Predicting clinical outcomes using baseline and follow-up laboratory data from the hepatitis C long-term treatment against cirrhosis trial.
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ABSTRACT:
SUBMITTER: Ghany MG
PROVIDER: S-EPMC3718548 | biostudies-literature | 2011 Nov
REPOSITORIES: biostudies-literature
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Predicting clinical outcomes using baseline and follow-up laboratory data from the hepatitis C long-term treatment against cirrhosis trial.
Ghany Marc G MG Kim Hae-Young HY Stoddard Anne A Wright Elizabeth C EC Seeff Leonard B LB Lok Anna S F AS
Hepatology (Baltimore, Md.) 20111101 5
<h4>Unlabelled</h4>Predicting clinical outcomes in patients with chronic hepatitis C is challenging. We used the hepatitis C long-term treatment against cirrhosis (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 f ...[more]
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Project description:<p>Reprinted from http://www.haltctrial.org/</p> <p><b>Purpose</b></p> <p>The <b>H</b>epatitis C <b>A</b>ntiviral <b>L</b>ong-term <b>T</b>reatment against <b>C</b>irrhosis (HALT-C) Trial is a randomized controlled trial designed to evaluate the safety and efficacy of long-term use of pegylated interferon for the treatment of chronic hepatitis C in patients who failed to respond to previous interferon therapy. The HALT-C Trial was developed to determine whether prolonged interferon therapy altered histological and clinical outcomes in a group of patients who had failed to eradicate hepatitis C virus with previous interferon treatment.</p> <p><b>Study Hypotheses</b></p> <p> <ol> <li>In patients with chronic hepatitis C and bridging fibrosis who failed to eradicate the virus with previous interferon therapy, long-term treatment with interferon is safe and can prevent progression to cirrhosis.</li> <li>In patients with cirrhosis secondary to chronic hepatitis C who failed to eradicate the virus with previous interferon therapy, long-term treatment with interferon is safe and can reduce the risks of hepatic decompensation or of hepatocellular carcinoma.</li> </ol> </p> <p><b>Study Design</b></p> <p>1145 patients with chronic HCV and advanced hepatic fibrosis (Ishak stage 3-6) who failed to respond to previous treatment with interferon were enrolled at 10 clinical centers and entered into a Lead-in phase. They were treated with a combination of pegylated interferon (Pegasys®, Hoffmann-La Roche) 180 µg/week and ribavirin (1000-1200 mg/day) for 24 weeks. Patients who had no detectable HCV-RNA at week 20 continued on combination therapy until week 48.</p> <p>662 patients who did not clear virus were randomly assigned at week 24 to either continue treatment with pegylated interferon alone (90 µg/week) for an additional 42 months, or to have treatment discontinued. All patients were followed at 3-month intervals following randomization. Liver biopsy was performed at baseline and after 1.5 and 3.5 years of treatment.</p> <p>Because of slower than expected enrollment and the approval by the FDA of peginterferon alfa-2b after the start of the trial, we modified the study protocol in three ways. First, criteria for admission to the trial were liberalized to allow patients to enter the trial with lower platelet and white blood cell counts than had been initially considered safe or tolerable. Second, 151 Lead-in patients and those continuing on therapy after 24 weeks who demonstrated return of viremia during or after their 48-week treatment period (called "Breakthrough" or "Relapse" patients, respectively) were allowed to return to enter the randomized trial. Third, 237 patients treated with peginterferon alfa-2b (or with peginterferon alfa-2a in licensing trials) outside the HALT-C Trial who in other respects met all study criteria, having received the equivalent of Trial Lead-in period therapy, were allowed to enter the long-term trial as "Express" patients.