Chronic liver disease (CLD) is a progressive deterioration of liver functions (synthesis of clotting factors/proteins, detoxification of harmful products of metabolism, and excretion of bile) for more than six months. It is a continuous process of inflammation, destruction, and regeneration of liver parenchyma, which leads to fibrosis and cirrhosis. Cirrhosis is the final stage of CLD that results in disruption of liver architecture, the formation of widespread nodules, vascular reorganization, neo-angiogenesis, and deposition of the extracellular matrix(1). Progressive hepatic fibrosis leads to increased intrahepatic resistance and portal hypertension(2). Liver cirrhosis is the most common cause of portal hypertension(3). In addition, portal venous pressure correlates significantly with the degree of disease chronicity and fibrosis in liver disease(4,5).
CLD has a wide variety of causes, including long-term alcoholism, chronic viral infection (hepatitis B and C viruses), autoimmune diseases, metabolic diseases (e.g., non-alcoholic fatty liver disease, NAFLD), and hereditary disorders(1,2).
As of 2021, there were 1.5 billion people living with CLD (including any stage of disease severity) worldwide(6). Currently, the pre-eminent causes of liver cirrhosis globally are NAFLD, hepatitis B virus (HBV), hepatitis C virus (HCV), and alcoholic liver disease, in that order(6). In sub-Saharan Africa, CLD accounted for an estimated 157,558.69 deaths (equivalent to 2.11% of all deaths) in 2017(7). The prevalence rates of HBV and HCV in our locality are 4.3–23.3% and 0.5–15%, respectively(8).
Liver biopsy has been the traditional gold standard for diagnosing liver disease, while hepatic venous pressure gradient (HPVG) is the standard for diagnosing portal hypertension(9–11). However, these procedures are highly invasive. Furthermore, liver biopsy is prone to significant sampling errors, as it samples only 1/50,000 part of the liver(12).
Ultrasonography is a key non-invasive method for diagnosing liver diseases using B-mode/grayscale imaging, elastography, and Doppler parameters. The diameter of the portal vein is variable, and various studies carried out to determine the sonographic value for their respective populations reveal a range of about 7–15 mm(13–15).
On Doppler interrogation, the normal flow through the portal vein is hepatopetal (towards the liver), a finding which may be absent or reversed in portal hypertension. The normal blood flow velocity in the portal vein is 13–55 cm/s. The portal waveform is monophasic with an undulating appearance due to its variations with cardiac activity and respiration(15–17).
The portal vein congestion index (PVCI) was first introduced and analyzed by Moriyasu
The aim of this study was to compare the PVCI of adult patients with CLD to that of healthy controls, and to evaluate the differences in PVCI, if any, between the common etiologies of CLD (CVH, ALD, and NAFLD).
This was a prospective descriptive comparative sonographic study done at the Radiology Department of the Delta State University Teaching Hospital from January 2020 to January 2021. A total of 160 participants (80 subjects and 80 controls) were enrolled. The Research and Ethics Committee of the institution approved the study protocol (HREC/PAN/2019/072/0324). Subjects were recruited into the study after an informed written consent had been granted following a thorough explanation of the aims and objectives of the study, methods of examination, and benefits.
The participants were adult patients (>18 years) diagnosed with CLD or liver cirrhosis at the gastroenterology clinic based on clinical (stigmata of CLD)(21) and laboratory parameters(1). The subjects were enrolled consecutively until the sample size was complete. The exclusion criteria included portal hypertension from other causes (e.g., portal vein thrombosis, right heart failure), prior therapies for portal hypertension, tachypnea, pregnancy, recent upper abdominal surgery, and medications (vasoactive drugs, diuretics or anti-inflammatory medications).
The control group included healthy volunteers, without any history or laboratory evidence of liver-related diseases (normal liver function test, LFT), recruited among patients’ relatives, staff and students of the hospital and affiliated university. The exclusion criteria for controls included obesity (BMI >30 kg/m2), hepatobiliary diseases, abnormal LFT, splenomegaly, cardiac diseases, recent abdominal surgery, tachypnea, pregnancy, and anatomical variants of the portal vein (e.g., double portal vein).
