Expression of Hepatocyte Hepatitis B Core Antigen and Hepatitis B Surface Antigen as a Marker in the Management of Chronic Hepatitis B Patients

BACKGROUND/AIMS: We aimed to clarify the association of hepatitis B surface antigen (HBsAg)/hepatitis B core antigen (HBcAg) with the disease status and treatment response in patients with chronic hepatitis B (CHB). METHODS: We investigated 171 biopsy-proven entecavir-treated CHB patients (109 hepatitis B e antigen [HBeAg]-positive, 62 HBeAg-negative). HBcAg expression was positive when ≥10% of hepatocytes stained, and classified into nuclear, mixed, and cytoplasmic patterns. HBsAg expressions were intracytoplasmic (diffuse, globular, and submembranous) and membranous. The histologic activity index (HAI) and fibrosis stage followed Ishak system. RESULTS: In HBeAg-positive patients, older age, increased HAI score, advanced fibrosis, and reduced viral load were observed when HBcAg expression shifted from nucleus to cytoplasm in HBcAg-positive patients, and HBsAg expression from non-submembranous to submembranous in HBcAg-negative patients (all, p<0.05). In HBeAg-negative patients, only intracytoplasmic HBsAg expression patterns had clinical relevance with decreased ALT levels and viremia. In HBeAg-positive patients without favorable predictors of virologic response, negative HBcAg and membranous HBsAg expression predicted greater virologic response (both, p<0.05). The probability of HBeAg seroclearance was higher in patients with increased HAI or lacking HBcAg expression (both, p<0.05). Higher serum HBsAg levels and hepatocyte HBcAg positivity were associated with reduced serum HBsAg during first and post-first year treatment, respectively (both, p<0.05). CONCLUSIONS: Hepatocyte HBcAg/HBsAg expression is a good marker for disease status and predicting treatment response.

Mycophenolate mofetil as an alternative treatment for autoimmune hepatitis

Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease characterized by hepatocellular inflammation, necrosis, and fibrosis, which can progress to cirrhosis and fulminant hepatic failure. The standard treatment for AIH includes corticosteroids alone or in combination with azathioprine. Although most patients achieve remission using the standard regimen, some patients do not respond due to either drug intolerance or refractory disease; in such cases alternative immunosuppressive agents should be explored. The second-line therapies are cyclophilin inhibitors such as cyclosporine A or tacrolimus, and nowadays mycophenolate mofetil (MMF) is widely used if azathioprine-based therapies are not tolerated. Although these are recommended as an alternative to the first-line regimen, there is insufficient evidence for the efficacy of second-line therapies, with the evidence based mainly on expert opinion. Therefore, we report an AIH patient receiving the standard regimen in whom remission did not occur due to side effects to azathioprine, but was successfully treated with MMF in combination with corticosteroids as an alternative to the standard regimen.

Caroli's disease misdiagnosed as intraductal papillary neoplasm of the bile duct

Caroli's disease is a rare autosomal-recessive disorder caused by malformation of the ductal plate during embryonic development. Although it is present at birth, Caroli's disease is typically not diagnosed until between the second and fourth decades of life, as it was in the present patient. Here we report a rare case of Caroli's disease limited to one liver segment, which was initially misdiagnosed as an intraductal papillary neoplasm of the bile duct. The asymptomatic patient was treated with liver segmentectomy.

Is propofol safe when administered to cirrhotic patients during sedative endoscopy?

BACKGROUND/AIMS: In patients with liver cirrhosis, drugs acting on the central nervous system can lead to hepatic encephalopathy and the effects may be prolonged. Recently, misuse of propofol has been reported and the associated risk of death have become an issue. Propofol is commonly used during sedative endoscopy; therefore, its safety in high-risk groups must be further investigated. We performed a pilot study of the safety and efficacy of propofol during endoscopy in Korean patients with cirrhosis. METHODS: Upper gastrointestinal endoscopy was performed under sedation with propofol along with careful monitoring in 20 patients with liver cirrhosis and 20 control subjects. The presence or development of hepatic encephalopathy was assessed using the number connection test and neurologic examination. RESULTS: Neither respiratory depression nor clinically significant hypotension were observed. Immediate postanesthetic recovery at 5 and 10 minutes after the procedure was delayed in the cirrhotic patients compared with the control group; however, at 30 minutes, the postanesthetic recovery was similar in both groups. Baseline psychomotor performance was more impaired in cirrhotic patients, but propofol was not associated with deteriorated psychomotor function even in cirrhotic patients with a minimal hepatic encephalopathy. CONCLUSIONS: Sedation with propofol was well tolerated in cirrhotic patients. No newly developed hepatic encephalopathy was observed.

