Low-level viremia and cirrhotic complications in patients with chronic hepatitis B according to adherence to entecavir.

BACKGROUND/AIMS: Low-level viremia (LLV) after nucleos(t)ide analog treatment was presented as a possible cause of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). However, detailed information on patients' adherence in the real world was lacking. This study aimed to evaluate the effects of LLV on HCC development, mortality, and cirrhotic complications among patients according to their adherence to entecavir (ETV) treatment. METHODS: We performed a retrospective observational analysis of data from 894 consecutive adult patients with treatment-naïve CHB undergoing ETV treatment. LLV was defined according to either persistent or intermittent episodes of <2,000 IU/mL detectable hepatitis B virus DNA during the follow-up period. Good adherence to medication was defined as a cumulative adherence ≥90% per study period. RESULTS: Without considering adherence in the entire cohort (n=894), multivariate analysis of the HCC incidence showed that LLV was an independent prognostic factor in addition to other traditional risk factors in the entire cohort (P=0.031). Good adherence group comprised 617 patients (69.0%). No significant difference was found between maintained virologic response and LLV groups in terms of the incidence of liver-related death or transplantation, HCC, and hepatic decompensation in good adherence group, according to multivariate analyses. CONCLUSION: In patients with treatment-naïve CHB and good adherence to ETV treatment in the real world, LLV during treatment is not a predictive factor for HCC and cirrhotic complications. It may be unnecessary to adjust their antiviral agent for patients with good adherence who experience LLV during ETV treatment.

Effect of Weight Changes on the Development of Erosive Esophagitis.

BACKGROUND: Gastroesophageal reflux disease is highly prevalent among overweight and obese individuals. This study aimed to investigate the effect of weight change on the development of erosive esophagitis (EE). METHODS: A retrospective review of medical records from a university hospital in South Korea identified 7,123 subjects who underwent routine health checkups in 2012 and 2014. We excluded participants with EE in 2012. Body mass index (BMI) changes were classified as loss, stable, mild gain, or moderate gain. RESULTS: Mild and moderate weight gain increased the odds of EE development (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.06-1.84 and OR, 2.80; 95% CI, 1.87-4.21, respectively) relative to weight stability. Weight loss decreased the odds of EE development (OR, 0.58; 95% CI, 0.38-0.90) relative to weight stability. After stratifying subjects into three groups by baseline BMI, those with mild and moderate weight gain in the obese group and moderate gain in the overweight group showed increased odds of EE development relative to members of those groups whose weights remained stable (OR, 2.08; 95% CI, 1.29-3.36; OR, 3.92; 95% CI, 1.99-7.73 in obese group, and OR, 3.30; 95% CI, 1.64-6.64 in overweight group, respectively). In comparison, weight loss in the normal weight group decreased the odds of EE development relative to weight stability (OR, 0.38; 95% CI, 0.15-0.97). CONCLUSION: Weight gain was positively associated with EE development in overweight or obese individuals. Weight loss was negatively associated with EE development in normal-weight individuals.

The risk of hepatocellular carcinoma within and beyond the first 5 years of entecavir in Korean patients with chronic hepatitis B.

BACKGROUND & AIMS: The development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) has decreased due to potent antiviral agents. However, it remains uncertain whether the risk of HCC will diminish after long-term antiviral therapy in Asia, where CHB is endemic and vertical transmission is common. This study aimed to compare the incidence of HCC within and beyond the first 5 years of entecavir (ETV) in treatment-naïve Korean patients with CHB. METHODS: We performed a retrospective observational analysis of data from 894 consecutive, adult patients with CHB undergoing ETV treatment at a tertiary referral hospital in Ulsan, Korea from January 1, 2007 through April 31, 2017. We compared the HCC incidence rates per 100 person-years within and beyond the first 5 years. Univariate and multivariate analyses for factors predictive of HCC were performed. RESULTS: The incidence rate of HCC in patients with CHB did not differ statistically when we compared within and beyond the first 5 years of ETV therapy (2.29% vs 1.66% per person-year, P = 0.217). Failure to achieve maintained virological response (MVR) was a major independent risk factor for HCC in patients at a follow-up of <5 years. In contrast, in patients with a follow-up of ≥5 years, achieving MVR was not significantly associated with HCC development. CONCLUSIONS: The incidence rate of HCC may not change significantly before and after 5 years of ETV therapy in Korean CHB patients. The risk of HCC in Asian CHB patients may remain in the long-term.

