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PubMed1999

Thin cutaneous malignant melanomas (< or =1.5 mm): identification of risk factors indicative of progression.

BACKGROUND: Although thin cutaneous melanomas generally have a favorable prognosis, in some cases they may undergo progression. The current study was undertaken to identify variables that may predict a more aggressive clinical outcome in these patients. In addition to classic clinicopathologic features, the authors tested the prognostic impact of three new morphometric quantitative parameters: 1) tumor thickness plus regression thickness (T+R), 2) percentage of skin thickness infiltrated by tumor cells (T/S ratio), and 3) percentage of skin thickness infiltrated by tumor cells and regression ([T+R]/S ratio). METHODS: The authors retrospectively evaluated 287 patients with invasive cutaneous melanoma < or = 1.5 mm in thickness. Disease free survival rates (Kaplan-Meier method) were compared by using the log rank test. A multivariate analysis (Cox proportional hazards model) was used to determine the independent effect of each variable on progression. Progression was defined as any documented cutaneous local and/or distant metastasis. RESULTS: Thirty-two of the 287 patients (11.1%) underwent disease progression. The overall 5-year and 10-year disease free survival rates were 89.3% and 84.6%, respectively. In the univariate analysis, the following factors were found to be significant predictors of progression: male gender (P = 0.01), acral-lentiginous histotype (P = 0.02), tumor thickness (P = 0.005), T+R (P = 0.001), T/S ratio > or = 50% (P = 0.03), (T+R)/S ratio > or = 50% (P = 0.006), vertical growth phase (P = 0.04), and absence of inflammatory response (P < 0.0001). Conversely, age, site, and Clark's level did not affect the risk of recurrences and/or metastases significantly. In the multivariate analysis, only T+R (P = 0.009) and inflammatory response (P < 0.0001) were found to be independent predictors of progression. Five-year disease free survival rates according to presence versus absence of inflammatory response were 93.4% and 63.8%, respectively (P < 0.0001). CONCLUSIONS: In the current study, peritumoral and intratumoral inflammatory infiltrate and T+R were found to be strong independent predictors of progression in thin cutaneous melanomas.

Adult↗
PubMed1999

Correlation of CD44S expression in renal clear cell carcinomas with subsequent tumor progression or recurrence.

BACKGROUND: Recent reports have shown altered expression of CD44 in renal cell carcinomas. However, to the authors' knowledge there are no data correlating CD44 expression in renal cell carcinomas with subsequent tumor progression or recurrence, nor is there information about the presence of particular splice variants of CD44 in these tumors. METHODS: The authors examined the immunohistochemical expression of CD44S, the standard isoform of CD44, in renal cell carcinomas from 43 patients using 2 different monoclonal antibodies, Mab2137 and Hermes-3. In addition, they stained the renal cell carcinomas with antibodies to 2 splice variants of CD44, CD44v3 and CD44v6. RESULTS: Increased staining of renal clear cell carcinomas with Mab2137 was observed in high grade versus low grade tumors (45% vs. 0%, P = 0.013), whereas increased staining of clear cell carcinomas with Hermes-3 was noted in high stage versus low stage tumors (40% vs. 0%, P = 0.006). Few tumors stained with antibodies to CD44v3. Although increased expression of the splice variant CD44v6 was noted in papillary versus clear cell carcinomas, and increased staining of papillary carcinomas with Mab2137 and with antibodies to CD44v6 was noted for low stage versus high stage tumors, these differences did not achieve statistical significance. Clinical follow-up of at least 43 months was available for 26 patients. Six of these patients (five with clear cell carcinoma and one with papillary carcinoma) developed progressive or recurrent disease. The primary tumors from all 5 patients with progressive or recurrent clear cell carcinoma showed staining with Mab2137, whereas the primary tumors from only 2 of the 15 patients with at least 43 months follow-up and no evidence of progressive or recurrent clear cell carcinoma (13%) showed staining with Mab2137 (P = 0.001). Alternatively, 5 of 7 clear cell carcinomas (71%) that stained with Mab2137 were from patients who subsequently developed recurrence or progression, compared with 0 of 13 clear cell carcinomas that did not stain. Similar findings were not observed for papillary carcinomas, which appeared to be biologically distinct from clear cell carcinomas. CONCLUSIONS: CD44S staining with Mab2137 correlates with progression or recurrence of clear cell renal cell carcinoma. CD44S may, therefore, play a pathogenetic role in tumor progression.

