Search

Background/aims: Four high-genetic barrier nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB), namely entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and besifovir dipivoxil maleate (BSV), have been established. The aim of this study is to investigate the efficacy of four high-genetic barrier NAs using a network meta-analysis of randomized trials and propensity score-matched cohorts., Methods: Systematic search was performed using PubMed, Cochrane library, and EMBASE and included randomized controlled trials and cohort studies that used propensity score matching. Studies on treatment-naïve CHB patients treated with ETV, TDF, TAF, or BSV were included. Outcomes included alanine aminotransferase normalization and hepatitis B e antigen seroclearance at week 48 and undetectable hepatitis B virus DNA at weeks 48 and 96. Network meta-analysis was performed to synthesize the results., Results: In total, 15,000 patients from 16 studies were included. In terms of 48- and 96-week virologic response (VR), TDF outperformed ETV with statistical significance (48 weeks: odds ratio [OR], 1.38; p < 0.001; 96 weeks: OR, 1.57; p = 0.004). ETV was ranked first for 48-week biochemical response (BR) and outperformed TDF (OR, 0.76; p = 0.028). In the sensitivity analyses, 48-week VR from randomized-controlled trials were compiled, and the same trend toward the superiority of TDF over ETV was found (OR, 1.51; p = 0.030)., Conclusion: Four high-genetic barrier NAs were compared, and TDF was more likely to achieve a VR after 48 weeks, while ETV provided a superior BR after 48 weeks.

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 &lt; 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.

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 &lt; 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.

Background/aims: Patients with liver cirrhosis (LC) have low levels of branched-chain amino acids (BCAAs). There is accumulating evidence that BCAAs have anti- fibrotic effects in cirrhosis. This study is aimed to evaluate the effect of BCAAs on the function and phenotype of activated hepatic stellate cells (HSCs)., Methods: LX-2, an immortalized human stellate cell line, was used in in vitro experiments. LX-2 cells were exposed to transforming growth factor β1 (TGF-β1) and BCAAs or to valine, leucine, and isoleucine, which are components of BCAAs. Activation of the TGF-β signaling pathway in LX-2 cells was observed using real-time quantitative polymerase chain reaction and Western blotting., Results: The increased expression of snail family transcriptional repressor 1 (SNAI1) was observed in LX-2 cells activated by TGF-β1. After BCAA treatment, its expression was significantly decreased at the mRNA level. The increased expression of Col1α1 and TIMP2 at the mRNA level and alpha smooth muscle actin at the protein level in activated LX-2 cells decreased after BCAA treatment. Among the BCAA components, leucine and valine significantly abrogated TGF-β-induced activation of LX-2 cells. BCAA treatment led to the decreased phosphorylation of Smad2 and p38 proteins, which are markers for Smad and Smad-independent p38 mitogen-activated protein kinase signaling pathways, respectively., Conclusion: BCAA treatment can improve hepatic fibrosis by directly affecting the activated state of hepatic stellate cells through inhibition of the TGF-β signaling pathway. Among BCAA components, leucine and valine mainly abrogated TGF-β-induced activation of HSCs. Our results suggest that BCAA may be used to attenuate the progression of liver fibrosis.

Background/aims: Biliary complications are the most common donor complication following living donor liver transplantation (LDLT). The aim of this study is to investigate the long-term outcomes of biliary complications in right lobe adult-to-adult LDLT donors, and to evaluate the efficacy of endoscopic treatment of these donors., Methods: The medical charts of right lobe donors who developed biliary complications between June 2000 and January 2008 were retrospectively reviewed., Results: Of 337 right lobe donors, 49 developed biliary complications, including 36 diagnosed with biliary leakage and 13 with biliary stricture. Multivariate analysis showed that biliary leakage was associated with the number of right lobe bile duct orifices. Sixteen donors, five with leakage and 11 with strictures, underwent endoscopic retrograde cholangiography (ERC). ERC was clinically successful in treating eight of the 11 strictures, one by balloon dilatation and seven by endobiliary stenting. Of the remained three, two were treated by rescue percutaneous biliary drainage and one by conservative care. Of the five patients with leakage, four were successfully treated using endobiliary stents and one with conservative care. In overall, total 35 improved with conservative treatment. All inserted stents were successfully retrieved after a median 264 days (range, 142 to 502) and there were no recurrences of stricture or leakages during a median follow-up of 10.6 years (range, 8 to 15.2)., Conclusions: All donors with biliary complications were successfully treated non-surgically, with most improving after endoscopic placement of endobiliary stents and none showing recurrence on long term follow-up.