Mortality, liver transplantation and hepatic complications in patients with treatment-naïve chronic hepatitis B treated with entecavir vs tenofovir.

Few studies have directly compared the long-term clinical outcomes of entecavir (ETV) and tenofovir disoproxil fumarate (TDF). This study aimed to compare the risk of mortality, liver transplantation and hepatic complications including hepatocellular carcinoma (HCC) and hepatic decompensation between these drugs in treatment-naïve chronic hepatitis B (CHB). We performed a longitudinal observational analysis of data from 1325 consecutive adult CHB patients with a cumulative adherence of ≥80% to treatment with ETV (n = 721) or TDF (n = 604) at a tertiary referral hospital in Ulsan, Korea, from 1 January 2007 through 31 April 2017. Among the patients, 708 were analysed using propensity score matching with a ratio of 1:1. In the follow-up period of up to 5 years, five patients (0.4%) died, three patients (0.2%) underwent liver transplantation (LT) and 54 patients (4.1%) developed HCC. Hepatic decompensation occurred in 24 (1.8%) patients. ETV therapy did not significantly differ from TDF therapy regarding the risk of liver-related death or LT (HR 0.96; 95% CI, 0.23-4.07; log-rank P = 0.955), HCC (HR, 1.36; 95% CI, 0.72-2.56; log-rank P = 0.340) and hepatic decompensation (HR, 1.64; 95% CI, 0.67-4.00; log-rank P = 0.276). In the 708 propensity-matched pairs, ETV and TDF were also not significantly different with respect to the risk of mortality, LT and hepatic complications. In this longitudinal observational study of 1325 patients with CHB, ETV and TDF therapies were not significantly different regarding the risk of mortality, HCC, LT and hepatic decompensation.

Silent invasion of Hem-O-Lok clip.

A 58-year-old man underwent laparoscopy-assisted distal gastrectomy (LADG) with Billroth I gastroduodenostomy due to early gastric cancer. During surgery, the perigastric vessels were ligated with Hem-o-Lok clips. Esophagogastroduodenoscopy (EGD) 6 months later showed a fungating mass at the anastomosis site. Repeat EGD 1 year after LADG showed a Hem-o-Lok clip at the fungating mass lesion. Because the patient was asymptomatic, with no major abnormalities on clinical examination, and endoscopic removal of the clip would have been difficult due to the presence of adhesions and inflammation, no attempt was made to remove the clip. The patient remained well after the exposed Hem-o-Lok clip was identified. A third EGD 6 months later showed that the clip had disappeared from the anastomosis site, and that this site was covered with normal mucosa surrounding the scar.

Association between non-alcoholic fatty liver disease and subclinical coronary atherosclerosis: An observational cohort study.

BACKGROUND & AIMS: There are limited data on the association between non-alcoholic fatty liver disease (NAFLD) and subclinical coronary atherosclerosis. This study investigated the influence of NAFLD on subclinical coronary atherosclerosis as detected by coronary computed tomography angiography (CCTA) in an asymptomatic population. METHODS: A total of 5,121 consecutive asymptomatic individuals with no prior history of coronary artery disease or significant alcohol intake voluntarily underwent abdominal ultrasonography and CCTA as part of a general health examination. Fatty liver was assessed by ultrasonography examination. The fatty liver index and NAFLD fibrosis score were also calculated. Coronary atherosclerotic plaques on CCTA were evaluated. The association between NAFLD and subclinical coronary atherosclerosis was determined by logistic regression analysis. RESULTS: Of the study participants, 1,979 (38.6%) had ultrasonography-diagnosed NAFLD. After adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios of NAFLD for calcified plaque (1.03; 95% CI 0.89-1.20; p = 0.673) and mixed plaque (1.15; 95% CI 0.93-1.42; p = 0.214). However, adjusted odds ratios for any atherosclerotic plaque (1.18; 95% CI 1.03-1.35; p = 0.016) and non-calcified plaque (1.27; 95% CI 1.08-1.48; p = 0.003) were significantly higher in NAFLD. In addition, there was a significant association of fatty liver index ≥30 with non-calcified plaque (1.37; 95% CI 1.14-1.65; p = 0.001) and NAFLD fibrosis score ≥-1.455 with non-calcified plaque (1.20; 95% CI 1.08-1.42; p = 0.030). CONCLUSIONS: In this large cross-sectional study of asymptomatic individuals undergoing CCTA, NAFLD was consistently associated with non-calcified plaque, suggesting an increased cardiovascular risk. LAY SUMMARY: In asymptomatic individuals, non-alcoholic fatty liver disease (NAFLD) was an independent risk factor for non-calcified plaque, which has been known as a vulnerable plaque associated with sudden and unexpected cardiac events. Therefore, appropriate medical therapy for NAFLD was required to reduce future cardiac events.