Coffee Enema for Preparation for Small Bowel Video Capsule Endoscopy: A Pilot Study

Coffee enemas are believed to cause dilatation of bile ducts and excretion of bile through the colon wall. Proponents of coffee enemas claim that the cafestol palmitate in coffee enhances the activity of glutathione S-transferase, an enzyme that stimulates bile excretion. During video capsule endoscopy (VCE), excreted bile is one of the causes of poor preparation of the small bowel. This study aimed to evaluate the feasibility and effect of coffee enema for preparation of the small bowel during VCE. In this pilot study, 17 of 34 patients were assigned to the coffee enema plus polyethylene glycol (PEG) 2 L ingestion group, whereas the 17 remaining control patients received 2 L of PEG only. The quality of bowel preparation was evaluated in the two patient groups. Bowel preparations in the proximal segments of small bowel were not differ between two groups. In the mid and distal segments of the small intestine, bowel preparations tend to be better in patients who received coffee enemas plus PEG than in patients who received PEG only. The coffee enema group did not experience any complications or side effects. Coffee enemas may be a feasible option, and there were no clinically significant adverse events related to coffee enemas. More prospective randomized studies are warranted to improve small bowel preparation for VCE.

Gastrectomy for the treatment of refractory gastric ulceration after radioembolization with 90Y microspheres

Transcatheter arterial radioembolization (TARE) with Yttrium-90 (90Y)-labeled microspheres has an emerging role in treatment of patients with unresectable hepatocellular carcinoma. Although complication of TARE can be minimized by aggressive pre-evaluation angiography and preventive coiling of aberrant vessels, radioembolization-induced gastroduodenal ulcer can be irreversible and can be life-threatening. Treatment of radioembolization-induced gastric ulcer is challenging because there is a few reported cases and no consensus for management. We report a case of severe gastric ulceration with bleeding that eventually required surgery due to aberrant deposition of microspheres after TARE.

Fasting Blood Sugar and Serum Triglyceride as the Risk Factors of Colorectal Adenoma in Korean Population Receiving Screening Colonoscopy

In several previously reported studies, metabolic syndrome (MS) was found to be associated with colorectal adenomas. While the incidence of colorectal adenoma is growing in Korean population, there are only few studies that examined the association between MS and colorectal adenoma in Korea. The aim of this study was to investigate relationships between prevalence of colorectal adenoma and MS components. We conducted a cross sectional study using data from individuals who had undergone complete colonoscopy for health examinations at the Health Promotion Center of Korea University Medical Center from July 1, 2004 to July 31, 2010. A total of 7481 subjects (4459 males and 3022 females) were included; 1733 subjects with pathologically proven adenoma were assigned to the case group, and other 5748 subjects were assigned to the non-case group. All the participants underwent colonoscopy and received blood biochemical tests (fasting blood sugar [FBS], insulin, lipid profile, hemoglobin, blood urea nitrogen [BUN], creatinine). Univariate analysis showed that the prevalence of colorectal adenoma was higher in individuals with higher blood pressure, body mass index (BMI), total cholesterol (TC), triglyceride (TG), FBS and lower high-density lipoprotein cholesterols (HDL-C) levels, compared to those with low levels. Multiple logistic regression analysis revealed that high levels of BMI (OR 1.17, 95% CI 1.01-1.34, P trend = 0.01), TG (OR 1.27, 95% CI 1.07-1.51, P trend = 0.006), and FBS (OR 1.19 95% CI 1.01-1.40, P trend = 0.05) were significantly associated with prevalence of colorectal adenoma. Subjects with high levels of BMI, TG and FBS have increased prevalence of developing colorectal adenoma in Korea.

