Ten year follow-up of Jarcho-Levin syndrome with thoracic insufficiency treated by VEPTR and MCGR VEPTR hybrid.

PURPOSE: Jarcho-Levin syndrome patients commonly suffer from repeated respiratory infections and become ventilator dependent due to an insufficient thoracic volume. Multiple congenital vertebral anomalies are associated with this genetic disorder and results in stunted spine growth. The purpose of this case report is to present the results of a hybrid vertical expandable prosthetic titanium rib (VEPTR) and magnetically controlled growing rod (MCGR) construct for the management of a patient with Jarcho-Levin syndrome. METHODS: A boy with Jarcho-Levin syndrome undergoes a hybrid VEPTR-MCGR construct to treat his thoracic insufficiency syndrome and spinal deformity. RESULTS: The patient could wean off ventilator and had reduced chest complications with the construct. He was also able to achieve some spine length gain with the distraction device. However, there were limitations in prolonged treatment as no spine height was gained once he reached 12 years old. Once no further growth can be achieved, the MCGR led to progressive kyphosis. Nevertheless, at latest follow-up after the removal of all implants, the patient could maintain satisfactory correction of both thoracic and spine deformities. CONCLUSIONS: A hybrid construct is necessary for managing Jarcho-Levin syndrome as the VEPTR deals with the thoracic cage deformity while the MCGR deals with the spine deformity.

Treatment of non-alcoholic steatohepatitis with Phyllanthus urinaria: a randomized trial.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is a common liver disease that may progress to cirrhosis and hepatocellular carcinoma. There is currently no approved pharmacological treatment for NASH. Phyllanthus urinaria is a commonly used hepatoprotective herb that ameliorates NASH in animal studies. We aimed to test the hypothesis that Phyllanthus was superior to placebo in improving histological non-alcoholic fatty liver disease (NAFLD) activity score. METHODS: This was a placebo-controlled parallel-group double-blind randomized controlled trial. Patients with histology-proven NASH were randomized to receive Phyllanthus or placebo for 24 weeks. The primary endpoint was change in NAFLD activity score from baseline to week 24. Secondary endpoints included changes in individual histological parameters, liver biochemistry and metabolic profile. RESULTS: We enrolled 60 patients (40 received Phyllanthus and 20 received placebo). The change in NAFLD activity score was -0.8 ± 1.4 in the Phyllanthus group and -0.3 ± 1.3 in the placebo group (P = 0.24). The change in steatosis, lobular inflammation, ballooning and fibrosis was also similar between the two groups. Within the Phyllanthus group, although there was reduction in hepatic steatosis (-0.2 ± 0.7; P = 0.039) and ballooning grades (-0.4 ± 0.5; P < 0.001), the change was small and of limited clinical significance. Furthermore, there was no significant difference in the changes in alanine aminotransferase, aspartate aminotransferase, fasting glucose and lipid profile between the two groups. CONCLUSIONS: Phyllanthus is not superior to placebo in improving NAFLD activity score in NASH patients.

Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography.

OBJECTIVE: Knowledge of the epidemiology of non-alcoholic fatty liver disease (NAFLD) is incomplete because liver biopsy cannot be performed on the general population to assess disease severity. New non-invasive tests allow accurate and safe assessment in healthy individuals. The aim of this study was to examine the prevalence of NAFLD and advanced fibrosis in the general Hong Kong Chinese population. METHODS: Subjects were recruited from the community by random selection from the government census database. Liver fat and fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography, respectively. RESULTS: Overall, 264 of 922 (28.6%) subjects had intrahepatic triglyceride content ≥5%. Excluding 12 subjects with significant alcohol consumption, the population prevalence of NAFLD was 27.3% (95% CI 24.5% to 30.2%). Each component of the metabolic syndrome increased the risk of fatty liver in a dose-dependent manner (prevalence of 4.5% in subjects without any component and 80.0% in those with all five components). 8 (3.7%) patients with fatty liver had liver stiffness ≥9.6 kPa, a level suggestive of advanced fibrosis. Body mass index and alanine aminotransferase level were independent factors associated with liver stiffness. Together with other clinical prediction scores, the estimated prevalence of advanced fibrosis in patients with fatty liver in the community was <10%. Compared with non-drinkers, modest drinkers (<10 g per day) did not have higher risk of fatty liver after adjustment for demographic and metabolic factors. The liver stiffness was 4.7±1.9 kPa in modest drinkers and 4.6±1.7 kPa in non-drinkers (p=0.54). CONCLUSION: NAFLD is found in over a quarter of the general adult Chinese population, but the proportion of patients with advanced fibrosis is low. Modest alcohol consumption does not increase the risk of fatty liver or liver fibrosis.

