Preduodenal portal vein, a rare anomaly, could be found in any age groups. In pediatrics it may present with a duodenal obstruction by itself or other coexisting anomalies; however it usually present with an asymptomatic or incidental findings during other surgery in adults. This anomaly has a clinical importance due to the possibility of accidental damage to portal vein. In addition to describing a series of 3 cases with different manifestation in infants, discuss about this anomaly with a review of relevant literature.
Preduodenal portal vein; Infant
Background and Aims
Predicting clinical outcomes in patients with chronic hepatitis C is challenging. We used the HALT-C Trial database to develop two models, using baseline values of routinely available laboratory tests together with changes in these values during follow-up to predict clinical decompensation and liver-related death/liver transplant in patients with advanced hepatitis C.
Patients randomized to no treatment and who had ≥2 year follow-up without a clinical outcome were included in the analysis. Four variables (platelet count, AST/ALT ratio, total bilirubin and albumin) with three categories of change (stable, mild or severe) over two years were analyzed. Cumulative incidence of clinical outcome was determined by Kaplan-Meier analysis and Cox regression was used to evaluate predictors of clinical outcome.
470 patients with 60 events were used to develop models to predict clinical decompensation. Baseline values of all four variables were predictive of decompensation. There was a general trend of increasing outcomes with more marked worsening of laboratory values over 2 years, particularly for patients with abnormal baseline values. A model that included baseline platelet count, AST/ALT ratio, bilirubin and severe worsening of platelet count, bilirubin and albumin was the best predictor of clinical decompensation. 483 patients with 79 events were used to evaluate predictors of liver-related death or liver transplant. A model that included baseline platelet count and albumin as well as severe worsening of AST/ALT ratio and albumin was the best predictor of liver-related outcomes.
Both the baseline value and the rapidity in change of the value of routine laboratory variables were shown to be important in predicting clinical outcomes in patients with advanced chronic hepatitis C.
Model; Clinical decomensation; Liver-related death; Liver transplant; Cirrhosis
Many useful statistics equal the ratio of a possibly noncentral chi-square to a quadratic form in Gaussian variables with all positive weights. Expressing the density and distribution function as positively weighted sums of corresponding F functions has many advantages. The mixture forms have analytic value when embedded within a more complex problem. The mixture forms also have computational value. The expansions work well with quadratic forms having few components and small degrees of freedom. A more general algorithm from earlier literature can take longer or fail to converge in the same setting. Many approximations have been suggested for the problem. a positively weighted noncentral quadratic form can always have two moments matched to a noncentral chi-square. For a single quadratic form, the noncentral form performs neither uniformly more or less accurately than older approximations. The approach also gives a noncentral F approximation for any ratio of a positively weighted noncentral form to a positively weighted central quadratic form. The method provides better accuracy for noncentral ratios than approximations based on a single chi-square. The accuracy suffices for many practical applications, such as power analysis, even with few degrees of freedom. Naturally the approximation proves much faster and simpler to compute than any exact method. Embedding the approximation in analytic expressions provides simple forms which correctly guarantee only positive values have nonzero probabilities, and also automatically reduce to partially or fully exact results when either quadratic form has only one term.
Cumulative distribution function; Mixture distribution; Noncentral F
This study aimed to identify the effects of the sintering conditions of dental zirconia on the grain size and translucency.
MATERIALS AND METHODS
Ten specimens of each of two commercial brands of zirconia (Lava and KaVo) were made and sintered under five different conditions. Microwave sintering (MS) and conventional sintering (CS) methods were used to fabricate zirconia specimens. The dwelling time was 20 minutes for MS and 20 minutes, 2, 10, and 40 hours for CS. The density and the grain size of the sintered zirconia blocks were measured. Total transmission measurements were taken using a spectrophotometer. Two-way analysis of variance model was used for the analysis and performed at a type-one error rate of 0.05.
There was no significant difference in density between brands and sintering conditions. The mean grain size increased according to sintering conditions as follows: MS-20 min, CS-20 min, CS-2 hr, CS-10 hr, and CS-40 hr for both brands. The mean grain size ranged from 347-1,512 nm for Lava and 373-1,481 nm for KaVo. The mean light transmittance values of Lava and KaVo were 28.39-34.48% and 28.09-30.50%, respectively.
Different sintering conditions resulted in differences in grain size and light transmittance. To obtain more translucent dental zirconia restorations, shorter sintering times should be considered.
