Liver transplantation for patients with hepatitis B: prevention of hepatitis B recurrence by intravenous antihepatitis B immunoglobulin and lamivudine.
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Adult↗
Biomedical subjects
M Y Lai
Publications and source records attributed to M Y Lai.
Hepatitis B genotypes and the response to interferon therapy.
BACKGROUND/AIMS: Possible pathogenic differences among hepatitis B virus (HBV) genotypes have been observed; however, the response to interferon therapy among HBV genotypes remains unknown. We therefore analyzed the efficacy of interferon alfa in the treatment of chronic hepatitis B patients with different HBV genotypes. METHODS: Fifty-eight genotype B or C infected chronic hepatitis B patients who had been treated with interferon alfa-2b were retrospectively studied. The response to interferon was defined as normalization of serum aminotransferase level, loss of hepatitis B e antigen and HBV DNA 48 weeks post-treatment. RESULTS: Baseline data of both groups of patients were comparable; however, genotype C patients had a higher serum aminotransferase level and a higher frequency of core promoter mutation. The response rate was 41% and 15% in genotype B and C patients, respectively (p=0.045). In those with higher serum aminotransferase levels, the response rate was 50% and 17%, respectively (p=0.025). Additionally, younger age and genotype B infection may predict a better response to interferon alfa. CONCLUSIONS: HBV genotype C, compared to genotype B, is associated with a higher frequency of core promoter mutation, and a lower response rate to interferon alfa therapy.
Adult↗
Firstline treatment for hepatitis C: combination interferon/ribavirin versus interferon monotherapy.
In the initial treatment of chronic hepatitis C, interferon-alfa (IFN-alpha) monotherapy for 24-48 weeks induces sustained response rates of only 10-20%. Combination therapy with IFN-alpha plus ribavirin induces a sustained response in 40-50% of patients, and can be now recommended as the firstline therapy for chronic hepatitis C. Stopping therapy at week 12 because of persistent viraemia is unnecessary with the combination therapy because later clearance of HCV RNA can still occur with a sustained response. Patients with HCV genotype 1 should receive 48 weeks of combination therapy, in contrast to 24 weeks for patients with genotypes 2 or 3. For patients who cannot tolerate the side effects of ribavirin, such as anaemia, IFN-alpha at 3 MU three times weekly for 48 weeks is preferred as the initial therapy. The long-acting pegylated IFN can be expected to enhance the efficacy of combination therapy in the treatment of chronic hepatitis C and appears to be much more potent as monotherapy. Further studies are needed to improve the current 'half-full' status of chronic hepatitis C treatment.
Antiviral Agents↗
Low incidence of hepatitis C virus transmission between spouses: a prospective study.
BACKGROUND: Interspousal transmission of hepatitis C virus (HCV) has been documented; however, the annual risk of interspousal transmission remains unclear. METHODS: A long-term prospective study to define the risk of interspousal transmission of HCV was conducted. One hundred and twelve index patients with chronic hepatitis C and their anti-HCV seronegative spouses were enrolled. RESULTS: The mean follow-up period was 45.9 months. Antibodies to HCV (anti-HCV) and HCV-RNA were tested for in each seronegative spouse every year. Seroconversion of anti-HCV occurred in only one spouse, 2 years after enrollment, with a concomitant acute hepatitis. This subject and his spouse were infected with HCV genotype 1b. Nucleotide sequence comparison of the hypervariable region of their HCV genomes showed a homology of 98%. Further phylogenetic analysis suggested that they had virtually the same isolate. Accordingly, the annual risk of interspousal transmission of HCV infection was 0.23% per year. CONCLUSIONS: These findings suggest a low incidence of interspousal transmission of HCV; however, the risk may be cumulative and such couples should be educated to avoid HCV infection from their spouses.
Disease Transmission, Infectious↗
Efficacy of consensus interferon in the treatment of chronic hepatitis C.