Background/aims: We compared the recurrence of hepatocellular carcinoma (HCC) and the survival of patients who received radiofrequency ablation (RFA) after transarterial chemoembolization (TACE) with patients treated with TACE or RFA alone., Methods: This study included 201 patients with HCC, who were consecutively enrolled at Seoul St. Mary's Hospital between December 2004 and February 2010. Inclusion criteria were a single HCC ≤ 5.0 cm or up to three HCCs ≤ 3.0 cm. We used a propensity score model to compare HCC patients (n = 87) who received RFA after TACE (TACE + RFA) with those who received TACE (n = 71) or RFA alone (n = 43)., Results: The median follow-up period was 33.3 months (range, 6.8 to 80.9). The TACE + RFA group showed significantly lower local recurrence than the RFA or TACE groups (hazard ratio [HR], 0.309; 95% confidence interval [CI], 0.130 to 0.736; p = 0.008; and HR, 0.352; 95% CI, 0.158 to 0.787; p = 0.011, respectively). The overall survival was significantly better in the TACE + RFA group compared to the RFA group (HR, 0.422; 95% CI, 0.185 to 0.964; p = 0.041). However, the survival benefit was not different between the TACE + RFA and TACE groups (p = 0.124). Subgroup analysis showed that among patients with a tumor size < 3 cm, the TACE + RFA group had significantly better long-term survival than those in the TACE or RFA groups (p = 0.017, p = 0.004, respectively)., Conclusions: TACE + RFA combination treatment showed favorable local recurrence and better overall survival rates in early-stage HCC patients. Patients with tumors < 3 cm are likely to benefit more from TACE + RFA combination treatment. Additional studies are needed for the selection of suitable HCC patients for TACE + RFA treatment.

Background/aims: Liver transplant patients are at high risk for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) colonization. We evaluated patients before and after liver transplant using active surveillance culture (ASC) to assess the prevalence of MRSA and VRE and to determine the effect of bacterial colonization on patient outcome., Methods: We performed ASC on 162 liver transplant recipients at the time of transplantation and 7 days posttransplantation to monitor the prevalence of MRSA and VRE., Results: A total of 142 patients had both nasal and rectal ASCs. Of these patients, MRSA was isolated from 12 (7.4%) at the time of transplantation (group 1a), 9 (6.9%) acquired MRSA posttransplantation (group 2a), and 121 did not test positive for MRSA at either time (group 3a). Among the three groups, group 1a patients had the highest frequency of developing a MRSA infection (p < 0.01); however, group 2a patients had the highest mortality rate associated with MRSA infection (p = 0.05). Of the 142 patients, VRE colonization was detected in 37 patients (22.8%) at the time of transplantation (group 1b), 21 patients (20%) acquired VRE posttransplantation (group 2b), and 84 patients did not test positive for VRE at either time (group 3b). Among these three groups, group 2b patients had the highest frequency of VRE infections (p < 0.01) and mortality (p = 0.04)., Conclusions: Patients that acquired VRE or MRSA posttransplantation had higher mortality rates than did those who were colonized pre-transplantation or those who never acquired the pathogens. Our findings highlight the importance of preventing the acquisition of MRSA and VRE posttransplantation to reduce infections and mortality among liver transplant recipients.

The role of radiotherapy in the treatment of hepatocellular carcinoma (HCC) has been limited to date, because the liver has a low tolerance to radiation. However, reconstructing tumors and surrounding organs via a three-dimensional conformal planning system can avoid excess radiotherapy exposure to the rest of the liver and adjacent organs. Recently, the concept of "adaptive radiotherapy," such as with helical tomotherapy, has been introduced for treating HCC. Helical tomotherapy obtains an image from the computed tomography component, which allows targeted regions to be visualized prior to, during, and immediately after each treatment and delivers intensity-modulated radiation therapy. We report two patients with advanced HCC who underwent tomotherapy treatment. One was a patient afflicted with advanced HCC and a portal vein tumor thrombus, which was treated with tomotherapy combined with transarterial chemolipiodolization. The other was a patient afflicted with multiple pulmonary metastases treated with tomotherapy followed by systemic chemotherapy.

Conventional radiation therapy (RT) is a widely recognized treatment for hepatocellular carcinoma (HCC). However, conventional RT plays only a limited role in HCC treatment because of its low efficacy and the low tolerance of the liver for this modality. Stereotactic body radiation therapy (SBRT) was recently developed and represents the most advanced radiation therapy technique currently available. It can deliver a high dose in a short time to well-defined hepatic tumors, with rapid dose fall-off gradients. We believe that SBRT with transarterial chemolipiodolization (TACL) may prove promising as a combined treatment modality for HCC due to its precision and relative safety. Here we present a case of successful treatment of advanced HCC with obstructive jaundice using this combined modality.