Grain size; Sintering; Translucency; Transmittance; Y-TZP; Zirconia
One of the most important factors in evaluating the quality of fixed dental prostheses (FDPs) is their gap. The purpose of this study was to compare the marginal and internal gap of two different metal-ceramic crowns, casting and selective laser sintering (SLS), before and after porcelain firing. Furthermore, this study evaluated whether metal-ceramic crowns made using the SLS have the same clinical acceptability as crowns made by the traditional casting.
MATERIALS AND METHODS
The 10 study models were produced using stone. The 20 specimens were produced using the casting and the SLS methods; 10 samples were made in each group. After the core gap measurements, 10 metal-ceramic crowns in each group were finished using the conventional technique of firing porcelain. The gap of the metal-ceramic crowns was measured. The marginal and internal gaps were measured by two-dimensional and three-dimensional replica techniques, respectively. The Wilcoxon signed-rank test, the Wilcoxon rank-sum test and nonparametric ANCOVA were used for statistical analysis (α=.05).
In both groups, the gap increased after completion of the metal-ceramic crown compared to the core. In all measured areas, the gap of the metal cores and metal-ceramic crowns produced by the SLS was greater than that of the metal cores and metal-ceramic crowns produced using the casting. Statistically significant differences were found between cast and SLS (metal cores and metal-ceramic crown).
Although the gap of the FDPs produced by the SLS was greater than that of the FDPs produced by the conventional casting in all measured areas, none exceeded the clinically acceptable range.
CAD-CAM; Marginal adaptation; Metal ceramics restorations; Replica techniques
The aim of this study was to measure the peri-implant bone length surrounding implants that penetrate the sinus membrane at the posterior maxilla and to evaluate the survival rate of these implants.
Treatment records and orthopantomographs of 39 patients were reviewed and analyzed. The patients had partial edentulism at the posterior maxilla and limited vertical bone height below the maxillary sinus. Implants were inserted into the posterior maxilla, penetrating the sinus membrane. Four months after implant insertion, provisional resin restorations were temporarily cemented to the abutments and used for one month. Then, a final impression was taken at the abutment level, and final cement-retained restorations were delivered with mutually protected occlusion. The complications from the implant surgery were examined, the number of failed implants was counted, and the survival rate was calculated. The peri-implant bone lengths were measured using radiographs. The changes in initial and final peri-implant bone lengths were statistically analyzed.
Nasal bleeding occurred after implant surgery in three patients. No other complications were found. There were no failures of the investigated implants, resulting in a survival rate of 100%. Significantly more bone gain around the implants (estimated difference=-0.6 mm, P=0.025) occurred when the initial residual bone height was less than 5 mm compared to the >5 mm groups. No significant change in peri-implant bone length was detected when the initial residual bone height was 5 mm or larger.
This study suggests that implants penetrating the sinus membrane at the posterior maxilla in patients with limited vertical bone height may be safe and functional.
Biomechanics; Biostatistics; Maxilla; Maxillary sinus; Sinus floor augmentation
Anorectal malformations are often associated with other anomalies, reporting frequency with 40-70%. Gastrointestinal anomalies have been known to be relatively less common than associated anomalies of other organ system. This study was performed to assess a distinctive feature of cases associated with esophageal atresia.
Clinical data (from January 2000 through December 2011) on the 196 subjects with anorectal malformations, managed in our Hospital, were reviewed. Total 14 neonates were identified with accompanying esophageal atresia and retrospective analysis was conducted.
The incidence was 7.1% and there were 8 male and 6 female subjects. Only 2 cases were associated with esophageal atresia without tracheoesophageal fistula. Although variable cases of anorectal malformation in female subjects, almost cases were anorectal malformations with rectourethral fistula in male. Other associated anomalies were identified in all cases, with more than 3 anomalies in 10 cases. There were 4 VACTERL (Vertebral abnormalities, Anal atresia, Cardiac anomalies, Tracheoesophageal fistula, Esophageal atresia, Renal and Limb anomalies) associations accounting for 28.6%, but could not identify chromosomal anomaly. Most cases were managed with staged procedure, usually primary repair of esophageal atresia and diverting colostomy. Overall mortality rate was 21.4%, mainly caused by heart problems.
This study shows that early diagnosis and rational surgical approach with multidisciplinary plan are mandatory in managing anorectal malformations with esophageal atresia, when considering a high frequency of associated anomaly and a relative high mortality.
