Transient elastography for the noninvasive assessment of liver fibrosis: a multicentre Canadian study

BACKGROUND

Liver stiffness measurement (LSM) using transient elastography (TE) is a promising tool for the noninvasive assessment of hepatic fibrosis.

OBJECTIVES

To determine the feasibility and performance of TE in a North American cohort of patients with chronic liver disease.

METHODS

LSMs were obtained using TE in 260 patients with chronic hepatitis B or C, or nonalcoholic fatty liver disease from four Canadian hepatology centres. The accuracy of TE compared with liver biopsy for the prediction of significant fibrosis (Metavir fibrosis score of F2 or greater), bridging fibrosis (Metavir fibrosis score of F3 or greater) and cirrhosis (Metavir fibrosis score of F4 ) was assessed using area under ROC curves (AUROCs), and compared with the aspartate aminotransferase-to-platelet ratio index. The influence of alanine aminotransferase (ALT) levels and other factors on liver stiffness was determined using linear regression analyses.

RESULTS

Failure of TE occurred in 2.7% of patients, while liver biopsies were inadequate for staging in 0.8%. Among the remaining 251 patients, the AUROCs of TE for Metavir fibrosis scores of F2 and F3 or greater, and F4 were 0.74 (95% CI 0.68 to 0.80), 0.89 (95% CI 0.84 to 0.94), and 0.94 (95% CI 0.90 to 0.97), respectively. LSM was more accurate than the aminotransferase-to-platelet ratio index for bridging fibrosis (AUROC 0.78) and cirrhosis (AUROC 0.88), but not significant fibrosis (AUROC 0.76). At a cut-off of 11.1 kPa, the sensitivity, specificity, and positive and negative predictive values for cirrhosis (prevalence 11%) were 96%, 81%, 39% and 99%, respectively. For significant fibrosis (prevalence 53%), a cut-off of 7.7 kPa was 68% sensitive and 69% specific, and had a positive predictive value of 70% and a negative predictive value of 65%. Liver stiffness was independently associated with ALT, body mass index and steatosis. The optimal LSM cut-offs for cirrhosis were 11.1 kPa and 11.5 kPa in patients with ALT levels lower than 100 U/L and 100 U/L or greater, respectively. For fibrosis scores of F2 or greater, these figures were 7.0 kPa and 8.6 kPa, respectively.

CONCLUSIONS

The major role of TE is the exclusion of bridging fibrosis and cirrhosis. However, TE cannot replace biopsy for the diagnosis of significant fibrosis. Because liver stiffness may be influenced by significant ALT elevation, body mass index and/or steatosis, tailored liver stiffness cut-offs may be necessary to account for these factors.     

Serum NX-DCP as a New Noninvasive Model to Predict Significant Liver Fibrosis in Chronic Hepatitis C

Background:

Finding a noninvasive method to predict liver fibrosis using inexpensive and easy-to-use markers is important.

Objectives:

We aimed to clarify whether NX-des-γ-carboxyprothrombin (NX-DCP) could become a new noninvasive model to predict liver fibrosis in hepatitis C virus (HCV) related liver disease.

Patients and Methods:

We performed a prospective cohort study on a consecutive group of 101 patients who underwent liver biopsy for HCV-related liver disease at Kobe University Hospital. Laboratory measurements were performed on the same day as the biopsy. Factors associated with significant fibrosis (F3-4) were assessed by multivariate analyses. A comparison of predictive ability between multivariate factors and abovementioned noninvasive models was also performed.

Results:

Increase in serum NX-DCP was significantly related to increase in fibrosis stage (P = 0.006). Moreover, NX-DCP was a multivariate factor associated with the presence of significant fibrosis F 3-4 (median 21 of F0-2 group vs. median 22 of F3-4 group with P = 0.002). The AUC of NX-DCP showed no significant differences compared with those of the AST-to-platelet ratio index (APRI), modified-APRI, the Göteborg University Cirrhosis Index (GUCI), the Lok index, the Hui score, cirrhosis discriminating score (CDS) and the Pohl score (P > 0.05).

