Extremity risk factors of sepsis for gastrointestinal endoscopy in patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis is a well-known risk factor of sepsis after emergent gastrointestinal (GI) endoscopy. Elective GI endoscopy before living donor liver transplantation (LDLT), however, may also carry the septic risk among these patients. METHODS: This retrospective study reviewed the medical records of 642 cirrhotic recipients who underwent GI endoscopy from 2008 to 2016. We analyzed the incidence and risk factors of post-endoscopy sepsis during 2008-2012 (experience cohort). Our protocol changed after 2013 (validation cohort) to include antibiotic prophylaxis. RESULTS: In experience cohort, 36 cases (10.5%) of the 342 LDLT candidates experienced sepsis within 48 h after endoscopy. The sepsis rate was significantly higher in patients with hepatic decompensation than patients without (22.2% vs. 9.6% vs. 2.6% in Child C/B/A groups respectively; ×2 = 20.97, P < 0.001). Using multivariate logistic regression analysis, the factors related to post-endoscopy sepsis were the Child score (OR 1.46; 95% CI 1.24-1.71), Child classes B and C (OR 3.80 and 14.13; 95% CI 1.04-13.95 and 3.97-50.23, respectively), hepatic hydrothorax (OR 4.85; 95% CI 1.37-17.20), and use of antibiotic prophylaxis (OR 0.08; 95% CI 0.01-0.64). In validation cohort, antibiotics were given routinely, and all cases of hepatic hydrothorax (n = 10) were drained. Consequently, 4 (1.3%) episodes of sepsis occurred among 300 LDLT candidates, and the incidence was significantly lower than before (1.3% vs. 10.5%, P < 0.001). CONCLUSIONS: Patients with decompensated cirrhosis and hepatic hydrothorax have higher risk of sepsis following endoscopy. In advanced cirrhotic patients, antibiotic prophylaxis and drainage of hydrothorax may be required to prevent sepsis before elective GI endoscopy.

Emerging Roles of Calcium Signaling in the Development of Non-Alcoholic Fatty Liver Disease.

The liver plays a central role in energy metabolism. Dysregulated hepatic lipid metabolism is a major cause of non-alcoholic fatty liver disease (NAFLD), a chronic liver disorder closely linked to obesity and insulin resistance. NAFLD is rapidly emerging as a global health problem with currently no approved therapy. While early stages of NAFLD are often considered benign, the disease can progress to an advanced stage that involves chronic inflammation, with increased risk for developing end-stage disease including fibrosis and liver cancer. Hence, there is an urgent need to identify potential pharmacological targets. Ca2+ is an essential signaling molecule involved in a myriad of cellular processes. Intracellular Ca2+ is intricately compartmentalized, and the Ca2+ flow is tightly controlled by a network of Ca2+ transport and buffering proteins. Impaired Ca2+ signaling is strongly associated with endoplasmic reticulum stress, mitochondrial dysfunction and autophagic defects, all of which are etiological factors of NAFLD. In this review, we describe the recent advances that underscore the critical role of dysregulated Ca2+ homeostasis in lipid metabolic abnormalities and discuss the feasibility of targeting Ca2+ signaling as a potential therapeutic approach.

Endoscopic injection sclerotherapy for pediatric bleeding esophageal varices complicated by gastric vein, main portal vein, splenic mesenteric junction, and splenic vein occlusion: a case report.