Risk Factors for Severe Diverticulitis in Computed Tomography-Confirmed Acute Diverticulitis in Korea

BACKGROUND/AIMS: Acute complicated diverticulitis can be subdivided into moderate diverticulitis and severe diverticulitis. Although there have been numerous studies on the risk factors for complicated diverticulitis, little research has focused on severe diverticulitis. This study was designed to identify the risk factors for severe diverticulitis in an acute diverticulitis attack using the modified Hinchey classification. METHODS: Patients were included if they had any evidence of acute diverticulitis detected by computed tomography. The patients were subdivided into severe diverticulitis (Hinchey class > or =Ib; abscesses or peritonitis) and moderate diverticulitis (Hinchey class Ia; pericolic inflammation) groups. RESULTS: Of the 128 patients, 25 exhibited severe diverticulitis, and 103 exhibited moderate diverticulitis. In a multivariate analysis, age >50 years (odds ratio [OR], 5.27; p=0.017), smoking (OR, 3.61; p=0.044), comorbidity (OR, 4.98; p=0.045), leukocytosis (OR, 7.70; p=0.003), recurrence (OR, 4.95; p=0.032), and left-sided diverticulitis (OR, 6.92; p=0.006) were significantly associated with severe diverticulitis. CONCLUSIONS: This study suggests that the risk factors for severe diverticulitis are age >50 years, smoking, comorbidity, leukocytosis, recurrent episodes, and left-sided diverticulitis.

Assessment on the Potential Role of Applying Cryoprobe for Tissue Ablation

BACKGROUND/AIMS: Cryotherapy is the therapeutic application for tissue ablation. Clinical applications of cryotherpy such as in pulmonology have increased. Until now, its development in gastroenterology has been insignificant. But, as clinical application such as mucosal ablation on Barrett's esophagus became possible, various applications have been developed. Therefore, it is important to make standards of tissue injury's extent in cryotherapy prior to clinical trial. We evaluated the tissue injury according to the application of cryoprobe with a pig model. METHODS: Cryoprobe was applied to several different segments of the esophagus and stomach for various lengths of time using various number of probe's contact in a pig model. After 48 hours, esophagus and stomach were harvested and histological tissue injury was assessed. The extent of tissue injury was decided by the injury of the deepest layer. RESULTS: Endoscopic application of cryoprobe on esophagus and stomach resulted in a dose-dependent injury: esophageal necrosis was limited to the submucosa after 10 seconds of cryotherapy, and extended to involve the transmural necrosis after over 15 seconds. Necrosis on stomach was extended to involve the transmural necrosis after over 20 seconds. CONCLUSIONS: Positive relationship was seen between the duration and frequency of cryoprobe application and the extent of tissue injury.

Feasibility of Obtaining Quantitative 3-Dimensional Information Using Conventional Endoscope: A Pilot Study

BACKGROUND/AIMS: Three-dimensional (3D) imaging is gaining popularity and has been partly adopted in laparoscopic surgery or robotic surgery but has not been applied to gastrointestinal endoscopy. As a first step, we conducted an experiment to evaluate whether images obtained by conventional gastrointestinal endoscopy could be used to acquire quantitative 3D information. METHODS: Two endoscopes (GIF-H260) were used in a Borrmann type I tumor model made of clay. The endoscopes were calibrated by correcting the barrel distortion and perspective distortion. Obtained images were converted to gray-level image, and the characteristics of the images were obtained by edge detection. Finally, data on 3D parameters were measured by using epipolar geometry, two view geometry, and pinhole camera model. RESULTS: The focal length (f) of endoscope at 30 mm was 258.49 pixels. Two endoscopes were fixed at predetermined distance, 12 mm (d12). After matching and calculating disparity (v2-v1), which was 106 pixels, the calculated length between the camera and object (L) was 29.26 mm. The height of the object projected onto the image (h) was then applied to the pinhole camera model, and the result of H (height and width) was 38.21 mm and 41.72 mm, respectively. Measurements were conducted from 2 different locations. The measurement errors ranged from 2.98% to 7.00% with the current Borrmann type I tumor model. CONCLUSIONS: It was feasible to obtain parameters necessary for 3D analysis and to apply the data to epipolar geometry with conventional gastrointestinal endoscope to calculate the size of an object.

Endoscopic Treatment of Duodenal Bleeding Caused by Direct Hepatocellular Carcinoma Invasion with an Ethanol Injection

We report a case of a man who developed duodenal bleeding caused by direct hepatocellular carcinoma (HCC) invasion, which was successfully treated with endoscopic ethanol injection. A 57-year-old man with known HCC was admitted for melena and exertional dyspnea. He had been diagnosed with inoperable HCC a year ago. Urgent esophagogastroduodenoscopy (EGD) showed two widely eroded mucosal lesions with irregularly shaped luminal protruding hard mass on the duodenal bulb. Argon plasma coagulation and Epinephrine injection failed to control bleeding. We injected ethanol via endoscopy to control bleeding two times with 14 cc and 15 cc separately without complication. Follow-up EGD catched a large ulcer with necrotic and sclerotic base but no bleeding evidence was present. He was discharged and he did relatively well during the following periods. In conclusion, Endoscopic ethanol injection can be used as a significantly effective and safe therapeutic tool in gastrointestinal tract bleeding caused by HCC invasion.