Conclusions:

NX-DCP correlated positively with fibrosis stage and could discriminate well between HCV-related patients with or without significant fibrosis. Moreover, NX-DCP had a similar predictive ability to the abovementioned models, and thereby could be a new noninvasive prediction tool for fibrosis.     

A Simple Noninvasive Score Based on Routine Parameters can Predict Liver Cirrhosis in Patients With Chronic Hepatitis C

Background

Liver biopsy has remained the gold standard for the diagnosis of chronic hepatitis C; even though, it has a low but non-negligible rate of both false negative and complications. Several authors have proposed noninvasive tools to diagnose cirrhosis. But none of them showed complete concordance with liver biopsy.

Objectives

To devise a score based on noninvasive routine parameters that discriminate between patients with a high risk, and those with a low risk of cirrhosis among patients with chronic hepatitis C without performing liver biopsy, and to compare this score with other ones using routine parameters devoted to this aim.

Patients and Methods

We reviewed the charts of patients with chronic hepatitis C who performed a liver biopsy between 2000 and 2004. Multivariate analysis was used to identify independent predictors of cirrhosis. An independent group of patients with chronic hepatitis C admitted for a liver biopsy between 2007 and 2012 constituted the validation set.

Results

We enrolled 249 patients who had complete laboratoristic data, and sufficient liver tissue for fibrosis staging. Age, AST, prothrombin activity, and platelets were identified as independent predictors of histological cirrhosis. We categorized these variables, and devised a novel score called CISCUN (Cirrhosis Score University of Naples), giving one point to each of the following predictors: age > 40 years; AST > 2 upper normal values; platelet count < 160.000/mmc; prothrombin activity < 100%. Cirrhosis rate was 2.9% for the 103 patients with a CISCUN = 0 or 1, 23.4% for the 124 patients with a CISCUN of 2 or 3, and 86.4% for the 22 patients with a CISCUN = 4. These results were confirmed in the independent validation group of 285 patients with similar characteristics.

Conclusions

Patients with chronic hepatitis C and with a CISCUN ≤ 1 had a very low rate of cirrhosis while those with a CISCUN = 4 had a high risk of cirrhosis. Patients with CISCUN = 2 or 3 had an intermediate rate of cirrhosis, and therefore needed to perform a liver biopsy to receive a reliable diagnosis.     

How efficient is acoustic radiation force impulse elastography for the evaluation of liver stiffness?

Background

In chronic liver diseases, a correct estimation of the severity of liver fibrosis is important for recommendations regarding the treatment. Nowadays, evaluation of fibrosis is done by noninvasive methods such as biochemical scores and transient elastography instead of liver biopsy. The lack of sensitivity to detect fibrosis, because of its heterogeneity is a drawback of liver biopsy (LB).

Objectives

To compare transient elastography (TE) and acoustic radiation force impulse (ARFI) for the evaluation of liver stiffness (LS), against percutaneous LB.

Patients and Methods

Our study comprised of 223 subjects; 52 without fibrosis (38 volunteers and 14 patients with F0 on LB), 36 with F1, 40 with F2, 26 with F3 and 69 with liver cirrhosis (46 with LB and 23 with signs of cirrhosis). For each patient we performed in the same session 10 TE and 5 ARFI measurements. The median values were calculated.

Results

A strong linear correlation (Spearman rho = 0.870) was found between TE and fibrosis (P < 0.0001); there was also a weaker correlation between ARFI and fibrosis (Spearman rho = 0.646; P < 0.0001). TE measurements were also correlated with ARFI measurements (Spearman rho = 0.733, P < 0.0001). The best test for predicting significant fibrosis (F ≥ 2) was TE with a cut-off value of 7.1 kPa (AUROC 0.953). For ARFI, the cut-off value was 1.27 m/s-area under ROC curve (AUROC): 0.890, sensitivity (Se) of 88.7%, specificity (Sp) of 67.5%, positive predictive value (PPV) of 64.5%, and negative predictive value (NPV) of 90% (P = 0.0044). For predicting cirrhosis (F = 4), the optimum cut-off values were 14.4 kPa for TE (AUROC: 0.985, Se: 95.6%, Sp: 94.7%, PPV: 89.2%, NPV: 98%) and 1.7 m/s for ARFI (AUROC: 0.931, Se: 93%, Sp: 86.7%, PPV: 73.6%, NPV: 96.9%) (P = 0.0102).

