Neoplasms

All Conditions

Digestive System Diseases

Infections

Symptoms and General Pathology

Carcinoma

Carcinoma, Hepatocellular

Hepatitis A

Hepatitis C

Hepatitis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Liver Diseases

Gastrointestinal Diseases

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Communicable Diseases

Blood-Borne Infections

Hepatitis, Viral, Human

Virus Diseases

Flaviviridae Infections

RNA Virus Infections

Anti-Infective Agents

All Drugs and Chemicals

Sofosbuvir

Ribavirin

Antimetabolites

Antiviral Agents

Patients taking Sofosbuvir and Daclatasvir

Patients taking Sofosbuvir,Daclatasvir, and Ribavirin

No intervention made this is an observational study to monitor the already existing protocols of the facility

Sofosbuvir 400 mg, Daclatasvir, Ribavirin

Nagwa A Sabri, Professor

Abd El Rahman El Naggar, Professor

Hasan A El Garem, Professor

Aya M Esawy, Assistant Lecturer

Sara M Zaki, Lecturer

May I Mehrez, Fellow

To evaluate the early detection of HCC in patients Taking Sofosbuvir and Daclatasvir.

Methodology:

Design:

Prospective, randomized study used to detect early incidence of HCC in patients taking Sofosbuvir and Daclatasvir to treat HCV.

Patients will be recruited from the National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Duration of study:

24 weeks from starting the DAAs

Methods:

Patients will go through examination and lab. Workup three times in this study:

* FIRST time:

  * Before starting antiviral therapy, all included patients will undergo through physical examination, lab workup including HCV-RNA quantitative, fasting plasma glucose or HbA1C if diabetic, serum creatinine, CBC, AST, ALT, prothrombin Concentration or INR, total bilirubin, serum albumin, Pregnancy test ( Ladies in child bearing period), AFP as a marker of HCC.
  * Included patients will also undergo through diagnostic procedures as Abdominal ultrasonography and ECG (men \>40, women\>50).
* Second time:

  * At the end of antiviral therapy (12 weeks), virological response to therapy will be assessed by quantitative HCV RNA detection, using PCR.
  * Patients will lab workup including , fasting plasma glucose or HbA1C if diabetic, serum creatinine, CBC, AST, ALT, prothrombin Concentration or INR, total bilirubin, serum albumin, AFP as a marker of HCC.
  * The abdominal ultrasonography will be repeated any suspected focal lesion of the liver will be evaluated with triphasic CT scan or MRI to assess the occurrence or the recurrence of HCC.
* Third and last time:

  * At 24 weeks ( Patients will be off treatment for the previous 12 weeks) , virological response to therapy will be assessed by quantitative HCV RNA detection, using PCR.
  * Patients will lab workup including, fasting plasma glucose or HbA1C if diabetic, serum creatinine, CBC, AST, ALT, prothrombin Concentration or INR, total bilirubin, serum albumin, AFP as a marker of HCC.
  * The abdominal ultrasonography will be repeated any suspected focal lesion of the liver will be evaluated with triphasic CT scan or MRI to assess the occurrence or the recurrence of HCC.

Study of the Early Occurrence of Hepatocellular Carcinoma (HCC) in Egyptian HCV Infected Patients Receiving Sofosbuvir and Daclatasvir

MTI University

Assistant Lecturer

Liver Cirrhosis

Fibrosis

Hematinics

Coagulants

Liver Extracts

Thrombin

The control group will be composed of patients who will be candidates for HCC surveillance, i.e. those with liver cirrhosis or chronic hepatitis of any aetiology without HCC seen at our institution.

Included in this group are:

1. Patients newly enrolled and who will be tested for α-FP, α-FP-L3%, and DCP as part of their regular follow-up;
2. Patients who had previously given consent for the storage of a serum sample in the Biobank and who had authorized the dosage of α-FP, α-FP-L3% and DCP.

The case group will be composed of patients with newly diagnosed HCC in the context of cirrhosis or any other aetiology during the same study period. This group will include:

1. Patients newly enrolled and who will be tested for α-FP, α-FP-L3%, and DCP as part of their regular follow-up;
2. Patients who had previously given consent for the storage of a serum sample in the Biobank and who had authorized the dosage of α-FP, α-FP-L3% and DCP at the time of tumor diagnosis.

The simultaneous dosage of the 3 serum biomarkers will be performed at the Clinical Pathology Laboratory, using the instrument: µTASWakoTM i30 (Micro Total Analysis System) - Fujifilm.

