Pine bark extract (Pycnogenol®) suppresses cigarette smoke-induced fibrotic response via transforming growth factor-β1/Smad family member 2/3 signaling / 한국실험동물학회지

Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of Pycnogenol® (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth factor-β1 (TGF-β1) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in TGF-β1/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.

Artemisia argyi attenuates airway inflammation in lipopolysaccharide induced acute lung injury model / 한국실험동물학회지

Artemisia argyi is used as a health supplement, tea, and food source in Korea. This study aimed to evaluate the effect of Artemisia argyi (AA) and its active compound, dehydromatricarin A (DA), on the attenuation of airway inflammation in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). The C57BL/6 mice were administered AA (50 mg/kg or 100 mg/kg) and DA (10 mg/kg or 20 mg/kg) by oral gavage from day 0 to 7 days and LPS treated by intranasal instillation 48 hours before the sacrifice. The treatment of AA and DA markedly decreased inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared with that in ALI-induced mice, which was accompanied by a significant reduction in the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in BALF. Furthermore, the administration of AA and DA clearly decreased inducible nitric oxide synthase (iNOS) expression and nuclear factor kappa B (NF-κB) phosphorylation in comparison with that in the ALI-induced mice. The histological examination of the lung tissue revealed that the administration of AA and DA suppressed the inflammatory cell infiltration into the peribronchial and alveolar lesions induced by LPS instillation. Collectively, our results indicated that AA and DA effectively decreased the airway inflammatory response induced by LPS instillation. Therefore, AA and DA may offer a potential therapy for airway inflammatory disease.

HemoHIM, a herbal preparation, alleviates airway inflammation caused by cigarette smoke and lipopolysaccharide / 한국실험동물학회지

HemoHIM, herbal preparation has designed for immune system recovery. We investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD) mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day (eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26. HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS exposure. HemoHIM reduced the inflammatory cell count and levels of tumor necrosis factor receptor (TNF)-α, interleukin (IL)-6 and IL-1β in the broncho-alveolar lavage fluid (BALF) induced by CS+LPS exposure. HemoHIM decreased the inflammatory cell infiltration in the airway and inhibited the expression of iNOS and MMP-9 and phosphorylation of Erk in lung tissue exposed to CS+LPS. In summary, our results indicate that HemoHIM inhibited a reduction in the lung inflammatory response on CS and LPS induced lung inflammation via the Erk pathway. Therefore, we suggest that HemoHIM has the potential to treat pulmonary inflammatory disease such as COPD.

Diallyl disulfide attenuates acetaminophen-induced renal injury in rats / 한국실험동물학회지

This study investigated the protective effects of diallyl disulfide (DADS) against acetaminophen (AAP)-induced acute renal injury in male rats. We also investigated the effects of DADS on kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), which are novel biomarkers of nephrotoxicity in renal tissues, in response to AAP treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) AAP (1,000 mg/kg), (3) AAP&DADS, and (4) DADS (50 mg/kg/day). AAP treatment caused acute kidney injury evidenced by increased serum blood urea nitrogen (BUN) levels and histopathological alterations. Additionally, Western blot and immunohistochemistry analysis showed increased expression of KIM-1 and NGAL proteins in renal tissues of AAP-treated rats. In contrast, DADS pretreatment significantly attenuated the AAP-induced nephrotoxic effects, including serum BUN level and expression of KIM-1 and NGAL proteins. Histopathological studies confirmed the renoprotective effect of DADS. The results suggest that DADS prevents AAP-induced acute nephrotoxicity, and that KIM-1 and NGAL may be useful biomarkers for the detection and monitoring of acute kidney injury associated with AAP exposure.

Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury / 한국실험동물학회지

In this study, the potential hepatotoxicity of 1,3-dichloro-2-propanol and its hepatotoxic mechanisms in rats was investigated. The test chemical was administered orally to male rats at 0, 27.5, 55, and 110 mg/kg body weight. 1,3-Dichloro-2-propanol administration caused acute hepatotoxicity, as evidenced by an increase in serum aminotransferases, total cholesterol, and total bilirubin levels and a decrease in serum glucose concentration in a dose-dependent manner with corresponding histopathological changes in the hepatic tissues. The significant increase in malondialdehyde content and the significant decrease in glutathione content and antioxidant enzyme activities indicated that 1,3-dichloro-2-propanol-induced hepatic damage was mediated through oxidative stress, which caused a dose-dependent increase of hepatocellular apoptotic changes in the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and immunohistochemical analysis for caspase-3. The phosphorylation of mitogen-activated protein kinases caused by 1,3-dichloro-2-propanol possibly involved in hepatocellular apoptotic changes in rat liver. Furthermore, 1,3-dichloro-2-propanol induced an inflammatory response through activation of nuclear factor-kappa B signaling that coincided with the induction of pro-inflammatory mediators or cytokines in a dose-dependent manner. Taken together, these results demonstrate that hepatotoxicity may be related to oxidative stress-mediated activation of mitogen-activated protein kinases and nuclear factor-kappa B-mediated inflammatory response.

New monoclonal antibody-based test for Helicobacter pylori urease in gastric tissue

BACKGROUND/AIMS: To evaluate a new monoclonal antibody for Helicobacter pylori urease in gastric tissue. METHODS: A total of 107 volunteers were enrolled. All subjects underwent a 13C-urea breath test and esophagogastroduodenoscopy. Gastric aspirates were analyzed for pH and ammonia. Six biopsy specimens in the gastric antrum and body were obtained for a rapid urease test and histology. The new monoclonal antibody-based H. pylori urease test (HPU) was performed to rapidly and qualitatively detect urease in two biopsy specimens. RESULTS: H. pylori infection was diagnosed in 73 subjects. The sensitivity and specificity of the HPU was 89% and 74%, respectively. The subjects were divided into two groups: one with true-positive and true-negative HPU results (n = 90) and the other with false-positive and false-negative HPU results (n = 17). Across all subjects, ammonia levels were 900.5 +/- 646.7 and 604.3 +/- 594.3 mumol/L (p > 0.05), and pH was 3.37 +/- 1.64 and 2.82 +/- 1.51 (p > 0.05). Sensitivity was higher in the presence of atrophic gastritis or intestinal metaplasia. CONCLUSIONS: HPU detected H. pylori in approximately 10 min. Gastric aspirate ammonia and pH levels did not affect the test results. Sensitivity was good in the presence of atrophic gastritis or intestinal metaplasia.

Evaluation of 2-week repeated oral dose toxicity of 100 nm zinc oxide nanoparticles in rats / 한국실험동물학회지

The aim of this study was to verify subacute oral dose toxicity of positively charged 100 nm zinc oxide (ZnO(AE100[+])) nanoparticles (NPs) in Sprague-Dawley rats. ZnO(AE100[+]) NPs were administered to rats of each sex by gavage at 0, 500, 1,000, and 2,000 mg/kg/day for 14 days. During the study period, clinical signs, mortality, body weight, food consumption, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. Increased mortality and clinical signs, decreased body weight, feed consumption, hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet (PT), and lymphocyte (LYM) and increased white blood cells (WBCs), neutrophils (NEUs), alkaline phosphatase (ALP), and histopathological alterations in the spleen, stomach, and pancreas were observed at 2,000 mg/kg/day. Increased clinical signs, decreased body weight, feed consumption, HB, HCT, MCV, MCH, MCHC, and LYM and increased WBCs, NEUs, ALP, and histopathological alterations in the spleen, stomach, and pancreas were seen at 1,000 mg/kg/day. Increased clinical signs, decreased MCV and MCH and increased histopathological alterations in the stomach and pancreas were found at 500 mg/kg/day. These results suggest that the target organs were the spleen, stomach, and pancreas in rats. The no-observed-adverse-effect level was <500 mg/kg for both sexes.