Conclusions

LS evaluation by means of ARFI is not superior to TE for the assessment of liver fibrosis. ARFI is an accurate test for the diagnosis of cirrhosis.     

Physicians’ practices for diagnosing liver fibrosis in chronic liver diseases: A nationwide,Canadian survey

OBJECTIVE:

To determine practices among physicians in Canada for the assessment of liver fibrosis in patients with chronic liver diseases.

METHODS:

Hepatologists, gastroenterologists, infectious diseases specialists, members of the Canadian Gastroenterology Association and/or the Canadian HIV Trials Network who manage patients with liver diseases were invited to participate in a web-based, national survey.

RESULTS:

Of the 237 physicians invited, 104 (43.9%) completed the survey. Routine assessment of liver fibrosis was requested by the surveyed physicians mostly for chronic hepatitis C (76.5%), followed by autoimmune/cholestatic liver disease (59.6%) and chronic hepatitis B (52.9%). Liver biopsy was the main diagnostic tool for 46.2% of the respondents, Fibroscan (Echosens, France) for 39.4% and Fibrotest (LabCorp, USA) for 7.7%. Etiology-specific differences were observed: noninvasive methods were mostly used for hepatitis C (63% versus 37% liver biopsy) and hepatitis B (62.9% versus 37.1% liver biopsy). For 42.7% of respondents, the use of noninvasive methods reduced the need for liver biopsy by >50%. Physicians’ characteristics associated with higher use of noninvasive methods were older age and being based at a university hospital or in private practice versus community hospital. Physicians’ main concerns regarding noninvasive fibrosis assessment methods were access/availability (42.3%), lack of guidelines for clinical use (26.9%) and cost/lack of reimbursement (14.4%).

CONCLUSIONS:

Physicians who manage patients with chronic liver diseases in Canada require routine assessment of liver fibrosis stage. Although biopsy remains the primary diagnostic tool for almost one-half of respondents, noninvasive methods, particularly Fibroscan, have significantly reduced the need for liver biopsy in Canada. Limitations in access to and availability of the noninvasive methods represent a significant barrier. Finally, there is a need for clinical guidelines and a better reimbursement policy to implement noninvasive tools to assess liver fibrosis.     

Non-Invasive Histologic Markers of Liver Disease in Patients With Chronic Hepatitis B

Background:

An exact histologic staging of liver fibrosis is essential for identifying the best therapeutic strategy and determining the disease prognosis in patients with chronic hepatitis B (CHB). While liver biopsy has a vital role in the management of liver diseases, it also sustains some limitations hampering its widespread use.

Objectives:

In this study, we evaluated and compared several available indices of the severity of liver diseases in patients with hepatitis.

Patients and Methods:

Exclusion criteria were as follows: decompensated liver disease, alcoholic liver disease or alcohol intake of 40 g or more per week; co-infection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus.

Results:

Results showed that AST to platelet ratio index (APRI) (odds ratio = 2.35, P = 0.01) and age (odds ratio = 1.04, P = 0.007) were independently predictive of the presence of significant liver necrosis and inflammation. On the other hand, AARPRI (odds ratio = 3.8, P = 0.07), age (odds ratio = 1.04, P = 0.02), and ALT levels (odds ratio = 1.01, P = 0.007) were predictive of a significant liver fibrosis. Further analysis with receiver-operating curve showed that none of these predictors had a fair diagnostic value (area under the curve < 70).