Biomarker dosage

Endrit Shahini, MD

Raffaele Cozzolongo, MD

The objective of this observational study is to evaluate the clinical utility of the combined assay of 3 biomarkers: α-FP, α-FP-L3 and DCP (simultaneously measured by µTASWakoTM i30 automated in vitro diagnostic system) in high-risk subjects to develop this neoplasm.

In particular, it aims to:

* Evaluate the clinical utility of the combined use of α-FP, α-FP-L3 and DCP in predicting the onset of HEPATOCARCINOMA (HCC);
* Evaluate the performance of GALAD and GALADUS scores in the early diagnosis of HCC;
* Evaluate the association between the levels of the three biomarkers (individually and in combination with each other) and the stage of HCC

HCC occurs in 70-95% of cases in patients with chronic liver disease, rarely in a "healthy" liver. Globally about 80% of HCCs are associated with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and their geographical distribution closely correlates with their epidemiology. Approximately 1/3 of patients with liver cirrhosis will develop HCC in the long term, with an annual risk ranging from 1%-8%.

Chronic viral hepatitis C (CHC) and chronic viral hepatitis B (CHB) together with cirrhosis of the liver respectively represent the most important risk factors in Western and Eastern Europe and therefore prolonged surveillance and prevention is recommended in these patients.

Therefore, early diagnosis of HCC is of paramount importance to prolong overall survival. Today, only about 30% of patients in Europe are diagnosed at an early stage, where curative treatments are possible.

Patients with a history of chronic liver disease are at risk of developing HCC and for this reason should undergo a screening program aimed at the early diagnosis of HCC. Asymptomatic patients but with familial predisposition on a genetic basis, according to recent international guidelines, they must be monitored periodically.

Imaging (ultrasonography, CT, and MRI), biopsy with histological examination, and blood alpha-fetoprotein measurements are used in diagnostics and staging. However, current screening/surveillance tools are not perfect.

The most popular screening tools for HCC are as follows and are performed on a semi-annual basis:

1. Abdominal ultrasound: Abdominal ultrasound is the diagnostic tool of first choice, with a sensitivity of 48% (95%CI:34-62%) and a specificity of 97% (95%CI:95-98%) as emerges from a rigorous systematic review of 14 studies of 2524 cases.
2. Tumor markers: Alpha-fetoprotein (α-FP) is a specific tumor marker. Its diagnostic sensitivity of HCC is 25-60% while its specificity is 76-96%. An α-FP level above 400 ng/mL is strongly diagnostic, but approximately two-thirds of patients with HCC \<4 cm has α-FP levels \<200 ng/mL and also approximately 20% of HCCs do not produce α-FP. The carbohydrate chain of α-FP is modified by fucosyltransferase during HCC development to give rise to lectin-bound α-FP (α-FP-L3) (sensitivity:40-90%; specificity:\>90%) . The ratio of fucosylated α-FP to total α-FP is expressed as α-FP-L3%. Des-γ-carboxy-prothrombin (DCP or PIVKA-II) is an immature prothrombin, lacking carboxylation at various residues of glutamate (sensitivity: 48-62%; specificity: 81-98%). α-FP-L3 and DCP have been used routinely for 20 years in Japan. The combined use of these markers has increased the possibility of early detection of small HCCs. Prothrombin is formed after γ-carboxylation of vitamin K-dependent propeptides. DCP is produced due to an acquired post-translational defect in the carboxylase-vitamin K-dependent sequence of malignant cells.

   Thus, DCP production is not increased in chronic hepatitis or cirrhosis, making it a potential marker to be used in the diagnosis of HCC. However, DCP measurement has no prognostic value in cases of vitamin K deficiency or inhibition of vitamin K function (for example in subjects on TAO with dicumarols) since its synthesis is also induced by the absence of vitamin K causing false values positive. For this reason DCP is also known as PIVKA-II (protein induced in vitamin K absence). Notwithstanding these limitations, many studies have demonstrated that PIVKA-II has a high sensitivity and specificity compared to α-FP in differentiating HCC from other chronic liver diseases. Liebman et al. demonstrated that PIVKA-II can be used not only as a very specific marker for HCC but also as a prognostic factor of HCC patients. The sensitivity, specificity, and odds ratio in HCC \<5 cm is 0.14-0.54, 0.95-0.99, and 6.86-29.7, respectively, with a cut-off of 40mAU /ml, and 0.07-0.56, 0.72-1 and 3.56-3 with a cut-off of 100mAU/ml. In a large study of 270 HCC patients who all had serum α-FP levels below 20 ng/mL, the combined use of the biomarkers α-FP-L3 and DCP detected 49% of all HCC patients of size less than 2cm. Furthermore, α-FP-L3 measurements with the highly sensitive method before treatment were more useful for the diagnosis and prognosis of HCC than with the conventional method. More recently, the three markers (α-FP, α-FP-L3 and DCP) showed a sensitivity and specificity of 85% (n=304 HCC patients versus 403 controls) in the early diagnosis of HCC in a German cohort.
3. Second-level investigations are CT and MRI: Useful in confirming the diagnosis and staging the disease in order to set up the correct therapeutic procedure.

