Association of Intensive Endoscopic Screening Burden With Gastric Cancer Detection.

Importance: The rapidly increasing number of gastric cancer examinations performed over a short period might influence screening performance. Accessing the association between calendar month and gastric cancer detection rates might improve policy and guide institutional support. Objective: To evaluate the association between the increased number of examinations over a certain period and gastric cancer detection rates among a large population included in the Korean National Cancer Screening Program (KNCSP). Design, Setting, and Participants: This retrospective, population-based cohort study used data from the KNCSP comprising 26 765 665 men and women aged 40 years or older who participated in the screening program between January 1, 2013, and December 31, 2016. Data were analyzed from November 1, 2019, to March 31, 2020. Exposures: Gastric cancer screening with endoscopy. Main Outcomes and Measures: The primary outcome was monthly gastric cancer detection rates in the KNCSP. A negative binomial regression model was used to evaluate the association between the screening month and detection rates. Results: In total, 21 535 222 individuals underwent endoscopy (mean [SD] age, 55.61 [10.61] years; 11 761 709 women [54.62%]). The quarterly number of participants was the highest in the last quarter of the study period (2013-2014: 4 094 951 [41.39%], 2015-2016: 4 911 629 [42.19%]); this proportion was 2.48 to 2.84 times greater than that of the first quarter. Cancer detection rates were the lowest in December (2013-2014: 0.22; 95% CI, 0.22-0.23; 2015-2016: 0.21; 95% CI, 0.21-0.22); this was approximately a 40.0% to 45.0% reduction compared with the rates in January. The age group was the significant factor for monthly detection rates. After adjustment for the age group and taking account of the number of screenings, the estimated coefficient range for the screening month was negative and the detection rate in December was significantly different than in January for both the consequent cycles (2013-2014: -0.05 to -0.18; P < .001; and 2015-2016: -0.06 to -0.19; P < .001). In the multivariable logistic model, the association of calendar month with detected cancer remained after adjusting for other confounding factors (December, 2013-2014: odds ratio, 0.82; 95% CI, 0.76-0.87; P < .001; 2015-2016: odds ratio, 0.83; 95% CI, 0.79-0.89; P < .001). Conclusions and Relevance: The findings of this cohort study suggest that the workload of endoscopists increased with the increasing number of examinations toward the end of the year, as demonstrated by the decreased cancer detection rates. These findings may help to improve gastric cancer detection rates of screening programs by controlling the monthly screening number and policy modifications.

Impact of previous metronidazole exposure on metronidazole-based second-line quadruple therapy for Helicobacter pylori infection.

BACKGROUND/AIMS: The negative effects on the eradication success of Helicobacter pylori infection after previous exposure to macrolides, including clarithromycin on clarithromycin-based first-line therapy have been demonstrated. However, whether this is true for metronidazole-based second-line quadruple therapy remains unclear. We investigated the relationship between past administration of metronidazole and the failure of metronidazole-based second-line quadruple therapy in patients with H. pylori infection. METHODS: Patients over 20 years of age who were diagnosed with H. pylori infection between January 1998 and March 2016 were enrolled in this study. The relationship between the clinical parameters and the results of a C13-urea breath test after metronidazole-based second-line quadruple therapy was analyzed in patients for whom clarithromycin-based triple therapy failed to eradicate H. pylori. RESULTS: The H. pylori eradication failure rate was significantly higher in patients with a history of metronidazole use than in patients without a history of metronidazole use (p = 0.011). Multivariable analysis showed that the odds ratio of previous metronidazole use for eradication failure was 3.468 (95% confidence interval, 1.391 to 8.649; p = 0.008). In the subgroup analysis of patients with a history of metronidazole use, the duration of metronidazole use and interval between its use and eradication therapy did not significantly affect H. pylori eradication failure. CONCLUSION: Previous exposure to metronidazole was a significant risk factor for treatment failure of metronidazole-based second-line quadruple therapy; therefore, this should be considered when establishing a treatment strategy for patients with H. pylori infection.