Conclusions:

The APRI had the highest sensitivity and specificity (64% and 71%, respectively) for prediction of the presence of liver disease. We suggest that APRI may be applicable for the detection of a severe liver disease.     

Hyaluronic Acid: From Biochemical Characteristics to its Clinical Translation in Assessment of Liver Fibrosis

Context:

Hyaluronic acid (HA) is a high molecular weight polysaccharide that is distributed in all bodily tissues and fluids. The liver is the most important organ involved in the synthesis and degradation of HA. Research has shown that liver cell injury can affect serum HA levels. In this review, authors aimed to describe the biochemical and physiological roles of this glycosaminoglycan and its changes in various liver diseases.

Evidence Acquisition:

Liver fibrosis and in more severe form, cirrhosis are results of an imbalance between fibrogenesis and fibrinolysis. Liver biopsy is the gold standard to assess liver necro inflammatory injuries. This method is invasive and has some major side effects; therefore it is an unfavorable method for both physicians and patients. Now, a wide variety of noninvasive methods have been introduced based on evaluating serum level of different markers. They are safe, readily available, and more favorable. Serum HA levels are used by some researchers to assess stages of liver fibrosis.

Results:

There are several scientific studies indicating HA as a biomarker for high score fibrosis and cirrhosis in various liver diseases alone or in algorithm models. It seems from various algorithm models that the use of HA as a major constituent has more diagnostic reliability and accuracy than the use of HA alone.

Conclusions:

Use of HA in an algorithm model, is an extra and valuable tool for assessing liver necro inflammatory injuries- in parallel with liver biopsy- but more comprehensive studies are needed to approve the use of HA as an appropriate clinical tool.     

Transient Elastography to Assess Hepatic Fibrosis in Hemodialysis Chronic Hepatitis C Patients

Summary

Background and objectives

Although percutaneous liver biopsy (PLB) is the gold standard for staging hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC) before renal transplantation or antiviral therapy, concerns exist about serious postbiopsy complications. Using transient elastography (TE, Fibroscan^®) to predict the severity of hepatic fibrosis has not been prospectively evaluated in these patients.

Design, setting, participants, & measurements

A total of 284 hemodialysis patients with CHC were enrolled. TE and aspartate aminotransferase-to-platelet ratio index (APRI) were performed before PLB. The severity of hepatic fibrosis was staged by METAVIR scores ranging from F0 to F4. Receiver operating characteristic curves were used to assess the diagnostic accuracy of TE and APRI, taking PLB as the reference standard.

Results

The areas under curves of TE were higher than those of APRI in predicting patients with significant hepatic fibrosis (≥F2) (0.96 versus 0.84, P < 0.001), those with advanced hepatic fibrosis (≥F3) (0.98 versus 0.93, P = 0.04), and those with cirrhosis (F4) (0.99 versus 0.92, P = 0.13). Choosing optimized liver stiffness measurements of 5.3, 8.3, and 9.2 kPa had high sensitivity (93–100%) and specificity (88–99%), and 87, 97, and 93% of the patients with a fibrosis stage of ≥F2, ≥F3, and F4 were correctly diagnosed without PLB, respectively.

Conclusions

TE is superior to APRI in assessing the severity of hepatic fibrosis and can substantially decrease the need of staging PLB in hemodialysis patients with CHC.     

Factors associated with the progression of fibrosis on liver biopsy in Alaska Native and American Indian persons with chronic hepatitis C

BACKGROUND:

Various factors influence the development and rate of fibrosis progression in chronic hepatitis C virus (HCV) infection.

OBJECTIVES:

To examine factors associated with fibrosis in a long-term outcomes study of Alaska Native/American Indian persons who underwent liver biopsy, and to examine the rate of fibrosis progression in persons with subsequent biopsies.

METHODS:

A cross-sectional analysis of the demographic, inflammatory and viral characteristics of persons undergoing liver biopsy compared individuals with early (Ishak fibrosis score of lower than 3) with those with advanced (Ishak score of 3 or greater) fibrosis. Persons who underwent two or more biopsies were analyzed for factors associated with fibrosis progression.

