Non-invasive Prediction of Esophageal Varices in Patients With Non-Alcoholic Fatty Liver Disease With Advanced Fibrosis
Condition: Esophageal Varices; Non-alcoholic Fatty Liver; Compensated Cirrhosis
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Esophageal and Gastric Varices; Varicose Veins
Study type: Observational

Summary: 
      Non-alcoholic fatty liver disease (NAFLD) is defined as accumulation of fat in the liver
      which is not related to either alcohol excess or other causes such viral infection,
      immune-mediated, or medication related which can lead to fibrosis and later-on, cirrhosis.
      Over the last years NAFLD related liver cirrhosis has become the commonest cause of chronic
      liver disease worldwide. Portal hypertension is the major complication caused by increased
      splanchnic blood flow which leads to development of oesophageal varices (OV). Almost all of
      the patients with portal hypertension can develop OV sometime in their life and one third of
      those will bleed, hence identifying the presence of OV is a an important aspect of diagnostic
      workup of these patients with portal hypertension.

      Upper digestive camera test/endoscopy is the only means to diagnose and grade OV but
      endoscopy is an invasive procedure and its cost effectiveness for screening is also
      questionable. These limitations and the ever-increasing workload on endoscopy units has led
      many researchers to identify some parameters that can non-invasively diagnose OV. Researchers
      have proposed use of platelet count/spleen diameter ratio, liver stiffness on Fibroscan among
      many non-invasive tools to predict OV in patients with portal hypertension with success.
      Recently criteria proposed in Baveno VI conference, (Baveno-IV Criteria) recommended that
      screening endoscopy can be avoided in patients with compensated advanced chronic liver
      disease (cACLD) with liver stiffness measurement (LSM) less than 20 kPa and a platelet count
      more than than 150,000/μL with an expanded Baveno-IV criteria suggesting platelet count >110
      × 109 cells/L and LSM <25 kPa can spare even more endoscopies with a risk of missing varices
      needing treatment (VNT) being minimal.
    

Detailed description: 
      Background:

      Non-alcoholic fatty liver disease (NAFLD) is defined as fatty infiltration of the liver not
      related to alcohol excess or other usual causes of hepatic steatosis e.g. viral or autoimmune
      hepatitis or secondary to medications and includes a spectrum ranging from steatosis,
      steatohepatitis, and fibrosis to cirrhosis; and is now the most common cause of chronic liver
      disease worldwide with prevalence of up to 30%. Although most patients with NAFLD may not
      progress to advanced fibrosis or cirrhosis, but as it has become so prevalent that still many
      patients develop cirrhosis and is now a leading indication for liver transplantation in
      Europe. In terms of global prevalence of NAFLD, it is quite high (32%) in the Middle East
      region. Portal hypertension is the major complication caused by increased splanchnic blood
      flow secondary to vasodilation and increased resistance to blood flow through periportal
      fibrosis which leads to development of oesophageal varices (OV). An estimated 90% of the
      portal hypertension patients will develop OV sometime in their life and 30% of those will
      bleed. Moreover 5-50% of the patients with acute variceal bleed will die within first days of
      the initial episode,6 hence identifying the presence of OV is a fundamental part of
      diagnostic workup of portal hypertension patients.

      Upper digestive endoscopy is the only means to diagnose and grade OV but endoscopy is an
      invasive procedure and its cost effectiveness for screening is also questionable. These
      limitations and the ever-increasing workload on endoscopy units has led many researchers to
      identify some parameters that can non-invasively diagnose OV. The factor most commonly
      associated with varices in most of these studies was thrombocytopenia, though it lacked
      sensitivity and specificity. Previously researchers proposed normalizing the platelet count
      to ultrasonographic spleen diameter and used platelet count/spleen diameter ratio of 909 to
      predict OV non-invasively in patients with portal hypertension, with 100% prevalence adjusted
      negative predictive value, and further validation studies showed the generalisability of
      results. Recent criteria in Baveno-IV conference, (Baveno-IV Criteria), recommends that
      screening endoscopy can be avoided in patients with compensated advanced chronic liver
      disease (cACLD) with liver stiffness measurement (LSM) less than 20 kPa and a platelet count
      more than than 150,000/μL. A new expanded Baveno-IV criteria suggesting platelet count >110 ×
      109 cells/L and LSM <25 kPa, likely to spare even more endoscopies with a risk of missing
      varices needing treatment (VNT) of only 1.6% (95% confidence interval, 0.7%-3.5%) in patients
      within the criteria and 0.6% (95% confidence interval, 0.3%-1.4%) in the overall population
      of 925 patients with cACLD.

      Aim:

      The purpose of this study is to compare the ability of various non-invasive methods including
      Baveno-IV & expanded Baveno-IV criteria, platelet count/spleen diameter, and platelet
      count/(spleen diameter + LSM), in prediction of VNT in NAFLD with advance liver fibrosis

      Patients & Methods:

      We plan to include minimum 100 patients of NAFLD related liver fibrosis as per selection
      criteria

      All the patients with NAFLD related liver fibrosis confirmed on Fibroscan referred to
      Endoscopy Unit, Tawam Hospital for screening of esophageal varices fulfilling the selection
      criteria will be selected from medical records and their documented demographic data and data
      pertaining to history of present illness and positive physical signs will be obtained. The
      biochemical workup (bilirubin, prothrombin time, albumin, creatinine), ultrasound for
      presence of ascites and bipolar splenic diameter, and data for liver stiffness measurement
      and results of upper GI endoscopy will be obtained. The Baveno-IV criteria and expanded
      Baveno-IV criteria and platelet count (in /mm3) to spleen diameter (in mm) ratio will be
      calculated/applied in all these patients and compared with outcomes of gold standard i.e
      Endoscopy results. All this information will be collected in excel sheet for further transfer
      on statistical software for further analysis.
    

Intervention name(s): Reviewing records retrospectively of patients undergoing screening endoscopy
Intervention type(s): Other
Intervention description(s): Reviewing records retrospectively of patients undergoing screening endoscopy to assess Baveno VI, expanded Baveno VI, Platelet count/spleen diameter and other non-invasive predictors of esophageal varices or varices needing treatment
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        The patients with Non-alcoholic fatty liver related advanced liver fibrosis confirmed on
        Fibroscan (stage F3 or F4) referred to Endoscopy Unit Tawam Hospital, Al Ain Abu Dhabi for
        screening of esophageal varices fulfilling the above-mentioned criteria will be selected.
        All consecutive patients over the last five years will be selected
      
Keywords: Platelet count; Spleen diameter; Baveno VI; non-invasive prediction; liver Stiffness; varices needing treatment; Endoscopy