Noninvasive Tests to Predict the Presence of Esophageal Varices in Patients With Liver Cirrhosis
Condition: Cirrhosis
MeSH terms: Liver Cirrhosis; Esophageal and Gastric Varices; Fibrosis
Study type: Observational

Summary: 
      Liver cirrhosis is caused by chronic liver diseases, varices exist in 30 - 60% of patients
      with liver cirrhosis. Variceal bleeding is one of the most important complications of
      cirrhosis, accelerating the progression of decompensation to a stage at which the patient is
      at an extremely high risk of death. Endoscopy is the gold standard for the diagnosis of
      varices, However, periodic endoscopic screening in all cirrhotic patients might unnecessarily
      induce an invasive and expensive procedure, ultimately increasing not only the medical
      workload of endoscopy units, but also the financial burden of patients. To avoid unnecessary
      endoscopy in low- risk patients, some simple, non-invasive and accurate tests have been
      developed to identify EVs. Such as Transient elastography (TE) , which is a noninvasive tool
      that measures liver stiffness (LS) correlating to liver fibrosis stage. Moreover, the
      LS-spleen size-to-platelet ratio score (LSPS), which is a combination of three simple
      examination methods (LS, spleen size and platelet count) has been established to accurately
      predict EVs in patients with cirrhosis. Therefore, investigators design this cross-sectional
      study to assess these non-invasive tests in predicting the presence of EVs in patients with
      cirrhosis.
    

Detailed description: 
      Liver cirrhosis is a result of excessive extracellular matrix deposition in the liver in
      response to chronic inflammatory injury triggered by chronic liver diseases. And Cirrhosis is
      classified in 2 distinct clinical stages, compensated (Currently, both terms : "compensated
      advanced chronic liver disease(cACLD)" and "compensated cirrhosis" are acceptable) and
      decompensated, defined by the presence or absence of overt clinical complications of
      cirrhosis (ascites, variceal hemorrhage, hepatic encephalopathy). Portal hypertension is a
      frequent complication of liver cirrhosis, a contributing fator for ascites and hepatic
      encephalopathy, and a direct cause of variceal hemorrhage. An increase in portal pressure
      leads to the development of portosystemic collateral circulation, of which varices are the
      most important clinical feature. In accordance with the Baveno II consensus conference,
      esophageal varices (EVs) were classified as absent, small (diameter < 5 mm) or large
      (diameter ≥ 5 mm). The presence of red wale marks on the variceal wall in EVs was also
      recorded. EVs at a high risk for bleeding were defined according to the Baveno V criteria as
      large EVs or small EVs with red signs or EVs in patients with Child-Pugh class C disease.
      varices exist in 30 - 60% of patients with liver cirrhosis, depending on the severity of
      Portal hypertension. The yearly rate of development of new cases is 5 - 10% , whereas the
      growth rate from small to large varices ranges between 5 and 30 %.

      Variceal bleeding is the most important and the most lethal complication of cirrhosis,
      accelerating the progression of decompensation to a stage at which the patient is at an
      extremely high risk of death. Therefore, the diagnosis, prevention, and management of EVs are
      important for patients with cirrhosis. And screening for EVs in all patients with cirrhosis
      is also strongly recommended across guidelines and consensus statements. Endoscopy is the
      gold standard for the diagnosis of varices, and is recommended as the screening method to
      identify those who should undergo prophylactic treatment when the diagnosis of cirrhosis is
      made. Nonselective β-blockers significantly reduce the bleeding rate in more than half of
      patients with high-risk EVs (HEVs). However, as the prevalence of HEVs at any given point in
      time is 15 - 25%, the majority of subjects undergoing screening endoscopy either do not have
      varices, or have varices that do not require prophylactic therapy. Therefore, periodic
      endoscopic screening in all cirrhotic patients, especially low-risk groups, might
      unnecessarily induce an invasive and expensive procedure, ultimately increasing not only the
      medical workload of endoscopy units, but also the financial burden to patients, as the number
      of patients with chronic liver disease increases and their survival improves. Furthermore,
      compliance may be limited, because even asymptomatic patients may be required to repeatedly
      undergo an unpleasant endoscopic procedure, which usually requires conscious sedation
      decreasing work productivity, It also carries rare but serious complications. Patients might
      be reluctant to receive endoscopy and become discouraged in starting preventive measures. All
      of these reasons lead to decline in patient compliance with treatment and follow-ups.
      Meanwhile, the endoscopy-related complications reported by a related article is close to 0.1%
      of incidence.

      To avoid unnecessary endoscopy in low-risk patients, some simple, non-invasive and accurate
      tests have been developed to identify EVs. Transient elastography (TE) is a noninvasive tool
      that measures liver stiffness (LS) correlating to liver fibrosis stage. While LS also shows
      potential in the prediction of EVs, its role is still under debate. Moreover, the LS-spleen
      size-to-platelet ratio score (LSPS), which is a combination of three simple examination
      methods (LS, spleen size and platelet count) has been established to accurately predict EVs
      in patients with cirrhosis. And recent Baveno VI recommended the combination of transient
      elastography and platelet count for ruling out HEVs in patients with chronic liver disease.

      Although there is a correlation between these non-invasive tools and the presence of EVS or
      HEVs, the optimal cut-offs and their validities vary in the different studies with different
      etiologies. In addition, the qualities of EVs assessment have not been provided in these
      studies. Therefore, investigators design this cross-sectional study to assess these
      non-invasive tests in predicting the presence of EVs in patients with cirrhosis. This could
      prevent unnecessary endoscopy with related complications and costs. And the results of
      noninvasive tests will be compared with endoscopy (ie, the gold standard for diagnosing EVs).
    

Observational model: Case-Crossover
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        In this cross-sectional study, we will prospectively collect patients with liver cirrhosis
        who fulfill all inclusion criterias and will be treated in the Department of
        Gastroenterology of the Second Affiliated Hospital of Xi'an Jiaotong University from March
        2018 to December 2018.
      
Keywords: cirrhosis,varices,variceal bleeding, noninvasive tests,TE