Diagnosis of liver fibrosis and cirrhosis using liver stiffness measurement: comparison between M and XL probe of FibroScan®.

BACKGROUND & AIMS: Unreliable results of liver stiffness measurement are obtained in 16% of cases and are independently associated with body mass index (BMI) greater than 30 kg/m(2). A new FibroScan® probe (XL probe) was designed specifically for obese patients. The aim of this study was to evaluate the accuracy of liver stiffness measurement using M and XL probes of Fibroscan® for the diagnosis of fibrosis and cirrhosis in a large cohort of patients. METHODS: Consecutive patients undergoing liver biopsies for chronic liver disease were prospectively recruited. Liver stiffness measurement was performed within 1 week before liver biopsy using both M and XL probes of FibroScan®. RESULTS: A total of 286 patients were evaluated. A reliable liver stiffness measurement using M probe was obtained in 79.7% of cases. In the other 21.3%, liver stiffness measurement using XL probe was obtained in 56.9% of patients. A strong correlation was found between M and XL values, regardless of BMI. In all groups, median liver stiffness measurement using the XL probe was significantly lower than liver stiffness measurement using the M probe. By multivariate analysis, unsuccessful liver stiffness examination with M probe was independently associated with age >50 years and BMI >30 kg/m(2). By univariate analysis, only BMI >30 kg/m(2) was associated with unsuccessful liver stiffness measurement with XL probe. No significant difference was observed between the M and XL probes for the diagnosis of liver fibrosis. CONCLUSIONS: Liver stiffness measurement with either M or XL probe is possible in 91.2% of patients with comparable diagnostic accuracy. In clinical practice, the M probe could be used as first step for liver stiffness measurement. In case of no valid shot or unreliable measurement, the XL probe could be used. This result could be useful for the assessment of liver fibrosis in NAFLD and/or obese patients.

Hepatitis B virus infection and fatty liver in the general population.

BACKGROUND & AIMS: In animal studies, expression of hepatitis B virus (HBV) proteins causes hepatic steatosis. We aimed to study the prevalence of fatty liver in people with and without HBV infection in the general population. METHODS: We performed a cross-sectional population study in Hong Kong Chinese. Intrahepatic triglyceride content (IHTG) was measured by proton-magnetic resonance spectroscopy. RESULTS: One thousand and thirteen subjects (91 HBV patients and 922 controls) were recruited. The median IHTG was 1.3% (0.2-33.3) in HBV patients and 2.1% (0-44.2) in controls (p <0.001). Excluding subjects with significant alcohol consumption, the prevalence of nonalcoholic fatty liver disease was 13.5% (95% confidence interval [CI] 6.4%, 20.6%) in HBV patients and 28.3% (95% CI 25.3%, 31.2%) in controls (p=0.003). The fatty liver prevalence differed in HBV patients and controls aged 40-59 years but was similar in those aged 60 years or above. After adjusting for demographic and metabolic factors, HBV infection remained an independent factor associated with lower risk of fatty liver (adjusted odds ratio 0.42; 95% CI 0.20, 0.88; p=0.022). HBV patients also had a lower prevalence of metabolic syndrome (11.0% vs. 20.2%; p=0.034), but the difference was mainly attributed to lower triglyceride levels. Among HBV patients, viral genotypes, HBV DNA level and hepatitis B e antigen status were not associated with fatty liver. CONCLUSIONS: HBV infection is associated with a lower prevalence of fatty liver, hypertriglyceridemia and metabolic syndrome. Viral replication may affect lipid metabolism and this warrants further studies.