"Biomarkers of HCC and their clinical significance"

Ideally, the use of serum biomarkers with adequate sensitivity and specificity could allow early diagnosis of HCC by avoiding surveillance with ultrasonography. A number of serum biomarkers, other than α-fetoprotein (α-FP) have been included in some score systems for the prediction of HCC.

However, at present, none of the biomarkers have been validated in phase III clinical trials and are used in clinical practice, except for α-FP and DCP (or PIVKAII), which are recommended by the Japanese HCC guidelines. This can be explained by the high heterogeneity of HCC biology, where alterations of different biochemical pathways are involved in the tumourigenesis process. Indeed, patients with HCC show various patterns of positivity for biomarkers of HCC.

CLINICAL STUDY DESIGN As previously indicated, this is a retrospective and prospective observational study in which the biomarkers useful for evaluating the possible progression of chronic liver disease in HCC will be dosed in two groups, a "Case" group and a "Control" group.

The need to identify biomarkers useful for predicting the possible onset of HCC in patients with chronic liver disease arises from the fact that:

1. For the majority of patients, HCC is completely asymptomatic;
2. HCCs can only be symptomatic if large;
3. α-FP tumor marker is a specific tumor marker but its diagnostic sensitivity is reduced and also about 20% of HCCs do not produce α-FP;
4. Although α-FP is being diagnosed and screened as a specific and well-established tumor marker, there is a pressing need to use highly specific and new generation biomarkers to allow an even earlier and more accurate diagnosis in patients at risk ;
5. Several studies have demonstrated that α-FP-L3 and DCP are complementary and essential markers in the early detection of HCC;
6. The combined use of α-FP, α-FP-L3 and DCP with HCC surveillance could increase the chance of detecting HCC at an early stage;
7. The combined use of these three markers would provide: Greater clinical sensitivity and effective prognostic and predictive value for early recognition of HCC;
8. The GALAD score (and GALADUS) demonstrated the efficacy of these new biomarkers in HCC prevention and surveillance programs especially in patients with liver cirrhosis almost regardless of etiology.

The following will be enrolled in the study, after signing the informed consent:

1. Patients newly diagnosed with HCC (Case group)
2. Follow-up patients with viral, NASH and/or alcoholic cirrhosis who carry out HCC prevention programs at the Gastroenterology Department I of the IRCCS "Saverio de Bellis". (control group).

The study will last for two years, and it is expected to enroll at least 30 patients for each group.

Upon enrollment and after 6 months, at follow-up, the patients belonging to both groups will have a blood sample taken to proceed with the dosage of the biomarkers.

The control group will be composed of patients who will be candidates for HCC surveillance, i.e. those with liver cirrhosis or chronic hepatitis of any aetiology without HCC seen at our institution.

Included in this group are:

1. Patients newly enrolled and who will be tested for α-FP, α-FP-L3%, and DCP as part of their regular follow-up;
2. Patients who had previously given consent for the storage of a serum sample in the Biobank and who had authorized the dosage of α-FP, α-FP-L3% and DCP.

Control patients will be required to undergo a 6-month follow-up following GALAD score evaluation to confirm the absence of HCC. These patients should have a negative multiphasic contrast-enhanced CT, MRI, or liver biopsy at the time of GALAD score evaluation.

The case group will be composed of patients with newly diagnosed HCC in the context of cirrhosis or any other aetiology during the same study period. This group will include:

1. Patients newly enrolled and who will be tested for α-FP, α-FP-L3%, and DCP as part of their regular follow-up;
2. Patients who had previously given consent for the storage of a serum sample in the Biobank and who had authorized the dosage of α-FP, α-FP-L3% and DCP at the time of tumor diagnosis.

Any patients undergoing therapy with Warfarin, an anticoagulant, will be excluded since it can increase DCP levels in the absence of HCC, risking giving false positives.

Considering that the study foresees a follow-up of at least 6 months of the recruited subjects and therefore rather long times are envisaged for its completion, it is conceivable that some patients will be lost and that the initial population will decrease. For this reason, recruitment will proceed throughout the study.

