[Treatment of hepatolithiasis by multiple operative methods with hepatico-subcutaneous stoma].

OBJECTIVE: To evaluate the mid-term and long-term outcomes of patients with hepatolithiasis after receiving multiple operative methods with hepatico-subcutaneous stoma. METHODS: A retrospective analysis was performed based on 156 patients with hepatolithiasis who underwent multiple operative methods with hepatico-subcutaneous stoma from Apr. 1993 to Mar. 2010 in Peking University Third Hospital. Thirty-seven of them had stone in the left lobe (23.7%), 22 in the right lobe (14.1%), and 97 in bilateral lobes (62.2%). Ninety-nine patients had hepatolithiasis combined with biliary stricture (63.5%). RESULTS: All of the patients underwent successful operations and recovered well with no death in perioperative period. The rate of operative complications was 35.9%. A total of 146 patients were followed up with a median time of 7 years. The rate of patients with cholangitis, recurrent stone, and biliary stricture newly detected was 13.0% (19/146), 21.9% (32/146) and 8.2% (12/146), respectively. Draining inflammatory bile and taking out recurrent stones by hepatico-subcutaneous stoma were carried out in 35 patients (24.0%). CONCLUSION: Treatment of hepatolithiasis with biliary stricture and its recurrence by multiple operative methods with hepatico-subcutaneous stoma is safe, effective, minimally invasive, and easy to perform.

The Effects of Exposure to Flupyradifurone on Survival, Development, and Foraging Activity of Honey Bees (Apis mellifera L.) under Field Conditions.

Flupyradifurone (FPF) is a novel systemic nAChR agonist that interferes with signal transduction in the central nervous system of sucking pests. Despite claims that FPF is potentially "bee-safe" by risk assessments, laboratory data have suggested that FPF has multiple sub-lethal effects on individual honey bees. Our study aimed to expand the studies to the effects of field-realistic concentration of FPF. We found a statistically significant decrease in the survival rate of honey bees exposed to FPF, whereas there were no significantly negative effects on larvae development durations nor foraging activity. In addition, we found that the exposed foragers showed significantly higher expression of ApidNT, CYP9Q2, CYP9Q3, and AmInR-2 compared to the CK group (control group), but no alteration in the gene expression was observed in larvae. The exposed newly emerged bees showed significantly higher expression of Defensin and ApidNT. These results indicate that the chronic exposure to the field-realistic concentration of FPF has negligible effects, but more important synergistic and behavioral effects that can affect colony fitness should be explored in the future, considering the wide use of FPF on crops pollinated and visited by honey bees.

Effects of a commercially formulated glyphosate solutions at recommended concentrations on honeybee (Apis mellifera L.) behaviours.

Glyphosate, the active ingredient of the most widely used commercial herbicide formulation, is extensively used and produced in China. Previous studies have reported sublethal effects of glyphosate on honeybees. However, the effects of commercially formulated glyphosate (CFG) at the recommended concentration (RC) on the chronic toxicity of honeybees, especially on their behaviours, remain unknown. In this study, a series of behavioural experiments were conducted to investigate the effects of CFG on honeybees. The results showed that there was a significant decline in water responsiveness at 1/2 × , 1 × and 2 × the RC after 3 h of exposure to CFG for 11 days. The CFG significantly reduced sucrose responsiveness at 1/2 × and 1 × the RC. In addition, CFG significantly affected olfactory learning ability at 1/2 × , 1 × , and 2 × the RC and negatively affected memory ability at 1/2 × and 1 × the RC. The climbing ability of honeybees also significantly decreased at 1/2 × , 1 × and 2 × the RC. Our findings indicated that, after they were chronically exposed to CFG at the RC, honeybees exhibited behavioural changes. These results provide a theoretical basis for regulating field applications of CFG, which is necessary for establishing an early warning and notification system and for protecting honeybees.

[Clinical effects of subcutaneous tunnel hepatocholangioplasty on the treatment of hepatolithiasis].

