Hayashi et al: Surg Today 2014) However, the efficacy for prev

Hayashi et al.: Surg Today. 2014). However, the efficacy for preventing pulmonary embolism (PE) after HBP surgery is still unclear. Methods: To assess the rate of VTE and hemorrhage after elective HBP surgery, as a general rule, enoxaparin or fondaparinux for postoperative thromboprophylaxis was administered from January 2009 to December 2012 (former period), whereas it was not administered from January 2013 to June 2014 (latter

period). In former and latter period, 366 of 490 (74.4%) and 8 of 161 (5%) patients received chemical thromboprophylaxis at the chief surgeon’s discretion, respectively. Results: VTE and PE were occurred to 29 (5.9%) and 5 (1.0%) patients in former period, and were occurred GW-572016 to 11 (6.8%) and 6 (3.7%) patients in

latter period, respectively. Administration of chemical thromboprophylaxis C646 research buy did not decrease VTE rate compared with non-administrated patients (4.8% vs 7.9%, respectively, p = 0.1025), but PE rate was significantly high in non-administration group (0.8% vs 2.9%, p = 0.0410). Postoperative hemorrhage was occurred at significantly high rate in administration group (23.9% vs 10.6%, p = 0.0001), but the rate of major hemorrhage, which required blood transfusion or hemostasis with surgery or IVR technique, was equivalent in both groups (5.9% vs 8.3%, MCE p = 0.2313). Logistic regression analysis showed age 69 or over is significant risk factor of VTE (p = 0.0091, odds ratio (OR): 2.40, 95% CI: 1.24–4.78) and PE (p = 0.0466, odds ratio (OR): 3.63, 95% CI: 1.02–16.96). Non-administration of chemical prophylaxis also significantly increased the risk of PE (p = 0.0433, odds ratio (OR): 3.67, 95% CI: 1.04–17.00). Conclusion: Administration of chemical thromboprophylaxis after

HBP surgery is safe and beneficial because it did not increase the major hemorrhage risk and decreases the risk of PE. Key Word(s): 1. venous thromboembolism; 2. pulmonary embolism; 3. thromboprophylaxis; 4. hepatobiliary-pancreatic surgery Presenting Author: KIYOSHI HIRAMATSU Additional Authors: TOSHIYUKI ARAI, SATOMI SAEKI, TAKESHI AMEMIYA, HIDENARI GOTO, TAKASHI SEKI Corresponding Author: KIYOSHI HIRAMATSU Affiliations: Anjo Kosei Hospital, Anjo Kosei Hospital, Anjo Kosei Hospital, Anjo Kosei Hospital, Anjo Kosei Hospital Objective: Major surgery for hemodialysis patients with nephropathy seems to be at high risk. In this report we analyzed short term outcome (postoperative mortality and morbidity) and long term outcome (over all survival) of the surgery for gastric cancer in patients with nephropathy under the maintenance of hemodialysis.

3:1 The table below showed the total number of new cases and ave

3:1. The table below showed the total number of new cases and average annual incidence rates of PIBD diagnosed before 15 years old, per 100 000 populations. 1970s 1980s 1990s 2000s 2010–2013 Key: CD, Crohn’s disease; UC, Ulcerative colitis; IBD-U,

IBD-unclassified. Conclusion: The incidence rate of PIBD in NSW Australia has increased nearly 30 fold in the past 5 decades, owing primarily to the increased incidence of CD. This is consistent with global trend of rising rates of PIBD. A SHARMA,1 M MARCON,1 G CHAVHAN,2 S MOHAN,2 P CHIU,3 P BRAHMAMDAN3 1Division of Paediatric Gastroenterology, Hepatology and Nutrition, 2Department of Diagnostic Imaging, and 3Division of Pediatric General and Thoracic Selleckchem RG-7388 Surgery, The Hospital for Sick Children, Toronto, Canada Background: Magnet ingestion and ingestion–related Lapatinib clinical trial injuries appear to be on the rise. The ingestion of multiple magnets simultaneously can lead to serious injury resulting from the attraction of the magnets positioned

along the length of the small bowel, resulting in ischemia, necrosis and perforation of the intervening soft tissue. Complications may include bowel perforation, fistula formation and even death. We report a case of ingestion of multiple magnets with gastrointestinal tract fistula formation and successful endoscopic management without requiring surgery. Case: A 7-year-old autistic boy was transferred from a peripheral hospital with a 3 day history of intermittent abdominal pain without vomiting, constipation or blood in stools. His abdominal radiographs revealed an L-shaped linear foreign body in the epigastrium that consisted of

