ebcr usg sirosis

Ultrasound in diagnosis of liver cirrhosis: How accurate is it? (An evidence-based review)

Siti SarahFaculty of Medicine University of Indonesia

AbstractBackground: Diagnosis of cirrhosis in chronic liver diseases is crucial for prognostic and management of the course of the disease. Ultrasonography (US) is a noninvasive and inexpensive procedure for diagnosis of parenchymal disease of liver. In a low-resources setting, a simple, low-cost and accurate method should be occupied in daily clinical practice. Therefore, the diagnostic values of this method should be comprehensively evaluated.

Aim: To compare the diagnostic values of US exam in diagnosing liver cirrhosis compared with liver biopsy.

Methods: The search on the Cochrane Library® and PubMed® was conducted with the keywords of “liver cirrhosis OR liver fibrosis” AND “ultrasound” OR “US examination”. We used diagnostic appraisal questions developed by Centre of Evidence-Based Medicine (CEBM), University of Oxford.

Result: Analysis of 4 studies involving 1082 patients with various chronic liver disease was conducted finding at the liver cirrhosis diagnostic values. Sensitifity(Se), specificity (Sp), Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of US examination in prediciting liver cirrhosis were varied considering the US parameters used, respectively 33-76%, 44-97%, 12-70%, and 86-95%. US scoring system used for US parameters was resulted in best diagnostic values compared with use of other single parameters.

Conlcusion: US examination had a wide range of diagnostic value depends on the parameters used in each studies. US examination could be occupied as a first line radiological examination to predict liver cirrhosis due to its simple, low-cost, and accurate profile

Keywords: Ultrasound, liver cirrhosis, accuracy, chronic liver disease

Background

Liver cirrhosis is considered as an end stage condition of chronic hepatitis virus B or

C infection.Error: Reference source not found It causes a parenchymal damage of

liver that secondarily lead to the systemic adverse effects due to the decreased

function of liver. Therefore, accurate diagnosis of cirrhosis in chronic liver diseases, is

crucial for prognostic and management of the course of the disease.Error: Reference

source not found

Histopathology examination of fibrosis and cirrhosis remains acknowledged as a gold

standard diagnostic tool. However, biopsy is invasive and cannot be used repeatedly

in order to monitor the progress of the disease. Moreover, it may produce false

negative results in approximately 30% of cases.Error: Reference source not found

Therefore, the noninvasive, reliable, and accurate methods were needed to be

developed.

Ultrasonography (US) is a noninvasive and inexpensive procedure for diagnosis of

parenchymal disease of liver.Error: Reference source not found However, correlation

between US and histologic diagnosis has not been fully studied in large series of

patients. Several attempts had been conducted to improve the accuracies of US

examination. The widely ranging technology from a conventional- to high-

technology devices were devloped i.e grey-scale US, Doppler sonographyError:

Reference source not found, Transient Elastography (TE), real Time Elastography

(RTE), Acoustic Radiation Force Impulse Imaging (ARFI) and more recently Shear

Wave Elastography (SWE).Error: Reference source not found

These modalities had been widely studied in several studies and resulted in promising

result.Error: Reference source not found However, to incorporate a modality in a

routine clinical practice, a comprehensive review and resources assessment should be

conducted. In a low-resources setting, a simple, low-cost and accurate method should

be occupied in daily clinical practice. Spleen length, portal velocity, liver surface,

liver length, liver parenchym, hepatic vessels, spleen index were evaluated using US

examination to establish the diagnosis of cirrhosis in a number of studies. Error:

Reference source not found Moreover, recent studies focused in assessing the

degreeError: Reference source not found and causesError: Reference source not found

of the disease.

We conducted a critical review on several diagnostic studies to compare the

accuracies of US exam in diagnosing liver cirrhosis with the gold standard

assessment. In this review we used liver biopsy as a gold standard to provide the

sensitivity and specificity value of each parameters in US examination.

Methods

Clinical question

Is conventional methods of ultrasound examination accurate as a diagnostic tool in

liver cirrhosis patient?

P (patients) : Patients with liver cirrhosis

I (intervention) : Conventional methods of ultrasound examination

C (comparison) : Liver Biopsy

O (objective) : Liver cirrhosis

METHODS

Search strategy

The search on the Cochrane Library® and PubMed® was conducted on January 11th

2015 with the keywords of “liver cirrhosis OR liver fibrosis” AND “ultrasound” OR

“US examination”. Reference lists of relevant articles were searched for other

possibly relevant studies (figure 1).

Figure 1. Searching Flow

Selection

After achieving the result, a first selection was done by screening the study title and

abstract. Studies that not used liver biopsy as comparison and studies with other

languages than english were excluded. (Fig. 1 ). Five articles were available as full

text, and four of them proceed into our appraisal study.

