Non-invasive Methods to Predict PHG in Cirrhosis
Non-invasive Methods to Predict PHG in Cirrhosis
Portal hypertensive gastropathy (PHG) is used to describe the endoscopic appearance of
 gastric mucosa in patients with cirrhotic portal hypertension, with a characteristic
 mosaic-like pattern with or without red spots. The severity of PHG can vary from mild to
 severe, and patients with PHG are at an increased risk of acute and chronic gastrointestinal
 bleeding. According to the study by Kim et al, severe PHG showed a significantly high-risk of
 mortality and reduced expected survival time than none or mild PHG. Therefore, we need to
 detect PHG as soon as possible.However, as an invasive examination, endoscopy examination may
 massive gastrointestinal bleeding or gastric perforation. Most patients are afraid and
 disable to tolerate it, which significantly reduces the real morbidity of PHG and delays the
 time for diagnosis and treatment. Therefore, there is a need to find effective non-invasive
 methods that can predict patients with PHG in the early stage, especially which require
 treatment.
Cirrhosis is the end-stage of every chronic liver disease. Histologically, cirrhosis is
 characterized by regenerative nodules surrounded by fibrous bands, which can be divided into
 compensated phase and decompensated one. Compensated phase is referred to as asymptomatic
 stages, also known as compensated advanced chronic liver disease (cACLD). Decompensated
 cirrhosis is a rapidly progressive phase marked by the development of complications of portal
 hypertension (PH) and/or liver dysfunction. As the disease progresses, the presence of PH and
 liver dysfunction can lead to the appearance of ascites, esophagogastric variceal bleeding
 (EVB), hepatic encephalopathy (HE) and so on, marking the transition from a compensated to a
 decompensated phase.

 Portal hypertensive gastropathy (PHG) is one of the common complications of cirrhosis as
 well, which is considered to be a potential cause of upper gastrointestinal bleeding (UGIB).
 PHG is used to describe the endoscopic appearance of gastric mucosa in cirrhosis patients,
 with a characteristic mosaic-like pattern with or without red spots, which was significantly
 underestimated due to its absence of typical clinical manifestations. The pathogenesis and
 risk factors of PHG in patients with liver cirrhosis are still controversial, but the
 pathogenesis are generally believed to be related to PH and advanced liver dysfunction. The
 presence of PHG is usually combined with esophageal varices (EVs). The severity degree of PHG
 can vary from no/mild to severe, and patients with PHG are at an increased risk of acute and
 chronic gastrointestinal bleeding . The overall prevalence of PHG varies from 4% to 98% . PHG
 accounts for 0.8-40% of UGIB in patients with cirrhosis and 8-50% of non-variceal UGIB, among
 which 2-12% of PHG can cause acute upper gastrointestinal bleeding (AUGIB), up to 95% of
 which is associated with severe PHG and may be life-threatening. The prevalence of chronic
 UGIB in patients with PHG ranges from 3 to 26%, which can lead to iron-deficiency anemia. The
 proportion of UGIB that also can be attributed to mild PHG (range, 3.5-31%). The mortality
 rate related to PHG bleeding is nearly 12.5%.

 According to the study by Kim et al., severe PHG showed a significantly high risk of
 mortality and reduced expected survival time than none or mild PHG. At present, most of the
 researches and guidelines usually do not recommend primary prevention for patients with mild
 PHG, however NSBB as primary prevention should be used for mild PHG combined with small EV
 (guidelines recommend don't need primary prevention for small EV). The risk of UGIB with
 severe PHG is higher than that with mild PHG, which means that NSBB should also be considered
 for prevention even without EVs. For PHG patients with chronic iron deficiency anemia, after
 excluding anemia caused by other causes, not only should use NSBB to reduce portal venous
 pressure and the risk of bleeding, but also should pay attention to iron supplementation.
 From the above, obviously, it is of great important to detect patients with PHG as soon as
 possible. Nowadays, upper gastrointestinal endoscopy (UGIE) is the gold standard for
 measuring PHG. However, as an invasive examination, endoscopy examination may massive
 gastrointestinal bleeding or gastric perforation. Most patients are afraid and disable to
 tolerate it, which significantly reduces the real morbidity of PHG and delays the time for
 diagnosis and treatment. Therefore, there is a need to find effective non-invasive methods
 that can predict patients with PHG in the early stage, especially which require treatment.