BACKGROUND: Endoscopic injection sclerotherapy (EIS) is a life-saving procedure for pediatric patients with bleeding gastric varices (GV) associated with advanced liver cirrhosis and severe portal hypertension. Because of the lack of an endoscopic banding ligation device for pediatric patients, EIS is usually performed for bleeding esophageal varices (EV) in infants with congenital biliary atresia. CASE PRESENTATION: We present a case of a 15-month-old female infant with type I biliary atresia with jaundice (total serum bilirubin, 22.2 mg/dL), hypoalbuminemia (serum albumin level, 2.58 g/dL), coagulopathy (prothrombin time > 20 s compared with that of a normal control), ascites, splenomegaly, portal hypertension (portal vein velocity, 3.9-5.6 cm/sec of hepatopetal flow), and repeated bleeding of the varices after receiving three doses of intravascularly administered Histoacryl 1 ampoule mixed with Lipiodol UF 8 mL in the EV. Prominent GV and EV were occluded by EIS. The sclerosing agent was also present in the main portal vein, splenic mesenteric junction, and splenic vein, causing an engorged inferior mesenteric vein. The patient underwent total hepatectomy and living donor liver transplantation (LDLT) by left lateral segment graft (segments 2, 3, and 4 of the middle hepatic vein trunk) and left portal vein graft to the recipient inferior mesenteric vein anastomosis. Portal vein stent placement via segment 4 of the portal vein stump was performed from the inferior mesenteric vein to the umbilical portion of the left portal vein. The patient is still alive and doing well after the LDLT. CONCLUSIONS: EIS is a life-saving procedure in cases involving bleeding EV complicated by gastric, main portal vein, splenic mesenteric junction, and splenic vein occlusions; hence, it should be kept in mind as a treatment for EV complications in pediatric patients.

Genetic polymorphisms of the hepatic pathways of fatty liver disease after living donor liver transplantation.

BACKGROUND & AIMS: Fatty liver disease is an important complication associated with liver transplantation, and the cytochrome P-450 system of the donor liver may be involved in its pathogenesis. To explore the effects of the CYP27A1, CYP27B1, CYP2R1, and vitamin D receptor pathways on vitamin D maintenance after living donor liver transplantation, we investigated the interplay between serum 25(OH)D and common variants in 60 paired donors and recipients who underwent living donor liver transplantation. METHODS: We prospectively collected 60 donor/recipient pairs from our liver transplantation programmes and extracted serum DNA to evaluate single nucleotide polymorphisms in CYP27A1 rs4674344, CYP27B1 rs10877012, CYP2R1 rs10741657, and VDR rs2228530 alleles using real-time polymerase chain reaction. We measured serum 25(OH)D concentrations of donors (D-D0) and recipients before (R-D0) and after (R-D30) living donor liver transplantation for comparison with repeated-measures analysis of variance in generalized estimating equations analysis. RESULTS: Fatty liver disease was noted in 28.3% of the cases after living donor liver transplantation, and the graft rejection rate was 25%. There were significant differences in low serum 25(OH)D concentrations between D-D0 and R-D0 and between R-D0 and R-30 groups. Significant associations were observed for serum CYP27A1 rs4674344 in recipients and donors as well as for graft liver tissue with VDR rs2228530. There was no significant relationship with serum CYP27B1 rs10877012 in recipients and donors or with graft liver tissue with CYP2R1 rs10741657. CONCLUSIONS: Donor/recipient CYP27A1 rs4674344 and graft VDR rs2228570 may be related to low serum 25(OH)D and may play a major role in the development of fatty liver disease in recipients after living donor liver transplantation.

Association between PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma in Asian chronic hepatitis C patients: A longitudinal study.

BACKGROUND/PURPOSE: Prdevious meta-analyses assess whether or not patatin-like phospholipase domain containing 3 (PNPLA3) (rs738409 C > G) was associated with increased risk of hepatocellular carcinoma (HCC) in Caucasians patients with hepatitis C virus (HCV)-related cirrhosis, these meta-analyses did not provide firm conclusions. Only one cross-sectional study involving Asian patients has previously been conducted to explore this issue. We aim to investigate this in a longitudinal cohort of Asian chronic hepatitis C (CHC) patients. METHODS: We consecutively enrolled 1011 CHC patients who underwent liver biopsy before initiating interferon-based therapy. These patients were followed-up and screened for HCC up to a median of 6.9 years. The influence of rs738409 (GG) genotype on the occurrence of HCC was assessed using the Kaplan-Meier method, then according to the multivariate Cox model. RESULTS: During follow-up, 143 (14.1%) patients developed HCC. rs738409 (GG) genotype was not associated with time-to-HCC development on multivariate Cox regression (P = 0.634). When considering the occurrence of these events over time, rs738409 (GG) genotype did not influence the risk of HCC development (log-rank = 0.12). Among 261 patients with liver cirrhosis, rs738409 (GG) genotype was not associated with time-to-HCC development on multivariate Cox regression (P = 0.737). When considering the occurrence of these events over time, rs738409 (GG) genotype did not influence the risk of HCC development (log-rank = 0.72). CONCLUSION: In this longitudinal study with liver biopsy to stage liver fibrosis, we affirm there is no influence of the rs738409 (GG) genotype on the occurrence of HCC in Asian CHC patients, including cirrhotic patients.

