Duck Joo Choi

8-Hydroxydeoxyguanosine: Not mere biomarker for oxidative stress, but remedy for oxidative stress-implicated gastrointestinal diseases

Reactive oxygen species (ROS) attack guanine bases in DNA easily and form 8-hydroxydeoxyguanosine (8-OHdG), which can bind to thymidine rather than cytosine, based on which, the level of 8-OHdG is generally regarded as a biomarker of mutagenesis consequent to oxidative stress. For example, higher levels of 8-OHdG are noted in Helicobacter pylori-associated chronic atrophic gastritis as well as gastric cancer. However, we have found that exogenous 8-OHdG can paradoxically reduce ROS production, attenuate the nuclear factor-κB signaling pathway, and ameliorate the expression of proinflammatory mediators such as interleukin (IL)-1, IL-6, cyclo-oxygenase-2, and inducible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1, NOX organizer-1 and NOX activator-1 in various conditions of inflammation-based gastrointestinal (GI) diseases including gastritis, inflammatory bowel disease, pancreatitis, and even colitis-associated carcinogenesis. Our recent finding that exogenous 8-OHdG was very effective in either inflammation-based or oxidative-stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdG can be a potential candidate for the treatment of inflammation-based GI diseases, as well as the prevention of inflammation-associated GI cancer. In this editorial review, the novel fact that exogenous 8-OHdG can be a functional molecule regulating oxidative-stress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced.

Antibiotic treatment for Helicobacter pylori: Is the end coming?

Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication.

Role of interleukin 28b-related gene polymorphisms in chronic hepatitis c and the response to antiviral therapy in koreans

Background: Genetic variations in interleukin 28B (IL28B) have been strongly associated with a sustained virological response (SVR) in European and African-American patients. Genetic variation of IL28B was investigated in healthy controls and chronic hepatitis C (CHC) patients, and the treatment response in the CHC patients was analyzed according to IL28B polymorphism in the Korean population. Methods: IL28B polymorphisms (rs12979860 and rs8099917) were studied in 200 healthy controls and in 167 CHC patients who were treated with peginterferon-&agr; and ribavirin. Results: The prevalence of rs12979860 in healthy controls is as follows: the CC-genotype was 88.5%, the CT-genotype was 11.5%, and the TT-genotype was not found. The prevalence of rs8099917 in healthy controls is as follows: the TT-genotype was 89.5%, the TG-genotype was 10.5%, and the GG-genotype was not found. The CC-genotype of rs12979860 and the TT-genotype of rs8099917 were found to be closely related (linkage disequilibrium; D′=1.0, &khgr; 2=0.9082). In 106 CHC patients treated with peginterferon and ribavirin, the SVR was 67.2% (n=58) for 1b, 91.6% (n=47) for 2a. In hepatitis C virus (HCV) genotype 1b with respect to rs12979860, the SVR in CC-genotype was 72.9% and that in CT-genotype was 40.0%. On investigating predictive factors for SVR, pretreatment low-HCV RNA levels, HCV genotype non-1, early virological response, and also the IL28B CC-genotype for rs12979860 were good indicators of an SVR. Conclusions: In Korea, genetic variation of IL28B is different from that in western countries in view of high prevalence of rs12979860 CC-genotype. It seems likely that a high SVR in Korean patients with genotype 1 CHC patients is due to the genetic polymorphism in IL28B.

Factors influencing hepatocellular carcinoma prognosis after hepatectomy: a single-center experience.

Background/Aims Recurrence after hepatic resection is one of the most important factors impacting the prognosis and survival of patients with hepatocellular carcinoma (HCC). We identified prognostic factors affecting overall survival (OS) and disease-free survival (DFS) in patients with HCC after hepatic resection. Methods This study was of a retrospective cohort design, and 126 patients who underwent hepatic resection for HCC at Gachon University Gil Medical Center between January 2005 and December 2010 were enrolled. Various clinical, laboratory, and pathological data were evaluated to determine the prognostic factors affecting OS and DFS. Results Two- and 4-year OS and 2- and 4-year DFS were 78.1% and 65% and 51.1% and 26.6%, respectively. In a multivariate analysis, preoperative α-fetoprotein (> 400 ng/mL), tumor size (≥ 5 cm), multiple tumors (two or more nodules), presence of portal vein invasion, modified Union for International Cancer Control (UICC) stage III/IV, and Barcelona Clinic Liver Cancer (BCLC) stage B/C were independent prognostic factors affecting a shorter OS. In the multivariate analysis, presence of microvascular invasion, modified UICC stage III/IV, and BCLC stage B/C were independent prognostic factors for a shorter DFS. Conclusions The presence of vascular invasion was an independent poor prognostic factor for OS and DFS in patients with HCC after hepatic resection. Thus, close postoperative surveillance for early detection of recurrence and additional treatments are urgently needed in patients with vascular invasion after hepatic resection.

