Quantitative analysis of the effects of audio biofeedback on weight-bearing characteristics of persons with transtibial amputation during early prosthetic ambulation

Author name used in this publication: Daniel H.K. ChowVersion of RecordPublishe

Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B

postprin

Rationale and design of the screening of pulmonary hypertension in systemic lupus erythematosus (SOPHIE) study

published_or_final_versio

Comparison of the efficacy of lamivudine and famciclovir in Asian patients with chronic hepatitis B: Results of 24 weeks of therapy

Lamivudine therapy improves hepatic necroinflammatory activity, decreases progression of fibrosis, and suppresses hepatitis B virus (HBV) replication. Famciclovir has also been shown to have some effect in the suppression of HBV replication. The aim of the study was to compare the effect of treatment with lamivudine and famciclovir on serum HBV DNA levels in patients with chronic hepatitis B and to assess safety. A prospective randomised clinical study was carried out on 100 patients with chronic hepatitis B infection (50 patients received lamivudine 100 mg daily and 50 patients received famciclovir 500 mg three times a day for 12 weeks. From the twelfth week onwards, patients were offered lamivudine 100 mg daily up to 48 weeks). Significantly more patients treated by lamivudine than by famciclovir had undetectable HBV DNA levels after 12 weeks of therapy (P < 0.001). The median HBV DNA levels were significantly lower in the lamivudine-treated patients from the second week of treatment onwards (P < 0.001 for all time points up to 12 weeks). At week 16, 4 weeks after the famciclovir treated patients were put on lamivudine, there was no longer any difference in HBV DNA levels between the two groups of patients. Both treatments were well tolerated and no serious adverse events were reported. It was concluded that in Chinese patients with chronic hepatitis B infection, lamivudine achieved effective suppression of HBV DNA levels within 4 weeks of therapy whereas famciclovir had a significantly weaker action. © 2002 Wiley-Liss, Inc.link_to_subscribed_fulltex

Sequential therapy using lamivudine in entecavir-treated patients with undetectable HBV DNA–results at 48 weeks

Background: The aim of this study was to determine the efficacyof entecavir-lamivudine sequential therapy in patients withundetectable viral load and normal ALT after initial entecavirtreatment. If effective, this may result in reducing the cost of ther-apy. Methods: This is a 2-year prospective trial of 50 patientstreated on entecavir 0.5 mg daily for over 6 months, and hadachieved normal ALT and undetectable HBV DNA (20 IU/mL on 3 consecutive measurements,were switched back to entecavir. Mutational analysis using line-probe assay would be performed at weeks 0, 24, 48, and 96.Results: Of the 50 patients, 48 patients had follow-up to 48weeks. There were no significant differences at the time of treat-ment assignment between the entecavir-entecavir and the ente-cavir-lamivudine group with respect to age, gender, HBeAgstatus, and duration of prior entecavir treatment. There was noelevation of ALT observed in any patients during the 48 weekperiod. At 24 weeks, 22/25 (88%) patients in the lamivudinearm continued to have undetectable HBV DNA, compared to25/25 (100%) patients in the entecavir arm (p=NS). Threepatients (12%) in the lamivudine arm had HBV DNA>20IU/mL, 2 at week 12 (43 IU/mL and 93 IU/mL) and 1 at week24 (86 IU/mL). None of these patients developed lamivudineresistant mutations, and were switched back to entecavir. Nofurther virological rebound was seen after 24 weeks. In patientswith follow-up to 48 weeks, all patients remaining on lamivu-dine, and those in the entecavir arm had undetectable HBVDNA. There was no difference in cumulative HBV DNArebound between the 2 groups at 48 weeks (p=NS). Conclu-sion: Preliminary results suggest that sequential therapy usingentecavir followed by lamivudine was effective in suppressingHBV DNA after initial optimal viral suppression with entecavir.Further follow-up will determine the long-term efficacy andresistance development of entecavir-lamivudine sequential ther-apy.link_to_OA_fulltex

Mild-to-moderate elevation of alanine aminotransferase may increase liver stiffness measurement by transient elastography in patients with chronic hepatitis B

