Aspartate aminotransferase to platelet ratio index (APRI) can predict liver fibrosis in chronic hepatitis B

BACKGROUND: There have been still few valuable markers that can be used as indirect markers of liver fibrosis in chronic hepatitis B. AIMS: This study aimed to evaluate efficacy of several indirect markers of liver fibrosis and to identify the most valuable test in chronic hepatitis B. PATIENTS AND METHODS: A total of 264 patients with chronic hepatitis B were consecutively enrolled. Fibrosis was staged by a single blinded pathologist according to the METAVIR system. Significant fibrosis was defined as stage >or=2. We investigated diagnostic accuracy of four indirect markers including aspartate aminotransferase to platelet ratio index for predicting significant fibrosis. RESULTS: Mean age was 28 years. 53% (141/264) had significant hepatic fibrosis. Of indirect markers, aspartate aminotransferase to platelet ratio index yielded the best area under the receiver operating characteristic curve (0.86; 95% confidence interval, 0.82-0.91). Positive predictive value/negative predictive value at 0.5, 1.5 and 2.0 of aspartate aminotransferase to platelet ratio index score for predicting significant fibrosis were 63%/91%, 83%/74% and 86%/65%, respectively. The odds ratio for aspartate aminotransferase to platelet ratio index >or=1.4 relative to less than aspartate aminotransferase to platelet ratio index of 1.4 was 17.971 (p<0.0001; 95% confidence interval, 9.677-33.376). CONCLUSIONS: Of simple markers already developed in chronic hepatitis C, aspartate aminotransferase to platelet ratio index may be the most accurate and simple marker for predicting significant fibrosis in chronic hepatitis B.     

Disease progression in chronic hepatitis C patients with normal alanine aminotransferase levels

AIM:To investigate whether the disease progression of chronic hepatitis C patients with normal alanine aminotransferase(ALT) levels differs by ALT levels.METHODS:A total of 232 chronic hepatitis C patients with normal ALT(< 40 IU/L) were analyzed.The patients were divided into "high-normal" and "low-normal" ALT groups after determining the best predictive cutoff level associated with disease progression for each gender.The incidence of disease progression,as defined by the occurrence of an increase of ≥ 2 points in the Child-Pugh score,spontaneous bacterial peritonitis,bleeding gastric or esophageal varices,hepatic encephalopathy,the development of hepatocellular carcinoma,or death related to liver disease,were compared between the two groups.RESULTS:Baseline serum ALT levels were associatedwith disease progression for both genders.The best predictive cutoff baseline serum ALT level for disease progression was 26 IU/L in males and 23 IU/L in females.The mean annual disease progression rate was 1.2% and 3.9% for male patients with baseline ALT levels ≤ 25 IU/L(low-normal) and > 26 IU/L(highnormal),respectively(P = 0.043),and it was 1.4% and 4.8% for female patients with baseline ALT levels ≤ 22 IU/L(low-normal) and > 23 IU/L(high-normal),respectively(P = 0.023).ALT levels fluctuated during the follow-up period.During the follow-up,more patients with "high-normal" ALT levels at baseline experienced ALT elevation(> 41 IU/L) than did patients with "lownormal" ALT levels at baseline(47.7% vs 27.9%,P = 0.002).The 5 year cumulative incidence of disease progression was significantly lower in patients with persistently "low-normal" ALT levels than "high-normal" ALT levels or those who exhibited an ALT elevation > 41 U/L during the follow-up period(0%,8.3% and 34.3%,P < 0.001).CONCLUSION:A "high normal" ALT level in chronic hepatitis C patients was associated with disease progression,suggesting that the currently accepted normal threshold of serum ALT should be lowered.     

Independent associations of alanine aminotransferase (ALT) levels with cardiovascular risk factor clustering in Chinese adolescents

