Efficacy comparison of high-genetic barrier nucleos(t)ide analogues in treatment-naïve chronic hepatitis B patients: a network meta-analysis

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). @*Conclusions@#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.

Anti-fibrotic effects of branched-chain amino acids on hepatic stellate cells

Background/Aims@#Patients with liver cirrhosis (LC) have low levels of branchedchain 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. @*Conclusions@#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.

Prevalence trends of non-alcoholic fatty liver disease among young men in Korea: A Korean military population-based cross-sectional study

Background/Aims@#Non-alcoholic fatty liver disease (NAFLD) has become a major concern in Korea since its emergence as a dominant cause of chronic liver disease. However, no study has explored its prevalence in adults under 30 years of age. Therefore, we performed a cross-sectional study to investigate the prevalence of NAFLD in Korean men in their early 20s. @*Methods@#We collected data of 596,359 Korean soldiers who participated in a health examination between January 2015 and July 2021. A total of 571,872 individuals were analyzed after excluding those with missing data and hepatitis B antigen positivity. Hepatic steatosis was determined using the hepatic steatosis index (HSI). Participants with HSI >36 were considered to have NAFLD. @*Results@#All participants were men, and the mean age was 20.9±1.3 years. Of the 571,872 participants screened, 77,020 (13.47%) were classified as having NAFLD. The prevalence of NAFLD consistently increased from 2015 to 2021 (10.66% vs. 16.44%, P<0.001). Increases from 2015 to 2021 were also noted in the prevalence of hypercholesterolemia, hyperglycemia, and hypertension (P<0.001 for all). The mean body mass index also increased from 23.3±3.0 kg/m2 to 23.9±3.1 kg/m2 between 2015 and 2021 (P<0.001). @*Conclusions@#The prevalence of NAFLD and of other metabolic dysfunctions in Korean men in their early 20s increased from 2015 to 2021.

Diagnostic performance of serum exosomal miRNA-720 in hepatocellular carcinoma

Background@#/Aim: Hepatocellular carcinoma (HCC) is associated with poor prognosis, largely due to late detection. Highly accurate biomarkers are urgently needed to detect early-stage HCC. Our study aims to explore the diagnostic performance of serum exosomal microRNA (miR)-720 in HCC. @*Methods@#Exosomal miRNA was measured via quantitative real-time PCR. A correlation analysis of exosomal miR-720 and tumor or clinico-demographic data of patients with HCC was performed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of serum exosomal miR-720 for HCC, in comparison with α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II). @*Results@#MiR-720 was chosen as a potential HCC marker via miR microarray based on significant differential expression between tumor and non-tumor samples. Serum exosomal miR-720 was significantly upregulated in patients with HCC (n=114) versus other liver diseases (control, n=30), with a higher area under the ROC curve (AUC=0.931) than the other markers. Particularly, serum exosomal miR-720 showed superior performance in diagnosing small HCC (< 5 cm; AUC=0.930) compared with AFP (AUC=0.802) or PIVKA-II (AUC=0.718). Exosomal miR-720 levels showed marginal correlation with tumor size. The proportion of elevated miR-720 also increased with intrahepatic tumor stage progression. Unlike AFP or PIVKA-II showing a significant correlation with aminotransferase levels, the exosomal miR-720 level was not affected by aminotransferase levels. @*Conclusions@#Serum exosomal miR-720 is an excellent biomarker for the diagnosis of HCC, with better performance than AFP or PIVKA-II. Its diagnostic utility is maintained even in small HCC and is unaffected by aminotransferase levels.

Multidisciplinary treatment with immune checkpoint inhibitors for advanced stage hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a cytotoxic chemotherapy-resistant tumor and most HCCs arise in a background of liver cirrhosis of various causes. Although the IMBrave150 trial showed remarkable advancements in the treatment of unresectable HCC with atezolizumab plus bevacizumab (AteBeva), therapeutic outcomes were unsatisfactory in more than half of the patients. Accordingly, many ongoing trials combine conventional modalities with new drugs such as immune checkpoint inhibitors for better treatment outcomes, and they are expected to benefit patients with limited responses to conventional treatment. Here, two patients with advanced stage HCC with preserved liver function and good performance status showed partial response after treatment with combination or sequential therapy of AteBeva, hepatic arterial infusion chemotherapy, radiation therapy, and transarterial chemoembolization. These findings indicate the efficacy of multidisciplinary treatment against advanced HCC. Additional studies are required to establish optimal treatment strategies.