Background: Recent studies have shown that in acute severeflares of hepatitis, liver stiffness measurements can be increaseddramatically. In contrast to severe hepatitis flares, it is notknown currently whether lesser degrees of hepatitis alsoincrease liver stiffness measurements. In the present study weaimed to investigate the effect of mild-to-moderate elevations ofALT on liver stiffness in patients with chronic hepatitis B. Patientsand Methods: Patients with chronic hepatitis B and elevated ALTwere included. Those patients with ALT elevations of greaterthan 10x upper limit of normal (ULN), indicating severe flareswere not included. All patients underwent liver biopsy and liverstiffness measurement for assessment of liver fibrosis prior tostarting antiviral therapy. Oral antiviral therapy (adefovir n=14, clevudine n= 24) was commenced after liver biopsy andliver stiffness measurement was performed. Once ALT normal-ization was achieved, a repeat liver stiffness measurement wasperformed. Results Thirty-eight patients were included, of which21 were male, with a median age of 39 years (range, 18-63).All patients achieved normalization of ALT after commencement of antiviral therapy, and the median time between the first andsecond liver stiffness measurement was 3 months (range, 1-7).There was a significantly lower mean liver stiffness measure-ments after the commencement of antiviral therapy with the nor-malization of ALT levels, compared to pre-treatment levels in the38 patients (7.5 vs 10.5 kPa respectively, p<0.001). Themedian liver stiffness reduction observed in patients with pre-treatment ALT of 1-2x ULN, 2-5X ULN, and 5-10x ULN were0.9, 1.4, and 3.9 kPa respectively, with an overall reduction of2.0 kPa. The higher the pre-treatment ALT, the higher the liverstiffness reduction observed (p=0.027). The AUROC curve fordiagnosing F2 fibrosis in patients with elevated ALT was 0.68,compared with 0.73 for the same patients after ALT normaliza-tion. No patients had evidence of cirrhosis on liver histology.Using the cutoff value of 11.0 kPa for cirrhosis, 12 (32%)patients would have been misclassified as having cirrhosisusing liver stiffness measurements taken at the time of ALT ele-vation. In contrast, 6 (16%) patients would have been misclas-sified as having cirrhosis using liver stiffness measurements atthe time where ALT had normalized. Conclusion: Even mild tomoderate elevation in ALT levels may increase liver stiffnessmeasurements independent of underlying liver fibrosis. HigherALT levels were associated with higher discrepancies in liverstiffness.link_to_OA_fulltex

Large population study in liver stiffness measurement: prevalence of significant fibrosis and correlation with Liver Biochemistry in Chronic Hepatitis B

This journal suppl. entitled: Abstracts of the 42nd Annual Meeting of the European Association for the Study of the Liver ... 2007Background and Aim: The prevalence of fibrosis in a large population of chronic hepatitis B (CHB) patients is not known. The aim ofthis study was to investigate the prevalence of significant fibrosis in a Chinese population with CHB by liver stifness measurement (LSM), and its correlation with liver biochemistry and demographic factors. Methods: All CHB patients seen at Hepatitis Clinic, Queen Mary Hospital, Hong Kong for CHB between January to July 2006 with LSM by transient elastography were included. Results: Of the 898 patients included with a median age of 44, 323 (36%) had significant fibrosis as defined by LSM of >8. 1 kPa. Males had a higher median liver stithess measurement (MLSM) than females (7.3 vs 5.9 kPa, p 0.001), and those positive for HBeAg had higher MLSM than HBeAgnegative patients (7.3 and 6.4kPa respectively, p = 0.017). In patients <25, 26-35, 36-45, 46-55, 56-65, and >65 years of age, the MLSM was 6.0, 6.0, 6.4, 7.6, 8.7and 11.6kPa respectively (p <0.001), with 56% of those aged over 55 years having significant fibrosis. LSM scores correlated well with serum bilirubin, ALT, AFP, and albumin levels (all p i 0.001). In patients with ALT i 0.5 upper limit of normal (ULN), 0.5-1 x ULN, I-~xULN, 2-5xULN and >5xULN, the MLSM was 5.7, 6.7, 8.4, 11.7 and 19.1 kPa respectively (p i 0.001). After multivariate analysis, age, bilirubin, ALT, albumin and gender remained significant factors associated with significant fibrosis. Using a combination of serum ALT, bilirubin and albumin levels to predict the presence of significant fibrosis, the sensitivity and specificity were 19% and 98% respectively, with positive predictive value of 84% and negative predictive value of 96%. Conclusion: The prevalence of significant fibrosis in Chinese CHB patients was high, affecting more than half of the patients over the age of 55 years. LSM correlated well with known factors associated with more severe disease, including older age, male sex, higher bilirubin and ALT, and lower albumin. The combination of serum bilirubin, ALT and albumin levels may be used to predict significant underlying fibrosis.link_to_subscribed_fulltex