Use of Blood Biomarkers for the Early Diagnosis of Hepatocellular Carcinoma (HCC)

Determine the GALAD alghoritm (Gender,Age, AFP-L3, AFP and Des-carboxy-prothrombin) by evaluating the values of AFP, AFP-L3, Des-carboxy-prothrombin for each patient, since the GALAD score had a high diagnostic performance as compared to each standalone markers in identifying HCC at any stage.

Dr. Raffaele Cozzolongo

Dr. Palma Aurelia Iacovazzi

Dr. Vito Giannuzzi

Dr. Francesco Losito

Dr. Marianna Zappimbulso

Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis

Principal Investigator

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Rare Diseases

Hepatitis B

Hepatitis B, Chronic

Acquired Immunodeficiency Syndrome

HIV Infections

Hepatitis, Chronic

Enterovirus Infections

Picornaviridae Infections

Hepadnaviridae Infections

DNA Virus Infections

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Herpes Simiae (B Virus)

Tenofovir

Reverse Transcriptase Inhibitors

Enzyme Inhibitors

Anti-HIV Agents

Anti-Retroviral Agents

Patients whose viral load, ALT value and fibrosis status does not meet EASL criteria for treatment and are observed 6 monthly

Patients who meet EASL treatment criteria who receive Tenofovir disoproxil

Tenofovir disoproxil

Mark Thursz, MD FRCP

The West African Treatment Cohort for Hepatitis B (WATCH) study is a component of the European Commission Funded FP7 project PROLIFICA. It aims to evaluate a number of steps required to successfully treat patients with chronic hepatitis B virus infection to prevent cirrhosis and liver cancer. The first step is to determine whether screening for hepatitis B using a point of care test is feasible and effective. The second is to monitor linkage from screening into care. The third is to evaluate cheap non-invasive assessments to determine the need for treatment. The fourth is to determine what proportion of patients meet treatment eligibility criteria. The fifth step is to establish a treatment cohort which can be used to measure adherence to therapy and avoidance of HBV related complications. A parallel untreated cohort will be established to determine whether treatment criteria are relevant in this West African setting by monitoring for complications of HBV infection.

Objectives Primary:

To determine whether suppression of HBV with a nucleotide analogue reduces the risk of liver cancer in West African populations.

Secondary:

To demonstrate that HBV replication can be effectively suppressed with a nucleotide analogue in West African populations To evaluate whether European treatment guidelines are applicable in West Africa To establish the applicability and efficacy of population based screening, clinical assessment and treatment in West Africa To enumerate the proportion of the adult population who carry HBV To evaluate the proportion of the HBV infected population who meet European Association for Study of the Liver (EASL) criteria for treatment

Endpoints Primary:

Incidence of Hepatocellular Carcinoma over the period of study in a treated cohort of patients with chronic HBV compared to historical controls

Secondary:

Proportion of adult population in Gambia and Senegal with chronic HBV infection Proportion of patients with chronic HBV infection who meet EASL treatment criteria Proportion of patients with undetectable HBV DNA \< 400 copies/ml at 1, 2, 3, 4 and 5 years of treatment.

Incidence of hepatocellular Carcinoma in patients who do not meet EASL treatment criteria.

Treatment adherence rate. Average change in Fibroscan score after 3 and 5 years of treatment Emergence of resistance to treatment

Study Phase 4

Study Design A two part study:

Part 1 - Population based screening for HBV infection using a point-of-care test.

Part 2 - Non-randomised, open label, treatment cohort with parallel observation cohort

Number of Subjects Part 1:

Approximately 13,500 adults from the general population.

Part 2:

300 subjects in the treatment group 600 subjects in the observation group

Study Population Part 1:

Males and females aged over 30 years

Part 2:

Patients with chronic hepatitis B virus infection identified through population based screening.

Treatment Cohort There will be a single treatment group of 300 patients who meet EASL treatment criteria.

Schedule of Study Visits Part 1:

A single visit to an individual at their home or workplace when screening for HBV infection will be performed using a point-of-care test..

Part 2:

One screening visit will be performed to determine viral load, liver function tests, clinical examination, ultrasound examination and liver fibrosis assessment.

A second visit, 1 - 3 months later, will be used to verify viral load and ALT values

For those on treatment cohort:

A baseline visit will take place 2 weeks after the second screening visit and study drug will be dispensed with instructions for the patient.

First follow-up will be at 1 month to check adherence Second follow-up will be at 3 months for viral load and liver functions tests Treatment subjects will be seen every 3 months to dispense study drug and check compliance Viral load, liver function, renal function, AFP and ultrasound will be performed every 6 months.

Serum/plasma and urine samples for biomarkers of cancer development will be taken at baseline and annually.