BACKGROUND AND AIMS: Consensus interferon (CIFN) is a newly developed type I interferon. The aim of this study was to investigate the safety and efficacy of CIFN in the treatment of patients with chronic hepatitis C and to determine the predictors for sustained response. METHODS: Patients were randomized to receive 3 micrograms or 9 micrograms CIFN three times a week for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum transaminase levels and disappearance of serum hepatitis C virus (HCV)-RNA at the end of treatment and at 24 weeks after stopping treatment. Histologic response was defined as a decrease of at least two points in the Knodell necroinflammatory score at week 48 and was compared with baseline. RESULTS: There were no serious adverse effects related to CIFN therapy. Overall, 44% of patients receiving 3 micrograms and 48% of patients receiving 9 micrograms had normalization of serum transaminase levels and disappearance of HCV viremia at the end of treatment. At 24 weeks after stopping treatment, 16% of patients in receiving 9 micrograms and 12% of patients receiving 3 micrograms had sustained responses. The histologic responses in patients receiving 9 micrograms and those receiving 3 micrograms were 60% and 36%, respectively. The necroinflammatory score was significantly reduced from baseline to week 48 in both groups. In addition, bodyweight < 60 kg and pretreatment serum HCV-RNA level < 0.5 MEq/mL can serve as predictors for sustained response to CIFN treatment. CONCLUSIONS: These findings suggest that 9 micrograms CIFN is safe and effective in the treatment of patients with chronic hepatitis C.
Adult↗
Interspousal transmission of TT virus: low efficiency and lack of apparent risk factors.
BACKGROUND: The TT virus (TTV) is a newly identified human DNA virus and little is known about its non-parenteral transmission. The aim of the present study was to explore the prevalence of TTV infection in spouses of index cases and the related risk factors. METHODS: Serum TTV-DNA was studied in spouses of 41 subjects with TT viremia. For couples in which both husband and wife had TT viremia, nucleotide sequences of the open reading frame-1 region were analyzed by phylogenetic tree constructions. RESULTS: Three (7%) of 41 spouses were positive for TTV-DNA. No differences were noted between index patients with seropositive spouses and those without seropositive spouses with regard to clinical characteristics, including parenteral risk factors and exposure duration. Nucleotide sequence comparison and phylogenetic tree analysis of the viral genome in three TTV-infected couples revealed the isolates to be closely related in two, with a homology of 97 and 98%, respectively. CONCLUSIONS: These results suggest that interspousal transmission of TTV does occur; however,the efficiency of transmission is low compared with hepatitis C virus and GB virus-C. There are no apparent risk factors for transmission between spouses and further studies are needed to clarify other modes of non-parenteral transmission.
Adult↗
Regenerative sprouting of retinal ganglion cells of adult hamsters induced by the epineurium of a peripheral nerve.
Although it is known that transplantation of a peripheral nerve (PN) to the damaged central nervous system (CNS) promotes axonal regeneration, the interactions of cellular components of the PN with CNS neurons are still not well defined. Schwann cells in the PN are thought to be the major element involved in supporting CNS regeneration, but very little information exists with regard to whether other PN components also play an active role. Using our previously established model of transplanting a PN segment into the vitreous to stimulate regenerative sprouting of retinal ganglion cells (RGCs), we found that the epineurium isolated from a PN which had been pre-injured by transection was able to induce RGC sprouting when implanted intravitreally. Since the epineurium is composed mainly of connective tissue components and is devoid of Schwann cells, our results suggest that other cellular elements of the PN besides Schwann cells may have the potential to support CNS regeneration.
Animals↗
Inhibition of hTAFII32-binding implicated in the transcriptional repression by central regions of mutant p53 proteins.
We previously identified a movable and regulable inactivation function within the central region (CRts247) of a temperature-sensitive p53 (p53(ts)) mutant, p53(N247I). Here we showed that central regions from several p53(ts) mutants behaved similarly, i.e. they repressed a neighboring activation domain only when existing in the mutant status. Using chimeric protein GAL4VP16-CRts247 as an example, we demonstrated that de novo protein synthesis was not required for the reactivation of the chimeric protein, indicating that a post-translational mechanism was involved in the control of CRts247 activity. The CRts247-conferred thermo-regulability did not work via a mechanism demanding either an alteration of the subcellular compartmentalization of or the inactivation of DNA-binding activity of the GAL4 chimera. Further, CRts247 did not function in trans, eliminating the possibility that the observed repression was because of the competition for a putative factor(s) by the mutant p53 domain. Rather, CRts247 bestowed temperature-dependent interaction with hTAFII32 to the VP16 activation domain. In a parallel experiment, CRts247 also caused a large reduction in the affinity of hTAFII32 to the p53 activation domain at the nonpermissive temperature. These results strongly suggested that inhibition of hTAFII32 binding could be one of the mechanisms responsible for the transcriptional repression by mutant p53 central regions.
