Affordable Membrane Permeability Calculations: Permeation of Short-Chain Alcohols through Pure-Lipid Bilayers and a Mammalian Cell Membrane.

Determination of membrane permeability to small molecules from first-principles represents a promising approach for screening lead compounds according to their permeation properties upstream in the drug discovery process and prior to their synthesis. Theoretical investigation of permeation events requires, at its core, a molecular model of the membrane, and the choice of this model impacts not only the predicted permeability but also its relation to the experimental measurements commonly performed in pharmaceutical settings with a variety of cell lines capable of mimicking intestinal passive permeation. Homogeneous single-lipid bilayers have traditionally been utilized in computer simulations of membrane permeability predictions due to the ease of sampling all the relevant configurations, as well as the availability of parameters for a range of components of the biological membrane.

Link between Membrane Composition and Permeability to Drugs.

Prediction of membrane permeability to small molecules represents an important aspect of drug discovery. First-principles calculations of this quantity require an accurate description of both the thermodynamics and kinetics that underlie translocation of the permeant across the lipid bilayer. In this contribution, the membrane permeability to three drugs, or drug-like molecules, namely, 9-anthroic acid (ANA), 2',3'-dideoxyadenosine (DDA), and hydrocortisone (HYL), are estimated in a pure 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and in a POPC:cholesterol (2:1) mixture.

Impact of IL28B and PNPLA3 polymorphisms on treatment outcomes in patients infected with genotype 6 hepatitis C virus.

Background/aims: Interleukin-28B (IL28B) and patatin-like phospholipase domain containing 3 (PNPLA3) gene polymorphisms are associated with hepatitis C virus (HCV) clearance and fatty liver, respectively. We aimed to test if their polymorphisms are associated with virologic responses in Chinese chronic hepatitis C (CHC) patients.

Methods: This was a retrospective-prospective cohort study.

Adverse effects of vitamin D deficiency on outcomes of patients with chronic hepatitis B.

Background & Aims: Vitamin D is an immunomodulator that might be involved in the pathogenesis of viral hepatitis. We investigated the effects of vitamin D deficiency on long-term outcomes of patients with chronic hepatitis B (CHB).

Methods: We performed a prospective cohort study of 426 patients with CHB (65% male; mean age, 41 ± 13 years), who were enrolled from 1997 through 2000.

Noninvasive assessments of liver fibrosis with transient elastography and Hui index predict survival in patients with chronic hepatitis B.

Background And Aims: The prognostic role of noninvasive assessments of liver fibrosis has been evolving. Our aim was to investigate the prognostic value of liver stiffness measurement (LSM) with transient elastography and serum-based Hui index to predict hepatic events and deaths in chronic hepatitis B (CHB) patients.

Methods: The main prospective cohort included 1555 consecutive CHB patients referred for transient elastography examination; a subgroup of 980 patients underwent follow-up assessments at least 3 years later formed the serial cohort.

On-treatment alpha-fetoprotein is a specific tumor marker for hepatocellular carcinoma in patients with chronic hepatitis B receiving entecavir.

Unlabelled: Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) surveillance, which is criticized as neither sensitive nor specific in active hepatitis and liver cirrhosis. The aim of this study was to determine the performance of AFP as a tumor marker for HCC in entecavir-treated patients with chronic hepatitis B (CHB). This was a retrospective-prospective cohort study of 1,531 entecavir-treated patients under regular HCC surveillance with AFP and ultrasonography.

Liver fibrosis progression is uncommon in patients with inactive chronic hepatitis B: a prospective cohort study with paired transient elastography examination.

Background And Aims: The European Association for the Study of the Liver (EASL) defines the inactive hepatitis B virus (HBV) carrier state based on HBV DNA and alanine aminotransferase (ALT) levels. This study aimed to evaluate the risk of disease progression in such patients.

Methods: Three hundred sixty-one patients negative for hepatitis B e antigen (HBeAg) with HBV DNA levels < 20,000 IU/mL and normal ALT and without advanced fibrosis at baseline underwent liver stiffness measurement (LSM) by transient elastography between 2006 and 2008 and again between 2010 and 2012.

