Next-generation sequencing analysis of hepatitis C virus resistance–associated substitutions in direct-acting antiviral failure in South Korea

Background/Aims@#We used next-generation sequencing (NGS) to analyze resistance-associated substitutions (RASs) and retreatment outcomes in patients with chronic hepatitis C virus (HCV) infection who failed direct-acting antiviral agent (DAA) treatment in South Korea. @*Methods@#Using prospectively collected data from the Korean HCV cohort study, we recruited 36 patients who failed DAA treatment in 10 centers between 2007 and 2020; 29 blood samples were available from 24 patients. RASs were analyzed using NGS. @*Results@#RASs were analyzed for 13 patients with genotype 1b, 10 with genotype 2, and one with genotype 3a. The unsuccessful DAA regimens were daclatasvir+asunaprevir (n=11), sofosbuvir+ribavirin (n=9), ledipasvir/sofosbuvir (n=3), and glecaprevir/pibrentasvir (n=1). In the patients with genotype 1b, NS3, NS5A, and NS5B RASs were detected in eight, seven, and seven of 10 patients at baseline and in four, six, and two of six patients after DAA failure, respectively. Among the 10 patients with genotype 2, the only baseline RAS was NS3 Y56F, which was detected in one patient. NS5A F28C was detected after DAA failure in a patient with genotype 2 infection who was erroneously treated with daclatasvir+asunaprevir. After retreatment, 16 patients had a 100% sustained virological response rate. @*Conclusions@#NS3 and NS5A RASs were commonly present at baseline, and there was an increasing trend of NS5A RASs after failed DAA treatment in genotype 1b. However, RASs were rarely present in patients with genotype 2 who were treated with sofosbuvir+ribavirin. Despite baseline or treatment-emergent RASs, retreatment with pan-genotypic DAA was highly successful in Korea, so we encourage active retreatment after unsuccessful DAA treatment.

Multicenter Analysis of Clinical Features and Prognosis of COVID-19 Patients with Hepatic Impairment

Background/Aims@#Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. @*Methods@#We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. @*Results@#Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID-19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. @*Conclusions@#Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.

Effectiveness and safety of elbasvir/grazoprevir in Korean patients with hepatitis C virus infection: a nationwide real-world study

Background@#/Aim: This study aimed to establish the real-world effectiveness and safety of grazoprevir/elbasvir (EBR/GZR) therapy in South Korea. @*Methods@#A total of 242 patients with chronic hepatitis C virus (HCV) genotype 1 or 4 infection who started EBR/GZR were consecutively enrolled from seven tertiary hospitals. Retrospective analysis of the fractions of patients that achieved sustained virological response (SVR) was performed, and the incidence of adverse events was noted. @*Results@#The mean age of enrolled patients was 59.0 ± 12.6 years and 47.5% were males. Patients with HCV genotype 1b accounted for 93.8% (n = 227), and patients with HCV of unspecified genotype 1 accounted for 5.8% (n = 14). Hypertension was the most common comorbid disease (29.8%) followed by diabetes (22.7%) and chronic kidney disease (CKD, 12.4%). SVR rates of treatment-naïve and treatment-experienced patients were 85.5% (182/213) and 93.1% (27/29), respectively, in the intention-to-treat analyses, whereas in the per-protocol analyses, those were 97.8% (179/183) and 100% (28/28), respectively. Fewer patients with HCV genotype 1 of unspecified subtype achieved SVR (81.8%, n = 11) compared to the patients with SVR infected with genotype 1b (99%, n = 198, p < 0.001). All patients with CKD showed SVR. Itching (12%) and dyspepsia (4.1%) were common adverse events. Of the four patients who discontinued the antiviral therapy, one experienced mild fatigue but neither treatment withdrawal was because of an adverse event. @*Conclusions@#EBR/GZR showed high real-world effectiveness and safety in Korean patients with chronic HCV infection regardless of the previous antiviral treatment, liver cirrhosis, or CKD status.