radio-opaque and radiolucent components 上海皓元医药股份有限公司 thought to be magnets along with a coin and a metallic ball. There was no evidence of intra or retroperitoneal free air on the radiographs. Gastroscopy (GF 180 Olympus) was performed. Two cylindrical magnets approximately 2 cm long with an attached 25 cent coin were found in the posterior- inferior wall of greater curvature of stomach. Gastroscope was then advanced to the distal duodenum near the duodeno-jejunal junction were two more magnets were found with a metal ball at the end. The anterior part of one of the duodenal magnets was stuck to the distal end of magnet in stomach though a gastro-duodenal fistula. Using various instruments including grasping forceps and snare, all the foreign bodies were successfully retrieved through the gastric end of the fistula. Repeat radiographs after the procedure did not show any free intra-peritoneal air. The patient did not require a laprotomy. Upper GI contrast study next day depicted a short gastro-duodenal fistula extending from the posterior wall of the body of the stomach up to the fourth part of the duodenum measuring approximately 1.8 cm. There was no leakage of contrast into the peritoneal or retroperitoneal compartments.

2C) Concordantly, SIRT2 depletion reduced DNA synthesis by 50% (

2C). Concordantly, SIRT2 depletion reduced DNA synthesis by 50% (P < 0.001), as measured by BrdU incorporation assay (Fig. 2D). Cell-cycle distribution, as determined by FACS analysis, revealed that SIRT2 silencing significantly induced G1 and G2 arrest find more in p53 WT (SK-Hep-1 and HepG2) and in p53-mutated (Huh-7 and PLC5) cells, respectively

(Fig. 2E). Nevertheless, unlike the knockdown of SIRT1,23 knockdown of SIRT2 neither resulted in cellular senescence nor apoptosis of HCC cells (data not shown). Taken together, these data suggested that SIRT2 depletion might inhibit cell growth by inducing cell-cycle delay. Next, we evaluated whether SIRT2 plays a role in the motility of HCC cells. Depletion of SIRT2 (shSIRT2-1 and shSIRT2-2), but not SIRT1 (shSIRT1-1), markedly reduced cell migration through transwell (P < 0.01) (Fig. 3A). Concordantly, knockdown of SIRT2 also diminished wound-healing capacity (P < 0.01) (Fig. 3B) and impaired cell invasion through Matrigel (P < 0.01) (Fig. 3C). In contrast, ectopic expression of WT SIRT2 promoted migration and invasion capacity in

L02 cells (Fig. 3D). Together, these data suggested a role of SIRT2 in the motility and invasiveness Talazoparib in vitro of HCC cells. EMT, the sequence of events that converts adherent epithelial cells into migratory cells, which invade the extracellular matrix,28 is associated with tumor metastasis.29 Therefore, we determined whether EMT is responsible for SIRT2-mediated change in cell motility. Knockdown of SIRT2 in HCC cells induced the expression of epithelial markers E-cadherin and α-catenin that was accompanied by a concomitant reduction of

mesenchymal marker N-cadherin and α-SMA. Nevertheless, the expression of vimentin, another mesenchymal marker, was not altered (Fig. 3E). F-actin distribution was also rearranged in SIRT2-depleted cells from a stress-fiber to a cortical pattern, suggestive of a conversion to the epithelial phenotype (Fig. 3F). Therefore, our data suggest a loss of mesenchymal-like features and reacquisition 上海皓元 of epithelial characteristics in SIRT2-depleted HCC cells. The role of SIRT2 in EMT was further supported by the reduced expression of E-cadherin and alpha-catenin, as well as the enhanced expression of N-cadherin and α-SMA in L02 cells, which SIRT2 was ectopically expressed (Fig. 3E). Reduced expression of E-cadherin and the activation of WNT signaling lead to the accumulation and nuclear import of β-catenin, where it interacts with TCF/LEF to induce the expression of genes responsible for the EMT process.30, 31 Therefore, we have elucidated whether SIRT2 plays a role in β-catenin signaling or not. Expression of SIRT2 shRNAs in SK-Hep1 and Huh7 cells markedly reduced the level of the total, as well as the active (dephosphorylated on Ser37 and Ser41), β-catenin (Fig. 4A).