Increase in liver stiffness measurements in severe hepatitis B flares

This journal suppl. entitled: Abstracts of the 43 Annual Meeting of the European Association for the Study of the LiverSession 05D. Viral Hepatitis – D) Hepatitis B – Clinical (Except Therapy) - PostersBACKGROUND: Liver stiffness measurement has been used as a non-invasive technique for assessing liver fibrosis. AIM: To assess the effect of severe hepatitis B flare on liver stiffness and determine factors predictive of normal liver stiffness measurements after severe hepatitis METHODS: Patients with severe flare of hepatitis B as defined by ALT>10× upper limit of normal were included. Transient elastography was performed at time of flare (baseline), and at 3−6 months after flare. Normal liver stiffness measurement was defined as < 6kPa. Routine liver biochemistry was recorded. RESULTS: Thirty-eight patients with severe hepatitis B flare patients were included with a median age of 46 years (range, 20−73), of which 32 (84%) were male. At the time of flare, the median bilirubin, peak ALT, albumin, platelet, and prothrombin time were 41 umol/L (range, 5−778), 1543 U/L (range, 539–3000), 38 g/L (range, 23−49), 180 x 109/L (range, 47–341), and 12.9 s (10.6−24.6) respectively. The median liver stiffness was 18.5 kPa (range, 6.9−73.5), with no patients having normal liver stiffness. At 3−6 months, the median liver stiffness measurement of 8.4kPa (range, 4.4−25.1), and 10 (26%) patients had normalized their liver stiffness measurement. Thirty-six (95%) patients had a decrease in liver stiffness, with a median decline of 9.7kPa. The median ALT at 3−6 months was 31 U/L (range, 11−60), with 86% having normal ALT. Patients who had normal liver stiffness at 3−6 months had higher platelet count and lower prothrombin time at baseline compared to patients with persistently abnormal liver stiffness (230 vs 170 x 109/L, p = 0.025 and 12.2 vs 13.8 s, p = 0.034 respectively). There was significant correlation with ALT levels and liver stiffness (r = 0.64, p < 0.01). CONCLUSION: Liver stiffness was affected by severe hepatitis flares, with 95% having a decline, and over 25% normalizing their liver stiffness by 3−6 months. The significant correlation between ALT levels and liver stiffness suggests that increased liver stiffness in patients with severe flares is likely due to inflammation and not due to fibrosis. Factor associated with normalization of liver stiffnessLink_to_subscribed_fulltex

Liver stiffness and histological features in healthy persons, and patients with occult hepatitis B, chronic active hepatitis B, and hepatitis B-related cirrhosis.

Background: Liver stiffness measurement using transient elas-tography has become a popular tool to assess liver fibrosis.Aim: To determine liver stiffness values and histological featuresin healthy subjects and patients with chronic hepatitis B.Patients and Methods: A total of 157 persons were included(28 healthy subjects, 18 occult hepatitis B infection, 102 activechronic hepatitis B, and 9 end-stage hepatitis B cirrhosis). His-tology and liver stiffness measurements were obtained from allpatients. Results: The median liver stiffness in healthy subjects,occult hepatitis B, active hepatitis B, and end-stage cirrhosiswere 4.6, 4.2, 8.7, and 33.8 kPa respectively, with signifi-cantly higher values in the latter 2 groups compared to the for-mer 2 groups (p11.0kPa, but only 4 (12%) had cirrhosis on histology. Using liverstiffness to predict cirrhosis in this group had a sensitivity of100%, specificity of 69%, a positive predictive value of 10%,and a negative predictive value of 100%. All 9 patients withend-stage liver cirrhosis had liver stiffness >11.0 kPa. The over-all AUROC for diagnosing cirrhosis using a cut-off of 11.3 kPawas 0.89. Conclusion: Liver stiffness measurement has an over-all good diagnostic accuracy with excellent negative predictivevalue. In chronic active hepatitis B, the diagnostic accuracymay be reduced when underlying inflammatory activity issevere.link_to_OA_fulltex

The effect of long-term Nucleoside/Tide Analogue Treatment on Intrahepatic Hbvdna and Covalently Closed Circular DNA in Chronic Hepatitis B patients

Poster Presentation - Session 7C: Viral Hepatitis: Hepatitis B & D - Clinical (Therapy, New Compounds, Resistance)Link_to_subscribed_fulltex