Integrated Approaches for Identifying Molecular Targets in Liver Disease
Integrated Approaches for Identifying Molecular Targets in Liver Disease
To provide a framework for successful clinical trials testing novel targets for therapy in
 liver disease.

 To identify molecular and cellular drivers of liver disease to provide a molecular
 classification and study the determinants or key drivers of disease progression.

 Consecutive patients admitted with steatohepatitis (alcoholic or non-alcoholic) will be
 enrolled in this study where liver tissue, blood and stool will be collected to discover and
 validate factors associated with diagnosis, severity, histological characteristics,
 development of decompensations, progression of disease and survival.
Patients with Alcoholic hepatitis:

 Inclusion:

 • Patients with a previous probable or possible AH episode will be defined following the
 guidelines proposed by the NIAAA.

 Exclusion

 -  Terminal illness with less than 6 months live expectancy (e.g. advanced hepatocellular

 -  carcinoma).

 -  Patients who are pregnant or breastfeeding.

 -  Complete portal vein thrombosis (PVT).

 -  Previous liver transplant recipient

 Patients with cirrhosis due to alcohol related liver disease without AH with or without a
 prior episode of decompensation.

 Inclusion:

 • Patients with a diagnosis of cirrhosis due to alcohol related liver disease according to
 clinical and/or analytic and/or radiological criteria.

 Exclusion

 -  Terminal illness with less than 6 months live expectancy (e.g. advanced hepatocellular
 carcinoma).

 -  Patients who are pregnant or breastfeeding.

 -  Complete portal vein thrombosis

 -  Previous liver transplant recipient

 -  Current alcoholic hepatitis episode

 Alcoholic liver disease with compensated never decompensated liver disease.

 Inclusion:

 -  Patients diagnosed with an alcohol use disorder identification test (AUDIT) total
 scores of 8 or more OR Patients with a score lower than 8 in the AUDIT test but for
 whom there is a high suspicion of current or recent (within one year) AUD based on
 medical history, self reported history of excessive alcohol use, stigmata of alcohol
 use on physical exam, liver chemistry abnormalities, or alcohol induced organ
 involvement other than decompensated liver disease.

 -  Patients who admit having a persistent alcohol intake of more than 40 g/daily for
 women and 60 g/daily for men.

 -  Any stage of liver disease: from simple elevation of transaminases to any METAVIR or
 Ishack score assess by liver biopsy or by any validated noninvasive fibrosis score.

 -  Patients without a preexistent liver fibrosis assessment for whom there is a high
 suspicion of liver disease according to clinical and/or analytic and/or radiological
 criteria will also be included.

 Exclusion

 -  Patients with a past history of decompensated advanced liver disease (i.e. jaundice
 episodes, ascites, hepatic encephalopathy, variceal bleeding, hepatorenal syndrome) or
 known hepatocellular carcinoma.

 -  Terminal illness with less than 6 months live expectancy (e.g. advanced hepatocellular
 carcinoma).

 -  Patients who are pregnant or breastfeeding.

 NonAlcoholic Fatty Liver (NAFL)

 Inclusion:

 • Patients with a biopsy proven steatosis or steatosis and mild lobular inflammation OR
 Patients without a biopsy but with a high suspicious of NAFL and with at least three of the
 next 5 components of metabolic syndrome. (Waist circumference≥102/≥88 cm (40/35 inches) for
 men/women, Arterial pressure≥130/85mmHg or treated for hypertension, Fasting glucose
 100mg/dl (5.6mmol/L) or treated for Type 2 diabetes, Serum triglyceride
 (triacylglycerols)>150mg/dL (>1.7mmol/L) if available, HDL cholesterol <40/50mg/dl for
 men/women (<1/<1.3 mmol/L) if available)

 Exclusion

 -  Terminal illness with less than 6 months live expectancy (e.g. advanced hepatocellular
 carcinoma).

 -  Patients who are pregnant or breastfeeding.

 -  Complete portal vein thrombosis

 -  Alcohol intake of more than 20g/daily.

 -  Absence of other possible diagnoses (HCV and HBV negative, ANA's < 1:160, ASMA <1:80)

 Patients with compensated early NASH.

