Histological improvement of long‐term antiviral therapy in chronic hepatitis B patients with persistently normal alanine aminotransferase levels

The aim of this study was to evaluate the histological outcomes of chronic hepatitis B (CHB) patients with persistently normal alanine aminotransferase (ALT) levels after long‐term antiviral therapy. Paired liver biopsies before and after lamivudine (LAM) treatment in CHB patients with normal and elevated ALT levels were compared. Histological response was defined as a 1‐point decrease according to the Scheuer scoring system, without worsening of fibrosis between pretreatment and posttreatment biopsies. Among the 48 patients who underwent paired liver biopsies, 17 had persistently normal baseline ALT level and 31 had elevated ALT level. The median age of the patients was 44 years and 72.9% of the patients were male. The median duration of antiviral treatment was 44.5 months (range 14–104). Long‐term follow‐up of liver biopsies revealed that 82.4% of patients in the normal ALT group and 61.3% in the elevated ALT group had a baseline fibrosis score of 4, which was reduced to 17.6% and 38.7% after long‐term therapy, respectively, indicating reversal of cirrhosis in a large proportion of both groups, especially in patients with normal baseline ALT levels. Long‐term antiviral treatment could achieve significant histological improvement in CHB patients with fibrosis or cirrhosis, regardless of ALT level.     

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.     

Impact of mild to moderate elevations of alanine aminotransferase on liver stiffness measurement in chronic hepatitis B patients during antiviral therapy

Aim: The accuracy of liver stiffness measurement (LSM) in the diagnosis of liver fibrosis is affected by elevated serum alanine aminotransferase (ALT) levels. The aim of this study was to assess the impact of mild to moderate elevations of ALT on LSM in patients with chronic hepatitis B (CHB) during antiviral therapy. Methods: A total of 58 CHB patients with their ALT levels falling into the range of ×2 to ×10 the upper limit of normal (ULN) were recruited. ALT and LSM values were periodically assessed at baseline and 12, 24 and 48 weeks. Results: The median ALT levels were 153.5 (76–544), 50.5 (11–475), 36.5 (9–265) and 30 (12–239) IU/L at baseline and 12, 24 and 48 weeks, respectively. The corresponding median value of LSM was 8.8 (3.2–47.3), 6.15 (3.2–31.2), 5.9 (3.1–29.1) and 5.5 (2.8–21.5) kpa. However, after the ALT levels were normalized by the treatment, the values of LSM did not vary significantly (6.1 [3.0–17.7] vs 5.25 [2.8–21.5] kpa, P = 0.381). Pretreatment fibrosis stages of liver biopsies corresponded with LSM after ALT normalization rather than baseline LSM (F0–1, 12/27 vs 23/25, P < 0.001). Conclusion: The LSM values decreased in parallel with the decline in ALT levels in CHB patients with mild to moderate elevation of ALT. LSM became more accurate when applied to document the liver fibrosis or cirrhosis in CHB patients after the elevated ALT level has been treated to normal level.     

血清ALT与慢性乙型肝炎、肝硬化FibroScan 弹性值动态检测结果的相关性

目的探讨肝脏弹性值（LSM）在慢性乙型肝炎发作过程中的变化及ALT对LSM影响。方法 43名慢性乙型肝炎感染者,包括慢性乙型肝炎（CHB）23人、肝炎肝硬化（LC）20人;入院时行腹部B超检查,住院期间每7～10天、出院后每1～3月行Fibroscan（FS）检测,同时行常规血液指标化验。结果 CHB组中LSM与ALT有显著相关性（r=0.324,P=0.004）,偏相关分析提示LSM与ALT无统计学相关性（r=0.190,P=0.098）;随ALT下降,LSM逐渐降至诊断肝硬化界值14.6 kPa以下,呈现持续下降、先升后降或下降后波动等三种模式。LC组中,LSM与ALT无统计学相关性;在ALT好转的11例中,LSM较入院当天下降（P=0.003）,但仍高于肝硬化临界值。结论在非肝硬化CHB患者中,LSM受ALT水平影响较大。动态观察单一患者ALT与LSM变化,可能提高LSM预测肝纤维化准确性。     

