The fatty liver index (FLI) is an algorithm involving the waist circumference, body mass index, and serum levels of triglyceride and gamma-glutamyl transferase to identify fatty liver. Although some ...studies have attempted to validate the FLI, few studies have been conducted for external validation among Asians. We attempted to validate FLI to predict ultrasonographic fatty liver in Taiwanese subjects.
We enrolled consecutive subjects who received health check-up services at the Taipei Veterans General Hospital from 2002 to 2009. Ultrasonography was applied to diagnose fatty liver. The ability of the FLI to detect ultrasonographic fatty liver was assessed by analyzing the area under the receiver operating characteristic (AUROC) curve.
Among the 29,797 subjects enrolled in this study, fatty liver was diagnosed in 44.5% of the population. Subjects with ultrasonographic fatty liver had a significantly higher FLI than those without fatty liver by multivariate analysis (odds ratio 1.045; 95% confidence interval, CI 1.044-1.047, p< 0.001). Moreover, FLI had the best discriminative ability to identify patients with ultrasonographic fatty liver (AUROC: 0.827, 95% confidence interval, 0.822-0.831). An FLI < 25 (negative likelihood ratio (LR-) 0.32) for males and <10 (LR- 0.26) for females rule out ultrasonographic fatty liver. Moreover, an FLI ≥ 35 (positive likelihood ratio (LR+) 3.12) for males and ≥ 20 (LR+ 4.43) for females rule in ultrasonographic fatty liver.
FLI could accurately identify ultrasonographic fatty liver in a large-scale population in Taiwan but with lower cut-off value than the Western population. Meanwhile the cut-off value was lower in females than in males.
The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear.
Eighty patients ...with CD20(+) lymphoma and resolved hepatitis B were randomly assigned to receive either prophylactic entecavir (ETV) before chemotherapy to 3 months after completing chemotherapy (ETV prophylactic group, n = 41) or to receive therapeutic ETV at the time of HBV reactivation and hepatitis B surface antigen (HBsAg) reverse seroconversion since chemotherapy (control group, n = 39).
Fifty-eight patients (72.5%) were positive for hepatitis B surface antibody, and HBV DNA was undetectable in 50 patients (62.5%). During a mean 18-month follow-up period, one patient (2.4%) in the ETV prophylactic group and seven patients (17.9%) in the control group developed HBV reactivation (P = .027). The cumulative HBV reactivation rates at months 6, 12, and 18 after chemotherapy were 8%, 11.2%, and 25.9%, respectively, in the control group, and 0%, 0%, and 4.3% in the ETV prophylactic group (P = .019). Four patients (50%) in the control group had HBsAg reverse seroconversion after HBV reactivation. The cumulative HBsAg reverse seroconversion rates at months 6, 12, and 18 since chemotherapy were 0%, 6.4%, and 16.3% in the control group, respectively, which were significantly higher than those in the ETV prophylactic group (P = .032). Patients with detectable or undetectable viral load could develop HBV reactivation and HBsAg reverse seroconversion.
Undetectable HBV viral load before chemotherapy did not confer reactivation-free status. Antiviral prophylaxis can potentially prevent rituximab-associated HBV reactivation in patients with lymphoma and resolved hepatitis B.
Because of the shared modes of transmission, hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection is not uncommon in highly endemic areas and among subjects with a high risk of parenteral ...infections. The worldwide prevalence of HBV/HCV coinfection is unknown and might be underestimated with the phenomenon of silent (occult) HBV infection. HCV superinfection in patients with chronic HBV infection was the most common clinical features of coinfection in Asia–Pacific countries. Further, most, but not all, clinical observations suggested that interference between the two viruses was more frequently characterized by an inhibition of HBV replication exerted by HCV. However, longitudinal follow‐up studies have demonstrated that the virological patterns in coinfection cases are widely divergent and have dynamic profiles over time. As compared with monoinfected patients, HBV/HCV coinfected persons tend to have more severe liver injury, a higher probability of liver cirrhosis and hepatic decompensation, and a higher incidence of hepatocellular carcinoma. Detailed serological and virological evaluations are required for coinfected patients before initiation of antiviral therapy. Previous studies demonstrated that HBV/HCV coinfected patients responded poorly to interferon (IFN) monotherapy. Currently, for patients with dominant HCV infection and low level HBV viremia (<104 IU/mL), IFN or pegylated IFN plus ribavirin can achieve comparable sustained virus response as expected with HCV monoinfection. However, phenomenon of reciprocal viral interference can happen, and resultant “flare” of hepatitis activity may cause liver function deterioration. For coinfected patients with dually‐active HBV/HCV, the optimal regimen for therapy remains unclear although adding oral nucleos(t)ide analogs to pegylated IFN and ribavirin seems a reasonable empiric option.
