Soo Hyung Ryu

Twenty‐four‐week clevudine therapy showed potent and sustained antiviral activity in HBeAg‐positive chronic hepatitis B

Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV. The present study evaluated the safety and efficacy of 30 mg clevudine once daily for 24 weeks and assessed the durable antiviral response for 24 weeks after cessation of dosing. A total of 243 hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B patients were randomized (3:1) to receive clevudine 30 mg once daily (n = 182) or placebo (n = 61) for 24 weeks. Patients were followed for a further 24 weeks off therapy. Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log10 copies/mL in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained off therapy, with 3.73 log10 reduction at week 34 and 2.02 log10 reduction at week 48. At week 24, 59.0% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (less than 300 copies/mL). The proportion of patients who achieved normalization of alanine aminotransferase (ALT) levels was 68.2% in the clevudine group and 17.5% in the placebo group at week 24 (P < 0.0001). ALT normalization in the clevudine group was well maintained during post‐treatment follow‐up period. The incidence of adverse events (AEs) was similar between the clevudine group and the placebo group. No resistance to clevudine was detected with 24 weeks of administration of drug. Conclusion: A 24‐week clevudine therapy was well tolerated and showed potent and sustained antiviral effect without evidence of viral resistance during treatment period in HBeAg‐positive chronic hepatitis B. (HEPATOLOGY 2007;45:1172–1178.)

Clevudine is highly efficacious in hepatitis B e antigen‐negative chronic hepatitis B with durable off‐therapy viral suppression

Clevudine is a pyrimidine analog with potent and sustained antiviral activity against HBV. In the present study, we evaluated the safety and efficacy of clevudine 30 mg daily for 24 weeks and assessed the durability of antiviral response for 24 weeks after cessation of dosing in hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B (e‐CHB). We randomized a total of 86 patients (3:1) to receive clevudine 30 mg (n = 63) or placebo (n = 23) daily for 24 weeks. We followed patients for an additional 24 weeks after withdrawal of treatment. The median changes in HBV DNA from baseline were −4.25 and −0.48 log10 copies/mL at week 24 in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained after withdrawal of therapy, with 3.11 log10 reduction at week 48. At week 24 and week 48, 92.1% and 16.4% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (<300 copies/mL). The proportion of patients who achieved ALT normalization was 74.6% and 33.3% in the clevudine and placebo groups at week 24, respectively (P = 0.0006). ALT normalization in the clevudine group was well‐maintained during the post‐treatment follow‐up period. The incidence of adverse events was similar in the 2 groups. No resistance to clevudine was detected during treatment. Conclusion: A 24‐week clevudine therapy was well‐tolerated and showed potent and sustained antiviral effect without evidence of viral resistance in e‐CHB patients. However, treatment for longer than 24 weeks would be needed to achieve durable remission. (HEPATOLOGY 2007.)

Clinical Characteristics of Colonic Diverticulosis in Korea: A Prospective Study

Background/Aims The prevalence of colonic diverticulosis has been reported to be lower in Korea than in Western countries. This disease also shows markedly different characteristics in the Korean population. We describe herein a prospective investigation, based on colonoscopic examination, of the prevalence, clinical characteristics, and factors associated with colonic diverticulosis in Korea. Methods The prevalence of colonic diverticulosis has been reported to be lower in Korea than in Western countries. This disease also shows markedly different characteristics in the Korean population. We describe herein a prospective investigation, based on colonoscopic examination, of the prevalence, clinical characteristics, and factors associated with colonic diverticulosis in Korea. Results The overall prevalence of colonic diverticulosis was 12.1% (103 / 848). The right side of the colon was involved in 84.5% of patients (87 / 103); patients with right side diverticula were, on average, younger than those with left side diverticulosis (p = 0.014). Multiple diverticula were observed in 60.2% (62 / 103) of patients. Age greater than 60 years, a high-fat diet, and alcohol consumption were significantly associated with the presence of colonic diverticulosis (p < 0.05). Conclusions The prevalence of colonic diverticulosis in Korea is increasing and is most commonly located in the right side of the colon. Further, old age and diet may affect the risk of development of this disease.

