Fibrotic Burden in the Liver Differs Across Metabolic Dysfunction-Associated Fatty Liver Disease Subtypes

Background/Aims@#Metabolic dysfunction-associated fatty liver disease (MAFLD) is categorized into three subtypes: overweight/obese (OW), leanormal weight with metabolic abnormalities, and diabetes mellitus (DM). We investigated whether fibrotic burden in liver differs across subtypes of MAFLD patients. @*Methods@#This cross-sectional multicenter study was done in cohorts of subjects who underwent a comprehensive medical health checkup between January 2014 and December 2020. A total of 42,651 patients with ultrasound-diagnosed fatty liver were included. Patients were classified as no MAFLD, OW-MAFLD, lean-MAFLD, and DM-MAFLD. Advanced liver fibrosis was defined based on the nonalcoholic fatty liver disease fibrosis score (NFS) or fibrosis-4 (FIB-4) index. @*Results@#The mean age of the patients was 50.0 years, and 74.1% were male. The proportion of patients with NFS-defined advanced liver fibrosis was the highest in DM-MAFLD (6.6%), followed by OW-MAFLD (2.0%), lean-MAFLD (1.3%), and no MAFLD (0.2%). The proportion of patients with FIB-4-defined advanced liver fibrosis was the highest in DM-MAFLD (8.6%), followed by lean-MAFLD (3.9%), OW-MAFLD (3.0%), and no MAFLD (2.0%). With the no MAFLD group as reference, the adjusted odds ratios (95% confidence intervals) for NFS-defined advanced liver fibrosis were 4.46 (2.09 to 9.51), 2.81 (1.12 to 6.39), and 9.52 (4.46 to 20.36) in OW-MAFLD, leanMAFLD, and DM-MAFLD, respectively, and the adjusted odds ratios for FIB-4-defined advanced liver fibrosis were 1.03 (0.78 to 1.36), 1.14 (0.82 to 1.57), and 1.97 (1.48 to 2.62) in OW-MAFLD, lean-MAFLD, and DM-MAFLD. @*Conclusions@#Fibrotic burden in the liver differs across MAFLD subtypes. Optimized surveillance strategies and therapeutic options might be needed for different MAFLD subtypes.

Treatment of Autoimmune Hepatitis / 대한소화기학회지

Autoimmune hepatitis (AIH) is a chronic liver disease, characterized by elevated levels of transaminases, immunoglobulin G, and positive autoantibodies. The disease course is dynamic and presents heterogeneous disease manifestations at diagnosis. This review summarizes the issues regarding the treatment and monitoring of AIH in adult patients. Glucocorticoids and azathioprine are the first line of treatment. Alternative first-line treatments include budesonide or mycophenolate mofetil (MMF). Although no randomized controlled trials have been performed, MMF, cyclosporine, tacrolimus, 6-mercaptopurine, 6-thioguanine, allopurinol, sirolimus, everolimus, infliximab, or rituximab have been attempted in patients not responding to or intolerant to first-line treatments. Most patients require life-long special monitoring, with or without maintenance treatment.

Efficacy of Pegylated Interferon Monotherapy versus Sequential Therapy of Entecavir and Pegylated Interferon in Hepatitis B e Antigen-Positive Hepatitis B Patients: A Randomized, Multicenter, Phase IIIb Open-Label Study (POTENT Study) / 中华医学杂志(英文版)

<p><b>Background</b>Until now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.</p><p><b>Methods</b>Between June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.</p><p><b>Results</b>HBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.</p><p><b>Conclusions</b>The current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.</p><p><b>Trial Registration</b>ClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.</p>

Clinical Utility of a New Automated Hepatitis C Virus Core Antigen Assay for Prediction of Treatment Response in Patients with Chronic Hepatitis C

Hepatitis C virus core antigen (HCV Ag) is a recently developed marker of hepatitis C virus (HCV) infection. We investigated the clinical utility of the new HCV Ag assay for prediction of treatment response in HCV infection. We analyzed serum from 92 patients with HCV infection who had been treated with pegylated interferon and ribavirin. HCV Ag levels were determined at baseline in all enrolled patients and at week 4 in 15 patients. Baseline HCV Ag levels showed good correlations with HCV RNA (r = 0.79, P < 0.001). Mean HCV Ag levels at baseline were significantly lower in patients with a sustained virologic response (SVR) than in those with a non SVR (relapse plus non responder) based on HCV RNA analysis (2.8 log10fmol/L vs. 3.27 log10fmol/L, P = 0.023). Monitoring of the viral kinetics by determination of HCV RNA and HCV Ag levels resulted in similarly shaped curves. Patients with undetectable HCV Ag levels at week 4 had a 92.3% probability of achieving SVR based on HCV RNA assay results. The HCV Ag assay may be used as a supplement for predicting treatment response in HCV infection, but not as an alternative to the HCV RNA assay.