Factors influencing the severity of acute viral hepatitis A

Background/Aims Most patients with acute viral hepatitis A have a favorable course, but a few of them suffer from severe forms of hepatitis such as fulminant hepatitis. This study was carried out to identify the factors influencing the severity of acute viral hepatitis A. Methods We retrospectively reviewed the medical records of 713 patients with acute hepatitis A, who were divided into two groups: severe hepatitis A (N=87) and non-severe hepatitis A (N=626). Severe hepatitis was defined as fulminant hepatitis or prolongation of prothrombin time (INR≥1.5). Clinical variables were compared between the two groups. Results The incidence of fulminant hepatitis was 1.4% (10/713) in patients with acute hepatitis A. Thirty-three (4.6%) cases exhibited HBsAg positivity. In multivariate analyses, significant alcohol intake and the presence of HBsAg were significant predictive factors of fulminant hepatitis A, and significant alcohol intake and age were significant predictive factors of severe hepatitis A. HBeAg and HBV-DNA status did not affect the clinical course of hepatitis A in chronic hepatitis B carriers. Conclusions While most patients with acute hepatitis A have an uncomplicated clinical course, our data suggest that a more-severe clinical course is correlated with being older, significant alcohol intake, and chronic hepatitis-B-virus infection.

Usefulness of liver stiffness measurement for predicting the presence of esophageal varices in patients with liver cirrhosis

BACKGROUND/AIMS Bleeding from esophageal varices (EV) is a major cause of death in patients with liver cirrhosis. Endoscopic screening is recommended for diagnosing EV, but various noninvasive parameters can also be used to predict EV. The liver stiffness measurement (LSM), a noninvasive technique for estimating liver fibrosis, was recently reported to be strongly correlated with the hepatic venous pressure gradient. This study evaluated the usefulness of LSM for predicting the presence and size of EV in patients with cirrhosis. METHODS The relationships of LSM with the presence and size of EV were analyzed in 112 patients with liver cirrhosis. Liver cirrhosis was diagnosed histologically or clinically. The presence and size of EV were assessed by endoscopy, and LSM was determined by the Fibroscan technique. RESULTS LSM was strongly correlated with the presence of EV (P<0.0001): the LSM value was 42.7+/-21.9 kPa (mean+/-standard deviation) in patients with EV (n=82) and 19.1+/-12.6 kPa in patients without EV (n=30). The area under the receiver operating characteristic curve was 0.818 (95% CI, 0.732-0.904) for predicting the presence of EV, and an LSM value of 19.7 kPa was predictive of the presence of EV with a sensitivity of 87%, a specificity of 70%, a PPV of 89%, and a NPV of 66%. However, there was a weak correlation between LSM and the size of EV. CONCLUSIONS LSM is useful for predicting the presence of EV in patients with cirrhosis but not their size.

The factors associated with longitudinal changes in liver stiffness in patients with chronic hepatitis B