BACKGROUND/AIMS: To establish the prevalence of elevated serum alanine aminotransferase (ALT) concentrations in Chinese adolescents, and to explore the nature of associations amongst ALT, obesity and cardiovascular risk factors. METHODS: Anthropometric measurements and fasting plasma glucose, insulin, lipids and ALT were measured in 2102 Chinese adolescents, aged 12-18 years, randomly selected from 14 secondary schools in Hong Kong. RESULTS: The prevalence of elevated ALT levels was 3.2% and 5.9% if abnormal ALT levels were defined as >40 IU/L and >30 IU/L respectively. Using the <25th, 25-75th and >75th percentile values of ALT, all subjects were divided into 3 ALT strata. Using the lowest ALT stratum as referent, the top ALT stratum was associated with obesity and clustering of cardiometabolic-inflammatory risk markers in both genders. After adjusting for age and body mass index (BMI), the highest ALT stratum remained independently associated with diastolic blood pressure and insulin resistance (fasting insulin and Homeostasis Model Assessment, HOMA-IR, HOMA-beta) in boys (p<0.05); and serum triglyceride and HOMA-beta (p=0.008 and 0.014, respectively) in girls. Repeat analysis after excluding subjects with ALT>30 (n=123) or >40 IU/L (n=67) yielded comparable results. CONCLUSIONS: In adolescents, top ALT stratum, albeit within normal range, is associated with clustering of cardiovascular risk factors, independent of obesity.     

Correlation between serum HCV RNA and aminotransferase levels in patients with chronic HCV infection

Cross-sectional studies on the correlation between serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels in patients with chronic hepatitis C have yielded conflicting results. We conducted a longitudinal study to examine the correlation between HCV viremia and serum ALT levels in individual patients over time. Serial samples (mean 9) from 25 patients with chronic HCV infection, including interferon-treated and untreated immunocompetent and immunosuppressed patients, collected over a period of 1–4.8 years (mean 2.6 years) were tested for HCV RNA and ALT levels using a highly reproducible quantitative (bDNA) assay. A significant correlation was found between serum HCV RNA and ALT levels in the patients who received IFN therapy, but no correlation was observed in the untreated patients. Among the untreated patients, the immunosuppressed patients had significantly higher HCV RNA levels (39±4 vs 3.6±8 Meq/ml,P<0.0001) but significantly lower ALT (56±11 vs 97±12 units/liter,P=0.03) levels when compared to the immunocompetent ones. In summary, we found no correlation between serum HCV RNA and ALT levels in chronic hepatitis C patients who are not receiving interferon therapy. Immunosuppression results in higher HCV RNA but lower ALT levels.     

Serum HCV RNA titer does not predict the severity of liver damage in HCV carriers with normal aminotransferase levels

AIMS/BACKGROUND: Many HCV RNA positive subjects with normal aminotransferase levels have significant liver damage despite normal liver biochemistry. In these patients it is not possible to discriminate between "healthy" carriers and subjects with chronic liver damage, unless liver biopsy is performed. The aim of this study was to evaluate the usefulness of HCV RNA quantitation as a non invasive tool to predict the severity of liver injury in a group of HCV carriers with normal amino-transferase levels. METHODS: 59 HCV RNA positive subjects (20 males) with persistently normal ALT levels were studied. All patients underwent HCV RNA quantitation and percutaneous liver biopsy. RESULTS: No correlation was found between serum HCV RNA titers and grading, while viraemia did correlate with staging. Patients were categorized into four subgroups, according to arbitrary serum HCV RNA cut-offs. Grading was not different between the four groups. Staging was significantly higher among subjects with viraemia > 1000 x 10(3) copies/mL than in patients with HCV RNA titers < 1000 x 10(3) copies/mL. CONCLUSIONS: In HCV carriers with normal aminotransferase levels viraemia does not predict the grade of HCV-related chronic liver disease (CLD), although subjects with higher HCV RNA levels seem to have more severe fibrosis. Although these data suggest that patients with higher viraemia might have more intense architectural changes and more severe progression of liver disease than those with lower levels of HCV replication, the weak and imprecise correlation leads us to conclude that HCV RNA quantitation is not a useful indicator in clinical practice in the selection of patients for liver biopsy.     

A prospective study on the causes of notably raised alanine aminotransferase (ALT)