Cyclic Change of Sphincter of Oddi Motility and Its Relationship with Small Bowel Migrating Motor Complex in Humans.

BACKGROUND: Several animal and human studies have reported that sphincter of Oddi (SO) motility shows cyclical changes during the fasting state. However, to date, the relationship between the SO motility and the migrating motor complex (MMC) of the small bowel (SB) remains unclear in humans. AIMS: We observed SO motility over a long study period and evaluated its relationship with the MMC of the SB in humans using percutaneous long-term manometry. METHODS: Our study included patients with hepatolithiasis who required percutaneous transhepatic catheter placement and subsequently underwent choledochoscopy and stone removal. Long-term percutaneous transhepatic SO manometry was performed after complete stone removal. SO and SB motility were simultaneously recorded. RESULTS: SO motility showed cyclical phasic changes with periodic high-frequency contractions similar to the MMC contractions of the SB. All high-frequency contractions of the SO coincided with phase III contractions of the MMC of the SB. The proportions of phase III contractions of SO and SB were similar, but the proportions of phase I (P = 0.001) and phase II (P = 0.002) contractions were significantly different. The mean basal SO pressure was observed to significantly increase in phase III compared to phase I (P = 0.001) and phase II (P = 0.001) contractions. CONCLUSIONS: SO motility in humans showed cyclical phasic changes closely coordinated with the MMC of the SB in a fasting state; however, the proportion of phases differed between the SO and the SB. The basal pressure significantly increased during physiological high-frequency phase III contractions of the SO.

Laparoscopy-assisted endoscopic full-thickness resection for gastric subepithelial tumors originated from the muscularis propria layer: a pilot study with literature review.

OBJECTIVE: Laparoscopy-assisted endoscopic full-thickness resection (LAEFTR) has been suggested as an alternative to laparoscopic wedge resection in the treatment of gastric subepithelial tumors (SETs). It is expected to minimize the resection of the tissue surrounding the tumors and maintain the function of the remnant stomach. Here, we performed a prospective pilot study to evaluate the efficacy of laparoscopy-assisted endoscopic full-thickness resection (LAEFTR) for patients with gastric SETs. MATERIAL AND METHODS: We enrolled twelve patients who were diagnosed with gastric SETs with an intraluminal growth pattern or which is located in the gastric antrum between October 2011 and September 2013. LAEFTR was performed endoscopically using an endoscopic knife to make an incision half way around the tumor circumference and a laparoscopic resection around the remaining tumor circumference, followed by its laparoscopic removal. The feasibility, safety, and effectiveness of LAEFTR for gastric SETs were evaluated. RESULTS: The median size of the tumors in twelve patients was 22 mm (21-33). Of the 12 patients, 8 received LAEFTR, while the others underwent conventional laparoscopic wedge resection, since their tumor outlines were clearly visible in laparoscopic view. In 8 patients who underwent LAEFTR, the mean total operation time (endoscopic procedure time/laparoscopic procedure time) were 117 (37/41) min. The tumors were completely resected with clear margin, and there was no perioperative and postoperative complications. CONCLUSIONS: LAEFTR currently seems to be the ideal treatment modality of intraluminal gastric SETs where their resection margins are difficult to define under laparoscopic guidance alone.

A Case of Amyloidosis Presenting as Chronic Cholecystitis, Misdiagnosed as Polymyalgia Rheumatica.

Amyloidosis is a rare disease defined by extracellular deposits of amorphous fibrillar proteins, derived from aggregations of misfolded proteins. Localization of amyloidosis in the gallbladder is uncommon; only eight cases have been reported. We describe a case of amyloidosis diagnosed by cholecystectomy, which possibly also affected the liver and kidney. The patient was misdiagnosed with polymyalgia rheumatica, but after a cholecystectomy to treat chronic cholecystitis, we ultimately diagnosed him with amyloidosis. We review amyloidosis with gallbladder involvement in the literature.