Anorectal malformation; Esophageal atresia; Neonates
Congenital infantile fibrosarcoma (CIF) is a rare soft-tissue tumor in the pediatric age group and seldom involves the gastrointestinal tract. A 2-day-old boy was transferred to our hospital with a pneumpoperitoneum. After emergency operation, we could find a solid mass wrapping around a sigmoid colon and performed a segmental resection of sigmoid colon including a mass. Histopathologic examination showed an infantile fibrosarcoma origining from the muscular layer of colon. The baby was discharged on the 17th hospital day and followed for 1 yr without recurrence.
Congenital Infantile Fibrosarcoma (CIF); Gastrointestinal
HIV-infected women, particularly those with advanced disease, may have higher rates of pregnancy loss (miscarriage and stillbirth) and neonatal mortality than uninfected women. Here we examine risk factors for these adverse pregnancy outcomes in a cohort of HIV-infected women in Zambia considering the impact of infant HIV status.
A total of 1229 HIV-infected pregnant women were enrolled (2001–2004) in Lusaka, Zambia and followed to pregnancy outcome. Live-born infants were tested for HIV by PCR at birth, 1 week and 5 weeks. Obstetric and neonatal data were collected after delivery and the rates of neonatal (<28 days) and early mortality (<70 days) were described using Kaplan-Meier methods.
The ratio of miscarriage and stillbirth per 100 live-births were 3.1 and 2.6, respectively. Higher maternal plasma viral load (adjusted odds ratio [AOR] for each log10 increase in HIV RNA copies/ml = 1.90; 95% confidence interval [CI] 1.10–3.27) and being symptomatic were associated with an increased risk of stillbirth (AOR = 3.19; 95% CI 1.46–6.97), and decreasing maternal CD4 count by 100 cells/mm3 with an increased risk of miscarriage (OR = 1.25; 95% CI 1.02–1.54). The neonatal mortality rate was 4.3 per 100 increasing to 6.3 by 70 days. Intrauterine HIV infection was not associated with neonatal morality but became associated with mortality through 70 days (adjusted hazard ratio = 2.76; 95% CI 1.25–6.08). Low birth weight and cessation of breastfeeding were significant risk factors for both neonatal and early mortality independent of infant HIV infection.
More advanced maternal HIV disease was associated with adverse pregnancy outcomes. Excess neonatal mortality in HIV-infected women was not primarily explained by infant HIV infection but was strongly associated with low birth weight and prematurity. Intrauterine HIV infection contributed to mortality as early as 70 days of infant age. Interventions to improve pregnancy outcomes for HIV-infected women are needed to complement necessary therapeutic and prophylactic antiretroviral interventions.
Perinatal mortality; Infant mortality; Risk factors; Adverse pregnancy outcome; HIV infection; Vertical transmission
Background & Aim
Previous studies have suggested that prior exposure to hepatitis B virus (HBV) infection may increase the risk of development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The aim of this study was to compare the prevalence of previous or occult HBV infection in a cohort of HBsAg-negative patients with histologically advanced chronic hepatitis C in the United States who did or did not develop HCC.
Stored sera from 91 patients with HCC and 182 matched controls who participated in the HALT-C Trial were tested for anti-HBc, anti-HBs and HBV DNA. Frozen liver samples from 28 HCC cases and 55 controls were tested for HBV DNA by real-time PCR.
Anti-HBc (as a marker of previous HBV infection) was present in the serum of 41.8% HCC cases and 45.6% controls (P=0.54); anti-HBc alone was present in 16.5% of HCC cases and 24.7% of controls. HBV DNA was detected in the serum of only one control subject and no patient with HCC. HBV DNA (as a marker of occult HBV infection) was detected in the liver of 10.7% HCC cases and 23.6% controls (P=0.18).
Although almost half the patients in the HALT-C Trial had serological evidence of previous HBV infection there was no difference in prevalence of anti-HBc in serum or HBV DNA in liver between patients who did or did not develop HCC. In the United States, neither previous nor occult HBV infection is an important factor in HCC development among patients with advanced chronic hepatitis C.
HBV DNA; hepatitis B core antibody; cirrhosis
The PROSPERO server analyzes sequence and experimental protein characterization results, then uses that analysis to predict crystallization outcome and suggest priorities for futher work on difficult targets. The server allows users to upload data from six types of experiment, to organize those data by sample and project, and to share those data with collaborators.
