Doppler study of hepatic vein in cirrhotic patients: Correlation between liver dysfunction and hepatic hemodynamics

Introduction

Cirrhosis is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules¹. It has a global prevalence of 4.5 to 9.5 %. In cirrhosis, changes occur in liver parenchyma as well as in the hepatic vasculature, including morphological changes of the hepatic vein. Furthermore, it has been observed that abnormalities in circulation are caused by hyper-dynamic circulation and persistence of intrahepatic shunt in a cirrhotic liver. Therefore, we can assume that an alteration in hepatic venous hemodynamics is present in a liver with altered function.²

Liver biopsy is still considered as the gold  standard to identify the typical features of cirrhosis³. Patients with deranged hepatic functions will have a compromised coagulation pathway. So by an invasive procedure like liver biopsy we are putting the patient at risk. By comparing hepatic vein hemodynamics with liver dysfunction, we are evaluating the efficacy of hepatic venous Doppler evaluation in diagnosing cirrhosis without biopsy.

So the intend of this study is to evaluate the hepatic venous hemodynamics using non-invasive Doppler ultrasonography in a Cirrhotic liver. Doppler waveform of the hepatic vein in healthy humans is a tri-phasic waveform, consisting of two negative waves and one positive wave. As for abnormal hemodynamics of the hepatic vein in cirrhotic liver, there are reports of Doppler studies suggesting that the waveform becomes flat when hepatocellular function is impaired, and some studies even proposed that flattening of the hepatic waveform could be used as a diagnostic tool for chronic parenchymal liver disease.²

Methodology 

The study was done for a period of 18 months from Dec 2017 to June 2019 at Department of Radiodiagnosis Khaja Banda Nawaz Institute of Medical Sciences, Kalaburagi Patients referred to department of Radiodiagnosis were selected for the study. Among  the patients those with different grades of hepatic dysfunction  were selected and grouped according to Child Pugh  score.  Sixty patients were selected and were grouped A B and C according to Child Pugh scoring. 60 controls were also selected with normal hepatic function using  inclusion and exclusion criteria.

Cases

Patients with deranged liver function (increased serum bilirubin, decreased serum albumin, increased Prothrombin time) and patients diagnosed with cirrhosis of any etiology are included, where as patients with enlarged inferior right hepatic vein, portal thrombosis, hepatofugal portal blood flow , tricuspid regurgitation, insufficient visualization of hepatic artery , right portal vein, and right hepatic vein, patients with advanced stages of hepatic encephalopathy are excluded.

Control

Patients without any pre-morbid illness and patient with normal liver function test are included, where as chronic alcoholics and patients on any chronic medications/ Hepato-toxic drugs are excluded.

After obtaining an informed consent from the patient they underwent detailed history taking and grey scale imaging of abdomen as well as Doppler evaluation for spectral wave pattern and velocimetry of right hepatic vein.

Results

The study had a sample size of 120 in the age group 19 to 69 years which contained patients of both sexes. 60 of them were of normal hepatic function and 60 had varying grades of hepatic dysfunction. Majority of the patients were in 3rd and 5th decade. Incidence of cirrhosis was more seen in this age group. While comparing both sexes males were found to have more chance of cirrhosis and the commonest aetiology for cirrhosis that we came across during the study was alcoholic liver disease followed by viral hepatitis.

The obtained data was tabulated and statistical analysis was done using IBM SPSS 20.0 version software. For qualitative data analysis chi-square test was applied, for quantitative data analysis unpaired t-test and ANOVA tests were applied for statistical significance. If P-value was less than 0.05 it was considered as statistically significant.

Primary assessment of the data showed a single wave pattern for the normal group, with a comparatively less mean hepatic vein velocity in 95% of cases the Mean Hepatic Vein Velocity (MHVV) values were within a margin of +/- 1sd. So a sample of 20 case were selected from the control group using simple random sampling for performing the statistical analysis.  The MHVV of normal subjects showed a mean value of 5.60 +/- 0.91cm/sec, Group A Child Pugh A showed a mean of 10.13 +/-1.41 cm/sec Child Pugh B class showed mean velocity of 14.23+/-2.33 cm/sec and Child Pugh C showed a mean of 21.01+/-2.72cm/ sec. The spectral wave pattern was triphasic for normal subjects, triphasic for Child Pugh class A, majority of Child Pugh B showed Biphasic and majority of Child Pugh C showed monophasic flow pattern.

