European Journal of Cardiovascular Medicine

Chronic Liver Disease (CLD) constitutes a combination of various hepatic diseases of different causes having various grades of severity wherein inflammation and fibrosis of liver cells progress for at least 6 months duration. Cirrhosis of liver is the consequence of all forms of Chronic Liver Disease; it is characterized by fibrosis of hepatic tissues and altered hepatic parenchymal architecture transforming into abnormal nodules with varied clinical manifestations and complications.1 The progression of cirrhosis of the liver often begins with an asymptomatic phase called "compensated" cirrhosis and then advances to a fast-escalating decompensated phase, characterized by the development of significant ascites or symptoms of Portal Hypertension.2 Uncontrolled esophageal varices (EV) are one of the primary cause of mortality in people with cirrhosis.3 Esophageal varices has been found to be present in approximate 40% cirrhotic patients without ascites and 60% of cirrhotic patients having ascites.4 It seems that size of varix is the most reliable clinical predictor for bleeding. By 2 years, patients with varices of diameter less than 5 mm have 7% chance of bleeding, while those with varices bigger than 5 mm have 30% risk. Hepatic venous pressure gradient (HVPG) is a crucial factor which determines the risk of bleeding in varices which is practically negligent when the HVPG are less than 12 mm Hg.5Currently the transient elastography (FIBROSCAN) is being used as simple assessment tool for fibrosis of the liver and prediction of esophageal varices in patients with cirrhosis.6

The main theme of my study is the early evaluation of CLD patients by noninvasive procedures like shear wave elastography and endoscopy findings and to correlate between fibrosis and varices so that early diagnosis of esophageal variceal bleed can be possible.

AIM AND OBJECTIVES

1. To evaluate the Shear wave Elastography for liver stiffness and endoscopic findings in patients with Chronic Liver Disease.
2. To correlate the Elastographic findings for liver stiffness with Upper Gastrointestinal Endoscopic findings for the presence of esophageal varices.

The study was carried out at Assam Medical College & Hospital, Dibrugarh, India for a period of 12 months. A prospective, observational, cross-sectional, study was carried out in the inpatient and outpatient medicine departments. The total sample size was calculated to be 60. The protocol was approved by the institutional ethics committee. The subjects agreed to sign a formal informed consent form covering the details of the research. The medical history and patient profile questionnaires were used to collect the patient’s data.

INCLUSION CRITERIA:

1)       All the patients with age more than 13 years with diagnosis of CLD.

2)       Those giving consent for the said study.

EXCLUSION CRITERIA:

1)       Less than 13 years of age.

2)       Patient refusing consent.

3)       Patients with a recent history of active UGI bleeding.

4)       Critically ill patients were not able to do invasive procedures UGI Endoscopy.

5)       Patients with thrombosis of portal vein, hepatocellular carcinoma, Budd Chiari syndrome and other causes of non-cirrhotic portal hypertension.

Data was calculated and a master chart was created using a predesigned and pretested Performa. For statistical analysis, data were put into a Microsoft Excel sheet and then analyzed by IBM SPSS-21.0. Data has been summarized as mean and standard deviation for numeric variables and numbers and percentages for categorical variables. To test significance, independent samples t-test were applied. The Receiver Operating Curve (ROC) was used to determine the cutoff values of Elastographic stiffness in Kpa and APRI score to detect PHTN and oesophageal varices of different grades. P values < 0.05 had be considered to be statistically significant.

TABLE 1: AGE-WISE DISTRIBUTION

In our study, patients aged more than 13 years were considered with ages ranging from 19-71 years. The majority of them were 41-60 years old. The mean age was 46.2(+12.3) years.

TABLE 2: ETIOLOGY-WISE DISTRIBUTION

In our study; most of the causes of CLD were found to be alcohol in 60 % of cases followed by MASLD in 17%, HBsAg in 5%, HCV in 3%, both HBsAg and HCV in 2% and others 13%.

TABLE 3: GENDER-WISE AGE DISTRIBUTION

In our study, most male (49%) and female (67 %) cases were in the 41-60 years age group.