Detection of Helicobacter pylori in Gastric Aspirates Using a Monoclonal Antibody-Based Test

BACKGROUND/AIMS: The objective of this study was to evaluate a monoclonal antibody-based test to detect Helicobacter pylori-specific antigen in gastric aspirates from humans. METHODS: Sixty-one volunteers were enrolled in the study. All of the subjects underwent a 13C-urea breath test (UBT) before esophagogastroduodenoscopy. Gastric aspirates were analyzed for pH and ammonia and used for polymerase chain reaction (PCR), culture, and monoclonal antibody-based detection of H. pylori. Multiple biopsies of the gastric antrum and body were obtained for a rapid urease test (RUT) and histological evaluation. RESULTS: Thirty-six subjects were H. pylori-positive and 25 were H. pylori-negative according to the UBT results. Compared with the H. pylori-negative subjects, H. pylori-positive subjects had a higher pH (4.77+/-1.77 vs 3.49+/-1.30, p<0.05) and ammonia level (1,130.9+/-767.4 vs 184.2+/-126.3, p<0.0001). The sensitivities and specificities of the PCR test, RUT, culture test, and monoclonal antibody-based test were 100% and 72%, 89% and 100%, 47% and 100%, and 78% and 100%, respectively. CONCLUSIONS: The monoclonal antibody-based test for diagnosing H. pylori infection in gastric aspirates has increased sensitivity compared with the culture test and specificity as high as that of the RUT. The test may be useful as an additive test for examining gastric aspirates.

A Case of a Pancreaticogastric Fistula Following Acute Pancreatitis / 대한소화기내시경학회지

A pancreatic fistula (PF) is an abnormal connection between the pancreas and adjacent or distant organs, structures, or spaces resulting from leakage of pancreatic secretions from disrupted pancreatic ducts. A PF is a rare complication that occurs during a acute and chronic pancreatitis or after traumatic or surgical disruption of the pancreatic duct. PFs are frequently classified as internal or external depending upon whether they communicate with an internal organ or the skin. Pancreatico- colonic fistulas are the most common, whereas pancreatico-gastric fistulas are the rarest. We report a rare case of a pancreatico-gastric fistula complicated by acute pancreatitis.

Culture and Polymerase Chain Reaction of Helicobacter pylori from Rectal and Terminal Ileal Fluid after Polyethylene Glycol (Colyte(R)) Ingestion in Healthy Adults with Positive Urea Breath Test / 대한소화기학회지

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) transmission route is not yet clearly understood. Isolating H. pylori from stool, saliva, and vomitus is very difficult. However, H. pylori could be cultured from feces in the setting of rapid gastrointestinal tract transit. The aim of this study was to isolate H. pylori by culture and PCR in the rectum and terminal ileum during colonoscopy. METHODS: Twenty subjects with positive UBT (urea breath test) were included. We performed polymerase chain reaction (PCR) test and culture of H. pylori with the rectal fluid and terminal ileal fluid during colonoscopy. RESULTS: H. pylori was cultured with rectal fluid from 9 (45.0%) of 20 subjects and with ileal fluid from 11 (55.0%) of 20 subjects. H. pylori was a little more frequently cultured from the terminal ileal fluid than the rectal fluid without statistical significance (p>0.05). PCR test detected flaA (16/20, 80.0% and 17/20, 85.0%), 16S rRNA gene (16/20, 80.0% and 17/20, 85.0%), cagA (10/20, 50.0% and 12/20, 60.0%), and ureC (9/20, 45% and 11/20, 54.5%) from the rectal fluid and the terminal ileal fluid, respectively. The specificity and sensitivity of ureC were 100%. CONCLUSIONS: H. pylori could be cultured from the rectal fluid and terminal ileal fluid in the setting of rapid gastrointestinal tract transit. These results suggest of fecal-oral transmission of H. pylori.