(liver cirrhosis OR liver fibrosis ) AND (ultrasound OR US examination) AND (liver biopsy)

(liver cirrhosis OR liver fibrosis ) AND (ultrasound OR US examination) AND (liver biopsy)

Pubmed: 231Pubmed: 231

1212 00

66

full-text availablefull-text available

55

reading full-textreading full-text

useful: 4 articlesuseful: 4 articles

Type: title/abstract, Filters: English,

Human

Type: title/abstract, Filters: English,

Human

Exclusion Criteria

Liver biopsy not as gold standardDouble publicationKorean language

Exclusion Criteria

Liver biopsy not as gold standardDouble publicationKorean language

Cochrane: 45Cochrane: 45

screening title and abstractscreening title and abstract

Critical appraisal

Appraisal of four diagnostic studies involving 1082 patients with various chronic liver

disease was conducted finding at the diagnostic values (sensitifity, specificity, PPV,

NPV) of US examination in diagnosing liver cirrhosis. We used diagnostic appraisal

questions developed by Centre of Evidence-Based Medicine (CEBM), University of

Oxford (available at: http://www.cebm.net/critical-appraisal/).

Result

We appraised 4 diagnostic studies to assess the diagnostic accuracies of ultrasound

examination to diagnose liver cirrhosis. The total of subjects is 1082 patients with

chronic liver disease. However, the ultrasound parameters used among studies were

varied.

Table 1. Critical Appraisal Result of 4 diagnostic studies

No Study No. of subject

Ultrasound Parameters

Cut-off value

Validity Result Applic-ability

TotalScore

1 2 34

4 (Sn)

5 (Sp)

6(PPV)

7 (NPV)

8

1. Lee, et al (2010)

203 Surface nodularity

- + + + 33.33 97.01 70.59 87.10 + 7/8

2. Wang, et al (2009)

312 US score 7 + + +

74.0 86.0 55.0 93.0 + 7/8

3. Shen, et al (2006)

324 length of spleen

12.1 cm

+ + + 60.0 75.3 19.8 94.8 + 5//8

diameter of spleen vein

8 mm 60.0 78.1 22.0 95.0

diameter of portal vein

12 mm

76.7 44.6 12.4 94.9

4. Aube, et al(1999)

243 11 variables (global accuracy)

- + + + ? ? 79.0 86.0 + 6/8

1, representative patients; 2 reference standard; 3, blind & independent; 4, sensitivity; 5, specificity; 6, positive predictive value; 7, negative predictive value; 8 detail methods to permit replication;US, ultrasound; +, adequate; −, inadequate; ?, unknown, no information given’. Every item was scored based on diagnostic study appraisal questions developed by CEBM (available at: http://www.cebm.net/critical-appraisal/)

Lee, et al conducted a diagnostic study included 203 chronic viral hepatitis patients

who underwent liver biopsy. They assessed ultrasonographic findings, including

surface nodularity, parenchyma echogenecity, and spleen size. Using multivariate

analysis, surface nodularity was the only US paramaters that had >95% specificity,

with the PPV and NPV were respectively 70.59% and 87.10%. Echogenicity and

spleen size were not correlated with the diagnosis of liver cirrhosis determined by

liver biopsy. Error: Reference source not found

Three-hundred and twenty patients with chronic hepatitis B (HBV) or hepatitis C

virus (HCV) infections, with indications for liver biopsy, were prospectively enrolled

in a study conducted by Wang, et al to compare the accuracy between FibroScan®

and US examination in predicting fibrosis score. US scoring system, including

assessment of liver surface, liver parenchyma, hepatic vessels and spleen

http://www.cebm.net/critical-appraisal/

http://www.cebm.net/critical-appraisal/

index, was developed to evaluate the degree of hepatic fibrosis. Primarily they

found that of FibroScan® is significantly superior to US in the prediction of all HCV-

related fibrosis scores. In addition, they stated that among all patients (inlcuding

HBV-and HCV-infected patients) the area under the curve (AUC) were 0.832 (95%CI

0.775-0.879) and 0.929 (95%CI 0.886 – 0.960), for respectively FibroScan® and US

examination.Error: Reference source not found

The liver cirrhosis diagnosis in 324 patients was evaluated by both needle biopsy and

ultrasonography in a study conducted by Shen, et al. Among the quantitative

parameters, cut-off value of spleen length (12.1 cm) had a sensitivity of 0.600 and a

specificity of 0.753 for diagnosis of liver cirrhosis. The diameters of spleen (8 mm)

and portal vein (12 mm) had a diagnostic sensitivity of 0.600 and 0.767, and a

diagnostic specificity of 0.781 and 0.446, respectively. Error: Reference source not

found

Aube studied the diagnostic accuracy of ultrasonography for cirrhosis or fibrosis.