Objective High levels of alanine aminotransferase (ALT) can be a marker of severe liver disease with variable aetiologies and prognosis. Very few prospective studies have been undertaken on the aetiology and prognosis of patients with high ALT levels. No population-based prospective study has systematically evaluated drug-induced liver injury (DILI) among these patients. The objective was to determine the aetiology and prognosis of patients with high ALT. Materials and methods In a catchment area of 160,000 inhabitants, a population-based prospective study identified all adult patients with serum level of ALT?>500 U/L during a 12-month period. All underwent thorough diagnostic work-up and follow-up. In suspected DILI, causality was assessed with Roussel Uclaf Causality Assessment Method. Results A total of 155 patients were identified with ALT?>500 U/L, 12 children and one with ALT of non-liver-related origin, leaving 142 patients for the analysis: 73 (51%) males, median age 52 (IQR 36–68, range 19–89 years). The most common causes were choledocholithiasis 48/142 (34%), ischaemic hepatitis 26 (18%), viral hepatitis 16 (11%) and DILI 15 (11%), hepatobiliary malignancy (n?=?6), surgery/interventions (n?=?8) and other aetiologies (n?=?23). No specific aetiology was found in 6% of cases. In the total study cohort 99 (70%) required hospitalisation, 78 (55%) had jaundice and 22 (16%) died, liver-related death in 10%, 35% in IH and 7% in DILI. Conclusions The most common cause of notably high ALT was choledocholithiasis. Ischaemic hepatitis was a common aetiology with approximately 35% liver-related mortality. Viral hepatitis and DILI were important aetiologies among these patients.     

丙氨酸转氨酶对FibroScan诊断慢性乙型肝炎肝纤维化分期的影响

目的 探讨慢性乙型肝炎(CHB)患者中,不同水平的ALT对FibroScan诊断不同肝纤维化分期准确性的影响.方法 回顾性分析213例慢性乙型肝炎患者,根据血清ALT水平分为ALT＜1×正常值上限(ULN)、1×ULN≤ALT＜2×ULN和ALT≥2×ULN 3组,分析3组采用FibroScan诊断不同肝纤维化分期的ROC曲线下面积,判断其诊断准确性.根据不同资料采用t检验、x2检验、受试者工作曲线或其曲线下面积(AUROC)进行统计学分析.结果在213例CHB患者中,FibroScan值与不同肝纤维化分期在3组患者中均有明显的相关性(rs值分别为0.773、0.889和0.412,P值均＜0.05).FibroScan诊断2级以上肝纤维化(F≥2,F0～1对比F2～4)和肝硬化(F=4,F0～3对比F4)的AUROC分别为0.916和0.971;其截断值分别为7.0kPa和13.0kPa;准确度分别为84.0%和93.4%.其诊断F≥2的AUROC和准确度均低于肝硬化.ALT＜1×ULN、1×ULN≤ALT＜2×ULN和ALT≥2×ULN 3组在诊断明显肝纤维化的AUROC分别为0.939、0.967和0.687,其敏感度分别为90.0%、89.7%和47.8%;准确度为90.5%、93.9%和68.4%.ALT≥2×ULN组的AUROC、敏感度和准确度明显低于另两组;而ALT＜2×ULN两组的AUROC和准确度相近.ALT＜1×ULN、1×ULN≤ALT＜2×ULN和ALT≥2×ULN 3组在诊断肝硬化的AUROC分别为0.970、0.985和0.952,其敏感度分别为93.8%、100%和100%;准确度分别为:88.9%、95.9%和92.1%.3组的AUROC、敏感度和准确度均较高,未随ALT升高而出现明显变化.结论 FibroScan是诊断2级以上肝纤维化,尤其是肝硬化可靠的检测方法; FibroScan诊断慢性乙型肝炎所致肝硬化的准确性可能受ALT升高的影响不明显;诊断2级以上肝纤维化的准确性对于ALT＜2×ULN的慢性乙型肝炎患者无明显影响,但是对ALT≥2×ULN的患者,其诊断的准确性降低.