Optimal time for repeating the IgM anti-hepatitis A virus antibody test in acute hepatitis A patients with a negative initial test / 대한간학회지

BACKGROUND/AIMS: The nonspecific clinical presentation of acute hepatitis A (AHA) mandates the detection of anti-hepatitis A virus IgM antibodies (IgM anti-HAV) in the serum for obtaining a definitive diagnosis. However, IgM anti-HAV might not be present during the early phase of the disease. The aim of this study was to determine the optimal time for repeating the IgM anti-HAV test (HAV test) in AHA patients with a negative initial test. METHODS: In total, 261 patients hospitalized with AHA were enrolled for this retrospective study. AHA was diagnosed when the test for IgM anti-HAV was positive and the serum alanine aminotransferase (ALT) level was > or =400 IU/L. Repeat HAV test was conducted after 1-2 weeks if the initial HAV test was negative but AHA was still clinically suspected. RESULTS: The results of the initial HAV test were negative in 28 (10.7%) patients. The intervals from symptom onset to the initial-HAV-test day and from the peak-ALT day to the initial-HAV-test day were significantly shorter in the negative-initial-HAV-test group, but on multivariate analysis only the latter was significantly associated with negative results for the initial HAV test (beta=-0.978; odds ratio [95% confidence interval]=0.376 [0.189-0.747]; P=0.005). The HAV test was positive in all patients when it was performed at least 2 days after the peak-ALT day. CONCLUSIONS: The results of HAV tests were significantly associated with the interval from the peak-ALT day to the HAV-test day. The optimal time for repeating the HAV test in clinically suspicious AHA patients with a negative initial HAV test appears to be at least 2 days after the peak-ALT day.

The Effects of Combined Treatment with an HMG-CoA Reductase Inhibitor and PPARgamma Agonist on the Activation of Rat Pancreatic Stellate Cells

BACKGROUND/AIMS: Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) and peroxisome proliferator-activated receptor gamma (PPARgamma) ligands can modulate cellular differentiation, proliferation, and apoptosis through various pathways. It has been shown that HMG-CoA reductase inhibitors and PPARgamma agonists separately inhibit pancreatic stellate cell (PaSC) activation. We studied the effects of a combination of both types of drugs on activated PaSCs via platelet-derived growth factor (PDGF), which has not previously been reported. The present study was performed to elucidate the underlying mechanisms of these effects by focusing on the impact of the signaling associated with cell-cycle progression. METHODS: Primary cultures of rat PaSCs were exposed to simvastatin and troglitazone. Proliferation was quantified using the BrdU method, and cell-cycle analysis was performed using a fluorescent activated cell sorter. The protein expression levels of smooth muscle actin (SMA), extracellular signal-regulated kinase (ERK), and a cell cycle machinery protein (p27Kip1) were investigated using Western blot analysis. RESULTS: Simvastatin reversed the effects of PDGF on cell proliferation in a dose-dependent manner. The combination of a low concentration of simvastatin (1 mM) and troglitazone (10 mM) synergistically reversed the effects of PDGF on cell proliferation but had no effect on cell viability. The expression of a-SMA was markedly attenuated by combining the two drugs, which blocked the cell cycle beyond the G0/G1 phase by reducing the levels of phosphorylated ERK and reversed the expression of p27Kip1 interrupted by PDGF. CONCLUSIONS: Simvastatin and troglitazone synergistically inhibited cell proliferation in activated PaSCs by blocking the cell cycle beyond the G0/G1 phase. This inhibition was due to the synergistic modulation of the ERK pathway and the cell cycle machinery protein p27Kip1.

