ORIGINAL�ARTICLE ABSTRACT Objective: To determine the association between Doppler Parameters of average peak portal vein velocity and flow direction and Child Pugh classes of patients suffering from the chronic liver disease. Study Design: It was a descriptive study. Place and Duration of Study: The study was conducted from December 2013 to January 2015 at the Radiology Department of Holy Family Hospital, Rawalpindi, Pakistan. Materials and Methods: Selected chronic liver disease (CLD) patients were examined with gray scale and Doppler USG for assessment of portal vein (PV). Average peak portal venous velocity (PVV) and direction of flow in the main portal vein were recorded. Doppler findings were correlated with clinical features and laboratory findings in three classes (A,B & C) of patients using Child Pugh criteria to establish any probable association between them (appendix: I). Results: Out of total 115 CLD patients studied, 47.8% were in Child Pugh class C. The main portal vein average PVV (cm/sec) in 24.34% patients with Child Pugh class A was 18.75 + 1.88, in 27.82% patients with Child Pugh class B was 14.25 + 0.98 and in 47.82% patients with Child Pugh class C was 8.15 + 1.84. This showed significant fall in portal vein average PVV with advancing Child Pugh class of cirrhosis. Only 10.4% patients showed continuous hepatofugal flow and 4.3% showed bidirectional flow. It was recorded only in Child Pugh class C patients. Conclusion: Doppler findings of average peak velocity in the main portal vein fall progressively with worsening of the Child Pugh class. In addition, the direction of flow is also reversed in cases of the Child Pugh class C cirrhosis. Key Words: Child, Cirrhosis, CLD, Doppler, Direction, Flow, Hypertension, Hepatic, Liver, Portal, Pugh, Transplant, Ultrasound, Vein, Velocity. Introduction Pakistan has been positioned in intermediate prevalence zone for viral hepatitis B and C that is responsible for >75% of cirrhosis and hepatocellular 1 carcinoma (HCC) in WHO EMRO region. The burden of the disease and its end-stage complications are a huge challenge for the healthcare providers because a majority of patients remain asymptomatic and unaware, leading to a silent epidemic and therefore resulting in significant morbidity and mortality in our 2,3 country. The chronic liver disease leads to many complications such as portal hypertension ( as cites , hyp ers p len is m, varices ) , systemic dysfunction (hypoalbuminemia, coagulopathy), hepatopulmonary and hepatorenal syndromes, encephalopathy, hepatocellular carcinoma, and the notorious cirrhosis which is the common endpoint of a w i d e va r i et y o f C L D p ro c e s s e s ca u s i n g 4 , 5 hepatocellular necrosis. The World Health Organization (WHO) has defined Cirrhosis as “a Association of Portal Vein Doppler Parameters with Chronic Liver Disease Child Pugh Classes: A Single Center Experience at Rawalpindi, Pakistan 1 2 3 4 5 6 Abdul Ahad Farooq , Ahsen Farooq , Muhammad Rashid , Junaid Haris Farooq , Salma Umbreen , Rabia Waseem Correspondence: Dr. Abdul Ahad Farooq Senior Registrar Rawalpindi Institute of Cardiology, Rawalpindi Associate Consultant Radiologist Quaid-e-Azam International Hospital, Islamabad E-mail: docahad@gmail.com 1 Department of Radiology Rawalpindi Institute of Cardiology, Rawalpindi Quaid-e-Azam International Hospital, Islamabad 2 Department of Radiology Islamic International Medical College, Rawalpindi Riphah International University, Islamabad 3 Department of Medicine / Nephrology KRL Hospital, Islamabad 4 Department of Internal Medicine Charleston Area Medical Center Charleston, West Virginia, USA 5 Department of Radiology Wah Medical College, Wah 6 Department of Radiology HITEC Institute of Medical Sciences, Taxila Funding Source: NIL; Conflict of Interest: NIL Received: October 24, 2018; Revised: February 13, 2019 Accepted: March 06, 2019 Association of Portal Vein Doppler & Child Pugh Classes of Patients with CLDJIIMC 2019 Vol. 14, No.1 33 onwards was included in the study. Child Pugh classification (A, B and C) was done as per standard 7 criteria by the medical and radiological department. (Appendix 