<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04466709</url>
  </required_header>
  <id_info>
    <org_study_id>5226</org_study_id>
    <nct_id>NCT04466709</nct_id>
  </id_info>
  <brief_title>The Relationship Betweensarcopenia And Myosteatosis With The Natural History Of Liver Cirrhosis</brief_title>
  <official_title>The Relationship Betweensarcopenia And Myosteatosis With The Natural History Of Liver Cirrhosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Roma La Sapienza</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Roma La Sapienza</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Malnutrition is a common figure associated with liver cirrhosis. The main component of&#xD;
      malnutrition in liver cirrhosis is represented by sarcopenia, a condition of a progressive&#xD;
      and generalized loss of muscle mass and strength. Many studies have reported that sarcopenia&#xD;
      is an independent predictor of morbidity and mortality in cirrhotic patients.&#xD;
&#xD;
      Moreover, cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of&#xD;
      adipose tissue, culminating in a condition of &quot;sarcopenic obesity&quot;.&#xD;
&#xD;
      As highlighted by a recent systematic review and meta-analysis [Van Vgut 2017] all the&#xD;
      studies on the impact of sarcopenia/sarcopenic obesity and myosteatosis in cirrhotic patients&#xD;
      are retrospective studies, mostly involving non-consecutive patients on the list for liver&#xD;
      transplantation. Moreover, most of the studies were produced by non-European centers&#xD;
      (Canadians,Americans, and Japanese) that published more papers on the same patient series.&#xD;
      All these factors have led to a possible selection bias.&#xD;
&#xD;
      Furthermore, the methods used to evaluate sarcopenia and myosteatosis were not homogeneous&#xD;
      (the entire muscle area, or area of the psoas or psoas diameter) as well as the cut-offs&#xD;
      used.&#xD;
&#xD;
      For these reasons, we propose a multicentric observational prospective study aimed at&#xD;
      analyzing the impact of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients&#xD;
      not listed for liver transplantation.&#xD;
&#xD;
      Primary endpoint:&#xD;
&#xD;
      - Evaluation of the impact of sarcopenia on the mortality of cirrhotic patients not on the&#xD;
      waiting list for liver transplantation.&#xD;
&#xD;
      Secondary end-point:&#xD;
&#xD;
        -  Evaluation of the impact of sarcopenic obesity and myosteatosis on the mortality of&#xD;
           cirrhotic patients not on the waiting list for liver transplantation.&#xD;
&#xD;
        -  Evaluation of the impact of sarcopenia/sarcopenic obesity and myosteatosis on the&#xD;
           development of complications (hepatic encephalopathy, bacterial infections, ascites, GI&#xD;
           bleeding) in cirrhotic patients not on the waiting list for liver transplantation.&#xD;
&#xD;
        -  Evaluation of the impact of sarcopenia/sarcopenic obesity and myosteatosis on the number&#xD;
           of admissions and the days of hospitalization for such complications.&#xD;
&#xD;
        -  Evaluation of the subcutaneous fat impact on mortality and morbidity of cirrhotic&#xD;
           patients not on the waiting list for liver transplantation.&#xD;
&#xD;
        -  Concordance analysis of the various methods used (different cut-off/area psoas vs. area&#xD;
           of all muscles) for the diagnosis of sarcopenia through the analysis of CT scan.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Malnutrition is a common figure associated with liver cirrhosis with an incidence ranging&#xD;
      from 5% to 99% of patients depending on the population studied and diagnostic tools used for&#xD;
      the diagnosis [Amodio Hepatology 2013; Merli ESPEN; Merli 2013]. Several factors are involved&#xD;
      in the pathogenesis of malnutrition in the patient with liver cirrhosis as an inadequate&#xD;
      dietary intake, altered nutrient uptake and alterations in the use of the substrate due to&#xD;
      liver disease [Tandon P 2017, Plauth M 2002]. Furthermore, a variety of acute events and&#xD;
      complications can reduce then patient's ability to take care of their food intake [Plauth&#xD;
      M2002]. Malnutrition is associated with an increased risk of mortality, higher prevalence of&#xD;
      portal hypertension-related complications and infections, as well as longer in hospital stay&#xD;
      [Merli 1996, Merli 2010, Merli 2013, Tandon P Liver Transplant 2012, Montano-Loza 2012].&#xD;