The relationship between the failure to eradicate Helicobacter pylori and previous antibiotics use.

BACKGROUND: The previous use of antibiotics is known to correlate positively with antibiotic resistance; whether this is also the case in the eradication of Helicobacter pylori infection is unclear. AIM: To investigate the relationship between the previous use of antibiotics and the failure of eradication therapy in H. pylori infection. METHODS: The relationship between the clinical parameters and the failure of H. pylori eradication was analyzed in patients administered standard triple therapy and then assessed for the eradication of H. pylori based on a C13-urea breath test. RESULTS: In a multivariate analysis, failure rates increased significantly in patients with a history of clarithromycin (odds ratio [OR], 4.445) or other macrolides (OR, 2.407) use, who were female (OR, 1.339), or who were older than 60 years of age (OR, 1.326). The eradication failure rate in patients with a history of macrolides use for >2 weeks was significantly higher than if the duration of use was <2 weeks (44.8% vs. 29.3%, p=0.047). CONCLUSIONS: A patient's history of macrolides is a useful predictor of the likelihood of standard triple therapy failure in H. pylori eradication. The alternatives such as a bismuth-based quadruple or a levofloxacin-containing therapy should be considered in patients treated with macrolides for >2 weeks.

Wire-guided cannulation over a pancreatic stent versus double guidewire technique in patients with difficult biliary cannulation.

BACKGROUND: In cases of difficult bile duct cannulation, the use of wire-guided cannulation over a pancreatic stent (WGC-PS) or the double guidewire technique (DGT) may facilitate biliary cannulation. The aim of this study was to compare the outcomes of WGC-PS and DGT in patients with difficult biliary cannulation. METHODS: We conducted a retrospective cohort study of all endoscopic retrograde cholangiopancreatographies (ERCPs) performed between July 2009 and November 2014 at a single tertiary referral center. WGC-PS or DGT was performed in patients for whom biliary cannulation was difficult and guidewire insertion into the pancreatic duct (PD) was inadvertently achieved while attempting the standard WGC technique. In those cases, we used the WGC-PS technique from July 2009 to January 2012 (WGC-PS group), and the DGT technique from February 2012 to November 2014 (DGT group). In the DGT group, WGC-PS was sequentially performed if successful biliary cannulation was not achieved during the DGT attempt. Consecutive patients who underwent DGT and/or WGC-PS with the aim of selective biliary cannulation were enrolled. The primary outcome parameter was the rate of initial successful biliary cannulation. RESULTS: During the study period 3270 ERCPs were performed and a total of 177 patients were enrolled. The rate of initial successful cannulation was 66.7 % (60/90) in the WGC-PS group and 70.1 % (61/87) in the DGT group (P = 0.632). In 26 cases of failed DGT, WGC-PS was sequentially performed in the DGT group, and cannulation was successful in 14 of these patients. The rate of successful cannulation without the needle-knife precut technique was significantly higher in the DGT group compared with the WGC-PS group (75/87, 86.2 % vs. 60/90, 66.7 %, P = 0.003). The incidence of post-ERCP pancreatitis was 3.3 % (3/90) in the WGC-PS group and 10.3 % (9/87) in the DGT group (P = 0.077). CONCLUSIONS: In patients for whom biliary cannulation was difficult and PD access was inadvertently achieved while attempting the standard WGC technique, both WGC-PS and DGT were equally effective. Furthermore, the stepwise approach using DGT followed by WGC-PS as needed facilitated successful biliary cannulation and reduced the need for the needle-knife precut technique.

Endoscopic ultrasound-guided sampling of solid pancreatic masses: 22-gauge aspiration versus 25-gauge biopsy needles.