1). Patients having portal vein thrombosis (PVT) were excluded from the study. Informed consent was obtained from all the patients fulfilling the inclusion criteria. Patients were subjected to conventional grayscale and Doppler ultrasound using Toshiba Nemio ultrasound machine equipped with multi-frequency linear and curvilinear transducer probes. The examination was performed or supervised at least by a registrar level radiologist. All the patients were examined preferably in the supine position. During the examination, every patient was required to hold breath in deep inspiration, to avoid motion artifacts. The scanning of the portal vein was carried out longitudinally throughout its entire length from an anterior abdominal subcostal and/or right intercostal approach. It was analyzed for the presence or absence of intra-luminal thrombus, blood flow velocity in cm/s and direction of blood flow within the portal vein. All the findings were reconfirmed by another consultant radiologist. Data were collected by the principal investigator on the study proforma. Data were entered and analyzed by Statistical Package for the Social Sciences (SPSS) version 22. Descriptive statistics were calculated. The quantitative variable of the study included; average peak venous velocity in the main portal vein compared with different Child Pugh classes A, B & C and expressed as Mean ± SD. The qualitative variable of the study included; the direction of portal vein blood flow compared with different Child Pugh classes A, B & C and expressed as frequency. Results A total of 125 CLD patients presented from December 2013 till January 2015. Ten patients were excluded from the study because of either incompletely available medical record or loss to follow up and portal vein thrombosis in 2 cases. Therefore, a total number of 115 CLD patients without PVT were included in this study. The age ranged from 21-77 years with a mean age of 40.6+11.54 years. Most of them (43, 37.4%) ranged between 31-40 year age group. Males were 70 (60.87%) and females 45 (39.13%) with M:F of 1.6:1 approximately. Majority of patients (47.8%) were in diffuse process characterized by fibrosis and conversion of normal liver architecture into 6 structurally abnormal nodules.” The Child Pugh classification system is the most commonly used tool for clinically predicting the prognosis in cirrhosis. Child and Turcotte first presented their criteria in 7 1964 that was later revised by Pugh in 1973. Chronic liver disease, especially in asymptomatic patients has been diagnosed mainly by the liver 8 biopsy which helps in its staging and grading. However, the risks and limitations associated with this invasive method have led to the development of safer methods of investigation. Grayscale USG is now an integral part of the routine liver examination and Doppler studies have been considered as the gold standard tool for evaluating the velocity and direction of blood flow in the portal 4,9 venous system. It is a non-invasive, rapid and cost- effective investigation and well accepted by the 4,10 patients. In Pakistan, now there are centers offering liver transplant as prospective management of CLD, therefore, use of Child Pugh classification and Doppler studies have become a vital assessment tool. Only a few studies have been conducted evaluating the role of Doppler ultrasound in the assessment of chronic liver disease patients in 2 Pakistan. The aim of this study was to explore the value of Doppler ultrasonography in the assessment of PV hemodynamics in CLD patients and to determine the association between Doppler Parameters of PPV and flow direction and Child Pugh classes of the Pakistani patients suffering from the chronic liver disease. Materials and Methods This descriptive cross-sectional study was conducted in the Department of Radiology in collaboration with the Department of Medicine at Holy Family Hospital Rawalpindi. Approval was taken from the hospital ethical committee. Nonprobability convenience consecutive sampling technique was used. Using WHO sample size calculator, the sample size of 115 was calculated by taking a confidence level