Trichuris trichiura Infection Diagnosed by Colonoscopy: Case Reports and Review of Literature

Trichuris trichiura, commonly referred to as a whipworm, has a worldwide distribution, particularly among countries with warm, humid climates. In Korea, trichuriasis was a highly prevalent soil-transmitted helminthiasis until the 1970s. However, the nationwide prevalence decreased to 0.02% in 2004 as a result of national control activities and improvement in the socioeconomic status of Koreans. Most infected individuals have no distinct symptoms, if lightly infected. The diagnosis is typically confirmed by detection of T. trichiura eggs on examination of a stool sample; few reports have described detection of the parasite during colonoscopy. Recently, we managed 4 patients with trichuriasis who were diagnosed by detection of the parasite on colonoscopy, and we reviewed the literature on the colonoscopic diagnosis of T. trichiura in Korea. We suggest that colonoscopy might be a useful diagnostic tool, especially when infected by only a few male worms with no eggs in the stool.

Predictive factors that influence the survival rates in liver cirrhosis patients with spontaneous bacterial peritonitis

Background/Aims Spontaneous bacterial peritonitis (SBP) has been known to greatly influence the survival rate of patients with liver cirrhosis. However, the factors that affect the survival rate in patients with SBP need to be clarified. Methods This study enrolled 95 liver cirrhosis patients diagnosed with SBP. The laboratory findings of their serum and ascitic fluid were examined and the characteristics of the isolated microorganisms in their peritoneal fluid were analyzed. Results The proportion of patients with culture-positive SBP was 41.1%, and 47 microorganisms were isolated from the ascitic fluid. The proportions of cultured bacteria that were Gram negative and Gram positive were 57.4% and 40.4%, respectively. The proportions of Escherichia coli, Klebsiella species, and Streptococcus species were 25.5%, 19.1%, and 19.1%, respectively. Enterococcus species represented 12.8% of the microorganisms cultured. The overall survival rates at 6, 12, and 24 months were 44.5%, 37.4%, and 32.2%, respectively. There was no relationship between the bacterial factors and the survival rate in SBP. Multivariate analysis revealed that the presence of hepatocellular carcinoma (HCC; P=0.001), higher serum bilirubin levels (≥3 mg/dL, P=0.002), a prolonged serum prothrombin time (i.e., international normalized ratio >2.3, P<0.001), renal dysfunction (creatinine >1.3 mg/dL, P<0.001), and lower glucose levels in the ascitic fluid (<50 mg/dL, P<0.001) were independent predictive factors of overall survival rate. Conclusions HCC, higher serum bilirubin levels, a prolonged serum prothrombin time, renal dysfunction, and lower ascitic glucose levels are associated with higher mortality rates in cirrhotic patients with SBP.

Metastatic tumor antigen in hepatocellular carcinoma: golden roads toward personalized medicine.

Hepatocellular carcinoma (HCC), a prototype of hypervascular tumors, is one of the most common malignancies in the world, especially hyperendemic in the Far East where chronic hepatitis B virus (HBV) infection is highly prevalent. It is characterized by the clinical feature of a poor prognosis or a high mortality due to its already far advanced stages at diagnosis. It is so multifactorial that hepatocarcinogenesis cannot be explained by a single molecular mechanism. To date, a number of pathways have been known to contribute to the development, growth, angiogenesis, and even metastasis of HCC. Among the various factors, metastatic tumor antigens (MTAs) or metastasis-associated proteins have been vigorously investigated as an intriguing target in the field of hepatocarcinogenesis. According to recent studies including ours, MTAs are not only involved in the HCC development and growth (molecular carcinogenesis), but also closely associated with the post-operative recurrence and a poor prognosis or a worse response to post-operative anti-cancer therapy (clinical significance). Herein, we review MTAs in light of their essential structure, functions, and molecular mechanism in hepatocarcinogenesis. We will also focus in detail on the interaction between hepatitis B x protein (HBx) of HBV and MTA in order to clarify the HBV-associated HCC development. Finally, we will discuss the prognostic significance and clinical application of MTA in HCC. We believe that this review will help clinicians to understand the meaning and use of the detection of MTA in order to more effectively manage their HCC patients.