Environmental risk factors and comorbidities of primary biliary cholangitis in Korea: a case-control study

Background/Aims@#The risk factors for the development of primary biliary cholangitis (PBC) is unclear. This study aimed to investigate the risk factors associated with PBC in Korea through a questionnaire survey. @*Methods@#Consecutively enrolled 103 PBC patients from six referral hospitals and 100 age- and sex-matched community controls participated in this study. A standardized questionnaire survey including demographics, lifestyle, individual and familial medical history and reproductive history was prospectively collected and analyzed. @*Results@#The PBC patients had a mean age of 58.3 years and a female proportion of 86.4%. The age- and sex-matched controls had a similar educational level and economic status to the PBC patients. Among the lifestyle factors, the multivariable analysis showed smoking including both first-hand and second-hand (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.06 to 3.93), history of autoimmune diseases (OR, 2.46; 95% CI, 1.06 to 6.35), and family history of PBC (OR, 17.76; 95% CI, 1.77 to 2,418.74) were significantly associated with PBC, whereas alcohol intake was negatively associated with PBC. Among reproductive factors, the number of induced abortions was significantly associated with PBC, while the number of full-term deliveries was negatively associated with PBC. @*Conclusions@#A family history of PBC, accompanying autoimmune diseases, and smoking were significantly associated with PBC. More induced abortions and less full-term deliveries were associated with PBC in women. In contrast, mild to moderate alcohol intake was negatively associated with PBC. Further studies are warranted to validate the results of this study and to search for clues about the pathogenesis of PBC.

Multicenter Analysis of Clinical Features and Prognosis of COVID-19 Patients with Hepatic Impairment

Background/Aims@#Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. @*Methods@#We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. @*Results@#Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID-19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. @*Conclusions@#Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.

Real-Life Effectiveness and Safety of Sofosbuvir-Based Therapy in Genotype 2 Chronic Hepatitis C Patients in South Korea, with Emphasis on the Ribavirin Dose

Background/Aims@#Sofosbuvir (SOF)-based therapy has been used in Korean patients with chronic hepatitis C virus (HCV) infection since January 2016. This study aimed to in-vestigate the real-life effectiveness and safety of SOF-based therapy in genotype 2 HCV infection. @*Methods@#From January to December 2016, 458 genotype 2 HCV-infected patients who received ≥1 dose of SOF-based therapy were consecu-tively enrolled in seven tertiary hospitals. Sustained virologic response (SVR) rates and safety were determined by inten-tion-to-treat (ITT) and per-protocol (PP) analyses. @*Results@#The mean age of the patients was 61.0 years; 183 (40%) were male, and 13.1% showed a high viral load (>6,000,000 IU/ mL). Among the 378 treatment-naïve patients, the SVR rates were 94.2% (ITT) and 96.7% (PP). Among the 80 treatmentexperienced patients, the SVR rates were 96.3% (ITT) and 98.7% (PP). Patients with a relatively high fibrosis-4 index score (>3.25) had similar SVR rates to those with a relatively low score (p=0.756). A total of 314 patients (68.6%) were treated with a reduced ribavirin dose at the prescriber’s dis-cretion, but they showed similar SVR rates to those treated with the weight-based dose (ITT: 95.5% and 92.3%, PP: 97.4% and 96.3%, respectively). Adverse events were ob-served in 191 patients (41.7%), including 86 (18.8%) with anemia, but only one (0.2%) discontinued antiviral therapy due to nausea. @*Conclusions@#SOF-based therapy showed high real-life efficacy and tolerability in Korean patients with genotype 2 chronic HCV infection, regardless of previous antiviral treatment experience and fibrosis score. A reduced ribavirin dose can be considered in this patient cohort.

Clinical outcomes of coronavirus disease 2019 in patients with pre-existing liver diseases: A multicenter study in South Korea

Background/Aims@#Although coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, the implication of pre-existing liver disease on the outcome of COVID-19 remains unresolved. @*Methods@#A total of 1,005 patients who were admitted to five tertiary hospitals in South Korea with laboratory-confirmed COVID-19 were included in this study. Clinical outcomes in COVID-19 patients with coexisting liver disease as well as the predictors of disease severity and mortality of COVID-19 were assessed. @*Results@#Of the 47 patients (4.7%) who had liver-related comorbidities, 14 patients (1.4%) had liver cirrhosis. Liver cirrhosis was more common in COVID-19 patients with severe pneumonia than in those with non-severe pneumonia (4.5% vs. 0.9%, P=0.006). Compared to patients without liver cirrhosis, a higher proportion of patients with liver cirrhosis required oxygen therapy; were admitted to the intensive care unit; had septic shock, acute respiratory distress syndrome, or acute kidney injury; and died (P @*Conclusions@#This study suggests liver cirrhosis is a significant risk factor for COVID-19. Stronger personal protection and more intensive treatment for COVID-19 are recommended in these patients.