Mutation↗
A multicentered clinical study of serum as adjuvant therapy for surgical treatment of macular holes. Vitrectomy for Macular Hole Study Group.
OBJECTIVE: To evaluate and compare the risks and benefits of autologous serum as an adjuvant therapy in macular hole surgery for stage 3 or 4 macular holes. METHODS: Comparison of 2 consecutive (nonrandomized) cohorts using standardized methods for the determination of hole size and for surgical procedures, and using the same study surgeons. The serum cohort consisted of 106 eyes using autologous serum as an adjuvant, and the no serum cohort consisted of 58 eyes without adjuvants. The primary end point was the closure of the macular hole as determined by the 6-month fundus photographs. Secondary end points included the number and types of postoperative complications. Comparison in outcomes between the 2 cohorts used chi2 and logistic regression procedures, adjusting for preoperative differences between the study cohorts. RESULTS: At 6 months, the (unadjusted) rate of hole closure was significantly greater for the eyes treated with serum than for the eyes not treated with serum (90 [85%] of 106 vs. 40 [69%] of 58, P = .04). However, after adjusting for preoperative differences in hole diameter and the prevalence of epiretinal membranes, no overall difference in hole closure rates due to serum was found (P = .44). In contrast, benefit due to serum for large holes (diameter >573 microm) was seen (12 [75%] of 16 vs 13 [57%] of 23, P = .04). No differences in complication rates were found between the cohorts. CONCLUSIONS: Any beneficial effect of serum used as an adjuvant to macular hole surgery is small, and, if present, the beneficial effect may be limited to larger holes. A randomized, prospective, controlled study in larger macular holes is needed.
Adult↗
Prevalence and implication of TT virus infection: minimal role in patients with non-A-E hepatitis in Taiwan.
TT virus (TTV) is a newly identified human DNA virus and little is known about its clinical significance. The aim of the study was to explore the prevalence of TTV infection in different risk populations and in patients with various liver diseases. Viral DNA was studied in 190 high-risk individuals, 97 household contacts, 52 patients with acute hepatitis A, 32 patients with non-A-E hepatitis including 13 fulminant hepatitis, 200 asymptomatic hepatitis B surface antigen (HBsAg) carriers, 100 patients with chronic hepatitis C, and 100 healthy adults. TTV infection was more frequent in high-risk groups (26-70%), patients with acute or fulminant non-A-E hepatitis (42-45%), and hepatitis C carriers (36%) than in healthy adults (10%) and hepatitis B carriers (15%). However, most of subjects with TTV infection alone had no or only mild hepatitis, and the same rate of TTV DNA in pre-hepatitis serum samples and constant serum TTV titers during hepatitis episodes were observed in two patients with acute non-A-E hepatitis. Phylogenetic analysis of the Taiwanese TTV isolates showed genetic heterogeneity and most (68%) isolates were TTV type 1. No particular strain was found to be associated with fulminant non-A-E hepatitis.
Acute Disease↗
Liver and peripheral blood mononuclear cells are not major sites for GB virus-C/hepatitis G virus replication.
