Ginsenoside Rg3 restores hepatitis C virus-induced aberrant mitochondrial dynamics and inhibits virus propagation.

Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct-acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their use in treating patients with chronic hepatitis C in interferon-sparing regimens occasionally produces undesirable side effects such as fatigue, migraine, and other conditions, which may be linked to mitochondrial dysfunction. Here, we show that clinically prescribed DAAs, including sofosbuvir, affect mitochondrial dynamics. To counter these adverse effects, we examined HCV-induced and DAA-induced aberrant mitochondrial dynamics modulated by ginsenoside, which is known to support healthy mitochondrial physiology and the innate immune system. We screened several ginsenoside compounds showing antiviral activity using a robust HCV cell culture system. We investigated the role of ginsenosides in antiviral efficacy, alteration of mitochondrial transmembrane potential, abnormal mitochondrial fission, its upstream signaling, and mitophagic process caused by HCV infection or DAA treatment. Only one of the compounds, ginsenoside Rg3 (G-Rg3), exhibited notable and promising anti-HCV potential. Treatment of HCV-infected cells with G-Rg3 increased HCV core protein-mediated reduction in the expression level of cytosolic p21, required for increasing cyclin-dependent kinase 1 activity, which catalyzes Ser616 phosphorylation of dynamin-related protein 1. The HCV-induced mitophagy, which follows mitochondrial fission, was also rescued by G-Rg3 treatment. CONCLUSION: G-Rg3 inhibits HCV propagation. Its antiviral mechanism involves restoring the HCV-induced dynamin-related protein 1-mediated aberrant mitochondrial fission process, thereby resulting in suppression of persistent HCV infection. (Hepatology 2017;66:758-771).

Clinical Features of Drug-induced Liver Injury According to Etiology.

Drug-induced liver injury (DILI) is an increasingly common cause of acute hepatitis. We examined clinical features and types of liver injury of 65 affected patients who underwent liver biopsy according DILI etiology. The major causes of DILI were the use of herbal medications (43.2%), prescribed medications (21.6%), and traditional therapeutic preparations and dietary supplements (35%). DILI from herbal medications, traditional therapeutic preparations, and dietary supplements was associated with higher elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels than was DILI from prescription medications. The types of liver injury based on the R ratio were hepatocellular (67.7%), mixed (10.8%), and cholestatic (21.5%). Herbal medications and traditional therapeutic preparations were more commonly associated with hepatocellular liver injury than were prescription medications (P = 0.002). Herbal medications and traditional therapeutic preparations induce more hepatocellular DILI and increased elevations in AST and ALT than prescribed medications.

Pre-existing YMDD mutants in treatment-naïve patients with chronic hepatitis B are not selected during lamivudine therapy.

Although the rate at which mutations in the tyrosine-methionine-aspartate-aspartate (YMDD) motif of hepatitis B virus polymerase form is high during prolonged lamivudine (LAM) therapy, these mutations sometimes occur naturally in treatment-naïve patients with chronic hepatitis B. The prevalence of natural YMDD mutants differs geographically, and its clinical significance during LAM therapy is unknown. This study aimed to investigate whether pre-existing YMDD mutants were selected during LAM therapy. It included 14 treatment-naïve patients who were treated with LAM for at least 9 months. LAM resistance was evaluated before and at 3-month intervals during treatment. Mutations were analyzed by direct sequencing, restriction fragment mass polymorphism (RFMP) assays, and a single-step multiplex polymerase chain reaction (PCR) test using dual-priming oligonucleotide (DPO) primers. DPO-based multiplex PCR showed two YMDD mutations in two patients before LAM therapy; rtM204V and rtL180M + rtM204V/I. Further, two patients had an rtL180M mutation without an accompanying rtM204V/I mutation. No mutant was detected in any patient by direct sequencing or the RFMP assay before LAM therapy. A virological response was observed at 3 months in all patients with pre-existing YMDD mutants. All mutations disappeared after 3 months of LAM therapy, and during the follow-up period, no re-emergence was detected by any of the three methods. Further, the viral load was suppressed optimally. In conclusion, pre-existing YMDD mutants were cleared early during the course of LAM therapy, which produced a consistent virological response, and the mutants were not selected by LAM therapy.