</p> <p>A total 1050 patients were randomized.</p> <p>Those patients who completed Month 48 were offered an "extended follow-up (observation only)" until October 2009. These visits will primarily be to identify outcome events, and to provide information to patients concerning the current status of the trial. Some questionnaires, blood tests, and an ultrasonogram will be performed.</p> <p><u>Quarterly (every 3 months)</u></p> <p> <ul> <li>Interval history of complications, adverse events</li> <li>Current medications</li> <li>Brief physical examination</li> <li>Laboratory tests: liver panel, CBC, INR, AFP</li> <li>Child-Pugh Score</li> <li>Stored serum</li> </ul> </p> <p><u>Annual</u></p> <p> <ul> <li>Complete physical examination</li> <li>Ultrasound of liver</li> </ul> </p> <p><u>1.5 years (M24 visit, middle of study)</u></p> <p> <ul> <li>Liver biopsy: formalin fixed histology, frozen liver tissue (subset of patients)</li> </ul> </p> <p><u>3.5 years (M48, end of study)</u></p> <p> <ul> <li>Liver biopsy: formalin fixed histology, frozen liver tissue (subset of patients)</li> <li>Endoscopy: evaluate esophageal varices and portal hypertension</li> </ul> </p> <p><u>After Month 48</u></p> <p> <ul> <li>Observation only (no treatment) to determine clinical outcomes</li> <li>Clinic visit every 6 months with current medications, brief PE, liver panel, CBC, AFP, stored</li> <li>Serum</li> <li>Ultrasound of liver every 6 months</li> </ul> </p> <p><b>Outcome Variables</b></p> <p>Primary outcome variables to be assessed in the two groups of patients include: <ul> <li>Development of cirrhosis on liver biopsy (progression of Ishak fibrosis score by 2 points or more)</li> <li>Development of hepatic decompensation, as shown by:</li> <ul> <li>Sustained increase in the Child-Turcotte-Pugh score to 7 points or higher</li> <li>Variceal hemorrhage</li> <li>Ascites</li> <li>Spontaneous bacterial peritonitis</li> <li>Hepatic encephalopathy</li> <li>Development of hepatocellular carcinoma</li> <li>Death</li> </ul> </ul> Secondary outcomes include quality of life, serious adverse events, events requiring dose reductions, and development of presumed hepatocellular carcinoma. </p>
| phs000430.v1.p1 | EGA
Project description:Deficiency of adenosine deaminase-2 (DADA2) is an autosomal recessive autoinflammatory disease with an extremely variable disease presentation. This paper provides a comprehensive overview of the Dutch DADA2 cohort. We performed a retrospective cohort study in 29 ADA2-deficient patients from 23 families with a median age at inclusion of 26 years. All patients had biallelic pathogenic variants in the ADA2 gene. The most common clinical findings included cutaneous involvement (79.3%), (hepato)splenomegaly (70.8%) and recurrent infections (58.6%). Stroke was observed in 41.4% of the patients. The main laboratory abnormalities were hypogammaglobulinemia and various cytopenias. Patients presented most often with a mixed phenotype involving vasculopathy, immunodeficiency and hematologic manifestations (62.1%). In this cohort, malignancies were reported in eight patients (27.6%), of whom five presented with a hematologic malignancy and two with a basal cell carcinoma. Four patients developed hemophagocytic lymphohistiocytosis (HLH) or an HLH-like episode, of whom three passed away during or shortly after the occurrence of HLH. TNF-inhibitors (TNFi) were effective in treating vasculopathy-associated symptoms and preventing stroke, but were hardly effective in the treatment of hematologic manifestations. Three patients underwent hematopoietic cell transplantation and two of them are doing well with complete resolution of DADA2-related symptoms. The overall mortality in this cohort was 17.2%. In conclusion, this cohort describes the clinical, genetic and laboratory findings of 29 Dutch DADA2 patients. We describe the occurrence of HLH as a life-threatening disease complication and report a relatively high incidence of malignancies and mortality.