&#xD;
      The main component of malnutrition in liver cirrhosis is represented by sarcopenia, a&#xD;
      condition of a progressive and generalized loss of muscle mass and strength [Dasarathy S&#xD;
      2012, Montano-Loza AJ 2012, Cruz-jentoft AJ 2010]. Many studies have reported that sarcopenia&#xD;
      is an independent predictor of morbidity and mortality in cirrhotic patients [Merli 2013,&#xD;
      Tandon P Liver Transplant 2012, Montano-Loza 2012].&#xD;
&#xD;
      Moreover, while overweight and obesity are endemic in Western countries, these conditions&#xD;
      have been associated with the development of chronic liver disease, worsening of liver&#xD;
      fibrosis and progression to cirrhosis [Everhart JE 2009; Raynard B 2002]; furthermore, the&#xD;
      body mass index(BMI) has been considered an independent risk factor for the development of&#xD;
      decompensation among cirrhotic patients of all causes [Berzigotti A 2010].&#xD;
&#xD;
      Cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of adipose&#xD;
      tissue, culminating in a condition of &quot;sarcopenic obesity&quot; [Montano-Loza AJ 2016]. This&#xD;
      observation is relevant because, despite its important role in the prognosis of cirrhosis,&#xD;
      sarcopenia in cirrhotic patients is frequently overlooked as body composition assessments can&#xD;
      be challenging in cirrhotic patients with fluid retention or who are overweight or frankly&#xD;
      obese [O'Brein 2008]. In addition, muscle depletion is characterized by both a reduction in&#xD;
      muscle size and an increased proportion of intermuscular and intramuscular fat denominated&#xD;
      'myosteatosis' [Montano-Loza AJ 2016]. Myosteatosis increases with age and adiposity and it&#xD;
      is associated with metabolic abnormalities, decreased strength and mobility [Montano-Loza AJ&#xD;
      2016, Correa-de-Araujo R 2017].&#xD;
&#xD;
      Montano-Loza and colleagues showed that cirrhotic patients with sarcopenic obesity or&#xD;
      myosteatosis had worse median survival compared to those patients with normal body&#xD;
      composition [Montano- Loza A J 2016]. In previous work, Kabori et al. demonstrated an&#xD;
      association between myosteatosis and the prevalence of diabetes mellitus in patients&#xD;
      undergoing hepatocellular carcinoma resection [Kaibori M 2015].&#xD;
&#xD;
      Assessment of sarcopenia and myosteatosis The European Consensus Statement has identified&#xD;
      computed tomography (CT) as the gold standard for the detection of muscle wasting in clinical&#xD;
      trials [Cruz-Jentoft 2010] nevertheless in clinical practice, the execution of CT and MRI is&#xD;
      difficult to be justified only for quantifying muscle mass.&#xD;
&#xD;
      However, most cirrhotic patients have imaging for surveillance of focal liver lesions,&#xD;
      hepatocellular carcinoma, vascular disease and pre-transplant evaluation [Dasarathy 2016]. CT&#xD;
      is more commonly used as some software enables specific tissue demarcation using precise HU&#xD;
      thresholds [Mitsiopoulos 1998]. There is excellent reliability between different software&#xD;
      systems, with a good reproducibility between the software package [Irving 2007]. Although&#xD;
      heterogeneity in the literature also exists about the abdominal muscles measured (psoas or&#xD;
      total abdominal wall) and the site of measurements (third or fourth lumbar vertebra) [Carey&#xD;
      2017], the measurement of the abdominal muscle area at L3-L4 is considered the gold standard&#xD;
      due to the relative independence from the activity level and water retention [Montano-Loza&#xD;
      2012].&#xD;
&#xD;
      CT images have been also the most utilized as a research tool to investigate myosteatosis. It&#xD;
      is basically assessed indirectly using muscle attenuation calculated, leading to a close&#xD;
      correlation with direct measurements of muscle lipid content [Machann et al., 2003;&#xD;
      Larson-Meyer et al., 2006].&#xD;
&#xD;
      Muscle radiation attenuation is a radiological characteristic that can be measured with&#xD;
      Hounsfield units (HU) [Goodpaster et al., 2000; Goodpaster, 2002]. When muscle&#xD;
      cross-sectional area and attenuation are reported, the most common practice is to use&#xD;
      pre-established HU ranges to define intermuscular fat (usually -190 to -30 HU) and muscle&#xD;
      tissue (usually -29 HU to 150 HU) [Aubrey et al., 2014].&#xD;