OBJECTIVE: To evaluate the therapeutic effect of subcutaneous tunnel hepaticoplasty on the treatment of hepatolithiasis. METHODS: The early complications and clinical effects of 99 hepatolithiasis cases who underwent subcutaneous tunnel hepaticoplasty from January 1993 to August 2006 were analyzed retrospectively. The stones of 28 (28.3%) patients were in the left lobe, 24.2% (24/99) in the right, and 47.5% (47/99) in bilateral lobe. Sixty-six patients (66.7%) had both stones and biliary strictures. During the procedure, a portion of the liver habouring stone was resected if necessary. The hepatic duct and strictures were opened, the stones were removed, and the porta hepatis was repaired by one end of a segment of jejunum. The other end of the jejunum was set subcutaneously. The gall bladders of 27 patients (27.3%) were used as subcutaneous tunnel instead. RESULTS: Ninety-five out of ninety-nine cases were followed up with an average of 4.2 years (1 month to 13.5 years). The rates of residual stone, recurrent stone and cholangitis were 23.2% (23/99), 20.0% (19/95) and 14.7% (14/95) respectively. Postoperatively, 34 cases who had residual or recurrent stones were underwent lithotomy by choledochoscope through the subcutaneous blind loop and the achievement ratio was 91.2% (31/34). CONCLUSIONS: Subcutaneous tunnel hepatocholangioplasty decreases the relapsing cholangitis effectively, and makes an easy way to take out residual or recurrent stones.

Sublethal effects of imidacloprid on targeting muscle and ribosomal protein related genes in the honey bee Apis mellifera L.

A sublethal concentration of imidacloprid can cause chronic toxicity in bees and can impact the behavior of honey bees. The nectar- and water-collecting, and climbing abilities of bees are crucial to the survival of the bees and the execution of responsibilities in bee colonies. Besides behavioral impact, data on the molecular mechanisms underlying the toxicity of imidacloprid, especially by the way of RNA-seq at the transcriptomic level, are limited. We treated Apis mellifera L. with sublethal concentrations of imidacloprid (0.1, 1 and 10 ppb) and determined the effect on behaviors and the transcriptomic changes. The sublethal concentrations of imidacloprid had a limited impact on the survival and syrup consumption of bees, but caused a significant increase in water consumption. Moreover, the climbing ability was significantly impaired by 10 ppb imidacloprid at 8 d. In the RNA-seq analysis, gene ontology (GO) term enrichment indicated a significant down-regulation of muscle-related genes, which might contribute to the impairment in climbing ability of bees. The enriched GO terms were attributed to the up-regulated ribosomal protein genes. Considering the ribosomal and extra-ribosomal functions of the ribosomal proteins, we hypothesized that imidacloprid also causes cell dysfunction. Our findings further enhance the understanding of imidacloprid sublethal toxicity.

Clinical application of plasma shock wave lithotripsy in treating impacted stones in the bile duct system.

AIM: To verify the safety and efficacy of plasma shock wave lithotripsy (PSWL) in fragmenting impacted stones in the bile duct system. METHODS: From September 1988 to April 2005, 67 patients (26 men and 41 women) with impacted stones underwent various biliary operations with tube (or T-tube) drainage. Remnant and impacted stones in the bile duct system found by cholangiography after the operation were fragmented by PSWL and choledochofiberscopy. A total of 201 impacted stones were fragmented by PSWL setting the voltage at 2.5-3.5 kV, and the energy output at 2-3 J for each pulse of PSWL. Then the fragmented stones were extracted by choledochofiberscopy. The safety and efficacy of PSWL were observed during and after the procedure. RESULTS: One hundred and ninety-nine of 201 impacted stones (99.0%) in the bile duct system were successfully fragmented using PSWL and extracted by choledochofiberscopy. The stone clearance rate for patients was 97% (65/67). Ten patients felt mild pain in the right upper quadrant of the abdomen, and could tolerate it well. Eleven patients had a small amount of bleeding from the mucosa of the bile duct. The bleeding was transient and stopped spontaneously within 2 min of normal saline irrigation. There were no significant complications during and after the procedure. CONCLUSION: PSWL is a safe and effective method for fragmenting impacted stones in the bile duct system.