A case of levocetirizine-induced liver injury

Levocetirizine is a second-generation nonsedative antihistaminic agent that has been demonstrated to be safe and effective for treating allergic disease. There was only one case report of levocetirizine-induced liver toxicity, but a liver biopsy was not performed. In this article, we present the first case of levocetirizine-induced liver injury with histologic findings. A 48-year-old man was hospitalized with jaundice and generalized pruritus that had developed after 2 months of therapy with levocetirizine for prurigo nodularis. Laboratory findings revealed acute hepatitis with cholestasis. A liver biopsy demonstrated portal inflammation and hepatitis with apoptotic hepatocytes. The patient fully recovered 3 weeks after withdrawing levocetirizine. Although levocetirizine is safe and effective, physicians should be aware of its potential hepatotoxicity.

Page kidney after botulinum toxin injection during chiropractic care / 영남의대학술지

Page kidney refers to the phenomenon of hypertension secondary to long-standing compression of renal parenchyma caused by renal subcapsular collection. The most common cause of renal subcapsular collection is a hematoma which usually occurs after a history of blunt trauma. A 42-year-old female patient who received botulinum toxin injection in her back during chiropractic care was admitted to the emergency room with sudden bilateral flank pain and hypertension. The computed tomography (CT) images demonstrated the presence of bilateral subcapsular renal hematoma. The patient was treated conservatively and recovered well. The follow up CT images showed markedly resolved bilateral hematoma.

Idiopathic hypereosinophilic syndrome presenting with urinary frequency, abdominal pain, and diarrhea

Idiopathic hypereosinophilic syndrome (IHES) is a rare disorder defined by persistent blood eosinophilia, evidence of eosinophil-associated organ dysfunction and absence of secondary causes. Eosinophilic infiltration and its mediator release can cause damage to multiple organs. Although IHES can involve every organ system, bladder involvement is rarely evidenced. We recently reported a case of IHES with both bladder and gastrointestinal tract involvement. A 43-year-old woman visited Hallym University Sacred Heart Hospital complaining of urinary frequency, abdominal pain, and diarrhea for several months. Abdominal pelvic computed tomographic scan showed diffuse wall thickenings in her bladder and colon with small pelvic ascites. Laboratory investigation showed a marked peripheral eosinophilia and tissue biopsies confirmed eosinophilic infiltration in the bladder wall, esophagus, and duodenum. The patient was treated with prednisolone and her eosinophilia and symptoms have gradually improved.

ERRATUM: Affiliation Correction. Evaluation of the association of vegetation of allergenic plants and pollinosis with meteorological changes

According to the author's request, in this paper, the eighth author's (Bong-Seong Kim) affiliation should be corrected.

Usefulness of the Controlled Attenuation Parameter for Detecting Liver Steatosis in Health Checkup Examinees

BACKGROUND/AIMS: The controlled attenuation parameter (CAP) implemented in FibroScan(R) is reported to be a non-invasive means of detecting steatosis (>10% steatosis). We aimed to evaluate the usefulness of CAP in detecting steatosis among health checkup examinees and to assess its correlation with ultrasonography (US). METHODS: Consecutive CAP results were retrospectively collected. A total of 280 subjects were included. RESULTS: Fatty liver was detected in 119 subjects (42.5%) by US, whereas it was detected in 160 subjects (57.1%) by the CAP. The numbers of subjects with S0:S1:S2:S3 steatosis according to the CAP value were 120:59:58:43, respectively. The mean CAP values were 203.34+/-28.39 dB/m for S0, 248.83+/-6.14 dB/m for S1, 274.33+/-8.53 dB/m for S2, and 322.35+/-22.20 dB/m for S3. CAP values were correlated with body weight (r=0.404, p<0.001), body mass index (r=0.445, p<0.001), and the fatty liver grade by US (r=0.472, p<0.001). Among the 161 subjects with normal US findings, steatosis was detected in 65 subjects (40.4%) using the CAP. CONCLUSIONS: The CAP seems to be useful for detecting very low-grade hepatic steatosis in health checkup examinees. Its role in predicting subjects with a risk of metabolic derangement needs to be evaluated.