The relevant demographic data and medical history were recorded in structured questionnaires, including the participants’ age, sex, height, weight, and body mass index [BMI = weight/height2 (kg/m2)]. BMI of <18.5 kg/m2, 18.5–24.9 kg/m2, 25.0–29.9 kg/m2, 30– 39.9 kg/m2, and >40 kg/m2 were classified as underweight, normal, overweight, obese, and morbidly obese, respectively(22). The last menstrual period (LMP) of female participants was documented and a pelvic ultrasound scan was done to exclude cyesis. Blood samples were collected from the participants under aseptic conditions and sent to the laboratory for liver function tests.
Abdominal ultrasound was done using the curvilinear transducer (2.8–5.2 MHz frequency) of a Siemens ultrasound machine with Doppler facility (Sonoline G50, Siemens Medical Solutions Inc., USA) or a Mindray DC-30 ultrasound scanner (Shenzhen Mindray Bio-Medical Electronic Co. Ltd. China). The participants were scanned in the supine position following a minimum of 4 hours fast (to minimize bowel gas and reduce the likelihood of portal venous hemodynamic alterations by nutrient load)(15,23). The liver was scanned to determine echogenicity, presence of nodules, and craniocaudal span at the midclavicular line(14). Liver spans <10 cm and >15 cm were defined as shrunken liver and hepatomegaly, respectively(24). The splenic span was also measured. Splenomegaly was defined as craniocaudal splenic span >12 cm(25).
A subcostal approach (with the transducer pointing posterocephalad) or a right intercostal approach (transducer pointing medially) was employed to evaluate the portal vein for thrombus(23). The transducer was placed at the epigastrium in both the transverse and longitudinal planes to assess the main portal vein during intermittent breath holds or quiet inspiration(23). Erect right anterior oblique or left posterior oblique views were employed to adequately visualize the distal extrahepatic portal vein whenever it was obscured by significant duodenal gas. The portal vein’s cross-sectional area and the mean flow velocity were measured at a point just distal to the union of the splenic and superior mesenteric veins(20). On grayscale imaging, a frozen transverse cut-section of a well demonstrated portal vein was obtained and the cross-sectional area was measured using the ellipse mode of the ultrasound machine. The ellipse was placed to approximate the inner margins of the echogenic wall of the portal vein (Fig. 1).
Portal vein Doppler waveforms were obtained using an insonation angle <60°, following which the mean flow velocity [also known as the Time Averaged Mean Velocity (TAmean)](26–28) was calculated automatically by the ultrasound machine. All measurements were taken three times by one investigator, and the average was calculated to reinforce the reliability of the outcome and minimize intra-observer variability. The portal vein congestion index (cm/sec) was computed using the formula: Cross-Sectional Area (cm2)/Mean Flow Velocity (cm/sec).
The study data collected were entered and subsequently analyzed using the IBM SPSS Statistics for Windows version 24 (IBM Corp., Armonk, New York, USA). Data normality was tested using the Kolmogorov-Smirnov test. Categorical data were expressed in proportion or percentages, while continuous data was expressed as mean (± standard deviation). For categorical data, the test of association between proportions was done using chi-square or odds ratio, as appropriate, while for continuous variables, Student’s t-test or analysis of variance (ANOVA) was used to test for difference. Confounding variables were controlled for by stratification or regression analysis.
One hundred and sixty (160) participants, comprising eighty (80) subjects with chronic liver disease (CLD) and eighty (80) healthy controls, were recruited. There were 56 (70%) males and 24 (30%) females in the CLD group, while the control group had 48 (60%) male and 32 (40%) female participants. The mean age for the study population was 40.28 ± 12.09 years. The other socio-demographic details are presented in Tab. 1.
