Predicting Hepatic Steatosis in Living Liver Donors Via Controlled Attenuation Parameter.

BACKGROUND: Hepatic steatosis (HS) can cause substantial problems for both donors and recipients in living donor liver transplantation. The controlled attenuation parameter (CAP) is a noninvasive method of measuring HS using a process based on transient elastography. AIM: To evaluate the accuracy of CAP in quantifying HS during living donor liver transplantation. METHODS: A total of 54 liver donors who received CAP and intraoperative liver biopsy (LB) were enrolled in this study. The performance of CAP compared with LB for diagnosing HS was assessed using areas under receiver operating characteristic curves. HS was defined by the presence of steatosis in >5% of hepatocytes. RESULTS: No HS was found in 47 donors, while the remaining 7 donors showed HS ranging from 10% to 30%. Using CAP, the area under receiver operating characteristic curve was 0.96 (95% CI, 0.91-1; P < .001) for HS; the optimal cutoff value for HS was 257 dB/m (sensitivity: 100%, specificity: 89.4%, positive predictive value: 58.3%, negative predictive value: 100%). Among the 42 candidates with CAP <257 dB/m, none had HS, while of the 12 candidates with CAP ≥257 dB/m, 7 had HS. In a multivariate linear regression analyses, body mass index (ß = 0.71, P < .001) was found to be independently associated with CAP in those without HS. CONCLUSIONS: CAP might be a promising tool to exclude HS in East Asian living liver donors. Body mass index was found to be independently associated with CAP values in those without HS.

Comparison of renal safety and efficacy of telbivudine, entecavir and tenofovir treatment in chronic hepatitis B patients: real world experience.

This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (tenofovir), telbivudine and entecavir. A retrospective study of 587 patients with chronic hepatitis B treated with tenofovir (n = 170), telbivudine (n = 184) and entecavir (n = 233) for at least 1 year. Renal function and efficacy were assessed. The estimated glomerular filtration rate (eGFR) decreased significantly in the tenofovir group after a mean of 17 months treatment (from 92.2 to 85.6 mL/min/1.73 m(2), p < 0.001), but increased in the telbivudine group after a mean of 32 months of treatment (from 86.1 to 95 mL/min/1.73 m(2), p < 0.001). There was no significant change in eGFR in the entecavir group after a mean of 44 months. By multivariate analysis, pre-existing renal insufficiency (p = 0.003), tenofovir (p = 0.007) and diuretic treatment (p = 0.001) were independent predictors for renal function deterioration. Cumulative virological breakthrough was 0% in tenofovir after 2 years, 3.4% in entecavir after 7 years and 22.9% in telbivudine after 5 years. Liver cirrhosis (p = 0.008) and virological breakthrough (p = 0.040) were independently associated with increased risk of hepatocellular carcinoma development. Tenofovir may lead to deterioration in renal function as assessed by serial eGFR measurements. Although telbivudine appeared to be associated with an improvement in eGFR, it was associated with high rates of virological breakthrough, which was an independent risk factor for HCC development. With low rates of virological breakthrough and preservation of renal function, entecavir could be the best choice among these three agents.

A comparison of efficacy and safety of 2-year telbivudine and entecavir treatment in patients with chronic hepatitis B: a match-control study.

There are limited data comparing the clinical outcomes between telbivudine and entecavir. We consecutively enrolled 115 telbivudine-naive and 115 entecavir-naive chronic hepatitis B patients, who were matched for age, sex, hepatitis B e antigen (HBeAg) status and cirrhosis, and treated for at least 2 years or less than 2 years but had developed resistance. Except for the rate of HBeAg seroconversion, which was similar, patients in the entecavir group had better clinical outcomes than those in the telbivudine group for alanine aminotransferase normalization (85.2% vs 78.4%, p <0.048), undetectable HBV DNA (96.5% vs 74.8%, p <0.001), and viral resistance (0.9% vs 21.7%, p <0.001) after 2 years of treatment, After applying roadmap or super-responders concepts, entecavir still had better outcomes than telbivudine in undetectable HBV DNA and viral resistance. The cumulative incidence of hepatocellular carcinoma development was similar between telbivudine-naive and entecavir-naive patients (p 0.565). In renal function analysis, there were significantly more patients with estimated glomerular filtration rate (eGFR) category improvement in both the telbivudine and entecavir groups at year 1 (p 0.006 and p 0.047, respectively). The rate of virological improvement was significantly higher with entecavir than with telbivudine after 2 years of treatment, whether applying the concepts of roadmap or super-responders. The incidence of hepatocellular carcinoma was similar between telbivudine and entecavir. Both telbivudine and entecavir were associated with eGFR improvement, especially in patients with renal insufficiency.

Role of hepatitis C virus substitutions and interleukin-28B polymorphism on response to peginterferon plus ribavirin in a prospective study of response-guided therapy.