Changes in Characteristics of Patients with Liver Cirrhosis Visiting a Tertiary Hospital over 15 Years: a Retrospective Multi-Center Study in Korea

Background@#Liver cirrhosis has become a heavy burden not only for patients, but also for our society. However, little is known about the recent changes in clinical outcomes and characteristics of patients with cirrhosis-related complications in Korea. Therefore, we aimed to evaluate changes in characteristics of patients with liver cirrhosis in Daegu-Gyeongbuk province in Korea over the past 15 years. @*Methods@#We retrospectively reviewed the medical records of 15,716 liver cirrhotic patients from 5 university hospitals in Daegu-Gyeongbuk province from 2000 to 2014. The Korean Standard Classification of Diseases-6 code associated with cirrhosis was investigated through medical records and classified according to the year of first visit. @*Results@#A total of 15,716 patients was diagnosed with cirrhosis. A number of patients newly diagnosed with cirrhosis has decreased each year. In 2000, patients were most likely to be diagnosed with hepatitis B virus (HBV) cirrhosis, followed by alcoholic cirrhosis. There was a significant decrease in HBV (P < 0.001), but alcohol, hepatitis C virus (HCV), and non-alcoholic fatty liver disease (NAFLD) showed a significant increase during the study period (alcohol, P = 0.036; HCV, P = 0.001; NAFLD, P = 0.001). At the time of initial diagnosis, the ratio of Child-Turcotte-Pugh (CTP) class A gradually increased from 23.1% to 32.9% (P < 0.001). The most common cause of liver-related hospitalization in 2000 was hepatocellular carcinoma (HCC) (25.5%); in 2014, gastrointestinal bleeding with esophageal and gastric varices (21.4%) was the most common cause. Cases of hospitalization with liver-related complication represented 76.4% of all cases in 2000 but 70.9% in 2014. Incidence rate of HCC has recently increased. In addition, HCC-free survival was significantly lower in CTP class A than in classes B and C. Finally, there was significant difference in HCC occurrence according to causes (P < 0.001). HBV and HCV cirrhosis had lower HCC-free survival than alcoholic and NAFLD cirrhosis. @*Conclusion@#In recent years, the overall number of cirrhosis patients has decreased. This study confirmed the recent trend in decrease of cirrhosis, especially of cirrhosis due to HBV, and the increase of HCV, alcoholic and NAFLD cirrhosis. Targeted screening for at-risk patients will facilitate early detection of liver diseases allowing effective intervention and may have decreased the development of cirrhosis and its complications.

An integrated analysis of elbasvir/grazoprevir in Korean patients with hepatitis C virus genotype 1b infection

BACKGROUND/AIMS: In the Republic of Korea, an estimated 231,000 individuals have chronic hepatitis C virus (HCV) infection. The aim of the present analysis was to evaluate the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) administered for 12 weeks in Korean patients who were enrolled in international clinical trial phase 3 studies.METHODS: This was a retrospective, integrated analysis of data from patients with HCV genotype (GT) 1b infection enrolled at Korean study sites in four EBR/GZR phase 3 clinical trials. Patients were treatment-naive or had previously failed interferon-based HCV therapy, and included those with human immunodeficiency virus coinfection or Child-Pugh class A cirrhosis. All patients received EBR 50 mg/GZR 100 mg once daily for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after completion of therapy (SVR12, HCV RNA <15 IU/mL).RESULTS: SVR12 was achieved by 73 of 74 (98.6%) patients. No patients had virologic failure and one discontinued from the study after withdrawing consent. SVR12 rates were uniformly high across all patient subgroups. A total of 16 patients had nonstructural protein 5A resistance-associated substitutions at baseline (16/73, 22%), all of whom achieved SVR12. Adverse events (AEs) reported in >5% of patients were fatigue (6.8%), upper respiratory tract infection (5.4%), headache (5.4%), and nausea (5.4%). Thirteen patients (17.6%) reported drug-related AEs, two serious AEs occurred, and two patients discontinued treatment owing to an AEs.CONCLUSIONS: In this retrospective analysis, EBR/GZR administered for 12 weeks was well-tolerated and highly effective in Korean patients with HCV GT1b infection.