RESULTS:

Of 253 HCV RNA-positive persons who underwent at least one liver biopsy, 76 (30%) had advanced fibrosis. On multivariate analysis, a Knodell histological activity index score of 10 to 14 and an alpha-fetoprotein level of 8 ng/mL or higher were found to be independent predictors of advanced liver fibrosis (P<0.0001 for each). When surrogate markers of liver inflammation (alanine aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio and alpha-fetoprotein) were removed from the model, type 2 diabetes mellitus (P=0.001), steatosis (P=0.03) and duration of HCV infection by 10-year intervals (P=0.02) were associated with advanced fibrosis. Among 52 persons who underwent two or more biopsies a mean of 6.2 years apart, the mean Ishak fibrosis score increased between biopsies (P=0.002), with progression associated with older age at initial biopsy and HCV risk factors.

CONCLUSIONS:

The presence of type 2 diabetes mellitus, steatosis and duration of HCV infection were independent predictors of advanced fibrosis in the present cohort, with significant fibrosis progression demonstrated in persons who underwent serial biopsies.     

Egy-Score Predicts Severe Hepatic Fibrosis and Cirrhosis in Egyptians With Chronic Liver Diseases: A Pilot Study

Background

Non-invasive methods for assessment of hepatic fibrosis are increasingly needed. Recent studies showed that combined elevation of tumor markers CA 19-9 and CA 125 is predictive of severe hepatic fibrosis or cirrhosis with high specificity.

Objectives

We aimed at developing a new panel of surrogate biomarkers for prediction of the stage of hepatic fibrosis by combining tumor markers with other known biomarkers of hepatic fibrosis.

Patients and Methods

A total of 92 patients with different types of chronic liver diseases (chronic hepatitis B, chronic hepatitis C and autoimmune hepatitis), were prospectively enrolled in our cohort. They were subjected to: ALT, AST, GGT, ALP, total bilirubin, INR, total cholesterol, albumin, platelet count, cancer antigen 19-9 (CA 19-9), cancer antigen 125 (CA 125), cancer antigen 15-3 (CA 15-3), haptoglobin, alpha-2-macroglobulin, apolipoprotein A1, abdominal ultrasound, liver biopsy and histological staging of hepatic fibrosis using the METAVIR system.

Results

Combined elevation of CA 19-9 and CA 125 with a summated value > 37 U/mL is predictive of severe hepatic fibrosis or cirrhosis (stage F3-F4 METAVIR) with a probability of 77.6%. Multivariate analysis showed that the most relevant collection of biomarkers for prediction of stage of hepatic fibrosis is: CA 19-9, age, alpha-2- macroglobulin, total bilirubin, platelet count & albumin. We developed a new score, named the “Egy-Score”, using a regression equation composed of this panel of biomarkers. Egy-Score could differentiate no or early fibrosis (stage F0-F2 METAVIR) from severe fibrosis or cirrhosis (stage F3-F4 METAVIR) with 83.7% accuracy.

Conclusions

Non-invasive assessment of hepatic fibrosis could be done using the Egy-Score. Egy-Score could differentiate no or early fibrosis (stage F0-F2 METAVIR) from severe fibrosis or cirrhosis (stage F3 - F4 METAVIR) with 83.7% accuracy.     

Fibrosis Evaluation by Transient Elastography in Patients With Long-Term Sustained HCV Clearance

Background

Reversibility of advanced fibrosis after HCV-clearance is an important goal of therapy.

Objectives

Measuring liver stiffness (LS) by transient elastography (TE) might be helpful in this setting.

Patients and Methods

We evaluated 104 patients with biopsy-proven chronic hepatitis C (CHC) and sustained virological response (SVR) after Peg-Interferon (IFN) plus ribavirin since at least 18 months. HCV-eradication was confirmed searching for serum HCV-RNA (TMA® sensitivity > 5-10 IU/ml). Data from literature reported the best LS cut-off values for different stages of liver fibrosis were 7.1 kPa for Metavir stage 2 (F2), 9.5 kPa for F3 and 12.5 for cirrhosis (F4).