A case of autoimmune hepatitis accompanied by systemic lupus erythematosus / 대한내과학회지

Autoimmune hepatitis accompanied by systemic erythematosus lupus is rare. Usually, lupus-related advanced liver involvement is indistinguishable from autoimmune hepatitis accompanied by lupus, as they share common clinical, biochemical, serological, and histological manifestations. However, each disease has its own diagnostic criteria, and they have been defined as two different categories. Therefore, distinguishing between the two diseases is important to determine the correct diagnosis and treatment. A 41-year-old woman was hospitalized with jaundice and a malar rash. The patient met the diagnostic criteria of both systemic erythematosus lupus and autoimmune hepatitis. After corticosteroid treatment, the patient's condition improved. Therefore, we report our experience of a rare case of autoimmune hepatitis accompanied by systemic erythematosus lupus with a review of the literature.

Apoptosis of the GABAergic interneuron in the dorsal horn of the chronic post-ischemic pain model / 대한마취과학회지

BACKGROUND: It is well known that the GABAergic inhibitory interneuronal system plays an important role in modulation of the noxious stimulation transmitted from the primary afferent input. Some studies have revealed the role that the GABA inhibitory interneuronal system plays in the modulation of pain transmission and the changes in the GABAergic interneurons that occur during the neuropathic pain. This study was conducted to evaluate the apoptosis of the GABAergic interneuron, which is assumed to contribute to neuropathic pain. METHODS: Male Sprague-Dawley rats weighing 290-310 g were used to create a CPIP (chronic post-ischemic pain) model, which was made by placing a tourniquet on the left hindpaw of the rats. The tourniquet was maintained for 3 hours, after which it was released to allow reperfusion. Thirty minutes prior to reperfusion, N-acetyl-L-cysteine (NAC group) or normal saline (control group) was injected. After reperfusion, mechanical allodynia and cold allodynia were measured. In addition, the release of cytochrome c into the cytosol was evaluated through western blot or immunohistochemistry of the spinal cord. RESULTS: Mechanical and cold allodynia developed and the number of GABA interneurons was reduced in the control group. Additionally, The cytochrome c from the GABA interneuron was released into the cytosol in the control group, but the amount released was reduced in response to treatment with NAC. CONCLUSIONS: The results of this study showed that the GABA interneuron in the Rexed laminae I, II released cytochrome c into the cytosol in CPIP neuropathic pain model, which is known to lead to apoptosis. However, treatment with N-acetyl-L-cysteine prevented this process.

A case of superior mesenteric artery syndrome with hematemesis / 대한내과학회지

Superior mesenteric artery (SMA) syndrome is a rare disorder, characterized by compression of the third segment of the duodenum by the mesenteric artery at the level of the SMA, resulting in duodenal dilatation. The most characteristic symptoms are postprandial epigastric pain, fullness, voluminous vomiting, and eructation. The diagnosis may be difficult, but can be confirmed by upper gastrointestinal (UGI) contrast studies. We report a case of SMA syndrome in a 66-year-old patient with hematemesis. Endoscopy showed deep circular ulcerations with bleeding in the distal esophagus. Computed tomography (CT) and an UGI contrast series revealed distension of the stomach and duodenum, with a cut-off in the third portion of the duodenum. We treated the patient conservatively, but the patient's symptoms did not improve. Ultimately, the patient underwent successful gastrojejunostomy with a favorable postoperative outcome.

