Real-world Effectiveness and Safety of Direct-acting Antiviral Agents in Patients with Chronic Hepatitis C Genotype 2 Infection: Korean Multicenter Study

Background@#The advancement of treatment with direct-acting antiviral (DAA) agents has improved the cure rate of hepatitis C virus (HCV) infection close to 100%. The aim of our study was to assess the real-world effectiveness and safety of DAA regimens for the treatment of patients with chronic HCV genotype 2. @*Methods@#We retrospectively analyzed the clinical data of patients treated with sofosbuvir plus ribavirin (SOF + RBV) or glecaprevir/pibrentasvir (G/P) for chronic HCV genotype 2 infection at seven university hospitals in the Korean southeast region. @*Results@#SOF + RBV therapy produced an 89% and 98.3% sustained virologic response 12 week (SVR12) after treatment completion in the full analysis set and per-protocol set, respectively, and the corresponding values for G/P therapy were 89.5% and 99.2%, respectively. The difference between the treatments was probably because 6.2% (59/953) of patients in the SOF + RBV group did not complete the treatment and 9.8% (14/143) in the G/P group did not test HCV RNA after treatment completion. Adverse events (A/Es) were reported in 59.7% (569/953) and 25.9% (37/143) of the SOF + RBV and G/P groups, respectively. In the SOF + RBV group, 12 (1.26%) patients discontinued treatment owing to A/Es, whereas no patients discontinued treatment because of A/Es in the G/P group. @*Conclusion@#In both treatment groups, SVR was high when treatment was completed.However, there was a high dropout rate in the SOF + RBV group, and the dropout analysis showed that these were patients with liver cirrhosis (LC; 43/285, 15.1%), especially those with decompensated LC (12/32, 37.5%). Therefore, an early initiation of antiviral therapy is recommended for a successful outcome before liver function declines. Furthermore, patients with decompensated LC who are considered candidates for SOF + RBV treatment should be carefully monitored to ensure that their treatment is completed, especially those with low hemoglobin and high alanine transaminase.

Real-world Effectiveness and Safety of Direct-acting Antiviral Agents in Patients with Chronic Hepatitis C Genotype 2 Infection: Korean Multicenter Study

Background@#The advancement of treatment with direct-acting antiviral (DAA) agents has improved the cure rate of hepatitis C virus (HCV) infection close to 100%. The aim of our study was to assess the real-world effectiveness and safety of DAA regimens for the treatment of patients with chronic HCV genotype 2. @*Methods@#We retrospectively analyzed the clinical data of patients treated with sofosbuvir plus ribavirin (SOF + RBV) or glecaprevir/pibrentasvir (G/P) for chronic HCV genotype 2 infection at seven university hospitals in the Korean southeast region. @*Results@#SOF + RBV therapy produced an 89% and 98.3% sustained virologic response 12 week (SVR12) after treatment completion in the full analysis set and per-protocol set, respectively, and the corresponding values for G/P therapy were 89.5% and 99.2%, respectively. The difference between the treatments was probably because 6.2% (59/953) of patients in the SOF + RBV group did not complete the treatment and 9.8% (14/143) in the G/P group did not test HCV RNA after treatment completion. Adverse events (A/Es) were reported in 59.7% (569/953) and 25.9% (37/143) of the SOF + RBV and G/P groups, respectively. In the SOF + RBV group, 12 (1.26%) patients discontinued treatment owing to A/Es, whereas no patients discontinued treatment because of A/Es in the G/P group. @*Conclusion@#In both treatment groups, SVR was high when treatment was completed.However, there was a high dropout rate in the SOF + RBV group, and the dropout analysis showed that these were patients with liver cirrhosis (LC; 43/285, 15.1%), especially those with decompensated LC (12/32, 37.5%). Therefore, an early initiation of antiviral therapy is recommended for a successful outcome before liver function declines. Furthermore, patients with decompensated LC who are considered candidates for SOF + RBV treatment should be carefully monitored to ensure that their treatment is completed, especially those with low hemoglobin and high alanine transaminase.

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.