The mitochondrial enzyme manganese superoxide dismutase (EC 11

The mitochondrial enzyme manganese superoxide dismutase (E.C. 1.15.1.1, SOD2)—a critical determinant of cellular defence against toxic insult to the liver—is the major scavenger of mitochondrial superoxide. The SOD2 mutant C allele (T > C polymorphism in codon 16 of the mitochondrial targeting sequence resulting in an alanine for valine substitution) allows the preprotein to be more efficiently imported into the mitochondrial matrix and subsequently enhanced mitochondrial activity of the mature protein.4 Surprisingly, the more efficient C variant allele

has been shown to increase the susceptibility to DILI, particularly related to antituberculosis drugs, but also to other drugs, in Taiwanese patients.5 Selleckchem SAR245409 This unexpected finding has been attributed to the accumulation of higher amounts of hydrogen peroxide generated by the enhanced SOD2 activity. In addition to SOD2, glutathione peroxidases can

modulate the intracellular level of hydrogen peroxide. Glutathione peroxidase 1 (E.C. 1.11.1.9, GPX1) is part of the cellular antioxidant defence system by catalyzing the reduction of hydrogen peroxide (and various organic hydroperoxides) to water using reduced glutathione as a co-substrate. GPX1 is the main glutathione peroxidase in the mammalian liver and plays a significant role in preventing mitochondrial beta-catenin signaling oxidative stress.6 A polymorphism in codon 200, initially assigned to codon 198 of the human GPX1 gene and designated as rs1050450, encodes for either a proline or a leucine amino acid. The presence of a leucine at this position has been shown to reduce enzyme activity by 40%.7 Scarce information

is available on polymorphisms in the SOD2 and GPX1 genes in Caucasian patients and their relevance in DILI development susceptibility. To perform a more comprehensive 上海皓元医药股份有限公司 approach to the study of mitochondrial antioxidant genetics in DILI, this study was undertaken to investigate potential associations between the SOD2 Val16Ala and GPX1 Pro200Leu polymorphisms and the risk of developing idiosyncratic hepatotoxicity. CI, confidence interval; CNS, central nervous system; DILI, drug-induced liver injury; GPX1, glutathione peroxidase-1; NSAID, nonsteroidal anti-inflammatory drug; OR, odds ratio; ROS, reactive oxygen species; SOD2, manganese superoxide dismutase. Cases of DILI were selected from those submitted to the Spanish DILI Registry, in use in southern Spain since 1994 and coordinated by two of the authors (R.J.A. and M.I.L.).The operational structure of the registry, data recording, and case ascertainment have been reported elsewhere.

The mitochondrial enzyme manganese superoxide dismutase (EC 11

The mitochondrial enzyme manganese superoxide dismutase (E.C. 1.15.1.1, SOD2)—a critical determinant of cellular defence against toxic insult to the liver—is the major scavenger of mitochondrial superoxide. The SOD2 mutant C allele (T > C polymorphism in codon 16 of the mitochondrial targeting sequence resulting in an alanine for valine substitution) allows the preprotein to be more efficiently imported into the mitochondrial matrix and subsequently enhanced mitochondrial activity of the mature protein.4 Surprisingly, the more efficient C variant allele

has been shown to increase the susceptibility to DILI, particularly related to antituberculosis drugs, but also to other drugs, in Taiwanese patients.5 learn more This unexpected finding has been attributed to the accumulation of higher amounts of hydrogen peroxide generated by the enhanced SOD2 activity. In addition to SOD2, glutathione peroxidases can

modulate the intracellular level of hydrogen peroxide. Glutathione peroxidase 1 (E.C. 1.11.1.9, GPX1) is part of the cellular antioxidant defence system by catalyzing the reduction of hydrogen peroxide (and various organic hydroperoxides) to water using reduced glutathione as a co-substrate. GPX1 is the main glutathione peroxidase in the mammalian liver and plays a significant role in preventing mitochondrial see more oxidative stress.6 A polymorphism in codon 200, initially assigned to codon 198 of the human GPX1 gene and designated as rs1050450, encodes for either a proline or a leucine amino acid. The presence of a leucine at this position has been shown to reduce enzyme activity by 40%.7 Scarce information

is available on polymorphisms in the SOD2 and GPX1 genes in Caucasian patients and their relevance in DILI development susceptibility. To perform a more comprehensive 上海皓元 approach to the study of mitochondrial antioxidant genetics in DILI, this study was undertaken to investigate potential associations between the SOD2 Val16Ala and GPX1 Pro200Leu polymorphisms and the risk of developing idiosyncratic hepatotoxicity. CI, confidence interval; CNS, central nervous system; DILI, drug-induced liver injury; GPX1, glutathione peroxidase-1; NSAID, nonsteroidal anti-inflammatory drug; OR, odds ratio; ROS, reactive oxygen species; SOD2, manganese superoxide dismutase. Cases of DILI were selected from those submitted to the Spanish DILI Registry, in use in southern Spain since 1994 and coordinated by two of the authors (R.J.A. and M.I.L.).The operational structure of the registry, data recording, and case ascertainment have been reported elsewhere.