Entecavir treatment in patients with severe acute exacerbation of chronic hepatitis B.

BACKGROUND & AIMS: Severe acute exacerbation of chronic hepatitis B is a unique clinical presentation with significant morbidity and mortality. Lamivudine was used in most previous studies, but the drug was limited by the development of resistance. Our objective is to study the safety and efficacy of entecavir in patients with severe acute exacerbation. METHODS: Consecutive patients with severe acute exacerbation of chronic hepatitis B were recruited from 1998 to 2009. All patients had serum alanine aminotransferase and bilirubin increased beyond 10 and 3 times the upper limit of normal, respectively. The primary endpoint was overall mortality at week 48. Virological and biochemical responses were also studied. RESULTS: Thirty-six patients and 117 patients were treated with entecavir and lamivudine, respectively. By week 48, 7 (19%) patients in the entecavir group and 5 (4%) patients in the lamivudine group died (adjusted hazard ratio 5.1, 95% confidence interval 1.5-17.2, p=0.010). Similarly, the entecavir group had higher liver-related mortality (adjusted hazard ratio 4.0, 95% confidence interval 1.0-15.7, p=0.044). Despite a lower prevalence of cirrhosis, more patients in the entecavir group developed prolonged jaundice, hepatic encephalopathy, and ascites. Entecavir resulted in more rapid and complete viral suppression, with 71% of patients achieving undetectable hepatitis B virus (HBV) DNA at week 48, compared to 40% in the lamivudine group (p=0.007). However, rapid HBV DNA reduction at week 4 was associated with prolonged jaundice. CONCLUSIONS: Entecavir treatment is associated with increased short-term mortality in patients with severe acute exacerbation of chronic hepatitis B but achieves better virological response in the long run.

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. RESULTS: Of 1106 patients, 711 (64%) were older than age 40, 370 (34%) had positive test results for hepatitis B e antigen (HBeAg), and 386 (35%) had increased serum levels of alanine aminotransferase. Of the patients, 524 (49%) had genotype B and 582 (51%) had genotype C HBV infection. Patients with genotype C infection had insignificant fibrosis less often (42% vs 55%; P < .0001) and advanced fibrosis more often (25% vs 19%; P = .015) than those infected with genotype B HBV. The difference in the severity of liver fibrosis between the 2 HBV genotypes was most marked among patients older than age 40 and those who tested negative for HBeAg. The mean age of patients infected by genotype C was greater than that of patients infected by genotype B HBV (41 vs 36 y). Among patients who were older than age 40 and tested negative for HBeAg, those with genotype C infection had higher levels of HBV DNA and alanine aminotransferase than those with genotype B HBV. CONCLUSIONS: Genotype C HBV was associated with more severe liver fibrosis than genotype B HBV, probably because of delayed HBeAg seroconversion and prolonged active disease.

Long-term follow-up of lamivudine treatment in patients with severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.

BACKGROUND: The long-term efficacy of lamivudine treatment for patients suffering from severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is unknown. METHODS: Consecutive patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B were prospectively recruited from 1999 to 2004 and treated with lamivudine. All patients had alanine aminotransferase (ALT) and serum bilirubin levels 10x and 3x above the upper limit of normal, respectively. HBeAg-positive patients without severe acute exacerbation served as controls. RESULTS: Forty-five patients with severe acute exacerbation and 31 controls were treated with lamivudine for a median of 2.8 (range 1.0-7.1) years and 3.8 (range 3.5-8.4) years, respectively. Compared with controls, patients with severe acute exacerbation had higher HBeAg seroconversion rates (78% versus 52%; P=0.02) and lower risk of virological breakthrough. However, 33% of patients with severe acute exacerbation still developed lamivudine resistance and virological breakthrough by year 5. HBV DNA levels at week 4 and prolonged baseline prothrombin time were independent factors associated with virological breakthrough. All patients with week 4 HBV DNA <3 log10 copies/ml had maintained virological response. Among 15 patients who stopped lamivudine after sustained HBeAg seroconversion for > or =6 months, 11 (73%) had virological relapse at a median of 1.4 (0.2-3.9) years. ALT increased beyond 10x the upper limit of normal in six (38%) patients who stopped lamivudine and two (7%) patients on maintained lamivudine treatment (P=0.02). CONCLUSION: Among patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B treated with lamivudine, virological breakthrough and post-treatment relapse are common despite a high rate of HBeAg seroconversion. Severe hepatitis flare is also common particularly among patients developing virological relapse after discontinuation of lamivudine.