Recent studies have indicated that amino acid (aa) substitutions in the core region and NS5A interferon sensitivity-determining region (ISDR) of hepatitis C virus (HCV) as well as genetic polymorphisms in the interleukin-28B (IL-28B) locus affect the outcome of interferon (IFN)-based therapies. We aimed to investigate the role of these factors on response to peginterferon plus ribavirin in a prospective study of response-guided therapy. The aa sequences in core region and ISDR and rs12979860 genotypes were analysed in 115 HCV-1 patients. The treatment was 24 weeks for patients achieving a rapid virological response (RVR), 48 weeks for those with an early virological response (EVR) and early terminated in those without an EVR. A sustained virological response (SVR) was achieved in 82% of 34 RVR patients, 45% of 74 EVR patients and 0% of seven non-EVR patients. Logistic regression analysis showed that ISDR mutation (≥2) [odds ratio(OR): 6.024], double core 70/91 mutations (OR: 0.136), and platelet counts≥15×10(4) /µL (OR: 3.119) were independent pretreatment factors associated with SVR. Apart from rs12979860 CC genotype, low viral load and ISDR mutation (≥2) were significant factors predictive of RVR. Combination of rs12979860 genotype and baseline viral characteristics (viral load and core/ISDR mutations) could predict RVR and SVR with positive predictive value of 100% and 91%, and negative predictive value of 80% and 54%, respectively. In conclusion, pretreatment screening rs12979860 genotype and aa substitutions in the core region and ISDR could help identifying patients who are good candidates for peginterferon plus ribavirin therapy.

A modified TNM-based Japan Integrated Score combined with AFP level may serve as a better staging system for early-stage predominant hepatocellular carcinoma patients.

BACKGROUND: Combinations of Child-Pugh classification and Liver Cancer Study Group of Japan/Tumor-Node-Metastasis (LCSGJ/TNM) have been reported as Japan Integrated Staging (JIS). We previously modified the 6th AJCC/TNM to serve as a better staging system than the 5th and 6th AJCC/TNM. AIMS: To develop a modified TNM-based JIS to predict the survival of hepatocellular carcinoma (HCC) patients more accurately. METHODS: 3764 HCC patients were enrolled from 1986 to 2002 (2882 patients from 1986 to 2000 and 882 patients from 2001 to 2002). We compared the performance of original JIS, modified TNM-based JIS, modified TNM-based JIS combined alpha-fetoprotein (AFP), BCLC, and CLIP. Lower Akaike information criteria (AIC) values indicated better discriminatory abilities. RESULTS: AIC value was lowest in CLIP during all periods. However, during 2001-2002, when early-stage HCC patients were predominant, AIC value was lowest when modified TNM-based JIS combined AFP was used. CONCLUSION: The CLIP system provided the best prognostic stratification in the present cohort of HCC patients who were mainly at late stages. However, early detection of HCCs has become more common in Taiwan in recent years, which has led to the predominance of early-stage HCC patients. Therefore, modified TNM-based JIS combined AFP may now be the most applicable system in recent years.

Association of amino acid variations in the NS5A and E2-PePHD region of hepatitis C virus 1b with hepatocellular carcinoma.

NS5A and E2 proteins of the hepatitis C virus (HCV) have the potential to repress protein kinase R (PKR) that exerts a tumour suppressor function. We investigated the relationship between amino acid variations in the NS5A-PKR-binding domain and E2-PKR-eIF2alpha phosphorylation homology domain (PePHD) region and the development of hepatocellular carcinoma (HCC) in chronic HCV-1b patients. In a cross-sectional, hospital-based setting, we compared the amino acid sequences of NS5A-PKR-binding domain and E2-PePHD in the sera of 104 chronic hepatitis, 44 cirrhosis and 96 HCC patients. The nucleotide sequences were inferred by direct sequencing of the amplified HCV products and deduced amino acid were compared with the sequence of HCV-J. By univariate analysis, old age, lower viral load, fewer amino acid substitutions in the NS5A-PKR-binding domain (codons 2209-2274) and the interferon sensitivity-determining region (ISDR; codons 2209-2248), and wild-type amino acid at codon 2209 and codon 2240 was significantly correlated with HCC, whereas substitutions in the E2-PePHD was not. Patients with a mutated-type (> or = 4) NS5A-ISDR had a lower prevalence of HCC than those with intermediate or wild type (P < 0.05). Based on stepwise logistic regression analysis, age [odds ratio (OR): 1.132, P < 0.001], viral load (OR: 0.305, P < 0.001) and mutated-type ISDR (OR: 0.137, P = 0.001) were independently associated with HCC. In conclusion, NS5A-ISDR variations may play an important role in the development of HCV-related HCC.

Mutations in the interferon sensitivity-determining region (nonstructural 5A amino acid 2209-2248) in patients with hepatitis C-1b infection and correlating response to combined therapy of pegylated interferon and ribavirin.