&#xD;
      As highlighted by a recent systematic review and meta-analysis [Van Vgut 2017] all the&#xD;
      abovementioned studies on the impact of sarcopenia/sarcopenic obesity and myosteatosis in&#xD;
      cirrhotic patients are retrospective studies, mostly involving non-consecutive patients on&#xD;
      the list for liver transplantation. Moreover, most of the studies were produced by&#xD;
      non-European centers (Canadians,Americans, and Japanese) that published more papers on the&#xD;
      same patient series. All these factors have led to a possible selection bias.&#xD;
&#xD;
      Furthermore, the methods used to evaluate sarcopenia and myosteatosis were not homogeneous&#xD;
      (the entire muscle area, or area of the psoas or psoas diameter) as well as the cut-offs&#xD;
      used.&#xD;
&#xD;
      AIMS and ENDPOINT For these reasons, we propose a multicentric observational prospective&#xD;
      study aimed at analyzing the impact of sarcopenia, sarcopenic obesity and myosteatosis in&#xD;
      cirrhotic patients not listed for liver transplantation.&#xD;
&#xD;
      Primary endpoint:&#xD;
&#xD;
      - Evaluation of the impact of sarcopenia on the mortality of cirrhotic patients not on the&#xD;
      waiting list for liver transplantation.&#xD;
&#xD;
      Secondary end-point:&#xD;
&#xD;
        -  Evaluation of the impact of sarcopenic obesity and myosteatosis on the mortality of&#xD;
           cirrhotic patients not on the waiting list for liver transplantation.&#xD;
&#xD;
        -  Evaluation of the impact of sarcopenia/sarcopenic obesity and myosteatosis on the&#xD;
           development of complications (hepatic encephalopathy, bacterial infections, ascites, GI&#xD;
           bleeding) in cirrhotic patients not on the waiting list for livertransplantation.&#xD;
&#xD;
        -  Evaluation of the impact of sarcopenia/sarcopenic obesity and myosteatosis on the number&#xD;
           of admissions and the days of hospitalization for such complications.&#xD;
&#xD;
        -  Evaluation of the subcutaneous fat impact on mortality and morbidity of cirrhotic&#xD;
           patients not on the waiting list for liver transplantation.&#xD;
&#xD;
        -  Concordance analysis of the various methods used (different cut-off/area psoas vs. area&#xD;
           of all muscles) for the diagnosis of sarcopenia through the analysis of CT scan.&#xD;
&#xD;
      PATIENTS Collection of a large national cohort of patients with liver cirrhosis not listed&#xD;
      for liver transplantation, undergoing CT-scan abdomen based on different indications (with or&#xD;
      without contrast). Each center needs to enroll at least 10 patients within 6 months for an&#xD;
      estimate of at least 20 participating Italian centers.&#xD;
&#xD;
      INCLUSION CRITERIA: all patients with liver cirrhosis (age 40 - 75 years) undergoing&#xD;
      abdominal CT-scan including the third lumbar L3 vertebrae for the clinical indication&#xD;
      (surveillance of focal liver lesions, vascular evaluation, pre-transplant evaluation,&#xD;
      pre-TIPS evaluation.) will be considered for the enrollment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 10, 2019</start_date>
  <completion_date type="Anticipated">January 1, 2022</completion_date>
  <primary_completion_date type="Actual">July 5, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>sarcopenia and mortality</measure>
    <time_frame>1 year</time_frame>
    <description>Evaluation of the impact of sarcopenia on the mortality of cirrhotic patients not on the waiting list for liver transplantation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>sarcopenic obesity/myosteatosis and mortality</measure>
    <time_frame>1 year</time_frame>
    <description>Evaluation of the impact of sarcopenic obesity and myosteatosis on the mortality of cirrhotic patients not on the waiting list for liver transplantation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>sarcopenia, sarcopenic obesity/myosteatosis and complication of liver disease</measure>
    <time_frame>1 year</time_frame>
    <description>Evaluation of the impact of sarcopenia/sarcopenic obesity and myosteatosis on the development of complications (hepatic encephalopathy, bacterial infections, ascites, GI bleeding) in cirrhotic patients not on the waiting list for livertransplantation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Methods Concordance</measure>
    <time_frame>1 year</time_frame>