Cytochrome P450 in living donor liver transplantation.

Cytochrome P450 metabolizes many drugs in the liver. Three genotypes of CYP2C19 with extensive, intermediate, and poor metabolizing activity, respectively, have been identified in peripheral blood of transplant recipients and new liver grafts in living donor liver transplantation (LDLT). The expression of the final genotype in liver graft biopsies depends on the donor, whereas the expression in peripheral blood mononuclear cells depends on the recipient. The metabolizing isoenzyme of the major anti-rejection agents passes through CYP3A4, CYP3A5 and MDR1, which have also been identified to have similar biological characteristics as genotype of CYP2C19 in liver tissue. Recently, pyrosequencing has been used to investigate the expressions of different genotypes in liver grafts in LDLT. This review focuses on recent findings regarding the biological expressions of the CYP2C19, CYP3A4, CYP3A5 and MRD1 genotypes in liver grafts before and after LDLT. The application of pyrosequencing may be beneficial in further research on liver transplantation. Laser capture microdissection of hepatocytes in liver grafts may be a direction for future research.

Prolonged survival by combined treatment with granulocyte colony-stimulating factor and dipeptidyl peptidase IV inhibitor in a rat small-for-size liver transplantation model.

AIM: Despite the great advances and excellent outcomes of liver transplantation (LT), small-for-size (SFS) graft syndrome is a life-threatening complication that remains to be overcome. In the present study, we investigated the therapeutic effect of combined treatment with granulocyte colony-stimulating factor (G-CSF) and a dipeptidyl peptidase IV (DPP-IV) inhibitor on SFS liver graft syndrome. METHODS: The transplantation of small-sized Lewis donor livers into green fluorescent protein (GFP) transgenic Wistar rats was performed and the recipients were randomly assigned to one of four groups (without treatment, DPP-IV inhibitor treatment, G-CSF treatment and G-CSF/DPP-IV inhibitor combination). Recombinant human G-CSF was injected s.c. at a dose of 2 µg/kg per day starting 5 days prior to transplantation. G-CSF was combined with the p.o. administration of a DPP-IV inhibitor (2 mg/kg per day) after transplantation until the end of the observation period. RESULTS: The post-transplant survival and liver function of rats treated with G-CSF/DPP-IV inhibitor combination therapy were significantly improved with an increased number of recipient-derived GFP positive cells into the liver grafts. A confocal microscopy study showed cytokeratin (CK)-18 and GFP positive hepatic progenitor cells in the parenchyma of the liver allografts. Untreated rats and rats treated with either G-CSF or DPP-IV inhibitor did not exhibit the prolonged survival and had less GFP and CK-18 positive cells in the liver grafts after SFS LT. CONCLUSION: Our results suggest that combined treatment with G-CSF and DPP-IV inhibitor may synergistically induce migration and differentiation of recipient-derived stem cells into the hepatic progenitor cells, resulting in the amelioration of SFS liver graft syndrome.

Telbivudine and adefovir combination therapy for patients with chronic lamivudine-resistant hepatitis B virus infections.