Cryptogenic pyogenic liver abscess as the herald of colon cancer.

BACKGROUND AND AIM: Colonic mucosal defects might be a route for bacterial invasion into the portal system, with subsequent hematogenous spread to the liver. We retrospectively investigated the results of colonoscopy and the clinical characteristics of patients with pyogenic liver abscess of colonic origin. METHODS: A total of 230 consecutive patients with pyogenic liver abscess were reviewed between 2003 and 2010. The 230 patients were categorized into three groups (pancreatobiliary [n = 135], cryptogenic [n = 81], and others [n = 14]). Of the 81 cryptogenic patients, 37 (45.7%) underwent colonoscopy. Colonic lesions with mucosal defects were considered colonic causes of abscess. RESULTS: In the 37 colonoscopic investigations, colon cancer was found in six patients (16.2%), laterally-spreading tumor (LST) in two patients (5.4%), multiple colon ulcers in one patient (2.7%), colon polyps in 17 patients (45.9%), and diverticula in four patients (10.8%). Nine (11%) of 81 cryptogenic abscesses were therefore reclassified as being of colonic origin (colon cancer = 6, LST = 2, ulcer = 1). Three cases were stage III colon cancer, and the others were stage I. Two LST were high-grade dysplasia. The percentage of patients with Klebsiella pneumoniae (K. pneumoniae) and diabetes mellitus (DM) of colonic origin was 66.7%, which was significantly higher than the 8.6% for other causes (P < 0.001). CONCLUSIONS: Of the 37 patients with cryptogenic pyogenic liver abscess who underwent colonoscopy, nine (24.3%) were diagnosed with a colonic cause. Colonoscopy should be considered for the detection of hidden colonic malignant lesions in patients with cryptogenic pyogenic liver abscess, especially for patients with K. pneumoniae and DM.

Cystatin C is a good predictor of hepatorenal syndrome and survival in patients with cirrhosis who have normal serum creatinine levels.

BACKGROUND/AIMS: We evaluated the usefulness of cystatin C as a prognostic marker in patients with liver cirrhosis and normal serum creatinine. METHODOLOGY: We retrospectively analyzed prospectively enrolled patients with liver cirrhosis and normal serum creatinine from February 2007 to March 2008. We checked liver function and kidney variables including serum creatinine, cystatin C and glomerular filtration rate from 51Cr-EDTA on the same day for all patients. The endpoints of the study were either development of hepatorenal syndrome or mortality. RESULTS: In total, 112 patients with liver cirrhosis were enrolled in the study (87 men and 25 women, age 52 ± 12 years). Twelve (11%), 59 (53%) and 41 (36%) patients were in Child-Pugh class A, B and C, respectively. Cystatin C was better correlated with glomerular filtration rate from 51Cr-EDTA than creatinine. The 1-year cumulative incidence of hepatorenal syndrome and the 1-year survival rate of patients were 20.5% and 79.5%, respectively. Cystatin C, Model for End-Stage Liver Disease and serum sodium were the independent predictive factors for hepatorenal syndrome. Cystatin C, serum sodium and prothrombin time were the independent factors for predicting survival. CONCLUSIONS: In patients with liver cirrhosis and normal creatinine levels, cystatin C is a useful marker for predicting hepatorenal syndrome and survival.

Two-dimensional shear wave elastography for assessing liver fibrosis in patients with chronic liver disease: a prospective cohort study.