Usefulness of the Controlled Attenuation Parameter for Detecting Liver Steatosis in Health Checkup Examinees

BACKGROUND/AIMS: The controlled attenuation parameter (CAP) implemented in FibroScan(R) is reported to be a non-invasive means of detecting steatosis (>10% steatosis). We aimed to evaluate the usefulness of CAP in detecting steatosis among health checkup examinees and to assess its correlation with ultrasonography (US). METHODS: Consecutive CAP results were retrospectively collected. A total of 280 subjects were included. RESULTS: Fatty liver was detected in 119 subjects (42.5%) by US, whereas it was detected in 160 subjects (57.1%) by the CAP. The numbers of subjects with S0:S1:S2:S3 steatosis according to the CAP value were 120:59:58:43, respectively. The mean CAP values were 203.34+/-28.39 dB/m for S0, 248.83+/-6.14 dB/m for S1, 274.33+/-8.53 dB/m for S2, and 322.35+/-22.20 dB/m for S3. CAP values were correlated with body weight (r=0.404, p<0.001), body mass index (r=0.445, p<0.001), and the fatty liver grade by US (r=0.472, p<0.001). Among the 161 subjects with normal US findings, steatosis was detected in 65 subjects (40.4%) using the CAP. CONCLUSIONS: The CAP seems to be useful for detecting very low-grade hepatic steatosis in health checkup examinees. Its role in predicting subjects with a risk of metabolic derangement needs to be evaluated.

Awareness of chronic obstructive pulmonary disease in current smokers: a nationwide survey

BACKGROUND/AIMS: Cigarette smoking is the most common risk factor for chronic obstructive pulmonary disease (COPD). However, few studies of the attitudes toward COPD of smokers, the group at risk of developing this condition, have been conducted. The purpose of this study was to explore the awareness of and attitudes toward COPD of current smokers. METHODS: The sample consisted of 502 individuals aged 45 and older from throughout Korea who smoked at least 10 packs of cigarettes per year. Telephone interviews using a structured questionnaire were conducted with respondents. RESULTS: First, we evaluated the health status of subjects, finding that 45.4% considered themselves to be in good health. We also asked about COPD-related symptoms, and 60.6% of subjects reported such symptoms. However, only 1.2% of subjects had been diagnosed with or treated for COPD, only 0.4% spontaneously mentioned COPD as a respiratory disease, and only 26.5% recognized COPD as a respiratory disease after seeing a list of such diseases. Television ranked as the top source of information about COPD. The willingness of 45.0% of subjects to stop smoking increased after being informed about COPD. CONCLUSIONS: Despite having COPD-related symptoms, most smokers did not know that COPD is a respiratory disease. The attitudes of smokers toward COPD and smoking cessation varied according to socioeconomic status. In summary, a continuous effort to increase the awareness of COPD among smokers is needed. Additionally, strategies tailored according to different socioeconomic groups will also be necessary.

High-Dose Vitamin C Promotes Regression of Multiple Pulmonary Metastases Originating from Hepatocellular Carcinoma

We report a case of regression of multiple pulmonary metastases, which originated from hepatocellular carcinoma after treatment with intravenous administration of high-dose vitamin C. A 74-year-old woman presented to the clinic for her cancer-related symptoms such as general weakness and anorexia. After undergoing initial transarterial chemoembolization (TACE), local recurrence with multiple pulmonary metastases was found. She refused further conventional therapy, including sorafenib tosylate (Nexavar). She did receive high doses of vitamin C (70 g), which were administered into a peripheral vein twice a week for 10 months, and multiple pulmonary metastases were observed to have completely regressed. She then underwent subsequent TACE, resulting in remission of her primary hepatocellular carcinoma.

Lipiodol-induced pneumonitis following transarterial chemoembolization for ruptured hepatocellular carcinoma / 영남의대학술지

Transarterial chemoembolization (TACE) is a widely accepted nonsurgical modality used for the treatment of multinodular hepatocellular carcinoma (HCC). The careful selection of the candidate is important due to the risk of developing various side effects. Fever, nausea, abdominal pain, and liver enzyme elevation are commonly known side effects of TACE. Hepatic failure, ischemic cholecystitis, and cerebral embolism are also reported, although their incidence might be low. Pulmonary complication after TACE is rare, and the reported cases of lipiodol pneumonitis are even rarer. A 53-year-old man was treated with TACE for ruptured HCC associated with hepatitis B virus infection. On day 19 after the procedure, the patient complained of dyspnea and dry cough. Chest computed tomography showed diffuse ground glass opacities in the wholelung fields, suggesting lipiodol-induced pneumonitis. After 2 weeks of conservative management, the clinical symptoms and radiologic abnormalities improved. Reported herein is the aforementioned case of lipiodol-induced pnemonitis after TACE, with literature review.