Fibrosis progression in initially mild chronic hepatitis C

The natural history of chronic hepatitis C presenting with no/minimal liver fibrosis is uncertain with controversies on risk of progression and need for antiviral treatment. We studied rates and determinants of fibrosis progression in initially mild chronic hepatitis C. One hundred and six patients (mean age 41.65 +/- 12.83 years) with chronic hepatitis C virus infection and no/minimal fibrosis in the initial liver biopsy (F0/F1 by METAVIR score) were followed prospectively while untreated with repeated biopsy after 5 or more years (mean interval 7.8 +/- 1.51 years). Patients showing fibrosis progression were compared with nonprogressors for baseline and follow-up parameters. Sixty-four patients (60.4%) showed fibrosis progression including 13 of 27 (49%) with F0 and 51 of 79 (65%) with F1. Progression to F3 or cirrhosis was seen in 36% of those with F1 initially. Fibrosis progression (DeltaF/year) was associated with age (P < 0.0001), baseline and follow-up alanine aminotransferase (ALT) (P = 0.005), histological activity (P = 0.004) and steatosis (P = 0.002) in the initial biopsy and use of alcohol (P = 0.008). Thus liver fibrosis progression occurs in two-thirds of patients with initially mild chronic hepatitis C within 5-10 years and advanced fibrosis/cirrhosis develops in one-third of those with F1 initially. Fibrosis is facilitated by older age and alcohol and associated with inflammatory activity and ALT levels. Antiviral therapy should be considered in mild chronic hepatitis C.     

Predictors of liver histological changes and a sustained virological response to peginterferon among chronic hepatitis B e antigen‐positive patients with normal or minimally elevated alanine aminotransferase levels

A proportion of chronic hepatitis B patients with normal or only minimally elevated alanine aminotransferase (ALT) levels display significant histologic changes and would benefit from antiviral therapy. We aim to evaluate the histologic abnormalities seen in these patients and then determine which of them would most likely respond to peginterferon therapy. One hundred and thirteen hepatitis B e antigen (HBeAg)‐positive patients with a normal or minimally elevated ALT level and moderate‐to‐severe histologic changes in their liver tissue were selected to receive peginterferon monotherapy and participate in a follow‐up analysis. A multiple logistic regression analysis indicated that increasing age (P=.049) and lower hepatitis B virus (HBV) DNA levels (P=.038) were associated with significant histological abnormalities in patients with a normal or minimally elevated ALT. Our predictive model which incorporated HBeAg testing at treatment week 12 combined with hepatitis B surface antigen (HBsAg) testing at treatment week 24 was able to identify which patients with a normal ALT level would achieve a sustained virological response (SVR) (positive predictive value [PPV]: 66.7%, negative predictive value [NPV]: 90.0%). Lower HBsAg and HBeAg levels at treatment week 24 were associated with a SVR in patients with a minimally elevated ALT level (PPV: 100.0%, NPV: 100.0%). A liver biopsy and antiviral therapy should be strongly considered when treating HBeAg‐positive patients with a normal or minimally elevated ALT level, low HBV DNA level, and aged >35 years. On‐treatment quantification of combined HBsAg and HBeAg test results may be useful for predicting a SVR to peginterferon monotherapy in these patients.     

High prevalence of significant histology in asymptomatic chronic hepatitis B patients with genotype C and high serum HBV DNA levels

Summary.  Current treatment guidelines suggest that antiviral therapy be considered for chronic hepatitis B (CHB) patients with high viral load if a biopsy shows significant liver disease despite alanine aminotransferase (ALT) levels two times or less than the upper limit of normal (ULN). We evaluated the histological findings in CHB patients with high viral load and persistently normal or slightly elevated serum ALT levels. Between January 2003 and June 2006, 105 consecutive treatment-naive patients with CHB who underwent ultrasonography-guided percutaneous liver biopsy, had detectable serum HBV DNA (>10⁵ copies/mL) in a direct hybridization assay and normal or slightly elevated serum ALT levels (≤2 × ULN) for at least 12 months were included in a prospective study. Histological assessment was based on the METAVIR scoring system. Significant histology was defined as fibrosis stage ≥F2 or necroinflammation grade ≥A2. Among the 105 CHB patients with high viral load and persistently normal or slightly elevated serum ALT levels for at least 12 months, significant fibrosis (F2–F4 fibrosis) was observed in 63 patients (60.0%) and the actual significant histology was found in 65 patients (61.9%). On multivariate analysis, serum ALT levels and age at which they entered the study were independent factors associated with significant histology. Odds ratios for significant histology increased progressively according to serum ALT levels and age. In conclusion, a large proportion of CHB patients with genotype C, high viral load and ALT ≤2 × ULN had significant liver disease on liver biopsy and should be considered for antiviral therapy.     