We evaluated second-line salvage therapy with adefovir + telbivudine (group 1), adefovir followed by adefovir + telbivudine (group 2), or lamivudine + adefovir followed by adefovir + telbivudine (group 3) in hepatitis B patients with an inadequate virologic response to lamivudine treatment. Simple linear regression analysis showed that for each additional month of treatment, the most significant reduction in viral load occurred in group 1 (HBV DNA [Log10 IU/mL]: group 1, -0.149; group 2, -0.081; group 3, -0.123). Generalized estimating equation analysis revealed that compared to group 1, hepatitis B virus (HBV) DNA levels were 1.203 and 0.443 Log10 IU/mL higher in groups 2 and 3, respectively. Overall, a significant reduction in viral load (-0.060 Log10 IU/mL) was observed for each additional month of treatment. Adefovir + telbivudine treatment resulted in a significant reduction in HBV DNA levels. Moreover, telbivudine treatment resulted in a significant reduction in viral load (-0.050 Log10 IU/mL) compared to lamivudine treatment after the emergence of lamivudine resistance.

Effect of liquid meals with different volumes on gastroesophageal reflux disease.

BACKGROUND AND AIM: Patients with gastroesophageal reflux disease (GERD) are often advised to avoid large meals, based on their complaints of increased symptoms after eating too much, and epidemiological evidence of a link between high volume intake and the presence of GERD. However, the precise effects of meal volume on gastroesophageal reflux have not been well studied. We aimed to clarify the effect of meal volume on acid regurgitation and symptoms in patients with GERD. METHODS: Fifteen patients (10 female, 5 male; mean 54 ± 10 years old) with GERD were studied twice each in random order, during 24 h ambulatory pH monitoring. On one day, they consumed a 600 mL liquid test meal three times (breakfast, lunch, and dinner), and on the other, they consumed a 300 mL test meal six times (breakfast, snack, lunch, snack, dinner, and snack). Gastric fundus and antral areas and antral contractions were measured by transabdominal ultrasound. Symptoms were recorded using questionnaires. RESULTS: During the 600 mL regimen, there were more reflux episodes (17 ± 4 vs 10 ± 2, P = 0.03) and a greater total acid reflux time (12.5 ± 5.9% vs 5.5 ± 3.6%; P = 0.045) than the 300 mL regimen. Both the cross-sectional area of the gastric fundus (P = 0.024) and the number of antral contractions (P = 0.014) were greater for the 600 mL regimen. CONCLUSIONS: Larger meals are associated with distension of the gastric fundus and an increase in gastroesophageal reflux when compared with smaller, more frequent meals.

Comparing the efficacy and clinical outcome of telbivudine and entecavir naïve patients with hepatitis B virus-related compensated cirrhosis.

BACKGROUND AND AIM: There is limited data on the efficacy and outcome of telbivudine (LdT) therapy in patients with chronic hepatitis B and compensated cirrhosis. We evaluated LdT as first-line therapy in these patients and compared with those treated with entecavir (ETV). METHODS: We consecutively enrolled 88 chronic hepatitis B patients with compensated cirrhosis primarily treated with LdT at least for 2 years or less than 2 years but developed resistance, and evaluated the efficacy and clinical outcomes. Meanwhile, we matched a control group who treated with ETV for comparison. RESULTS: In LdT group, alanine aminotransferase normalization (65.8%), hepatitis B e antigen seroconversion (39.8%), hepatitis B virus (HBV) DNA undetectablility (71.6%), and virologic resistance (23.9%) were noted after 2 years treatment. Compared with ETV group, there were significant difference in HBV DNA undetectablility (P < 0.001) and virologic resistance (P < 0.001). In addition, the decline of serum hepatitis B surface antigen levels, hepatocellular carcinoma development, mortality, disease progression, and the change of renal function were similar. Cox regression analysis showed that pretreatment low albumin level and high model for end-stage liver disease scores were risk factors for disease progression. CONCLUSIONS: These results indicated that although LdT and ETV are similar in clinical outcomes for patients with HBV-related compensated cirrhosis, LdT still had lower HBV undetectablility and higher resistant rate after 2 years treatment, which was a challenge for being as first-line therapy in these patients who need lifelong therapy.

Calreticulin regulates hepatic stellate cell activation through modulating TGF-beta-induced Smad signaling.

Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM) as a wound healing process. Activated hepatic stellate cells (HpSCs) are the major producer of the ECM and play a central role in liver fibrogenesis. It has been widely accepted that elimination of activated HpSCs or reversion to a quiescent state can be a feasible strategy for resolving the disease, further highlighting the urgent need for novel therapeutic targets. Calreticulin (CRT) is a molecular chaperone that normally resides in the endoplasmic reticulum (ER), important in protein folding and trafficking through the secretory pathway. CRT also plays a critical role in calcium (Ca2+) homeostasis, with its Ca2+ storage capacity. In the current study, we aimed to demonstrate its function in directing HpSC activation. In a mouse liver injury model, CRT was up-regulated in HpSCs. In cellular experiments, we further showed that this activation was through modulating the canonical TGF-ß signaling. As down-regulation of CRT in HpSCs elevated intracellular Ca2+ levels through a form of Ca2+ influx, named store-operated Ca2+ entry (SOCE), we examined whether moderating SOCE affected TGF-ß signaling. Interestingly, blocking SOCE had little effect on TGF-ß-induced gene expression. In contrast, inhibition of ER Ca2+ release using the inositol trisphosphate receptor inhibitor 2-APB increased TGF-ß signaling. Treatment with 2-APB did not alter SOCE but decreased intracellular Ca2+ at the basal level. Indeed, adjusting Ca2+ concentrations by EGTA or BAPTA-AM chelation further enhanced TGF-ß-induced signaling. Our results suggest a crucial role of CRT in the liver fibrogenic process through modulating Ca2+ concentrations and TGF-ß signaling in HpSCs, which may provide new information and help advance the current discoveries for liver fibrosis.

Immune Responses to Anti-Hepatitis C Virus Antibodies during Pre-Liver Transplantation Direct-Acting Antiviral Therapy in Hepatitis C Virus-Infected Recipients Associated with Post-Liver Transplantation Allograft Injury.

BACKGROUND AND AIMS: The impact of antibody responses following direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV)-infected recipients before and after liver transplantation (LT) is still undetermined. METHODS: In this observational cohort study, we aimed to explore the association between changes in anti-HCV antibody titers following pre-LT DAA therapy and allograft injury, including biliary complications (BCs) and acute cellular rejection (ACR). RESULTS: A total of 153 cases were enrolled from January 2015 to February 2021. Serum anti-HCV antibody titers were assessed before and after (day 30) LT. Among all recipients, 31/153 (20.3%) had pre-LT DAA therapy (the DAA group) and 122/153 (79.7%) did not undergo pre-LT DAA therapy (the DAA-naïve group). A higher incidence of post-LT BCs was observed in the DAA group (p = 0.028). Compared with the DAA-naïve group, the DAA group had a significantly higher mean level of anti-HCV titer upregulation (p = 0.0024); furthermore, among the recipients with BCs (n = 28) and ACR (n = 41), those in the DAA group exhibited significantly higher mean levels of anti-HCV antibody titer upregulation (p < 0.005). CONCLUSIONS: In conclusion, we speculate that the upregulation of anti-HCV antibody titers, which might have been induced via the restoration of HCV-specific immune responses through pre-LT DAA therapy, was associated with post-LT allograft injury.

The effects of endoscopic-guided balloon dilations in esophageal and gastric strictures caused by corrosive injuries.

BACKGROUND: Esophageal stricture (ES) and gastric outlet obstruction (GOO) can occurred in patients injured by the ingestion of corrosive agents. These complications may occur concurrently but has not been reported in the literature. The aims of this study are to assess the effects and complications of endoscopic-guided balloon dilations (EBD) in patients with corrosive-induced upper gastrointestinal strictures, either ES or GOO alone and simultaneous occurrences of both (ES + GOO). METHODS: From July 2002 to December 2009, 36 patients with corrosive-induced upper gastrointestinal strictures in a tertiary hospital were recruited into this study. The patients were divided into three groups, ES group (n = 18), GOO (n = 7), and ES + GOO group (n = 11). All strictures were dilated under direct visualization by using through-the-scope balloon catheters to the end point of 15 mm. The end-point of treatment was successful ingestion of a solid or semisolid diet without additional dilation for more than 12 months. RESULTS: These 36 patients included 15 males and 21 females with average age of 47 years ranging from 25 to 79 years. The success rates for ES group is significantly better than GOO and ES + GOO group (83.3% vs. 57.1% vs. 36.4% p = 0.035). Less complications were observed in ES group than in GOO and ES + GOO group (16.7% vs. 42.9% vs. 36.4%, p = 0.041). GOO group needed more sessions of dilations in order to achieve success dilations than ES and GOO groups (13.7 ± 4.9 vs. 6.1 ± 4.7 vs. 5.5 ± 2.1, p = 0.011). CONCLUSIONS: Corrosive injuries complicated with ES can be effectively and safely treated by EBD. However, the success rates declined significantly in patients with GOO with or without ES and amore complications occurred.