Adult↗
PubMed1999

1q23 gain is associated with progressive neuroblastoma resistant to aggressive treatment.

Neuroblastoma is one of the most common malignant tumors of childhood and is characterized by regressive and progressive disease. Genetic factors that define progression of neuroblastomas are still unknown. We performed comparative genomic hybridization (CGH) on 27 neuroblastomas and dual-color fluorescence in situ hybridization (FISH) to identify genetic aberrations associated with progressive neuroblastoma showing resistance to aggressive treatment. 17q21-q25 gains and MYCN amplification were associated with stage 4 neuroblastomas; however, these genetic aberrations had no significant relation to the progression of stage 4 neuroblastomas. A novel chromosomal gain at 1q21-q25 was found in 8 of 16 cases (50%) of stage 4 neuroblastoma. Gain of 1q21-q25 was observed in all of the progressive cases (8/8), which showed resistance to chemotherapy, including 5 fatal neuroblastomas in stage 4, whereas 1q21-q25 gain was not found in any of the 8 remission cases in stage 4. Survival analysis also showed that 1q21-q25 gain was associated with a poor outcome. High xenotransplantability in nude mice was observed for the tumors with 1q21-q25 gain (4/5; 80%). These data show that 1q21-q25 gain is strongly associated with progression of stage 4 neuroblastoma. Furthermore, by dual-color FISH analysis using cosmid clones, the 1q21-q25 gain was narrowed to increase in DNA copy number on 1q23 in the fatal type of stage 4 neuroblastoma showing this gain. These results suggest that DNA amplification at 1q23 may play a role in the development of progressive neuroblastoma in an advanced stage.

Animals↗
PubMed1998

Radiographic progression in rheumatoid arthritis: a long-term prospective study of 109 patients.

OBJECTIVE: To investigate the long-term radiographic course as a mathematical function of disease duration in individual patients and in a group of patients with rheumatoid arthritis (RA). METHODS: In 109 patients with RA, radiographic examinations of 46 diarthrodial joints were performed at regular intervals of 1-3 years, for up to 30 years after disease onset. RESULTS: Five main types of progression were identified: 1) a rare type (<1%), with no radiographic progression at all; 2) a type with a slow or moderate onset, but an increasing progression rate (9% exponential growth type and 30% linear type); 3) a type with a moderate-to-fast onset and a stable progression rate (the square-root type; 11%); 4) a type with a fast onset, but a later decreasing progression rate (the first-order kinetics type, 30%); and 5) a type characterized by slow onset, then acceleration and later deceleration (the sigmoid type, 20%). CONCLUSION: The progression of radiographic damage in RA followed mathematical functions of time. The identification of progression type may be used in the prediction of outcome in patients with RA.

Adolescent↗
PubMed2000

Differential progression of motor impairment in levodopa-treated Parkinson's disease.

OBJECTIVE: To monitor comparative progression of clinical impairment over 4 years in patients with Parkinson's disease (PD) who present on levodopa at two different levels of Hoehn and Yahr (HY) stages, II and III. BACKGROUND: The rate of clinical impairment progression in patients with PD being treated with levodopa has not been studied in detail using current, standardized assessment tools. Sample size estimates for all levodopa adjunctive treatment studies and proper definition of study groups require a solid estimate of longitudinal motor impairment progression. DESIGN/METHODS: From our computer database, we identified two groups of patients with PD being treated with levodopa based on their initial HY stage at presentation to our center (II or III). Fifty randomly selected subjects in each stage were monitored in the ON state with annual Unified Parkinson's Disease Rating Scale (UPDRS) motor scores, dyskinesia ratings, and antiparkinsonian medication doses using a repeated measures analysis of variance. RESULTS: The stage II and stage III subjects had similar disease duration. In stage II subjects, parkinsonian impairment was maintained without progression over 4 years, but in association with significantly higher dyskinesia scores and dopaminergic medication doses. In stage III subjects, UPDRS motor scores deteriorated despite more medication and increased dyskinesias. Of the established six factors comprising the UPDRS motor scale, bradykinesia accounted for the increased impairment. Initial UPDRS motor score and disease duration did not influence progression of motor impairment. CONCLUSION: In subjects with similar disease duration, progression of PD motor impairment differs significantly between stage II and stage III subjects over 4 years. Whereas in stage II subjects, parkinsonian impairment can be stabilized at the expense of increased dyskinesia and dopaminergic drugs, once subjects reach stage III, motor impairment progresses. Power estimates and sample size calculations for these groups of patients should be calculated separately.

