Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Carcinoma

Liver Cirrhosis

Carcinoma, Hepatocellular

Acquired Immunodeficiency Syndrome

HIV Infections

Coinfection

Fibrosis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Communicable Diseases

Hematinics

All Drugs and Chemicals

Liver Extracts

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

Rare Diseases

Hepatitis A

Hepatitis C

Hepatitis

Hepatitis B

Hepatitis B, Chronic

Hepatitis, Chronic

Hepatitis C, Chronic

Hepatitis, Viral, Human

Virus Diseases

Enterovirus Infections

Picornaviridae Infections

RNA Virus Infections

Blood-Borne Infections

Flaviviridae Infections

Hepadnaviridae Infections

DNA Virus Infections

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Anti-Infective Agents

Central Nervous System Depressants

Lipid Regulating Agents

Ethanol

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Antiviral Agents

Enzyme Inhibitors

Angiotensin-Converting Enzyme Inhibitors

Group conformed by patients experiencing improvement in the noninvasive markers of fibrosis, Fibrotest/Fibrosure and transient elastography, while enrolled in the study.

Group conformed by patients not showing the predefined improvement in the noninvasive markers of fibrosis, Fibrotest/Fibrosure and transient elastography, while enrolled in the study.

Regression of fibrosis will be defined by assessing yearly evolution of noninvasive markers in patients who received antiviral therapy before start of the study, and by comparing baseline markers before start of antiviral therapy to those on subsequent yearly visits in patients prospective recruited (\>50% of cases).

Regression of fibrosis

Such as: family history of liver cancer; body mass index; alcohol, smoking and recreational drug use status; dietary habits, including use of caffeinated drinks; comorbidities such as type 2 diabetes mellitus; use of medications for other chronic diseases such as statins and angiotensin-converting enzyme inhibitors.

Specific risk factors related to hepatocellular carcinoma

Andres Duarte-Rojo, MD, MSc

Jonathan A Dranoff, MD

This study aims to demonstrate that patients with chronic hepatitis C (CHC) and B (CHB) experiencing regression of liver cirrhosis after effective antiviral therapy have decreased risk for hepatocellular carcinoma (HCC). Primary aim is to determine the incidence of HCC in patients with cirrhosis secondary to CHC and CHB, after treatment is provided, and to identify the magnitude of the decreased risk for HCC in patients experiencing regression of fibrosis. As a secondary aim, environmental risk factors for HCC development will be sought, in order to determine a subset of patients in whom it will be safe to stop surveillance.

Cirrhosis is the final pathway of chronic liver disease, and up to 30% of patients develop hepatocellular carcinoma (HCC) within 5 years of diagnosis of cirrhosis. Worldwide, chronic hepatitis C (CHC) and B (CHB) account for the majority of cases of cirrhosis. Successful antiviral treatment results in regression of fibrosis in the majority of patients. Surveillance programs for early detection of HCC mandate the use of imaging (ultrasound/CT-scan) every 6 months. It has been shown in CHC and CHB that the risk of HCC is greatly reduced after viral disease is eradicated/inactive. However, the impact that regression of fibrosis and other factors could have in abating the incidence of HCC has not been systematically investigated. Currently, all patients with eradicated/inactive viral disease continue to be enrolled in HCC surveillance programs, generating anxiety in patients and very high costs to our healthcare system. Fibrotest (FT) and transient elastography (TE) are noninvasive tools proven to be useful for serial assessment of liver fibrosis.

OBJECTIVES: The proposed hypothesis is that patients with regression of liver fibrosis have decreased risk for HCC. Primary aim is to determine the incidence of HCC in patients with cirrhosis secondary to CHC and CHB, during the 3-7 years after treatment is provided, and to identify the magnitude of the decreased risk for HCC in patients experiencing regression of fibrosis. As a secondary aim, environmental risk factors for HCC development will be sought, in order to determine a subset of patients in whom it will be safe to stop surveillance.