Among 243 patients, they found that the diagnostic accuracy of ultrasound was 84%

using spleen length and portal velocity as the US parameters. Finally, they conluded

that cirrhosis can be correctly diagnosed in 82-88% of patients with chronic liver

disease using a few ultrasonographic signs.Error: Reference source not found

On Lee, et al found that value of true positive, false positive, false negative and true

negative are 22, 16, 19 and 151. So, if sensitivity, specificity, PPV and NPV are

calculated on 2x2 table :

+ -

USG + 22 16 38

USG - 19 151 170

41 167 208

from the table above, if the value of the sensitivity, specificity, PPV, NPV,

prevalence, LR +, LR -, pretest odds, post test odds and post-test probability are

calculated will get results 54% (the proportion of people with disease who have a

positive test are 54%), 10% (the proportion of people free of disease who have a

negative test), 58% (the probability that a person with a positive test results has, or

will get the disease are 58% ), 89% (a numerical value of the proportion of individuals

with a negative test results who are free of the target condition are 89%), 20% (the

proportion of a population that is affected by the disease at a specific time are 20%),

0,6 (the probability of a person who has a disease testing positive divided by the

probability of a person who does not have the disease testing positive is 0,6. So it can

be concluded that the study of Lee likelihood ratio of 0.6 is not too supportive

sensitivity), LR - 4,9 (with a value of 4.9 it can be concluded that the specificity of the

US to the exclusion of liver cirrhosis in screening are pretty good), pretest odds 0,26

(The odds that the patient has the target disorder before the test is carried out is not

good enough), post-test odds 0,14 (The odds that the patient has the target disorder

after the test is carried out is not good enough), and post-test probability 12% (The

proportion of people with the target disorder in the population at risk at a specific time

or time interval is 12% and that is not good enough). These results it can be concluded

that ultrasound in the study of Lee, et al is not too good for screening but to be false

positive results is very small.

On Aube, et al found that value of true positive, false positive, false negative and true



+ -

USG + 93 25 118

USG - 18 107 125

111 132 243






will get the disease are 79%), 86% (a numerical value of the proportion of individuals




probability of a person who does not have the disease testing positive is 0,6. So it can

be concluded that the study of Lee likelihood ratio of 0.6 is not too supportive


US to the exclusion of liver cirrhosis in screening are not good enough), pretest odds

0,82 (The odds that the patient has the target disorder before the test is carried out is

not good enough), post-test odds 0,84 (The odds that the patient has the target

disorder after the test is carried out is good), and post-test probability 46% (The



that ultrasound in the study of Lee, et al is good for diagnosed cirrhosis but not good

for screening but to be false positive results is very small.

On Wang, et al found that value of true positive, false positive, false negative and true



+ -

USG + 48 41 89

USG - 17 226 243

65 267 332






will get the disease are 54%), 93% (a numerical value of the proportion of individuals




probability of a person who does not have the disease testing positive is 0,87. So it

can be concluded that the study of Wang likelihood ratio of 0.87 is not too supportive

sensitivity), LR - 1,71 (with a value of 1,71 it can be concluded that the specificity of

the US to the exclusion of liver cirrhosis in screening are not good enough), pretest

odds 0,24 (The odds that the patient has the target disorder before the test is carried

out is good enough), post-test odds 0,21 (The odds that the patient has the target

disorder after the test is carried out is not good enough), and post-test probability 17%

(The proportion of people with the target disorder in the population at risk at a

specific time or time interval is 17% and that is not good enough). These results it can

be concluded that ultrasound in the study of Wang, et al is good for diagnosed

cirrhosis but not good for screening but to be false positive results is very small.

On Shen, et al found that value of true positive, false positive, false negative and true



+ -

USG + 13 66 79

USG - 9 236 242

22 302 324






will get the disease are 16% ), 98% (a numerical value of the proportion of individuals




probability of a person who does not have the disease testing positive is 0,75. So it

can be concluded that the study of Lee likelihood ratio of 0.6 is not too supportive


US to the exclusion of liver cirrhosis in screening are not good enough), pretest odds

0,07 (The odds that the patient has the target disorder before the test is carried out is

good enough), post-test odds 0,05 (The odds that the patient has the target disorder

after the test is carried out is not good enough), and post-test probability 5% (The



that ultrasound in the study of Shen, et al is not good enough for diagnosed cirrhosis,

bad for screening but to be false positive results is very small.

Discussion

Four diagnostic studies were assessed to determine the accuracies of ultrasound

examination to diagnose liver cirrhosis. The total of subject is 1082 patients diagnosed

with chronic liver disease, including alcoholic liver disease, hepatitis B and hepatitis

C. However, the ultrasound parameters used among studies were varied, from a single

parematers to the combined parameters including several anatomical indices. Surface

nodularity,length of spleen, diameter of spleen vein, and diameter of portal vein were

mostly used as parameters among studies included in this review.