Aged↗
PubMed1990

Differing patterns of striatal 18F-dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.

Using positron emission tomography (PET), we studied regional striatal 18F-dopa uptake in 16 patients with L-dopa-responsive Parkinson's disease (PD), 18 patients with multiple system atrophy, and 10 patients with progressive supranuclear palsy. Results were compared with those of 30 age-matched normal volunteers. The patients with PD showed significantly reduced mean uptake of 18F-dopa in the caudate and putamen compared to controls, but while function in the posterior part of the putamen was severely impaired (45% of normal), function in the anterior part of the putamen and in the caudate was relatively spared (62% and 84% of normal). Mean 18F-dopa uptake in the posterior putamen was depressed to similar levels in all patients. Unlike patients with PD, the patients with progressive supranuclear palsy showed equally severe impairment of mean 18F-dopa uptake in the anterior and posterior putamen. Caudate 18F-dopa uptake was also significantly lower in patients with progressive supranuclear palsy than in patients with PD, being depressed to the same level as that in the putamen. Mean 18F-dopa uptake values in the anterior putamen and caudate in patients with multiple system atrophy lay between PD and progressive supranuclear palsy levels. Locomotor disability of individual patients with PD or multiple system atrophy correlated with decline in striatal 18F-dopa uptake, but this was not the case for the patients with progressive supranuclear palsy. We conclude that patients with PD have selective nigral pathological features with relative preservation of the dopaminergic function in the anterior putamen and caudate, whereas there is progressively more extensive nigral involvement in multiple system atrophy and progressive supranuclear palsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission.

OBJECTIVE: To assess whether radiologic progression occurs during clinical remission in patients with rheumatoid arthritis (RA). METHODS: One hundred eighty-seven patients with RA in clinical remission were followed up clinically and radiologically for 2 years. Clinical remission was defined according to a modification of the American College of Rheumatology criteria (i.e., the criterion of fatigue was omitted, and patients had to fulfill 4 of the 5 remaining criteria). Radiologic joint damage was assessed by the Sharp/van der Heijde method. RESULTS: After 2 years of followup, remission persisted in 52% of patients. The median radiologic score for the total group of patients increased from 21 (interquartile range [IQR] 5, 65) at the time of entry to 25 (IQR 7, 72) after 2 years (P < 0.001). The median score for radiologic progression between baseline and 2 years was 0.5 (IQR 0, 2.5). Among patients with an exacerbation of RA (n = 86), the median score for progression over 2 years was 1.0 (IQR 0, 4.5) (P < 0.001), and in patients with a persistent remission (n = 93) it was 0 (IQR -0.5, 2.0) (P < 0.001). Clinically relevant progression of damage was more frequent in patients with exacerbation (23%) than in those with persistent remission (7%) (P = 0.001). However, in 15% of patients with persistent remission, an erosion developed in a previously unaffected joint. In the logistic regression analysis, the area under the curve of the Disease Activity Score, a continuous measure, was related to the chance of radiologic progression, regardless of the absolute disease activity level. Results were similar when other definitions of remission were used. CONCLUSION: Although rare, clinically relevant progression of joint damage does occur in patients with RA in prolonged remission. This suggests the need for markers that predict progression during periods of low disease activity and for drugs that prevent damage that is independent of disease activity.

Aged↗
PubMed1995

The role of HLA antigens as indicators of disease progression in psoriatic arthritis. Multivariate relative risk model.

OBJECTIVE: To identify HLA markers for the development of severe disease in psoriatic arthritis (PsA). METHODS: Patients with PsA who were followed up prospectively over a 14-year period were included. Clinical and laboratory assessments of both active inflammation and clinical damage were performed at 6-month intervals according to a standard protocol, which also included serologic HLA typing for class I and II antigens. Progression of damage was defined as transition into higher damage states, defined by the number of damaged joints. Both univariate and multivariate models were developed to identify predictors for progression of damage. RESULTS: Univariate analysis revealed that the HLA antigens B27, B39, and DQw3 were associated with disease progression, while HLA-DR7 was "protective." The best multivariate model identified the HLA antigens B27, when DR7 was present, and DQw3, when DR7 was not present, as predicting disease progression across all transitions, while HLA-B39 was associated with progression in early disease. The addition of these HLA indicators to a model containing clinical variables resulted in a significant improvement in fit. CONCLUSION: The HLA antigens associated with PsA, B27 and B39, are risk factors for disease progression, as is the HLA class II antigen DQw3. In combination with clinical measures of disease, these HLA variables are the dominant predictors of progression.