The growth of diffracting crystals from purified proteins is often a major bottleneck in determining structures of biological and medical interest. The PROSPERO web server, http://skuld.bmsc.washington.edu/prospero, is intended both to provide a means of organizing the potentially large numbers of experimental characterizations measured from such proteins, and to provide useful guidance for structural biologists who have succeeded in purifying their target protein but have reached an impasse in the difficult and poorly understood process of turning purified protein into well diffracting crystals. These researchers need to decide which of many possible rescue options are worth pursuing, given finite resources. This choice is even more crucial when attempting to solve high-priority but relatively difficult structures of eukaryotic proteins. The site currently uses the HyGX1 predictor, which was trained and validated on protein samples from pathogenic protozoa (eukaryotes) using results from six types of experiment. PROSPERO allows users to store, analyze and display multiple results for each sample, to group samples into projects, and to share results and predictions with collaborators.
protein crystallography; protein characterization; PROSPERO; computer programs
Background & Aims
Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The Hepatitis C anti-viral long-term treatment against cirrhosis (HALT-C) trial showed that 4 years of maintenance therapy with peginterferon does not reduce liver disease progression. We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer post-treatment follow-up period.
The study included 1,048 patients with chronic Hepatitis C (Ishak fibrosis scores ≥3) who did not have a sustained virological response (SVR) to therapy. They were randomly assigned to groups given a half-dose of peginterferon or no treatment (controls) for 3.5 years and followed for a median 6.1 (maximum 8.7) years.
Eighty-eight patients developed HCC (68 definite, 20 presumed): 37/515 that were given peginterferon (7.2%) and 51/533 controls (9.6%; P=0.24). There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis, but not fibrosis, based on analysis of baseline biopsy samples. After 7 years, the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio [HR]=0.45; 95% confidence interval [CI]: 0.24–0.83); in treated and control patients with fibrosis they were 8.3% and 6.8%, respectively (HR=1.44; 95% CI: 0.77–2.69). Treated patients with a ≥2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs. 9.4%; P=0.03).
Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs. Patients with cirrhosis who received peginterferon treatment had a lower risk for HCC than controls.
Interferon therapy; hepatitis C clinical trial; interferon non-responders; liver cancer
Advances in the management of thalassemia have resulted in increased life expectancy and new challenges. We conducted the first survey of education and employment status of people with thalassemia in North America.
A total of 633 patients (349 adults and 284 school age children) enrolled in the Thalassemia Clinical Research Network (TCRN) registry in Canada and the US were included in the data analysis. Predictors considered for analysis were age, gender, race/ethnicity, site of treatment (Canada vs. United States), transfusion and chelation status, serum ferritin, and clinical complications.
Seventy percent of adults were employed of which 67 percent reported working full-time. Sixty percent had a college degree and 14% had achieved some post college education. Eighty-two percent of school age children were at expected grade level. In a multivariate analysis for adults, Whites (OR=2.76, 95% CI: 1.50-5.06) were more likely to be employed compared to Asians. Higher education in adults was associated with older age (OR=1.67, 95% CI: 1.29-2.15), female gender (OR=2.08, 95% CI: 1.32-3.23) and absence of lung disease (OR=14.3, 95% CI: 2.04-100). Younger children (OR=5.7 for 10 year increments, 95% CI: 2.0 – 16.7) and Canadian patients (OR=5.6, 95% CI: 1.5-20) were more likely to be at the expected education level. Neither transfusion nor chelation was associated with lower employment or educational achievement.
Individuals with thalassemia in North America can achieve higher education; however, full-time employment remains a problem. Transfusion and chelation do not affect employment or education status of this patient population.
Employment; Education; Thalassemia
Background & Aims
Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response (SVR) have a lower risk of hepatic decompensation and hepatocellular carcinoma (HCC). In this prospective analysis, we compared the rate of death from any cause or liver transplantation, and of liver-related morbidity and mortality, after antiviral therapy among patients who achieved SVR, virologic nonresponders (NR) and those with initial viral clearance but subsequent breakthrough or relapse (BT/R) in the HALT-C Trial.
Laboratory and/or clinical outcome data were available for 140 of the 180 SVR patients. Nonresponders (n=309) or BT/R (N=77) were evaluated every 3 months for 3.5 years and then every 6 months thereafter. Outcomes included death, liver-related death, liver transplantation, decompensated liver disease, and HCC.