Prevalence and Factors Associated with Nonalcoholic Fatty Liver Disease in a Nonobese Korean Population

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is an emerging problem in Asia, but little is known about the disease in the nonobese population. The aims of this study were to investigate the prevalence of NAFLD and the factors associated with it in a nonobese Korean population and to compare the clinical characteristics of nonobese and obese subjects with NAFLD. METHODS: This cross-sectional study used data from 2,058 subjects who participated in a medical checkup program. RESULTS: The prevalence of NAFLD was 12.4% (213/1,711) in the nonobese population. A higher body mass index (BMI), higher homeostasis model assessment of insulin resistance (HOMA-IR) values, higher alanine aminotransferase (ALT) levels, triglyceride concentrations 150 mg/dL, and hyperuricemia were independently associated with the presence of NAFLD in the nonobese subjects. Compared with the obese subjects with NAFLD, the nonobese subjects with NAFLD were composed of a higher proportion of females and had lower BMIs, smaller waist circumferences, lower HOMA-IR values, and fewer metabolic irregularities. CONCLUSIONS: Higher BMIs, HOMA-IR values, ALT levels, hypertriglyceridemia, and hyperuricemia were associated with NAFLD in the nonobese subjects. Clinicians should be particularly aware of the possibility of NAFLD in nonobese Asian people.

Early monitoring for detection of antituberculous drug-induced hepatotoxicity

BACKGROUND/AIMS: We investigated the time of onset of antituberculous drug-induced hepatotoxicity (ADIH) and related characteristics. METHODS: Adult patients (n = 1,031) treated with first-line antituberculous drugs between February 2009 and January 2013 were enrolled. RESULTS: Of the 1,031 patients, 108 patients (10.5%) developed ADIH a mean of 39.6 +/- 43.7 days after treatment initiation. Twenty-eight patients (25.9%) developed ADIH within 7 days, 73 (67.6%) within 30 days, and the rest after 30 days. The 30-day group. In subgroup analysis, the 40 IU/L (odds ratio [OR], 2.995; 95% confidence interval [CI], 1.580 to 5.680; p = 0.001) and presence of anti-hepatitis C virus (OR, 4.204; 95% CI, 1.822 to 9.700, p = 0.001) were independent risk factors for development of ADIH. CONCLUSIONS: Approximately 70% of the cases of ADIH occurred in the first month of antituberculous treatment, and were associated with continuation of the first-line drug regimen.

Prediction of the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients after Sustained Virological Response by Aspartate Aminotransferase to Platelet Ratio Index

BACKGROUND/AIMS: Following sustained virological response (SVR) for chronic hepatitis C (CHC) infection, patients with advanced fibrosis require regular monitoring for hepatocellular carcinoma (HCC). The aspartate aminotransferase to platelet ratio index (APRI) is a simple noninvasive surrogate marker known to reflect fibrosis. METHODS: We retrospectively analyzed 598 patients who achieved SVR with interferon-based therapy for CHC. RESULTS: Over a median of 5.1 years of follow-up, there were eight patients diagnosed with HCC and a 5-year cumulative incidence rate of 1.3%. The median pretreatment APRI was 0.83, which decreased to 0.29 after achieving SVR (p<0.001). Both the pre- and posttreatment indices were associated with HCC development. The 5-year cumulative HCC incidence rates were 0% and 2.8% for patients with pretreatment APRI <1.0 and ≥1.0, respectively (p=0.001) and 0.8% and 12.8% for patients with posttreatment APRI <1.0 and ≥1.0, respectively (p<0.001). Pretreatment APRI at a cutoff of 1.0 had a 100% negative predictive value until 10 years after SVR. CONCLUSIONS: HCC development was observed among CHC patients who achieved SVR. The pre- and post-treatment APRI could stratify HCC risk, indicating that the APRI could be a useful marker to classify HCC risk in CHC patients who achieved SVR. However, given the small number of HCC patients, this finding warrants further validation.

Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma

Recent studies have shown that circulating microRNAs are a potential biomarker in various types of malignancies. The aim of this study was to investigate the feasibility of using serum exosomal microRNAs as novel serological biomarkers for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We measured the serum exosomal microRNAs and serum circulating microRNAs in patients with CHB (n=20), liver cirrhosis (LC) (n=20) and HCC (n=20). Serum exosomal microRNA was extracted from 500 mul of serum using an Exosome RNA Isolation kit. The expression levels of microRNAs were quantified by real-time PCR. The expression levels of selected microRNAs were normalized to Caenorhabditis elegans microRNA (Cel-miR-39). The serum levels of exosomal miR-18a, miR-221, miR-222 and miR-224 were significantly higher in patients with HCC than those with CHB or LC (P<0.05). Further, the serum levels of exosomal miR-101, miR-106b, miR-122 and miR-195 were lower in patients with HCC than in patients with CHB (P=0.014, P<0.001, P<0.001 and P<0.001, respectively). There was no significant difference in the levels of miR-21 and miR-93 among the three groups. Additionally, the serum levels of circulating microRNAs showed a smaller difference between HCC and either CHB or LC. This study suggests that serum exosomal microRNAs may be used as novel serological biomarkers for HCC.

Pegylated Interferon and Ribavirin in the Retreatment of Chronic Hepatitis C in Korea

BACKGROUND/AIMS: Pegylated interferon (peginterferon) and ribavirin is the current standard therapy for chronic hepatitis C. The aims of this study were to evaluate the efficacy of peginterferon and ribavirin and to identify predictors of a sustained virological response (SVR) to the retreatment of chronic hepatitis C in Korea. METHODS: The clinical records of 91 patients with chronic hepatitis C who were retreated with peginterferon and ribavirin were retrospectively analyzed. None of the patients had previously attained a SVR, and the patients were categorized according to their previous responses (nonresponder, relapser, or inadequate treatment) to conventional interferon/ribavirin. RESULTS: The overall SVR rate was 54.9%. Independent predictors of a SVR were genotypes 2 and 3, relapse, an adherence to peginterferon of over 80%, and an early virological response (EVR). For genotype 1 patients, an adherence to peginterferon of over 80% was an independent predictor of a SVR. CONCLUSIONS: Peginterferon and ribavirin therapy is effective for the retreatment of Korean chronic hepatitis C patients who have failed interferon/ribavirin, especially in patients with genotypes 2 and 3, relapse, an adherence to peginterferon over 80%, and an EVR. For genotype 1 patients, retreatment was effective in patients with an adherence to peginterferon over 80%.

The Seroconversion Rate of Hepatitis A Virus Vaccination among Patients with Hepatitis B Virus-Related Chronic Liver Disease in Korea

BACKGROUND/AIMS: The aim of this study was to evaluate the seroconversion rate of a hepatitis A virus (HAV) vaccination in patients with hepatitis B virus (HBV)-related chronic liver disease (CLD). METHODS: Analyses were conducted using clinical records from 94 patients with chronic HBV infection who were seronegative for IgG anti-HAV antibodies between September 2008 and June 2009. Two doses of an HAV vaccine were administered 24 weeks apart. A third vaccine dose was administered only for patients seronegative for anti-HAV antibodies at week 48. RESULTS: The seroconversion rate of anti-HAV following the two-dose vaccination was 86.17%. The seroconversion rate of anti-HAV was not significantly different according to age or status of liver disease. The rate was higher in female than in male patients. A third HAV vaccine dose was administered to 13 patients seronegative for anti-HAV after the two-dose regimen, and 84.62% of these patients showed seroconversion at week 72. CONCLUSIONS: HAV vaccination is effective in most Korean patients with HBV-related CLD, and it might be necessary to evaluate three-dose vaccination approach for non-responders to the conventional regimen to maximize the success of an HAV vaccination program.

A gastric schwannoma presenting as an abdominal mass / 대한내과학회지

Schwannomas or neurilemmomas of the gastrointestinal tract are very rare and constitute less than 1% of all gut neoplasms. We experienced a case of schwannoma in the stomach, which is an extremely rare site. The patient was a 55-year-old woman who complained of an abdominal mass. At endoscopy, a 10-cm ulcerated submucosal mass was seen in the posterior wall of the body of the stomach. Computed tomography showed a heterogenous mass in the stomach without metastasis. The tumor was resected with the stomach. Both histological and immunohistochemical staining with S-100 protein revealed that it was a schwannoma.