Concurrent Chemoradiotherapy Shows Long-Term Survival after Conversion from Locally Advanced to Resectable Hepatocellular Carcinoma

PURPOSE: For locally unresectable hepatocellular carcinoma (HCC) patients, concurrent chemoradiotherapy (CCRT) has been applied as a loco-regional treatment. After shrinkage of tumors in selected patients, surgical resection is performed. The aim of this study was to evaluate prognostic factors and long-term survivors in such patients. MATERIALS AND METHODS: From January 2000 to January 2009, 264 patients with HCC were treated with CCRT (45 Gy with fractional dose of 1.8 Gy), and intra-arterial chemotherapy was administered during radiotherapy. Eighteen of these patients (6.8%) underwent hepatic resection after showing a response to CCRT. Cases were considered resectable when tumor-free margins and sufficient remnant volumes were obtained without extrahepatic metastasis. Prior to operation, there were six patients with complete remission, 11 with partial remission, and six with stable disease according to modified Response Evaluation Criteria in Solid Tumors. RESULTS: In pathologic review, four patients (22.2%) showed total necrosis and seven patients (38.9%) showed 70-99% necrosis. A high level of necrosis (> or =80%) was correlated with low risk for extrahepatic metastasis and long-term survival. In univariate analyses, vessel invasion and capsular infiltration were significantly correlated with disease free survival (DFS) (p=0.017 and 0.013, respectively), and vessel invasion was significantly correlated with overall survival (OS) (p=0.013). In multivariate analyses, capsule infiltration was a significant factor for DFS (p=0.016) and vessel invasion was significant for OS (p=0.015). CONCLUSION: CCRT showed favorable responses and locally advanced HCC converted into resectable tumor after CCRT in selected patients. Long-term survivors showed the pathological features of near total necrosis, as well as negative capsule and vessel invasion.

Evaluation of the association of vegetation of allergenic plants and pollinosis with meteorological changes

PURPOSE: There are a number of reports suggesting that widespread propagation of weeds and high concentration of weed pollen have been contributed to climate change. We investigated the interrelationship between allergenic pollen concentration, allergic symptom and meteorological factor. METHODS: We collected data of pollen concentration and meteorological factors in 7 stations nationwide during between 1998 and 2012. We recruited total 297 allergic patients sensitized to weed pollens from each station, conducted a survey about allergic symptom, and calculated symptom index. We surveyed the vegetation area of ragweed and Japanese hop. Based on these data, we performed the long-term trend analysis (X11-ARIMA, autoregressive integrated moving average) on regional pollen concentration, and correlation analysis to investigate the interrelation between weed pollen concentration, allery symptom index and meteorological factor. We have also done regression analysis on vegetation area and maximal pollen concentration. RESULTS: Long-term trend analysis showed the increasing trend of pllen concentration in Seoul. Weed pollen concentration, allergy symptom index and each meteorological factor were not correlated significantly. Regression analysis revealed that increase of weed vegetation area results in increase of weed pollen concentration. Through this regression equation, we estimated the vegetation area that can product pollen concentration triggering allergenic risk. CONCLUSION: Meteorological factors, pollen concentration and allergic symptoms should be consistently assessed and the relationship between each factor should be analyzed, considering climate change. It is necessary to verify the equation for pollen estimation by vegetation area and set up a policy for vegetation control focused on the reduction of allergenic pollen.

Omega-3 polyunsaturated fatty acid and ursodeoxycholic acid have an additive effect in attenuating diet-induced nonalcoholic steatohepatitis in mice

Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen alpha1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor alpha showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH.