The Degree of Disease Knowledge in Patients with Gastroesophageal Reflux Disease: A Multi-center Prospective Study in Korea.

BACKGROUND/AIMS: Patient education has been shown to be beneficial in several diseases. To properly educate patients with gastroesophageal reflux disease (GERD), it is necessary to understand how much they already know about their disease. However, no study has examined the degree of disease knowledge in Korean patients with GERD. Therefore, we conducted this study to assess the degree of knowledge in such patients. METHODS: This multicenter prospective study was conducted from January 2014 to January 2015. A total of 746 patients (mean age, 52 years; 57.6% female) were enrolled from 7 hospitals in Korea. Inclusion criteria were diagnosis of GERD and ability to properly complete a survey. Degree of disease knowledge was assessed using the translated, validated Korean Urnes questionnaire, which consists of 22 items related to GERD. RESULTS: Mean percentage of correct answers was 46.3% and mean GERD knowledge score was 9.6. Degree of knowledge (mean percentage of correct answers) regarding etiology, prognosis, and treatment of GERD were 49.5%, 36.7%, and 37.5%, respectively. Degree of disease knowledge differed significantly according to age (P < 0.001), education (P < 0.001), income (P = 0.028), and occupation (P < 0.001). In multivariate analysis, using multiple logistic regression, the higher knowledge score group tended to have higher education and professional occupation. CONCLUSIONS: The surveyed Korean patients had relatively low disease knowledge, suggesting that a GERD educational program may be beneficial in Korea. Formulation of a program is underway.

A Review of Diagnosis of GERD.

The prevalence of gastroesophageal reflux disease (GERD) and the incidence of some of its complications have risen strikingly over the last few decades. With the accumulation in our understanding on the pathophysiology of GERD along with the development of proton pump inhibitors, the diagnostic and therapeutic approaches to the GERD have changed dramatically over the past decade. However, The GERD still poses a problem to many clinicians since the spectrum of the disease has evolved to encompass more challenging presentations such as refractory GERD and extraesophageal manifestations. The aim of this article was to provide a review of available current diagnostic tests of the GERD, includes proton pump inhibitor test, ambulatory pH monitoring, impedance pH monitoring, mucosa impedance, and high resolution manometry. This review discusses different modalities for the work up of GERD.

[Current Status of Translational Research on Gastroesophageal Reflux Disease].

The prevalence of gastroesophageal reflux disease (GERD) and the incidence of some of its complications have risen strikingly over the last few decades. With the increase in our understanding of the pathophysiology of GERD along with the development of proton pump inhibitors, the diagnostic and therapeutic approaches to GERD have changed dramatically over the past decade. However, GERD still poses a problem to many clinicians since the spectrum of the disease has evolved to encompass more challenging presentations such as refractory GERD and extra-esophageal manifestations. The aim of this article is to provide a review of available current translational research on GERD. This review includes acid pocket, ambulatory pH monitoring, impedance pH monitoring, mucosa impedance, and high resolution manometry. This article discusses current translational research on GERD.

Efficacy of Tenofovir-based Rescue Therapy in Lamivudine-resistant Chronic Hepatitis B Patients With Failure of Lamivudine and Adefovir Combination.