Adolescent↗
PubMed2005

Hip abduction moment and protection against medial tibiofemoral osteoarthritis progression.

OBJECTIVE: To test the hypothesis that a greater peak internal hip abduction moment is associated with a reduced likelihood of ipsilateral medial tibiofemoral osteoarthritis (OA) progression. METHODS: Fifty-seven persons with knee OA (by definite osteophyte presence and symptoms) were evaluated. Baseline assessments included kinematic and kinetic gait parameters, obtained with an optoelectronic camera system and force platform, with inverse dynamics used to calculate 3-dimensional moments at the joints; pain, using a separate visual analog scale for each knee; and alignment, using full-limb radiographs. Radiographs of the knee in a semiflexed position, with fluoroscopic confirmation of tibial rim alignment, were obtained at baseline and 18 months later. Disease progression was defined as worsening of the grade of medial joint space narrowing. Logistic regression obtained with generalized estimating equations was used to estimate odds ratios (ORs) for progression per unit of hip abduction moment, after excluding knees with the worst joint space grade at baseline (which could not progress). RESULTS: The 57 participants (63% women) with mild to moderate OA had a mean age of 67 years and a mean body mass index of 29. A greater internal hip abduction moment during gait was associated with a reduced likelihood of medial tibiofemoral OA progression, with OR/unit hip abduction moment of 0.52 and a 95% confidence interval (95% CI) of 0.32-0.85. This protective effect persisted after adjustment for age, sex, walking speed, knee pain severity, physical activity, varus malalignment severity, hip OA presence, and hip OA symptom presence, with an adjusted OR of 0.43 a 95% CI of 0.22-0.81. CONCLUSION: A greater hip abduction moment during gait at baseline protected against ipsilateral medial OA progression from baseline to 18 months. The likelihood of medial tibiofemoral OA progression was reduced 50% per 1 unit of hip abduction moment.

Aged↗
PubMed2006

Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: A meta-analysis.

OBJECTIVE: Although early initiation of disease-modifying antirheumatic drugs (DMARDs) is effective in controlling short-term joint damage in individuals with rheumatoid arthritis (RA), the long-term benefit in disease progression is still controversial. We examined the long-term benefit of early DMARD initiation on radiographic progression in early RA. METHODS: We identified published and unpublished clinical trials and observational studies from 1966 to September 2004 examining the association between delay to treatment initiation and progressive radiographic joint damage. We included studies of persons with RA disease duration <2 years and DMARD therapy of similar efficacy during followup. The differences in annual rates of radiographic progression between early and delayed therapy were pooled as standardized mean differences (SMDs). RESULTS: A total of 12 studies met the inclusion criteria. The pooled estimate of effects from these studies demonstrated a significant reduction of radiographic progression in patients treated early (-0.19 SMD, 95% confidence interval [95% CI] -0.34, -0.04), which corresponded to a -33% reduction (95% CI -50, -16) in long-term progression rates compared with patients treated later. Patients with more aggressive disease seemed to benefit most from early DMARD initiation (P = 0.04). CONCLUSION: These results support the existence of a critical period to initiate antirheumatic therapy, a therapeutic window of opportunity early in the course of RA associated with sustained benefit in radiographic progression for up to 5 years. Prompt initiation of antirheumatic therapy in persons with RA may alter the long-term course of the disease.

Antirheumatic Agents↗
PubMed2005

Combined c-Myc and caveolin-1 expression in human prostate carcinoma predicts prostate carcinoma progression.