BACKGROUND: Biopsy needles have recently been developed to obtain both cytological and histological specimens during endoscopic ultrasound (EUS). We conducted this study to compare 22-gauge (G) fine needle aspiration (FNA) needles, which have been the most frequently used, and new 25G fine needle biopsy (FNB) needles for EUS-guided sampling of solid pancreatic masses. METHODS: We conducted a retrospective cohort study of all EUS-guided sampling performed between June 2010 and October 2013. During the study period, 76 patients with pancreatic masses underwent EUS-guided sampling with a 22G FNA needle (n = 38) or a 25G FNB needle (n = 38) for diagnosis. An on-site cytopathologist was not present during the procedure. Technical success, the number of needle passes, cytological diagnostic accuracy, cytological sample quality (conventional smear and liquid-based preparation), histological diagnostic accuracy, and complications were reviewed and compared. RESULTS: There were no significant differences in technical success (100% for both), the mean number of needle passes (5.05 vs. 5.55, P = 0.132), or complications (0% for both) between the 22G FNA group and the 25G FNB group. The 22G FNA and 25G FNB groups exhibited comparable outcomes with respect to cytological diagnostic accuracy (97.4% vs. 89.5%, P = 0.358) and histological diagnostic accuracy (34.2% vs. 52.6%, P = 0.105). In the cytological sample quality analysis, the 25G FNB group exhibited higher scores for the amount of diagnostic cellular material present (22G FNA: 0.92 vs. 25G FNB: 1.32, P = 0.030) and the retention of appropriate architecture (22G FNA: 0.97 vs. 25G FNB: 1.42, P = 0.010) in the liquid-based preparation. The 25G FNB group showed a better histological diagnostic yield for specific tumor discrimination compared with the 22G FNA group (60 % vs. 32.4%, P = 0.018). CONCLUSIONS: Use of the 25G FNB needle was technically feasible, safe, efficient, and comparable to use of the standard 22G FNA needle in patients with solid pancreatic masses in the absence of an on-site cytopathologist. The cytological sample quality in the liquid-based preparation and the histological diagnostic yield for specific tumor discrimination of EUS-guided sampling using a 25G FNB needle were significantly higher than those using a 22G FNA needle.

Partially covered versus uncovered self-expandable nitinol stents with anti-migration properties for the palliation of malignant distal biliary obstruction: A randomized controlled trial.

OBJECTIVE: Covered self-expandable metal stents (SEMSs) are increasingly used as alternatives to uncovered SEMSs for the palliation of inoperable malignant distal biliary obstruction to counteract tumor ingrowth. We aimed to compare the outcomes of partially covered and uncovered SEMSs with identical mesh structures and anti-migration properties, such as low axial force and flared ends. MATERIALS AND METHODS: One hundred and three patients who were diagnosed with inoperable malignant distal biliary obstruction between January 2006 and August 2013 were randomly assigned to either the partially covered (n = 51) or uncovered (n = 52) SEMS group. RESULTS: There were no significant differences in the cumulative stent patency, overall patient survival, stent dysfunction-free survival and overall adverse events, including pancreatitis and cholecystitis, between the two groups. Compared to the uncovered group, stent migration (5.9% vs. 0%, p = 0.118) and tumor overgrowth (7.8% vs. 1.9%, p = 0.205) were non-significantly more frequent in the partially covered group, whereas tumor ingrowth showed a significantly higher incidence in the uncovered group (5.9% vs. 19.2%, p = 0.041). Stent migration in the partially covered group occurred only in patients with short stenosis of the utmost distal bile duct (two in ampullary cancer, one in bile duct cancer), and did not occur in any patients with pancreatic cancer. CONCLUSIONS: For the palliation of malignant distal biliary obstruction, endoscopic placement of partially covered SEMSs with anti-migration designs and identical mesh structures to uncovered SEMSs failed to prolong cumulative stent patency or reduce stent migration.

Non-neoplastic pathology results after endoscopic submucosal dissection for gastric epithelial dysplasia or early gastric cancer.