1999, Darienko et al 2010) Discovery of species diversity in co

1999, Darienko et al. 2010). Discovery of species diversity in coccoid microchlorophytes is still a work in progress and to date it is still not possible to provide an accurate estimate of the number of species. New species and genera continue to be discovered at a steady rate (e.g., Gaysina et al. 2013, Neustupa et al. 2013a,b) and there is no reason to expect that this will stop in the near future; in fact, with facilitated access to poorly sampled regions and the use of improved

molecular techniques, this trend might actually increase. Field-based investigations have revealed an unexpected diversity of these algae in natural environments, even in habitats supposedly hostile to the survival of algae. The microbial flora of GSK-3 activation American deserts see more is a well-documented case; studies focused on this community revealed a surprising species diversity (Flechtner 2007) and concluded that in desert environments, green microalgae are not just a transient presence, but have become specialists in these regions (Lewis and Lewis 2005). In recent years, the first full genomes of coccoid greens have become available (Blanc et al. 2010, 2012) providing further surprising discoveries,

such as the presence of functional meiotic genes in putatively asexual species and the acquisition of chitinous cell walls by horizontal gene transfer from an algal virus or a fungus (Blanc et al. 2010). It is now well established

that coccoid forms represent a polyphyletic assemblage of taxa distributed in the classes Chlorophyceae, Trebouxiophyceae, and Ulvophyceae (Lewis and McCourt 2004, Leliaert et al. 2012). In some orders and families, the coccoid habit is dominant, whereas in others, it coexists with more complex morphologies. This is the case for the chlorophycean order Sphaeropleales, which is best known for multicellular representatives such as Hydrodictyon, Pediastrum, and Scenedesmus. In this issue, Fučíková et al. (2013) provide a taxonomic reassessment of the Sphaeropleales based on phylogenetic analysis of a 7-gene MCE公司 data set (three ribosomal and four plastid). In terms of gene sampling, this is one of the most extensive molecular data sets used thus far for the phylogenetic study of an individual green algal taxon. The phylogenetic analyses are optimized by an accurate search for the best partitioning strategy and verification of the phylogenetic concordance among the seven genes. The resulting phylogeny recovers 16 well-supported lineages that fit harmoniously within a traditional taxonomic scheme and are recognized at the level of family.

Postoperative bleeding control was judged to be effective (bleedi

Postoperative bleeding control was judged to be effective (bleeding was stopped completely or reduced considerably) for 34/38 procedures (89%) in patients with congenital AG-014699 supplier haemophilia A, 10/13 procedures (77%) in patients

with congenital haemophilia B, and 4/5 procedures (80%) in patients with acquired haemophilia. Tranexamic acid was used concomitantly for 36/56 procedures (64%). Safety was analysed for 66 procedures in 37 patients. Adverse effects potentially related to rFVIIa treatment included mild superficial thrombophlebitis, mild decrease in platelet count, and mild elevation of the serum alanine transaminase level in one patient each. All adverse effects resolved without treatment. Administration of rFVIIa provided adequate haemostasis without serious adverse effects in the majority of cases. The efficacy and safety data in Japanese patients Cell Cycle inhibitor were similar to previously published data from other countries. “
“Summary.  The development of inhibitory anti-factor VIII (FVIII) antibodies in patients with haemophilia A following replacement therapy is associated with several

types of risk factors. Among these, the purity of FVIII concentrates, and in particular the presence of von Willebrand factor (VWF), was controversially proposed to influence the immunogenicity of exogenous FVIII. We re-assessed in vivo and in vitro the immuno-protective effect of VWF towards FVIII. The immuno-protective effect of VWF towards FVIII was investigated