Acute pancreatitis induced by traditional acupuncture therapy

Although rare, it is possible for acute pancreatitis to develop after blunt or penetrating abdominal trauma. We report here a very rare case of acute pancreatitis induced by traditional acupuncture therapy. A 42-year-old woman with a low body mass index had suffered from functional dyspepsia for one year. She visited an acupuncture clinic and underwent long needle (13 cm) and gold thread needle (3 mm) acupuncture therapy. Five hours later, she presented at our emergency room complaining of severe periumbilical pain. Levels of serum amylase (1162 U/l, normal <220 U/l), and lipase (5195 IU/l, normal <60 IU/l) were high, and an abdominal computed tomography scan showed a diffusely swollen pancreas and ill-defined infiltration of the peripancreatic fat, indications of possible acute pancreatitis. Multiple small acupunctured gold thread needles were also found on the anterior abdominal wall and back muscles. After excluding other possible causes of pancreatitis, traumatic pancreatitis was diagnosed as an adverse effect of the long acupuncture needle therapy.

Heat shock proteins and autophagy in rats with cerulein-induced acute pancreatitis.

Background/Aims Heat shock proteins (HSPs) protect rats from cerulein-induced acute pancreatitis (AP) by preventing the subcellular redistribution of cathepsin B and the activation of trypsinogen. Autophagy plays a critical role in the secretion of digestive enzymes and triggering of cerulein-induced AP via the colocalization of trypsinogen and lysosomes. Therefore, using a rat cerulein-induced AP model, we investigated whether HSPs prevent AP by regulating autophagy. Methods Twelve hours after fed standard laboratory chow and water, the experimental groups (cerulein, water-immersion [WI]-cerulein and heat-shock [HS]-cerulein) and the control groups (control, WI, and HS) received one intraperitoneal injection of cerulein (50 µg/kg) or saline, respectively. All of the rats were sacrificed at 6 hours after injection. The severity of the AP was assessed based on the serum amylase level and the histological and electron microscopy findings. Western blotting was also performed for HSP60/70 and LC3B-II. Results WI and HS induced HSP60 and HSP70, respectively. The induced HSP60/70 effectively prevented the development of cerulein-induced AP. Autophagy developed in the rats with cerulein-induced AP and was documented by the expression of LC3-II and electron microscopy findings. The WI-stressed rats and HS-treated rats did not develop cerulein-induced autophagy. Conclusions HSPs exert protective effects against cerulein-induced AP in rats by inhibiting autophagy.

Genomic change in hepatitis B virus associated with development of hepatocellular carcinoma

AIMnTo determine the genomic changes in hepatitis B virus (HBV) and evaluate their role in the development of hepatocellular carcinoma (HCC) in patients chronically infected with genotype C HBV.nnnMETHODSnTwo hundred and forty chronic hepatitis B (CHB) patients were subjected and followed for a median of 105 mo. HCC was diagnosed in accordance with AASLD guidelines. The whole X, S, basal core promoter (BCP), and precore regions of HBV were sequenced using the direct sequencing method.nnnRESULTSnAll of the subjects were infected with genotype C HBV. Out of 240 CHB patients, 25 (10%) had C1653T and 33 (14%) had T1753V mutation in X region; 157 (65%) had A1762T/G1764A mutations in BCP region, 50 (21%) had G1896A mutation in precore region and 67 (28%) had pre-S deletions. HCC occurred in 6 patients (3%). The prevalence of T1753V mutation was significantly higher in patients who developed HCC than in those without HCC. The cumulative occurrence rates of HCC were 5% and 19% at 10 and 15 years, respectively, in patients with T1753V mutant, which were significantly higher than 1% and 1% in those with wild type HBV (P < 0.001).nnnCONCLUSIONnThe presence of T1753V mutation in HBV X-gene significantly increases the risk of HCC development in patients chronically infected with genotype C HBV.

Solitary Intra-abdominal Tuberculous Lymphadenopathy Mimicking Duodenal GIST

Tuberculosis remains prevalent in developing countries and has recently re-emerged in the Western world. Intra-abdominal tuberculosis can mimic a variety of other abdominal disorders, and here we describe a patient with solitary tuberculous mesenteric lymphadenopathy mimicking duodenal gastrointestinal stromal tumor (GIST). A 22-year-old woman complained of epigastric discomfort and was presumed to have a duodenal GIST after an endoscopic examination and abdominal CT scan. However, exploratory laparotomy revealed an enlarged node penetrating the duodenal bulb, which was diagnosed histopathologically as tuberculous lymphadenitis. This case suggests that in regions with a high prevalence of tuberculosis, intra-abdominal tuberculosis is often mistaken as a malignant neoplasm. A high index of suspicion and the accurate nonsurgical diagnosis of intra-abdominal tuberculosis continues to be a challenge.