A higher alanine aminotransferase level correlates with earlier hepatitis B e antigen seroconversion in lamivudine‐treated chronic hepatitis B patients

Background/Aims: A pretherapy serum alanine aminotransferase (ALT) level above five times the upper limit of normal (ULN) is known to predict hepatitis B e antigen (HBeAg) seroconversion during lamivudine therapy for chronic hepatitis B patients. However, whether an even higher pretherapy serum ALT value or other viral factors could affect treatment responses remains unclear. Patients and methods: A total of 253 HBeAg‐positive chronic hepatitis B patients who had a pretherapy serum ALT level over five times ULN and received lamivudine for 12–18 months were retrospectively collected. Among these patients, 38% had received prior lamivudine treatment. HBeAg seroconversion was the primary endpoint of treatment. Baseline clinical and viral features were compared between responders and non‐responders at the end of treatment and 6 months post‐treatment. Results: At the end of therapy, the overall HBeAg seroconversion rate was 33.6%. For lamivudine‐naïve patients, the HBeAg seroconversion rate was 37.8%. Subgroup analysis showed that patients with pretherapy ALT levels over 10 times ULN had a significantly higher HBeAg seroconversion rate than those with a pretherapy ALT level between five and 10 times ULN at 3 months (P=0.045) and 6 months (P=0.037) of lamivudine treatment. No significant difference was found in terms of pretherapy serum ALT values, viral load and genotypes between seroconverters and non‐seroconverters. Conclusions: For lamivudine‐treated HBeAg‐positive patients with pretherapy ALT levels over five times ULN, an even higher ALT level could predict earlier HBeAg seroconversion; however, neither ALT levels nor viral factors correlate with higher response rates after 12–18 months of treatment.     

Relationships between serum aminotransferase levels, liver histologies and virological status in patients with chronic hepatitis C in Taiwan

In patients with chronic hepatitis C, the relationships between serum alanine aminotransferase (ALT) levels, histological liver injury and serum hepatitis C virus (HCV) RNA titres remain controversial. To evaluate these relationships, 93 Chinese patients with histological diagnosis of chronic hepatitis C were enrolled for this study. Serum ALT levels, HCV-RNA titres and HCV genotypes were examined. The histology was evaluated according to a modified histological activity score based on the degree of periportal necro-inflammation, intralobular necro-inflammation, portal inflammation, total necro-inflammation and fibrosis. The mean serum ALT level was significantly higher in patients with severe intralobular necro-inflammation activity than in patients with mild or no activity (P= 0.013). However, scores of intralobular activity were only weakly correlated with serum ALT levels (r= 0.27) and could not be used to adequately predict ALT values. Serum ALT levels showed no significant correlation with the scores of portal inflammation, periportal necro-inflammation, total necro-inflammation and fibrosis. Also, there was no significant difference in the mean serum ALT level among different serum HCV-RNA levels and HCV genotypes. Serum HCV-RNA titres and genotypes showed no significant correlation with liver histology and serum HCV-RNA titres were only weakly correlated with the total necro-inflammatory score (r= 0.27). In conclusion, although serum ALT levels were higher in patients with more severe intralobular necro-inflammatory activity, the correlation was not strong enough to adequately predict ALT values. Serum HCV-RNA titres and genotypes also showed no significant correlation with serum ALT levels and liver histologies.     

Hypervariable region 1 quasispecies in hepatitis C virus genotypes 1b and 3 infected patients with normal and abnormal alanine aminotransferase levels

The role of hepatitis C virus (HCV) heterogeneity in the severity of chronic hepatitis C infectionremains unclear. Our aim was to study the hypervariable region 1 (HVR1) heterogeneity in patients with chronic hepatitis C infected with genotype 1b or 3 and with normal or abnormal alanine aminotransferase (ALT). HVR1 quasispecies were assessed by single strand conformational polymorphism (SSCP) in 67 patients with chronic hepatitis C, including 35 with persistently normal ALT and 32 with abnormal ALT. Sixty-two patients underwent a liver biopsy. Among the 67 patients, 40 were infected with genotype 1b and 27 with genotype 3. In univariate analysis, low heterogeneity (≤ 3 bands at SSCP) was significantly associated with normal ALT ( P  < 0.001), milder histological lesions (activity, P =0.02; fibrosis, P =0.04), and at the limit of significance for genotype 1b ( P =0.07). In multivariate analysis, low heterogeneity was significantly and independently associated with normal ALT ( P =0.09) and genotype 1b ( P =0.03). In patients with chronic hepatitis C, a low viral heterogeneity is significantly and independently associated with normal ALT and genotype 1b. These results are consistent with the view that patients with normal ALT have a different immune response against HCV resulting in a low HCV heterogeneity.     