Metastatic breast cancer from a hepatocellular carcinoma: a case report

Breast metastases from extramammary malignancies are rare. Here, we report a case of breast metastasis from hepatocellular carcinoma (HCC) after breast mass excision in a 63-year-old woman. A new breast nodule was noticed after transarterial chemoembolization, transarterial radioembolization, and stereotactic body radiation therapy for HCC. Breast ultrasound and core needle biopsy were performed to differentiate between the breast tumors. The biopsy result was invasive breast carcinoma, and wide excision of the breast was performed. The final pathological diagnosis was HCC breast metastasis based on histological findings and immunohistochemical staining results. After 9 months of follow-up, HCC and breast metastasis recurred. Despite palliative treatment, the patient died due to complications and general health deterioration. Although breast metastasis due to HCC is very rare, HCC breast metastasis should be considered when a new breast mass is discovered in a patient with a history of HCC for effective treatment and management.

Efficacy and Safety of Glecaprevir/Pibrentasvir in Korean Patients with Chronic Hepatitis C: A Pooled Analysis of Five Phase II/III Trials

Background/Aims@#Glecaprevir/pibrentasvir (G/P) is the first pan-genotypic direct-acting antiviral combination therapy approved in Korea. An integrated analysis of five phase II and III trials was conducted to evaluate the efficacy and safety of G/P in Korean patients with chronic hepatitis C virus (HCV) infection. @*Methods@#The study analyzed pooled data on Korean patients with HCV infection enrolled in the ENDURANCE 1 and 2, SURVEYOR II part 4 and VOYAGE I and II trials, which evaluated the efficacy and safety of 8 or 12 weeks of G/P treatment. The patients were either treatment-naïve or had received sofosbuvir or interferon-based treatment. Efficacy was evaluated by assessing the rate of sustained virologic response at 12 weeks posttreatment (SVR12). Safety was evaluated by monitoring adverse events (AEs) and laboratory assessments. @*Results@#The analysis included 265 patients; 179 (67.5%) were HCV treatment-naïve, and most patients were either subgenotype 1B (48.7%) or 2A (44.5%). In the intention-to-treat population, 262 patients (98.9%) achieved SVR12. Three patients did not achieve SVR12: one had virologic failure and two had non-virologic failures. Most AEs were grade 1/2; eight patients (3.0%) expe-rienced at least one grade ≥3 AE. No serious AEs related to G/P treatment were reported, and grade ≥3 hepatic laboratory abnormalities were rare (0.8%). @*Conclusions@#G/P therapy was highly efficacious and well tolerated in Korean patients with HCV infection, with most patients achieving SVR12. The safety profile was comparable to that observed in a pooled analysis of a global pan-genotypic population of patients with HCV infection who received G/P.

Persistence of intrahepatic hepatitis B virus DNA integration in patients developing hepatocellular carcinoma after hepatitis B surface antigen seroclearance

Background/Aims@#The role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance. @*Methods@#Using probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated. @*Results@#HBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC. @*Conclusions@#The biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAgserocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.

Upregulation of C-Reactive Protein by Placenta-Derived Mesenchymal Stem Cells Promotes Angiogenesis in A Rat Model with Cirrhotic Liver

Background and Objectives@#Liver cirrhosis is accompanied by abnormal vascular shunts. The Wnt pathway is essential for endothelial cell survival and proliferation. C-reactive protein (CRP), which is produced by hepatocyte, activates angiogenesis in cardiovascular diseases. @*Methods@#and Results: The expression of CRP in CCl 4 -injured rat livers was detected using qRT-PCR and Western blotting after transplantation of placenta-derived mesenchymal stem cells (PD-MSCs) into rats. To determine whether CRP functions in hepatic regeneration by promoting angiogenesis through the Wnt pathway, we detected VEGF and β-catenin in liver tissues and BrdU and β-catenin in hepatocytes by immunofluorescence. The expression levels of CRP, Wnt pathway-related and angiogenic factors were increased in CCl 4 -injured and PD-MSCs transplanted rat livers. In vitro, the expression levels of Wnt signaling and angiogenic factors were decreased in siRNA-CRP-transfected rat hepatocytes. @*Conclusions@#CRP upregulation by PD-MSCs participates in vascular remodeling to promote liver regeneration via the Wnt signaling pathway during hepatic failure.

Successful Sequential Therapy Involving Regorafenib after Failure of Sorafenib in a Patient with Recurrent Hepatocellular Carcinoma after Liver Transplantation

The efficacy and safety of sequential systemic therapy for the treatment of recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) are not well established. This study describes a successful experience where sequential therapy with sorafenib followed by regorafenib was used to treat recurrent HCC in a 54-year old male LT recipient. After HCC recurred in both lungs 10 months after LT, sorafenib was administered with radiation therapy to treat pulmonary metastases. However, after 4 months of sorafenib treatment showed progressive pulmonary metastases, sequential regorafenib treatment was started. After 3 months (cycles) of regorafenib treatment, tumor response was partial, and after 6 months (cycles), disease status remained stable without signs of progression or drug-related serious adverse events. This case suggests that sequential systemic therapy is feasible in patient with recurrent HCC after LT.