Clinical Significance of the Detection of Antinuclear Antibodies in Patients with Acute Hepatitis A

BACKGROUND/AIMS: The findings of several recent studies suggest that antinuclear antibodies (ANAs) are frequently detected in patients with acute hepatitis A (AHA). However, the clinical significance of a positive ANA test remains uncertain. This study was performed to evaluate the clinical significance of ANAs in AHA patients. METHODS: All patients admitted with AHA were consecutively enrolled in this study. An ANA assay was performed by indirect immunofluorescence during hospitalization. ANA positivity was defined as an ANA titer > or =1:80. The peak international normalized ratio (INR), peak alanine aminotransferase (ALT) and peak bilirubin levels were assessed over the duration of the hospitalization, and the incidence of AHA complications was evaluated. RESULTS: A total of 422 patients were enrolled in this study (age, 31+/-7 years), of which 260 (61.6%) were men. ANAs were detected in 179 AHA patients (42.4%). The proportion of ANA-positive patients varied significantly with AHA status on the day of the ANA assay (4.7% during the prodromal period vs 52.1% during the icteric or recovery period, p<0.001) and sex (56.2% in women vs 33.8% in men, p<0.001). The ANAs became undetectable in all ANA-positive patients within 3 months. The incidence of complications, including mortality, fulminant hepatic failure, renal dysfunction, relapse, and cholestatic hepatitis, did not differ significantly between ANA-positive and ANA-negative patients. CONCLUSIONS: ANAs were detected frequently and transiently in patients with AHA, especially after their peak-ALT day. The presence of ANAs may not be associated with the clinical outcome of AHA, but simply with AHA status on the ANA assay day.

The Efficacy of Early Scheduled Follow-Up Endoscopic Retrograde Cholangiopancreatography after Common Bile Duct Stone Removal

BACKGROUND/AIMS: To investigate the efficacy of early scheduled follow-up endoscopic retrograde cholangiopancreatography (ERCP) after common bile duct (CBD) stone removal. METHODS: Patients who underwent endoscopic CBD stone removal and who had at least one risk factor for stone recurrence were enrolled. Six months after complete clearance of the CBD, patients underwent follow-up ERCP at an ambulatory care center, irrespective of symptoms. RESULTS: The incidence of symptoms and cholangitis at follow-up ERCP was significantly lower in Group A (ERCP at 6 months after stone removal) than that in Group B (ERCP at >6 months) (14.3% vs 71.4%, p=0.00; 9.5% vs 33.3%, p=0.02, respectively). However, the recurrence rates of CBD stones were not different between Groups A and B (33.3% vs 47.6%). When comparing the subgroups, Group AR (stone recurrence in Group A) displayed significantly fewer symptoms and lesser cholangitis and spent fewer days in the hospital than did Group BR (stone recurrence in Group B) (21.4% vs 70%, p=0.02; 14.3% vs 60%, p=0.02; 2.43+/-1.87 vs 6.10+/-3.35, p=0.00, respectively). CONCLUSIONS: Our data suggest that, irrespective of symptoms, early scheduled follow-up ERCP for patients who are at a high risk of recurrence is effective and safe.

Comparison on the Efficacy of Disinfectants Used in Automated Endoscope Reprocessors: PHMB-DBAC versus Orthophthalaldehyde

BACKGROUND/AIMS: Since endoscopes are reusable apparatus classified as semicritical item, thorough reprocessing to achieve high-level disinfection is of utmost importance to prevent spread of infection. To improve disinfection efficacy and safety, disinfectants and endoscope reprocessors are continuously evolving. This study aimed to compare the efficacy of the combination of polyhexamethylenebiguanide hydrochloride-alkyldimethylbenzylammonium chloride (PHMB-DBAC) and orthophthalaldehyde (OPA) used respectively in ultrasonographic cleaning incorporated automated endoscope reprocessors: COOLENDO (APEX Korea) or OER-A (Olympus Optical). METHODS: A total of 86 flexible upper endoscopes were randomly reprocessed with either COOLENDO/PHMB-DBAC or OER-A/OPA. Culture samplings were done at two sites (endoscope tip and working channel) which were later incubated on blood agar plate. Bacterial colonies were counted and identified. RESULTS: The culture-positive rate at the endoscope tip and working channel was 0% and 2.33% for COOLENDO/PHMB-DBAC and 4.65% and 0% for OER-A/OPA. Staphylococcus hominis was cultured from one endoscope reprocessed with COOLENDO/PHMB-DBAC and Pseudomonas putida was isolated from two endoscopes reprocessed with OER-A/OPA. CONCLUSIONS: The reprocessing efficacy of COOLENDO/PHMB-DBAC was non-inferior to that of OER-A/OPA (p=0.032; confidence interval, -0.042 to 0.042). During the study period, significant side effect of PHMB-DBAC was not observed.