Liver fibrosis progression in chronic hepatitis B patients positive for hepatitis B e antigen: a prospective cohort study with paired transient elastography examination.

Background And Aim: Chronic hepatitis B patients in immune-reactive hepatitis B e antigen (HBeAg)-positive phase may have more rapid progression than those in immune-tolerant phase. We aimed to evaluate the risk of liver fibrosis progression in HBeAg-positive patients at different phases.

Methods: Two hundred forty-seven HBeAg-positive patients without advanced fibrosis at baseline underwent liver stiffness measurement (LSM) by transient elastography in 2006-2008 and again in 2010-2012.

Serum hepatitis B surface antigen kinetics in severe reactivation of hepatitis B e antigen negative chronic hepatitis B patients receiving nucleoside/nucleotide analogues.

Background: Kinetics of serum hepatitis B surface antigen (HBsAg) level in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients presented with severe reactivation and received oral antiviral therapy is unknown. We aimed to investigate the kinetics of HBsAg level among these patients.

Methods: HBeAg-negative patients on antiviral therapy with follow-up for 2 years were studied.

Molecular characterization of the fecal microbiota in patients with nonalcoholic steatohepatitis--a longitudinal study.

Background: The human gut microbiota has profound influence on host metabolism and immunity. This study characterized the fecal microbiota in patients with nonalcoholic steatohepatitis (NASH). The relationship between microbiota changes and changes in hepatic steatosis was also studied.

Antiviral drug resistance testing in patients with chronic hepatitis B.

Background: Antiviral drugs against hepatitis B virus are limited by the emergence of drug resistance.

Aims: We aimed to study the impact of drug resistance testing on treatment decisions.

Methods: In part 1 of this study, consecutive patients with chronic hepatitis B who had antiviral drug resistance testing were studied.

Viral determinants of hepatitis B surface antigen seroclearance in hepatitis B e antigen-negative chronic hepatitis B patients.

Background: We studied whether quantification of serum HBsAg and HBV DNA levels could predict spontaneous HBsAg clearance in patients with negative hepatitis B e antigen (HBeAg).

Methods: Serum HBsAg and HBV DNA levels were measured at baseline among a longitudinal cohort of 103 HBeAg-negative patients recruited since 1997.

Results: Twelve (12%) patients developed HBsAg seroclearance after 88 ± 26 months (range, 21-139) of follow-up.

A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B.

Unlabelled: Serum hepatitis B surface antigen (HBsAg) quantification has been suggested to reflect the concentration of covalently closed circular DNA in the liver. We aimed to investigate the HBsAg levels at different stages of chronic hepatitis B and the changes in HBsAg level during the natural progression of disease. One hundred seventeen untreated patients with chronic hepatitis B were studied with longitudinal follow-up for 99 ± 16 months.

Durability of peginterferon alfa-2b treatment at 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B.

Unlabelled: Approximately 30%-40% of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B treated with peginterferon and/or lamivudine achieve HBeAg seroconversion 6 months after the end of treatment. The durability and long-term effect of treatment are unknown. In this study, 85 HBeAg-positive patients who received peginterferon alfa-2b 1.

Reactivation of hepatitis B virus infection with persistently negative HBsAg on three HBsAg assays in a lymphoma patient undergoing chemotherapy.

In patients with occult hepatitis B virus (HBV) infection, acute exacerbation may occur when they become immunocompromised. Usually, these patients develop hepatitis B surface antigen (HBsAg) seroreversion during the flare. Here we report on a patient with occult HBV infection, who developed HBV exacerbation after chemotherapy for diffuse large B-cell lymphoma.

Hepatitis B virus genotype C is associated with more severe liver fibrosis than genotype B.

Background & Aims: Histologic analyses of liver fibrosis have been limited by small sample sizes and the predominance of samples from patients with active hepatitis.

Methods: We performed a prospective study of transient elastography in treatment-naive patients with chronic hepatitis B, to investigate the relationship between hepatitis B virus (HBV) genotype and liver fibrosis. A validated liver stiffness measurement algorithm was used to define insignificant fibrosis and advanced fibrosis.