PURPOSE: In chronic hepatitis B patients, lamivudine (LAM) and adefovir (ADV) combination therapy is commonly used as a rescue therapy for LAM resistance, but it often results in incomplete viral suppression. We investigated the antiviral efficacy of tenofovir (TDF)/LAM combination therapy versus TDF monotherapy in LAM-resistant chronic hepatitis B (CHB) patients who failed to respond to LAM plus ADV rescue therapy. METHODS: Among 108 patients with LAM-resistant CHB who had a partial virologic response (VR) to LAM and ADV combination therapy, Eighty one patients were finally included in this study. FINDINGS: Resistance to ADV (ADV-R) was present in 32 patients (39.5%), and the remaining 49 patients (60.5%) had a partial virologic response to LAM/ADV combination (ADV-P). The study subjects were treated with TDF alone (n=15) or TDF/LAM combination (n=66). VR was achieved in 61 patients (75.3%). The rates of VR at 6 and 12 months were not significantly different between TDF monotherapy and TDF/LAM combination therapy groups (46.7 vs. 68.2% at 6 months, and 66.7 vs. 75.9% at 12 months, log-rank P=0.357). Treatment efficacy of TDF alone or TDF/LAM combination was not statistically different according to pre-existing ADV or LAM resistant strains. In multivariate analysis, absolute HBV DNA levels at the start of TDF rescue treatment (P<0.001; OR, 0.556; 95% CI, 0.422-0.731) were the only significantly associated with VR. IMPLICATIONS: TDF monotherapy was as effective as TDF/LAM combination therapy in maintaining viral suppression in patients with LAM-resistant patients who failed to respond to LAM/ADV combination therapy.

Tenofovir-based rescue therapy for chronic hepatitis B patients who had failed treatment with lamivudine, adefovir, and entecavir.

BACKGROUND AND AIM: In the past decade, many chronic hepatitis B (CHB) patients have undergone sequential treatment with lamivudine (LAM), adefovir (ADV), and entecavir (ETV) to manage antiviral resistance or insufficient suppression of HBV-DNA. Very limited data are available on the efficacy of tenofovir (TDF) rescue regimens in patients with multidrug resistance (MDR). METHODS: We investigated the antiviral efficacy of TDF/LAM combination therapy versus TDF/ETV combination therapy in 52 patients who failed three previous antiviral therapies. RESULTS: The study subjects were treated with TDF/LAM combination therapy (n = 25) or TDF/ETV combination therapy (n = 27) for more than six months. Virologic response (VR) occurred in 39 (75%) patients (19 patients belonged to the TDF/LAM group and 20 patients belonged to the TDF/ETV group). The VR rates were not different between the TDF/LAM and TDF/ETV groups (56.0% vs 51.9% at month 12, and 72.0% vs 78.8% at month 18; log rank P = 0.515). In addition, treatment efficacy of TDF/LAM combination or TDF/ETV combination was not statistically different according to types of MDR. In multivariate analysis, absolute HBV-DNA level at the start of TDF rescue treatment (P < 0.001; OR, 0.452; 95% CI, 0.306-0.666) was only significantly associated with VR. CONCLUSIONS: TDF/ETV combination therapy was not associated with higher rate of VR compared with TDF/LAM combination therapy in MDR CHB patients. These results raise the suspicion about the superiority of the combination therapy over TDF monotherapy. The lower HBV-DNA levels at the start of TDF-based rescue therapy were associated with higher VR.

[Current issues on gastroesophageal reflux disease].

Gastroesophageal reflux disease (GERD) is one of the most common problems in gastrointestinal disorders. With the increase in our understanding on the pathophysiology of GERD along with the development of proton pump inhibitors, the diagnostic and therapeutic approaches to GERD have changed dramatically over the past decade. However, GERD still poses a problem to many clinicians since the spectrum of the disease has evolved to encompass more challenging presentations such as refractory GERD and extraesophageal manifestations. This has led to significant confusion regarding the optimal approach to these patients. This article aims to discuss current issues on GERD.

The effectiveness of endoscopic submucosal resection with a ligation device for small rectal carcinoid tumors: focused on previously biopsied tumors.

PURPOSE: To evaluate the effectiveness of endoscopic submucosal resection with a ligation device (ESMR-L) on histologic complete resection for the treatment of small rectal carcinoid tumors in comparison with the treatment with endoscopic mucosal resection (EMR) alone. METHODS: Thirty-five patients with small rectal carcinoid tumors were enrolled prospectively for ESMR-L, and we retrospectively reviewed 74 carcinoid tumor patients who underwent EMR. The comparison between ESMR-L and EMR groups was analyzed including endoscopic and histologic complete resection and complications after resection. We also evaluated the associations of histologic complete resection with clinical and procedure-related factors. RESULTS: The histologic complete resection rate was significantly higher in ESMR-L than in EMR (94.3% vs. 75.7%, P=0.019). In addition, the resection time was significantly shorter in ESMR-L than in EMR (4.16±1.48 min vs. 5.11±2.47 min, respectively, P=0.014). Moreover, previously biopsied rectal carcinoid tumors were significantly associated with histologic incomplete resection, especially in patients who underwent EMR (odds ratio, 6.28; 95% confidence interval, 1.92-20.58; P=0.002). CONCLUSIONS: Compared with EMR, ESMR-L is a safe and effective method for histologic complete resection of small rectal carcinoid tumors, especially in patients with previously biopsied carcinoid tumors.

