticulosis. The mean age of 1,030 patients were 52.2 yr and 59.3% were male. The prevalence of diverticulosis was 19.7% (203/1,030). Of 203 diverticulosis patients 85.2% were in proximal group, 5.4% in distal group and 9.4% in both group. Six (3.0%) patients were found to have diverticulitis. Multivariate logistic regression analysis showed that an old age, diabetes and the presence of polyp were significant factors associated with proximal or both diverticulosis. A significant difference was demonstrated between the patients of distal diverticular group and the controls for the symptom frequency scores within the previous 4 weeks. The items, which showed difference, were hard stool, urgency, flatus, chest discomfort and frequent urination. In conclusion, old age, diabetes and the presence of colon polyp were associated with proximal diverticulosis. The temporal symptoms were more frequent in distal diverticulosis than in proximal diverticulosis in the study subjects.

[A case of ulcerative colitis found in a patient whose parent has Crohn's disease].

Inflammatory bowel diseases (IBD) is heterogeneous, chronic relapsing disorder. Inappropriate and exaggerated immune response for the luminal antigen is known as a main pathogenesis. Genetic, infectious, and environmental factors are responsible for unbalanced immune response, but the definite pathogenesis is still unclear. Genetic factor is the most important role of all. That is based on high concordance rate of identical twins and family history. The incident rate and prevalence of IBD for the Asian population is relatively lower than Western population, and the lack of NOD2 or TLR4 genetic polymorphisms in Korea and Japanese population suggests the difference in genetic background between Asian and Western population. In Korea, the case of familial aggregation of IBD is pretty rare. We report a case of the daughter with ulcerative colitis and her mother with Crohn's disease who have a -159C/T promoter polymorphism of CD14 gene for IBD.

[Clinical features and prognosis of primary biliary cirrhosis in Korea].

BACKGROUND/AIMS: This study investigated the clinical features and prognosis of primary biliary cirrhosis (PBC) in Korea. METHODS: Clinical data of patients diagnosed as PBC between 1997 and 2008 at eight referral hospitals were analyzed retrospectively. PBC was diagnosed based on liver function tests, presence of serum antimitochondrial antibody (AMA), and histopathological findings. RESULTS: In total, 251 patients (218 females, 33 males; mean age 54 years) were enrolled, and the mean follow-up duration was 33.5 months. At the diagnosis, 61% of the patients were asymptomatic, 12% had decompensated liver cirrhosis, and 98% were positive for AMA. The serum alkaline phosphate (ALP) level was 2.6 times the upper limit of normal, aspartate aminotransferase was 105 U/L, and bilirubin was 2.0 mg/dL. The mean Mayo risk score was 5.5, and the Child-Pugh class was A, B, and C in 79%, 19%, and 2% of the patients, respectively. Ursodeoxycholic acid (UDCA) was used for treatment in 88% of the patients, among which 70% exhibited biochemical responses defined as normalization or a > 40% decrease in ALP at 6 months. Eight deaths occurred during the follow-up; the causes were variceal bleeding, hepatic failure, and sepsis. The overall 5-year survival rate was 95%. The poor prognostic factors were being older than 60 years, high bilirubin, low albumin, ascites, high Mayo risk score, Child-Pugh class C, and initial presence of hepatic decompensation. CONCLUSIONS: Most patients diagnosed as PBC were asymptomatic, and these patients had a favorable short-term prognosis. The prognosis of PBC was dependent on the initial severity of liver disease.

Noninvasive Serum Fibrosis Markers are Associated with Coronary Artery Calcification in Patients with Nonalcoholic Fatty Liver Disease.

Background/Aims: Advanced hepatic fibrosis is associated with cardiovascular disease (CVD) in patients with nonalcoholic fatty liver disease (NAFLD). We investigated the association between noninvasive serum fibrosis markers and the coronary artery calcium score (CACS) in subjects with NAFLD. Methods: We analyzed 665 NAFLD subjects without chronic liver disease or heart disease between 2011 and 2015. The noninvasive fibrosis markers that were used to evaluate the severity of hepatic fibrosis included the NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4) score, Forn's index, and the aspartate aminotransferase to platelet ratio index (APRI). Results: The areas under the receiver operating characteristics curves for the NFS, FIB-4 score, Forn's index and APRI for predicting CACS >100 were 0.689, 0.683, 0.659, and 0.595, respectively. According to the multivariate analysis, older age, increased body mass index (BMI), and decreased estimated glomerular filtration rate (eGFR) were significant factors associated with CACS >100. The NFS, FIB-4 score and APRI were significantly associated with CACS >100 after adjusting for age and gender (p=0.006, p=0.012, and p=0.012, respectively) and after adjusting for age, gender, BMI and eGFR (p=0.013, p=0.022, and p=0.027, respectively). Scores integrating noninvasive fibrosis markers and other risk factors improved the predictive accuracy. Conclusions: The NFS and FIB-4 score were associated with coronary atherosclerosis in subjects with NAFLD. Furthermore, scores integrating these noninvasive scores and risk factors for CVD showed good discriminatory power in predicting CACS >100. Therefore, noninvasive serum fibrosis markers may be useful tools for identifying NAFLD subjects at a high risk for CVD.

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<0.001). Among 43 infants (two cases of twins), HBsAb was not detected in two, subsequently confirmed to have HBV infection. Biochemical flare was observed in two of 11 mothers followed >12 months, and an antiviral agent was administered. CONCLUSION: 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.