Reliability of Rod Lengthening, Thoracic, and Spino-Pelvic Measurements on Biplanar Stereoradiography in Patients Treated With Magnetically Controlled Growing Rods.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To assess the inter- and intraobserver reliability of thoracic, spino-pelvic, and rod lengthening measurements made on biplanar spinal stereoradiography (EOS imaging) in children treated with magnetically controlled growing rod (MCGR). SUMMARY OF BACKGROUND DATA: MCGR treatment aims to gain spine length while gradually correcting the spinal deformity. Monitoring thoracic and spino-pelvic parameters is crucial for successful management. EOS imaging is widely used for diagnosis and monitoring of children with Early Onset Scoliosis. However, there is a paucity of literature on the reliability of thoracic and spino-pelvic parameters on EOS imaging in children treated with MCGR. METHODS: Three independent reviewers independently read a random assortment of 20 whole spine posteroanterior and lateral radiographs from patients treated with MCGR. The measurements were repeated 4 weeks after the initial read. The following radiological parameters were measured: Cobb angle of the main and compensatory curves, coronal balance, coronal T1-S1 and T1-T12 length, chest width and depth at T6, pelvic inlet width, MCGR distracted lengths, global kyphosis, proximal and distal junctional angle, lordosis, sagittal balance, pelvic incidence, pelvic tilt and sacral slope. Statistical analysis was performed with paired t test and Cronbach alpha for inter- and intraobserver reliability. RESULTS: All measurements had good or excellent intra- and interobserver reliability (α>0.8; P < 0.05), except measurements of the proximal junctional angle which showed only poor intra- and interobserver reliability for patients with an upper instrumented vertebra cranial to T4. CONCLUSION: EOS imaging is reliable for diagnosis and monitoring of children with Early Onset Scoliosis treated with MCGR. EOS imaging is particularly excellent for assessment of MCGR lengthening. Diagnosis and interpretation of early proximal junctional kyphosis within the cervicothoracic junction should be made with caution. LEVEL OF EVIDENCE: 3.

Predictability of Supine Radiographs for Determining In-Brace Correction for Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective radiographic study. OBJECTIVE: To assess whether flexibility as revealed by the supine radiograph, predicts in-brace curve correction. SUMMARY OF BACKGROUND DATA: Currently there is no consensus regarding a standard method to assess curve flexibility and immediate brace effectiveness in treating adolescent idiopathic scoliosis (AIS). Brace fabrication methods may be variable but ideally it should achieve maximal curve correction. Curve flexibility governs the degree of curve correction in-brace and hence dynamic radiographs are commonly performed prior to brace fitting. METHODS: This was a radiographic analysis of AIS patients treated with underarm bracing. Correlation of pre-brace, supine, and immediate in-brace Cobb angles was performed. Relationship with possible contributing factors including age, sex, body height, weight, age at menarche and Risser staging was studied. Major and minor curves were compared independently for correlation but the regression model was constructed based on the major curve only. RESULTS: From 105 patients with mean age of 12.2 ±â€Š1.2 years at brace fitting, supine Cobb angle measurement has significant correlation with immediate in-brace Cobb angle (r = 0.740). Univariate analyses showed no significant relationship with age, weight, height, date of menarche, Risser stage or pre-brace Cobb angle. Our regression model (in-brace Cobb angle = 0.809 × supine Cobb angle) had good fit of the data. CONCLUSION: Supine radiograph predictably determines the flexibility of the scoliotic curve to brace treatment. It can be used as a guideline to determine the amount of correction achievable with brace-wear. The effectiveness of the brace is dependent on the inherent flexibility of the curve rather than its size or type. LEVEL OF EVIDENCE: 3.