Infiltration of T Cells and Programmed Cell Death Ligand 1-expressing Macrophages as a Potential Predictor of Lenvatinib Response in Hepatocellular Carcinoma

Background/Aims@#Lenvatinib was recently proven to be non-inferior to sorafenib in treating unresectable hepatocellular carcinoma (HCC) in a phase-3 randomized controlled trial. In this study, we investigated whether the response to lenvatinib was affected by tumor immunogenicity. @*Methods@#Between May 2019 and April 2020, nine patients with intermediate-to-advanced HCC, who were treated with lenvatinib after liver biopsy, were enrolled. Immunohistochemical staining and multi-color flow cytometry were performed on specimens obtained from liver biopsy. @*Results@#Among the nine patients enrolled, four showed objective responses (complete responses+partial responses). Immunohistochemical staining for CD3, CD68, and programmed cell death ligand 1 (PD-L1) demonstrated that patients with objective responses showed marked infiltration of T cells and PD-L1-expressing macrophages in intra-tumoral and peri-tumoral tissues compared to those without objective responses. A significant difference in the numbers of infiltrated T cells, both in the intra-tumoral (P<0.01) and peri-tumoral regions (P<0.05), were identified between responders and non-responders. Regarding the number of infiltrated macrophages, no significant difference was found between the responders and non-responders, although the number of PD-L1-expressing tumor-associated macrophages was significantly higher in responders than that in non-responders (P<0.05). @*Conclusions@#Tumor immunogenicity, as indicated by T cell and PD-L1-positive macrophage infiltration, affects lenvatinib response in unresectable HCC.

Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response

Background/Aims@#Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV. @*Methods@#This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded. @*Results@#Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P<0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs. -0.37 log10 IU/mL, P<0.001). Multivariate analysis indicated that high baseline HBV DNA level (P=0.005) and LAM/LdT+ADV maintenance therapy (P=0.001) were negatively associated with virologic response. At week 48, additional ADV- or ETV-associated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/LdT+ADV group (P=0.106). The two groups had similar rates of adverse events. @*Conclusions@#ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).

Early Onset Polymorphic Post-transplant Lymphoproliferative Disease Mimicking a Solitary Necrotizing Abscess in a Graft Liver

Although post-transplantation lymphoproliferative disease (PTLD) after liver transplantation is very rare, its prognosis is worse than that of PTLD following other types of solid organ transplantation. Here, we report a rare case of early onset polymorphic PTLD in a graft liver occurring five months after deceased-donor liver transplantation due to hepatocellular carcinoma and hepatitis C virus infection. Initially, findings from contrast-enhanced magnetic resonance imaging mistakenly suspected the lesion was a necrotizing abscess with central necrosis. However, ¹⁸F-fluorodeoxyglucose positron emission tomography and biopsy findings confirmed an Epstein-Barr virus (EBV)-associated, B cell type polymorphic PTLD with central necrosis. Our case suggests regular monitoring of EBV serologic status for liver transplant recipients who were initially in an EBV seronegative state. Although early-onset PTLD is very rare after liver transplantation, PTLD should be suspected when recipients show the seroconversion for EBV proteins and the development of new tumors with various clinical presentations.

Clinical outcome of 1,000 consecutive cases of liver transplantation: a single center experience

PURPOSE: The aim of this study was to analyze survival outcomes in 1,000 consecutive liver transplantations (LTs) performed at a single institution from 1993 to April 2017. METHODS: The study population was divided into 2 groups based on donor type: deceased donor LT (DDLT; n = 181, 18.1%) and living donor LT (LDLT; n = 819; 81.9%), and into 3 periods based on the number of cases (first 300 cases, middle 300 cases, last 400 cases). RESULTS: Infection was the most common cause of death, accounting for 34.8% (95 of 273). Mortality due to hepatocellular carcinoma recurrence occurred most frequently between 1 and 5 years after transplantation. Mortality rate by graft rejection was highest between 5 and 10 years after transplantation. And mortality by de novo malignancy occurred most frequently after 10 years after transplantation. The patient survival rates for the entire population at 5 and 10 years were 74.7%, and 68.6%, respectively. There was no difference in survival rate between the LDLT and DDLT groups (P = 0.188). Cause of disease, disease severity, case period, and retransplantation had a significant association with patient survival (P = 0.002, P = 0.031, P = 0.003, and P = 0.024, respectively). CONCLUSION: Surgical techniques and perioperative management for transplant patients have improved and undergone standardization. Controlling perioperative infection and managing patients with HCC as LT candidates will result in better outcomes.

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.

Outcome of donor biliary complications following living donor liver transplantation

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.