BACKGROUND: Most reports suggest that mutations in the interferon sensitivity-determining region (ISDR) correlate with response to conventional interferon-based therapies in hepatitis C virus-1b (HCV-1b) patients. However, the correlation between ISDR region mutations and response to pegylated interferon plus ribavirin therapy in HCV-1b patients remains unclear. AIM: To assess whether ISDR mutations correlate with response to Peg interferon plus ribavirin therapy in HCV-1b patients. PATIENTS AND METHODS: Sixty HCV-1b naive patients who had undergone 6 months of Peg interferon alpha-2b plus ribavirin and a 6-month follow-up were enrolled. The amino acid sequences of the nonstructural 5A-interferon-induced RNA-dependent protein kinase (NS5A-PKR)-binding domain were determined by polymerase chain reaction and sequencing. RESULTS: Thirty (50%) patients achieved sustained virological response (SVR). Univariate analysis showed that the proportion of patients with ISDR mutations >or=4 and rapid virological response rate was higher in the sustained virological response group than in the non-SVR group. Viral load was lower in the SVR group than in the non-SVR group. Multivariate analysis revealed that ISDR mutations >or=4 and ribavirin >or=14 mg/kg/day were independent predictors of SVR. CONCLUSION: Mutations of the ISDR correlate with SVR to Peg interferon alpha-2b plus ribavirin therapy in HCV-1b patients.

Antiemetic and analgesic-sparing effects of diphenhydramine added to morphine intravenous patient-controlled analgesia.

BACKGROUND: This study was designed to examine the analgesic and dose-related antiemetic efficacy of diphenhydramine-morphine mixture for intravenous patient-controlled analgesia (PCA). METHODS: Healthy women, undergoing abdominal total hysterectomy were recruited to this double-blinded randomized placebo-controlled study. Patients were randomly allocated to one of three groups (n=40 each). In group 1, patients received saline at induction and morphine 1 mg ml(-1) alone for postoperative PCA. Patients in groups 2 and 3 received diphenhydramine 30 mg i.v. at induction and were given a 1.2:1 or a 4.8:1 ratio, respectively, of diphenhydramine-morphine mixture for postoperative PCA. RESULTS: A total of 112 patients completed the study. The incidence of postoperative nausea (31.6% vs 67.6%, P<0.01) and vomiting (15.8% vs 40.5%, <0.05) was significantly lower in group 3 than in group 1. Furthermore, the incidence of severe nausea was significantly lower in group 3 than in group 1 (2.6% vs 24.3%, P<0.05). The rescue antiemetic requirements were also significantly less in group 3 than in group 1 (5.3% vs 24.3%, P<0.05). However, there was no significant difference between group 2 and group 1 in any of the comparisons. Pain intensity, 24-h morphine consumption and diphenhydramine-related side-effects, such as sedation or dry mouth, did not differ among the three groups. CONCLUSION: An initial bolus of diphenhydramine 30 mg at anaesthetic induction followed by postoperative PCA with a 4.8:1, but not 1.2:1, diphenhydramine-morphine mixture provides an effective antiemetic efficacy without morphine-sparing effects.

Experimental study of substrate temperature.

Substrate temperature is one of the most important processing parameters for optical coating deposition. The distribution of substrate temperature during deposition has been measured and calculated. Two kinds of heating method have been compared. The experiments show that the use of halogen lamps in a front surface heating system can achieve better uniformity of temperature distribution and diminish the influence of the evaporating source. The experiments provide some very useful production processing parameters.

Wideband monitoring and measuring system for optical coatings.

A wideband system, controlled by an IBM PC/XT computer, has been established for monitoring and measuring optical coatings in vacuum. With supporting software, it is adaptable to various monitoring methods, which include using merit functions as criteria for terminating deposition, and the simultaneous display of transmittance functions T, partial differentialT/ partial differentialt, and partial differentialT/ partial differentiallambda at a particular wavelength. It can also be used in the measurement of optical constants of dielectric layers in vacuum. The design considerations of the system are discussed, and experimental results are given.

Determining optical constants using an infrared ellipsometer.

In the infrared region high refractive index coating materials, such as PbTe and Ge, are normally semiconductors. Their optical constants n, k, and d are strongly dependent on the deposition process. For the most practical coating designs, the layers are usually not very thick, of the order of a half or quarter wavelength, and are weakly absorbing. To determine the optical constants of such thin films using an infrared ellipsometer, some problems exist which must be solved: (1) the precision of n, k, and d and (2) multiple solutions. In this paper these problems are solved by theoretical analysis and experimental arrangement. Experimental results are given and an experimental measurement method is presented.

Extension of nasopharyngeal carcinoma and otitis media with effusion.

In 35 patients with nasopharyngeal carcinoma that occupied the fossa of Rosenmüller, the relationship of the tumor, assessed by computed tomographic scans, to otitis media with effusion and ventilatory function of the eustachian tube was examined. Incidence of otitis media with effusion was low when the tumor was limited to the fossa of Rosenmüller (stage I), and high when the tumor extended from the fossa to the parapharyngeal space (stage II). Passive opening of the eustachian tube remained normal until the tumor occupied the parapharyngeal space (stage III). However, active tubal opening was impaired in stage I and the impairment increased with the tumor stage. These results indicate that tumor extension from the fossa of Rosenmüller to the parapharyngeal space and resultant poor active tubal opening cause the development of otitis media with effusion in patients with nasopharyngeal carcinoma.