Socio-demographic characteristics of the study population
Controls | CLD | Total | Test statistics | ||||||
---|---|---|---|---|---|---|---|---|---|
(%) | (%) | (%) | |||||||
7 | 8.8 | 0 | 0.0 | 7 | 4.4 | χ2 = 17.948 | |||
21 | 26.3 | 12 | 15.0 | 33 | 20.6 | ||||
17 | 21.3 | 23 | 28.7 | 40 | 25.0 | ||||
23 | 28.7 | 22 | 27.5 | 45 | 28.1 | ||||
12 | 15.0 | 16 | 20.0 | 28 | 17.5 | ||||
0 | 0.0 | 5 | 6.3 | 5 | 3.1 | ||||
0 | 0.0 | 2 | 2.5 | 2 | 1.3 | ||||
36.81 ±11.60 | 43.74 ± 11.63 | 40.28 ±12.09 | t = -3.770 | ||||||
48 | 60.0 | 56 | 70.0 | 104 | 65.0 | χ2 = 1.758 | 0.185 | ||
32 | 40.0 | 24 | 30.0 | 56 | 35.0 | ||||
4 | 5.0 | 7 | 8.8 | 11 | 6.9 | χ2 = 17.140 | |||
15 | 18.8 | 28 | 35.0 | 43 | 26.9 | ||||
26 | 32.5 | 9 | 11.3 | 35 | 21.9 | ||||
35 | 43.8 | 32 | 40.0 | 67 | 41.9 | ||||
0 | 0.0 | 4 | 5.0 | 4 | 2.5 | ||||
45 | 56.3 | 38 | 47.5 | 83 | 51.9 | χ2 = 3.143 | 0.871 | ||
8 | 10.0 | 10 | 12.5 | 18 | 11.3 | ||||
12 | 15.0 | 9 | 11.3 | 21 | 13.1 | ||||
5 | 6.3 | 8 | 10.0 | 13 | 8.1 | ||||
2 | 2.5 | 4 | 5.0 | 6 | 3.8 | ||||
3 | 3.8 | 4 | 5.0 | 7 | 4.4 | ||||
4 | 5.0 | 6 | 7.5 | 10 | 6.3 | ||||
1 | 1.3 | 1 | 1.3 | 2 | 1.3 |
The mean weight of subjects in the CLD group was 72.63 ± 4.87 kg, while in the control group it was 73.02 ± 5.13 kg (
Increased liver echogenicity was observed in 45/80 (56.3%) of the CLD group, comprising 36/57 (63.2%) of the ALD subgroup and in 9/23 (39.1%) of the CVH subgroup (
B-mode liver findings in the CLD subgroups
Alcoholic liver disease | Chronic viral hepatitis | Total | χ2 | P-value | |||||
---|---|---|---|---|---|---|---|---|---|
(%) | (%) | (%) | |||||||
36 | 63.2 | 9 | 39.1 | 45 | 56.3 | χ2 = 3.844 | 0.051 | ||
17 | 29.8 | 5 | 21.7 | 22 | 27.5 | χ2 = 11537 | 0.464 | ||
19 | 33.3 | 6 | 26.1 | 25 | 31.3 | χ2 = 0.402 | 0.818 | ||
27 | 47.4 | 12 | 52.2 | 39 | 48.8 | ||||
11 | 19.3 | 5 | 21.7 | 16 | 20.0 |
Twenty-four (30%) patients with CLD had ascites, out of which 19 (33.3%) were in the ALD subgroup and 5 (21.7%) in the CVH subgroup. The total number of study participants that had splenomegaly was 20 (25%), with 16 (28.1%) in the ALD subgroup and 4 (17.4%) in the CVH subgroup.
The mean congestion index in the CLD study subjects was 1.1037 ± 0.03 cm/sec, and this showed a significant weak positive correlation with the presence of ascites (r = 0.24,
Tab. 3 and Tab. 4 show the differences in portal vein diameter (PVD), portal vein cross-sectional area (PVSA), portal vein mean velocity (PVMV), and portal vein congestion index (PVCI) between the study groups and subgroups. Table 5 is a post-hoc analysis which shows that all the intergroup differences were statistically significant.