Significant hepatic histopathology in chronic hepatitis B patients with serum ALT less than twice ULN and high HBV-DNA levels in Indonesia

OBJECTIVE: To study the prevalence of significant hepatic histopathology in chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) ≤ twice upper limit of normal (ULN) and its association with age, HBeAg status, hepatitis B virus (HBV)‐DNA level and viral genotype. METHODS: A prospective study was conducted over a 3‐year period in treatment‐naive CHB patients with ALT ≤ twice ULN. Patients with a history of acute flare hepatitis, use of alcohol and hepatotoxic drugs, hepatitis C, hepatitis D and human immunodeficiency virus (HIV) co‐infection were excluded from the study. Hepatic histopathology was assessed according to the METAVIR scoring system. RESULTS: A total of 145 patients were recruited, 81 (55.9%) of whom were male. The patients’ mean age was 41.50 ± 10.74 years (range 16–70 years). Significant hepatic inflammation was found in 59.3% of these patients, and significant hepatic fibrosis was found in 62.1%, the latter being associated with hepatitis B e antigen status, ALT levels and serum HBV‐DNA, but not with their age group or viral genotype. Significant hepatic fibrosis was found in 24 of 35 CHB patients (68.6%) who were previously considered in an immunotolerance phase. CONCLUSIONS The prevalence of significant hepatic histopathology in CHB patients with serum ALT levels ≤ twice ULN is high. Delayed antiviral treatment can be harmful.     

ALT小于2倍正常值上限的慢性乙型肝炎患者显著肝脏炎症的简易血清标志物探索

目的探索有效预测ALT2倍正常值上限(ULN)的慢性乙型肝炎(CHB)患者显著肝脏炎症的简易血清标志物。方法回顾性纳入278例ALT2×ULN(ULN=40 U/L)的CHB患者。显著肝脏炎症定义为炎症程度(G)≥2。计量资料满足正态分布的组间比较采用t检验;不满足正态分布的采用Kruskal-Wallis秩和检验,计数资料组间比较采用χ2检验。多因素回归分析筛查ALT2×ULN的CHB患者显著肝脏炎症的独立预测因素。受试者工作特征(ROC)曲线评估血清标志物对显著肝脏炎症的诊断价值。结果 278例患者中175例(62.9%)无显著肝脏炎症(G0~1组);103例(37.1%)伴显著肝脏炎症(G2~4组)。2组在ALT、AST、ALP、GGT、白蛋白(Alb)、球蛋白(Glb)、凝血酶原时间(PT)、血小板(PLT)、中性粒细胞绝对数(ANC)、透明质酸(HA)、甘胆酸(CG)、Ⅲ型前胶原(PCⅢ)和IV型胶原(ⅣC)等方面的差异均有统计学意义(P值均0.05)。单因素回归分析发现ALT、AST、ALP、GGT、Glb、PT、HA、CG、PCⅢ和ⅣC的水平越高,伴显著肝脏炎症的可能性越大[比值比(OR)均1,P值均0.05];PLT、Alb和ANC的水平越低,伴显著肝脏炎症的可能性越大(OR均1,P值均0.05)。多因素回归分析发现GGT、PT、IVC和HA是ALT2×ULN CHB患者显著肝脏炎症的独立预测因素(OR值分别为1.015、1.600、1.151、1.014,P值分别为0.008、0.021、0.003、0.018)。GGT、PT、IVC和HA诊断显著肝脏炎症的ROC曲线下面积依次为0.804、0.722、0.707和0.632。GGT≥48.5 U/L预测显著肝脏炎症的特异性为90.3%、阴性预测值为74.6%。结论 GGT、PT、IVC和HA是ALT正常或2倍以内升高CHB患者显著肝脏炎症的独立预测因素,其中以GGT的预测价值最大。     

Development of hepatocellular carcinoma in elderly patients with chronic hepatitis C with or without elevated aspartate and alanine aminotransferase levels

