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PRéCIS:: A large cohort undergoing cataract extraction was retrospectively analyzed to ascertain the degree of real-world intraocular pressure (IOP) reduction in normal eyes and those with glaucoma, and a predictive formula was developed., Purpose: The purpose of this study was to define the real-world degree of IOP reduction after cataract extraction to guide its role as an isolated intervention for glaucoma., Materials and Methods: A retrospective analysis was carried out of clinical data collected in 8 clinical sites in the United Kingdom from an electronic medical record system between January 2006 and May 2015. A total of 20,508 eyes without known pathology and 2251 eyes from patients with glaucoma undergoing phacoemulsification and intraocular lens insertion were included. Eyes with intraoperative complications, undergoing additional procedures, axial lengths outside 22 to 26.5 mm, preoperative IOP under 6 mm Hg or over 30 mm Hg, and copathology, except for amblyopia or glaucoma, were excluded. The main outcome measure was the change in preoperative IOP compared with the next recorded visit for up to 12 weeks., Results: In eyes without pathology, the mean reduction in IOP was 1.40 mm Hg (±3.74) compared with 1.03 (±5.02), P-value <0.001, in eyes with a diagnosis of glaucoma. A multiple linear regression model identified preoperative IOP, a glaucoma diagnosis, preoperative corrected visual acuity, age, and axial length as determinants of IOP reduction. The model was validated against an independent cohort., Conclusions: We quantify mean IOP reduction achieved in a real-world setting from cataract surgery alone. In glaucomatous eyes where angle closure is not differentiated, phacoemulsification alone yields only a modest reduction of IOP.

Background: Portal or bridging fibrosis is an indication for antiviral treatment in patients with chronic hepatitis B (CHB). An early marker predictive of liver fibrosis in hepatitis B e antigen (HBeAg)-negative CHB patients can alert clinicians to plan for treatment before disease progression., Goals: To predict early and significant liver fibrosis (Ishak score ≥2) in HBeAg-negative CHB by validating several noninvasive markers derived from CHC., Study: One hundred seventy-seven consecutive treatment-naive HBeAg-negative CHB patients who underwent liver biopsy were divided into a training group (n=121) and a validation group (n=56). Factors associated with liver fibrosis were analyzed., Results: Multivariate analysis identified Lok's model ≥0.87, cirrhosis discriminant score greater than 4, and positive alanine aminotransferase ratio platelet score as independent factors associated with liver fibrosis in the training group. The area under the receiver operating characteristic curve revealed that Lok's model was better than cirrhosis discriminant score in predicting liver fibrosis in both the training and the validation groups. In patients with hepatitis B virus DNA greater than 2000 IU/mL or greater than 20,000 IU/mL, Lok's model showed equal prediction value (area under the receiver operating characteristic curve 0.709 and 0.704, respectively). Lok's model could also discriminate high and low hepatitis B virus DNA loads. In general, liver biopsy can be avoided in one-third (58 of 177) of patients by Lok's model., Conclusions: Lok's model ≥0.87 can be an early marker of liver fibrosis in HBeAg-negative CHB patients. Lok's model has clinical applications not only for CHC, but also for HBeAg-negative CHB.

Hepatitis B virus (HBV) recurrence rates of 0-16% had been reported in patients maintained on nucleoside analogues (NA) after hepatitis B immunoglobulin (HBIG) discontinuation after orthotopic liver transplantation (OLT). However, follow-up in most studies was short. We aimed to determine the long-term risk of HBV recurrence using this strategy. All HBV patients who received > or =7 doses of intravenous HBIG after OLT, with no HBV recurrence while receiving HBIG, and who eventually discontinued HBIG and were maintained on NA, were included. HBV recurrence was defined as HBsAg-positive or HBV DNA > or =5 log copies/mL on 2 consecutive occasions. Twenty-one patients met the inclusion criteria. Immediate post-OLT prophylaxis was combination HBIG and NA in 15 patients, whereas 6 patients received HBIG monotherapy for 62-109 months before NA was added. HBIG was discontinued a median of 26 (range, 0.2-121) months after OLT. Median follow-up post-HBIG discontinuation was 40 (range, 5-51) months. Only 1 patient, who had 12 months of HBIG and was noncompliant to NA therapy, had HBV recurrence, 34 months after HBIG discontinuation. One patient had HBV DNA of 3.3 log copies/mL 47 and 48 months after HBIG discontinuation but remained HBsAg-negative. Lamivudine-resistant mutations were detected in both patients. Probability of HBV recurrence was 0% and 9% at 2 and 4 years after HBIG discontinuation. Three patients had 1-2 episodes of transiently detectable HBV DNA. All were HBV DNA and HBsAg negative on repeated tests over a period of 2-36 months. Maintenance therapy with NA after discontinuation of long-term HBIG therapy is associated with a low risk of HBV recurrence after OLT in compliant HBV patients., ((c) 2007 AASLD.)