A Case of Macroscopically Unvisualized Mucin-hypersecreting Biliary Papillomatosis Diagnosed by Microscopy / 대한소화기학회지

The mucin-hypersecreting biliary papillomatosis is a premalignant neoplasm characterized by intraductal papillary proliferation involving extensive areas of the intrahepatic and/or extrahepatic bile duct. We report a case of mucin-hypersecreting biliary papillomatosis manifested as obstructive jaundice and diagnosed only by microscopy, with a review of literatures. A 74-year-old female, who had a past history of cholecystectomy about 13 years ago, was admitted to our hospital with jaundice. A CT scan showed marked dilatation of intrahepatic and extrahepatic bile duct without intraductal filling defect or extrabiliary mass. During endoscopic retrograde cholangiopancreatography, mucin extrusion from the duodenal major papilla and dilated common bile duct with amorphous filling defects was noted. Percutaneous transhepatic biliary drainage for cholangioscopy was failed. In the operation field, there was a lot of mucin but was no visible mass at the common bile duct with bare eyes and cholangioscopy. However, papilloma was detected at the random biopsy specimen by microscopy. The patient underwent partial resection of common bile duct and choledocho-jejunal anastomosis.

Dieulafoy's Lesion Coexisting with Early Gastric Cancer / 대한소화기내시경학회지

Dieulafoy's lesion is an uncommon cause of gastrointestinal (GI) bleeding, but can be associated with massive, life-threatening GI bleeding. This lesion is an isolated protruding vessel of the submucosal artery associated with a small mucosal defect and normal surrounding mucosa. Although this lesion can occur throughout the GI tract (esophagus, stomach, duodenum, colon, rectum, etc), it has been rarely reported elsewhere than the stomach. Especially, there have been no reports of Dieulafoy lesion coexistent with early gastric cancer in Korea. We report the successful application of endoscopic hemoclipping for the treatment of a very rare Dieulafoy lesion coexistent with early gastric cancer.

Immunohistochemical comparison of the telomerase expression between low-grade and high-grade gastric dysplasia / 대한내과학회지

BACKGROUND: Telomeres are simple repeats elements located at each end of the chromosomes of eukaryotic cells. The main function of telomeres is to cap the chromosome end and protect it from enzymatic attack. Telomerase that facilitates the synthesis of telomere has been detected in not only cancer, but also in precancerous lesion. In this study, we compared the telomerase expression between low-grade and high-grade gastric dysplasia. METHODS: The telomerase expression of 43 patients with gastric dysplasia (22 low-grade and 21 high-grade) was evaluated by immunohistochemical staining in tissues. RESULTS: The telomerase expression was much higher in the tissues from the patients with high-grade gastric dysplasia than in those tissues of the patients with low-grade gastric dysplasia. CONCLUSIONS: Activation of telomerase may be related with the malignant potentiality in gastric cells. Further studies are needed to define the role of telomerase in gastric tumorigenesis.

Telomerase Expression in Colorectal Tubular Adenoma Determined by Immunohistochemical Staining / 대한소화기학회지

BACKGROUND/AIMS: Telomeres are simple repeat elements located at each chromosome end of eukaryotic cells. The main function of telomeres is to cap the chromosome end and protect it from enzymatic attack. Telomerase that facilitates the synthesis of telomere has been detected in not only cancer but also precancerous lesion. In this study, we compared the telomerase expression between low grade and high grade colorectal tubular adenoma. METHODS: Among thissues from forty eight patients with colorectal tubular adenoma (23 low grade and 25 high grade colorectal dysplasia), telomerase expressions were evaluated by immunohistochemical staining. RESULTS: We classified 48 patients into two groups by the extent of nuclei staining pattern. High telomerase expression was a group which showed staining nucleus pattern above 50% in tubular adenoma. Low telomerase expression was a group which showed staining pattern nucleus below 50%. Twelve in 25 high grade colorectal dysplasia showed high telomerase expression (48%). Only one in 23 low grade colorectal dysplasia showed high telomerase expression (4%). Telomerase expression was much higher in the tissues from the patients with high grade than in those with low grade colorectal dysplasia (p<0.05). CONCLUSIONS: Activation of telomerase may be related to the malignant potential in colorectal epithelial cells. Further studies are needed to define the role of telomerase in colorectal tumorigenesis.