Results

TE was not reliable in four SVR obese patients. Metavir-stage of biopsy was F0-1 in 28, F2 in 47, F3 in 17 and F4 in eight patients. The median interval elapsed since achieving SVR was 36 months (range: 18-77, SD¬¬:18). Stratifying patients according to the histological stage assessed before treatment, a clear-cut gradient of LS values was observed from F0-1: median: 3.8 kPa (range: 3.5-4.9) to F2: 4.6 kPa (3.8-6.0), F3: 6.2 kPa (4.8-8.6) and F4: 8.4 kPa (6.2-9.2) (P = 0.001). Overall, 86 patients had lower values of LS than the expected LS values according to Metavir-stage. At multivariate logistic analysis γ-GT and histological steatosis were independently associated with persistence of higher values of LS.

Conclusion

Long term responders to IFN-based therapies have lower LS values than those who are untreated and still viraemic. High levels of γ-GT and liver steatosis, all markers of insulin resistance, may hamper reduction of liver stiffness after HCV-clearance.     

Correlation Between Patatin-Like Phospholipase Domain-Containing Protein 3 Gene Polymorphisms and Liver Cirrhosis in a Chinese Han Population With Chronic Hepatitis B

Background:

A single nucleotide polymorphism (SNP) of patatin-like phospholipase domain-containing 3 (PNPLA3) genes (rs738409) is associated with the severity of fibrosis and cirrhosis in patients with fatty liver disease. However, in a small group of Italian patients, there was no significant correlation between the rs738409 SNP and hepatitis B virus (HBV) infection-associated liver cirrhosis.

Objectives:

This study aimed to investigate whether PNPLA3 polymorphisms are a risk factor for liver cirrhosis in a Chinese Han population with chronic hepatitis B (CHB).

Patients and Methods:

The study population consisted of 344 Chinese Han patients with CHB, among which 203 presented with liver cirrhosis (LC group) and 141 had no sign of liver cirrhosis (CHB group). TaqMan genotyping assay was used to investigate the association of two PNPLA3 SNPs (rs738409 and rs2281135) with the risk of liver cirrhosis.

Results:

The allele and genotype distributions of PNPLA3 rs738409 and rs2281135 were not significantly different between the CHB and LC groups. After segregation on the basis of sex, no significant correlation between PNPLA3 (rs738409 and rs2281135) genotypes/alleles and liver cirrhosis was detected. Moreover, none of the haplotypes in PNPLA3 (rs738409 and rs2281135) was found to be statistically different between the two groups.

Conclusions:

Our results showed no association between PNPLA3 polymorphisms (rs738409 and rs2281135) and the susceptibility to HBV-related liver cirrhosis in a Chinese Han population.     

Serum aspartate aminotransferase level and previous histopathological findings enable reduction of protocol liver biopsies after liver transplantation for hepatitis C

BACKGROUND:

Hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) worldwide. Recurrent hepatitis C following LT is universal, and significant fibrosis (SF, Metavir fibrosis stage ≥2) apparent on protocol biopsy typically prompts antiviral therapy.

OBJECTIVE:

To determine the optimal timing of protocol liver biopsies in this setting.

METHODS:

A total of 151 patients who underwent LT related to HCV infection between July 2004 and December 2009 were analyzed retrospectively. Data regarding protocol liver biopsies at six, 12 and 24 months post-LT, conventional laboratory parameters and demographic information were obtained.

RESULTS:

The 151 patients included in the present study had significantly lower serum aspartate aminotransferase (AST) levels than the four patients who progressed to receive antiviral treatment for SF before six months post-LT (P<0.001). AST level, but not alanine aminotransferase level, histological activity or fibrosis stage at the six-month biopsy was independently associated with the progression to SF at 12 months (P<0.05). However, AST level, histological activity and fibrosis stage at the 12-month biopsy emerged as independent parameters associated with progression to SF at 24 months (P<0.05).