Induction of antinuclear antibodies by de novo autoimmune hepatitis regulates alloimmune responses in rat liver transplantation.

Concanavalin A (Con A) is a lectin originating from the jack-bean and well known for its ability to stimulate T cells and induce autoimmune hepatitis. We previously demonstrated the induction of immunosuppressive antinuclear autoantibody in the course of Con A-induced transient autoimmune hepatitis. This study aimed to clarify the effects of Con A-induced hepatitis on liver allograft rejection and acceptance. In this study, we observed the unique phenomenon that the induction of transient de novo autoimmune hepatitis by Con A injection paradoxically overcomes the rejection without any immunosuppressive drug and exhibits significantly prolonged survival after orthotopic liver transplantation (OLT). Significantly increased titers of anti-nuclear Abs against histone H1 and high-mobility group box 1 (HMGB1) and reduced donor specific alloantibody response were observed in Con A-injected recipients. Induction of Foxp3 and IL-10 in OLT livers of Con A-injected recipients suggested the involvement of regulatory T cells in this unique phenomenon. Our present data suggest the significance of autoimmune responses against nuclear histone H1 and HMGB1 for competing allogeneic immune responses, resulting in the acceptance of liver allografts in experimental liver transplantation.

Telbivudine-Induced Myopathy: Clinical Features, Histopathological Characteristics, and Risk Factors.

BACKGROUND AND PURPOSE: Oral nucleos(t)ide analogs (NAs) are the mainstay treatment for chronic hepatitis B (CHB). Myotoxicity is an important extrahepatic effect related to NA treatment. Telbivudine is the NA for CHB that is frequently associated with muscle-related side effects. The risk factors for telbivudine-induced myopathy (TIM) are not yet clear. METHODS: This study characterized the clinical, magnetic resonance images (MRI), and pathological features of 12 TIM cases. A group of telbivudine-tolerant (TT) patients with CHB who received regular telbivudine treatment during the same period without the occurrence of myopathy was collected. Demographic and clinical factors were compared between the patients with TIM and the TT controls. Factors independently associated with TIM were identified using logistic regression analysis. RESULTS: The patients with TIM (males/females: 7/5, mean age: 57 years) developed myopathy after using telbivudine for a median period of 19.5 months. Muscle histopathology revealed abnormal proliferation, subsarcolemmal or sarcoplasmic accumulations, and ultrastructural defects of mitochondria. When compared with TT cases, patients with TIM had a lower estimated glomerular filtration rate and were more frequently positive for hepatitis B e antigen (HBeAg). CONCLUSIONS: Mitochondrial abnormalities are characteristic histopathological features, and impaired renal function and HBeAg positivity are risk factors for TIM. Telbivudine-induced mitochondrial dysfunction and immune activation related to mitochondrial damage and HBeAg serostatus changes may underlie TIM. Constant clinical surveillance of myopathy during telbivudine treatment is needed due to the significant latency of its development. Dose adjustment for impaired renal function does not eliminate the risk of TIM occurrence.

The effect of exogenous histone H1 on rat adipose-derived stem cell proliferation, migration, and osteogenic differentiation in vitro.