[Prognostic analysis of T1 and T2 stage gallbladder cancer with invasion within the gallbladder wall].

OBJECTIVE: To explore the impact of different treatment procedure on the prognosis of T1 and T2 stage gallbladder cancer with the invasion within the gallbladder wall. METHODS: A retrospective analysis was conducted on 45 patients with pathologic stage T1 and T2 gallbladder cancer who had undergone surgical resection from 1990 and 2005. RESULTS: Depth of invasion (T), radical cholecystectomy and postoperative adjuvant chemotherapy were independent prognostic factors on Cox multivariate analysis. The 5-year survival rates of patients with T1a, T1b and T2 stage gallbladder cancer who underwent simple cholecystectomy without postoperative adjuvant chemotherapy were 100%, 67% and 0, respectively. The survival rate in T2 was significantly lower than those in T1a and T1b. Without postoperative adjuvant chemotherapy, the 5-year survival rates of patients with T2 stage gallbladder cancer who underwent simple cholecystectomy and radical cholecystectomy were 0 and 63%, respectively. There was significant difference between the survival time of T2 patients who had undergone simple cholecystectomy with and without postoperative adjuvant chemotherapy. CONCLUSIONS: The prognosis of patients with T1 stage gallbladder cancer is much better than that of T2 stage. The 5-year survival rates of patients with T1a and T1b stage gallbladder cancer who received simple cholecystectomy are relatively good. Radical cholecystectomy and postoperative adjuvant chemotherapy can improve the prognosis of patients with T2 gallbladder cancer.

Bt Cry1Ie Toxin Does Not Impact the Survival and Pollen Consumption of Chinese Honey Bees, Apis cerana cerana (Hymenoptera, Apidae).

The cry1Ie gene may be a good candidate for the development of Bt maize because over-expression of Cry1Ie is highly toxic to Lepidopteran pests such as Heliothis armigera Hübner and Ostrinia furnacalis Guenée. The Bt cry1Ie gene also has no cross resistance with other insecticidal proteins such as Cry1Ab, Cry1Ac, Cry1Ah, or Cry1F. Chinese honey bees (Apis cerana cerana) are potentially exposed to insect-resistant genetically modified (IRGM) crops expressing Cry1Ie toxin via the collection of IRGM crop pollen. In this study, we tested whether Chinese honey bee workers are negatively affected by sugar syrup containing 20, 200, or 20,000 ng/ml Cry1Ie toxin and 48 ng/ml imidacloprid under controlled laboratory conditions. Our results demonstrated that the Cry1Ie toxin does not adversely impact survival and pollen consumption of Chinese honey bees. However, imidacloprid decreases Chinese honey bee survival and the total pollen consumption on the 5th, 6th, and 18th d of exposure. The described bioassay is suitable to assess the effects of GM expressed toxins against honey bee.

[FTIR spectroscopic explorations of clinical practice of breast cancer].

The authors detected ten normal breast tissue samples and eight breast cancer samples by FTIR spectroscopy with an ATR probe. Nineteen variables of thirteen bands in the spectra were compared using standard statistic methods. The results demonstrated that bands of protein, lipid, carbohydrate, and nucleic acid from cancerous samples were significantly different from those from normal ones: (1) The relative intensity of N-H band increased and amide I band shifted to lower wave number significantly; (2) Symmetric and antisymmetric vibrations of -CH2 group, C=O vibration, and relative intensity of (-CH2)n decreased; (3) The intensity of 1160 cm(-1) band was much weaker than that of 1120 cm(-1); (4) The band of P=O or P-O-C shifted toward lower wave number. The authors believe that FTIR spectroscopy has a promising future in breast cancer diagnosis.

[Nodular goiter surface detection by FTIR spectroscopy].