Population Screening (Part 1 only) Communities will be sensitised about the study prior to visits by fieldworkers to individual homes, places of work or recreational facilities. A point-of-care test based on the detection of hepatitis B surface antigen (HBsAg) in a finger-prick blood sample will be used for screening. Subjects with a positive test will be given a hospital appointment for full clinical assessment.

Efficacy Evaluations (Part 2 only) Detection of liver cancer - Surveillance for liver cancer will be made using ultrasound and serum AFP every 6 months on all subjects. In some centres further imaging will be available.

Liver cancer will be diagnosed according to the following criteria:

* Liver mass with typical features of hepatocellular carcinoma on two imaging modalities (ultrasound, bubble ultrasound or CT), or
* liver mass on ultrasound and AFP \> 400 iu/ml or
* histological or cytological confirmation of diagnosis.

Viral Load - viral load will be measure on EDTA plasma samples using an in-house real-time PCR assay verified for accuracy against commercial assays every 6 months.

Safety Evaluations (Part 2 only) Liver function tests, serum phosphate and renal function will be tested every 6 months

Evaluation of treatment guidelines Subjects who do not meet the EASL treatment criteria at baseline will be enrolled in the observational study with surveillance for liver cancer every 6 months

Detection of viral resistance Viral load monitoring of patients in the treatment study every 6 months will be used to detect possible virological resistance. A rise in viral load from nadir values or reappearance of detectable viraemia in patients who had achieved undetectable viral load will be investigated for emergence of viral sequence variants and for adherence to therapy

PROLIFICA - West African Treatment Cohort for Hepatitis B

Prevention of Liver Fibrosis and Cancer in Africa. Observational Study of Screening, Assessment and Treatment for Chronic Hepatitis B Virus Infection

Sensitivity and specificity of capillary blood sample HBsAg test applied at point of care

Sensitivity, specificity and ROC analysis of Fibroscan, APRI and FIB4 tests compared to liver biopsy to assess liver fibrosis

Subjects will be reviewed 6 monthly with liver biochemistry and ultrasound to detect onset of hepatocellular carcinoma or decompensated cirrhosis

Proportion of community subjects who accept screening tests

Proportion of patients who test positive for HBsAg

Proportion of patients who test positive for HBsAg who attend clinic for assessment

Proportion of patients with HBsAg who meet EASL treatment criteria

Medical Research Council Unit, The Gambia

Department of State for Health and Social Welfare, The Gambia

UFR Sante de Thies, Senegal

Cheikh Anta Diop University, Senegal

Institut National de la Santé Et de la Recherche Médicale, France

International Agency for Research on Cancer

Imperial College London

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Hemochromatosis

Hemosiderosis

Hemochromatosis Type 3

Central Nervous System Depressants

Ethanol

Ultrasonographic screening

Jean-Claude Trinchet, Pr, MD, PhD

Liver carcinoma is becoming the main complication of cirrhosis. Treatment of symptomatic or large tumors is disappointing. Regular ultrasonographic screening of small (curable) tumors is currently recommended, but the best periodicity is unknown.This randomized trial is aimed to compare 6-month (current recommendation) and 3-month ultrasonographic screenings.

Patients: All consecutive patients with compensated HBV, HCV, alcohol or hemochromatosis-related cirrhosis (without any previous clinical complication including liver cancer).

Randomization: factorial: ultrasonography (3-month versus 6-month); serum alfa-fetoprotein assay (none versus 6-month).

End points: rate of small tumors (first main criteria); survival (second main criteria).

Screening of Hepatocellular Carcinoma in Patients With Compensated Cirrhosis

Screening of Hepatocellular Carcinoma in Patients With Compensated Cirrhosis. A Randomized Trial Comparing Two Periodicities of Ultrasonographic Surveillance: 3-month vs 6-month

Ministry of Health, France

UNICANCER

Assistance Publique - Hôpitaux de Paris

Sylla KHAOUSSOU

Patient will be contacted for automated reminders within one month before the six-month interval indicating they are due for HCC screening.

The patient navigator will coordinate with the provider and subject to schedule the appropriate office visit and imaging for HCC screening as needed within one month before the test is due.

At the time consent is obtained, members of the research team will collect data about how a subject prefers to be contacted for automated reminders (i.e. text messages, postcard, email, MyChart)

Automated reminders

The patient navigator will attempt to provide a reminder to the subject one to three days before the scheduled imaging and also offer to accompany the subject to the test.