    <description>Concordance analysis of the various methods used (different cut-off/area psoas vs. area of all muscles) for the diagnosis of sarcopenia through the analysis of CT scan.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">374</enrollment>
  <condition>Sarcopenia</condition>
  <condition>Sarcopenic Obesity</condition>
  <condition>Cirrhosis, Liver</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>none intervention type</intervention_name>
    <description>This is an observational study, no intervention</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The sample size has been planned using results from an analogous retrospective study, where&#xD;
        the HR for sarcopenia was estimated as 2.2, the 1-y event rate was 30%, and 40% of the&#xD;
        sample had sarcopenia. We therefore conservatively assume a sHR equal to 2, 20% 1-y&#xD;
        cause-specific event rate, 40% baseline sarcopenia. According to these data, a total of 68&#xD;
        cause-specific events are needed to guarantee the power of at least 80% with a type I error&#xD;
        rate of 5%. Since we assume a 20% event rate, with a follow-up of 1y as planned 340&#xD;
        patients (68/0.2) will be enrolled. Considering a possible 10% drop-out, a total of 374&#xD;
        patients will be enrolled in the study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        all patients with liver cirrhosis (age 40 - 75 years) undergoing abdominal CT-scan&#xD;
        including the third lumbar L3 vertebrae for the clinical indication (surveillance of focal&#xD;
        liver lesions, vascular evaluation, pre-transplant evaluation, pre-TIPS evaluation.) will&#xD;
        be considered for the enrollment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Active list for liver transplantation (LT) (patients at evaluation for LT will&#xD;
             beenrolled);&#xD;
&#xD;
          2. hepatocellular carcinoma HCC;&#xD;
&#xD;
          3. previous LT or listing for multivisceral or living-related LT;&#xD;
&#xD;
          4. concomitant neuromuscular disease;&#xD;
&#xD;
          5. Patients with acute or subacute liver failure without underlying cirrhosis;&#xD;
&#xD;
          6. Evidence of current malignancy except for non-melanocytic skin cancer;&#xD;
&#xD;
          7. Presence or history of severe extra-hepatic diseases (e.g., chronic renal failure&#xD;
             requiring hemodialysis, severe heart disease (NYHA III-IV); severe chronic pulmonary&#xD;
             disease (GOLD &gt; III), severe neurological and psychiatric disorders);&#xD;
&#xD;
          8. HIV-positive patients;&#xD;
&#xD;
          9. Patients who decline to participate or who cannot provide prior written informed&#xD;
             consent and when there is documented evidence that the patient has no legal surrogate&#xD;
             decision maker and it appears unlikely that the patient will regain consciousness or&#xD;
             sufficient ability to provide delayed informed consent;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Manuela Merli, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sapeinza University of Roma</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Manuela Merli, Professor</last_name>
    <phone>0649972002</phone>
    <email>manuela.merli@uniroma1.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>Gastroenterology Department, Sapienza University of Rome</name>
      <address>
        <city>Rome</city>
        <zip>00100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manuela Merli</last_name>
      <phone>+39 06 49972002</phone>
      <email>manuela.merli@uniroma1.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>July 7, 2020</last_update_submitted>
  <last_update_submitted_qc>July 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Roma La Sapienza</investigator_affiliation>
    <investigator_full_name>Manuela Merli</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>sarcopenia</keyword>
  <keyword>myosteatosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Sarcopenia</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04466709
org study id: 5226
nct id: NCT04466709
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Malnutrition is a common figure associated with liver cirrhosis. The main component of
      malnutrition in liver cirrhosis is represented by sarcopenia, a condition of a progressive
      and generalized loss of muscle mass and strength. Many studies have reported that sarcopenia
      is an independent predictor of morbidity and mortality in cirrhotic patients.