Median follow-up for SVR, BT/R, and NR patients was 86, 85, and 79 months, respectively. At 7.5 years, the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group (2.2% and 2.7%, respectively) was significantly lower than that in NR (21.3% and 27.2%, p<0.001 for both) but not the BT/R (4.4% and 8.7%). The adjusted hazard ratio [HR] for time to death/liver transplantation (HR=0.17, 95% CI: 0.06–0.46), or development of liver-related morbidity/mortality (HR=0.15, 95% CI: 0.06–0.38) or HCC (HR=0.19, 95% CI: 0.04–0.80) was significant for SVR compared to NR. Laboratory tests related to liver-disease severity improved following SVR.
Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation, and in liver-related morbidity/mortality, although they remain at risk for HCC.
hepatitis C treatment; peginterferon; survival analysis; hepatocellular carcinoma
BACKGROUND & AIMS
With the limited efficacy of current therapy for chronic hepatitis C, modifiable risk factors for liver disease progression are important to identify. Because obesity is associated with liver disease, we examined the effects of weight-related conditions on disease outcomes in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial.
Of 1050 patients, 985 could be evaluated for predefined progression of liver disease not related to hepatocellular carcinoma. Clinical outcomes were determined over 3.5 years for all patients and progression to cirrhosis on protocol biopsy among patients who had bridging fibrosis (56.5% of cohort) at entry.
At study entry, median body mass index was high (29.2 kg/m2) and accompanied by other weight-related conditions, including diabetes (24.9%), high median waist circumference, and insulin resistance (by updated homeostasis model assessment of insulin resistance; HOMA2-IR). Among noninvasive measures, HOMA2-IR was most strongly associated with outcomes with hazard ratio (HR) of 1.26 per quartile increase (95% CI, 1.09 –1.45). Presence of steatosis on baseline biopsy was associated with an increased outcome rate among patients with bridging fibrosis (P < .0001) and a decreased rate among patients with cirrhosis (P = .006). Presence of Mallory bodies was associated with outcomes (HR, 1.59; 95% CI, 1.10 –2.31) as was significant weight change of ≥5% in the first year after randomization (HR, 1.25 per category increase in weight, 95% CI, 1.01–1.55).
Insulin resistance, histologic features of fatty liver disease, and weight change were associated with outcomes of chronic hepatitis C. Improvement in these weight-related factors might modify disease progression.
We assessed the effects of long-term peginterferon therapy and disease progression on health-related quality of life (HRQOL), symptoms, and sexual health in patients with chronic hepatitis C (CHC) and advanced fibrosis or cirrhosis.
517 HALT-C Trial patients received peginterferon alfa-2a (90 μg/week); 532 received no additional treatment for 3.5 years. Patients were followed for outcomes of death, hepatocellular carcinoma and hepatic decompensation. Sexual health, SF-36 scores, and symptoms were serially assessed by repeated measures analyses of covariance.
Patients with cirrhosis (n=427) reported lower general well-being and more fatigue (p<0.001) than patients with fibrosis (n=622). Physical scores declined significantly over time, independent of treatment, and patients with cirrhosis reported lower scores. Vitality scores were lower in those with cirrhosis, and treated patients experienced a greater decline over time than untreated patients; HRQOL rebounded after treatment ended. Patients with a clinical outcome had significantly greater declines in all SF-36 and symptom scores. Among men, sexual health scores were significantly worse in treated patients and in those with a clinical outcome.
Clinical progression of CHC and maintenance peginterferon therapy led to worsening of symptoms, HRQOL, and, in men, sexual health in a large patient cohort followed over 4 years.
health related quality of life; sexual functioning; hepatitis; viral type C; SF-36; cirrhosis
Mahogunin Ring Finger-1 (Mgrn1) null mutant mice have a pleiotropic phenotype that includes the absence of yellow hair pigment, abnormal head shape, reduced viability and adult-onset spongiform neurodegeneration. Mgrn1 encodes a highly conserved E3 ubiquitin ligase with 4 different isoforms which are differentially expressed and predicted to localize to different subcellular compartments. To test whether loss of specific isoforms causes different aspects of the mutant phenotype, we generated transgenes for each isoform and bred them onto the null mutant background. Mice expressing only isoform I or III appeared completely normal. Isoform II rescued or partially rescued the mutant phenotypes, while isoform IV had little or no effect. Our data show that different Mgrn1 isoforms are not functionally equivalent in vivo and that the presence of only isoform I or III is sufficient for normal development, pigmentation and neuronal integrity.