Patient navigation

Ponni Perumalswami, MD

Approximately half of the patients receiving treatment for chronic hepatitis C virus (HCV) infection in the United States have advanced liver disease. Patients with advanced fibrosis/cirrhosis who achieve a sustained virological response (SVR) to treatment and are clinically cured of HCV continue to have an elevated risk of developing hepatocellular carcinoma (HCC). According to guidelines from several professional societies and from the American Association for the Study of Liver Diseases (AASLD), in particular, patients with advanced fibrosis/cirrhosis should undergo life-long bi-annual screening for incident HCC whether they achieve an SVR, or not. The number of patients who need post-SVR HCC screening has risen dramatically in recent years due to the confluence of three factors: Increased screening for HCV, which has allowed more people to realize that they have this often "silent" infection; the availability of safe and highly effective direct acting antiviral drugs (DAAs) for HCV, which has allowed a much higher percentage of treated patients to achieve an SVR; and the long duration of HCV infection in many patients, which has allowed enough time for advanced fibrosis/cirrhosis to develop. To investigate post-SVR patients in the era of DAAs and to promote HCC screening, the objective of this study is to conduct a randomized, unblinded, two-arm prospective intervention trial comparing rates of HCC screening between patients randomized to either personalized patient navigation or automated reminders (e.g. electronic or mailed). Both interventions represent improved care over current standard of care (no patient navigation or automated reminders). There is no evidence to suggest one intervention is better than the other. Healthcare providers who agree to participate in the study will be contacted to confirm the liver disease status of their patients and during the clinical trial the providers of patients in both arms of the trial will be sent reminders about the need to schedule patients for screening visits.

Post Sustained Virological Response (SVR) Hepatocellular Carcinoma (HCC) Screening

Ratio of Number of on-time screening visits to number of missed screening visits

Percentage for patients completing timely screening visit

Icahn School of Medicine at Mount Sinai

Cholangitis

Choledochal Cyst

Cysts

Hepatitis, Autoimmune

Cholangitis, Sclerosing

Biliary Atresia

Bile Duct Diseases

Biliary Tract Diseases

Congenital Abnormalities

Digestive System Abnormalities

Autoimmune Diseases

Bile Duct Cysts

Autoimmune Hepatitis

Primary Sclerosing Cholangitis

The internal cohort was retrospectively enrolled in West China Hospital, Sichuan University from June 2010 and December 2020. It is a training and internal validation cohort.

The same inclusion/exclusion criteria were applied for the same center prospectively. It is a external validation cohort.

Clinical models were developed and validated to predict liver-related complications and survival outcomes in pediatric patients with biopsy-proven with cirrhosis.

Prediction model

Yuhan Yang, MD

The aim of this study was to developed and validated models to predict hepatic decompensation and survivals in pediatric patients with cirrhosis and compared these models with currently available models.

Noninvasive liver fibrosis tests such as the NAFLD fibrosis score (NFS), Hepascore, and transient elastography were specifically developed to predict fibrosis and can help predict patients with NAFLD at the highest risk of developing liver-related complications. These tests have been widely applied in adult cirrhosis. The accuracy of these models, however, may be influenced by patient factors including age, body mass index, and diabetes, potentially limiting their prognostic accuracy and clinical practicability in children. Therefore, it is currently unknown how to best predict hepatic decompensation and survival outcomes among pediatric patients with cirrhosis. To fill this knowledge gap, the investigators performed a retrospective-prospective cohort study with the aim of developing and validating a clinical model to predict liver-related complications and survival outcomes in pediatric patients with biopsy-proven with cirrhosis. Secondly, the investigators aimed to compare the predictive accuracy with currently available noninvasive model.

Predictive Models of Hepatic Decompensation and Survival Outcomes in Pediatric Patients With Cirrhosis

The primary outcome was the first event of hepatic decompensation, defined by the occurrence of any of the following: ascites (identified or confirmed by abdominal ultrasound), upper gastrointestinal bleeding secondary to portal hypertension (confirmed by endoscopy in the presence of gastroesophageal varices or portal hypertensive gastropathy), or hepatic encephalopathy (established by clinical parameters, neuropsychological tests, or electroencephalogram)

The endpoint was defined as the occurrence of death or the last follow-up. Patients were followed from the day of liver biopsy until the occurrence of death, liver transplant, or last visit. The outcome was evaluated by an experienced hepatologist in each center every 3-6 months. At each visit, a medical history, physical examination, and standard laboratory tests were performed.

West China Hospital

Associate Professor

Coinfection

Nicolás Merchante, MD PhD

Prospective multicenter cohort recruiting consecutive patients from 7 hospitals in Andalusia, southern Spain, according to following criteria: 1) HIV infection, 2) Chronic active HCV infection, 3) Older than 18 years, 4) New diagnosis of liver cirrhosis on the basis of a liver stiffness above 14 kiloPascals, 5) No previous or concomitant decompensation of liver disease. Patients are prospectively followed-up according to a uniform protocol of care. Epidemiological, clinical and laboratory variables are periodically recorded. The primary outcomes are the emergence of a liver decompensation (including hepatocellular carcinoma), liver transplant or death. The predictors of these outcomes are analyzed.