TABLE 4: FREQUENCY DISTRIBUTION OF PRESENCE OF PORTAL HYPERTENSION

TABLE 5: TYPES OF PORTAL HYPERTENSION

TABLE 6: FREQUENCY DISTRIBUTION OF PRESENCE OF ESOPHAGEAL VARICES

TABLE 7 : FREQUENCY DISTRIBUTION OF GRADES OF ESOPHAGEAL VARICES

TABLE 8: ASSOCIATION OF ELASTOGRAPHIC VALUE, APRI SCORE, PLATELET COUNT WITH PORTAL HYPERTENSION

In our study, Mean values of Elastography, APRI Score, and platelet count with portal hypertensive patients were compared. Mean values of elastography, APRI score, and Platelet counts in patients with PHTN were 25.7(+6.7) Kpa, 1.65(+0.51), and 1.16(+0.6) in lakhs/cumm respectively. Mean values of elastography, APRI score, and Platelet counts in patients without Portal Hypertension were 13.7(+6.6) Kpa, 0.59 (+0.08), and 1.91(+0.67) respectively. The P-value was <0.005 and it is statistically significant.

TABLE 9: ASSOCIATION OF ELASTOGRAPHIC VALUE, APRI SCORE, PLATELET COUNT WITH PRESENCE OF ESOPHAGEAL VARICES

Mean values of Elastography, APRI Score, and platelet count in cases with or without the presence of esophageal varices were compared. Mean values of elastography, APRI score, and Platelet counts in cases with the presence of esophageal varices were 25.9(+6.8) Kpa, 1.83(+0.97), and 0.98(+ 0.30) in lakhs/cumm respectively. Mean values of elastography, APRI score, and Platelet counts in patients without the presence of esophageal varices were 16.3(+7.9) Kpa, 0.51 (+0.07), and 2.11(+0.69) respectively. P value was calculated to be < 0.05 and it is statistically significant.

TABLE 10: ASSOCIATION OF ELASTOGRAPHIC VALUE WITH GRADES OF VARICES

In our study, Mean Elastography values were compared with the grading of esophageal varices. Mean Elastography values in patients without esophageal varices; with Grade One varices, with Grade Two varices, and with Grade Three varices were 16.33(+7.9) Kpa, 17.9(+5.4) Kpa, 24.6(+5.81) Kpa and 31.52(+3.50) respectively (P value <0.001).

Patient's age group of more than 13 years were included ranging from 19-71 years. Out of 60 cases, 1 (2%) was in the age group 13-20, 19 (32%) belonged to the 21-40 followed by 32 (53%) in 41-60, and 8 cases (13%) aged 60 years and above. It is seen that the majority of cases were in 41-60 years of age group. Mean age was 46.2(+12.3) years.

In 2021, Danish et al.7 found that out of 204 cases, 11.8% cases were aged less than 18 years, 22.5% belonged to 18-35 years age group, 35.3% were in 36-50, and 30.4% aged more than 50 years.

In our study shows that out of 60 patients, most of the causes of CLD were found to be alcohol in 36 (60 %) of cases followed by MASLD in 10(17%), HBsAg in 3(5%), HCV in 2(3%), both HBsAg and HCV in 1(2%) and others 8(13%).

In 2022, Debnath et al.8 found that 43 % had alcoholic liver disease followed by NAFLD in 42% of cases and 10 % of cases in chronic viral hepatitis.

Out of 60 patients, 45 (75%) cases were male and the remaining 15 (25%) were female with 3:1 male-to-female ratio.

In our study, the majority of males 22 (49%), and females 10 (67%) belonged to 41-60 years followed by males 16 (36%), and females 3 (20%) belonged to 21-40 years.

In 2017, Ghamdi et al.9 found that the majority (52%) belonged to the male gender and the remaining (48%) were with 1.08:1 male to female ratio.

Out of 44 Portal Hypertensive cases, esophageal Varices were found to be in 32(73%) cases, followed by Portal hypertensive gastropathy (PHG) in 4 (9%) cases, both in 7(16%) cases and isolated gastric varices in 1(2%).

In 2022, Debnath et al.8 found that 74.6% of cases had features of Portal Hypertension; out of which 71% had PHG, 53% varix, and 50% had both.

Out of 60 cases, esophageal varices were found to be in 39 (65%) cases and not found in 21 (35%).

