Hepatitis B virus (HBV) infections continue to occur in adult hemodialysis units. A possible contributing factor is the presence of occult HBV (serum hepatitis B surface antigen [HBsAg] negative but HBV DNA positive). Two hundred forty-one adult hemodialysis patients were screened for occult HBV. HBV DNA testing was performed by real-time polymerase chain reaction (PCR) with 2 independent primer sets (core promoter and surface). Two (0.8%) of the 241 patients were HBsAg positive. Of the remaining 239 HBsAgnegative patients, 9 (3.8%) were HBV DNA positive. Viral loads in these individuals were low (10 2 -10 4 viral copies/mL). Seven of the 9 (78%) were nt 587 mutation (sG145R mutant) positive. Demographic, biochemical, and HBV serological testing did not help to identify those with occult HBV. In conclusion, the prevalence of occult HBV in adult hemodialysis patients in this North American urban center is approximately 4 to 5 times higher than standard HBsAg testing would suggest. The majority of these infections are associated with low viral loads and a high prevalence of the sG145R mutant. Finally, the demographic, biochemical, and/or serological features of HBV DNA-positive subjects do not distinguish these individuals from the remainder of the dialysis patient population. (HEPATOLOGY 2004; 40:1072-1077.) D espite the development of an effective hepatitis B virus (HBV) vaccine and extensive infection control guidelines, HBV infections continue to occur in dialysis units throughout North America and Europe. 1-3 Based on the results of hepatitis B surface antigen (HBsAg) testing, the incidence of such infections is thought to be 0.05%-1% per year. 4 However, this likely represents an underestimate of the true incidence, as the use of more sensitive monoclonal-based assays for HBsAg detection increase positive findings in dialysis patients by 120%. 5 The relatively low acceptance and response rates to the HBV vaccine among dialysis patients likely contributes to ongoing transmission, as does the need for vaccine boosts to maintain antibody to HBsAg (anti-HBs) at protective levels. 4,6 -8 Additional contributing factors include "breakdowns" in the application of universal and/or dialysis-specific infection control measures. 4,7,9 With the development of specific and sensitive polymerase chain reaction (PCR)-based testing for HBV DNA, the presence of occult HBV infection (HBV DNA positivity in the setting of negative serum HBsAg) represents yet another possible explanation for ongoing transmission.To date, few studies have documented the prevalence of occult HBV infection in renal dialysis patients. In 3 small studies of 33, 5, and 67 HBsAg-negative dialysis patients, 50%, 40%, and 0%, respectively, were HBV DNA positive. 10 -12 Of note, the majority of HBV DNApositive individuals in these studies had serological evidence of previous HBV infection (HBV seropositive), but as many as 39% were HBV seronegative.The present study documents the prevalence of HBV DNA positivity in a large, North American renal dialys...

Traditional anti-diabetic drugs may have negative or positive effects on risk of bone fractures. Yet the relationship between the new class glucagon-like peptide-1 receptor agonists (GLP-1 RA) and risk of bone fractures has not been established. We performed a meta-analysis including randomized controlled trials (RCT) to study the risk of bone fractures associated with liraglutide or exenatide, compared to placebo or other active drugs. We searched MEDLINE, EMBASE, and clinical trial registration websites for published or unpublished RCTs comparing the effects of liraglutide or exenatide with comparators. Only studies with disclosed bone fracture data were included. Separate pooled analysis was performed for liraglutide or exenatide, respectively, by calculating Mantel-Haenszel odds ratio (MH-OR). 16 RCTs were identified including a total of 11,206 patients. Liraglutide treatment was associated with a significant reduced risk of incident bone fractures (MH-OR=0.38, 95% CI 0.17-0.87); however, exenatide treatment was associated with an elevated risk of incident bone fractures (MH-OR=2.09, 95% CI 1.03-4.21). Publication bias and heterogeneity between studies were not observed. Our study demonstrated a divergent risk of bone fractures associated with different GLP-1 RA treatments. The current findings need to be confirmed by future well-designed prospective or RCT studies.

No abstract

Smads are intracellular signaling molecules of the transforming growth factor-β (TGF-β) superfamily that play an important role in the activation of hepatic stellate cells (HSCs) and hepatic fibrosis. Excepting the regulation of Smad7, receptor-regulated Smad gene expression is still unclear. We employed rat HSCs to investigate the expression and regulation of the Smad1 gene, which is a bone morphogenetic protein (BMP) receptor-regulated Smad. We found that the expression and phosphorylation of Smad1 are increased during the activation of HSCs. Moreover, TGF-β significantly inhibits Smad1 gene expression in HSCs in a time- and dose-dependent manner. Furthermore, although both TGF-β1 and BMP2 stimulate the activation of HSCs, they have different effects on HSC proliferation. In conclusion, Smad1 expression and phosphorylation are increased during the activation of HSCs and TGF-β1 significantly inhibits the expression of the Smad1 gene.

The aim of the present study was to determine whether alterations in hepatic energy expenditure following partial hepatectomy (PHx), as documented by in vivo hepatic 31 P-MRS, correlate with standard parameters of hepatic regeneration and/or liver function. In addition, we sought to determine whether changes in hepatic energy levels are proportional to the extent of hepatic resection. Adult male Sprague-Dawley rats (4-7 per group) underwent a 40%, 70%, or 90% PHx or sham surgeries. Magnetic resonance spectroscopy (MRS) examinations were performed on each animal 24 or 48 hours thereafter. After MRS examinations, [ 3 H]thymidine incorporation into hepatic DNA, proliferating cell nuclear antigen (PCNA) protein expression, and serum bilirubin determinations were performed on each rat. Twenty-four hours following surgery, rats that had undergone 70% PHx had unchanged adenosine triphosphate (ATP) levels but significantly lower ATP/inorganic phosphate (Pi) ratios (P < .05), whereas, at 48 hours post-PHx, both ATP and ATP/Pi levels were lower than in sham-and nonoperated controls (P < .05). Hepatic regeneration and liver dysfunction mirrored these changes; correlations existed between ATP/Pi ratios and [ 3 H]thymidine incorporation (r ‫؍‬ ؊0.61, P < .005), PCNA protein expression (r ‫؍‬ ؊0.62, P < .005), and serum bilirubin (r ‫؍‬ ؊0.49, P < .05). For rats that had undergone graded resections, depleted energy levels 48 hours post-PHx were proportional to the extent of resection, degree of enhanced regenerative activity, and liver dysfunction. In conclusion, 31 P-MRS-generated ATP/Pi index is a noninvasive, robust determination that correlates with standard parameters of hepatic regeneration and function. (HEPATOLOGY 2002;36:345-353.)