| S-EPMC10499949 | biostudies-literature
Project description:<p>Reprinted from http://www.haltctrial.org/</p> <p><b>Purpose</b></p> <p>The <b>H</b>epatitis C <b>A</b>ntiviral <b>L</b>ong-term <b>T</b>reatment against <b>C</b>irrhosis (HALT-C) Trial is a randomized controlled trial designed to evaluate the safety and efficacy of long-term use of pegylated interferon for the treatment of chronic hepatitis C in patients who failed to respond to previous interferon therapy. The HALT-C Trial was developed to determine whether prolonged interferon therapy altered histological and clinical outcomes in a group of patients who had failed to eradicate hepatitis C virus with previous interferon treatment.</p> <p><b>Study Hypotheses</b></p> <p> <ol> <li>In patients with chronic hepatitis C and bridging fibrosis who failed to eradicate the virus with previous interferon therapy, long-term treatment with interferon is safe and can prevent progression to cirrhosis.</li> <li>In patients with cirrhosis secondary to chronic hepatitis C who failed to eradicate the virus with previous interferon therapy, long-term treatment with interferon is safe and can reduce the risks of hepatic decompensation or of hepatocellular carcinoma.</li> </ol> </p> <p><b>Study Design</b></p> <p>1145 patients with chronic HCV and advanced hepatic fibrosis (Ishak stage 3-6) who failed to respond to previous treatment with interferon were enrolled at 10 clinical centers and entered into a Lead-in phase. They were treated with a combination of pegylated interferon (Pegasys®, Hoffmann-La Roche) 180 µg/week and ribavirin (1000-1200 mg/day) for 24 weeks. Patients who had no detectable HCV-RNA at week 20 continued on combination therapy until week 48.</p> <p>662 patients who did not clear virus were randomly assigned at week 24 to either continue treatment with pegylated interferon alone (90 µg/week) for an additional 42 months, or to have treatment discontinued. All patients were followed at 3-month intervals following randomization. Liver biopsy was performed at baseline and after 1.5 and 3.5 years of treatment.</p> <p>Because of slower than expected enrollment and the approval by the FDA of peginterferon alfa-2b after the start of the trial, we modified the study protocol in three ways. First, criteria for admission to the trial were liberalized to allow patients to enter the trial with lower platelet and white blood cell counts than had been initially considered safe or tolerable. Second, 151 Lead-in patients and those continuing on therapy after 24 weeks who demonstrated return of viremia during or after their 48-week treatment period (called "Breakthrough" or "Relapse" patients, respectively) were allowed to return to enter the randomized trial. Third, 237 patients treated with peginterferon alfa-2b (or with peginterferon alfa-2a in licensing trials) outside the HALT-C Trial who in other respects met all study criteria, having received the equivalent of Trial Lead-in period therapy, were allowed to enter the long-term trial as "Express" patients.</p> <p>A total 1050 patients were randomized.</p> <p>Those patients who completed Month 48 were offered an "extended follow-up (observation only)" until October 2009. These visits will primarily be to identify outcome events, and to provide information to patients concerning the current status of the trial. Some questionnaires, blood tests, and an ultrasonogram will be performed.</p> <p><u>Quarterly (every 3 months)</u></p> <p> <ul> <li>Interval history of complications, adverse events</li> <li>Current medications</li> <li>Brief physical examination</li> <li>Laboratory tests: liver panel, CBC, INR, AFP</li> <li>Child-Pugh Score</li> <li>Stored serum</li> </ul> </p> <p><u>Annual</u></p> <p> <ul> <li>Complete physical examination</li> <li>Ultrasound of liver</li> </ul> </p> <p><u>1.5 years (M24 visit, middle of study)</u></p> <p> <ul> <li>Liver biopsy: formalin fixed histology, frozen liver tissue (subset of patients)</li> </ul> </p> <p><u>3.5 years (M48, end of study)</u></p> <p> <ul> <li>Liver biopsy: formalin fixed histology, frozen liver tissue (subset of patients)</li> <li>Endoscopy: evaluate esophageal varices and portal hypertension</li> </ul> </p> <p><u>After Month 48</u></p> <p> <ul> <li>Observation only (no treatment) to determine clinical outcomes</li> <li>Clinic visit every 6 months with current medications, brief PE, liver panel, CBC, AFP, stored</li> <li>Serum</li> <li>Ultrasound of liver every 6 months</li> </ul> </p> <p><b>Outcome Variables</b></p> <p>Primary outcome variables to be assessed in the two groups of patients include: <ul> <li>Development of cirrhosis on liver biopsy (progression of Ishak fibrosis score by 2 points or more)</li> <li>Development of hepatic decompensation, as shown by:</li> <ul> <li>Sustained increase in the Child-Turcotte-Pugh score to 7 points or higher</li> <li>Variceal hemorrhage</li> <li>Ascites</li> <li>Spontaneous bacterial peritonitis</li> <li>Hepatic encephalopathy</li> <li>Development of hepatocellular carcinoma</li> <li>Death</li> </ul> </ul> Secondary outcomes include quality of life, serious adverse events, events requiring dose reductions, and development of presumed hepatocellular carcinoma. </p>
| phs000430 | dbGaP