Portal vein parameters of the control and CLD groups
Controls ( |
Chronic liver disease ( |
|||
---|---|---|---|---|
1.16 ± 0.14 | 1.34 ± 0.15 | t = -7.604 | ||
1.07 ± 0.26 | 1.42 ± 0.32 | t = -7.500 | ||
14.01 ± 1.60 | 13.90 ± 1.47 | t = 0.462 | 0.645 | |
0.0775 ± 0.02 | 0.1037 ± 0.03 | t = -6.735 |
PV – portal vein;
Portal vein parameters of the ALD and CVH subgroups
Alcoholic liver disease ( |
Chronic viral hepatitis ( |
|||
---|---|---|---|---|
1.36 ± 0.16 | 1.28 ± 0.10 | t = 2.234 | ||
1.47 ± 0.35 | 1.29 ± 0.20 | t = 2.330 | ||
13.90 ± 1.50 | 13.90 ± 1.42 | t = 0.008 | 0.993 | |
0.1077 ± 0.03 | 0.0939 ± 0.02 | t = 2.006 |
PV – portal vein;
Post-hoc analysis of intergroup differences in portal vein congestion index
Total | |||
---|---|---|---|
0.0775 ± 0.02 | 6.735 | ||
0.1037 ± 0.03 | |||
0.1077 ± 0.03 | 2.006 | ||
0.0939 ± 0.02 | |||
0.0775 ± 0.02 | 47.562 | ||
0.1077 ± 0.03 | |||
0.0775 ± 0.02 | 47.562 | ||
0.0939 ± 0.02 |
The highest mean PVCI (0.0817 ± 0.022 cm/sec) in the control group was found in subjects in the third decade, while the lowest mean PVCI (0.0731 ± 0.021 cm/sec) in the same group was found in the fourth decade. By contrast, in the CLD group, the lowest mean PVCI (0.0980 ± 0.040 cm/sec) and the highest mean PVCI (0.1287 ± 0.010 cm/sec) were found in the seventh and eighth decades, respectively. The differences in mean PVCI among the different age groups in both the control and CLD study groups were not statistically significant (
Effect of age, sex, and BMI on PVCI in the ALD and CVH subgroups
Mean ± SD | Alcoholic liver disease | Chronic viral hepatitis | χ2 | |||||
---|---|---|---|---|---|---|---|---|
Mean ± SD | ||||||||
0.1196 ± 0.041 | 7 (12.3) | 0.0863 ± 0.010 | 5(21.7) | 3.675 | 0.597 | |||
0.0997 ± 0.027 | 19 (33.3) | 0.0848 ± 0.008 | 4(17.4) | 1.359 | 0.250 | |||
0.1143 ± 0.030 | 16 (28.1) | 0.0994 ± 0.020 | 6 (26.1) | |||||
0.1101 ± 0.035 | 10 (17.5) | 0.0986 ± 0.020 | 6 (26.1) | |||||
0.0852 ± 0.019 | 4 (7.0) | 0.0773 | 1 (4.3) | |||||
0.1356 | 1 (1.8) | 0.1217 | 1 (4.3) | |||||
0.1072 ± 0.033 | 41 (71.9) | 0.0911 ± 0.018 | 15 (65.2) | 0.352 | 0.553 | |||
0.1090 ± 0.028 | 16 (28.1) | 0.0992 ± 0.016 | 8 (34.8) | 0.173 | 0.678 | |||
0.1006 ± 0.027 | 4 (7.0) | – | – | 1.822 | 0.402 | |||
0.1022 ± 0.030 | 30 (52.6) | 0.0919 ± 0.016 | 14 (60.9) | 1.652 | 0.198 | |||
0.1161 ± 0.033 | 23 (40.4) | 0.0970 ± 0.020 | 9 (39.1) |
ALD – alcoholic liver disease, CVH – chronic viral hepatitis, BMI – body mass index, PVCI – portal vein congestion index
The mean PVCI was higher in females than males in both study groups, with males in the control group having a mean PVCI value of 0.0742 ± 0.020 cm/sec, and females having a mean PVCI of 0.0825 ± 0.019 cm/sec. In the CLD group, males and females had mean PVCI values of 0.1029 ± 0.030 cm/sec and 0.1058 ± 0.024 cm/ sec, respectively. The gender differences in PVCI were not statistically significant (
Portal hypertension is a common finding in decompensated chronic liver disease/liver cirrhosis, and several researchers have validated the suitability of Doppler sonography for evaluating portosystemic changes within the liver(14). In this study, the hepatic and portal venous changes in 80 participants with CLD were compared to healthy controls.