Objective. Hepatocellular carcinoma (HCC) in the elderly infected with hepatitis C virus (HCV) is expected to increase globally within the next two decades. The purpose of the study was to define the natural history of elderly patients with chronic hepatitis C needs in order to prevent HCC from arising in these patients. Material and methods. Treatment-naive patients aged ≥65 years with platelet counts >120×10³/mm³ were classified as 120 with aspartate and alanine aminotransferase (ASAT and ALAT) levels ≦40 IU/l (group A) and 212 with either or both levels ≥41 (group B) and followed-up for 3 years or longer without antiviral treatment. Results. Cirrhosis and HCC developed more frequently in group B than in group A (p<0.001 for both). In particular, of the patients aged 65–69 years at entry, cirrhosis and HCC developed more frequently in group B than in group A (p<0.001 and p=0.001, respectively). Liver-related causes of death were more common in group B than in group A (20/34 (59%) versus 1/9 (11%), p=0.021). HCC developed more frequently in men than in women (p=0.033). Conclusions. In elderly patients with chronic hepatitis C, cirrhosis and HCC develop more frequently in those with elevated transaminase levels than in those without elevated transaminase levels. Therefore, transaminase levels need to be suppressed below ≦40 IU/l, using antiviral treatments or other agents, in order to prevent cirrhosis and HCC arising in these patients. In view of rare liver-related deaths, aggressive antiviral treatment would not be necessary in the elderly with chronic hepatitis C who have normal transaminase levels.     

Effects of Silybum marianum on serum hepatitis C virus RNA, alanine aminotransferase levels and well-being in patients with chronic hepatitis C

Background/Aims: Silybum marianum is a herbal preparation commonly used by subjects with chronic hepatitis C (CHC). The aims of this pilot study were to assess the efficacy and safety of S. marianum on serum hepatitis C virus (HCV) RNA, alanine aminotransferase levels and well‐being in patients with CHC. Methods: Twenty‐four subjects with CHC were enrolled into a randomized, double‐blind, placebo‐controlled, crossover study. Subjects received 12 weeks of S. marianum (either 600 mg or 1200 mg/day) and placebo separated by a 4‐week washout interval. Baseline biochemical, virological, psychological and quality‐of‐life tests were performed, with biochemical tests repeated monthly, and HCV RNA titer and quality‐of‐life and psychological assessments repeated at the end of both treatment periods. Results: Seventeen patients completed the trial. Mean changes in HCV RNA titers, serum ALT levels and Short Form‐36 scores were not significantly different for subjects on S. marianum compared to those on placebo. There was no significant change in mean State‐Trait Anxiety Inventory State‐Anxiety scores on S. marianum from baseline. Adverse events were similar with S. marianum and placebo. Conclusions: S. marianum is well tolerated in subjects with CHC, but does significantly affect serum HCV RNA, alanine aminotransferase levels, quality of life or psychological well‐being in subjects with this condition.     

Prevalence and etiology of elevated serum alanine aminotransferase level in an adult population in Taiwan

BACKGROUND: The prevalence and etiologies of elevated alanine aminotransferase (ALT) have geographic variations and they are rarely reported in Taiwan. Through a population-based screening study, the prevalence and etiologies of elevated ALT in an adult population of Taiwan were assessed. METHODS: A cross-sectional community study in a rural village of Taiwan was conducted in 3260 Chinese adults (age >or=18 years) undergoing ultrasonography (US), blood tests, and interviews with a structured questionnaire. The diagnostic criteria of non-alcoholic fatty liver disease (NAFLD) included alcohol intake <20 g/week for women or <30 g/week for men, negative hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, no known etiologies of liver disease, and US consistent with fatty liver. RESULTS: The prevalence of elevated ALT was 11.4% (372/3260). The probable cause of this elevation was excess alcohol consumption in 0.8%, HBV in 28.5%, HCV in 13.2%, both HBV and HCV in 2.2%, NAFLD in 33.6%, and unexplained cause in 21.8%. The etiologic distribution of elevated ALT was similar in both genders, although elevation was more common in men compared to women (17.3%vs 6.1%, P < 0.05). The prevalence of elevated ALT in NAFLD was 18.1% (125/691), and the positive predictive value was 33.6% (125/372). The development of NAFLD was related to increasing age (age between 40 years and 64 years, odds ratio [OR] 1.59, 95% confidence interval [CI]: 1.25-2.01; age >or= 65 years, OR 1.46, 95%CI: 1.08-1.96), fasting plasma glucose (FPG) >or= 126 mg/dL (OR 1.54, 95%CI: 1.11-2.14), body mass index (BMI) >or= 25 kg/m(2) (OR 5.01, 95%CI: 4.13-6.26), triglyceridemia >or= 150 mg/dL (OR 1.96, 95%CI: 1.58-2.42), and hyperuricemia (OR 1.50, 95%CI: 1.22-1.84). Elevated ALT was related to male gender, BMI >or= 25 kg/m(2), and triglyceridemia >or= 150 mg/dL in subjects without known etiologies of liver disease (all P < 0.05). CONCLUSIONS: Non-alcoholic fatty liver disease appears to be the commonest cause of elevated ALT and presumed liver injury in Taiwan. The development of NAFLD is closely associated with many metabolic disorders. Metabolic disorders are also related to elevated ALT in subjects without known etiologies of liver disease.     