Project description:ContextDespite tremendous interest in hypoparathyroidism, large cohort studies describing typical treatment patterns, laboratory parameters, and rates of complications are lacking.ObjectiveOur objective was to characterize the course of disease in a large cohort of hypoparathyroid patients.Design and settingWe conducted a chart review of patients with permanent hypoparathyroidism identified via a clinical patient data registry. Patients were seen at a Boston tertiary-care hospital system between 1988 and 2009.PatientsWe identified 120 patients. Diagnosis was confirmed by documented hypocalcemia with a simultaneous low or inappropriately normal PTH level for at least 1 yr. Mean age at the end of the observation period was 52 ± 19 (range 2-87) yr, and the cohort was 73% female.Main outcome measureWe evaluated serum and urine laboratory results and renal and brain imaging.ResultsWe calculated time-weighted average serum calcium measurements for all patients. The time-weighted average for calcium was between 7.5 and 9.5 mg/dl for the majority (88%) of patients. Using linear interpolation, we estimated the proportion of time within the target calcium range for each patient with a median of 86% (interquartile range 67-98%). Of those with a 24-h urine collection for calcium (n = 53), 38% had at least one measurement over 300 mg/d. Of those with renal imaging (n = 54), 31% had renal calcifications, and 52% of those with head imaging (n = 31) had basal ganglia calcifications. Rates of chronic kidney disease stage 3 or higher were 2- to 17-fold greater than age-appropriate norms.ConclusionsHypoparathyroidism and its treatment carry a large burden of disease. Renal abnormalities are particularly common.
| S-EPMC3513540 | biostudies-literature
Project description:PURPOSE: To assess the long-term follow-up results of laparoscopic pyeloplasty for ureteropelvic junction obstruction. MATERIALS AND METHODS: Sixty-five patients (mean age, 43.8 years) who underwent standard laparoscopic pyeloplasty by transperitoneal approaches were enrolled in this study. The chief complaint was flank pain (n=57 patients); the remaining cases were detected incidentally. Twenty-three patients had undergone previous abdominal surgeries, including open pyeloplasty and endopyelotomy. Mean stricture length was 1.06 cm. Grade 3/4 and 4/4 hydronephrosis was detected in 36 and 14 patients, respectively. An obstructive pattern was present on the renal scan in 53 patients (81.5%). RESULTS: Fifty-seven patients were treated with dismembered Anderson-Hynes pyeloplasty and eight patients with Fenger pyeloplasty. During the operation, crossing vessels were found in 27 patients (41.5%). Mean operating time was 159.42 minutes. Although there were no cases of open conversion, two patients with colon and spleen injuries were detected postoperatively. The mean starting time of postoperative ambulation and diet was 1.54 days and 1.86 days, respectively. Mean hospital stay was 8.09 days. Mean follow-up period was 36.5 months. Follow-up intravenous pyelography and renal scan showed improvements in 59 patients, and the radiologic success rate was 90.8%. Eight patients showed failure on radiologic or symptomatic evaluation, and the overall success rate was 87.7%. In the comparative analysis between the success and failure groups, drained amount was the only risk factor related to failure (554.41 mL. vs. 947.70 mL, p=0.024). CONCLUSIONS: Long-term follow-up results support laparoscopic pyeloplasty as the standard treatment for ureteropelvic junction obstruction. Drained amount is a risk factor for failure of the operation.
| S-EPMC4198764 | biostudies-literature
Project description:BackgroundPrognostic factors are lacking in cardiac sarcoidosis (CS), and the effects of immunosuppressive treatments are unclear.ObjectivesTo identify prognostic factors and to assess the effects of immunosuppressive drugs on relapse risk in patients presenting with CS.MethodsFrom a cohort of 157 patients with CS with a median follow-up of 7 years, we analysed all cardiac and extra-cardiac data and treatments, and assessed relapse-free and overall survival.ResultsThe 10-year survival rate was 90% (95% CI, 84-96). Baseline factors associated with mortality were the presence of high degree atrioventricular block (HR, 5.56, 95% CI 1.7-18.2, p = 0.005), left ventricular ejection fraction below 40% (HR, 4.88, 95% CI 1.26-18.9, p = 0.022), hypertension (HR, 4.79, 95% CI 1.06-21.7, p = 0.042), abnormal pulmonary function test (HR, 3.27, 95% CI 1.07-10.0, p = 0.038), areas of late gadolinium enhancement on cardiac magnetic resonance (HR, 2.26, 95% CI 0.25-20.4, p = 0.003), and older age (HR per 10 years 1.69, 95% CI 1.13-2.52, p = 0.01). The 10-year relapse-free survival rate for cardiac relapses was 53% (95% CI, 44-63). Baseline factors that were independently associated with cardiac relapse were kidney involvement (HR, 3.35, 95% CI 1.39-8.07, p = 0.007), wall motion abnormalities (HR, 2.30, 95% CI 1.22-4.32, p = 0.010), and left heart failure (HR 2.23, 95% CI 1.12-4.45, p = 0.023). After adjustment for cardiac involvement severity, treatment with intravenous cyclophosphamide was associated with a lower risk of cardiac relapse (HR 0.16, 95% CI 0.033-0.78, p = 0.024).ConclusionsOur study identifies putative factors affecting morbidity and mortality in cardiac sarcoidosis patients. Intravenous cyclophosphamide is associated with lower relapse rates.