Clinical course of patients with insufficient viral suppression during entecavir therapy in genotype C chronic hepatitis B.

BACKGROUND/AIMS: The clinical course of patients with insufficient virologic suppression diagnosed with chronic hepatitis B undergoing entecavir therapy is unclear. METHODS: We retrospectively investigated the long-term clinical outcomes of entecavir treatment for more than 12 months in 355 nucleos(t)ide-naïve chronic hepatitis B patients, particularly those with primary non-response or partial virologic response. RESULTS: The median duration of entecavir therapy was 40 months (range, 12-64 months). Virologic response was achieved in 315 patients (88.7%). One hundred forty-four (96.6%) of 149 HBeAg-negative patients achieved virologic response. Among 206 HBeAg-positive patients, 52 (25.2%) achieved HBeAg seroconversion. Virologic breakthrough was observed in 7 patients (2.0%). Of these 7 patients, 5 (1.4%) had genotypic resistance to entecavir. Primary non-response and partial virologic response were evident in 6 (1.7%) and 63 (17.7%) patients, respectively. During continuous prolonged entecavir therapy, virologic response of patients with primary non-response and partial virologic response was achieved in 6 (100%) and 28 (44.4%) patients, respectively. CONCLUSION: The vast majority of chronic hepatitis B patients in this study achieved virologic response through prolonged entecavir therapy, with only 1.4% chance of viral resistance. Furthermore, all patients with primary non-response were able to achieve virologic response without adjustment of antiviral therapy.

The expression kinetics of CD137 in chronic hepatitis C patients treated with pegylated-interferon and ribavirin.

OBJECTIVE: CD137, a member of the tumor necrosis factor receptor family, generates co-stimulatory signals leading to T-cell activation and proliferation for viral eradication. We examined the expression kinetics of CD137 to validate whether it can affect treatment outcomes of chronic hepatitis C (CHC) patients. METHODS: The expression of CD137 on peripheral blood mononuclear cells (PBMC) from 50 CHC patients and 20 healthy controls was analyzed by flow cytometry. CD137 expression levels were examined before treatment, and every 4 weeks during treatment until week 24 or 48, and at the 24-week follow-up. RESULTS: CD137 expression on PBMC was significantly lower in CHC patients than controls (15.5 ± 7.8% vs 23.4 ± 5.2%; p < 0.05). Patients with sustained virological response (SVR) showed higher level of CD137 expression on PBMC than treatment failures at week 4 (20.11% vs 10.97%; p < 0.05) and week 12 (15.48% vs 5.74%; p < 0.01). CD137 expression on CD4 T cells was also higher in patients with SVR at week 8 (7.75% vs 3.29%; p < 0.05). CD137 expression on PBMC from patients with SVR recovered to the control level at the 24-week follow-up. In multivariate analysis, the increased expression of CD137 at week 4 and genotype non-1 were significantly associated with SVR. CONCLUSIONS: The increased expression of CD137 within 12 weeks after the initiation of interferon therapy might be associated with a successful treatment outcome. Modulation to improve expression of CD137 might improve efficacy of CHC treatment.

Endoscopic enucleation for gastric subepithelial tumors originating in the muscularis propria layer.

BACKGROUND: Subepithelial tumors (SETs) of the stomach are considered benign. However, they have the potential for malignant transformation, especially if they originate in the muscularis propria layer. This study aimed to determine the feasibility of endoscopic enucleation (EEN) for SETs in the muscularis propria layer and to evaluate the diagnostic efficacy and safety of EEN for SETs. METHODS: A total of 65 lesions in 64 patients were eligible for inclusion in the study during the period between June 2006 and September 2009. En bloc enucleation using an insulated-tip knife and snare was attempted for removal of gastric SETs from the muscularis propria. RESULTS: A total of 60 tumors were successfully resected by EEN (success rate, 92.3%). The mean tumor size, determined by endoscopic ultrasound, was 13.8 mm (range, 5-30 mm). A histologic diagnosis was obtained for 63 tumors (diagnostic yield, 96.9%), which was leiomyoma for 32 lesions, gastrointestinal stromal tumor for 26 tumors, and other for 5 tumors. The rate for complete resection in relation to the location of the lesion in the stomach was higher for the cardia, the mid/lower body (100%), and the high body (96%) than for the fundus (75%) or the antrum (50%, p=0.006). The rate of perforation was significantly higher for the fundus (50%) than for other locations (0% for the cardia and 4% for the high body) (p<0.001). CONCLUSIONS: Endoscopic enucleation of gastric SETs originating in the muscularis propria layer was a safe and effective method for the histologic diagnosis and removal of small gastric SETs, especially those located in the cardia and the high body of the stomach.