BACKGROUND: Over-expression of the oncogene c-Myc has been implicated in the development and progression of human prostate carcinoma. However, previous assessments of c-Myc expression have not revealed its potential for predicting prostate carcinoma progression. Caveolin-1 is associated with prostate carcinoma progression and is a downstream target gene of c-Myc. The observation that caveolin-1 can suppress c-Myc-induced apoptosis suggested the potential for cooperation between c-Myc and caveolin-1 in malignant progression. In this study, the authors evaluated the prognostic potential of combined c-Myc and caveolin-1 expression in human prostate carcinoma progression. METHODS: Immunostaining with c-Myc and caveolin-1-specific antibodies was performed on paraffin sections from 104 radical prostatectomy specimens from men with lymph node negative prostate carcinoma. Combined c-Myc and caveolin-1 immunostaining scores were related with the clinical and pathologic features and the probability of prostate-specific antigen recurrence after surgery. RESULTS: The combination of c-Myc and caveolin-1 immunopositivity correlated positively with Gleason score (rho = 0.219; P = 0.0253) and positive surgical margin (rho = 0.333; P = 0.0006). The combination of positive c-Myc and caveolin-1 in patients with clinically confined prostate carcinoma was a significant prognostic marker for the time to disease progression after surgery in both univariate analysis (P = 0.0039; hazard ratio, 3.035) and multivariate analysis (P = 0.0114; hazard ratio, 2.916). CONCLUSIONS: The coexpression of c-Myc and caveolin-1 showed potential as a useful prognostic marker for human prostate carcinoma. The current results suggest interactions between c-Myc and caveolin-1 in the progression of human prostate carcinoma.

Adenocarcinoma↗
PubMed2005

The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system.

BACKGROUND: The objective of this study was to compare the accuracy of disease progression prediction of the molecular genetics and morphometry-based Endometrial Intraepithelial Neoplasia (EIN) and World Health Organization 1994 (WHO94) classification systems in patients with endometrial hyperplasias. METHODS: A multicenter, multivariate analysis was conducted on 477 patients with endometrial hyperplasia who were required to have a 1-year minimum disease-free interval from the time of the index biopsy (1-18 years of follow-up). The results from that analysis were compared with the results from 197 patients who had < 1 year of follow-up. RESULTS: Twenty-four of 477 hyperplasias (5.0%) progressed to malignant disease over an average of 4 years (maximum, 10 years). According to the WHO94 classification, 16 of 123 atypical hyperplasias (13%) and 8 of 354 nonatypical hyperplasias (2.3%) progressed (hazard ratio [HR] = 7). Twenty-two of 118 EINs (19%) and 2 of 359 non-EINs (0.6%) progressed (HR = 45). EIN was prognostic within each WHO94 subcategory. Progression rates were 3% in simple hyperplasias, 22% in complex hyperplasias, 17% in simple atypical hyperplasias, and 38% in complex atypical hyperplasias with EIN, compared with progression rates of 0.0-2.0% in all hyperplasias if EIN was absent. EIN detected precancerous lesions (sensitivity, 92%) better than WHO94 atypical hyperplasias collectively (67%) or complex atypical hyperplasias alone (46%). In a Cox regression analysis, EIN was the strongest prognostic index of future endometrial carcinoma. The same was true for patients with < 1 year of follow-up (HR for EIN, atypical hyperplasia, and complex atypical hyperplasia: 58, 7, and 8, respectively). CONCLUSIONS: The EIN classification system predicted disease progression more accurately than the WHO94 classification and identified many women with benign changes that would have been regarded as high risk according to the WHO94 classification system.

Adult↗
PubMed2007

Prostate cancer progression in the presence of undetectable or low serum prostate-specific antigen level.

BACKGROUND: The serum prostate-specific antigen (PSA) level after definitive treatment for prostate cancer (PC) is a powerful predictor of outcome. Occasionally, PC progression can occur despite low or undetectable PSA levels. The authors report on the clinical and pathologic characteristics of patients who experienced PC progression with undetectable or low PSA levels. METHODS: From an electronic database of all patients with PC who were treated at The University of Texas M. D. Anderson Cancer Center between 1999 and 2004, a group of 46 patients was identified who had progression to metastatic PC detected with concomitant PSA levels from 0.1 ng/mL to 2 ng/mL. Patient charts were reviewed for tumor stage, Gleason score, pretreatment PSA level, and the presence of atypical histologic variants (ie, ductal, sarcomatoid, or small cell cancers). The nadir PSA level after treatment and the PSA level at the time metastatic PC was detected were determined. The patients were followed semiannually, and imaging studies were obtained at the discretion of treating physicians. The sites of metastasis and histologic confirmation were reported when available. RESULTS: Twenty-three of 46 patients underwent radical prostatectomy, 11 patients received radiation therapy, and 12 received hormone treatment as their initial form of therapy. Progression to metastatic disease with concomitant, undetectable PSA levels occurred in 10 patients, including 3 patients who had not received treatment with hormones. The sites of metastasis included bone (n = 35 patients), liver (n = 7 patients), retroperitoneal lymph nodes (n = 5 patients), lungs (n = 4 patients), and brain (n = 1 patient). Aggressive and locally advanced PC were common features in these patients: Eighty-five percent had Gleason scores >or=7, 63% had clinical T3 or T4 tumors, and 41% had pretreatment PSA levels >10 ng/mL. Atypical histologic variants were observed in 21 patients (46%) and in 8 of 10 patients who progressed with undetectable PSA levels. In 10 patients (22%), metastasis were detected in the presence of an undetectable PSA level. Eight of those patients had small cell carcinoma. In 19 patients (41%), progression to metastasis occurred without any increase in their PSA from the nadir level. Thirty-one patients (67%) were asymptomatic at the time metastasis was detected, and the detection of metastasis in these patients occurred only because of routine imaging studies. CONCLUSIONS: Progression of PC may occur despite undetectable or low PSA levels. Complete physical evaluation and imaging studies may be indicated in the surveillance of patients with high-grade, locally advanced tumors, especially when atypical histologic variants are present.