of 95 % and population mean of 18.33. All the patients of either gender and of age more than 20-year, having clinical, biochemical and radiological evidence of chronic liver disease, presenting to the departments of medicine and radiology from December 2013 34 JIIMC 2019 Vol. 14, No.1 Association of Portal Vein Doppler & Child Pugh Classes of Patients with CLD aetiologies. Since long, liver biopsy has been considered as the gold standard for diagnosing, staging and grading the liver damage in CLD, 8 especially in asymptomatic patients. This invasive method has several risks and limitations, including morbidity and mortality, sampling error, diagnostic inaccuracy, interobserver and intraobserver 11 variability, and difficulties in follow-up. Therefore, it led to the development of safer methods for evaluation of CLD and its complications. The non- invasive Grayscale and Doppler USG studies have now been considered as an essential part of the investigation battery for assessing the CLD 9,10. patients. With increasing accessibility of liver transplant facility for the management of end stage CLD world over, the use of Child Pugh classification as a valuable indicator of the prognosis in CLD patients 9 have become vital as well. Combined together imaging, pathological and clinical assessment methods help explore new therapeutic avenues. The role of ultrasound imaging in the evaluation of 4,12,13,14,15 CLD / cirrhosis is well known. Doppler USG is an important diagnostic modality for the analysis of 9,10,16,17 the hepatic vasculature and blood flow. The standard dynamics of blood flow in the hepatic artery, hepatic veins, and the portal vein, have been 4,9,10,15,17 well defined in the literature. Changes in hepatic blood flow dynamics might be alternate markers for significant parenchymal changes in 9.10,11 chronic liver diseases and their complications. The Child Pugh classification is mostly used to stage chronic liver disease based on clinical and laboratory parameters that is ascites, encephalopathy, bilirubin and albumin levels, and prothrombin time. There are three stages of the Child Pugh classification system, 7 A, B and C depicting increasing severity of CLD. (Appendix-I) On Doppler US, the characteristic portal vein hemodynamic features of liver cirrhosis include reducing blood-flow velocity, absent pulsatility, and change in flow direction from hepatopetal to 9,10,11,15,16,17 hepatofugal in more advanced cases. The normal portal vein velocity ranges from 16 to 40 15,16 cm/sec with variations caused by respiration. Portal venous flow velocities progressively fall with rising portal venous pressure because back pressure limits forward velocity that is characteristic for portal hypertension and also due to collaterals formation, Child Pugh class C (Table-I). Doppler findings of the average peak venous velocity (PVV) and the direction of blood flow in the main portal vein were evaluated in all the subjects and were compared with Child Pugh classes A, B, and C. The main portal vein average PVV (cm/sec) in 28 (24.34%) patients with Child Pugh A was 18.75 + 1.88, in 32 (27.82%) patients with Child Pugh B was 14.25 + 0.98 and in 55 (47.82%) patients with Child Pugh C was 8.15 + 1.84 (Table-II). Only 17 (14.7%) patients demonstrated non hepatopetal flow (hepatofugal / bidirectional), 12 (10.4%) showed continuous hepatofugal flow and 5 (4.3%) showed bidirectional flow (Table-III). It was recorded only in Child Pugh class C patients. Table I: Distribu�on of Child Pugh Classes A, B, and C among the Pa�ents Table II: Comparison of Average Peak Venous Velocity in the Main Portal Vein in Child Pugh Classes A, B, and C Table III: Pa�erns of Flow in the Main Portal Vein among Child Pugh's Classes A, B, and C. Discussion Accurate evaluation of liver parenchymal damage and altered vascular hemodynamics is crucial for therapeutic decisions, surveillance, and assessment of the prognosis in chronic liver diseases of various 35 JIIMC 2019 Vol. 14, No.1 Association of Portal Vein Doppler & Child Pugh Classes of Patients with CLD % of patients which all corresponds to the Child Pugh 9 class C. Afif, et al in 