BACKGROUND AND STUDY AIMS: Endoscopists sometimes face paradoxical cases in which the endoscopic submucosal dissection (ESD) specimen reveals a non-neoplastic pathology result. The aims of the study were to determine the reasons for such results, and to compare the endoscopic characteristics of non-neoplastic and conventional neoplastic pathology groups after ESD. PATIENTS AND METHODS: A total of 1186 gastric ESDs performed between February 2005 and December 2011 were retrospectively reviewed. The ESD specimens included 52 (4.4 %) that were confirmed as negative or indefinite for neoplasia. Patient characteristics and endoscopic and pathological data were reviewed and compared. RESULTS: Non-neoplastic pathology after ESD was due to complete removal of the lesion at biopsy in 45 cases (86.5 %), pathology overestimation in 5 (9.6 %), and incorrect localization of the original tumor with subsequent ESD performed at the wrong site in 2 (3.8 %). The mean length and surface area of the non-neoplastic lesions were 9.2 ±â€Š2.6 mm and 49.6 ±â€Š23.6 mm (2), respectively. Mean sampling ratios were 3.0 ±â€Š1.5 mm/fragment and 16.3 ±â€Š10.0 mm(2)/fragment. Compared with 1134 cases confirmed as neoplastic on the final ESD specimen, non-neoplastic cases showed a significantly smaller tumor size and surface area, and lower sampling ratios in a logistic regression analysis adjusted for potential confounders (P < 0.001 for all). CONCLUSIONS: Complete lesion removal by biopsy, pathology overestimation, and incorrect localization of the original tumor with subsequent ESD at the wrong site were the main reasons for non-neoplastic results after ESD. Small tumor size and surface area, and low sampling ratios were associated with non-neoplastic pathology results after ESD.

Technical skills and training of upper gastrointestinal endoscopy for new beginners.

The incidence of gastric cancer remains high in South Korea. Upper gastrointestinal (GI) endoscopy, i.e., esophagogastroduodenoscopy (EGD), has a higher diagnostic specificity and sensitivity than the upper GI series. Additionally, EGD has the ability to biopsy, through taking a tissue of the pathologic lesion. Successful training of EGD procedural skills require a few important things to be learned and remembered, including the posture of an examinee (e.g., left lateral decubitus and supine) and examiner (e.g., one-man standing method vs one-man sitting method), basic skills (e.g., tip deflection, push forward and pull back, and air suction and infusion), advanced skills (e.g., paradoxical movement, J-turn, and U-turn), and intubation techniques along the upper GI tract (e.g., oral cavity, pharynx, larynx including vocal cord, upper and middle and lower esophagus, gastroesophageal junction, gastric fundus, body, and antrum, duodenal bulb, and descending part of duodenum). In the current review, despite several limitations, we explained the intubation method of EGD for beginners. We hope this will be helpful to beginners who wish to learn the procedure.

Comparison of the efficacy and safety of sodium phosphate tablets and polyethylene glycol solution for bowel cleansing in healthy Korean adults.

PURPOSE: Bowel cleansing is generally regarded as time-consuming and unpleasant among patients. Patients commonly state that bowel preparation provokes more discomfort than the actual colonoscopic examination. The purpose of this study was to compare two regimens of sodium phosphate (NaP) tablets versus polyethylene glycol (PEG) solution for bowel preparation in healthy Korean adults. MATERIALS AND METHODS: This was a single center, prospective, open-label, investigator-blinded, randomized, controlled-pilot study. A total of 62 healthy Korean subjects were randomly assigned to two groups (NaP vs. PEG). Efficacy, safety, and patient-related outcomes, as well as procedural parameters, were evaluated. RESULTS: Although there were no significant differences in total Ottawa bowel quality score, fluid scores and the rate of adequate bowel preparation were significantly better in the NaP group than the PEG group. Additionally, the NaP group showed better results regarding patient tolerance, satisfaction, preference, and rate of adverse events than the PEG group. Significant fluctuations in specific serum electrolytes were common and of a greater magnitude in the NaP group than the PEG group. However, these abnormalities were transient and did not result in serious complications and side effects. CONCLUSION: In this study, NaP tablets were shown to be an effective, well-tolerated, and acceptable regimen for bowel preparation. Also, our study suggests that NaP tablets may be safe and can be used as a bowel cleansing agent in healthy adults undergoing elective colonoscopy. Further multicenter, large scale studies are needed to confirm these findings.