Abstract：

Objective To analyze whether or not the accuracy of liver stiffness measurement (LSM)with transient elastography (FibroScan) for the diagnosis of liver fibrosis influenced by serum alanine aminotransferase (ALT) levels in patients with chronic hepatitis B. Methods 213 consecutive CHB patients who underwent liver biopsy and LSM were enrolled and divided into three groups by the criteria of ALT＜1×ULN, 1×ULN≤ALT＜2×ULN and ALT≥2×ULN. The areas under the receiver operating curve (AUC) were analyzed and the accuracy of FibroScan for the diagnosis of liver fibrosis were detected in the three groups. Results Significant correlation existed between the stages of liver fibrosis and LSM (rs=0.773,0.889 and 0.412, P＜0.05). AUCs of LSM in all patients for significant fibrosis (F≥2, F0-1 vs F2-4)and cirrhosis (F=4, F0-3 vs F4) were 0.916 and 0.971 respectively.The accuracy of diagnosis for significant fibrosis and cirrhosis were 84.0% and 93.4% respectively.AUCs of LSM in ALT＜1×ULN,1×ULN≤ALT＜2×ULN and ALT≥2×ULN groups for significant fibrosis were 0.939, 0.967 and 0.687 respectively.The sensitivity of the three groups was 90.0%, 89.7% and 47.8% respectively. The accuracies of the three groups was 90.5%, 93.9% and 68.4% respectively. The AUC, sensitivity and accuracy of ALT≥2×ULN group for significant fibrosis were significantly lower than the other two groups. AUCs of LSM in three groups for cirrhosis were 0.970, 0.985 and 0.952 respectively. The sensitivities of the three groups were 93.8%,100% and 100% respectively. The accuracies of the three groups were 88.9%, 95.9% and 92.1% respectively.The AUCs, sensitivity and accuracy for cirrhosis of the three groups didn't change with elevated ALT. Conclusion Transient elastography (FibroScan) is a reasonable noninvasive tool to diagnose significant fibrosis,especially liver cirrhosis in CHB patients. The accuracy of FibroScan for diagnosis of liver cirrhosis may not be influenced by elevated ALT. While in ALT≥2 ×ULN group, the accuracy of FibroScan for diagnosis of significant fibrosis was significantly lower as compared to the ALT≤2×ULN groups.     

Alanine aminotransferase (ALT) levels in a normal population and interferon therapy in chronic hepatitis C patients with normal ALT

BACKGROUND/AIMS: The aims of this study were to determine the distribution of serum alanine aminotransferase levels in a normal population and to clarify whether interferon treatment is justified in HCV-infected patients with persistently normal alanine aminotransferase levels. METHODOLOGY: The distribution of alanine aminotransferase levels was examined among 949 normal subjects who were negative for hepatitis viruses, denied regular alcohol use. Nineteen patients with chronic hepatitis C and persistently normal alanine aminotransferase levels were treated with alpha interferon (six or ten million units thrice weekly for six months). RESULTS: Peaks of alanine aminotransferase distribution among the normal subjects were seen at 16-20 IU/L and 11-15 IU/L in males and females, respectively. Fourteen of the 19 patients who received interferon treatment had favorable factors of response to interferon (eight with low pretreatment virus load, four with HCV genotype 2 and two with both). A sustained virological response was achieved in eight (57%) of 14, and alanine aminotransferase levels decreased significantly to within the normal range after interferon treatment in six of eight. CONCLUSIONS: Patients with chronic hepatitis C and persistently normal alanine aminotransferase levels should be treated with high doses of interferon if they have favorable factors of response to interferon treatment.     

Correlation of serum HCV RNA and alanine aminotransferase levels in chronic hepatitis C patients during treatment with ribavirin

to evaluate the effect of ribavirin on serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels, 22 patients with chronic HCV infection were treated with oral ribavirin 1200 mg daily in three divided doses for 4 weeks. At the end of 4 weeks treatment, the serum ALT decreased in all but one patient and became normal in three individuals. The mean pretreatment serum ALT was reduced significantly from 193 ± 45 i.u./L to 95 ± 16 i.u./L after 4 weeks therapy (P= 0.009). However, 8 weeks after cessation of treatment, the serum ALT rose to a mean value of 154 ± 21 i.u./L. The mean pretreatment serum HCV RNA was not significantly decreased at the end of 4 weeks treatment (7.0 × 10⁵vs 4.1 × 10⁵ copies/mL, P > 0.05). However, serum HCV RNA levels were decreased in 12 and increased in 10 patients at the end of 4 weeks therapy. Eight weeks after cessation of therapy, the serum HCV RNA of 22 patients rose to a mean value of 4.9 ± 10⁵ copies/mL. Six patients who continued to have elevated serum ALT and positive HCV RNA after the initial 4 weeks treatment received oral ribavirin at the same dosage for an additional 24 weeks. The serum ALT again decreased in all six patients during therapy, but rose to pretreatment values by 8 weeks after cessation of the treatment. In addition, no significant changes were noted in the mean serum HCV RNA levels during and after 24 weeks of ribavirin therapy. Our results indicate that oral ribavirin only transiently lowered serum ALT values and did not efficiently suppress HCV synthesis in patients with chronic hepatitits C infection.     

Relationship between serum alanine aminotransferase levels and liver histology in chronic hepatitis C-infected patients.