Malik et al.10  in 2010 found that 51% was the prevalence of esophageal varices in CLD

Out of 60 cases; varices were not detected in 21 cases (35%) and 7 (12%) cases were in Grade One, 18 (30%) in Grade Two, and 14 (23%) in Grade Three. There were not so many differences between Grade Two and Grade Three. Saad et al.11  in 2013 found that out of 32 cases, 12(37.5%) had no varices, 10(31.25%) had small varices and 10(31.25%) had large varices. Mean values of elastography, APRI score, and Platelet counts in cases with PHTN were 25.7 (+6.7) Kpa, 1.65 (+0.51), and 1.16 (+0.6) in lakhs/cumm respectively. Mean values of elastography, APRI score, and Platelet counts in patients without PHTN were 13.7 (+6.6) Kpa, 0.59 (+0.08), and 1.91 (+0.67) respectively. P value was found to be < 0.05 which is statistically significant.

In 2017, Ghamdi et al.9 found the mean value of liver elastographic score was 34.5 Kpa among CLD cases with PHTN and 25.8 Kpa among cases without PHTN.

In 2022, Debnath et al.8 observed the mean values of elastography and APRI scores in cases with features of Portal Hypertension were 39.99 (22.7) Kpa and 2.1 (5.5) respectively. The mean values of elastography and APRI scores in patients without features of Portal Hypertension were 13.6 (11.7%) Kpa and 0.97 (0.59) respectively. Mean values of Elastography, APRI Score, and platelet count in cases with or without esophageal varices were compared. Mean values of elastography, APRI score, and Platelet counts in cases with the presence of esophageal varices were 25.9 (+6.8) Kpa, 1.83 (+0.97), and 0.98) (+ 0.30) in lakhs/cumm respectively. Mean values of elastography, APRI score, and Platelet counts in patients without the presence of esophageal varices were 16.3 (+7.9) Kpa, 0.51 (+0.07), and 2.11 (+0.69) respectively. P value was calculated to be < 0.05 and it is statistically significant.Saad et al.11 in 2013 found that mean values of liver stiffness were significantly greater in cases with varices compared to cases without varices (49.4 Kpa vs 27 Kpa). However, there was a decreased Platelet count in varices patients compared to non-varices patients (1.07 lakhs /cumm vs 0.729 lakhs /cumm). Mean Elastography values were correlated with the grading of esophageal varices. Mean Elastography values in patients without Gastroesophageal varices were found to be 16.33(+7.9) Kpa. It was 17.9(+5.4) Kpa among cases with Grade One varices, 24.6(+5.81) Kpa among Grade Two, and 31.52(+3.50) Kpa among cases with Grade Three varices (P value < 0.01). Measurement of elastographic values for the liver has both diagnostic and prognostic values for the detection of esophageal varices. Even low platelet counts as a result of hypersplenism may predict the future risk of varices. Shivam et al.12 in 2021 found that there was a big change in the average liver stiffness value from not having any varix (14.60 ±0.88) Kpa to having small-sized esophageal varix (15.51 ± 2.76) Kpa to having large sized esophageal varix(23.80 ± 3.17) Kpa and this change was linked to the severity of the varices. The mean liver stiffness measurement for identifying varices was 15.51 ± 2.76 kilopascals (kPa), but for large varices, it was 23.80 ± 3.17 kPa.

Using the ROC curve, cutoffs were taken. Using the cutoff values for liver stiffness using Elastography- 19.3 Kpa; a Sensitivity of 82.1% and a Specificity of 66.7 % were calculated for Elastography to detect the esophageal varices and with 1.1 cutoff values for APRI; a Sensitivity of 70.4 % and a Specificity of 52% were calculated. Again, Using the cutoff values for liver stiffness using Elastography-27.1 Kpa; a Sensitivity of 85.7%, and a Specificity of 84.8% were calculated for Elastography to detect the presence of Large sized (Grade Three) oesophageal Varices, and with 1.45 cutoff values for APRI; a Sensitivity of 78.6 % and a Specificity of 76.1% were calculated. Omar et al.13 in 2023 found that cases who had oesophageal varices had more liver stiffness than those who did not. The diagnostic accuracy for evaluating hepatic stiffness was 95% sensitive and 98% specific at the optimal cutoff value of 27.3 Kpa. Additionally, those with extensive varices had significantly higher liver stiffness scores than those with small varices. With an ideal cutoff value of 40.9 Kpa, the liver stiffness test had 93% sensitivity and 52% specificity.