Ectopic sebaceous glands in the oesophagus: a case report and review of literature.

INTRODUCTION: Most ectopic sebaceous glands have been reported in the tissues of ectodermal origin. However, there are relatively a few reports of ectopic sebaceous glands in the oesophagus, an organ of endodermal origin. CASE PRESENTATION: We report the case of an asymptomatic 54-year-old man with ectopic oesophageal sebaceous glands. These lesions were incidentally observed in the distal oesophagus during screening endoscopy of gastric neoplasm and confirmed by histologic analysis. CONCLUSION: Surveillance or resection with regard to ectopic sebaceous glands in the oesophagus is generally not required since there is no known malignant potential. However, anti-reflux treatment may be sometimes needed, if such symptoms are present in patients. Also, these lesions should be differentiated from other pathologic lesions of oesophagus that need to be treated. Thus, greater attention of endoscopists is required for detection and differential diagnosis of these lesions. The narrow-band imaging mode and/or endoscopic biopsy may be helpful.

Colonic mucosa-associated lymphoid tissue lymphoma identified by chromoendoscopy.

Colonic mucosa-associated lymphoid tissue (MALT) lymphomas are a rare occurrence and the definitive treatment has not been established. Solitary or multiple, elevated or polypoid lesions are the usual appearances of MALT lymphoma in the large intestine and sometimes the surface may reveal abnormal vascularity. Herein, we report a case of MALT lymphoma and review the relevant literature. Upon colonoscopy, a suspected pathologic lesion was observed in the proximal transverse colon. The lesion could be distinguished more prominently after using narrow-band imaging mode and indigo carmine-dye spraying chromoendoscopy. Histopathologic examination of this biopsy specimen revealed lymphoepithelial lesions with diffuse proliferation of atypical lymphoid cells effacing the glandular architecture and centrocyte-like cells infiltrating the lamina propria. Immunohistochemical analyses showed that tumor cells were positive for CD20 and Bcl-2e, and negative for CD10, CD23, and Bcl-6. According to Ann-Arbor staging system, the patient had stage IIE. A partial colectomy with dissection of the paracolic lymph nodes was performed. Until now, there is no recurrence of lymphoma at follow-up.

[Factors affecting initial virologic response and emergence of resistant mutants after adefovir treatment in lamivudine-resistant chronic hepatitis B patients].

BACKGROUND/AIMS: Adefovir dipivoxil (adefovir) effectively inhibits both wild-type and lamivudine-resistant hepatitis B virus (HBV) replication. The development of adefovir resistance is both delayed and infrequent compared with lamivudine resistance. The aim of this study was to characterize the serologic, biochemical, and virologic response to adefovir, and to explore the factors affecting initial virologic response (IVR, defined as a decrease in serum HBV below 4 log10copies/mL after 6 month of treatment) and adefovir resistance in lamivudine resistant HBV-infected patients. METHODS: This study population comprised 76 patients with lamivudine-resistance who had received adefovir for more than 12 months between March 2004 and December 2006. The adefovir-resistant mutant was assayed at 6 months and 12 months during adefovir administration. Restriction-fragment mass polymorphism analysis was used for detecting YMDD and adefovir mutants. RESULTS: After adefovir administration, an IVR was observed in 31% of the patients with lamivudine resistance. Factors associated with an IVR were HBeAg negativity (P=0.04) and the presence of liver cirrhosis (P=0.04). Age, sex, pretreatment levels of alanine aminotransferase and aspartate aminotransferase, pretreatment HBV DNA levels, presence of precore mutation, and type of YMDD mutants were not related to an IVR during adefovir treatment. The prevalence of adefovir resistance was 5% and 13% at 6 months and 12 months after therapy, respectively. Mixed infection of the precore mutant was a risk factors for the emergence of adefovir resistance (P=0.01). CONCLUSIONS: Lamivudine-resistant HBV patients exhibiting HBeAg negativity and liver cirrhosis were more likely to achieve an IVR after adefovir therapy. Adefovir resistance was associated with mixed infection of the precore mutant.