BACKGROUND/AIMS: The objective of this study was to determine whether the newly developed two-dimensional shear wave elastography (2D-SWE, RS85, Samsung-shearwave imaging) was more valid and reliable than transient elastography (TE) for predicting the stage of liver fibrosis. METHODS: The study prospectively enrolled a total of 116 patients with chronic liver disease who underwent 2D-SWE, TE, laboratory testing, and liver biopsy on the same day from two tertiary care hospitals. One patient with unreliable measurement was excluded. The measurement of 2D-SWE was considered acceptable when a homogenous color pattern in a region of interest of at least 10 mm was detected at 10 different sites. Diagnostic performance was calculated using area under the receiver operating characteristic curve (AUROC). RESULTS: Liver fibrosis stages included F0 (18%), F1 (19%), F2 (24%), F3 (22%), and F4 (17%). Interclass correlation coefficient for inter-observer agreement in 2D-SWE was 0.994 (95% confidence interval [CI], 0.988 to 0.997). Overall, the results of 2D-SWE and stages of histological fibrosis were significantly correlated (r = 0.601, p < 0.001). For The 2D-SWE showed good diagnostic ability (AUROC, 0.851; 95% CI, 0.773 to 0.911) comparable to TE (AUROC, 0.859; 95% CI, 0.781 to 0.916) for the diagnosis of significant fibrosis (≥ F2), and the cut-off value was 5.8 kPa. AUROC and optimal cut-off of 2D-SWE for the diagnosis of liver cirrhosis were 0.889 (95% CI, 0.817 to 0.940) and 9.6 kPa, respectively. TE showed similar diagnostic performance in distinguishing cirrhosis (AUROC, 0.938; 95% CI, 0.877 to 0.974; p = 0.08). CONCLUSION: 2D-SWE is comparable to TE in diagnosing significant fibrosis and liver cirrhosis with high reliability.

[A case of locally invasive obstructive jejunal cancer with curative resection after stenting and chemotherapy].

Small bowel adenocarcinoma is a relatively rare malignancy. In Korea, 13.1% of small bowel adenocarcinoma occurs in the jejunum. The absence of effective screening methods and relatively obscure symptoms contribute to the higher percentage of advanced cases at the time of diagnosis. Although curative resection is the mainstay of treatment, it is often impossible. Chemotherapy and radiotherapy have shown a disappointing treatment result for advanced staged small bowel adenocarcinoma. We report a 54-year-old woman with locally invasive jejunal cancer who underwent curative resection after stent insertion with enteroscopy and chemotherapy.

Detection of distant metastasis to skeletal muscle by 18F-FDG-PET in a case of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma is a rare malignancy that originates from the epithelial cells of the intrahepatic bile ducts. Intrahepatic cholangiocarcinoma can metastasize in lymphatic chains, including the hepatoduodenal ligament, and it often invades adjacent organs or metastasizes to other visceral organs such as the lungs, bones, adrenal glands, and brain. However, distant skeletal muscle metastasis is very rare. Moreover, a metastatic skeletal muscle tumor rarely shows specific symptoms, making it difficult to identify in a routine examination. A 45-year-old man with a chief complaint of right upper quadrant abdominal pain was admitted to our hospital. Abdominal ultrasound and computed tomography with contrast enhancement showed a malignant mass in the right hepatic lobe, and 2-[18F] fluoro-2-deoxy-D-glucose positron-emission tomography revealed distant skeletal muscle metastases in the thorax and buttock. The patient underwent an ultrasound-guided percutaneous needle biopsy for the metastatic low-echo masses in the skeletal muscle.

[Occurrence of diabetic ketoacidosis and autoimmune thyroiditis in a patient treated with pegylated interferon-alpha 2b and ribavirin for chronic hepatitis C].

Combined pegylated interferon and ribavirin therapy for chronic hepatitis C infection cause a wide range of side effects, including flu-like syndrome, hematological abnormalities, cardiovascular symptoms, gastrointestinal symptoms, pulmonary dysfunction, depression, and retinopathy. Interferon-alpha has been shown to be related to the development of various autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, autoimmune thyroid disease, and type 1 diabetes mellitus (DM). Type 1 DM and thyroid disease respectively develop in 0.08-2.61% and 10-15% of patients treated with combined interferon-alpha and ribavirin for chronic hepatitis C. The coexistence of type 1 DM and autoimmune thyroiditis was rarely reported. We report a case of a 33-year-old female patient with chronic hepatitis C who simultaneously developed diabetic ketoacidosis and autoimmune thyroiditis after treatment with pegylated interferon-alpha 2b and ribavirin.

[The usefulness of transient elastography to diagnose cirrhosis in patients with alcoholic liver disease].