Successful outcomes of endoscopic resection for gastric adenomas and early cancers located on the pyloric ring (with video).

BACKGROUND: Endoscopic resection is difficult to perform in patients who have gastric neoplasms located on the pyloric ring, especially for lesions that extend from the pyloric area to the duodenal bulb, where it is difficult to retroflex the endoscope, and the risk of perforation is increased. OBJECTIVE: To assess the results of endoscopic resection of early gastric neoplasms located on the pyloric ring. DESIGN: Case series. SETTING: Tertiary-care referral center. PATIENTS: This study involved 16 patients with 5 gastric adenomas and 11 early cancers that were located on the pyloric ring. INTERVENTIONS: After a retroflexion trial within the duodenum for evaluation of tumor extension from the pyloric area to the duodenal bulb, en bloc resection was attempted. Endoscopic submucosal dissection was attempted at the duodenal bulb with an endoscope retroflexed for cases of duodenal invasion. MAIN OUTCOME MEASUREMENTS: The curative resection rate, en bloc resection rate, and complications were determined. RESULTS: The success rate of retroflexion within the duodenum was 88% (14 of 16). The curative resection rate was 81.3% (13 of 16), and the en bloc resection rate was 75% (12 of 16). En bloc resection was possible for 3 of 4 (75%) cases of duodenal bulb extension. Major procedure-related complications were not encountered. LIMITATIONS: Small number of patients. CONCLUSION: Endoscopic resection appears to be a feasible and effective treatment for early gastric neoplasms located on the pyloric ring, including lesions that extend from the pyloric area to the duodenal bulb.

Clinical usefulness of sequential hepatitis B virus DNA measurement (the roadmap concept) during adefovir treatment in lamivudine-resistant patients.

BACKGROUND: Sequential on-treatment monitoring of hepatitis B virus (HBV) DNA levels, known as the roadmap concept, might predict the efficacy of oral therapy with nucleoside/nucleotide analogues among patients naive to this treatment. The goal of this study was to verify the usefulness of the roadmap concept to predict clinical outcomes of adefovir dipivoxil monotherapy in hepatitis B e antigen (HBeAg)-positive patients with lamivudine resistance. METHODS: In 231 patients, serum HBeAg, antibody against HBeAg and HBV DNA levels were measured at weeks 12, 24 and 48 of treatment and every 3 months thereafter. RESULTS: Complete (HBV DNA<60 IU/ml by PCR), partial (HBV DNA 60-<2,000 IU/ml) and inadequate (HBV DNA> or =2,000 IU/ml) virological responses at week 24 were observed in 49 (21.2%), 66 (28.6%) and 116 (50.2%) lamivudine-resistant patients, respectively, who were treated with adefovir dipivoxil monotherapy. At final assessment, rates of complete virological response in these groups were 100%, 71.2%, and 22.4%. Of the total 42 virological breakthroughs, 33 (78.6%) and 8 (19.1%) developed in the inadequate and partial response groups, respectively. Among the 91 patients who had HBV DNA<200 IU/ml at week 48, complete virological response and HBeAg seroconversion were finally achieved in 87 (95.6%) and 39 (42.9%) patients, respectively. Of these 91 patients, virological breakthrough and genotype mutations developed in only 4 (4.4%) and 3 (3.3%) patients. The roadmap concept predicted virological response, HBeAg seroconversion and breakthrough (odds ratios 3.68, 9.67 and 0.15, respectively). CONCLUSIONS: The roadmap concept is useful for choosing between continuation of adefovir dipivoxil monotherapy or early switching to another therapy, or to suggest additional therapy in patients showing lamivudine resistance.