CONCLUSION:

The protocol liver biopsy at six months could be eliminated, especially in patients who consistently exhibit low AST levels. Histological activity, the presence or absence of fibrosis, and AST values at the 12-month biopsy may lead to the decision to defer the protocol biopsy at 24 months or result in earlier introduction of antiviral therapy.     

Serum Levels of Annexin A2 as a Candidate Biomarker for Hepatic Fibrosis in Patients With Chronic Hepatitis B

Background:

Hepatologists have studied serologic markers of liver injury for decades. Annexins are a prominent group of such markers and annexin A2 (AnxA2) is one of the best characterized annexins. AnxA2 inhibits HBV polymerase among other functions. Its expression is up-regulated in regenerative hepatocytes.

Objectives:

To determine if serum AnxA2 level has a role in estimating liver damage in chronic HBV infection and investigate whether AnxA2 levels correlate with hepatic fibrosis.

Patients and Methods:

This study included 173 patients with chronic hepatitis B (CHB) and 51 healthy controls. Liver fibrosis was graded histologically on liver biopsy samples. Blood samples were taken from patients during biopsy and serum AnxA2 levels were measured with ELISA.

Results:

In a group of adult patients with CHB, AnxA2 values were far higher than those of the control group (P = 0.001). When we assessed AnxA2 levels based on fibrosis stages, serum AnxA2 levels of patients with early stage fibrosis (stages 1 - 3) were significantly higher than those of patients with advanced stage fibrosis (stages 4 - 5; P = 0.001).

Conclusions:

AnxA2 is a useful biomarker for early stage fibrosis in patients with CHB.     

Evaluation of the Relation Between Hepatic Fibrosis and Basic Laboratory Parameters in Patients With Chronic Hepatitis B Fibrosis and Basic Laboratory Parameters

Background:

The hepatitis B virus is an important healthcare problem. According to current clinical practice, a liver biopsy is required for the diagnosis and treatment of chronic liver disease. However, a liver biopsy is an invasive, inconvenient procedure, which requires an expert pathologist opinion. Therefore requirement of biochemical tests, which are considered to indicate hepatic fibrosis and may be repeated easily, increases gradually today.

Objectives:

This study evaluated the correlation between hepatic fibrosis and routine laboratory values in patients with chronic hepatitis B.

Patients and Methods:

The files of 456 patients with CHB (chronic hepatitis B) who were referred to the infectious diseases and clinical microbiology clinic between January 2009 and March 2012 were screened retrospectively. Liver biopsy samples were examined according to Ishak scoring. Laboratory parameters and histopathology reports were recorded, and correlations between the fibrosis grade and laboratory parameters were analyzed.

Results:

There were 320 male and 136 female patients, with a mean age 36.7 ± 12.1 years. According to liver biopsy results, a low fibrosis score (stage 0-2) was detected in 281 patients (61.6%), and a high fibrosis score (stage 3-5) was detected in 175 patients (38.4%). Patients with a high fibrosis score had significantly higher ALT (alanine amino transferase), AST (aspartate aminotransferase), and HBV-DNA values and a significantly lower platelet count compared with those with a low fibrosis score (P = 0.001, 0.001, 0.025, and 0.001, respectively). A positive correlation was detected between the fibrosis score and age, BMI, HAI, ALT, and AST values, and a negative correlation was detected between the fibrosis score and albumin and platelet counts. In the regression analysis performed to evaluate the factors associated with high-stage fibrosis, fibrosis was determined to be associated with thrombosis, ALT, and gender. The results of the regression analysis demonstrated that the risk of fibrosis was 4.6 fold higher in men.

Conclusions:

According to the results obtained in our study, advanced age, higher BMI, AST, ALT, and HBV-DNA levels, and low albumin and platelet levels are correlated with advanced fibrosis in patients with CHB.     