BACKGROUNDS/AIMS: It is not easy to differentiate between patients with cirrhosis and those with alcoholic liver disease. Liver biopsy is generally considered the gold standard for assessing hepatic fibrosis; however, this protocol frequently carries a risk of severe complications and false-negative results. Transient elastography (Fibroscan, Echosens, Paris, France), which is a noninvasive method of measuring liver stiffness, has become available for assessing liver fibrosis. Liver stiffness reportedly differs markedly with the cirrhosis etiology. The aim of this study was thus to determine the diagnostic accuracy of the Fibroscan in the detection of cirrhosis in patients with alcoholic liver disease. METHODS: We enrolled 45 patients with alcoholic liver disease. Fibroscan, abdominal ultrasonography, aspartate aminotransferase/platelet ratio index (APRI), and liver biopsy were performed on all patients. Fibrosis stage was assessed using the Batts-Ludwig scoring system. RESULTS: The stage of fibrosis (F1-F4) was distributed among the cohort as follows: 5 patients at F1, 4 patients at F2, 7 patients at F3, and 29 patients at F4. Liver stiffness differed significantly between each fibrosis stage (P<0.001). For the diagnosis of cirrhosis, the area under the receiver operating characteristic curve was 0.97 for transient elastography (95% confidence interval, CI, 0.93-1.01), 0.81 for ultrasonography (95% CI, 0.68-0.94), and 0.83 for APRI score (95% CI, 0.70-0.95). The optimal cut-off value of liver stiffness for detecting cirrhosis was 25.8 kPa, with a sensitivity of 90% and a specificity of 87%. CONCLUSIONS: Transient elastography is a useful method for diagnosing cirrhosis in patients with alcoholic liver disease.

Usefulness of noninvasive methods including assessment of liver stiffness by 2-dimensional shear wave elastography for predicting esophageal varices.

BACKGROUND: The aim of this study was to predict the presence of esophageal varices (EVs) by noninvasive tools combined with 2-dimensional shear wave elastography (2D-SWE), and to compare the diagnostic capabilities of 2D-SWE with those of transient elastography (TE). METHODS: Between January 2015 and December 2017, 289 patients with compensated advanced chronic liver disease (cACLD) who underwent consecutive 2D-SWE and EGD were enrolled. Capabilities for predicting the presence of EVs of 2D-SWE and models combining 2D-SWE with other noninvasive tools (modified LS-spleen-diameter-to-platelet-ratio score [mLSPS], platelet-spleen ratio score) were compared. A subgroup analysis was performed on 177 patients who also underwent simultaneous TE. RESULTS: The area under receiver operating characteristics (AUROCs) for detecting EVs for 2D-SWE alone vs. mLSPS, which included 2D-SWE, were 0.757 (95% confidence interval [CI], 0.701-0.810) and 0.813 (95% CI, 0.763-.857), respectively. The AUROCs for predicting varices needing treatment (VNT) for 2D-SWE and mLSPS were 0.712 (95% CI, 0.621-0.738) and 0.834 (95% CI, 0.785-0.875), respectively. For the 195 patients who underwent simultaneous TE and 2D-SWE, no differences in diagnostic performance were observed. CONCLUSIONS: The diagnostic performance of 2D-SWE is similar to that of TE for predicting the presence of EVs. The mLSPS, which includes 2D-SWE, seemed to be useful for predicting EVs.

Platelet count is associated with sustained virological response rates in treatments for chronic hepatitis C.