Daclatasvir and asunaprevir combination therapy for patients with chronic hepatitis C virus genotype 1b infection in real world

BACKGROUND/AIMS@#Previous studies have reported a high rate of sustained virologic response (SVR) and a low rate of serious adverse events with the use of daclatasvir (DCV) and asunaprevir (ASV) combination therapy. We evaluated the efficacy and safety of DCV and ASV combination therapy for patients with chronic hepatitis C virus (HCV) genotype 1b infection in real world.@*METHODS@#We enrolled 278 patients (184 treatment-naïve patients) from five hospitals in Daegu and Gyeongsangbuk-do. We evaluated the rates of rapid virologic response (RVR), end-of-treatment response (ETR), and SVR at 12 weeks after completion of treatment (SVR12). Furthermore, we investigated the rate of adverse events and predictive factors of SVR12 failure.@*RESULTS@#The mean age of patients was 59.5 ± 10.6 years, and 140 patients (50.2%) were men. Seventy-seven patients had cirrhosis. Baseline information regarding nonstructural protein 5A (NS5A) sequences was available in 268 patients. Six patients presented with pretreatment NS5A resistance-associated variants. The RVR and the ETR rates were 96.6% (258/267) and 95.2% (223/232), respectively. The overall SVR12 rate was 91.6% (197/215). Adverse events occurred in 17 patients (7.9%). Six patients discontinued treatment because of liver enzyme elevation (n = 4) and severe nausea (n = 2). Among these, four achieved SVR12. Other adverse events observed were fatigue, headache, diarrhea, dizziness, loss of appetite, skin rash, and dyspnea. Univariate analysis did not show significant predictive factors of SVR12 failure.@*CONCLUSIONS@#DCV and ASV combination therapy showed high rates of RVR, ETR, and SVR12 in chronic HCV genotype 1b-infected patients in real world and was well tolerated without serious adverse events.

Factors Associated with Health-Related Quality of Life in Korean Patients with Chronic Hepatitis C Infection Using the SF-36 and EQ-5D

BACKGROUND/AIMS: This study aimed to describe the health-related quality of life (HRQoL) outcomes for Korean chronic hepatitis C patients and to investigate the impact of patient and virus-related factors on HRQoL. METHODS: HRQoL was assessed in 235 hepatitis C virus (HCV)-infected patients from seven nationwide tertiary hospital, including those with liver cirrhosis and hepatocellular carcinoma (HCC), using the Shor-Form 36 (SF-36) version 2 and the European quality of life questionnaire-5 dimensions (EQ-5D-3L). RESULTS: The SF-36 physical (48.8±8.3) and mental (46.2±11.7) component summary scores of the HCV-infected patients were below normal limits. Of the eight domains, general health, vitality, and mental health tended to show low scores. Patients with decompensated cirrhosis had the lowest HRQoL, while HCC and chronic hepatitis patients had similar HRQoL results. The EQ-5D index was low (0.848±0.145) in the HCV infected patients. Multivariable analysis showed age ≤65 years, high monthly family income (>$2,641), low comorbidity score, and sustained virologic response (SVR) were independently associated with favorable HRQoL. CONCLUSIONS: HRQoL in Korean patients with chronic HCV infection was low and was affected by cirrhosis severity, SVR, and comorbidity as well as income, which had the strongest effect. Therefore, HRQoL may be improved by antiviral therapy with reasonable costs to prevent cirrhosis progression.

Chronic Hepatitis B Infection Is Significantly Associated with Chronic Kidney Disease: a Population-based, Matched Case-control Study

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m² or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m² (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m² along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m². CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m² and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.