A case of liver abscess due to Klebsiella oxytoca / 대한내과학회지

Klebsiella are opportunistic pathogens that cause a wide spectrum of severe diseases, such as septicemia, pneumonia, urinary tract infection, and soft tissue infection. Klebsiella oxytoca is rarely isolated from human clinical specimens, and bacteremia due to Klebsiella oxytoca remains relatively uncommon. We experienced a case of liver abscess due to Klebsiella oxytoca in a 71-year-old male with a history of pylorus-preserving pancreaticoduodenectomy (PPPD) 4 years earlier. The patient was diagnosed with hemobilia secondary to a pseudo-aneurysm at the lower pole of the abscess cavity during antibiotic treatment and was treated successfully with selective percutaneous transcatheter embolization

A case of esophageal carcinosarcoma / 대한내과학회지

Carcinosarcoma of the esophagus is a rare malignant neoplasm that consists of both carcinomatous and sarcomatous components, accounting for approximately 1~2% of all esophageal neoplasms. The terms previously used to describe this tumor include pseudosarcoma, pseudosarcomatous carcinoma, polypoid carcinoma, so-called carcinosarcoma, true carcinosarcoma, and spindle cell carcinoma. Although about 11 cases of esophageal carcinosarcoma have been reported in Korea, none have included findings from positron emission tomography. Here, we report a case of esophageal carcinosarcoma in a 63-year-old man who presented with a 3 month history of progressive dysphagia and weight loss. Positron emission tomography shows expanding hot uptake (mSUV, 9.94) in the distal esophagus.

Reactivation of Pulmonary Tuberculosis in a Patient with Polygonum multiflorum Thunb-Induced Hepatitis

Several cases of Polygonum multiflorum Thunb-induced hepatitis have been reported worldwide. Anthraquinone is an active ingredient of P. multiflorum Thunb. that has been thought to play a role in its hepatotoxicity. Here we report the case of a 34-year-old Korean man who had P. multiflorum Thunb-induced hepatitis and reactivation of pulmonary tuberculosis caused by bone marrow suppression, which developed simultaneously. He was admitted to our hospital with recently developed fatigue and aggravated jaundice. He was a previously healthy man except for the sequelae of pulmonary tuberculosis seen on chest X-ray. He had a 30-day history of ingesting the root of P. multiflorum as a form of liquor and tea. The patient was diagnosed with P. multiflorum Thunb-induced hepatitis after excluding all other potential causes of acute hepatitis. Liver function gradually improved following the total cessation of the consumption of the material. However, he suffered from spiking fever with progressive pancytopenia during the hospital stay. A bone marrow biopsy showed markedly hypocellular marrow, suggesting transient bone marrow suppression, which was probably caused by extrinsic factors such as drugs, toxins, and viral infection. Although he began to complain of a dry cough, repeated sputum investigations revealed positive acid-fast bacillus staining. The fever subsided and pancytopenia improved after treatment for pulmonary tuberculosis. These observations suggest that P. multiflorum Thunb induces both bone marrow suppression and hepatotoxicity.

A Case of Gastric Suture Granuloma Suspected of Malignant Submucosal Tumor / 대한소화기내시경학회지

A gastric suture granuloma is an uncommon postsurgical complication. When nonabsorbable sutures are used, the inflammation can persist months after the original procedure with the subsequent formation of an abscess around the sutures surrounded by granulation tissue. Suture granulomas are usually asymptomatic, and have clinical importance as a differential diagnosis of a gastric submucosal tumor. The incidence of suture granuloma is low using absorbable sutures in gastrointestinal anastomosis. We report a case of a 70 year old man diagnosed with a suture granuloma. Approximately 30 years earlier, he underwent primary closure due to gastric ulcer perforation. When a gastroscopy was performed to assess upper abdominal soreness, it revealed a submucosal tumor that indicated a malignancy, which was diagnosed as a suture granuloma after surgery.

A Case of Primary Esophageal Small Cell Carcinoma with Intraperitoneal Multiple Lymph Node Metastasis / 대한소화기내시경학회지

Two cases of esophageal small cell carcinoma were reported on for the first time in 1952. There have been only a few published series on the patients with esophageal small cell carcinoma, and only 19 cases have been reported in Korea. As in the case of small cell carcinoma of the lung, the esophageal small cell carcinoma is known to show rapid progression and early metastasis. Yet much remains to be uncovered about the clinical features, optimal treatment and natural history of this disease. We report here on a case of primary esophageal small cell carcinoma with intraperitoneal multiple lymph node metastasis. The size of the tumor was markedly decreased by combination chemotherapy.