in vivo, in a model of haemophilia A. We studied the endocytosis MCE of FVIII by murine bone marrow-derived dendritic cells and evaluated the capacity of VWF to block the internalization of FVIII. We characterized the relevance of VWF for the accumulation of FVIII in the marginal zone of the spleen, a secondary lymphoid organ where the immune response to therapeutically administered FVIII initiates. Our results confirm that VWF reduces the immunogenicity of FVIII in FVIII-deficient mice. Paradoxically, VWF is important for the accumulation of FVIII in the marginal zone of the spleen. We propose that VWF exerts at least two non-mutually exclusive immunoprotective roles towards FVIII in haemophilic mice: VWF prevents the endocytosis of FVIII by professional antigen-presenting cells by blocking the interaction of FVIII with as yet unidentified endocytic receptor(s). Hypothetically, VWF, by virtue of increasing the half-life of FVIII in the circulation, may allow an increased contact time with tolerogenic marginal zone B cells in the spleen. “
“Summary.  To describe the study design, procedures and baseline characteristics of the Haemophilia Utilization Group Study – Part Va (HUGS Va), a US multi-center observational study evaluating the cost of care and burden of illness in persons with factor VIII deficiency.

IF studies indeed showed redistribution of β-catenin from the nuc

IF studies indeed showed redistribution of β-catenin from the nucleus to the cytoplasm after CCRK knockdown compared with control in two different cell lines. The authors further

demonstrated decreased protein levels of active but not of total β-catenin in this situation. Mechanistically, they determined that CCRK knockdown decreased phosphorylation of GSK3β and the ensuing decrease in β-catenin activity. Conversely, ectopic expression of CCRK led to increased phosphorylation of GSK3β culminating in enhanced β-catenin signaling. Phosphorylation of GSK3β has been shown to mediate β-catenin activation through inhibition of β-catenin degradation complex. 9 In addition, the authors see more demonstrated that knockdown of CCRK abrogated

some known β-catenin downstream targets such as epidermal growth factor receptor (EGFR) and cyclin-D1, which was reversed by ectopic CCRK expression. These targets have independently been shown to regulate proliferation in HCC. 10, 11 Knockdown of β-catenin despite Selleck EGFR inhibitor ectopic expression of CCRK led to decreased tumor cell proliferation, and additional functional studies such as soft agar assays and tumor xenograft studies further validated these observations. The authors then asked whether the modulation of β-catenin activity by CCRK had any impact on AR expression and function because β-catenin–AR crosstalk has been previously reported. 12 Indeed, the authors determined that ectopic CCRK expression 上海皓元医药股份有限公司 led

to increased total and Ser81-phosphorylated AR, which has independently been shown to induce AR promoter activity and in turn tumor cell growth. 13 This effect was abrogated upon β-catenin silencing, suggesting that CCRK-induced β-catenin activation indeed regulates AR expression and its biological effects. Lastly, knockdown of AR affected β-catenin activity, which could be rescued by CCRK overexpression, and ectopic AR expression could increase active-β-catenin levels, which could be blocked by inhibition of CCRK. Thus, the authors established a unique AR/CCRK/β-catenin feed-forward circuitry (Fig. 1), which was also evident in a significant subset of HCC patients as concomitant up-regulation of AR/CCRK/β-catenin using both western blot analysis and immunohistochemistry. Further examination also revealed a significant correlation between overexpression of CCRK and advanced tumor stage reflected by shorter overall survival. The current study has identified a novel circuitry that consists of an AR/CCRK/β-catenin axis that may provide at least one major mechanism of hepatocarcinogenesis in this male-predominant tumor type, thus presenting unique molecular interactions that may be exploited for therapeutic intervention. This study also suggests at least one additional mechanism by which Wnt/β-catenin signaling may in fact cause tumor progression in males.

However, we did not find an association

between SERT and

However, we did not find an association

between SERT and GNβ3 C825T genetic polymorphisms and overlap syndrome, including FD and IBS, in our previous study in a Korean population. We therefore undertook a validation study of the Rome III criteria for FGIDs by factor analysis of symptoms. The sensitivity and specificity of Rome III criteria in discriminating FGIDs from organic diseases of the upper GI tract was 60% and 53%, respectively, while the sensitivity and specificity of these criteria for the lower GI tract was 80% and 50%, BIBW2992 cost respectively, partially supporting the use of the Rome III criteria in Korea. “
“Wilson disease (WD) is a rare autosomal recessive disease of copper metabolism characterized by copper accumulation in hepatocytes and in other extra hepatic organs. Homozygous or compound heterozygous mutations in the ATP7B gene, which codes for an ATP-dependent copper see more export pump, are its cause. It should always be considered in a patient <40 years of age who presents with unexplained liver, neurological or neuropsychiatric disease. Presence of low serum ceruloplasmin levels, increased urine copper excretion and Kayser–Fleischer rings help in diagnosis of WD. Combined treatment with low copper diet, chelators, zinc and liver transplantation has proven lifesaving and even curative. "
“In the February 2011 issue of Hepatology, in the article titled