[Liver stiffness measurement for the diagnosis of hepatic fibrosis in patients with chronic viral hepatitis].

BACKGROUND AND AIMS: FibroScan is a new medical device that noninvasively measures liver stiffness. The aim of this study was to assess the accuracy of the liver stiffness measurement by FibroScan for making the diagnosis of liver fibrosis in patients with chronic viral hepatitis. METHODS: We studied 103 patients with chronic viral hepatitis B or C and they underwent FibroScan and liver biopsy between October 2005 and August 2006. Liver fibrosis was staged on a 0-4 scale according to the Korean Society of Pathologists Scoring System. The diagnostic accuracy was assessed by analysis of the receiver operator characteristics (ROC). RESULTS: The liver stiffness was 3.5-57.1 kPa (mean: 11.8, SD: 8.9). The mean value of liver stiffness in each fibrosis stage group (F1, F2, F3 and F4) was 5.8+/-1.8 kPa, 11.3+/-6.8 kPa, 11.8+/-6.0 kPa and 23.4+/-16.5 kPa, respectively. Liver stiffness measured by FibroScan showed reliable correlation with the liver fibrosis stage as confirmed by liver biopsy (r=0.56, p<0.001). The AUROC (95% CI) of > or = F2, > or = F3 and F4 was 0.93 (0.86-0.99), 0.72 (0.62-0.82) and 0.80 (0.67-0.92), respectively. The sensitivity and specificity of 7.5 kPa, which was the cutoff value for > or = F2, was 84% and 90%, respectively. CONCLUSIONS: FibroScan is a reliable method for the diagnosis of significant fibrosis (> or =F2) and cirrhosis in patients with chronic liver disease. The liver stiffness measurement by FibroScan showed good diagnostic performance for significant fibrosis.

[Association of interleukin-12 gene polymorphism with persistence of hepatitis B virus infection and hepatocellular carcinoma].

BACKGROUND/AIMS: Infection with hepatitis B virus (HBV) may result in various conditions. Natural course of HBV infection is influenced by various host immune factors and cytokines play a crucial role in host immune defense. This study was undertaken to investigate the association between HBV persistence and development of hepatocelluar carcinoma (HCC) and single nucleotide polymorphisms (SNPs) of interleukin (IL)-12A. METHODS: Between March 2002 and December 2004, seven hundred thirty Korean patients with HBV infection and 320 healthy individuals who recovered from HBV infection were enrolled. We assessed polymorphisms and haplotype in IL-12A, and the genotype distributions of the HBV clearance and persistence groups were compared in order to investigate the association between HBV persistence and SNPs of IL-12A. Moreover, the genotypic distributions between patients with HCC and without HCC were compared to investigate the association between the development of HCC and SNPs of IL-12A. RESULTS: We asssesed the SNPs of IL-12A at position +6400, +6624 and +7003. On the basis of logistic regression analysis, no statistically significant association with HBV persistence was observed with IL-12A exon 7 +6400, +6624, 3' UTR +7003 SNP and haplotype of IL-12A +6400/+6624/+7003. Furthermore, no statistically significant association of HCC development with IL-12A exon 7 +6400, +6624, 3' UTR +7003 SNP and haplotype of IL-12A +6400/+6624/+7003 was observed. CONCLUSIONS: These results suggest that SNPs and haplotype of IL-12A are not associated with HBV persistence and development of HCC. Further studies are needed to identify the host genetic factors in immune defense including cytokine gene polymorphisms of both IL-12A and IL-12B.