Cheng-Liang Liu

Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update

Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts’ personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.

Donor–acceptor polymers for advanced memory device applications

Organic materials for memory devices have attracted significant scientific interest recently due to the advantages of rich structure flexibility, low cost, solution processability, and three-dimensional stacking capability. This minireview highlights the recent developments in donor–acceptor polymers for resistive switching memory device applications including conjugated polymers, functional polyimides, non-conjugated pendent polymers, and polymer composites. It emphasizes the structure-memory characteristic relationship of donor–acceptor polymers for advanced memory device applications.

Polymeric charge storage electrets for non-volatile organic field effect transistor memory devices

In this review, we present the effects of the chemical structure and composition of polymer or composite electrets on tuning the memory characteristics of the non-volatile organic field effect transistor (OFET) memory devices, including surface polarity, π-conjugation length, architecture, donor–acceptor strength, and interface energy barrier. The recent progress in developing polymer-based charge storage electrets is highlighted in order to provide insights into understanding the operation mechanism and the molecular design–memory properties relationship, as well as improving the overall performance of OFET memory devices.

Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in Taiwan

Summary.  Previous studies in Caucasian patients showed treatment of chronic hepatitis C with pegylated interferon/ribavirin was well tolerated, and produced a higher response rate especially in genotype 1 infections. However, it is unknown whether this conclusion can be extrapolated to patients with Chinese ethnic origin. A total of 153 patients with biopsy‐proven chronic hepatitis C were randomly assigned to receive either weekly injection of peginterferon α‐2b 1.5 mcg/kg plus oral ribavirin (1000 or 1200 mg/day, depending on body weight) (PEG group, n = 76) or 3 MU of interferon α‐2b t.i.w. plus ribavirin (IFN group, n = 77) for 24 weeks. Sustained virological response (SVR) was defined as the sustained disappearance of serum hepatitis C virus (HCV) RNA at 24 weeks after the end of treatment by polymerase chain reaction assay. Baseline demographic, viral and histological characteristics were comparable between the two groups. Using an intent‐to‐treat analysis, HCV genotype 1 patients showed a significantly higher SVR in patients receiving PEG‐IFN rather than IFN (65.8%vs 41.0%, P = 0.019), but no difference was found in genotype non‐1 patients (PEG vs IFN: 68.4%vs 86.8%, P = 0.060). Genotype 1 patients (28.6%) in the PEG‐IFN group relapsed, as compared with 52.9% in the IFN group (P = 0.040). Multivariate analyses showed early virological response at week 12 of therapy and genotype non‐1 were significant predictors to SVR. As compared with the IFN group, patients receiving PEG‐IFN had a significantly higher rate of discontinuation, dose reduction, fever, headache, insomnia, leucopenia and thrombocytopenia. In genotype 1 chronic hepatitis C Chinese patient, PEG‐IFNα2b ribavirin had significantly better SVR and lower relapse rate when compared to IFN/ribavirin. Both regimens can be recommended for genotype non‐1 chronic hepatitis C Chinese patients. However, a higher rate of adverse events and discontinuance of therapy were noted in patients treated with PEG‐IFNα2b ribavirin.

Pegylated interferon α-2a versus standard interferon α-2a for treatment-naïve dialysis patients with chronic hepatitis C: a randomised study

Background: Chronic hepatitis C virus (HCV) infection is prevalent in dialysis patients, and standard interferon monotherapy is the current standard of care for such patients. Aim: To investigate whether pegylated interferon has a better therapeutic efficacy and safety profile than standard interferon in dialysis patients with chronic hepatitis C. Methods: 50 such patients were randomly assigned to receive either pegylated interferon α-2a 135 μg subcutaneously once per week or standard interferon α-2a 3 million units subcutaneously thrice per week for 24 weeks. The primary efficacy and safety end points were sustained virological response (SVR) by intention-to-treat analysis and treatment-related withdrawal rate during the study. Results: In univariate analysis, patients receiving pegylated interferon α-2a tended to have a higher sustained virological response (SVR) than those receiving standard interferon α-2a (48% vs 20%, p = 0.07). By using multivariate analysis, treatment with pegylated interferon α-2a (p = 0.02) and pretreatment HCV RNA level <800 000 IU/ml (p = 0.007) were independently predictive of an SVR. All patients failing to achieve a rapid virological response (RVR) could not achieve an SVR. In addition, patients receiving pegylated interferon α-2a had a significantly lower treatment-related withdrawal rate than those receiving standard interferon α-2a (0% vs 20%, p = 0.04). Conclusions: Pegylated interferon α-2a once weekly provides more effective and safer therapy than standard interferon α-2a thrice weekly for treatment-naïve dialysis patients with chronic hepatitis C.