The most common cause of CLD was alcoholic liver disease (ALD), which was seen in 57 (71.3%) subjects. The number of CLD patients with ALD was significantly higher than those diagnosed with CVH. This is at variance with studies which found chronic viral hepatitis B to be the most common cause of CLD(29–31). The higher prevalence of ALD in this study was probably due to the high rate of alcohol consumption (locally brewed gin called ‘ogogoro’ or ‘kai-kai’) in our region(32).
A greater number of subjects in the ALD group showed more features of hepatic decompensation (ascites, splenomegaly, hepatic nodularity, shrunken liver with irregular outline) than the CVH group. This can probably be explained by the fact that subjects with alcoholic liver disease were more inclined to show signs of more advanced signs of liver disease due to late presentation, poor level of compliance and higher rates of relapse. Some of the hepatic and extrahepatic sonographic findings in the CLD group of this study were similar to those documented by Maàji
The portal vein diameter (PVD) was significantly higher in the CLD group than the controls. This is in agreement with the findings from the study by Achim
The mean PVCSA of the CLD group was significantly higher than that of controls. This was similar to the findings by Moriyasu
The CLD group had a mean PVCI of 0.104 ± 0.03 cm/sec, which was significantly higher than the value for controls. Of the two CLD subgroups, the ALD subgroup showed a significantly higher mean PVCI than the CVH subgroup. The reason ALD patients had a higher mean PVCI than CVH patients may be due to the poor health seeking behavior of this category of patients, leading to more advanced liver disease states at presentation. This is probably worsened by the higher number of males than females in this subcategory, as men in this society have been shown to have worse health seeking habits than women(36). Furthermore, non-compliance may also play a significant role, as alcoholics tend to show poor compliance with health intervention strategies, with higher rates of relapse to the detriment of their liver health.
Other studies also found a significant difference in PVCI between CLD cases and controls(19,26,37–39). Ehtisham
Chakravarthy and co-researchers(19), on the other hand, subdivided the CLD participants into three subcategories of ALD, CVH, and non-alcoholic fatty liver disease (NAFLD), and measured the PVCI in each of these subgroups. The PVCI values recorded for each of these conditions were significantly higher than the value obtained in their controls, i.e., medians of 0.027, 0.050 and 0.060 for NAFLD, CVH, and ALD, respectively. The absolute values in their study differed significantly from those of the index research possibly due to interobserver variability, differing Doppler angles, and racial differences.
Similarly, Iliopoulos
Haag
Bolognesi
We encountered some limitations in this study. Firstly, due to the location of the portal vein, a large body habitus or significant bowel gas usually made scanning difficult. Oblique views were employed to overcome this limitation. The subjects whose portal veins could still not be assessed were excluded from the study. Secondly, we could not correlate the PVCI with the Child-Pugh classification.
In conclusion, the patients with CLD had a significantly higher PVCI than healthy controls. Similarly, the PVCI of the ALD subgroup was significantly higher than that of the CVH subgroup. The significant difference in PVCI between the control and CLD groups suggests that PVCI can be an adjunct parameter for detecting chronic liver diseases.