The overall commonest etiology of CLD is alcohol, then MASLD due to lifestyle modification and sedentary lifestyle or mass immunization against hepatitis B in our locality. In the present study, risk for Esophageal Varices was predict by assessing stiffness of liver using Elastography. Elastography is simple, cheap, easy to perform, and nowadays become almost available everywhere.  Non-invasive tools like Point shear elastography for measuring liver stiffness or APRI score can be used nowadays to detect Portal Hypertension and its complications like esophageal varices. Elastography can also provide an excellent idea about large varices which are going to bleed. However among non-invasive measures, Elastography has a better diagnostic and prognostic value in predicting the chances of varices in the esophagus. From the discussion of our study, we can tell that diagnostic endoscopic invasive procedures for esophageal varices may be delayed for those CLD patients having lower elastographic liver stiffness values that ranged fall below the cirrhotic range. Non-invasive methods can predict the existence of varices in esophagus or stomach and can limit the need for endoscopy to those patients who are less likely to have varices and can benefit on planning the management and need for prophylaxis to prevent varices in CLD patients developing cirrhosis.

With a shortage of skilled Gastroenterologists and Endoscopic Surgeon in rural settings, Fibro Scan and APRI score- the non-invasive markers may be consider precise modalities for identifying PHTN and predicting the presence of high-risk varices.

1.       Standish RA, Cholongitas E, Dhillon A, Burroughs AK, Dhillon AP. An appraisal of the histopathological assessment of liver fibrosis. Gut. 2006 Apr;55(4):569–78.

2.       Pinzani M, Rosselli M, Zuckermann M. Liver cirrhosis. Best Pract Res Clin Gastroenterol. 2011 Apr;25(2):281–90.

3.       Fallatah HI, Al Nahdi H, Al Khatabi M, Akbar HO, Qari YA, Sibiani AR, et al. Variceal hemorrhage: Saudi tertiary center experience of clinical presentations, complications and mortality. World J Hepatol. 2012 Sep 27;4(9):268–73.

4.       Bosch J, Abraldes JG, Groszmann R. Current management of portal hypertension. J Hepatol. 2003;38 Suppl 1:S54-68.

5.       Escorsell A, Bordas JM, Castañeda B, Llach J, García-Pagán JC, Rodés J, et al. Predictive value of the variceal pressure response to continued pharmacological therapy in patients with cirrhosis and portal hypertension. Hepatol Baltim Md. 2000 May;31(5):1061–7.

6.       Foucher J, Chanteloup E, Vergniol J, Castéra L, Le Bail B, Adhoute X, et al. Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut. 2006 Mar;55(3):403–8.

7.       Danish M, Ismail H, Tulsi R, Mehmood N, Laeeq SM, Hassan Luck N. Liver Elastography as a Predictor of Esophageal Varices in Patients With Cirrhosis. Cureus. 13(10):e18593.

8.       Debnath G, Chakraborty A. A Study on FibroScan and Endoscopic Finding in Patients of Chronic Liver Disease attending Tripura Medical College and Dr. B.R. Ambedkar Memorial Teaching Hospital. J Assoc Physicians India. 2022 Jun;70(6):11–2.

9.       Alghamdi M, Fallatah H, Akbar H. Transient Elastography (Fibroscan) Compared to Diagnostic Endoscopy in the Diagnosis of Varices in Patients with Cirrhosis. 2017 Jan 24;5:55.

10.    Malik R, Lai M, Sadiq A, Farnan R, Mehta S, Nasser I, et al. Comparison of transient elastography, serum markers and clinical signs for the diagnosis of compensated cirrhosis. J Gastroenterol Hepatol. 2010;25(9):1562–8.

11.    Saad Y, Said M, Idris MO, Rabee A, Zakaria S. Liver stiffness measurement by fibroscan predicts the presence and size of esophageal varices in egyptian patients with HCV related liver cirrhosis. J Clin Diagn Res JCDR. 2013 Oct;7(10):2253–7.

12.    Shivam D, Haria JM, Singh VK, Mishra AK, Singhal A, Dubey P, et al. To Predict the Occurrence of Esophageal Varices in Chronic Liver Disease Patients Using Transient Elastography (Fibroscan). Acad J Med. 2021 May 10;4(1):13–20.

13.    Omar M, Salama ZA, Saad Y, Abdelghaffar MM. Fibroscan in Grading and Prediction of the Risk of Bleeding of Gastro-Esophageal Varices in HCV related Cirrhotic Patients. Egypt J Hosp Med. 2023 Apr 1;91(1):5157–61.