Characteristics of Synchronous and Metachronous Multiple Gastric Tumors after Endoscopic Submucosal Dissection of Early Gastric Neoplasm

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been widely accepted as a method of treatment of early gastric tumor. This study aimed to identify the incidence and characteristics of multiple gastric tumors after ESD. METHODS: Patients with early gastric tumors who were treated by ESD from January 2004 to June 2012 and followed up with endoscopic examination periodically for at least 1 year were enrolled. All multiple gastric lesions were subsequently treated with ESD and the medical records of the patients were retrospectively reviewed. RESULTS: In total, 643 patients were included. The mean duration of endoscopic follow-up was 45.27±27.59 (range, 12–148) months. Overall, 144 patients (22.4%) showed multiple gastric tumors during the follow-up period (44 synchronous [6.8%] and 100 metachronous [15.5%]). The cumulative incidence rate steadily increased during the follow-up period. More than 50% of the tumors that developed at the same longitudinal location of the stomach were of the same macroscopic and histological type as the primary lesions. CONCLUSIONS: Because synchronous and/or metachronous gastric tumors are common, considerable attention should be paid to detect multiple gastric lesions after ESD of early gastric neoplasm.

Current status and strategies for hepatitis B control in Korea

Hepatitis B virus (HBV) infection is the most common cause of chronic liver diseases in Korea. After the introduction of the universal HBV vaccination program, the prevalence of hepatitis B surface antigen was markedly reduced, and Korea is now classified as an area of intermediate endemicity for HBV. However, there are still hurdles for elimination of hepatitis B, such as immunoprophylaxis failure against vertical transmission, occurrence of acute hepatitis B among peoples who did not have vaccination at younger age, and rapid increase of immigrant populations from HBV endemic areas. To achieve the World Health Organization goal of viral hepatitis elimination by 2030 in Korea, we suggest comprehensive policies for more effective control of hepatitis B as following: i) insurance coverage for antiviral prophylaxis in mothers with high viremia, ii) screening for hepatitis B seromarkers and catch-up HBV vaccinations of susceptible persons with hepatitis B, iii) establishment of an independent ‘viral hepatitis sector’ in Centers for Disease Control & Prevention to organize and execute comprehensive strategy for management of viral hepatitis, iv) encourage of management of HBV infection in immigrant populations, v) national campaign to promote awareness of hepatitis B.

Final Report of Unmet Needs of Interferon-Based Therapy for Chronic Hepatitis C in Korea: Basis for Moving into the Direct-Acting Antiviral Era

BACKGROUND/AIMS: To evaluate the era of direct acting antivirals (DAAs), we must understand the treatment patterns and outcomes of interferon-based therapy for hepatitis C virus (HCV) infection. We aimed to elucidate the treatment rate, factors affecting treatment decisions, and efficacy of interferon-based therapy in a real-world setting. METHODS: This nationwide cohort study included 1,191 newly diagnosed patients with chronic HCV infection at seven tertiary hospitals in South Korea. Subjects were followed retrospectively until March 2015, which was just before the approval of DAA therapy. RESULTS: In total, 48.2% and 49.3% of the patients had HCV genotypes 1 and 2, respectively. Interferon-based therapy was initiated in 541 patients (45.4%). The major reasons for no treatment included ineligibility (18.9%), concern about adverse events (22.3%), cost (21.5%), and an age >75 years (19.5%). Interferon-based therapy was discontinued (18.5%) mainly due to adverse events (n=66). The intent-to-treat analysis found that the sustained virologic response (SVR) rate was 58.3% in genotype 1 patients and 74.7% in non-genotype 1 patients. CONCLUSIONS: Approximately one-third of newly diagnosed HCV patients in South Korea received interferon-based therapy and showed a suboptimal SVR rate. Diagnosis of patients at younger ages and with a less advanced liver status and reducing the DAA therapy cost may fulfill unmet needs.