      Moreover, cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of
      adipose tissue, culminating in a condition of "sarcopenic obesity".

      As highlighted by a recent systematic review and meta-analysis [Van Vgut 2017] all the
      studies on the impact of sarcopenia/sarcopenic obesity and myosteatosis in cirrhotic patients
      are retrospective studies, mostly involving non-consecutive patients on the list for liver
      transplantation. Moreover, most of the studies were produced by non-European centers
      (Canadians,Americans, and Japanese) that published more papers on the same patient series.
      All these factors have led to a possible selection bias.

      Furthermore, the methods used to evaluate sarcopenia and myosteatosis were not homogeneous
      (the entire muscle area, or area of the psoas or psoas diameter) as well as the cut-offs
      used.

      For these reasons, we propose a multicentric observational prospective study aimed at
      analyzing the impact of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients
      not listed for liver transplantation.

      Primary endpoint:

      - Evaluation of the impact of sarcopenia on the mortality of cirrhotic patients not on the
      waiting list for liver transplantation.

      Secondary end-point:

        -  Evaluation of the impact of sarcopenic obesity and myosteatosis on the mortality of
           cirrhotic patients not on the waiting list for liver transplantation.

        -  Evaluation of the impact of sarcopenia/sarcopenic obesity and myosteatosis on the
           development of complications (hepatic encephalopathy, bacterial infections, ascites, GI
           bleeding) in cirrhotic patients not on the waiting list for liver transplantation.

        -  Evaluation of the impact of sarcopenia/sarcopenic obesity and myosteatosis on the number
           of admissions and the days of hospitalization for such complications.

        -  Evaluation of the subcutaneous fat impact on mortality and morbidity of cirrhotic
           patients not on the waiting list for liver transplantation.

        -  Concordance analysis of the various methods used (different cut-off/area psoas vs. area
           of all muscles) for the diagnosis of sarcopenia through the analysis of CT scan.
Malnutrition is a common figure associated with liver cirrhosis with an incidence ranging
      from 5% to 99% of patients depending on the population studied and diagnostic tools used for
      the diagnosis [Amodio Hepatology 2013; Merli ESPEN; Merli 2013]. Several factors are involved
      in the pathogenesis of malnutrition in the patient with liver cirrhosis as an inadequate
      dietary intake, altered nutrient uptake and alterations in the use of the substrate due to
      liver disease [Tandon P 2017, Plauth M 2002]. Furthermore, a variety of acute events and
      complications can reduce then patient's ability to take care of their food intake [Plauth
      M2002]. Malnutrition is associated with an increased risk of mortality, higher prevalence of
      portal hypertension-related complications and infections, as well as longer in hospital stay
      [Merli 1996, Merli 2010, Merli 2013, Tandon P Liver Transplant 2012, Montano-Loza 2012].