Background/aims: The virologic response of Koreans to combination therapy for chronic hepatitis C is similar to westerns; however, dose modification occurs more frequently in Koreans. We evaluated the rates of peginterferon alpha-2a and ribavirin dose modifications and their effect on the virologic response in Koreans., Methods: Patients with detectable HCV RNA and enrolled from multicenters were treated with peginterferon alpha-2a (180 microg/week) and ribavirin (800 mg/day) for 24 weeks (genotype non-1, n=37) or peginterferon alpha-2a (180 microg/week) and ribavirin (1,000-1,200 mg/day) for 48 weeks (genotype 1, n=55)., Results: Early virologic response (EVR) and sustained virologic response (SVR) were 77.2% (genotype 1, 75%; non-1, 81%) and 66.3% (genotype 1, 56%; non-1, 81%), respectively. The frequency of dose modification was 32.6% within the first 12 weeks and 52.2% during the entire treatment period. No difference was found in SVR regardless of dose modification. However, the SVR for patients using >or=80% of the peginterferon dose was significantly higher than for those using <80% (81.3 vs. 50.0%, p=0.007), despite varying ribavirin doses. No difference was found in SVR regardless of whether the ribavirin dose was <80% or not. These results did not change based on genotype., Conclusions: We suggest that using at least 80% of the peginterferon alpha-2a dose in Koreans not only maintains SVR but also reduces drug side effects during the entire treatment period. A lower dose of ribavirin may be as efficacious as a standard dose.

A 57-yr-old woman previously diagnosed with chronic hepatitis B was admitted via the emergency room because she suddenly developed epigastric pain with abdominal distension. On computed tomography (CT), a round enhancing mass was found on the left hepatic lobe with ascites in the peritoneal space. Bloody ascites were found upon tapping the ascites, and this led to the diagnosis of ruptured hepatocellular carcinoma (HCC). The patient was immediately treated with transcatheter arterial chemoembolization (TACE) including 50 mg of adriamycin and 10 mL of lipiodol, and then we performed left lateral segmentectomy 20 days later. To prevent recurrence of HCC by any micrometastasis, the patient subsequently received 8 cycles of adjuvant systemic chemotherapy (a regimen of epirubicin (50 mg/m(2)), cisplatin (60 mg/m(2)) and 5-fluorouracil (200 mg/m(2))) at monthly intervals. After this, the patient has been regularly followed up and she shows no signs of tumor recurrence 7 years later. This case suggests that surgical resection and subsequent adjuvant systemic chemotherapy with using an ECF regimen may provide long-term survival for patients ruptured HCC.

Background: Spontaneous delayed clearance of hepatitis B surface antigen (HBsAg) in patients with chronic HBV infection is a rare event. The aim of this study was to investigate the incidence of delayed clearance of serum HBsAg in chronic HBV infection and to determine the characteristics and clinical outcomes of HBsAg delayed clearance in Korean patients., Methods: From April 1981 to June 2003, 4,061 patients who were positive for HBsAg were evaluated retrospectively. The following assessments were undertaken in 47 patients who had spontaneous delayed clearance: liver biochemistry, viral markers, alpha-fetoprotein levels, and radiographic examinations including ultrasonography every three to six months for 6-264 months (median 87.9 months)., Results: Twenty-four of 47 patients were asymptomatic carriers. The others included seven patients with chronic hepatitis, seven with liver cirrhosis and nine with hepatocellular carcinoma. The estimated annual incidence of HBsAg seroclearance was 0.4%. The time span from positive HBsAg to HBsAg seroclearance in the AHC, CH, LC, and HCC was 62.9, 141, 63, and 95.3 months during follow up. Twenty-four of 24 AHC remained normal, 5 of 7 CH remained as CH and 2 patients remained normal, 1 of 7 with LC developed HCC and 6 of the LC remained as LC, and 4 of 9 HCC patients died., Conclusion: The clinical course following delayed clearance of HBsAg had diverse outcomes from AHC to HCC. Therefore, these patients require close follow up for the possible development of hepatocellular carcinoma following HBsAg clearance.

Budd-Chiari syndrome (BCS) is a disorder caused by occlusion of the hepatic vein or inferior vena cava. The clinical presentation include abdominal pain, hepatomegaly, ascites, leg edema, collateral venous dilatation of the body trunk, and portal hypertension. In addition, BCS can cause hepatocellular carcinoma (HCC) in some patients, although its pathogenesis is not yet completely understood. The average reported time lag from diagnosis of BCS to full-blown HCC ranges from several years to several decades. Hepatic carcinogenesis in patients with BCS perhaps reflects a prolonged and persistent liver injury in that it occurs in the primary inferior vena cava obstruction rather than the primary hepatic vein thrombosis. Among patients with BCS, membranous obstruction of the vena cava (MOVC) usually presents an insidious and chronic illness, whereas primary hepatic vein thrombosis presents an acute or subacute illness. We experienced a case of a patient with BCS, which progressed rapidly that HCC developed only nine months after the diagnosis of BCS. The factors causing this rapid progression are still unclear and remain to be investigated.