“Excessive hepatomegaly of mice with hepatocyte-targeted elimination of integrin linked kinase following treatment with 1,4-bis [2-(3,5-dichaloropyridyloxy)] benzene” (volume 53, pages 587-595; doi: 10.1002/hep.24040), by Shashikiran Donthamsetty, Vishakha S. Bhave, Corrine S. Kliment, William C. Bowen, Wendy M. Mars, Aaron W. Bell, Rachel E. Stewart, Anne Orr, Chuanyue Wu and George K. Michalopoulos, the upper left photomicrograph of Fig. 4D, showing Myc expression in nonhepatectomized wild-type mice, was erroneously taken from the liver of a nonhepatectomized

ILK knockout mouse. The following image is derived from wild-type mice and corrects the image published in the original article. The publisher regrets the error. “
“To the Editor: We read the study by Dam et al.[1] with great interest. They compared the 上海皓元医药股份有限公司 cerebral oxygen metabolism (CMRO2), cerebral blood flow (CBF), and metabolic rate of blood ammonia (CMRA) in patients with cirrhosis during and after recovery from hepatic encephalopathy (HE) and concluded that the changes in CMRO2 and CBF could not link to ammonia concentration or CMRA. Their findings are of great potential for clinical applications; however, we have some concerns. First, the authors reported that CBF increased significantly and arterial ammonia concentration decreased markedly after recovery from HE, which tended to show a negative correlation between them.

In this study, they indicated that ETV given at 1 mg/day for 48 w

In this study, they indicated that ETV given at 1 mg/day for 48 weeks resulted in lesser hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) reduction in the LAM/ADV-resistant group than compared with the LAM-resistant group. They also noted that HBV

DNA loss was significantly higher in the LAM-resistant group compared with the LAM/ADV-resistant group (34% versus 10%). However, they showed that virological breakthrough was similar in both groups. They also underlined that virological response at 12 weeks determined the degree of HBV DNA reduction over 48 weeks of therapy, regardless of previous antiviral MK-2206 ic50 treatment. In their study, Shim et al. underlined the importance of multidrug resistance in cases with inappropriate use of antivirals in HBV infection. The same authors suggested, in the introduction section, that “in terms of salvage therapy for LAM-resistant or ADV-resistant chronic hepatitis B infection, the American Association for the Study of Liver Diseases (AASLD) practice guideline recommended switching to ETV” monotherapy as an optimal Inhibitor Library order strategy. However, according to the current guidelines,

including AASLD 2009,2 European Association for the Study of the Liver 2009,3 and Asian Pacific Association for the Study of the Liver 2008,4 what the authors did seemed to be inappropriate to suggest to the readers. The guidelines mentioned above unanimously indicated that

ETV can be recommended as a rescue therapy only for ADV-resistant chronic HBV infection having Asp236-to-Thr236 (N236T) and/or Ala181-to-Thr181/Val181 (A181T/V) substitutions. Contrary to what the authors MCE公司 wrote in the introduction section of their article, AASLD guidelines in 20092 on HBV infection clearly indicate that ETV is not an optimal treatment for LAM-refractory HBV. It is clearly known that Leu180-to-Met180 (L180M) + Met204-to-Val204 (M204V) and L180M + M204V + Asn236-to-Thr236 (N236T) mutants behaved 6.25-fold resistant to ETV compared with wild-type HBV.5 We also know that genotypic resistance to ETV will develop at a rate of 43% at the end of 4 years.6 Expectedly, two patients in the series of Shim et al.1 developed virological breakthrough with Ser202-to-Gly202 (S202G) ETV resistance substitutions at 36 weeks of treatment, and one patient developed biochemical breakthrough in the LAM-resistant group of patients. Unfortunately, the readers were not informed in this article how the authors treated these two cases in their series. Another relevant article in this field showed that although HBV DNA suppression was achieved in a higher percentage of patients, there was an emergence of nearly 8% resistance to ETV monotherapy in cases with previous LAM resistance in year 2.7 Thus, this strategy led to selection of multidrug-resistant HBV strains with maximal viral resistance in the near future.