Variants in the precore (G(1896)A) and core promoter (A(1762)T, G(1764)A) regions of hepatitis B virus (HBV) may be related to serum HBV DNA levels and severity of liver disease. The aims of this nationwide study were to determine the prevalence of HBV precore/core promoter variants in the United States and the association between these variants and patient demographics, HBV genotypes, serum HBV DNA level, and severity of liver disease. A total of 694 consecutive chronic HBV-infected patients seen in 17 U.S. liver centers during a 1-year period were enrolled. Demographic, clinical, and laboratory data were collected. Sera were tested for HBV genotypes as well as precore and core promoter variants by line-probe assays. Quantitative HBV DNA levels were determined using Cobas Amplicor HBV Monitor kits. Precore and core promoter variants were found in 27% and 44% of patients with chronic HBV infection in the United States. Precore and core promoter variants were more common in hepatitis B e antigen (HBeAg)-negative than in HBeAg-positive patients (precore, 38% vs. 9%; core promoter, 51% vs. 36%; respectively, P <.001). The prevalence of these variants was related to ethnicity, place of birth, and HBV genotypes. Patients with core promoter variants were more likely to have hepatic decompensation. Precore and/or core promoter variants were associated with higher serum HBV DNA levels in HBeAg-negative but not in HBeAg-positive patients. In conclusion, HBV precore and core promoter variants are not rare in the United States. Physicians should be aware of the existence of HBV precore and core promoter variants and the clinical condition of "HBeAg-negative chronic hepatitis."

Hepatitis B virus (HBV) genotype and precore/core promoter mutations have been implicated in spontaneous and interferon alfa (IFN-alpha)-related hepatitis B e antigen (HBeAg) seroconversion. We performed a retrospective analysis of a previously reported randomized controlled trial to determine the effects of HBV genotype and precore/core promoter mutations on IFN-alpha response in patients with HBeAg-positive chronic hepatitis. Clinical data and stored sera from 109 (95%) patients in the original trial were analyzed. Seventy-three patients received IFN-alpha and 34 received no treatment (controls). Almost all patients had HBV genotypes B (38%) and C (60%). Antiviral response was achieved in 39% and 17% of IFN-alpha-treated patients (P =.03) and in 10% and 8% of untreated controls (P =.88) with HBV genotype B and C, respectively. Multivariate analysis identified HBV genotype B, elevated pretreatment alanine aminotransferase (ALT) levels, and low pretreatment HBV-DNA levels but not IFN-alpha treatment as independent factors associated with antiviral response. Among the 66 patients with elevated pretreatment ALT level, antiviral response was achieved in 57% and 21% of IFN-alpha-treated patients (P =.019), and in 25% and 8% of untreated controls (P =.45) with HBV genotype B and C, respectively. Multivariate analysis showed that genotype B and low pretreatment HBV-DNA levels were independent predictors of antiviral response. In conclusion, our data showed that HBV genotype B was associated with a higher rate of IFN-induced HBeAg clearance compared with genotype C. Stratification for HBV genotypes should be considered in future clinical trials of antiviral therapy of chronic hepatitis B.

The goals of this retrospective study were to determine whether there is a threshold hepatitis B virus (HBV) DNA value associated with spontaneous or antiviral therapy-related hepatitis B e antigen (HBeAg) clearance. We also investigated whether there is an HBV DNA value that can be used for differentiating inactive carriers from patients with HBeAg-negative chronic hepatitis B. HBV DNA levels in sequential serum samples of 165 Chinese patients with different stages of chronic HBV infection were quantified by a polymerase chain reaction (PCR)-based assay. Our results showed that almost all of the patients (89%) who remained HBeAg-positive had HBV DNA levels that were persistently above 10(5) copies/mL. Serum HBV DNA levels decreased by a mean of 3 log(10) in patients with HBeAg loss, but 51% had levels above 10(5) copies/mL at the time HBeAg first became undetectable. Mean serum HBV DNA levels were significantly lower in HBeAg-negative patients. HBV DNA value above 10(5) copies/mL would exclude all inactive carriers, but 45% of patients with HBeAg-negative chronic hepatitis would also be excluded if testing were only performed at presentation and 30% would be excluded if testing were performed on 3 occasions. In conclusion, serum HBV DNA levels decreased significantly in patients with HBeAg loss, but there was no threshold HBV DNA level associated with HBeAg clearance. Given the fluctuating course of HBeAg-negative chronic hepatitis, it is not possible to define a single cutoff HBV DNA value for differentiating inactive carriers from patients with HBeAg-negative chronic hepatitis.