2017, studied the maximum velocities in portal vein, hepatic vein and hepatic artery and hepatic artery resistive index in liver cirrhosis patients of the Singapore population. They found that flattening of the hepatic vein waveforms was related to the degree of liver cirrhosis. The cirrhotic patients showed higher maximum hepatic vein velocity. However, they had lower maximum portal vein velocity and there was a further decrease in average maximum portal vein velocity as the severity of liver cirrhosis worsened. In our study of 115 Pakistani CLD patients, the main portal vein average PVV was 18.75 + 1.88, 14.25 + 0.98 and 8.15 + 1.84 cm/sec in the Child Pugh classes A, B and C respectively (Table-II). This showed a significant fall in portal vein average PVV with the increasing severity grade of cirrhosis based on the Child Pugh class. The results are consistent with results of Chawla et al, Shi et al and by Vyaset al 19,20,21 studies. Normal individuals display a hepatopetal portal 15,16,17 venous blood flow. In deteriorating CLD, portal venous flow progressively slows down with rising portal venous resistance and pressure, first nearing the level of stagnation demonstrated by the 16,17 phenomenon of a to-and-fro (bidirectional) flow. Later with advancing cirrhosis, obstruction of the hepatic venules and sinusoids due to fibrosis and architectural distortion, and further by arterioportal and porto-systemic shunting, eventually leading to hepatofugal (reversed) portal venous flow and fall in 4,16,17 velocity. In our study, only 4.3% patients showed bidirectional flow and 10.4% showed continuous hepatofugal flow (Table-III). It was recorded only in the Child Pugh class C. None of the patient in the Child Pugh class A and B demonstrated hepatofugal flow. Gaiani et al have 22 reported the similar patterns. It implies that with more reversal of the portal venous flow, there is increased deterioration of liver function and hence poorer the Child Pugh score. Despite the single center's small study and some limitations of the final diagnoses and follow up, the results of our study are by and large supported by the various international studies. This study imparts a deeper insight into the non-invasive and cost- effective mode for the assessment of progression 4,16 which is caused by cirrhosis in most of the cases. With this background, not many studies have been conducted evaluating the role of Doppler ultrasound in the assessment of chronic liver 2 disease patients in Pakistan. Likewise, few regional studies have examined the association of Doppler parameters of direction and velocity of flow in the 9,18 main portal vein with the Child Pugh class. O u r s t u d y h a s d e t e r m i n e d t h a t D o p p l e r ultrasonography is a valuable modality for the assessment of portal vein hemodynamics in the Pakistani patients suffering from the chronic liver disease. It has established an association between Doppler findings of average peak velocity and flow direction in the main portal vein and Child Pugh classes of cirrhosis. Doppler findings of average peak velocity in the main portal vein fell progressively with worsening of the Child Pugh class. In addition, the direction of flow was also reversed in cases of the Child Pugh class C cirrhosis. A study by Mittal, et al published in 2011, have examined the association of Doppler findings of flow velocity and direction in the main portal vein with the Child Pugh class in the Iranian population. This study shows average peak portal venous velocity of 18.33 + 2.22,14.59 + 3.57 and 10.96 + 2.33 cm/s in the Child Pugh class A, B and C respectively and non- hepatopetal flow (hepatofugal or bidirectional) in 12 Appendix I: Child Pugh Classifica�on for Liver Cirrhosis 36 JIIMC 2019 Vol. 14, No.1 Association of Portal Vein Doppler & Child Pugh Classes of Patients with CLD Iranian Journal of Radiology. 2011; 8(4): 211. 10. El-Shabrawi MHF, El-Raziky M, Sheiba M, El-Karaksy HM, El- Raziky M, Hassanin F, et al. Value of duplex Doppler ultrasonography in non-invasive assessment of children with chronic liver disease. World J Gastroenterol. 2010, 16(48): 6139–44. 