Diagnostic accuracy of liver stiffness measurement in chronic hepatitis B patients with normal or mildly elevated alanine transaminase levels

Scientific Reports, Mar 2018

We aimed to evaluate the diagnostic accuracy of liver stiffness measurement (LSM) in 188 chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤ twice the upper limit of normal (ULN). Liver fibrosis was staged using METAVIR scoring system. Define significant fibrosis as F2-F4, severe fibrosis as F3-F4, and cirrhosis as F4. To predict F2-F4, the AUROC of LSM was higher than that of APRI (0.86 vs 0.73, p = 0.001) and FIB-4 (0.86 vs 0.61, p < 0.001). To predict F4, the AUROC of LSM was also higher than that of APRI (0.93 vs 0.77, p = 0.012) and FIB-4 (0.93 vs 0.64, p < 0.001). Patients with ALT levels 1–2 ULN had higher cut-off values than patients with normal ALT levels for the diagnosis of F2-F4 (6.5 vs 6 kPa) and F4 (10.2 vs 7.8 kPa). Using cut-off values regardless of ALT levels, the diagnostic accuracy of LSM was 81% for F2-F4, and 89% for F4. Applying ALT-stratified cut-off values, the diagnostic accuracy of LSM was 82% for F2-F4, and 86% for F4. In conclusion, LSM is a reliable noninvasive test for the diagnosis of liver fibrosis. Applying ALT-stratified cut-off values did not enhance diagnostic accuracy of LSM in CHB patients with ALT ≤ 2 ULN.

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Diagnostic accuracy of liver stiffness measurement in chronic hepatitis B patients with normal or mildly elevated alanine transaminase levels

RepoRts | Diagnostic accuracy of liver stiffness measurement in chronic hepatitis B patients with normal or mildly elevated alanine transaminase levels Qiang Li Liang Chen Yu Zhou OPEN Published: xx xx xxxx We aimed to evaluate the diagnostic accuracy of liver stiffness measurement (LSM) in 188 chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤ twice the upper limit of normal (ULN). Liver fibrosis was staged using METAVIR scoring system. Define significant fibrosis as F2-F4, severe fibrosis as F3-F4, and cirrhosis as F4. To predict F2-F4, the AUROC of LSM was higher than that of APRI (0.86 vs 0.73, p = 0.001) and FIB-4 (0.86 vs 0.61, p < 0.001). To predict F4, the AUROC of LSM was also higher than that of APRI (0.93 vs 0.77, p = 0.012) and FIB-4 (0.93 vs 0.64, p < 0.001). Patients with ALT levels 1-2 ULN had higher cut-off values than patients with normal ALT levels for the diagnosis of F2-F4 (6.5 vs 6 kPa) and F4 (10.2 vs 7.8 kPa). Using cut-off values regardless of ALT levels, the diagnostic accuracy of LSM was 81% for F2-F4, and 89% for F4. Applying ALT-stratified cut-off values, the diagnostic accuracy of LSM was 82% for F2-F4, and 86% for F4. In conclusion, LSM is a reliable noninvasive test for the diagnosis of liver fibrosis. Applying ALT-stratified cut-off values did not enhance diagnostic accuracy of LSM in CHB patients with ALT ≤ 2 ULN. - Hepatitis B virus (HBV) infection is still a major public health burden. In China, the prevalence of hepatitis B surface antigen (HBsAg) is 9.75% in 1992, and 7.18% in 20061. A study published in 2016 showed that the HBsAg positive rate was 6.0% in men aged 21–49 years in rural China2. Another study showed that the HBsAg positive rate was 6.1% in Northeastern China in 20163. In the last decade, the prevalence of HBV in China has changed from highly endemic to intermediate endemic2. However, in China, the absolute number of patients with HBV infection is still large because of its vast denominator. The assessment of the severity of liver fibrosis is important to identify patients for treatment and hepatocellular carcinoma (HCC) surveillance. Liver biopsy has traditionally been considered the reference method for evaluation of liver fibrosis. However, liver biopsy is a costly and invasive procedure, carrying potential complications. Therefore, non-invasive diagnostic method would be more acceptable to patients. Liver stiffness measurement (LSM) has been introduced as a new, non-invasive method for the diagnosis of liver fibrosis. Many studies found that LSM could predict liver fibrosis accurately in patients with chronic hepatitis C (CHC)4–7. In recent years, several studies have been performed to apply LSM to patients with chronic hepatitis B (CHB)6,8–10. However, these studies were mainly performed in European and United States, and the results cannot be extrapolated to Chinese patients with CHB. First, HBV genotype A is highly prevalent in Europe and United States, while genotypes B and C are common in China. Second, most CHB patients are HBeAg positive and high HBV DNA levels in China, while most CHB patients are HBeAg negative and low HBV DNA levels in Europe and United States11,12. Therefore, further studies should be performed in Chinese patients with CHB. According to EASL clinical guidelines, patients with HBV DNA > 20,000 IU/ml and ALT > 2 ULN should start antiviral therapy regardless of the degree of fibrosis13. For these patients, liver fibrosis assessment may provide additional useful information, but it does not usually change the decision for treatment. In patients with ALT ≤ 2 ULN, liver fibrosis assessment should be used for decision on treatment indications. Patients with at least significant fibrosis should be treated13. Thus, patients with ALT ≤ 2 ULN have more needs for liver fibrosis assessment than those with ALT > 2 ULN. In this study, we aimed to: ( 1 ) assess the diagnostic accuracy of LSM in Chinese patients with CHB; ( 2 ) compare the diagnostic accuracy of LSM with serum fibrosis models (APRI and FIB-4); ( 3 ) evaluate the impact of ALT levels on LSM in patients with ALT ≤ 2 ULN. Material and Method Study population. A total of 305 consecutive CHB patients from the Ruian people’s hospital, Wenzhou, Zhejiang, China, between July 2013 and July 2015, were retrospectively analyzed. Inclusion criteria: ( 1 ) the persistent presence of serum HBsAg for more than 6 months; ( 2 ) ATL ≤ 2 ULN (the ULN is 40 IU/L); ( 3 ) had liver biopsy, LSM, and routine laboratory tests. Exclusion criteria: ( 1 ) significant alcohol consumption (>20 g/day) (n = 24); ( 2 ) co-infection with HCV or HDV (n = 10); ( 3 ) accompanied with autoimmune liver disease (ALD) or nonalcoholic fatty liver disease (NAFLD) (n = 14); ( 4 ) prior or current antiviral therapy (n = 32); ( 5 ) body mass index (BMI) >28 kg/m2 (n = 13); ( 6 ) inappropriate biopsy samples (n = 8); ( 7 ) unreliable LSM values (n = 16). Finally, 188 pa (...truncated)


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Qiang Li, Liang Chen, Yu Zhou. Diagnostic accuracy of liver stiffness measurement in chronic hepatitis B patients with normal or mildly elevated alanine transaminase levels, Scientific Reports, 2018, Issue: 8, DOI: 10.1038/s41598-018-23646-2