      The main component of malnutrition in liver cirrhosis is represented by sarcopenia, a
      condition of a progressive and generalized loss of muscle mass and strength [Dasarathy S
      2012, Montano-Loza AJ 2012, Cruz-jentoft AJ 2010]. Many studies have reported that sarcopenia
      is an independent predictor of morbidity and mortality in cirrhotic patients [Merli 2013,
      Tandon P Liver Transplant 2012, Montano-Loza 2012].

      Moreover, while overweight and obesity are endemic in Western countries, these conditions
      have been associated with the development of chronic liver disease, worsening of liver
      fibrosis and progression to cirrhosis [Everhart JE 2009; Raynard B 2002]; furthermore, the
      body mass index(BMI) has been considered an independent risk factor for the development of
      decompensation among cirrhotic patients of all causes [Berzigotti A 2010].

      Cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of adipose
      tissue, culminating in a condition of "sarcopenic obesity" [Montano-Loza AJ 2016]. This
      observation is relevant because, despite its important role in the prognosis of cirrhosis,
      sarcopenia in cirrhotic patients is frequently overlooked as body composition assessments can
      be challenging in cirrhotic patients with fluid retention or who are overweight or frankly
      obese [O'Brein 2008]. In addition, muscle depletion is characterized by both a reduction in
      muscle size and an increased proportion of intermuscular and intramuscular fat denominated
      'myosteatosis' [Montano-Loza AJ 2016]. Myosteatosis increases with age and adiposity and it
      is associated with metabolic abnormalities, decreased strength and mobility [Montano-Loza AJ
      2016, Correa-de-Araujo R 2017].

      Montano-Loza and colleagues showed that cirrhotic patients with sarcopenic obesity or
      myosteatosis had worse median survival compared to those patients with normal body
      composition [Montano- Loza A J 2016]. In previous work, Kabori et al. demonstrated an
      association between myosteatosis and the prevalence of diabetes mellitus in patients
      undergoing hepatocellular carcinoma resection [Kaibori M 2015].

      Assessment of sarcopenia and myosteatosis The European Consensus Statement has identified
      computed tomography (CT) as the gold standard for the detection of muscle wasting in clinical
      trials [Cruz-Jentoft 2010] nevertheless in clinical practice, the execution of CT and MRI is
      difficult to be justified only for quantifying muscle mass.

      However, most cirrhotic patients have imaging for surveillance of focal liver lesions,
      hepatocellular carcinoma, vascular disease and pre-transplant evaluation [Dasarathy 2016]. CT
      is more commonly used as some software enables specific tissue demarcation using precise HU
      thresholds [Mitsiopoulos 1998]. There is excellent reliability between different software
      systems, with a good reproducibility between the software package [Irving 2007]. Although
      heterogeneity in the literature also exists about the abdominal muscles measured (psoas or
      total abdominal wall) and the site of measurements (third or fourth lumbar vertebra) [Carey
      2017], the measurement of the abdominal muscle area at L3-L4 is considered the gold standard
      due to the relative independence from the activity level and water retention [Montano-Loza
      2012].

      CT images have been also the most utilized as a research tool to investigate myosteatosis. It
      is basically assessed indirectly using muscle attenuation calculated, leading to a close
      correlation with direct measurements of muscle lipid content [Machann et al., 2003;
      Larson-Meyer et al., 2006].

      Muscle radiation attenuation is a radiological characteristic that can be measured with
      Hounsfield units (HU) [Goodpaster et al., 2000; Goodpaster, 2002]. When muscle
      cross-sectional area and attenuation are reported, the most common practice is to use
      pre-established HU ranges to define intermuscular fat (usually -190 to -30 HU) and muscle
      tissue (usually -29 HU to 150 HU) [Aubrey et al., 2014].