New random copolymers with pendant carbazole donor and 1,3,4-oxadiazole acceptor for high performance memory device applications

New non-conjugated random copolymers containing pendent electron-donating 9-(4-vinylphenyl)carbazole (VPK) and electron-accepting 2-phenyl-5-(4-vinylphenyl)-1,3,4-oxadiazole (OXD) or 2-(4-vinylbiphenyl)-5-(4-phenyl)-1,3,4-oxadiazole (BOXD) were successfully synthesized by nitroxide-mediated free radical polymerization (NMRP) method. The prepared random copolymers are denoted as P(VPKxOXDy) or P(VPKxBOXDy) with three different electron donor/acceptor (x/y) ratios of 8/2, 5/5, and 2/8. The electrical switching behavior based on the ITO/polymer/Al device configuration could be tuned through the donor/acceptor ratio or acceptor trapping ability. Both experimental and theoretical results indicated that the charge transfer between the pendant donor and acceptor was relatively weak without significant orbital hybridization. In addition, the low-lying HOMO energy level of OXD or BOXD units as compared to VPK units created the trapping environment. Therefore, distinct electrical current–voltage (I–V) characteristics changed between the diode, the volatile memory, and the insulator depending on the relative donor/acceptor ratios of 10/0, 8/2, and (5/5, 2/8 and 0/10), respectively. The memory device based on P(VPK8OXD2) or P(VPK8BOXD2) copolymers exhibited volatile static random access memory (SRAM) behavior with an ON/OFF current ratio of approximately 104–105, up to 107 read pulses, and retention time of more than 1 h. The unstable ON state in the device was due to the shallow trapped holes with spontaneously back transferring of charge carriers when the electric field was removed and thus exhibited a volatile nature. The slightly lower HOMO level of OXD moieties than that of BOXD led to the P(VPK8OXD2) device storing the charge for a longer period of time. The present study suggested the high performance polymer memory devices could be achieved by changing the donor/acceptor ratio or chemical structure.

Single‐Crystal C60 Needle/CuPc Nanoparticle Double Floating‐Gate for Low‐Voltage Organic Transistors Based Non‐Volatile Memory Devices

Low-voltage organic field-effect transistor memory devices exhibiting a wide memory window, low power consumption, acceptable retention, endurance properties, and tunable memory performance are fabricated. The performance is achieved by employing single-crystal C60 needles and copper phthalocyanine nanoparticles to produce an ambipolar (hole/electron) trapping effect in a double floating-gate architecture.

Non-volatile memory devices based on polystyrene derivatives with electron-donating oligofluorene pendent moieties.

We report bistable non-volatile memory devices based on polystyrene derivatives containing pendent electron-donating mono-, di-, and tri(9,9-dihexylfluorene), which are denoted as poly(St-Fl), poly(St-Fl(2)), and poly(St-Fl(3)), respectively. The effects of the oligofluorene chain lengths and polymer surface structures on the memory characteristics were explored. Poly(St-Fl)-, poly(St-Fl(2))-, and poly(St-Fl(3))-based devices exhibited a flash memory characteristic with different turn-on threshold voltages of 2.8, 2.0, and 1.8 V, respectively, which was on the reverse trend with the highest occupied molecular orbital levels of -5.86, -5.80, and -5.77 eV. Moreover, the memory device showed a high ON/OFF current ratio of 2.5 x 10(4) and a long retention time of 10(4) s. The possible mechanism of the switching behavior was explained by the space-charge-limited-current theory and filamentary conduction. The larger aggregation domain size of the polymer thin film processed from the mixed solvent of chlorobenzene/N,N-dimethylformamide probably promoted the diffusion of the Al atoms into the polymer film and formed the conduction channel. Thus, it significantly reduced the turn-on threshold voltage on the studied polymer memory devices. The present study suggested that the polymer memory characteristics could be efficiently tuned through the pendent conjugated chain length and surface structures.

A poly(fluorene-thiophene) donor with a tethered phenanthro[9,10-d]imidazole acceptor for flexible nonvolatile flash resistive memory devices.

A conjugated poly(fluorene-thiophene) donor and a tethered phenanthro[9,10-d]imidazole acceptor (PFT-PI) was used as the active layer in flexible nonvolatile resistor memory devices with low threshold voltages (±2 V), low switching powers (∼100 μW cm(-2)), large ON/OFF memory windows (10(4)), good retention (>10(4) s) and excellent endurance against electric and mechanical stimulus.

Flexible polymer memory devices derived from triphenylamine–pyrene containing donor–acceptor polyimides

Organic polymer based electrical memory devices have attracted significant scientific interest for flexible electronics. However, molecular design principles of polymers with specified memory characteristics on flexible substrates remain challenges. Herein we developed new triphenylamine–pyrene containing donor–acceptor polyimides (PIs) on flexible poly(ethylene naphthalate) (PEN)/Al/PIs/Al cross-point devices, which showed the memory characteristics changing from volatile to nonvolatile via the relative copolymer ratio. The PIs were prepared from the diamines 4,4′-diamino-4′′-methyltriphenylamine (AMTPA) or N,N-bis(4-aminophenyl)aminopyrene (APAP) and the dianhydride 4,4′-(hexafluoroisopropylidene)diphthalic anhydride (6FDA), with relative AMTPA/APAP molar compositions of 100/0, 95/5, 90/10 and 0/100. As the APAP content increased, the memory device characteristics changed from volatile to nonvolatile behavior of flash and write once read many (WORM), since the pyrene moiety could stabilize the radical cation of the APAP moieties. The threshold voltage, ON/OFF ratio, and retention ability were within −3 V, more than 104, and 104 s, respectively. Additionally, the endurance and bending cyclic measurements confirmed that the flexible PI memory devices exhibited excellent reliability and mechanical stability. A possible switching mechanism based on the charge transfer interaction was proposed through molecular simulation and fitted with physical conduction models in OFF and ON states. The manipulation of the memory volatility through tailoring the molecular design and plastic electronic devices demonstrated promising applications of donor–acceptor PIs in integrated memory devices.