Larger biopsies evaluation of transient elastography for detecting advanced fibrosis in patients with compensated chronic hepatitis B

Background and Aim: Although larger biopsies sample had been recommended for the study of non‐invasive liver fibrosis assessment, few studies with larger biopsies for transient elastography (TE) detecting liver fibrosis had been reported. The present study tries to re‐evaluate the performance of TE for detecting advanced fibrosis (≥F3) with larger biopsies in patients with compensated chronic hepatitis B. Methods: A total of 375 compensated patients were analyzed, who had undergone liver biopsy, reliable TE and routine blood tests. Results: The area under the receiver operating characteristic curve (AUC) was influenced by liver biopsy sample: 0.873 (95% confidence interval 0.838–0.909) in total patients, 0.880 (0.844–0.917) in length ≥ 15 mm, 0.897 (0.863–0.932) in length ≥ 20 mm and 0.911 (0.874–0.949) in length ≥ 25 mm. In patients with sample length ≥ 20 mm, the cutoffs to exclude and confirm advanced fibrosis were 7.1 kPa and 12.7 kPa, respectively. Stratified by alanine aminotransferase of two times the upper limit of normal (ALT 2 × ULN), transient elastography detecting advanced fibrosis with the most efficiency by 72.5% of patients obviated from liver biopsy. In patients with normal bilirubin and ALT < 2 × ULN, the area was 0.921 (0.860–0.982), and cutoffs for excluding and confirming diagnosis were 7.4 kPa and 10.6 kPa, respectively; 80% of patients could be classified with or without advanced fibrosis (AF). In patients with normal bilirubin and ALT ≥ 2 × ULN, the corresponding numbers were 0.885 (0.824–0.947), 7.5 kPa, 12.7 kPa and 79.2%, respectively. Conclusions: Inadequate sample study would underestimate the efficiency of TE on detecting advanced fibrosis. With ALT 2 × ULN stratified cutoffs, TE determined nearly 80% of patients with normal bilirubin as AF or non‐AF and obviated them from liver biopsies.     

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.     

Molecular and serological characterization of hepatitis B virus in deferred Ghanaian blood donors with and without elevated alanine aminotransferase

Candidate blood donors in Ghana are frequent carriers of hepatitis B virus (HBV). A comparative study of 117 donor samples including 46 with alanine aminotransferase (ALT) > or = 60 IU/L and 71 with < or =40 IU/L level was undertaken. S and the basic core promoter-precore regions (BCP/PC) sequencing was used to identify genotypes and variants relevant to HBV natural history, respectively. Age, viral load, HBe status were correlated with molecular data. HBV genotype E (87%) was dominant with little genotypes A (10%) and D (3%). Comparing individuals with or without liver disease, an association between liver disease and older age (P = 0.004) and higher viral load (P = 0.002) whether as a whole population or only genotype E was found. Compared with a commercial assay, BCP/PC sequencing had lower sensitivity to detect mixtures of wild-type and variant viruses but detected BCP deletions. BCP 1762/1764 variants were positively correlated with older age (P < 0.0001) and elevated ALT levels (P = 0.01). PC 1896 stop codon was marginally correlated with viral load (P = 0.09). HBV genotype E infection natural history appears different from genotypes B and C prevalent in Asia. Donors with liver disease being older, with higher viral load and higher BCP variant proportion may be at higher risk of cirrhosis and hepatocellular carcinoma.