      As highlighted by a recent systematic review and meta-analysis [Van Vgut 2017] all the
      abovementioned studies on the impact of sarcopenia/sarcopenic obesity and myosteatosis in
      cirrhotic patients are retrospective studies, mostly involving non-consecutive patients on
      the list for liver transplantation. Moreover, most of the studies were produced by
      non-European centers (Canadians,Americans, and Japanese) that published more papers on the
      same patient series. All these factors have led to a possible selection bias.

      Furthermore, the methods used to evaluate sarcopenia and myosteatosis were not homogeneous
      (the entire muscle area, or area of the psoas or psoas diameter) as well as the cut-offs
      used.

      AIMS and ENDPOINT For these reasons, we propose a multicentric observational prospective
      study aimed at analyzing the impact of sarcopenia, sarcopenic obesity and myosteatosis in
      cirrhotic patients not listed for liver transplantation.

      Primary endpoint:

      - Evaluation of the impact of sarcopenia on the mortality of cirrhotic patients not on the
      waiting list for liver transplantation.

      Secondary end-point:

        -  Evaluation of the impact of sarcopenic obesity and myosteatosis on the mortality of
           cirrhotic patients not on the waiting list for liver transplantation.

        -  Evaluation of the impact of sarcopenia/sarcopenic obesity and myosteatosis on the
           development of complications (hepatic encephalopathy, bacterial infections, ascites, GI
           bleeding) in cirrhotic patients not on the waiting list for livertransplantation.

        -  Evaluation of the impact of sarcopenia/sarcopenic obesity and myosteatosis on the number
           of admissions and the days of hospitalization for such complications.

        -  Evaluation of the subcutaneous fat impact on mortality and morbidity of cirrhotic
           patients not on the waiting list for liver transplantation.

        -  Concordance analysis of the various methods used (different cut-off/area psoas vs. area
           of all muscles) for the diagnosis of sarcopenia through the analysis of CT scan.

      PATIENTS Collection of a large national cohort of patients with liver cirrhosis not listed
      for liver transplantation, undergoing CT-scan abdomen based on different indications (with or
      without contrast). Each center needs to enroll at least 10 patients within 6 months for an
      estimate of at least 20 participating Italian centers.

      INCLUSION CRITERIA: all patients with liver cirrhosis (age 40 - 75 years) undergoing
      abdominal CT-scan including the third lumbar L3 vertebrae for the clinical indication
      (surveillance of focal liver lesions, vascular evaluation, pre-transplant evaluation,
      pre-TIPS evaluation.) will be considered for the enrollment.
observational model: Cohort
time perspective: Prospective
measure: sarcopenia and mortality
time frame: 1 year
description: Evaluation of the impact of sarcopenia on the mortality of cirrhotic patients not on the waiting list for liver transplantation.
measure: sarcopenic obesity/myosteatosis and mortality
time frame: 1 year
description: Evaluation of the impact of sarcopenic obesity and myosteatosis on the mortality of cirrhotic patients not on the waiting list for liver transplantation.
measure: sarcopenia, sarcopenic obesity/myosteatosis and complication of liver disease
time frame: 1 year
description: Evaluation of the impact of sarcopenia/sarcopenic obesity and myosteatosis on the development of complications (hepatic encephalopathy, bacterial infections, ascites, GI bleeding) in cirrhotic patients not on the waiting list for livertransplantation.
measure: Methods Concordance
time frame: 1 year
description: Concordance analysis of the various methods used (different cut-off/area psoas vs. area of all muscles) for the diagnosis of sarcopenia through the analysis of CT scan.
intervention type: Other
intervention name: none intervention type
description: This is an observational study, no intervention
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: No
last name: Manuela Merli, Professor
role: Principal Investigator
affiliation: Sapeinza University of Roma
last name: Manuela Merli, Professor
phone: 0649972002
email: manuela.merli@uniroma1.it
facility: 
status: Recruiting
contact: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Roma La Sapienza
investigator full name: Manuela Merli
investigator title: Professor
mesh term: Liver Cirrhosis
mesh term: Sarcopenia
mesh term: Fibrosis
sharing ipd: No