The pathogenesis and replication sites of GB virus-C/hepatitis G virus (GBV-C/HGV) in humans remain unclear. The presence of GBV-C/HGV and hepatitis C virus (HCV) RNA sequences in matched serum, peripheral blood mononuclear cells (PBMC) and liver samples in 10 patients with GBV-C/HGV infection, 8 of whom were coinfected with HCV was explored. Positive- and negative-strand GBV-C/HGV and HCV RNA were detected by strand-specific reverse-transcription polymerase chain reaction (RT-PCR), and virus titers were quantified by competitive PCRs. Positive-strand GBV-C/HGV RNA was detected in 7 of 10 PBMC samples of the patients with serum GBV-C/HGV RNA, but negative-strand GBV-C/HGV RNA was not found in these cells. Positive-strand GBV-C/HGV RNA was found in 9 liver samples, and 2 (22%) of them also had negative strand. In contrast, negative-strand HCV RNA was frequently found in PBMC and liver samples. A positive correlation between the titer of viral RNA in liver tissue and that in serum sample was demonstrated in HCV infection, but not in GBV-C/HGV infection. These findings suggest that liver and PBMC are not the major replication sites for GBV-C/HGV and that GBV-C/HGV is not a primary hepatotropic virus.
Adult↗
Silicone oil in the repair of pediatric complex retinal detachments: a prospective, observational, multicenter study.
OBJECTIVE: To report anatomic and visual acuity outcomes, as well as complications, after using 1000-centistoke silicone oil as a retinal tamponade for the treatment of complex retinal detachments in a pediatric population. DESIGN: A prospective, observational, multicenter study. PARTICIPANTS: The study cohort consisted of 205 patients 16 years of age or younger (211 eyes) treated at community and university-based ophthalmology clinics for complex retinal detachments associated with trauma, proliferative vitreoretinopathy (PVR), giant retinal tear (GRT), or retinopathy of prematurity (ROP). INTERVENTION: Vitrectomy surgery for complex retinal detachment with 1000-centistoke silicone oil as the retinal tamponade. MAIN OUTCOME MEASURES: Anatomic outcomes include complete retinal attachment and macular attachment. Visual acuity outcomes include ambulatory vision (> or = 4/200) and preservation of preoperative visual acuity. Complications include rates of secondary intraocular pressure (IOP) elevation (> or = 30 mmHg), hypotony (< or = 5 mmHg), corneal opacification (including band keratopathy, corneal edema, and corneal abrasions), oil emulsification, and cataract. All outcome measures were assessed 6, 12, and 24 months after surgery and at last examination. RESULTS: At the 6-month examination, the retina was completely attached in 43 (57%) of 76 eyes in the trauma group, 24 (63%) of 38 PVR eyes, 23 (68%) of 34 GRT eyes, and 6 (33%) of 18 ROP eyes. The macula was attached in 60 (79%), 33 (87%), 26 (76%), and 8 (44%) eyes, respectively. Ambulatory vision was achieved in 19 (25%) eyes in the trauma group, 18 (47%) PVR eyes, 19 (56%) GRT eyes, and 4 (22%) ROP eyes. Visual acuity was preserved in 53 (70%), 26 (68%), 28 (82%), and 9 (50%) eyes, respectively. The corresponding rates of complications for traumatic, PVR, GRT, and ROP eyes were: elevated IOP-3 (4%) of 76, 1 (3%) of 38, 1 (3%) of 34, and 0 (0%) of 18; hypotony--9 (12%), 3 (8%), 2 (6%), and 2 (11%); corneal opacity--25 (33%), 8 (21%), 15 (44%), and 5 (28%); emulsification--4 (5%), 1 (3%), 3 (9%), and 1 (6%); and cataract in phakic eyes--1 (33%) of 3, 2 (67%) of 3, 2 (50%) of 4, and 1 (33%) of 3. CONCLUSIONS: Retinal reattachment and preserved visual acuity were achieved in the majority of eyes using vitrectomy and silicone oil retinal tamponade. Complete retinal and macular attachment was achieved less frequently in ROP eyes than in eyes in the other diagnostic groups. Use of 1000-centistoke silicone oil can be considered in the management of pediatric complex retinal detachments associated with multiple etiologies.
Adolescent↗
Minimal role of GB virus-C/hepatitis G virus in fulminant and subfulminant hepatitis in Taiwan.