METHODS: Patients 18-70 year-old with cirrhosis will be identified from hepatology clinics in 4 academic centers in North America. FT/TE will be obtained before the start of antivirals and yearly thereafter (prospective arm). A retrolective arm of all patients treated no earlier than Jan/2009 will also be included. In this group, baseline FT/TE will be performed off treatment (CHC) or after initial phase of therapy (CHB), and yearly thereafter. During baseline and yearly visits other factors possibly affecting HCC development will be investigated (family history, comorbidities, BMI, diet, etc.). Patients will be classified as having or having not undergone regression of fibrosis after a 3-year follow up, depending on FT and TE evolution. During follow up, all patients will undergo 6-month imaging as part of their routine HCC surveillance. Based on power calculations, enrollment should stop after 924 patients have been recruited. Kaplan-Meier and Cox regression models will be used to analyze data.

PATIENT OUTCOMES: ROLFH study uses state-of-the-art noninvasive markers of liver fibrosis to test whether reversed fibrosis decreases the risk of HCC. We believe this study will lead to a better understanding of HCC risk factors, improved patient counseling and decision making, optimized screening and allocation of health resources, and decreased healthcare costs.

The Regression of Liver Fibrosis and Risk for Hepatocellular Carcinoma (ROLFH) Study

According to Fibrotest/Fibrosure and transient elastography

According to standard imaging surveillance protocol, and confirmatory CT/MRI/biopsy

Positive family history of liver cancer, BMI, active/previous smoking, active/previous alcohol consumption, caffeine consumption in diet, diabetes mellitus, use of drugs for chronic medical conditions

Composite of regression of fibrosis plus other specific conditions decreasing incidence of hepatocellular carcinoma to \<1.5% / year

University of North Carolina, Chapel Hill

University of Toronto

University of Calgary

University of Arkansas

Nutritional and Metabolic Diseases

Blood and Lymph Conditions

Syndrome

Iron Overload

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Metabolic Diseases

Iron Metabolism Disorders

Micronutrients

Iron

Patients with myelodysplastic syndrome among these include also patients with chronic myelomonocytic leukemia with myelodysplasia, patients with acute myeloid leukemia progressed from myelodysplastic syndrome and patients with myelodysplastic/myeloproliferative neoplasm, unclassifiable

All patients will have a transient elastography performed as a measure of liver stiffness.

Transient elastography

Klas Raaschou-Jensen

Patients with myelodysplastic syndrome (MDS) have an ineffective hemopoiesis and often suffer from anemia. This can lead to red blood cell transfusion dependency and iron overload. Iron overload can affect the liver and lead to liver fibrosis and worst case cirrhosis. Ferritin is usually used to monitor the iron overload. In this study MDS patients will have a transient elastography performed which measures the liver's stiffness. The purpose is to investigate whether liver stiffness measurements are coherent to ferritin levels.

Transient elastography is noninvasive and has no side effects. No liver biopsy will be performed due to serious side-effects and risks in this patientgroup.

The results of the transient elastography will be compared to the patient's ferritin levels and the numbers of months the patients have had MDS to find out if there is a correlation. Furthermore we will compare the liver stiffness measurements in the patients with higher ferritin levels to those who have lower ferritin levels. We will also compare the liver stiffness measurements in patients who are red blood cell transfusion dependent compared to those who are red blood cell transfusion independent. We will also compare liver stiffness measurements in the patients with a high alanine aminotransferase (ALAT) compared to those with normal ALAT.

Iron Overload and Transient Elastography in Patients With Myelodysplastic Syndrome

Liver stiffness is measured in kilopascal (kPa)

Ferritin is measured in micrograms per liter

Period of disease will be calculated in months

Transfusion dependency will be defined as having at least one red blood cell transfusion every other eight weeks over a period of four months prior to the date of the fibroscan. Red blood cell dependency will be either "yes" or "no"

Alanine aminotransferase is measured in units per liter

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
The Regression of Liver Fibrosis and Risk for Hepatocellular Carcinoma (ROLFH) Study	NCT01831037	Chronic Hepatit... Chronic Hepatit...	Regression of f... Specific risk f...	18 Years - 70 Years	University of Arkansas
Iron Overload and Transient Elastography in Patients With Myelodysplastic Syndrome	NCT02262312	Myelodysplastic...	Transient elast...	18 Years -	Zealand University Hospital

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