A novel non-invasive diagnosis method of nodular goiter is proposed in the present study by recording FTIR spectra on the skin overlying thyroids using fiber optical technique and attenuated total reflection probe. FTIR spectra from 20 nodular goiters and 34 normal controls were collected. Twenty seven spectral variables of 13 bands including peak position and relative intensities were extracted from the FTIR spectra so that statistic work could be conducted using SPSS. The results demonstrate that peak positions of 2 925 and 1 250 cm(-1) both shifted toward lower wave number (P < 0.05) in the FTIR spectra of nodular goiter. The relative intensity ratios of H1 740/H1 460, H1 160/H1 460, and H1 160/H1 120 decreased significantly in FTIR spectra of nodular goiter (P < 0.05). Inversely, H1 080/H1 460 increased significantly (P < 0.05) in nodular goiter. The above statistic differences suggest that nodular goiter may produce some characteristic chemical substance which can diffuse onto the surface of skin and therefore be detectable using FTIR spectroscopy with fiber optic techniques. These differences are the basis of diagnosing nodular goiter by FTIR surface detection.

Oddi sphincter preserved cholangioplasty with hepatico-subcutaneous stoma for hepatolithiasis.

AIM: To evaluate the long-term outcomes of Oddi sphincter preserved cholangioplasty with hepatico-subcutaneous stoma (OSPCHS) and risk factors for recurrence in hepatolithiasis. METHODS: From March 1993 to December 2012, 202 consecutive patients with hepatolithiasis underwent OSPCHS at our department. The Oddi sphincter preserved procedure consisted of common hepatic duct exploration, stone extraction, hilar bile duct plasty, establishment of subcutaneous stoma to the bile duct. Patients with recurrent stones can undergo stone extraction and/or biliary drainage via the subcutaneous stoma which can be incised under local anesthesia. The long-term results were reviewed. Cox regression model was employed to analyze the risk factors for stone recurrence. RESULTS: Ninety-seven (48.0%) OSPCHS patients underwent hepatic resection concomitantly. The rate of surgical complications was 10.4%. There was no perioperative death. The immediate stone clearance rate was 72.8%. Postoperative cholangioscopic lithotomy raised the clearance rate to 97.0%. With a median follow-up period of 78.5 mo (range: 2-233 mo), 24.8% of patients had recurrent stones, 2.5% had late development of cholangiocarcinoma, and the mortality rate was 5.4%. Removal of recurrent stones and/or drainage of inflammatory bile via subcutaneous stoma were conducted in 44 (21.8%) patients. The clearance rate of recurrent stones was 84.0% after subsequent choledochoscopic lithotripsy via subcutaneous stoma. Cox regression analysis showed that residual stone was an independent prognostic factor for stone recurrence. CONCLUSION: In selected patients with hepatolithiasis, OSPCHS achieves excellent long-term outcomes, and residual stone is an independent prognostic factor for stone recurrence.

Role of activation-induced cell death in pathogenesis of patients with chronic hepatitis B.

AIM: To study and compare the difference of activation-induced cell death (AICD) in peripheral blood T-lymphocytes(PBL-Ts) from patients with chronic hepatitis B (CHB) and the normal people in vitro, and to explore the role of AICD in chronic hepatitis B virus (HBV) infection and the pathogenesis of CHB. METHODS: Twenty-five patients and fourteen healthy people were selected for isolation of PBL-Ts. During cultivation, anti-CD3 mAb, PMA and ionomycin were used for AICD of PBL-Ts. AICD ratio of PBL-Ts was detected with TdT-mediated dUTP nick end labeling and assessed by flow cytometry. RESULTS: When induced with anti-CD3, PMA and ionomycin in vitro, AICD ratio of PBL-Ts from CHB patients was significantly higher than that from healthy control (17.24+/-1.21 vs. 6.63+/-1.00, P<0.01) and that from CHB patients without induction (17.24+/-1.21 vs. 9.88+/-1.36, P<0.01). There was a similar AICD ratio of PBL-Ts between induction group and without induction group, but no difference was found before and after induction in healthy control. The density of INF-gamma in culture media of induction groups of CHB was lower than that of other groups (P<0.01). There was no difference between these groups in density of IL-10 (P>0.05). CONCLUSION: When induced during cultivation in vitro, PBL-Ts from CHB have AICD very commonly. This phenomenon has a potentially important relation with pathogenesis of CHB and chronicity of HBV infection.