Triphasic pattern showed a sensitivity of 90% for Child Pugh A, Biphasic pattern showed a sensitivity of 60% for Child Pugh B and monophasic showed a sensitivity of 90% for Child Pugh C hepatic dysfunction.

Study observed that, the mean hepatic vein velocity was 5.60 ± 0.91cm/sec that is  significantly lower in the normal group, whereas the mean hepatic vein velocity values were 10.13 ± 1.41cm/sec, 14.23 ± 2.33cm/sec and 21.01 ± 2.27cm/sec in the group A, group B and group C respectively. From the data it was observed that the mean hepatic vein velocity increases with progression of hepatic dysfunction.

There was statistically significant difference of mean values of mean hepatic vein velocity in the groups. (P<0.001) (Graph-1)

Comparison of wave pattern in the groups (Table 1) observed that, in the normal group all wave pattern were triphasic type. In group A triphasic wave pattern cases were 18 (90.0%) and biphasic wave pattern cases were 2 (10.0%). In group B triphasic wave pattern cases were 8 (40.0%) and biphasic wave pattern cases were 12 (60.0%) and in group C triphasic wave pattern cases were 0 (0.0%), biphasic wave pattern cases were 2 (10.0%) and monophasic wave pattern were 18 (90.0%).

There was statistically significant difference of distribution of wave patterns in cases between the above groups (P<0.001) (Graph-2)

Comparison of mean hepatic vein velocity with respective wave pattern within the group (Table 2) reveals that, the mean hepatic vein velocity in the triphasic wave pattern in the normal group was 5.60 ± 0.91cm/sec.

In the group A the mean hepatic vein velocity in the triphasic wave pattern was 9.82 ± 1.18 cm/ sec and mean hepatic vein velocity in the biphasic wave was 12.63 ± 2.12cm/sec and there was statistically significant difference of mean hepatic vein velocity among triphasic and biphasic wave patterns.

In the group B the mean hepatic vein velocity in the triphasic wave pattern was 11.96 ± 0.93cm/sec and mean hepatic vein velocity in the biphasic wave was 15.74 ± 1.74 cm/sec and there was statistically significant difference of mean hepatic vein velocity among triphasic and biphasic wave patterns.

In the group C the mean hepatic vein velocity in the biphasic wave pattern was 17.13 ± 0.26cm/sec and mean hepatic vein velocity in the monophasic wave was 21.43 ± 2.59cm/sec and there was statistical significant difference of mean hepatic vein velocity among biphasic and monophasic wave patterns.

This data proves that there is statistically significant relationship between wave pattern and level of hepatic dysfunction in normal, Group A, and group C with triphasic , triphasic and monophasic wave pattern respectively . In Group B we were able to see overlap of biphasic and triphasic wave pattern among studied subjects but majority showed biphasic pattern

In case of mean hepatic vein velocity, the range of velocity in different groups shows discrete values which increases with increasing grade of hepatic dysfunction (Graph-3).

From the graph it is clear that in any class the change in wave pattern is associated with an increase in velocity. There by we can assume that appearance of wave pattern belonging to the group with higher grade of hepatic dysfunction is an indicator for progression of disease.

Comparison of mean hepatic vein velocity with respective wave pattern between the groups ( Table 3) reveals that comparison between Normal and Group A, Normal and Group B, Normal and group C, Group A and Group B, Group A and Group C and Group B and Group C all showed statistically significant difference of mean hepatic vein velocity. (P<0.001)

Discussion          

Cirrhosis is defined by its histological hallmark findings on liver biopsy (regenerative nodules surrounded by fibrotic tissue) and is considered as the final evolution stage of any progressive liver disease, irrespective of its aetiology.

The natural history of cirrhosis is marked by the transition from the compensated stage (with good prognosis) to the occurrence of decompensating events, such as ascites, variceal bleeding, jaundice and hepatic encephalopathy. If the diagnosis of cirrhosis is relatively straightforward during the decompensated stage then the treatment may be problematic, on the contrary, diagnosing cirrhosis while it is still in the compensated stage is more challenging. The progression of fibrosis parallels the increase in portal pressure and, frequently, patients with severe fibrosis in the pre-cirrhotic stage have a hepatic venous pressure gradient (HVPG) >5mmhg.⁴³ Since chronic liver disease is a continuum, and due to the inhomogeneity of fibrosis within the liver⁴⁴, the border between severe fibrosis and compensated cirrhosis is often unclear.