Laparoscopic gastric bypass (GB) is reportedly more effective than laparoscopic sleeve gastrectomy (SG) in the treatment of patients with a low body mass index and type 2 diabetes mellitus. However, ...the mechanism remains speculative. We compared the postprandial gut hormone patterns between patients undergoing laparoscopic GB and laparoscopic SG at 2 years after surgery in a hospital-based, prospective study.
A total of 16 laparoscopic GB and 16 laparoscopic SG patients were followed up and appraised for glucose homeostasis. Two years after surgery, the mixed meal test and gut hormones were evaluated in 13 laparoscopic GB and 13 laparoscopic SG patients who had been included in the previous randomized trial.
The preoperative characteristics, such as body mass index, body weight, waist circumference, and duration of T2DM were comparable between the 2 groups. T2DM remission was achieved in 13 (81%) laparoscopic GB and 3 (19%) laparoscopic SG patients (P < .05) 2 years after surgery. The laparoscopic GB patients had lost more weight and had a smaller waist circumference and lower levels of glucose and hemoglobin A1c, and lower insulin resistance than the SG patients. Significant differences were found in acyl ghrelin, des-acyl ghrelin, cholecystokinin, and resistin between the 2 groups, but none in obestatin, gastric inhibitory peptide, glucagon-like peptide-1, and leptin.
Both laparoscopic GB and laparoscopic SG have strong hindgut effects after surgery, but GB has a significant duodenal exclusion effect on cholecystokinin. The laparoscopic SG group had lower acyl ghrelin and des-acyl ghrelin levels but greater concentrations of resistin than the laparoscopic GB group.
A breakthrough using "reverse pharmacology" identified and characterized acyl ghrelin from the stomach as the endogenous cognate ligand for the growth hormone (GH) secretagogue receptor (GHS-R) 1a. ...The unique post-translational modification of O-n-octanoylation at serine 3 is the first in peptide discovery history and is essential for GH-releasing ability. Des-acyl ghrelin, lacking O-n-octanoylation at serine 3, is also produced in the stomach and remains the major molecular form secreted into the circulation. The third ghrelin gene product, obestatin, a novel 23-amino acid peptide identified from rat stomach, was found by comparative genomic analysis. Three ghrelin gene products actively participate in modulating appetite, adipogenesis, gut motility, glucose metabolism, cell proliferation, immune, sleep, memory, anxiety, cognition, and stress. Knockdown or knockout of acyl ghrelin and/or GHS-R1a, and overexpression of des-acyl ghrelin show benefits in the therapy of obesity and metabolic syndrome. By contrast, agonism of acyl ghrelin and/or GHS-R1a could combat human anorexia-cachexia, including anorexia nervosa, chronic heart failure, chronic obstructive pulmonary disease, liver cirrhosis, chronic kidney disease, burn, and postsurgery recovery, as well as restore gut dysmotility, such as diabetic or neurogenic gastroparesis, and postoperative ileus. The ghrelin acyl-modifying enzyme, ghrelin O-Acyltransferase (GOAT), which attaches octanoate to serine-3 of ghrelin, has been identified and characterized also from the stomach. To date, ghrelin is the only protein to be octanylated, and inhibition of GOAT may have effects only on the stomach and is unlikely to affect the synthesis of other proteins. GOAT may provide a critical molecular target in developing novel therapeutics for obesity and type 2 diabetes.