BACKGROUND/AIMS: This study was conducted to clarify the sustained virological response (SVR) prediction ability of baseline and treatment-related factors in patients with chronic hepatitis C virus (HCV) infection. METHODS: This retrospective study collected data at four tertiary referral hospitals between June 2004 and July 2012. Out of 476 patients, 330 treatment-naïve patients with chronic HCV infection were recruited. Pegylated interferon α-2a/- 2b plus ribavirin was administered for either 24 or 48 weeks depending on the HCV genotype. The baseline and treatment-related predictive factors of SVR were evaluated by analyzing data measured before treatment (i.e., baseline) and during treatment. RESULTS: SVR rates for genotypes 1 and 2 were 63% (97/154) and 79.5% (140/176), respectively (p = 0.001). Multivariate analysis for baseline factors revealed that young age (p = 0.009), genotype 2 (p = 0.001), HCV RNA level of < 800,000 IU/mL (p < 0.001), and a baseline platelet count of > 150 × 103 /µL (p < 0.001) were significant SVR predictors, regardless of the genotype. In particular, predictive accuracy for achievement of SVR was 87.3% for a baseline platelet count of > 150 × 103 /µL. In multivariate analysis for treatment-related factors, SVR was associated with achievement of a rapid virological response (RVR; p < 0.001), treatment adherence of ≥ 80/80/80 (p < 0.001). CONCLUSION: Young age, genotype 2, low HCV RNA level, RVR, and treatment adherence were significantly associated with SVR. In addition, platelet count was an independent predictive factor for SVR. Therefore, platelet count could be used to develop individualized treatment regimens and to optimize treatment outcomes in patients with chronic HCV infection.

Clinical outcomes of patients with a single hepatocellular carcinoma less than 5 cm treated with transarterial chemoembolization.

BACKGROUND/AIMS: Transarterial chemoembolization (TACE) is performed for single hepatocellular carcinoma (HCC) that are not eligible for surgery or ablation therapy. We investigated the clinical outcomes of patients with a single HCC ≤ 5 cm treated with TACE. METHODS: This study analyzed 175 consecutive patients who underwent TACE as an initial treatment for single HCC ≤ 5 cm. Predictive factors for complete response (CR), recurrence after CR, and overall survival (OS) were evaluated. RESULTS: Total 119 patients (68%) achieved CR after TACE. Tumor size < 3 cm and hepatitis B virus infection were significant predictors of CR (p < 0.05). Recurrent HCC was detected in 73 patients (61.3%) after CR. Age > 65 years and absence of liver cirrhosis were predictive factors for non-recurrence after CR (p < 0.05). The OS for all patients was 80.7 ± 5.6 months, and the 1-, 3-, and 5-year OS rates were 88.1%, 64.8%, and 49.9%, respectively. In multivariate analysis for OS, CR (hazard ratio [HR], 0.467; 95% confidence interval [CI], 0.292 to 0.747) and Child class A (HR, 0.390; 95% CI, 0.243 to 0.626) were significant factors. The OS for the CR and Child class A group were 92 and 93.6 months, respectively, and that of the non-CR and Child B, C group were 53.3 and 50.7 months, respectively (p < 0.001). CONCLUSION: TACE can be a valid treatment in patients with a single HCC ≤ 5 cm not suitable for curative treatment, especially in patients with Child class A and CR after TACE.

[Significance of microsatellite instability in early gastric cancer treated by endoscopic submucosal dissection].

BACKGROUND/AIMS: Microsatellite instability (MSI) is defined as a change of any length due to either insertion or deletion of repeating units, in a microsatellite within a tumor when compared to normal tissue. MSI is closely related with genetic instability, particularly in hereditary nonpolyposis colorectal cancer. MSI is found in 10-50% of all gastric cancers, suggesting that MSI may play an important role in carcinogenesis. The aim of this study was to investigate the relationship between microsatellite instability and clinicopathologic features in early gastric cancers (EGCs) treated by endoscopic submucosal dissection (ESD). METHODS: We analyzed clinicopathological features of 95 specimens of EGCs including MSI, histologic type, mucin phenotype, p53, VEGF, location of cancer, depth of invasion, incidence of synchronous and metachronous cancer, age, and gender derived from 94 patients, treated by ESD during recent 19 months were analyzed in this study. RESULTS: According to microsatellite stability, MSI was observed in 13 (13.7%) cases of 95 specimens. The incidence of MSI was increased in patients with cancer at lower part of stomach and female gender. There was no significant relation between MSI and clinicopathologic features including histologic type, mucin phenotype, p53, VEGF, and depth of invasion. CONCLUSIONS: Our results demonstrate that there is no relationship between MSI and clinicopathologic features except tumor location and gender in ECGs treated by ESD. However, further studies are needed to evaluate the significance of MSI in EGCs.

Clinical significance of radiation-induced liver disease after stereotactic body radiation therapy for hepatocellular carcinoma.