Aged↗
PubMed2006

Role of different etiological factors in progression of cervical intraepithelial neoplasia.

Implication of high risk-human Papillomavirus in the process of cervical carcinogenesis is well documented. However, carcinogenesis in the cervix is recognized as multifactorial and other unknown etiological factors are also presumed to contribute to development of cancer. The present communication was aimed to investigate the role of risk factors such as age, parity, cervical lesions, and gynecological symptoms in the progression of the intra-epithelial cervical neoplasia. The study followed 571 cytologically diagnosed cases of high-grade squamous intraepithelial lesions (HSIL) during 35 yr of cytological screening, which is in progress at Gynae OPD of Queen Mary's Hospital of the University since April 1971 and until June 2005, a total of 33,658 cervical smears have been cytologically evaluated. Analysis of different risk factors in 571 HSIL cases revealed high parity coupled with increasing age to play a significant role in the progression of SIL. Further aggravated cervical lesions such as suspicious and unhealthy cervix and persistent vaginal discharge were found to be contributing factor in the progression of SIL. All these factors were predominantly seen in 35 cases of severe dysplasia that have shown progression from moderate dysplasia. The study indicates that women of high parity, especially with high age, are more prone to progression of SIL and hence this group needs mandatory cytological evaluation. Further adequate treatment of mild cervical lesions and persistent vaginal discharge is necessary to avoid the aggravation of the lesion/symptom and subsequent progression of dysplasia.

Adult↗
PubMed2004

Progression of liver fibrosis in women infected with hepatitis C: long-term benefit of estrogen exposure.

Female sex is a protective factor for the progression of fibrosis in patients with chronic hepatitis C virus (HCV) infection. Experimental data suggest that estrogens may have an antifibrotic effect. The objective of this study was to evaluate the influence of past pregnancies, oral contraceptives, menopause, and hormone replacement therapy (HRT) on liver fibrosis progression in HCV-infected women. Four hundred seventy-two HCV-infected women received a survey regarding prior pregnancies, menopause, and the use of oral contraceptives and HRT. The impact of these variables on liver fibrosis and its progression were evaluated using multivariate analyses considering all putative confounding factors. Two hundred one women completed the survey (43% response rate), 157 of whom had an estimated date of HCV infection (96 postmenopausal women, 96 women with previous pregnancies, and 105 women with past use of oral contraceptives). Through multivariate analyses, the estimated rate of fibrosis progression was higher in postmenopausal (P < .05) and nulliparous (P = .02) women and was associated with greater histological activity (P < .001). Prior use of oral contraceptives had no significant influence. Among postmenopausal women, the estimated rate of fibrosis progression (+/-SE) was lower in women who received HRT compared with untreated patients (0.099 +/- 0.016 vs. 0.133 +/- 0.006 METAVIR units/yr; P = .02) and was similar to that of premenopausal women (0.093 +/- 0.012 METAVIR units/yr; P value not significant). In conclusion, menopause appears to be associated with accelerated liver fibrosis progression in HCV-infected women, an effect that may be prevented by HRT. Pregnancies may have a beneficial impact on the long-term progression of liver fibrosis.

Adult↗
PubMed2000

Characteristics of hepatitis C viral genome associated with disease progression.