BACKGROUND: The role of GB virus-C/hepatitis G virus (GBV-C/HGV) in fulminant hepatitis (FH) and subfulminant hepatitis (SFH) remains unclear. METHODS: Thirty-two FH or SFH patients, with adequate clinical information and serum specimens, were studied. Serum samples were tested for hepatitis markers and genomes of hepatitis A-E viruses, as well as GBV-C/HGV. RESULTS: Of the cases of FH/SFH studied, one (3%) was caused by anti-tuberculosis agents, 26 (81%) had hepatotropic virus infection, and five (16%) had no identifiable cause. Of the 26 patients with hepatotropic virus infection, five had acute hepatitis B infection (one with acute hepatitis D virus (HDV) co-infection), one had acute hepatitis C infection, 16 were hepatitis B surface antigen carriers with reactivation or superimposed by unidentified agent(s) (two had triple virus infections), three were hepatitis B carriers with HDV superinfection, and one had GBV-C/HGV infection in addition to exposure to halothane. GBV-C/HGV-RNA was detected in only three of 32 patients (9%) and all had a history of blood transfusion or co-existing causative factors. Of the 26 patients with hepatotropic virus infection, 18 were tested for antibodies against GBV-C/HGV envelope protein and seven were reactive, suggesting past infection. CONCLUSIONS: The role of GBV-C/HGV in causing FH and SFH is minimal in Taiwan and HBV infection remains the major aetiology. These findings also suggest the existence of as yet unrecognized agents, responsible for such catastrophic illnesses.
Adult↗
Comparison of two methods for quantification of hepatitis B viral DNA.
BACKGROUND: Quantitation of serum hepatitis B virus (HBV) DNA has proven useful in assisting with patient management and treatment and several commercially available assays have been developed to quantify serum HBV-DNA levels. METHODS: The performance of the cross-linking assay and the branched-DNA signal amplification (bDNA) assay for the quantitative measurement of HBV-DNA was studied in 99 hepatitis B surface antigen-positive and viraemic patients. RESULTS: Of these samples, 82 (83%) were positive for HBV-DNA by both assays and four (4%) were below the cut-off for both assays. Of the remaining 13 samples, 10 contained measurable levels of HBV-DNA by the cross-linking assay alone and three other samples contained measurable levels of HBV-DNA by the bDNA assay alone. The sensitivity gain of the cross-linking assay relative to bDNA assay in this study population was 10/92 (11%). In addition, a linear regression analysis showed that the HBV-DNA levels obtained from both assays was significantly correlated (gamma=0.974, P< 0.0001). CONCLUSIONS: These findings suggest that the recently developed cross-linking assay is more sensitive than the bDNA assay for the quantitative determination of HBV-DNA.
DNA, Viral↗
Interferon-ribavirin for chronic hepatitis C with and without cirrhosis: analysis of individual patient data of six controlled trials. Eurohep Study Group for Viral Hepatitis.
BACKGROUND & AIMS: The aim of this study was to compare interferon (IFN)-ribavirin combination therapy with IFN monotherapy in chronic hepatitis C with particular focus on its efficacy in cirrhosis. METHODS: A multivariate analysis of individual patient data of all randomized controlled trials using an IFN-ribavirin arm, reported between 1991 and March 1998, was performed. Centers included 1 Asian and 5 European university-based referral centers for liver disease. A total of 197 patients with chronic hepatitis C received IFN-alpha (3 MU three times weekly) and ribavirin (1-1.2 g daily) for 6 months, and 147 patients received IFN-alpha (3 MU three times weekly) for 6 months. Patients were characterized according to previous IFN therapy, presence of cirrhosis, and genotype 1. Efficacy of therapy was evaluated by assessing the sustained response rate by logistic regression analysis. RESULTS: Patients without cirrhosis treated with IFN-ribavirin had a significantly higher sustained response rate than those treated with IFN, approximately 3-fold for previously untreated patients (IFN-ribavirin: genotype 1, 33%; genotype 2/3, 65%; IFN: genotype 1, 8%; genotype 2/3, 24%). In cirrhosis, sustained response rates with IFN-ribavirin (previously untreated: genotype 1, 7%; genotype 2/3, 24%) were also significantly higher than those with IFN (previously untreated: genotype 1, 1%; genotype 2/3, 5%). Clinical relevant superiority of combination therapy over IFN monotherapy was also observed for relapse; the same trend was observed for nonresponders. Tolerance for IFN-ribavirin was similar for patients with or without cirrhosis. CONCLUSIONS: Combination with ribavirin significantly enhances the sustained response rate of IFN therapy in major patient types (cirrhosis, genotype 1) with chronic hepatitis C. Thus, IFN-ribavirin combination is likely to become the antiviral therapy of choice for cirrhosis caused by hepatitis C.