BACKGROUND/AIMS: The aim of this study was to investigate parameters that predict radiation-induced liver disease (RILD) following stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma (HCC) and to identify the clinical significance of RILD. METHODS: We retrospectively reviewed the medical records of 117 HCC patients who were treated by SBRT from March 2011 to February 2015. RILD was defined as elevated liver transaminases more than five times the upper normal limit or a worsening of Child-Pugh (CP) score by 2 within 3 months after SBRT. All patients were assessed at 1 month and every 3 months after SBRT. RESULTS: Median follow-up was 22.5 months (range, 3 to 56) after SBRT. RILD was developed in 29 of the 117 patients (24.7%). On univariate analysis, significant predictive factors of RILD were pretreatment CP score (p < 0.001) and normal liver volume (p = 0.002). Multivariate analysis showed that CP score was a significant predictor of RILD (p < 0.001). The incidence of RILD increased above a CP score of 6 remarkably. The rate of recovery from RILD decreased significantly above a CP score of 8. Survival analysis showed that CP score was an independent prognostic factor of overall survival (p = 0.001). CONCLUSION: CP score is a significant factor to predict RILD in patients with chronic liver disease. RILD can be tolerated by patients with a CP score ≤ 7. However, careful monitoring of liver function is needed for patients with a CP score 7 after SBRT.

Effect of tenofovir on renal function in patients with chronic hepatitis B.

Tenofovir disoproxil fumarate (TDF) is widely used to treat patients with hepatitis B virus (HBV) infection. We investigated the effect of TDF on renal insufficiency in patients with chronic hepatitis B (CHB).A consecutive cohort analysis was applied to CHB patients taking prescribed TDF from January 2012 to May 2016 at Soonchunhyang University Seoul Hospital. Alterations over time in corrected calcium, phosphate, creatinine, and estimated glomerular filtration rate (eGFR) were analyzed using the generalized estimating equation method. The percentage increase in creatinine from baseline to the maximum creatinine level (delta creatinine) was compared according to the underlying disease using the Mann-Whitney U test. Cox proportional hazard regression model was used to determine risk factors associated with renal insufficiency.The baseline creatinine, eGFR, corrected calcium, and phosphate levels were 0.72 ±â€Š0.01 mg/dL (mean ±â€ŠSD), 106.37 ±â€Š1.06 mL/min/1.73 m, 8.82 ±â€Š0.04 mg/dL, and 3.42 ±â€Š0.05 mg/dL, respectively. The creatinine level had increased significantly at 12, 24, 48, 72, and 96 weeks, while the eGFR level had decreased significantly at these 5 time points. Multivariate analysis confirmed that age ≥60 years and the baseline bilirubin level were independently associated with the risk of renal insufficiency. Delta creatinine was significantly higher in patients with diabetes mellitus (DM) than in patients without DM.Renal function was decreased from baseline in CHB patients receiving TDF therapy, which indicates that the renal function of patients undergoing treatment with TDF should be monitored regularly. Old age, DM, and serum bilirubin were risk factors for the development of renal insufficiency in CHB patients receiving TDF therapy.

Tenofovir disoproxil fumarate monotherapy is superior to entecavir-adefovir combination therapy in patients with suboptimal response to lamivudine-adefovir therapy for nucleoside-resistant HBV: a 96-week prospective multicentre trial.

BACKGROUND: A complete virological response is closely related to the long-term outcome of patients with chronic hepatitis B and prevention of emerging HBV mutations. We aimed to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) monotherapy compared to entecavir-adefovir dipivoxil (ETV-ADV) combination therapy in patients with suboptimal responses to long-term lamivudine-adefovir dipivoxil (LAM-ADV) therapy for nucleoside analogue-resistant chronic hepatitis B. METHODS: Patients (n=60) were randomized to TDF monotherapy or ETV-ADV combination therapy for 96 weeks. All patients had the rt204I/V mutation and serum HBV DNA was measured (>60 IU/ml) during LAM-ADV therapy. The primary end point was a complete virological response (HBV DNA <20 IU/ml) at week 96. RESULTS: The median duration of prior LAM-ADV rescue therapy was 43 (7-108) months. A complete virological response was achieved in 86.6% and 53.3% of patients in the TDF and ETV-ADV groups, respectively, at week 96 (P=0.005). Reduction in serum HBV DNA was significantly greater in the TDF group than in ETV-ADV group (-3.2 ±1.2 versus -2.6 ±1.2; P=0.01). Hepatitis B e antigen loss (22.2% versus 16.6%; P=0.731) and biochemical responses (76.7% versus 73.3%; P=0.766) were not different between the TDF and ETV-ADV groups. No newly emerged mutations were detected. Both therapies demonstrated favourable safety profiles. CONCLUSIONS: TDF therapy achieved a better complete virological response than ETV-ADV therapy in chronic hepatitis B patients with suboptimal response to long-term LAM-ADV rescue therapy. (KCT0000627).