Three Sporadic Cases of Acute Hepatitis E / 대한소화기학회지

Acute hepatitis E is an endemic disease, commonly reported in Indian subcontinent, China, Africa, Central America, and so forth. It is a self-limiting disease like other acute hepatitis except in pregnant patient. Although sporadic hepatitis E is noted all over the world, most of them are associated with travel history to HEV-endemic area. In Korea, Hepatitis E is rarely reported. Moreover, sporadic acute hepatitis E without travel history to HEV-endemic area is very rare. We experienced three sporadic cases of acute hepatitis E, without travel history. All of them presented acute hepatitis symptoms, elevated aminotransferase, and positive IgM HEV Ab. Symptoms and aminotransferase levels were normalized during hospitalization and IgM HEV Ab converted negative after 4-8 months. We report three sporadic cases of onset-acute hepatitis E without travel history to HEV-endemic area.

The Effects of the Lidocaine or Fentanyl Pretreatment on Inhalational Induction with Sevoflurane / 대한마취과학회지

BACKGROUND: Sevoflurane has been widely used for inhalation induction and intubation in children and adults. There are some reports about hemodynamic instability and respiratory effects during inhalation induction. We evaluated the effects of fentanyl, lidocaine, or both on inhalation induction and intubation using sevoflurane without neuromuscular blocking agents. METHODS: Forty healthy adult female patients, 20 to 60 years old, premedicated with midazolam 3 mg were randomly received iv saline (Group A), lidocaine 1 mg/kg (Group B), fentanyl 1microgram/kg (Group C) or both lidocaine 1 mg/kg and fentanyl 1microgram/kg (Group D). Anesthesia was induced with 8% sevoflurane inhalation and intubation was done without muscle relaxant. A blind observer recorded the change of blood pressure, heart rate, BIS score, and the time needed for induction and intubation. RESULTS: The mean times for BIS score below 40 were 87 +/- 34 seconds and there were no significant difference among groups. The mean time for loss of self respiration and intubation in group A were significantly longer than those of other groups. The heart rates during induction and intubation of group A were significantly greater than those of other groups. There was no significant difference in blood pressure and side effects during intubation among groups. CONCLUSIONS: Pre-treatment with fentanyl or lidocaine makes smoother and faster induction and intubation during vital capacity rapid inhalation induction with sevoflurane.

Clinical Outcomes after Discontinuation of Lamivudine in Chronic Hepatitis B Patients with Lamivudine Resistant HBV Mutant / 대한간학회지

BACKGROUND/AIMS: The therapeutic strategies of applying adefovir for treating lamivudine resistant HBV mutants are controversial. Thus, we observed the clinical outcomes after discontinuation of lamivudine to establish the timing to initiate adefovir therapy. METHODS: Fifty chronic hepatitis B (CHB) patients with lamivudine resistant HBV mutants who had received lamivudine for more than 12 months were included in the study. We investigated the clinical outcomes at 6 months after the end of treatment (EOT). We compared the serial clinical outcomes among respective groups based on serum ALT at the EOT and the clinical characteristics of patients with or without acute exacerbation (AE) and the HBeAg loss. We also investigated the predictive parameters of AE and HBeAg loss. RESULTS: Fifteen patients (30%) had experienced AE at 6 months after the EOT. Four patients received antiviral agents because of their hepatic decompensation. Patients with AE had higher serum ALT values and lower HBV DNA titers at EOT compared with those patients without AE. Serum ALT at the EOT was the predictive parameter of AE. Eight patients (21.6%) had newly developed HBeAg loss at 6 months after EOT. The total bilirubin at EOT was the predictive parameter of HBeAg loss. CONCLUSIONS: CHB patients with lamivudine resistant HBV mutants had favorable clinical outcomes at 6 months after EOT. Therefore, we can consider observing the clinical courses after discontinuation of lamivudine and it is not always required to overlap the adefovir for treating lamivudine resistant HBV mutants except for the treatment of patients with a high risk of developing decompensation.