 Inclusion:

 • Patients with a biopsy proven NASH and Metavir fibrosis score (or equivalent score) of
 F0-F2 OR Patients without a biopsy but with a high suspicious of NASH, with at least three
 of the next 5 components of metabolic syndrome and with a validated noninvasive score of
 F0-F2. (Waistcircumference≥102/≥88 cm (40/35 inches) for men/women, Arterial
 pressure≥130/85mmHg or treated for hypertension, Fasting glucose 100mg/dl (5.6mmol/L) or
 treated for Type 2 diabetes, Serum triglyceride (triacylglycerols) >150mg/dL (>1.7mmol/L)
 if available, HDL cholesterol <40/50mg/dl for men/women (<1/<1.3 mmol/L) if available)

 Exclusion

 -  Terminal illness with less than 6 months live expectancy (e.g. advanced hepatocellular
 carcinoma).

 -  Patients who are pregnant or breastfeeding.

 -  Complete portal vein thrombosis.

 -  Alcohol intake of more than 20g/daily.

 -  Absence of other possible diagnoses (HCV and HBV negative, ANA's < 1:160, ASMA <1:80).

 -  Decompensated liver diseases.

 Patients with NASH advance fibrosis or cirrhosis compensated or decompensated.

 Inclusion:

 • Patients with a biopsyproven NASH and a METAVIR fibrosis score (or equivalent score) of
 F3-F4 OR Patients without a biopsy proven but with a high suspicious of NASH, with at least
 three of the next 5 components of metabolic syndrome and with a validated noninvasive
 fibrosis test score of F2-F3. (Waist circumference≥102/≥88 cm (40/35 inches) for men/women,
 Arterial pressure≥130/85mmHg or treated for hypertension, Fasting glucose 100mg/dl
 (5.6mmol/L) or treated for Type 2 diabetes, Serum triglyceride (triacylglycerols)>150mg/dL
 (>1.7mmol/L) if available, HDL cholesterol <40/50mg/dl for men/women (<1/<1.3 mmol/L) if
 available)

 Exclusion

 -  Terminal illness with less than 6 months live expectancy (e.g. advanced hepatocellular
 carcinoma).

 -  Patients who are pregnant or breastfeeding.

 -  Complete portal vein thrombosis.

 -  Alcohol intake of more than 20g/daily.

 -  Absence of other possible diagnoses (HCV and HBV negative, ANA's < 1:160, ASMA <
 1:80).

 Dual NonAlcoholic Fatty Liver Disease and Alcoholic fatty liver disease (DAFLD) compensated
 or decompensated.

 Inclusion:

 -  Patients diagnosed with an alcohol use disorder identification test (AUDIT) total
 scores of 8 or more or Patients with a score lower than 8 in the AUDIT test but for
 whom there is a high suspicion of current or recent (within one year) AUD based on
 medical history, self reported history of excessive alcohol use, stigmata of alcohol
 use on physical exam, liver chemistry abnormalities, or alcohol induced organ
 involvement other than decompensated liver disease.

 -  Patients who admit having a persistent alcohol intake of more than 40 g/daily for
 women and 60 g/daily for men.

 -  At least three of the next 5 components of metabolic syndrome (Waist
 circumference≥102/≥88 cm (40/35 inches) for men/women, Arterial pressure≥130/85mmHg or
 treated for hypertension, Fasting glucose 100mg/dl (5.6mmol/L) or treated Type 2
 diabetes, Serum triglyceride (triacylglycerols)>150mg/dL (>1.7mmol/L), HDL <40/50mg/dl
 for men/women (<1/<1.3 mmol/L).)

 -  BMI≥30

 -  Any stage of liver disease: from simple elevation of transaminases to any METAVIR
 orIshack score assess by liver biopsy or by any validated noninvasive methods.

 -  Patients without a preexistent liver fibrosis assessment for whom there is a high
 suspicion of liver disease according to clinical and/or analytic and/or radiological
 criteria will also be included.

 Exclusion

 -  Terminal illness with less than 6 months live expectancy (e.g. advanced hepatocellular
 carcinoma).

 -  Patients who are pregnant or breastfeeding.

 -  Complete portal vein thrombosis.

 -  Absence of other possible diagnoses (HCV and HBV negative, ANA's < 1:160, ASMA <
 1:80).

 -  A probable or possible episode of Alcoholic Hepatitis as defined by the NIAAA
 guidelines.