| S-EPMC7500618 | biostudies-literature
Project description: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. METHODS: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. RESULTS:At study entry, median body mass index was high (29.2 kg/m(2)) 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 >or=5% in the first year after randomization (HR, 1.25 per category increase in weight, 95% CI, 1.01-1.55). CONCLUSIONS: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.
| S-EPMC3148692 | biostudies-literature
Project description:BackgroundSilymarin is the most commonly used herbal product for chronic liver disease; yet, whether silymarin protects against liver disease progression remains unclear.AimTo assess the effects of silymarin use on subsequent liver disease progression in 1049 patients of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had advanced fibrosis or cirrhosis and had failed prior peginterferon plus ribavirin treatment.MethodsPatients recorded their use of silymarin at baseline and were followed up for liver disease progression (two point increase in Ishak fibrosis score across baseline, year 1.5, and year 3.5 biopsies) and over 8.65 years for clinical outcomes.ResultsAt baseline, 34% of patients had used silymarin, half of whom were current users. Use of silymarin was associated (P < 0.05) with male gender; oesophageal varices; higher ALT and albumin; and lower AST/ALT ratio, among other features. Baseline users had less hepatic collagen content on study biopsies and had less histological progression (HR: 0.57, 95% CI: 0.33-1.00; P-trend for longer duration of use=0.026). No effect was seen for clinical outcomes.ConclusionsSilymarin use among patients with advanced hepatitis C-related liver disease is associated with reduced progression from fibrosis to cirrhosis, but has no impact on clinical outcomes (Clinicaltrials.gov #NCT00006164).
| S-EPMC3490214 | biostudies-literature
Project description:BackgroundMesenchymal stem cell (MSC) infusion was reported to improve liver function in patients with decompensated liver cirrhosis (DLC); however, whether the medication can improve outcome of these patients is poorly understood.MethodsThis prospective, open-labeled, randomized controlled study enrolled 219 patients with HBV-related DLC who were divided into control group (n = 111) and umbilical cord-derived MSC (UC-MSC)-treated group (n = 108), then all of them received a follow-up check from October 2010 to October 2017. The treated patients received three times of UC-MSC infusions at 4-week intervals plus conventional treatment that was only used for control group. The overall survival rate and HCC-free survival rate were calculated as primary endpoints and the liver function and adverse events associated with the medication were also evaluated.ResultsDuring the follow-up check period from 13 to 75th months, there was a significantly higher overall survival rate in the treated group than the control group, while the difference of the hepatocellular carcinoma event-free survival rate between the treated and control groups was not observed during the 75-month follow-up. UC-MSC treatment markedly improved liver function, as indicated by the levels of serum albumin, prothrombin activity, cholinesterase, and total bilirubin during 48 weeks of follow-up. No significant side effects or treatment-related complications were observed in the UC-MSC group.ConclusionsTherapy of UC-MSC is not only well tolerated, but also significantly improves long-term survival rate, as well as the liver function in patients with HBV-related DLC. UC-MSC medication, therefore, might present a novel therapeutic approach for the disease.
| S-EPMC8651584 | biostudies-literature
Project description:BACKGROUND:A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. OBJECTIVES:To assess long-term effects of a psilocybin-facilitated smoking cessation program at ?12 months after psilocybin administration. METHODS:The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ?12 months, and related data on subjective effects of psilocybin. RESULTS:All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (?16 months) follow-up, with a mean interval of 30 months (range = 16-57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives. CONCLUSION:These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.
| S-EPMC5641975 | biostudies-literature