Background/Aims Hepatitis B virus (HBV) levels correlate with the development of hepatocellular carcinoma (HCC), but the role of viral load in HCC recurrence after tumor resection remains unclear. ...Herein we aimed to investigate the role of viral load in HCC recurrence following tumor resection. Methods From 1990 to 2002, 193 HBV-related HCC patients who underwent tumor resection in Taipei Veterans General Hospital were enrolled. Serum HBV DNA level and mutations were analyzed for association with early and late recurrence, together with other clinical variables. Results During a follow-up of 58.2 ± 44 months, 134 patients had HCC recurrence. Multivariate analysis showed that multinodularity (Hazard ratio HR, 95% confidence interval CI; 2.232, 1.021–4.878), macroscopic venous invasion (4.693, 1.645–13.391), AFP >20 ng/ml (3.891, 1.795–8.475), and cut margin ⩽1 cm (3.333, 1.487–7.470) were correlated with early recurrence (within two years of operation) of HCC. In addition, multivariate analysis determined that Ishak hepatic inflammatory activity >6 (4.658, 1.970–11.017), multinodularity (3.266, 1.417–7.526), ICG-15 >10% (2.487, 1.095–5.650) and HBV DNA level >106 copies/ml (2.548, 1.040–6.240) were significantly associated with late recurrence (>two years after resection). Patients with high viral loads tended to have higher Ishak inflammatory (7.00 ± 3.07 vs. 5.33 ± 2.96, p = 0.001) and fibrosis scores (4.17 ± 2.01 vs. 3.20 ± 2.41, p = 0.007) than those with lower loads. Conclusions Tumor factors were associated with early HCC recurrence while high viral loads and hepatic inflammatory activity were associated with late recurrence. Pre- and post-operative antiviral and anti-inflammatory therapies may be crucial in reducing late recurrence.
Gastric bypass (GB) is an effective treatment for those who are morbidly obese with coexisting type 2 diabetes mellitus (T2DM) or non-alcoholic fatty liver disease (NAFLD). Fibroblast growth factors ...(FGFs) are involved in the regulation of energy metabolism.
We investigated the roles of FGF 19, FGF 21, and total bile acid among those with morbidly obese and T2DM undergoing GB. A total of 35 patients were enrolled. Plasma FGF 19, FGF 21, and total bile acid levels were measured before surgery (M0), 3 months (M3), and 12 months (M12) after surgery, while the hepatic steatosis index (HSI) was calculated before and after surgery.
Obese patients with T2DM after GB presented with increased serum FGF 19 levels (
= 0.024) and decreased total bile acid (
= 0.01) and FGF 21 levels (
= 0.005). DM complete remitters had a higher FGF 19 level at M3 (
= 0.004) compared with DM non-complete remitters. Fatty liver improvers tended to have lower FGF 21 (
= 0.05) compared with non-improvers at M12.
Changes in FGF 19 and FGF 21 play differential roles in DM remission and NAFLD improvement for patients after GB. Early increases in serum FGF 19 levels may predict complete remission of T2DM, while a decline in serum FGF 21 levels may reflect the improvement of NAFLD after GB.
Background & Aims: Entecavir demonstrated superior benefit to lamivudine at 48 weeks in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). We evaluated ...continued entecavir and lamivudine treatment through 96 weeks. Methods: 709 HBeAg-positive CHB patients were randomized to entecavir 0.5 mg (n = 354) or lamivudine 100 mg (n = 355) once daily. At week 52, protocol-defined virologic responders could continue blinded treatment for up to 96 weeks. Patients continuing in year 2 (entecavir, n = 243; lamivudine, n = 164) were assessed for serum hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT) normalization, HBeAg seroconversion, and safety. Cumulative confirmed proportions of all treated patients who achieved these responses were also analyzed. Results: Among patients treated in year 2, 74% of entecavir-treated versus 37% of lamivudine-treated patients achieved HBV DNA <300 copies/mL by polymerase chain reaction (PCR), and 79% of entecavir-treated versus 68% of lamivudine-treated patients normalized ALT levels. Similar proportions of entecavir-treated and lamivudine-treated patients achieved HBeAg seroconversion (11% vs 12%, respectively). Higher proportions of entecavir-treated than lamivudine-treated patients achieved cumulative confirmed HBV DNA <300 copies/mL by PCR (80% vs 39%; P < .0001) and ALT normalization (87% vs 79%; P = .0056) through 96 weeks. Cumulative confirmed HBeAg seroconversion occurred in 31% of entecavir-treated versus 25% of lamivudine-treated patients ( P = NS). Through 96 weeks, no patient experienced virologic breakthrough due to entecavir resistance. The safety profile was comparable in both groups. Conclusions: Entecavir treatment through 96 weeks results in continued benefit for patients with HBeAg-positive CHB.
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