The clinical presentations of chronic hepatitis C are not uniform. Some patients show persistently high serum alanine transaminase (ALT) values and develop liver cirrhosis and hepatocellular carcinoma (HCC), whereas serum ALT values stay normal in other patients. The mechanism causing this diversity remains to be elucidated. The aim of this study was to identify genomic characteristics of hepatitis C virus (HCV) genotype 1b associated with disease progression. Full length sequences of HCV were determined in 14 patients who showed persistently normal serum ALT values (normal ALT group) and 13 cirrhotics with HCC (HCC group). Residues in which amino acid usage was different between these 2 groups were extracted, and Progression score was defined as the total number of residues with 7 amino acids, more frequently present in the HCC group than in the normal ALT group. In the validation of this Progression score in 9 patients with normal ALT and 25 with HCC, the score was significantly higher in the HCC group (3.1 +/- 1.1 vs. 2.0 +/- 0.9, P =.019). Finally, the correlation between the score and clinical markers related to disease progression was analyzed. In a total of 107 patients with chronic HCV infection, the Progression score was correlated significantly with platelet counts (r = -0.31, P =.0024) by multivariate analysis. In conclusion, high Progression scores were associated with the presence of HCC and low platelet counts. Sequences of the HCV-1b genome may be related to the progression of chronic hepatitis C.

Amino Acids↗
PubMed1995

The presence of persistent high-risk HPV genotypes in dysplastic cervical lesions is associated with progressive disease: natural history up to 36 months.

To evaluate the clinical significance of HPV genotyping for the prediction of progressive cervical intraepithelial neoplasia (CIN) in women with cytomorphologically abnormal smears, a prospective, blind, non-intervention study was performed. A total of 342 patients screened with cytomorphologically abnormal cervical smears were monitored every 3-4 months by cervical cytology, colposcopy and HPV testing using PCR. Women with progressive CIN disease were defined as patients developing lesions with a colposcopic impression of CIN III over more than 2 quadrants or resulting in a cytological smear equivalent to Pap 5. These patients were subsequently treated according to standard procedures. If any doubt arose about the true status of the patients (n = 75) these patients were censored and biopsied. The mean follow-up time was 16.5 months (range 3-36 months). Nineteen women showed progressive CIN disease and all appeared to be continuously HPV-positive from the start of the study. At biopsy, all these patients were histologically classified as CIN III. Seventeen of these women were positive for high-risk HPV types. Two cases were classified as still unidentified HPV. No progression was seen in the absence of HPV DNA or in the presence of low-risk HPV types. In life-table analysis the cumulative rate of progressive, histologically verified CIN disease was 17% after 36 months. Further analyses showed that other risk factors such as age, sexarche, number of sexual partners or smoking hardly influenced the effect of HPV on progression. The results show that the continuous presence of high-risk HPV types in women with cytomorphologically abnormal smears is a strong marker for progressive CIN disease.

Adolescent↗
PubMed2003

Effect of multiple herpesvirus infections on the progression of HIV disease in a cohort of HIV seroconverters.

The effects of herpesviruses infection on the progression of HIV disease remain controversial, with some studies showing accelerated progression and others showing no effect. Furthermore, the effect of concurrent infection with more than one herpesvirus on the progression of HIV disease has never been investigated. To this end, the rates of progression of HIV disease were determined after stratifying for the presence of up to five different herpesvirus infections. The study population consisted of 359 HIV-infected persons for whom the date of seroconversion was estimated (part of the Italian Seroconversion Study). One serum sample from each participant was tested for antibodies to five herpesviruses: HSV-2, CMV, HHV-6, HHV-7, and HHV-8. Univariate analysis showed that HSV-2 and HHV-8 were significantly associated with progression to AIDS, yet when adjusting for age at HIV seroconversion and for the presence of the other herpesvirus infections, only HHV-8 infection showed a significant association. The age-adjusted risk of progression to AIDS with Kaposi's sarcoma increased with the number of herpesvirus infections and was significant in individuals with four infections. The risk of progression to AIDS without Kaposi's sarcoma also increased with the number of infections, although not significantly. Similar results were found when considering CD4+ cell count <200 x 10(6) cells/L as the endpoint. Concurrent infection with more than one herpesvirus does not appear to have a significant effect on the course of HIV disease, except for the known association between HHV-8 and Kaposi's sarcoma. However, even after excluding Kaposi's sarcoma from the AIDS-defining endpoints, a slightly increased risk for participants with four herpesvirus infections remained.

AIDS-Related Opportunistic Infections↗