Results of liver transplantation (LT) for hepatitis B have improved significantly with the use of hepatitis B immune globulin (HBIG) and/or lamivudine. The aim of this study is to review the long-term outcome of patients who underwent LT for hepatitis B. Records of 41 patients who underwent LT for hepatitis B and survived 3 months or longer post-LT were reviewed. Twenty patients were administered no immunoprophylaxis or short-term intramuscular HBIG, whereas 21 patients were administered high-dose intravenous (IV) HBIG. Median post-LT follow-up in these 2 groups was 76 months (range, 4 to 155 months) and 25 months (range, 4 to 68 months), respectively. Hepatitis B recurred in 15 (75%) and 4 patients (19%) who underwent LT in the pre-HBIG and post-HBIG eras, respectively. Cumulative rates of recurrent hepatitis B at 1 and 3 years post-LT in these 2 groups were 66% and 77% and 20% and 20%, respectively (P <.001). Recurrent hepatitis B in the post-HBIG era correlated with antibody to hepatitis B surface antigen titer less than 100 IU/L. Nine patients with recurrent hepatitis B were administered lamivudine for 13 to 49 months (median, 28 months); 6 patients continued to have stable or improved liver disease, whereas 3 patients developed virological breakthrough with slow deterioration of liver disease. Long-term IV HBIG is effective in preventing recurrent hepatitis B. The risk for recurrent hepatitis B is negligible after the first year post-LT. Among patients with no virological breakthrough, lamivudine can stabilize or improve liver disease for up to 4 years in patients with recurrent hepatitis B post-LT.

Portal hypertension is associated with increased hepatic and collateral resistance to an increased portal blood flow. Endothelin-1 (ET-1) can induce intrahepatic vasoconstriction and consequently increase portal pressure. It is unknown if ET-1 also modulates portal pressure by a direct vasoconstrictive effect on collaterals. This study investigated the collateral vascular responses to ET-1, the receptors in mediation, and the regulation of ET-1 action by nitric oxide and prostaglandin. The portal-systemic collaterals of partially portal vein-ligated rats were tested by in situ perfusion. The concentration-response curves of collaterals to graded concentrations of ET-1 (10(-10)-10(-7) mol/L) with or without BQ-123 (ET(A) receptor antagonist, 2 x 10(-6) mol/L), BQ-788 (ET(B) receptor antagonist, 10(-7) mol/L) or both were recorded. In addition, the collateral responses to ET-1 with preincubation of n(omega)-nitro-L-arginine (NNA; 100 mol/L), indomethacin (INDO; 10 mol/L), or in combination were performed. ET-1 increased the perfusion pressure of collaterals and its effect was significantly suppressed by BQ-123 alone and BQ-123 plus BQ-788, but not BQ-788 alone (P <.05). Incubation with NNA, INDO, or both significantly enhanced the response of collaterals to ET-1 (P < .05). These results show that ET-1 produces a direct vasoconstrictive effect on the collateral vessels of portal hypertensive rats. This effect is mediated by ET(A,) but not ET(B), receptors. Both nitric oxide and prostaglandin modulate the collateral vascular response to ET-1 and may therefore participate in the development and maintenance of portal hypertension.

This study investigated the effect of vasopressin on portal-systemic collaterals in portal hypertensive rats and the influence of nitric oxide (NO) and prostaglandin on the responsiveness of collateral vessels to vasopressin. The vascular responsiveness to graded concentrations of vasopressin was tested with or without the incubation of n(omega)-nitro-L-arginine (NNA) (100 micromol/L) and/or indomethacin (10 micromol/L) in perfused collateral vascular beds of rats with portal hypertension induced by partial portal vein ligation. In addition, concentration-response curves to vasopressin with incubation of a vasopressin V(1) receptor antagonist d(CH(2))(5)Tyr(Me) arginine vasopressin and concentration-response curves to a V(2) receptor agonist 1-desamino-8-D-arginine vasopressin were performed. Vasopressin significantly increased the perfusion pressure of collaterals, and this effect was suppressed by the addition of the V(1) receptor antagonist. Perfusion with the V(2) receptor agonist had no effect on the collaterals. Incubation with NNA, indomethacin, or both significantly potentiated the response of collaterals to vasopressin. In addition, the pressor response to vasopressin in the combination group was significantly higher than that in the NNA-alone group. The results show that vasopressin produces a direct vasoconstrictive effect on the portal-systemic collaterals of portal hypertensive rats. This effect is mediated by the vasopressin V(1,) but not V(2), receptors. The attenuation of the response to vasopressin by NO and prostaglandin suggest a function role of both mediators in the regulation of the portal-systemic collateral circulation in portal hypertensive rats.