Assessment of Hepatic Fibrosis Regression by Transient Elastography in Patients with Chronic Hepatitis B Treated with Oral Antiviral Agents

Transient elastography (TE) has been used as a non-invasive method for liver stiffness measurement (LSM) in patients with chronic liver disease. This study was performed to assess the change of LSM by TE and to assess its clinical usefulness during long-term oral antiviral therapy in patients with chronic hepatitis B (CHB). We retrospectively reviewed 83 CHB patients. The mean interval between two LSM was 411.5 +/- 149.5 days. Initial and follow-up LSM was 16.15 +/- 12.41 kPa and 11.26 +/- 7.36 kPa, respectively (P or = 14.1 kPa (cirrhosis) at 1st LSM, 12 (40%) proved to no longer have cirrhosis (> or = 1 decrease in fibrosis stage) at 2nd LSM. LSM significantly decreased in both baseline high (> upper limit of normal [ULN] x 2) and low (< or = ULN x 2) alanine aminotransferase groups during antiviral therapy (P < 0.001; P = 0.001, respectively). Long-term oral antiviral therapy resulted in the improvement of liver stiffness in a substantial portion of patients with CHB. TE may be used a useful clinical tool to assess disease progression in CHB patients.

A Case of Intraductal Papillary Mucinous Neoplasm of the Pancreas with Pancreatoduodenal Fistula Diagnosed by Pancreatoscopy Using a Standard Upper Endoscope / 대한췌담도학회지

Intraductal papillary mucinous neoplasm of the pancreas (IPMN) is characterized by the production of mucin and marked dilatation of pancreatic duct. There are only several cases reports about fistula formation with adjacent organs in IPMN. A 61-year-old man was admitted due to jaundice and weight loss. CT scans showed that multiloculated cystic mass had replaced the body and tail of the pancreas. Interestingly, a fistula was found between cystic mass and duodenal bulb. With a diagnosis of malignant IPMN and pancreatoduodenal fistula, endoscopic forcep-biopsy was performed at the orifice of the fistula and pancreatic duct, through the fistula, under a fluoroscopic guidance. Pathologic examination showed only inflammatory cells. Direct peroral pancreatoscopy was performed through the pancreatoduodenal fistula using a standard upper endoscope with saline irrigation. Endoscopic forcep-biopsy was performed on the papillary tumor. Pathologic examination revealed intestinal type IPMN and radical total pancreatectomy was performed. Pathologic examination of the surgical specimen showed tubular adenocarcinoma arising from 15 cm sized intestinal type IPMN.

A Case of Hyponatraemic Seizure Following Terlipressin Therapy for a Variceal Hemorrhage in a Patient with Liver Cirrhosis / 대한내과학회지

Terlipressin has splanchnic vasoconstrictive effects, and is generally used for the management of gastroesophageal variceal bleeding secondary to liver cirrhosis. Terlipressin is a synthetic arginine vasopressin (AVP) analog containing a nonapeptide sequence. Terlipressin has increased selectivity for the V1 receptor, compared with AVP; hence, it is considered to be a safe vasoconstrictor. However, side effects such as hyponatremia and seizure, although very rare, have been reported. Hyponatremia related to terlipressin may be caused by the syndrome of inappropriate antidiuresis (SIAD), which is a disorder of sodium and water balance characterized by hypotonic hyponatremia without elevation of the antidiuretic hormone level. Here, we report a case of hyponatremic seizure induced by an infusion of terlipressin in a 52-year-old female who had isolated gastric variceal bleeding secondary to alcoholic liver cirrhosis.

Quasispecies and Pre-Existing Drug-Resistant Mutations of Hepatitis B Virus in Patients with Chronic Hepatitis B

BACKGROUND/AIMS: To investigate pre-existing hepatitis B virus (HBV) quasispecies and the genotypic evolution of several variants. METHODS: From six patients with lamivudine (LAM) failure, serum samples at pretreatment, 6 months of LAM therapy, and virologic breakthrough were obtained. One hundred clones with HBV inserts in each patient were sequenced at each time point. Pretreatment serum samples were also analyzed from six patients who achieved good responses to LAM therapy. RESULTS: Among the six patients with LAM failure, the analysis of 100 clones from patient 1 revealed the substitutions L180M in 1% of clones and V173L in 2% of clones. Patient 2 had substitutions of L80V, W153Q, and L180M. In patient 3, mutations conferring resistance to adefovir at V84I (5%), I169L (1%), and N236H (7%) and entecavir at S202G (2%) were detected. Patient 4 had mutations at T128N (1%), I169L (1%), V173L (2%), A181V (1%), and Q215H (1%). In patient 5, M204V/I was detected in 1% and 2% of clones, respectively. L80I and V173L were also identified in patient 6. In the six patients who responded to LAM, the degree of overall quasispecies was less than those with LAM failure. CONCLUSIONS: Various HBV quasispecies associated with drug resistance existed before treatment, and the quasispecies dynamically changed through LAM therapy.