Background: Although the polyproteins of hepatitis C virus(HCV) are processed and formed in nearly equimolar amounts, individual functional proteins have a discrepancy in their time of appearance following HCV infection and eliciting immune response. This study was conducted to compare the reactivity toward regional specific HCV protein in relation to virological characteristics, including HCV genotype and HCV replication., Methods: Sera from forty-five patients with chronic HCV infection were analyzed through the experiments of the recombinant immunoblot assay(RIBA-2), HCV genotyping and HCV RNA quantitation., Results: The frequencies of seropositivity to C22-3, C33C, C100-3 and 5-1-1 proteins were 91.1%, 91.1%, 64.4% and 53.3%, respectively, of all the patients, and thus the antibodies to C22-3 and C33C proteins were found more frequently (p < 0.05). The antibody responses between core or NS3 proteins and NS4 proteins showed more discrepancy in the HCC group than that in the CH group, implying a possibility of oncogenic potential of core or NS3 gene in hepatocarcinogenesis. The detection rate of antibodies to C22-3 and C33C, in accordance with serum HCV RNA levels, was significantly higher in highly viremic patients than that in low viremic patients (p < 0.05). Antibodies to C22-3, C33C, C100-3 and 5-1-1 were also found more frequently in patients with HCV genotype 1b, compared to those with HCV genotype 2a (p < 0.05)., Conclusion: These results suggest that antibody detection of HCV may depend on the virological characteristics of HCV, the levels of HCV replication and HCV genotype and, therefore, HCV RNA detection using RT-PCR technique is essential for confirmatory diagnosis for HCV infection. Furthermore, the HCV core or NS3 Protein may play important role in hepatocarcinogenesis.

Objectives: Interferon is the only established treatment for chronic hepatitis C but the host-dependent or virus-related factors affecting the response rate to interferon therapy are not yet clear. The purpose of this study was to investigate the factors predictive of response to interferon-alfa therapy in chronic hepatitis C., Methods: Twenty-five consecutive patients with chronic hepatitis C were randomized to three regimens of interferon-alfa: group A (n = 7, 3 MU every day for 3 months), group B (n = 8, 3 MU every other day for 3 months) and group C (n = 10, 3 MU every other day for 6 months). We quantified serum HC RNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR) and performed HCV genotyping using type-specific primers deduced form the NS5 region of the HCV genome. We also attempted to identify which demographic, biochemical and histologic factors in addition to virus-related factors would significantly predict beneficial response to interferon by multivariate analysis., Results: Sustained responders were 8 (36.4%), nonsustained responders were 2 (9.1%) and nonresponders were 12 (54.5%) of 22 patients who had received complete therapy. The initial HCV RNA level (logarithmic transformed copy numbers per ml of serum) in sustained responders (5.75 +/- 0.39) was significantly lower than that of nonsustained responders (6.80 +/- 0.71) and nonresponders (6.70 +/- 0.52) (p < 0.05). In multivariate multiple logistic regression analysis, the serum HCV RNA level before therapy was only the independent predictor of a sustained response to interferon-alfa therapy (p = 0.001)., Conclusions: Serum HCV RNA level before therapy was the most useful predictor of a sustained response to interferon-alfa therapy for chronic hepatitis C.

The authors investigated the distribution of HCV genotypes in patients with various chronic liver diseases in Korea. Study population was 70 individuals, positive for second generation anti-HCV EIA, consisting of 37 cases with sporadic non-A, non-B (NANB) chronic hepatitis (CH), 12 NANB hepatocellular carcinoma, 16 post-transfusion NANB hepatitis, 4 non-B blood donors and 1 healthy family member of a patient with sporadic CH. Molecular typing was performed by RT-nested PCR with type-specific primer sets deduced from the NS-5 region of HCV. The prevalence of type II was 75.0% and type III was 25.0% in sera. In liver tissues, type II HCV was shown in 63.0%, type III HCV in 3.7% and co-infections with type II and III HCV were observed in 18.5% of 27 samples biopsied. In the sera of patients with chronic hepatitis, typing results were relatively well correlated with those in tissues (75%), but type III could not be observed. Among 12 HCC patients, type III HCV appeared only in tissues, not in sera. These results suggest that type II HCV may be the major HCV type in Korea, and co-infections with type II and-III HCV may not be rare in chronic liver diseases with HCV.