Laparoscopic hepaticoplasty using gallbladder as a subcutaneous tunnel for hepatolithiasis.

AIM: To investigate the feasibility, efficacy and safety of laparoscopic hepaticoplasty using gallbladder as subcutaneous tunnel and sphincter-of-Oddi preservation for hepatolithiasis. METHODS: From January 2010 to July 2013, six patients with hepatolithiasis were treated at our institution. All the patients underwent laparoscopic surgery. The procedures included common hepatic duct exploration, stone clearance by fiberoptic choledochoscopy, hilar bile duct hepaticoplasty with preservation of the sphincter of Oddi, anastomosis between the hilar bile duct and neck of the gallbladder, and establishment of a subcutaneous tunnel with the gallbladder. Two patients underwent left lateral hepatectomy simultaneously. Clinical data including operation time, intraoperative blood loss, operative morbidity, hospital mortality, stone clearance, and recurrence rate were analyzed. RESULTS: All patients successfully completed laparoscopic surgery. The mean length of hospital stay was 4.5 ± 0.9 d (range: 3-6 d). The mean blood loss of the hepatectomy was 450 mL (range: 200-700 mL), and the blood loss of the other four was 137 ± 151 mL (range: 50-400 mL). The mean operative time was 318 ± 68 min (range: 236-450 min). The operative morbidity and hospital mortality were zero. The immediate stone clearance rate was 100%. All patients were followed up for an average of 17 mo (range: 7-36 mo). One of the six patients had abdominal mass with pain, and subcutaneous tunnel cholangiography showed severe gallbladder-biliary anastomotic stricture at 4 mo postoperatively. There was no stone recurrence and no cholangitis during follow-up. CONCLUSION: Laparoscopic hepaticoplasty using gallbladder with a subcutaneous tunnel and preserving the sphincter of Oddi is feasible, safe and effective for hepatholithiasis.

Strategies for diagnosis of xanthogranulomatous cholecystitis masquerading as gallbladder cancer.

BACKGROUND: Patients with xanthogranulomatous cholecystitis sometimes exhibit imaging and intraoperative findings that are similar to those of advanced gallbladder cancer, thus these patients are easily misdiagnosed. The present study aimed to investigate the characteristics of xanthogranulomatous cholecystitis masquerading as gallbladder cancer that could potentially aid in the correct diagnosis of this condition. METHODS: The clinical, serological, radiological and operative features of twelve patients with obviously wall-thickening or mass-forming xanthogranulomatous cholecystitis were retrospectively analyzed. Additionally, the patient preoperative features were compared to those of 36 patients with advanced gallbladder cancers. RESULTS: Twelve patients with xanthogranulomatous cholecystitis exhibited one to three episodes of acute cholecystitis within 0.5 to 7 months prior to admission to the hospital. Five of these patients exhibited concomitant choledocholithiasis, whereas no concomitant choledocholithiasis was identified in patients with advanced gallbladder cancer. The incidence of abdominal pain (χ(2) = 6.588, P = 0.010), acute cholecystitis (χ(2) = 29.176, P = 0.000), acute cholangitis (χ(2) = 6.349, P = 0.012), choledocholithiasis (χ(2) = 16.744, P = 0.000), carcinoembryonic antigen test (P = 0.007), CA125 (P = 0.001), and diffuse gallbladder wall thickening (χ(2) = 6.031, P = 0.014), continued mucosal line (χ(2) = 15.745, P = 0.000), homogeneous enhancement of mucosal line (χ(2) = 19.947, P = 0.000), submucosal hypoattenuated nodules or band (χ(2) = 18.607, P = 0.000) in computed tomography demonstrated statistically significant differences between cases of xanthogranulomatous cholecystitis and gallbladder cancer. Furthermore, all the twelve patients with xanthogranulomatous cholecystitis exhibited at least one positive computed tomography imaging feature aside from past acute cholecystitis episode, and no patient with advanced gallbladder cancer simultaneously exhibited past acute cholecystitis episode and at least one positive computed tomography imaging feature. CONCLUSIONS: The accurate preoperative diagnosis of xanthogranulomatous cholecystitis includes an integrated review of past acute cholecystitis episode, choledocholithiasis, and positive computed tomography imaging features. Besides, we present an algorithm for intraoperative diagnosis.