Interferon-free treatment for hepatitis C virus infection induces normalization of extrahepatic type I interferon signaling

BACKGROUND/AIMS: Hepatitis C virus (HCV) replicates in the peripheral blood mononuclear cells (PBMCs), leading to the production of type I interferons (IFNs). It is well known that the gene expression profile of PBMC is similar to that of the liver. The present study explored the dynamic gene expression profile of PBMCs collected from HCV-infected patients undergoing direct-acting antiviral (DAA) therapy. METHODS: A prospective cohort comprising 27 patients under DAA therapy was formed. Expression level of IFN-β and its downstream interferon-stimulated genes (ISGs) was measured in PBMCs before and after DAA treatment. Furthermore, immunoblotting was performed to identify the signaling molecules involved in the expression of ISGs. RESULTS: The pretreatment expression level of interferon-induced protein 44 (IFI44) and C-X-C motif chemokine ligand 10 (CXCL10) correlated with the pretreatment expression level of IFN-β. After DAA treatment, a significant decrease in the expression levels of IFN-β, IFI44, and CXCL10 was observed in the PBMCs. Furthermore, the pretreatment expression level of IFN-β and ISGs correlated with the level of signal transducer and activator of transcription 1 (STAT1) phosphorylation, and DAA treatment abrogated STAT1 phosphorylation. CONCLUSIONS: Pretreatment activation of IFN-β response is rapidly normalized after DAA treatment. The present study suggests that the decreased type I IFN response by the clearance of HCV might contribute to DAA-induced alleviation of extrahepatic manifestation of chronic HCV infection.

Transarterial Chemolipiodolization for Hepatocellular Carcinoma with Central Bile Duct Invasion Causing Conjugated Hyperbilirubinemia: Safety and Prognostic Factors for Survival

BACKGROUND/AIMS: The treatments and outcomes of hepatocellular carcinoma (HCC) with bile duct invasion are not well known. We aimed to confirm the safety of transarterial chemolipiodolization (TACL) and identify prognostic factors for patients with bile duct invasion treated with TACL. METHODS: Fifty patients with central bile duct invasion treated with TACL between 2005 and 2017 were enrolled. Patients were divided into three groups: hyperbilirubinemia (total bilirubin ≥2.5 mg/dL) with pre-TACL biliary drainage, hyperbilirubinemia without biliary drainage, and without hyperbilirubinemia. Tumor response to TACL, survival outcomes, length of hospitalization, adverse events using Common Terminology Criteria for Adverse Events (CTCAE), and factors affecting overall survival were compared. RESULTS: TACL-induced changes of mean CTCAE grades for albumin, alanine aminotransferase, creatinine, prothrombin time, and platelet were not significantly different among patients with or without initial hyperbilirubinemia. Serum bilirubin level was not significantly changed after TACL in all the three groups. Overall survival was not significantly different among the three groups (P=0.097). On multivariate analysis, alpha-fetoprotein < 400 ng/dL (hazard ratio [HR]=0.477, P=0.048) and highest total bilirubin level of < 2.5 mg/dL within one month after TACL (HR=0.335, P=0.004) were significantly associated with longer survival. CONCLUSIONS: TACL was a safe treatment for HCC patients with central bile duct invasion, irrespective of the presence of initial hyperbilirubinemia.

Development of bronchiolitis obliterans organizing pneumonia during standard treatment of hepatitis C with Peg-IFNα2b

No abstract available.

Reactivation of Hepatitis C Virus and Its Clinical Outcomes in Patients Treated with Systemic Chemotherapy or Immunosuppressive Therapy

BACKGROUND/AIMS: According to the results of several studies, the outcome of hepatitis C virus (HCV) reactivation is not as severe as the outcome of hepatitis B virus reactivation. The aim of this study was to evaluate the effect of pharmacological immunosuppression on HCV reactivation. METHODS: The medical records of patients who underwent systemic chemotherapy, corticosteroid therapy, or other immunosuppressive therapies between January 2008 and March 2015 were reviewed. Subsequently, 202 patients who were seropositive for the anti-HCV antibody were enrolled. Exclusion criteria were: unavailability of data on HCV RNA levels, a history of treatment for chronic hepatitis C, and the presence of liver diseases other than a chronic HCV infection. RESULTS: Among the 120 patients enrolled in this study, hepatitis was present in 46 patients (38%). None of the patients were diagnosed with severe hepatitis. Enhanced replication of HCV was noted in nine (27%) of the 33 patients who had data available on both basal and follow-up HCV RNA loads. Reappearance of the HCV RNA from an undetectable state did not occur after treatment. The cumulative rate of enhanced HCV replication was 23% at 1 year and 30% at 2 years. CONCLUSIONS: Although enhanced HCV replication is relatively common in HCV-infected patients treated with chemotherapy or immunosuppressive therapy, it does not lead to serious sequelae.