Adult↗
Bacterial infections associated with hepatic arteriography and transarterial embolization for hepatocellular carcinoma: a prospective study.
Sepsis and liver abscess are serious complications following transarterial embolization (TAE) for hepatocellular carcinoma (HCC). However, the exact incidence and the necessity of antibiotic prophylaxis remain undetermined. Between November 1996 and November 1997, we prospectively studied bacterial infections in 231 HCC patients who underwent 287 angiographic procedures without antibiotic prophylaxis, including 176 TAEs and 111 hepatic arteriographies (HAs). Four of the 111 HAs were complicated by transient asymptomatic bacteremia. Of the 176 TAEs, 2 were associated with asymptomatic bacteremia, and 7 (4%) were associated with symptomatic bacterial infection, including 3 cases of sepsis, 2 of liver abscess, and 2 of infected biloma. For patients with HCC, TAE was associated with a higher risk of developing symptomatic bacterial infections than was HA (4% vs. 0, respectively; P = .03). Previous gastrectomy was the only possible risk factor for liver abscess. Finally, early diagnosis and treatment of these infectious complications usually result in successful outcome.
Aged↗
Opportunistic hepatic infections in AIDS patients with fever of unknown origin.
The clinical features and histopathologic manifestations of hepatic opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS) in Taiwan remain unexplored. We report 28 AIDS patients (25 men, 3 women; mean age, 34 years) with fever of unknown origin who underwent 31 liver biopsies from December 1995 to May 1997. In most cases, the biochemical tests showed moderate to markedly elevated alkaline phosphatase concentrations, but normal or mildly elevated aminotransferase concentrations. The most common histopathologic finding was macrosteatosis, which was noted in 15 of the 28 patients. Another important histopathologic finding indicating the etiology of hepatic opportunistic infection was granuloma, which was found in 11 patients. Histochemical stain and culture of liver specimens yielded Mycobacterium avium complex (MAC) in eight patients, Mycobacterium tuberculosis in two patients, Histoplasma capsulatum in one patient, and cytomegalovirus in one patient with concomitant MAC infection. Therefore, a definitive diagnosis in AIDS patients with fever of unknown origin was made in 11 of the 28 cases with the assistance of liver biopsy. During follow-up, late extrahepatic involvement by the same infectious agents was found in six patients. Thus, hepatic manifestations could be a harbinger of disseminated opportunistic infections in AIDS patients.
AIDS-Related Opportunistic Infections↗
Time trend of substance use among adolescent students in Taiwan, 1991-1996.
The purpose of this study was to determine the prevalence and time trend of cigarette, alcohol, and illicit substance use among adolescent students in Taiwan, from 1991 through 1996. Subjects were selected through a two-stage random-sampling procedure. In the first stage, the strata were based on the type of school: middle school (13-15 years), high school (16-18), vocational school (16-18), and junior college (first 3 years only, 16-18). In the second stage, the strata were based on grade: one class each for 1st, 2nd, and 3rd grades were randomly selected from each type of school. Students were guaranteed anonymity before the questionnaire was administered. About 12,000 students from 100 schools participated each year in 1991 and 1994-1996. In 1993, 8,320 students from 65 schools participated. The prevalence of smoking and drinking decreased between 1991 and 1994, and then increased between 1994 and 1996. In 1996, the prevalence of illicit substance use was 15.4% for smoking, 16.7% for drinking, and 1.5% for illicit substance use. The rate of illicit substance use was lowest among high school students, followed by middle school students, and higher among students in vocational schools and junior colleges. The percentage of smokers and drinkers who had started early (at age 12 or earlier) rose every year. The prevalence of smoking and drinking habits among girls increased consistently during the study period. The most commonly abused substance was amphetamine. However, in 1996, sniffing glue became more prominent among middle school students, and flunitrazepam became the second most commonly abused substance among high school students.
Adolescent↗