Serum samples are collected and immediately frozen for criopreservation

Natural History of Liver Cirrhosis Diagnosed by Transient Elastography in HIV/HCV-coinfected Patients

Episodes of liver decompensation will include those episodes of ascites, spontaneous bacterial peritonitis, portal hypertensive gastrointestinal bleeding, hepatorrenal syndrome, hepatic encephalopathy, hepatocellular carcinoma, non obstructive jaundice and acute on chronic liver failure. These episodes will be diagnosed according to standard definitions of clinical practice guidelines in the field (i.e. HCC diagnosis will be diagnosed according to AASLD criteria, spontaneous bacterial peritonitis and hepatorenal syndrome will be diagnosed following the EASL criteria, portal hypertensive gastrointestinal bleeding according Baveno VI consensus definition,...)

Probability of liver-related death after enrollment

Hospital Universitario Virgen Macarena

Complejo Hospitalario Universitario de Huelva

Hospital de La Línea

Hospital Universitario Reina Sofia de Cordoba

Hospital Universitario Virgen de la Victoria

Complejo Hospitalario de Jaén

Hospital Universitario Puerto Real

Hospital Universitario de Valme

MD, PhD

Antineoplastic Agents

Interferons

Interferon-alpha

Peginterferon alfa-2a

Interferon alpha-2

Immunologic Factors

Triple combination with Telaprevir, PegIFN alfa-2a and Ribavirin administered for 12 weeks, followed by dual therapy with PegIFN alfa-2a and Ribavirin. Dual therapy continued for 48 weeks of total duration of therapy, as standard of care treatment for cirrhotic patients, or until day of transplantation, whichever comes first. Starting doses for standard of care pegylated interferon (PegIFN) alfa-2a 180 mcg subcutaneously once weekly, for ribavirin (RBV) 1,000 mg orally daily (\< 75 kg) and 1,200 mg orally daily (≥ 75 kg), and for telaprevir 750 mg taken orally 3 times a day.

Starting dose: 180 mcg subcutaneously once weekly.

Pegylated Interferon Alfa 2a

Starting dose: 750 mg by mouth 3 times a day.

Telaprevir

Harrys A. Torres, MD

The goal of this clinical research study is to learn if the antiviral combination of telaprevir, pegylated Interferon Alfa 2a (PegIFN alfa-2a) and ribavirin (RBV) can prevent the virus from coming back after the liver transplant.

Telaprevir, PegIFN alfa-2a, and RBV are different antiviral drugs that work in combination at different stages of the HCV infection to stop the virus.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take telaprevir 3 times a day. You will take RVB by mouth 2 times a day. You will receive PEGIFN alfa-2a by an injection under the skin 1 time a week.

Study Visits:

On the first day you take the study drug:

* You will have an eye exam performed by the study doctor.
* You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate).
* Blood (about 2 teaspoons) will be drawn for routine tests and to check for the hepatitis virus.
* You will be asked about any drugs you are taking or side effects you may be having.

Every Week while you are on study:

* You will have a physical exam, including measurement of your vital signs.
* Blood (about 2 teaspoons) will be drawn for routine tests and to check for the hepatitis C virus. If part of the blood sample is left over after the Hepatitis C testing, it will be stored in the laboratory as a back-up sample, in case the original samples get lost. This sample may also be used to check if the Hepatitis C virus has become resistant to the study drug. No extra blood will be drawn for this storage.
* You will be asked about any drugs you are taking or side effects you may be having.
* At Weeks 12, 24, 36, and 42, urine will be collected to check for infection and any other side effects to the drugs.

If you can become pregnant, you will have a urine pregnancy test every 4 weeks

Length of Treatment:

You may continue receiving the antiviral therapy for up to 48 weeks, as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the follow-up visits.

Follow-Up Visits:

Beginning the day after you stop taking antiviral therapy (or the day of transplantation, whichever comes first), you will have up to 24 weeks of follow-up testing performed. About 4 and 20 weeks after your last dose:

* You will have a physical exam, including measurement of your vital signs.
* Blood (about 2 teaspoons) will be drawn for routine tests and to check for the hepatitis C virus.
* You will be asked about any side effects you may be having.
* At week 4 only, urine will be collected to check for infection and any other side effects to the drugs.

This is an investigational study. Telaprevir, PegIFN alfa-2a, and RBV are all FDA approved and commercially available for the treatment of HCV infection. The use of these drugs in preventing the HCV infection is investigational.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.