Presently the gold standard for diagnosis is histopathology. But as patients with cirrhosis will have an altered coagulation mechanism invasive procedure always have high risk. Other investigations like MRI and CT are effective but they have risks of radiation exposure and higher expense. The importance of finding the correlation between hepatic venous velocity and spectral wave pattern is to establish Doppler of hepatic vein as an effective tool to diagnose cirrhosis and different stages of hepatic dysfunction without risking radiation exposure and at a low cost.

In normal hepatic wave pattern there are two negative waves and one positive wave of hepatic vein (HV) in healthy human when studied by Doppler giving it a triphasic appearance 39. The phaticity is caused by the changes in cardiac cycle, predominantly the change in right atrial pressure.⁴⁵ It consists of large ante grade systolic and diastolic waves, and small retrograde v, a, and rarely c waves.⁴⁶ It is widely regarded that the waveform becomes flat when hepatocellular function is impaired. Some studies even suggest that flattening of the hepatic waveform can be used as diagnostic tool for chronic parenchymal liver disease.11,40,42

Our study was done in 120 patients of whom 60 were with normal hepatic function and 60 with varying grades of hepatic dysfunction grouped into three according to Child Pugh scoring. Many studies have been published till now with varying results but none were able to define a clear demarcation between the Sonographic findings between different grades of hepatic dysfunction due to various reasons.

Subjects we studied came under a wide range of age between 18 and 69 yrs of age including both sexes. Incidence of cirrhosis was seen more in patients between 3rd and 4th decade of life. Cirrhosis was more common in the males in the studied population.

Among the cases studied the most common aetiology was chronic alcoholism followed by viral hepatitis, NASH, Biliary diseases, drug induced and metabolic disorders.

The most accurate single sign for the diagnosis of cirrhosis, which can be found even in early phases and should be always specifically investigated, is nodularity of the liver surface.^47,48 False-positive findings are rare but have been described (e.g. fulminant hepatitis leading to the collapse of large parenchyma areas). The combination of nodular liver surface and portal vein mean velocity below 12 cm/sec holds an accuracy of 80% for discriminating between patients with chronic hepatitis with severe fibrosis and those with cirrhosis.⁴⁹

In patients with clinical suspicion of cirrhosis and confounding conditions, the detection of nodular liver surface is an excellent non-invasive method to rule in cirrhosis, while the combination of ultrasound and TE(time of echo) allows the best diagnostic performance.⁴⁸

In the present study we were able to find out that a significant relation between the spectral wave pattern and grade of hepatic dysfunction. Flattening of wave form were seen in the higher grades of hepatic dysfunction with statistical values comparable to that obtained by Sudhamshu and coworkers, in their study.²

However overlap of wave forms in Child Pug B class were observed. On contrary to their study we obtained a higher percentage of monophasic wave forms in the Child Pugh C category which may be due to the fact that many of our child Pugh C patients were terminal with extreme derangement of hepatic function.

The flow velocity of hepatic vein was found out to show an increasing trend with increase in the grade of hepatic dysfunction. The MHVV of normal subjects showed a mean value of 5.60 +/- 0.91cm/ sec, Child Pugh A showed a mean of 10.13 +/-1.41 cm/sec Child Pugh B class showed mean velocity of 14.23+/-2.33 cm/sec and Child Pugh C showed a mean of 21.01+/-2.72cm/sec.

These values were comparable with a number of studies conducted prior on the same condition.

Studies by Colli et al.¹⁰ von Herbay et al.¹² and Arda et al.¹¹ had also reported incidence of flattened HV waveform in patients with cirrhosis in 57%, 43% and 18.2% respectively. The phenomenon has been attributed to increased parenchymal stiffness impairing HV compliance, thereby resulting in the loss of HV phaticity.

Conclusion            

Liver cirrhosis is associated with alterations in the parenchyma which reduces the compliance of the hepatic vessels. This will reflect in the flow pattern as well as the mean velocity of blood flow through all the vessels. By evaluation of the spectral wave pattern and mean hepatic vein velocity in patients with different stages of hepatic dysfunction and comparing them with that of the normal subjects we were able to establish a relation between them.

Spectral wave pattern was specific for normal subjects and those with Child Pugh A and C hepatic dysfunctions, whereas that for Child Pugh B showed significant overlap of wave patterns. But the mean hepatic vein velocity was showing clearly different values which increased with advancements in stage of hepatic dysfunction.

The overlap of wave pattern in class B can be overcome by including additional criteria of mean hepatic vein velocity.

Doppler evaluation of hepatic vein is of value in cirrhotic patient as a non-invasive method to assess the level of hepatic dysfunction and it can be used a diagnostic tool with significant results.