[Long-term results of endoscopic histoacryl (N-butyl-2-cyanoacrylate) injection for treatment of gastric varices--a 10-year experience].

BACKGROUND/AIMS: Gastric variceal bleeding is an infrequent but serious complication of portal hypertension. Endoscopic injection of Histoacryl (N-butyl-2-cyanoacrylate) has been approved as an effective treatment for gastric variceal bleeding. The aim of this study was to evaluate the long-term efficacy and safety of the endoscopic injection of Histoacryl for the treatment of gastric varices. METHODS: Between January 1994 and January 2005, eighty-five patients with gastric varices received endoscopic injections of Histoacryl. Among these 85 patients, 65 received the procedure within 1 week after gastric variceal bleeding, and 13 received as a prophylactic procedure. According to the Sarin classification, 32 patients were GOV1 and 53 were GOV2. Most of the varices were large (F2 or F3, 75 patients). The average volume of Histoacryl per each session was 1.43 ml. Among 85 patients, 72 patients were followed-up and the median duration was 24.5 months. RESULTS: The rate of initial hemostasis was 98.6% and recurrent bleeding occurred in 29.2% (21 of 72). When rebleeding occurred, 76.2% was within 1 year after the initial injection. Treatment failure-related mortality rate was 1.4% (1 of 85). Twenty-seven patients died, mostly due to hepatocelluar carcinoma or liver failure. Two patients experienced pulmonary embolism and one experienced splenic infarction. They recovered without specific treatment. Rebleeding rate had a tendency to increase in patients with hepatocelluar carcinoma (p=0.051) and GOV2 (p=0.061). CONCLUSIONS: Histoacryl injection therapy is a effective treatment method for gastric varices with high initial hemostasis rate and low major complications.

[Effectiveness and tolerance of duodenoscopic bowel preparation for colonoscopy].

BACKGROUND/AIMS: Bowel preparation for colonoscopy remains an unpleasant experience because oral solutions have unpleasant tastes and may provoke abdominal pain, nausea, vomiting, and sleep disturbance. Duodenoscopic bowel preparation is an alternative method for patients who are unwilling to take oral preparation solution or for those who are supposed to have both gastroscopic and colonoscopic examination on the same day. We assessed the effectiveness and tolerance of duodenoscopic bowel preparation. METHODS: Patients in group OA (orally administered) ingested 45 mL of sodium phosphate (NaP) in the evening before the day of procedure and in the morning on the day of colonoscopy, whereas patients in group EA (endoscopically administered) were prepared for the procedure by duodenoscopic infusion of 90 mL of NaP diluted with 180 mL of water into the second portion of the duodenum. After 4 hours, we assessed the overall quality of colonic cleansing, using a range of excellent to inadequate. The patients completed a questionnaire on their preparation-associated symptoms, tolerance, and preference. RESULTS: In group EA, sleep disturbance (p0.05) and nausea (p0.05) occurred less frequently than in group OA. Overall, the tolerance rating for preparation was higher in group EA. However, the quality of colonic cleansing and cecum intubation time was not different between the two groups. Patients in group EA who had ingested NaP in the past preferred duodenoscopic bowel preparation. CONCLUSIONS: Duodenoscopic bowel preparation may play a role in colonic cleansing especially for patients who are scheduled to undergo gastroscopic and colonoscopic examination on the same day and for those who are unwilling to ingest NaP.