Clinical Implications of the Serum Apelin Level on Portal Hypertension and Prognosis of Liver Cirrhosis

Background/Aims

Levels of serum apelin (s-apelin), an endogenous ligand for angiotensin-like receptor 1, have been shown to be related to hepatic fibrosis and hemodynamic abnormalities in preclinical studies. We investigated the clinical implications of s-apelin as a noninvasive prognostic biomarker for chronic liver disease (CLD).

Methods

From January 2009 to December 2012, 215 CLD patients were enrolled and underwent clinical data collection, hepatic venous pressure gradient (HVPG) measurement, and liver biopsy. s-apelin was detected with a human total apelin enzyme-linked immunosorbent assay kit. All patients were prospectively observed during the median follow-up period of 23.0±12.9 months for decompensation and mortality.

Results

A total of 42 patients (19.5%) died during the follow-up period. s-apelin was significantly correlated with measurements of liver stiffness (R²=0.263, p<0.001) and collagen proportional area (R²=0.213, p<0.001) measured from liver biopsy tissue and HVPG (R²=0.356, p<0.001). In a multivariate analysis using a Cox regression hazard model, s-apelin was a weakly significant predictor of decompensation (hazard ratio [HR], 1.002; p<0.001) and mortality (HR, 1.003; p<0.001).

Conclusions

s-apelin showed a significant relationship with CLD severity. However, its significance as a noninvasive biomarker for disease severity and prognosis was weak.     

Dichlorvos Induced Autoimmune Hepatitis: A Case Report and Review of Literature

Introduction:

Drug-induced liver injury is a frequent cause of hepatic dysfunction. Several drugs have been identified to cause autoimmune hepatitis (AIH). Environmental chemicals are capable of triggering a certain degree of liver injury. However, toxin induced AIH is rare.

Case Presentation:

We reported a woman with chronic (long-term) exposures to dichlorvos, which resulted in liver injury and cirrhosis. She was diagnosed after a second liver biopsy, which was correlated with laboratory findings. At the same time, she experienced hepatic cortical blindness during her first admission.

Conclusions:

Chronic (long-term) exposures to dichlorvos can lead to AIH. A detailed inquiry of medical history and liver biopsy are necessary for the diagnosis of toxin-induced AIH. Corticosteroid therapy is associated with favorable evolution.     

Low Serum Hepatitis B Surface Antigen Level Predicts Compensated Cirrhosis Caused by Chronic Hepatitis B in HBeAg Positive Patients in East China

Backgrounds:

Serum hepatitis B surface antigen (HBsAg) levels are associated with fibrosis in patients with chronic hepatitis B (CHB) infection.

Objectives:

The aim of our study was to evaluate serum HBsAg level as a biomarker for compensated cirrhosis in hepatitis B e antigen (HBeAg) positive CHB patients.

Patients and Methods:

Two-hundred and one HBeAg-positive Chinese CHB patients with or without cirrhosis were enrolled in this retrospective study. Cirrhosis was diagnosed based on liver biopsy. Furthermore, patients with decompensated cirrhosis were excluded. A statistical analysis was performed regarding the association between serum HBsAg level and compensated cirrhosis.

Results:

Patients with compensated cirrhosis had a significantly lower mean serum HBsAg level compared to those without cirrhosis (3.27 Log₁₀ IU/mL VS 4.17 Log₁₀ IU/mL, P < 0.001). Furthermore, examining the correlation with compensated cirrhosis revealed that lower level of serum HBsAg was a significant factor in multivariate analysis. The area under the receiver operating characteristics curve of serum HBsAg was 0.856 for compensated cirrhosis. A positive predictive value of 66.2% and negative predictive value of 90.7% were obtained with a cut-off value of < 3.60 Log₁₀ IU/mL (4000 IU/mL) of serum HBsAg. Moreover, the rate of compensated cirrhosis increased to 75.0% after combining with APRI > 2.

Conclusions:

In HBeAg positive CHB patients, low serum HBsAg level is a useful predictor of compensated cirrhosis.