Adipose-derived stem cells (ASCs) are of great interest for the development of novel cell therapies due to their ease of isolation and expansion, immunosuppressive activity, and multilineage differentiation potential. However, the mechanisms underlying the therapeutic potential of ASCs remain to be elucidated. Others and we have shown that nuclear proteins such as histone H1 and high mobility group box 1 (HMGB1) play important roles in the maturation of dendritic cells (DCs). Furthermore, we previously demonstrated translocation of histone H1 from the nucleus to the cytoplasm and activation of mitogen-activated protein kinases (MAPKs) in DCs. In the present study, we confirmed that histone H1 does not alter the immunophenotype and immunosuppression potential of ASCs, but that histone H1 enhanced wound healing and increased interleukin (IL)-6 expression. Moreover, histone H1 treated-ASCs showed up-regulation of MAPKs extracellular-regulated kinase 1/2 (ERK1/2) and sequential NF-κB translocation. Finally, we found that culture in differentiation media supplemented with histone H1 enhanced ASC osteogenesis. In contrast, inhibition of histone H1 by small interfering RNA (siRNA) reduced osteogenic differentiation markers including ALP. These results suggest that histone H1 may be useful for induction of mesenchymal stem cells in tissue engineering and future potential ASC therapies.

A comparison of telbivudine and entecavir for chronic hepatitis B in real-world clinical practice.

OBJECTIVES: To evaluate the efficacy of telbivudine and entecavir in chronic hepatitis B (CHB) patients over a 1 year period. METHODS: Ninety-seven telbivudine-naive and 98 entecavir-naive CHB patients who had been treated for at least 1 year were enrolled. Serial serum hepatitis B virus (HBV) DNA levels were checked at baseline and at weeks 24 and 48 after treatment. RESULTS: Entecavir and telbivudine groups had similar baseline HBV DNA levels (5.9 ± 1.7 versus 6.0 ± 1.5 log copies/mL, P=0.529). The undetectable rate of HBV DNA after 1 year of treatment was significantly higher in the entecavir group than the telbivudine group (94.9% versus 82.0%, P=0.009). Resistance developed in 6.7% of the telbivudine-naive patients after 1 year compared with none of the entecavir-naive patients (P=0.009). However, there was a significant difference between the telbivudine and entecavir groups in hepatitis B e antigen (HBeAg) seroconversion 24 weeks after treatment (40% versus 12.5%, P=0.007). Multiple logistic regression analysis revealed that baseline alanine aminotransferase (ALT) >200 IU/L (P=0.008) was independently associated with HBeAg seroconversion. Applying the roadmap concept with ALT >2× upper limit of normal at baseline, telbivudine and entecavir had favourable outcomes in PCR negativity, ALT normalization, HBeAg seroconversion and resistance. CONCLUSIONS: In real-world clinical practice, telbivudine resulted in higher rates of HBeAg seroconversion and drug resistance at week 48 compared with entecavir. A combination with baseline ALT plus 24 week HBV DNA levels led to the lowest rates of resistance in HBeAg-positive telbivudine-naive patients and had the highest probability of HBeAg seroconversion in both entecavir- and telbivudine-naive patients.

Homogenous phenomenon of graft liver CYP2C19 genotypes after living donor liver transplantation.

BACKGROUND: The donor liver grafts with different allelic patterns do not affect CYP2C19 genotypes in the peripheral blood of living donor liver transplantation (LDLT) recipients. AIM: This study investigated the influence of graft liver CYP2C19 genotypes on recipients who received the same or different CYP2C19 genotypes from donors after LDLT. METHODS: There were 30 donors and 30 recipients with the same CYP2C19 genotypes and 47 donors and 47 recipients with different CYP2C19 genotypes. Genomic DNA was isolated from the liver tissue of recipients. The CYP2C19 haplotypes were determined by polymerase chain reaction. RESULTS: A homogenous phenomenon in the sequences of graft liver CYP2C19 genotypes was indicated because the recipients showed mixed patterns that were similar to that of the original donor after LDLT. A significant decrease in homozygous extensive metabolizer (HomEM) and an increase in poor metabolizer (PM) distribution were observed in recipients with different CYP2C19 genotypes from their donors compared with recipients with the same CYP2C19 genotype as their donors (P < 0·05). CONCLUSIONS: Homogenous phenomenon of sequence changes in graft liver CYP2C19 from the different genotypes between the donors and the recipients may play a role in graft stability by causing decreased HomEM and increased PM after LDLT.