Background/Aims Liver stiffness (LS) as assessed by transient elastography (TE) can change longitudinally in patients with chronic hepatitis B (CHB). The aim of this study was to identify the factors that improve LS. Methods Between April 2007 and December 2012, 151 patients with CHB who underwent two TE procedures with an interval of about 2 years were enrolled. Ninety-six of the 151 patients were treated with nucleos(t)ide analogues [the antiviral therapy (+) group], while the remaining 55 patients were not [the antiviral therapy (-) group]. The two groups of patients were stratified according to whether they exhibited an improvement or a deterioration in LS during the study period (defined as an LS change of ≤0 or >0 kPa, respectively, over a 1-year period), and their data were compared. Results No differences were observed between the antiviral therapy (+) and (-) groups with respect to either their clinical characteristics or their initial LS. The observed LS improvement was significantly greater in the antiviral therapy (+) group than in the antiviral therapy (-) group (-3.0 vs. 0.98 kPa, P=0.011). In the antiviral therapy (+) group, the initial LS was higher in the LS improvement group (n=63) than in the LS deterioration group (n=33; 7.9 vs. 4.8 kPa, P<0.001). However, there were no differences in any other clinical characteristic. In the antiviral therapy (-) group, the initial LS was also higher in the LS improvement group (n=29) than in the LS deterioration group (n=26; 8.3 vs. 6.5 kPa, P=0.021), with no differences in any other clinical characteristic. Conclusions A higher initial LS was the only factor associated with LS improvement in patients with CHB in this study.

The impact of inosine triphosphatase variants on hemoglobin level and sustained virologic response of chronic hepatitis C in Korean.

Two variants of the inosine triphosphatase (ITPA: rs1127354, rs7270101) gene cause ITPA deficiency and protect against the hemolytic toxicity of ribavirin. We investigated the clinical significance of ITPA variants in Korean patients treated with pegylated interferon (PEG-IFN) plus ribavirin. Of the 133 patients, 108 were CC and 25 were non-CC at rs1127354 (groups A and B, respectively). On the other hand, at rs7270101 all 133 were AA. The mean values of Hemoglobin (Hgb) after 4, 8, and 12 weeks of treatment in groups A and B were 12.2 and 14.0, 11.8 and 13.2, and 11.5 and 12.9, respectively (P=0.001, 0.036, 0.036). Sustained virologic response (SVR) was achieved in 67.8% (40/59) of genotype 1 patients and in 75% (27/36) of non-genotype 1 patients. Regarding ITPA variants, SVR was achieved by 66% and 80% of genotype 1 (P=0.282), and by 78% and 71% (P=0.726) of non-genotype 1. SVR was not significantly different in groups A and B. In conclusion, non-CC at rs1127354 without involvement of rs7270101 is strongly associated with protection from ribavirin-induced anemia, however, ITPA genotype is not associated with SVR.

Efficacy of peginterferon and ribavirin is associated with the IL28B gene in Korean patients with chronic hepatitis C

Background/Aims Sustained virologic response (SVR) for the treatment of chronic hepatitis C (CHC) may differ with ethnicity due to differences in genetic traits. This study evaluated the efficacy of peginterferon and ribavirin, and the association between IL28B genotypes and the treatment efficacy in Korean CHC patients. Methods This was a retrospective cohort study using data from medical records. Eighty-five CHC patients were eligible for assessment of the efficacy of antiviral therapy, and 47 patients were available for an IL28B genetic study, which was performed using the Multiplex tetra-primer PCR method for rs12979860. Results Overall, the early virologic response rate was 87.1%: 84.9% in HCV genotype 1 and 90.6% in genotype 2. The overall end-of-treatment virologic response rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. The overall SVR rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. For rs12979860, the frequencies of polymorphisms were 89% for the CC type, 11% for the CT type, and 0% for the TT type. Their overall SVR rate was 87% (39/47): 90.5% (38/42) for the CC type and 20% (1/5) for the CT type. For genotype 1, SVR rates were 88% (21/24) for the CC type and 0% (0/4) for the CT type. Multivariate analysis revealed that the IL28B-CC type was a good predictor for SVR. Conclusions The SVR of the combination therapy in Koreans was higher than that observed in Western countries. This finding might be attributable to the high prevalence of IL28B-CC type among Koreans, which may be a good predictor of SVR.

A case of amoxicillin-induced hepatocellular liver injury with bile-duct damage

Amoxicillin, an antibiotic that is widely prescribed for various infections, is associated with a very low rate of drug-induced liver injury; hepatitis and cholestasis are rare complications. Here we present a case of a 39-year-old woman who was diagnosed with abdominal actinomycosis and received amoxicillin treatment. The patient displayed hepatocellular and bile-duct injury, in addition to elevated levels of liver enzymes. The patient was diagnosed with amoxicillin-induced cholestatic hepatitis. When amoxicillin was discontinued, the patients symptoms improved and her liver enzyme levels reduced to near to the normal range.