Mahogunin Ring Finger-1; isoforms; spongiform neurodegeneration; pigmentation; craniofacial patterning; transgenesis
Background and Aims:
The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. The aim of this study was to compare the accuracy of alpha fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) in the early diagnosis of HCC.
Among 1031 patients randomized in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial, a nested case-control study of 39 HCC cases (24 early stage) and 77 matched controls was conducted to compare the performance of AFP and DCP. Testing was performed on sera from 12 months prior (month −12) to the time of HCC diagnosis (month 0).
The sensitivity and specificity of DCP at month 0 was 74% and 86% at a cutoff of 40 mAU/mL and 43% and 100% at a cutoff of 150 mAU/mL. The sensitivity and specificity of AFP at month 0 was 61% and 81% at a cutoff of 20 ng/mL and 22% and 100% at a cutoff of 200 ng/mL. At month −12, the sensitivity and specificity at the low cutoff was 43% and 94% for DCP and 47% and 75% for AFP. Combining both markers increased the sensitivity to 91% at month 0 and 73% at month 12 but the specificity decreased to 74% and 71%. Diagnosis of early HCC was triggered by surveillance ultrasound in 14, doubling of AFP in 5 and combination of tests in 5 patients.
Biomarkers are needed to complement ultrasound in the detection of early HCC but neither DCP nor AFP is optimal.
hepatitis C; interferon; cirrhosis
We consider the optimal configuration of a square array group testing algorithm (denoted A2) to minimize the expected number of tests per specimen. For prevalence greater than 0.2498, individual testing is shown to be more efficient than A2. For prevalence less than 0.2498, closed form lower and upper bounds on the optimal group sizes for A2 are given. Arrays of dimension 2 × 2, 3 × 3, and 4 × 4 are shown to never be optimal. The results are illustrated by considering the design of a specimen pooling algorithm for detection of recent HIV infections in Malawi.
We derive the operating characteristics of three-dimensional array-based testing algorithms for case identification in the presence of testing error. The operating characteristics investigated include efficiency (i.e., expected number of tests per specimen) and error rates (e.g., sensitivity, specificity, positive, and negative predictive values). The methods are illustrated by comparing the proposed algorithms with previously studied hierarchical and two-dimensional array algorithms for detecting recent HIV infections in North Carolina. Our results indicate that three-dimensional array-based algorithms can be more efficient and accurate than previously proposed algorithms in settings with test error and low prevalence.
Array; Group testing; Hierarchical; HIV; Predictive value; Sensitivity; Specificity
Hepatic steatosis is a common histologic feature in patients with chronic hepatitis C (CHC) but there are no large longitudinal studies describing the progression of steatosis in CHC. We examined changes in steatosis on serial biopsies among CHC patients participating in the HALT-C Trial. All 1,050 patients in the trial had advanced fibrosis at baseline biopsy and were documented not to have had a sustained virological response to peginterferon and ribavirin. Most (94%) patients had genotype 1 infection. At least 1 protocol follow-up biopsy was read on 892 patients, and 699 had the last biopsy performed 3.5 years after randomization. At enrollment, 39% had cirrhosis and 61% had bridging fibrosis; 18%, 41%, 31% and 10% had steatosis scores of 0, 1, 2, and 3 or 4, respectively. Mean steatosis score decreased in the follow-up biopsies in both the interferon-treated patients and controls with no effect of treatment assignment (p=0.66). A decrease in steatosis score by ≥1 point was observed in 30% of patients and was associated with both progression to cirrhosis and continued presence of cirrhosis (p=0.02). Compared to patients without decrease in steatosis, those with decrease in steatosis had worse metabolic parameters at enrollment; and were more likely to have decrease in alcohol intake, improvement in metabolic parameters and worsening liver disease (cirrhosis, esophageal varices, and deterioration in liver function).
In conclusion, serial biopsies demonstrated that in patients with chronic hepatitis C steatosis recedes during progression from advanced fibrosis to cirrhosis. Decreased alcohol intake and improved metabolic parameters are associated with decline in steatosis and may modulate hepatitis C progression.
insulin resistance; interferon treatment; liver fibrosis; cirrhosis