Surveillance culture monitoring of double-balloon enteroscopy reprocessing with high-level disinfection.

BACKGROUND: Inadequate reprocessing of double-balloon enteroscopy (DBE) or of endoscopic accessories may result in iatrogenic infections and present a risk to public health. AIM: To use microbiological surveillance culture monitoring (SCM) to assess the adequacy of high-level disinfection (HLD) with standard reprocessing procedures of DBE. MATERIALS AND METHODS: We performed a prospective study on cultures collected from DBEs that had been treated by HLD by an automated endoscope washing machine (AEWM) decontamination cycle. This study included 42 cases with 57 cultures, which were collected consecutively between October 2009 and December 2010. In 31 cases, 31 cultures were collected from oral route DBE (mean patient age, 68·9 years), and in 23 cases, 26 cultures were collected from anal route DBE (mean patient age, 67·9 years). The results obtained were compared with those of our previous study of SCM on gastroscopy (GS) and colonoscopy (CS). The samples were collected by flushing 50 mL sterile distilled water into the suction channel and collecting the flow-through in a sterile container. The samples were then incubated at 37 °C and examined for bacterial growth. RESULTS: Before HLD, the positive culture rate was 83·9% (26/31) for the oral route DBE and 100% (26/26) for the anal route DBE (P = 0·0406). After HLD, the positive culture rate was 12·9% (4/31) for the oral route DBE and 19·2% (5/26) for the anal route DBE (P > 0·05). A linear trend relationship was found between positive SCM and the length and category of diagnostic instruments--GS, CS, oral route DBE and anal route DBE. CONCLUSIONS: Surveillance culture monitoring is a useful method to assess the effectiveness of HLD reprocessing of DBE. Machine washing may not achieve complete disinfection. Using AEWM regularly is mandatory to minimize cross-contamination and to ensure quality assurance. Additional procedures are necessary to employ for the longer and anal route DBE.

Randomized comparison of two non-bismuth-containing second-line rescue therapies for Helicobacter pylori.

BACKGROUND: Classical second-line anti-Helicobacter pylori includes proton-pump inhibitor, tetracycline, metronidazole, and bismuth salts, but alternative therapies are required owing to the restricted availability of the latter. Levofloxacin-containing triple therapy is recommended but is expensive. Besides, quinolone resistance in an endemic tuberculosis infection area like Taiwan is concerned. The low in vitro antibiotic resistance to amoxicillin and tetracycline in Taiwanese H. pylori strains implies that in vivo esomeprazole/amoxicillin/tetracycline (EAT) second-line rescue therapy may be effective. This study compared the efficacy of esomeprazole/amoxicillin/levofloxacin (EAL) and EAT second-line eradication therapies and determines the clinical factors influencing the efficacy of salvage regimens. MATERIALS AND METHODS: One hundred and twenty-eight patients who failed H. pylori eradication using the standard triple therapy for 7 days are randomly assigned to either EAL group (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, and levofloxacin 500 mg once daily) for 7 days or EAT group (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, tetracycline 500 mg four times daily) for 14 days. Follow-up endoscopy or urea breath test was performed 8 weeks later to assess treatment response. RESULTS: The eradication rates of EAL and EAT groups were 78.1 versus 75.0%, p = .676 (in intention-to-treat analysis) and 80.3 versus 80%, p = .0964 (per-protocol analysis). Both groups exhibited similar drug compliance (95.3 vs 96.9%, p = .952) but more adverse events in the EAT group (6.3 vs 12.5%, p = .225). CONCLUSIONS: Despite low in vitro drug resistances to amoxicillin and tetracycline, the efficacy of 14-day EAT regimens attained an unacceptable report card of 75% eradication rates in intention-to-treat analysis and was not even superior to the 7-day EAL regimen. Drug-drug interaction between combined antibiotics should be considered other than in vivo drug resistances.