Lamivudine monoprophylaxis and adefovir salvage for liver transplantation in chronic hepatitis B: a seven-year follow-up study.

In Asia Pacific countries, lamivudine is used frequently as the sole prophylaxis for hepatitis B virus (HBV) recurrence after liver transplantation due to financial consideration. The aim was to evaluate the long-term outcome of lamivudine monoprophylaxis with adefovir salvage for liver transplantation in chronic hepatitis B. Consecutive chronic hepatitis B patients who received liver transplantation from 1999 to 2003 and with at least 12 months follow up were studied.

Genotype-specific genomic markers associated with primary hepatomas, based on complete genomic sequencing of hepatitis B virus.

We aimed to identify genomic markers in hepatitis B virus (HBV) that are associated with hepatocellular carcinoma (HCC) development by comparing the complete genomic sequences of HBVs among patients with HCC and those without. One hundred patients with HBV-related HCC and 100 age-matched HBV-infected non-HCC patients (controls) were studied. HBV DNA from serum was directly sequenced to study the whole viral genome.

High viral load and hepatitis B virus subgenotype ce are associated with increased risk of hepatocellular carcinoma.

Purpose: We aimed to investigate the impact of hepatitis B virus (HBV) DNA and HBV genotypes/subgenotypes on the risk of hepatocellular carcinoma (HCC).

Patients And Methods: A prospective cohort of patients infected with chronic HBV in a surveillance program for HCC since 1997 was studied. Ultrasound and alpha-fetoprotein evaluation were regularly performed to detect HCC.

Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response.

Background & Aims: We aimed to evaluate serum hepatitis B surface antigen (HBsAg) quantitation as a surrogate marker for covalently closed circular DNA (cccDNA) and intrahepatic hepatitis B virus (HBV) DNA, and as a predictor of sustained virologic response to peginterferon and lamivudine combination therapy.

Methods: Twenty-six hepatitis B e antigen-positive chronic hepatitis B patients receiving combination treatment of 32-week peginterferon alfa-2b and 2-year lamivudine were studied. All patients had liver biopsy before and after treatment for cccDNA and intrahepatic HBV DNA measurement.

Phylogenetic, virological, and clinical characteristics of genotype C hepatitis B virus with TCC at codon 15 of the precore region.

Hepatitis B virus (HBV) with T-1856 of the precore region is always associated with C-1858 (i.e., TCC at nucleotides 1856 to 1858), and it is reported only in genotype C HBV isolates.

Epidemiological and virological characteristics of 2 subgroups of hepatitis B virus genotype C.

Background: We aimed to investigate the characteristics of hepatitis B virus (HBV) genotype C subgroups in Hong Kong and their relationship with HBV genotype C in other parts of Asia.

Methods: Full-genome nucleotide sequences of 49 HBV genotype C isolates from Chinese patients with chronic hepatitis B were compared with the sequences of 69 HBV genotype C isolates and 12 non-genotype C isolates in the GenBank database. Phylogenetic analysis was performed to define the subgroups of HBV genotype C on the basis of >4% heterogeneity of the entire HBV genome.

Genotype B hepatitis B virus is associated with severe icteric flare-up of chronic hepatitis B virus infection in Hong Kong.

Objective: We aimed to investigate the association of viral genotype and the development of icteric flare-up (IF) in chronic hepatitis B virus (HBV) infection.

Methods: Twenty-one consecutive patients suffering from IF of chronic HBV infection, defined as elevation of ALT over five times the upper limit of normal, together with either bilirubin > 50 IU/L or elevated bilirubin plus PT > 3 s prolonged, were studied. Patients from three stages of HBV-related chronic liver disease were studied as controls: 1) asymptomatic carriers (31 patients), defined as persistent normal ALT for at least 2 yr; 2) active early cirrhosis (49 patients), defined as Child's A liver cirrhosis plus HBV DNA > 106 Eq/ml; and 3) decompensated cirrhosis (31 patients), defined as Child's B or C liver cirrhosis with complications.