Survival outcomes of hepatic resection compared with transarterial chemoembolization or sorafenib for hepatocellular carcinoma with portal vein tumor thrombosis

BACKGROUND/AIMS: Treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as treatments for HCC with PVTT. METHODS: Patients diagnosed as HCC with PVTT between January 2000 and December 2011 who received treatment with sorafenib, HR, or TACE were included. Patients with main PVTT, superior mesenteric vein tumor thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of 172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment were performed is 40, 80, and 52 patients respectively. PVTT was classified as either involving the segmental branch (type I) or extending to involve the right or left portal vein (type II). RESULTS: The median survival time was significantly longer in the HR group (19.9 months) than in the TACE and sorafenib groups (6.6 and 6.2 months, respectively; both p<0.001), and did not differ significantly between the latter two groups (p=0.698). Among patients with CTP class A, type I PVTT or unilobar-involved HCC, the median survival time was longer in the HR group than in the TACE and sorafenib groups (p=0.006). In univariate analyses, the initial treatment method, tumor size, PVTT type, involved lobe, CTP class, and presence of cirrhosis or ascites were correlated with overall survival. The significant prognostic factors for overall survival in Cox proportional-hazards regression analysis were initial treatment method (HR vs. TACE: hazard ratio=1.750, p=0.036; HR vs. sorafenib: hazard ratio=2.262, p=0.006), involved lobe (hazard ratio=1.705, p=0.008), PVTT type (hazard ratio=1.617, p=0.013), and CTP class (hazard ratio=1.712, p=0.012). CONCLUSIONS: Compared with TACE or sorafenib, HR may prolong the survival of patients with HCC in cases of CTP class A, type I PVTT or unilobar-involved HCC.

Direct Acting Antivirals for Treatment of Hepatitis C Infection in Patients with Advanced Liver Disease / 대한소화기학회지

No abstract available.

Predictive factors of mortality within 30 days in patients with nonvariceal upper gastrointestinal bleeding

BACKGROUND/AIMS: Nonvariceal upper gastrointestinal bleeding (NVUGIB) is a common medical emergency that can be life threatening. This study evaluated predictive factors of 30-day mortality in patients with this condition. METHODS: A prospective observational study was conducted at a single hospital between April 2010 and November 2012, and 336 patients with symptoms and signs of gastrointestinal bleeding were consecutively enrolled. Clinical characteristics and endoscopic findings were reviewed to identify potential factors associated with 30-day mortality. RESULTS: Overall, 184 patients were included in the study (men, 79.3%; mean age, 59.81 years), and 16 patients died within 30 days (8.7%). Multivariate analyses revealed that comorbidity of diabetes mellitus (DM) or metastatic malignancy, age > or = 65 years, and hypotension (systolic pressure or = 65 years, and hemodynamic instability during hospitalization were predictors of 30-day mortality in patients with NVUGIB. These results will help guide the management of patients with this condition.

Primary Hepatic Tuberculosis Mimicking Hepatocelluar Carcinoma in Patient with Chronic Viral Hepatitis B and C / 계명의대학술지

Hepatic tuberculosis (TB) is usually associated with pulmonary or miliary TB, but primary hepatic TB is rare less than 1% of all cases of TB. Because hepatic TB lacks typical clinical manifestations as well as typical imaging findings, it is difficult to differentiate TB from the malignancies such as hepatic metastasis, intrahepatic cholangiocarcinoma and hepatocellular carcinoma. A 76-year-old woman was presented with single liver mass detected on routine examination. She was clinically diagnosed with hepatocellular carcinoma and underwent surgical excision of the lesion. However, histologic examination revealed caseous necrotizing granuloma and the PCR test for Myco-bacterium tuberculosis was positive. The final diagnosis was primary hepatic TB. Here we report the case with primary hepatic TB who was initially misdiagnosed with hepatocellular carcinoma and underwent surgical excision.

Treatment of Special Populations with Hepatitis C Virus Infection: Chronic Kidney Disease / 대한내과학회지

Hepatitis C virus (HCV) infection is prevalent in patients with chronic kidney disease, especially those on hemodialysis. Chronic HCV infection in patients with end-stage renal disease is associated with increased morbidity and mortality in the pre- and post-kidney transplant periods. Increased mortality is associated with liver complications and an elevated cardiovascular risk in HCV-infected patients on hemodialysis. Antiviral treatment may improve the prognosis of patients with HCV, and standard interferon remains the cornerstone of treatment. Direct-acting antiviral agents (DAA) are a potential new treatment modality for chronic HCV infection. Whatever DAA combination is administered, the use of ribavirin is still problematic in this population and this might affect the virological outcomes of some anti-HCV therapies.