We found all studies had conducted a valid study regarding to the methods they used.

Four studies enrolled patients who were consecutively admitted to the hospital

so that selection bias is minimized. In addition, US scans were performed by 1

to 4 hepatologists who were experienced with medical ultrasound

examinations. The US was performed within the same day or at least at the

same week with the liver biopsy, therefore the results would not be

significantly differed between examinations.

Overall studies show moderate to good accuracies of US examination to predict liver

biopsy. However the sensitivity was found to be more than 70% if the diameter of

portal vein or combination of scores were used as the US parameters. The specificity

of surface nodularuty and US scores to predict liver cirrhosis were respectively 97%

and 86%. All studies shown a good NPV of US examination, it was ranging from

86% to 95%. These values was comparable to other methods of diagnostic. Thierry

found that the specificity/senitifity was for FibroTest® 0.87/0.41, liver stiffness

measurement (LSM) 0.93/0.39, alanine aminotramsferase (ALT) 0.78/ 0.08 and

biopsy 0.95/0.51 (Table 2).Error: Reference source not found On our literature

searching, laparoscopy had the best specificity to diagnose liver cirrhosis, which

approximately 99%.Error: Reference source not found Eventhough several diagnostic

studies declared that several methods could avoid liver biopsy in clinical

practiceError: Reference source not found, in our institution liver biopsy remains a

gold standard tool for liver cirrhosis.

Table 2. Comparison of several diagnostic values for liver cirrhosis diagnosis Error: Reference source not foundLSM, liver stiffness measurement; ALT, alanine aminotramsferase

Examination Sensitifity SpecificityUltrasound 33% - 76% 44 – 97%FibroTest® 41% 87%LSM 39% 93%ALT 8% 78%Tranisent elastography 53.5% 98.6%Magnetic elastography 74.4% 98.6 %Laparoscopy 68% 98%Biopsy 51% 95%

Conclusion

In this review we found the sensitifity, specificity, PPV, and NPV of ultrasound

examination in predicting liver cirrhosis were respectively 33-76%, 44-97%, 12-70%,

and 86-95%. In conclusion, ultrasound examination had a wide range of diagnostic

value depends on the US parameteres used. US scoring system used for US

parameters was resulted in best diagnostic values compared with the use of other

single parameters.

Recommendation

US examination could be occupied as a first line radiological examination to predict

liver cirrhosis due to its simple, low-cost and accurate profiles.

ReferencesError: Reference source not found

Aube, et al

+ -

USG + 93 25 118

USG - 18 107 125

111 132 243

Sensitivity : a/a+c = 93/111 = 0,837 = 84%

Specificity : b/b+d = 25/132 = 0,189 = 19%

PPV : a/a+b = 93/118 = 0,778 = 78%

NPV : d/c+d = 107/125 = 0,856 = 86%

Prevalence : (a+c)/(a+b+c+d) = 111/243 = 0,45 = 45%

LR + = Sn/(1-Sp) = 0,837/1-0,189 = 0,837/0,811 = 1,032

LR - = (1-Sn)/Sp = 1-0,837/0,189 = 0,862

Pretest Odds = Prevalence/(1-Prevalence) = 0,45/1-0,45 = 0,45/0,55 = 0,818

Post-Test Odds =Pretest odds x LR = 0,818 x 1,032 = 0,844

Post-Test Probability = Post-Test Odds/1+Post-test Odds = 0,844/1,844 = 0,457 = 46%

Wang, et al

+ -

USG + 48 41 89

USG - 17 226 243

65 267 332

Sensitivity : a/a+c = 48/65 = 0,738 = 74%

Specificity : b/b+d = 41/267 = 0,153 = 15%

PPV : a/a+b = 48/89 = 0,54 = 54%

NPV : d/c+d = 226/243 = 0,930 = 93%


LR + = Sn/(1-Sp) = 0,837/1-0,189 = 0,837/0,811 = 1,032

LR - = (1-Sn)/Sp = 1-0,837/0,189 = 0,862


Post-Test Odds =Pretest odds x LR = 0,818 x 1,032 = 0,844


Shen, et al

+ -

USG + 13 66 79

USG - 9 236 242

22 302 324

Sensitivity : a/a+c = 13/22 = 0,59 = 59%

Specificity : b/b+d = 66/302 = 0,218 = 22%

PPV : a/a+b = 13/79 = 0,164 = 16%

NPV : d/c+d = 236/242 = 0,975 = 98%


LR + = Sn/(1-Sp) = 0,59/1-0,218 = 0,59/0,782 = 0,75

LR - = (1-Sn)/Sp = 1-0,59/0,218 = 0,41/0,218 = 1,880


Post-Test Odds = Pretest odds x LR = 0,071 x 0,75 = 0,053


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