BACKGROUND: The efficacy of serum alanine aminotransferase (ALT) levels in predicting the severity of hepatitis C virus (HCV) infection is unclear. OBJECTIVE: To compare histologic scoring of liver pathology in patients with chronic HCV infection with normal or elevated serum ALT. METHODS: Liver biopsies were performed in patients with HCV infection and either normal (n=40) or elevated (n=76) serum ALT levels, and scored for activity and fibrosis using the modified histological activity index. RESULTS: Patients with normal ALT and elevated ALT had similar demographic features. Median (range) histological activity grade was higher in patients with elevated ALT than in those with normal ALT (6 [1-15] vs. 5 [0-11], respectively; p=0.001), as was the fibrosis stage (2 [0-6] vs. 1[0-6]; p=0.02). Two patients with normal ALT and 4 with elevated ALT had liver cirrhosis. CONCLUSIONS: Among patients with chronic HCV infection, liver lesions are milder in those with normal serum ALT levels than those with abnormal ALT levels. However, some patients with normal ALT too may have advanced liver disease.     

The presence of steatosis and elevation of alanine aminotransferase levels are associated with fibrosis progression in chronic hepatitis C with non-response to interferon therapy

BACKGROUND/AIMS: Interferon (IFN) therapy leads to regression of hepatic fibrosis in chronic hepatitis C patients who achieve a sustained virologic response (SVR), while the beneficial effect is limited in those who fail to do so. The aim of the present study was to define factors associated with progression of fibrosis in patients who do not achieve a SVR. METHODS: Fibrosis staging scores were compared between paired liver biopsies before and after IFN in 97 chronic hepatitis C patients who failed therapy. The mean interval between biopsies was 5.9 years. Factors associated with progression of fibrosis were analyzed. RESULTS: Fibrosis progressed in 23%, remained unchanged in 47% and regressed in 29%. Steatosis and a high average alanine aminotransferase (ALT) between biopsies were independent factors for progression of fibrosis with risk ratios of 5.53 and 4.48, respectively. Incidence and yearly rate of progression of fibrosis was 64% and 0.22+/-0.29 fibrosis units per year in those with both risk factors compared to 8% and -0.04+/-0.17 fibrosis units per year in those negative for both factors. CONCLUSIONS: Hepatic steatosis and elevated ALT levels are risk factors for progression of fibrosis in chronic hepatitis C patients who fail to achieve a SVR to IFN therapy and therefore may be therapeutic targets to halt the potentially progressive disease.     

丙氨酸转氨酶正常的慢性乙型肝炎病毒感染者的肝脏病理学分析

目的 了解ALT正常的慢性HBV感染者的肝脏病理学改变及其影响因素.方法 观察632例ALT正常的慢性HBV感染者,采用超声定位穿刺取肝组织,行HE染色、纤维Masson染色,HBsAg和HBcAg免疫组织化学染色,观察Knodell坏死炎症评分和Ishak纤维化评分,并分析它们与年龄、ALT水平、血清HBV DNA载量、HBsAg和HBcAg肝组织表达的关系.两均数比较采用t检验,多均数比较采用单因素方差分析及q检验,计数资料采用x2检验.结果 632例ALT正常的HBV感染者中,中度炎症坏死167例,占26.4%,重度炎症坏死26例,占4.1%,中度纤维化217例,占34.3%,重度纤维化(肝硬化)52例,占8.2%.Knodell坏死炎症评分和Ishak纤维化评分在高ALT层次组比低ALT层次组高,在女性高ALT层次组比男性高ALT层次组高,在年龄＞40岁组比年龄≤20岁组高(q=19.63,P＜0.05).肝组织损伤程度在HBV DNA载量≤5×105拷贝/L组明显轻于HBV DNA 5×105～1×107拷贝/L、1×107～1×109拷贝/L和＞1×109拷贝/L组(Knodell评分,q=3.87、2.87、6.34;Ishak评分,q=2.64、2.64、5.54;均P＜0.05),在不同HBV DNA载量复制组之间差异无统计学意义(F=1.35,P＞0.05).HBsAg(F=1.65、0.73,均P＞0.05)和HBcAg(F=0.17、1.29,均P＞0.05)肝组织表达与Knodell坏死炎症评分和Ishak纤维化评分差异均无统计学意义.结论 可检测到HBV DNA的ALT持续正常的慢性HBV感染患者应考虑进行肝组织活检,特别是年龄＞40岁且ALT在(0.75～1.00)×正常值上限者.