Solitary Primary Gastric Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a relatively rare subgroup of non-Hodgkin's lymphoma that is characterized by an aggressive and severe disease course with frequent involvement of regional lymph nodes and/or early metastasis. Because most cases of MCL are diagnosed in the advanced stages, clinical data on extranodal or early stage MCL is lacking, and MCL that is both extranodal and diagnosed during the early stages is even more rare. There have been several case reports on primary gastric MCL, which comprise a type of extranodal MCLs. However, to our knowledge, there have been no reports on solitary primary gastric MCL without regional lymph node involvement or distant metastasis. Recently, the authors experienced an uncommon case of MCL with the aforementioned characteristics that was managed with chemotherapy followed by allogenic stem cell transplantation.

A Case of Pyoderma Gangrenosum of the Face Associated with Ulcerative Colitis

Ulcerative colitis is associated with various extra-intestinal manifestations, including rheumatic, dermatologic, ophthalmologic, biliary, and hematologic manifestations. Cutaneous findings are common extra-intestinal manifestations of ulcerative colitis, occurring in 10-20% of patients. Cutaneous manifestations include erythema nodosum, pyoderma gangrenosum, aphthous stomatitis, and acute febrile neutrophilic dermatosis. Treatments for these cutaneous manifestations include corticosteroids, cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine, and infliximab. A 48-year-old male presented with an acute exacerbation of ulcerative colitis associated with multiple skin lesions on his face, thumbs, thighs, and feet. The final impression was neutrophilic folliculitis, which is an early form of pyoderma gangrenosum. The patient's skin lesions and colitis both improved with corticosteroids. There are rare published case reports of ulcerative colitis exacerbations associated with pyoderma gangrenosum that initiated as neutrophilic folliculitis of the face. This case report includes a review of the literature.

A Case of Cronkhite-Canada Syndrome Presenting with Hematochezia

Cronkhite-Canada syndrome (CCS) is a rare, non-familial hamartomatous polyposis syndrome characterized by multiple polyps in the entire gastrointestinal tract, nail dystrophy, skin pigmentation, and systemic alopecia. The clinical symptoms of this syndrome include diarrhea, abdominal pain, and alopecia often accompanied by taste disturbances, hypoalbuminemia, recurrent infections, nutritional absorption disturbances, heart failure, and gastrointestinal bleeding. We report a patient with CCS who was admitted complaining of hematochezia, melena, and a 1 month history of diarrhea, nail changes, taste disturbances, and alopecia. Upper endoscopy, colonoscopy, and capsule endoscopy were performed and showed numerous polyps in the stomach, small intestine, and large intestine. Histological sections of these polyps showed edematous stroma and cystically dilated foveolar epithelium, which was consistent with CCS. We diagnosed CCS based on the clinical symptoms and the histological findings of the polyps found via endoscopy. We report on this case and review this syndrome.

Virologic response is not durable after adefovir discontinuation in lamivudine-resistant chronic hepatitis B patients / 대한간학회지

BACKGROUND/AIMS: We investigated the durability of the biochemical and virologic responses after adefovir (ADV) discontinuation in lamivudine-resistant (LMV-R) chronic hepatitis B (CHB) patients, and the outcomes of ADV discontinuation compared to that of ADV maintenance. METHODS: The indication for ADV treatment cessation was an undetectable level of hepatitis B virus (HBV) DNA documented on two occasions at least 6 months apart. All patients received additional ADV for at least 12 months after the confirmation of undetectable HBV DNA (Cobas TaqMan PCR assay, <70 copies/mL). Of 36 patients who had a sufficient ADV therapeutic effect, 19 discontinued ADV treatment, while the others maintained it. A virologic rebound was arbitrarily defined as the redetection of HBV DNA at a level higher than 105 copies/mL. RESULTS: In the ADV discontinuation group, ADV treatment and additional therapy were administered for medians of 33 months (range, 12-47 months) and 18 months, respectively. The patients were followed for a median of 12 months (range, 3-30 months) after ADV cessation. During that period, 18 of 19 patients (95%) experienced viral relapse. Viral rebound was observed in six patients (32%). However, 12 of 18 patients (67%) exhibited serum HBV DNA levels of less than 105 copies/mL. Biochemical relapses were observed in four of the six patients with viral rebound. In the ADV maintenance group, patients were treated for a median of 53 months (range, 31-85 months), and 9 patients (53%) experienced viral breakthrough. CONCLUSIONS: During short-term follow-up after ADV discontinuation, most patients (95%) exhibited viral relapse, whereas and viral breakthrough occurred in about half of patients (53%) maintained on ADV therapy. Therefore, the durability of virologic response after ADV discontinuation in LMV-R patients was unsatisfactory. In addition, and viral breakthrough was not infrequent in the ADV continuation group.