[Correction of claw hand deformity after burns by elastic traction].

OBJECTIVE: To investigate a new method for correction of claw hand deformity after burns. METHODS: From May 2006 to Jul. 2010, 12 patients with claw hands deformities after burns were treated with skin grafts (11 hands) and skin flap (1 hand) with unsatisfactory results. Then elastic traction (skin traction or skeletal traction) were performed with individual functional brace. RESULTS: All patients were followed up for 0.5 to 2 years. Elastic traction was effective in the correction of metacarpophalangeal joint deformity, buttonhole deformity, thumb-in-palm deformity, scar contracture, and palmar arch deformity. CONCLUSIONS: Elastic traction is a simple and effective way for the correction of claw hand deformity after burns with less morbidity and stable results.

An end-to-end anastomosis model of guinea pig bile duct: A 6-mo observation.

AIM: To establish the end-to-end anastomosis (EEA) model of guinea pig bile duct and evaluate the healing process of bile duct. METHODS: Thirty-two male guinea pigs were randomly divided into control group, 2-, 3-, and 6-mo groups after establishment of EEA model. Histological, immunohistochemical and serologic tests as well as measurement of bile contents were performed. The bile duct diameter and the diameter ratio (DR) were measured to assess the formation of relative stricture. RESULTS: Acute and chronic inflammatory reactions occurred throughout the healing process of bile duct. Serology test and bile content measurement showed no formation of persistent stricture in 6-mo group. The DR revealed a transient formation of relative stricture in 2-mo group in comparation to control group (2.94 ± 0.17 vs 1.89 ± 0.27, P = 0.004). However, this relative stricture was released in 6-mo group (2.14 ± 0.18, P = 0.440). CONCLUSION: A simple and reliable EEA model of guinea pig bile duct can be established with a good reproducibility and a satisfactory survival rate.

Long-term outcomes of choledochoduodenostomy for hepatolithiasis.

BACKGROUND: Oddi sphincter plays an important role in preventing reflux cholangitis. There exists the controversy on application of choledochoduodenostomy in hepatolithiasis management. The present study aimed at evaluating long-term outcomes of choledochoduodenostomy for the treatment of hepatolithiasis. METHODS: Forty-six consecutive cases of hepatolithiasis who underwent choledochoduodenostomy were analyzed retrospectively. The pre- and postoperative rates of recurrent cholangitis and acute cholangitis severe type were compared. Paired chi-square test was applied. RESULTS: The mean follow-up time was 17.3 years ranging from 1.6 to 40 years with a follow-up rate of 97.8% (45/46). High rates of remnant stones (39.1%, 18/46), recurrent stones (31.1%, 14/45), uncorrected strictures (85%, 17/20), and mortality (24.4%, 11/45) were observed in this group. Regurgitation of food debris and duodenal content into the biliary tract through the anastomosis was observed. The rate of recurrent cholangitis was equal to the preoperative period (93.3%, 42/45). The rate of acute cholangitis severe type after choledochoduodenostomy (46.7%, 21/45) increased significantly (P<0.01) when compared to the preoperative period (20.0%, 9/45). CONCLUSIONS: Choledochoduodenostomy did not entirely achieve the goal of clearance of stones, correction of strictures, and removing of hepatobiliary lesions by itself. Choledochoduodenostomy without cholangioplasty resulted in an increase of severe reflux cholangitis due to the loss of the anti-reflux function of the sphincter of Oddi. Therefore, choledochoduodenostomy is not an ideal approach to reduce cholangitis in hepatolithiasis and is not the best choice in the management of hepatolithiasis.