11. Zytoon AA, Allah AN, Faisal A. The prediction of liver disease status using Doppler observations of the hepatic and portal venous system compared with liver biopsy in patients with chronic hepatitis C. Research and Reports in Focused Ultrasound. 2014; (2): 1-11. 12. Gerstenmaier JF, Gibson RN. Ultrasound in chronic liver disease. Insights Imaging. 2014; 5(4): 441-55. 13. Afzal S, Masroor I, Beg M. Evaluation of Chronic Liver Disease: Does Ultrasound Scoring Criteria Help?. Int J Chron Dis. 2013; 31(7), 1-6. 14. Memon SK. Ultrasonographic Findings of Liver in Chronic Liver Disease and its Complications and Their Association with the Duration of the Disease. J Coll Physicians Surg Pak. 2017; 27(3): 127-30. 15. Rumack CM, Levine D. Diagnostic Ultrasound E-Book. Elsevier Health Sciences; 2017. 16. McNaughton DA, Abu-Yousef MM. Doppler US of the Liver Made Simple. RadioGraphics. 2011; 31(1):161-88. 17. Iranpour P, Lall C, Houshyar R, Helmy M, Yang A, Choi JI, et al. Altered Doppler flow patterns in cirrhosis patients: an overview. Ultrasonography. 2016; 35(1): 3–12. 18. Afif AM, Chang JP, Wang YY, Lau SD, Deng F, Goh SY et al. A sonographic Doppler study of the hepatic vein, portal vein and hepatic artery in liver cirrhosis: Correlation of hepatic hemodynamics with clinical Child Pugh score in Singapore. Ultrasound. 2017; 25(4): 213-21. 19. Chawla Y, Santa N, Dhiman RK, Dilawari JB. Portal hemodynamics by duplex Doppler sonography in different grades of cirrhosis. Dig Dis Sci. 1998; 43(2): 354-7. 20. Shi BM, Wang XY, Mu QL, Wu TH, Xu J. Value of portal hemodynamics and hypersplenism in cirrhosis staging. World J Gastroenterol. 2005; 11(5): 708-11. 21. Vyas K, Gala B, Sawant P, Das HS, Kulhalli PM, Mahajan SS. Assessment of portal hemodynamics by ultrasound color Doppler and laser Doppler velocimetry in liver cirrhosis. Indian J Gastroenterol. 2002; 21(5): 176-8. 22. Gaiani S, Bolondi L, Li Bassi S, Zironi G, Siringo S, Barbara L. Prevalence of spontaneous hepatofugal portal flow in liver cirrhosis. Clinical and endoscopic correlation in 228 patients. Gastroenterology. 1991; 100(1): 160-7. and subsequent management of the patients suffering from the deadly disease of chronic liver disease in Pakistan. Conclusion Doppler ultrasonography is a valuable modality for assessing the complex hemodynamics of hepatic vasculature (portal vein in our study), in patients with chronic liver disease and its progression as well. Doppler findings of average peak velocity in the main portal vein fall progressively with worsening of the Child Pugh class. In addition, the direction of flow is also reversed in cases of the Child Pugh class C cirrhosis. The findings of our study are in line with other published studies. REFRENCES 1. Butt AS. Epidemiology of viral hepatitis and liver diseases in Pakistan. Euroasian journal of hepato-gastroenterology. 2015; 5(1): 43. 2. Umar M, Bilal M. Hepatitis C, a mega menace: a Pakistani perspective. Journal of Pioneering Medical Sciences. 2012; 2(2): 68. 3. Khalid A, Farooq JH, Jahangir S. Hepatitis C virus Risk and Protective factors in Pakistan. LAP LAMBERT Academic Publishing (October, 2017). 4. Gupta AK, Garg A, Khandelwal N. Diagnostic Radiology: Gastrointestinal and Hepatobiliary Imaging. JP Medical Ltd; 2017; 215-30. 5. Schuppan D, Afdhal NH. Liver cirrhosis. The Lancet. 2008; 371(9615): 838-51. 6. Anthony PP, Ishak KG, Nayak NC, Poulsmn HE, Scheuer PJ, Sobin LH. The morphology of cirrhosis: definition, nomenclature, and classification. Bulletin of the World Health Organization. 1977; 55(4): 521-40. 7. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. "Transection of the oesophagus for bleeding oesophageal varices". . Br. J. Surg. 1973; 60: 646–49 8. Samuel DO, Oluleke I, Omotara SM. Safety of Liver Biopsy as a Day Procedure in Abuth Zaria, Nigeria. J Coll Physicians Surg Pak. 2012; 22(10): 675-76. 9. Mittal P, Gupta R, Mittal G, Kalia V. Association between portal vein color Doppler findings and the severity of disease in cirrhotic patients with portal hypertension. 37 JIIMC 2019 Vol. 14, No.1 Association of Portal Vein Doppler & Child Pugh Classes of Patients with CLD