 Recently, there had been significant efforts in the last decade to assess the utility of
 non-invasive techniques and methods for the evaluation of liver fibrosis (LS) and portal
 pressure as well as the presence of EVs in patients with cirrhosis. Recently, the most
 promising technique is the measurement of LS by transient elastography (TE), either alone or
 combined with other parameters, had confirmed to be evaluated the seviety of liver fibrosis
 in patients with chronic liver disease, predicted the presence of clinically significant
 portal hypertension (CSPH) and ruled out high-risk esophageal varices (HEVs) in patients with
 cirrhosis. The use of TE alone can effectively assess liver fibrosis and portal hypertension
 by liver stiffness measurement (LSM), but the diagnostic accuracy of EVs is limited.The
 Baveno VI report guidelines acknowledged this application and recommend that LS combined with
 platelet count (PLT) can rule out HEVs in patients with cACLD, it means that LS<20 kPa plus
 PLT>150×109/L had a very low risk of having HEVs and therefore do not require routine
 screening endoscopy. The criteria were validated and expanded extent to allow more people to
 avoid endoscopic screening. According to the studies by Kim et al, LS-spleen diameter to
 platelet ratio score (liver stiffness×spleen diameter/platelet count, LSPS) , LS combined
 with other parameters，was clearly superior to the performance of LS alone for predicting EVs
 in patients with hepatitis B-related cirrhosis, and subsequently validated as a reliable
 predictor for CSPH in patients with cirrhosis by several studies. The PH risk score
 (-5.953+0.188×LS + 1.583 ×sex (1: male; 0: female) +26.705×spleen diameter/platelet count)
 has been firstly developed by Berzigotti et al.for diagnosis of CSPH in patients with
 cirrhosis of any cause. In addition, platelet count to spleen diameter ratio (PSR) and
 aspartate transaminase to platelet ratio (APRI) have also been confirmed by some studies that
 can partly predict the seviety of liver fibrosis and EVs.

 Some recent studies have reported that non-invasive methods also can predict PHG in patients
 with cirrhosis to some extent. Zhang et al.established a model for predicting PHG combined
 with ultrasound examination related indicators, but the model was complex and diagnostic
 accuracy was poor. Yang et al.proposed a VAP scoring system combined spleen volume, platelet
 count and albumin, which can predict the presence of EVs and PHG in patients with chronic
 liver disease, but the results of this study have not been validated. Mandhwani et
 al.explored the efficacy of PSR and right liver lobe diameter to albumin ratio (PLAR) in
 predicting PHG in patients with cirrhosis, PSR was the better predictor better than PLAR.
 More recently, a study suggested that the accuracy of LS in predicting the presence of PHG in
 patients with hepatitis B-related cirrhosis was good. However, few high-quality studies used
 non-invasive methods combined LS and other parameters to predict the PHG in patients with
 liver cirrhosis, considering portal hypertension was the common pathogenesis of EVs and PHG,
 we speculated that the above non-invasive methods combined LS and other routine parameters
 are also suitable for predicting PHG in patients with cirrhosis.

 The aim of this study was to establish a new predictive model (PHG risk score) for diagnosing
 PHG in patients with cirrhosis, then to compare the diagnostic accuracy of PHG risk score,
 the non-invasive models combined with LS and other non-invasive models combined with routine
 parameters in predicting PHG in patients with cirrhosis.
Inclusion Criteria:

 1. aged 18-80 years old.

 2. confirmed patients with cirrhosis : Cirrhosis is diagnosed using standard laboratory,
 radiological, and physical examination findings, or by liver histology in equivocal
 cases

 3. paired noninvasive tests (blood tests, TE, and CT/enhanced CT) and gastroscopy within
 3 months;

 4. The nature of the present study was explained to all patients and informed consent was
 obtained from each case.

 Exclusion Criteria:

 1. the presence of severe ascites that might significantly hamper the accurate assessment
 of LSM , obesity (body mass index>35kg/m2) or intercostal space was too narrow;

 2. severe cardiopulmonary diseases, renal failure, acute illness, infectious diseases,
 acute liver failure or cholestasis or hepatic congestion;

 3. malignant tumors or other serious medical diseases (such as hepatocellular carcinoma,
 gastric cancer, pancreatic cancer and colon cancer) that may reduce expected survival
 time;

 4. non-cirrhotic portal hypertension and those with portal vein thrombosis;

 5. previous or ongoing treatment for portal hypertension, spleen diameter<4cm or
 splenectomy;

 6. pregnant women and patients with implanted pacemakers;

 7. patients can not cooperate with the endoscopy, CT/enhanced CT, FibroTouch /FibroScan
 and other related examination.