Characterization of potential antiviral resistance mutations in hepatitis B virus reverse transcriptase sequences in treatment-naïve Chinese patients.

Full-length hepatitis B virus (HBV) reverse transcriptase (RT) sequences were amplified and sequenced among 192 nucleos(t)ide analogue (NA)-naïve Chinese patients with chronic hepatitis B. Deduced amino acids (AAs) at 42 previously reported potential NA resistance (NAr) mutation positions in RT region were analyzed. Patients were found with either B-genotype (28.65%) or C-genotype (71.35%) infections. Rt53, rt91, rt124, rt134, rt221, rt224, rt238 and rt256 were identified as B- and C-genotype-dependent polymorphic AA positions. AA substitutions at 11 classical NAr mutation positions, i.e. rt80, rt169, rt173, rt180, rt181, rt184, rt194, rt202, rt204, rt236 and rt250, were not detected. However, potential NAr mutations were found in 30.73% (59/192) isolates, which involved 18 positions including rt53, rt207, rt229, rt238 and rt256, etc. The concomitant AA changes of HBsAg occurred in 16.67% (32/192) isolates including sG145R mutation. One-third of mutation positions were located in functional RT domains (e.g. rt207 and rt233), A-B interdomains (overlapping HBsAg 'a' determinant and showing most concomitant immune-associated mutations) and non-A-B interdomains (e.g. rt191 and rt213), respectively. Genotypes B and C each showed several preferred positions to mutate. These results might provide insights into understanding the evolution and selection basis of NAr HBV strains under antiviral therapy.

Profile of HBV antiviral resistance mutations with distinct evolutionary pathways against nucleoside/nucleotide analogue treatment among Chinese chronic hepatitis B patients.

BACKGROUND: Antiviral drug-resistant HBV mutants under a variety of treatment protocols are complex and only partly understood. Here, a population-based cross-sectional study was performed to analyse the profile of resistance mutations in distinct evolutionary pathways refractory to different nucleoside/nucleotide analogues (NAs). METHODS: Serum samples of 199 chronic hepatitis B patients undergoing NA treatment from five hospitals in four northern cities of China were obtained between January 2007 and July 2009. The genotypic resistance of HBV in these samples was characterized. The full-length HBV reverse transcriptase region was amplified, sequenced and analysed with particular focus on the following NA-resistant changes: rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204, rtN236 and rtM250. RESULTS: Among 199 HBV isolates, 30 (15.08%) and 169 (84.92%) were genotypes B and C, respectively, and 65 (32.66%) harboured NA-resistant mutations. The prevalence of mutations at rtM204 was 34.33% in 134 patients who had received or who had been exposed to lamivudine-based therapy. Five cases of rtN236 mutations were detected exclusively among 75 patients receiving adefovir-dipivoxil-based therapies. A total of 19 cases of multidrug resistance rtA181 mutations were observed in those with lamivudine-, adefovir-dipivoxil- or telbivudine-based treatment (186 cases), but not in those undergoing entecavir treatment (13 cases). Mutations were not found at rtI169, rtT184, rtA194 or rtS202. rtM204 mutations (27 rtM204I, 15 rtM204V and 5 rtM204I/V cases) were detected at the highest frequency among 65 mutants (72.30% [47/65]) and found to display 16 combination mutation patterns, in which rtM204I and rtM204V were significantly associated with rtL80I/V and rtL180M, respectively (P<0.01). CONCLUSIONS: One-third of the studied population harboured NA-resistant HBV with complicated mutation patterns. Monitoring HBV genotypic resistance mutation markers and patterns is therefore shown to be beneficial for optimizing antiviral therapies and for avoiding clinical deterioration.