Telaprevir Plus Standard of Care (SOC) in HCV Associated Hepatocellular Carcinoma (HCC)

Telaprevir in Combination With Standard of Care in Hepatitis C Genotype 1 Infection in Patients With Hepatocellular Carcinoma Awaiting Liver Transplantation

The primary endpoint is number of participants with undetectable viral load at 12 weeks post-transplant (Post-transplant virological response, (PTVR)) which is defined as undetectable Hepatitis C Virus ribonucleic acid (HCV-RNA) 12 weeks after liver transplantation). In order to have undetectable HCV RNA viral load after transplant, participants need to have undetectable viral load before the liver transplant.

Response rate based on the modified intent-to-treat (ITT) population where ITT population is defined as those patients who have achieved an undetectable HCV-RNA level before the transplant. If patients drop out the study early due to severe toxicity or treatment failure including treatment-related death, they will be counted as non-responders when evaluating the response rate.

Sustained virological response (SVR) defined as a single undetectable HCV-RNA measurement 12 weeks after the 48-week treatment period for those still waiting for transplantation. The treatment duration will be summarized with descriptive statistics. Additional analyses based on evaluable patients also conducted regarding the PTVR response rate. The evaluable patients are defined as those patients who complete at least 16 weeks of treatment and have the 12 weeks post-transplant response measurement. The rate will also be computed stratified by the HCV treatment time (i.e., the 48-week HCV treatment versus less than 48 week HCV treatment) considering the different times under HCV. The SVR rate will be estimated, along with the exact 95% confident interval.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of the Early Occurrence of Hepatocellular Carcinoma (HCC) in Egyptian HCV Infected Patients Receiving Sofosbuvir and Daclatasvir	NCT03247296	Hepatitis C	Sofosbuvir 400 ...	18 Years - 75 Years	MTI University
Use of Blood Biomarkers for the Early Diagnosis of Hepatocellular Carcinoma (HCC)	NCT05781568	HCC Cirrhosis, Live... NAFLD HBV HCV	Biomarker dosag...	-	Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
PROLIFICA - West African Treatment Cohort for Hepatitis B	NCT02129829	Hepatitis B, Ch... Hepatocellular ...	Tenofovir disop...	18 Years -	Imperial College London
Use of Blood Biomarkers for the Early Diagnosis of Hepatocellular Carcinoma (HCC)	NCT05781568	HCC Cirrhosis, Live... NAFLD HBV HCV	Biomarker dosag...	-	Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
Screening of Hepatocellular Carcinoma in Patients With Compensated Cirrhosis	NCT00190385	Compensated Cir...	Ultrasonographi...	30 Years - 75 Years	Assistance Publique - Hôpitaux de Paris
PROLIFICA - West African Treatment Cohort for Hepatitis B	NCT02129829	Hepatitis B, Ch... Hepatocellular ...	Tenofovir disop...	18 Years -	Imperial College London
Study of the Early Occurrence of Hepatocellular Carcinoma (HCC) in Egyptian HCV Infected Patients Receiving Sofosbuvir and Daclatasvir	NCT03247296	Hepatitis C	Sofosbuvir 400 ...	18 Years - 75 Years	MTI University
Post Sustained Virological Response (SVR) Hepatocellular Carcinoma (HCC) Screening	NCT02833298	Hepatocellular ... HCC Hepatitis C HCV	Automated remin... Patient navigat...	21 Years -	Icahn School of Medicine at Mount Sinai
Predictive Models of Hepatic Decompensation and Survival Outcomes in Pediatric Patients With Cirrhosis	NCT05181332	Cirrhosis Biliary Atresia Choledochal Cys... Primary Scleros... HBV HCV Autoimmune Hepa...	Prediction mode...	0 Years - 18 Years	West China Hospital
Natural History of Liver Cirrhosis Diagnosed by Transient Elastography in HIV/HCV-coinfected Patients	NCT02693847	Liver Cirrhosis Hepatocellular ... HIV HCV Coinfection		18 Years -	Hospital Universitario de Valme
Telaprevir Plus Standard of Care (SOC) in HCV Associated Hepatocellular Carcinoma (HCC)	NCT01821963	Infection	Pegylated Inter... Ribavirin Telaprevir	18 Years - 69 Years	M.D. Anderson Cancer Center
Telaprevir Plus Standard of Care (SOC) in HCV Associated Hepatocellular Carcinoma (HCC)	NCT01821963	Infection	Pegylated Inter... Ribavirin Telaprevir	18 Years - 69 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for hcv

Every month we try and update this database with for hcv cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hcv

Every month we try and update this database with for hcv cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hcv cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.