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.     

Steatosis and bile duct damage in chronic hepatitis C: distribution and relationships in a group of Northern Italian patients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) related disease follows a long, benign course and most affected patients have mild disease. Liver biopsy is mandatory to grade and stage the disease. Characteristic, though non-specific, HCV histological lesions such as bile duct damage and steatosis have been singled out but their association with non-histological parameters has not been completely defined. Our aim was to study the relationships among these histological lesions and clinical, biochemical, functional and virological characteristics in a group of Northern Italian patients with chronic hepatitis. METHODS: We studied 172 patients with HCV-related chronic hepatitis. Patients were divided into groups on the basis of histology including bile duct damage and steatosis. Clinical, biochemical, functional and virological profiles were related to histological findings. RESULTS: Histological grading and staging of disease increased as the age of patients increased. Steatosis was present in 70% of our patients and was related to a higher degree of fibrosis and to decreased functional activity. The prevalence of bile duct damage was 20%. This lesion was present in older patients with higher staging and impaired liver function. Biochemically it was associated with an increase in aspartate aminotransferase, gammaglutamyltranspeptidase, alkaline phosphatase, and total bilirubin. CONCLUSIONS: In the population we studied, HCV chronic hepatitis was predominantly a mild disease. Moreover both steatosis and bile duct damage were also mild. Steatosis was associated with fibrosis and this might influence liver metabolic function. Bile duct lesions were found in older patients with advanced disease showing biochemical evidence ofcholestasis. The molecular role HCV might play in the pathogenesis of these histological features should be addressed in further studies.     

Progressive hepatic fibrosis in healthy carriers of hepatitis C virus with a transaminase breakthrough

In short-term studies, patients with chronic hepatitis C virus (HCV) infection, consistently normal serum aminotransferase (ALT) levels, and minimal or mild necro-inflammatory changes in the liver, did not progress to histologically severe hepatitis. There are no data on longer term outcome of liver disease in these patients. We describe two patients with HCV infection (genotype 2c) with a rise in serum ALT values greater than 10 times the upper normal value that occurred after an 8- and 15-year period of persistently normal or minimally elevated ALT levels. In both patients, the rise in ALT values lasted more than 16 weeks and was not associated with any symptom or risk factor for acute hepatitis. A liver biopsy performed 4 and 18 months after the ALT flare showed clear-cut progression from chronic hepatitis with mild activity to chronic hepatitis with severe activity and central to portal septal fibrosis (Ishak score: grading 14 and 6; staging: 4 and 5, respectively). Hence, extended surveillance of HCV carriers with consistently normal or minimally elevated ALT values is warranted as these patients are at risk of ALT flares and may develop progressive liver disease.     

Correlation of serum aminotransferases with HCV RNA levels and histological findings in patients with chronic hepatitis C: the role of serum aspartate transaminase in the evaluation of disease progression

OBJECTIVES: To investigate whether HCV RNA levels can be considered to be predictors of hepatocellular injury in patients with chronic hepatitis C, and whether aminotransferase levels are markers of liver damage. METHODS: We performed a retrospective study on 112 patients with chronic hepatitis C. For each patient, we considered the baseline alanine aminotransferase (ALT) and serum aspartate transaminase (AST) levels, baseline HCV RNA, HCV genotype, histological evaluation and the mean aminotransferase levels measured in the 6 months following liver biopsy. RESULTS: We found a statistically significant correlation between HCV RNA and aminotransferase levels measured during the follow-up (AST: r = 0.24, P = 0.01; ALT: r = 0.27, P = 0.004). We also observed a statistically significant correlation between HCV RNA levels and histological activity index (HAI) (r = 0.25, P = 0.008), as well as between the HAI and both baseline AST (r = 0.34, P = 0.0002) and ALT levels (r = 0.23, P = 0.01). These findings were confirmed by the mean aminotransferase values during follow-up. In the regression analysis, the fibrosis score was significantly and independently associated with baseline AST and ALT values. CONCLUSIONS: Our results demonstrate a statistically significant correlation of aminotransferase values with the histological parameters, and an even stronger correlation with the AST values. Our study therefore suggests that aminotransferase values, especially AST, may correlate with liver damage.     

Steatosis and bile duct damage in chronic hepatitis C: distribution and relationships in a group of Northern Italian patients

Abstract: Background/Aims: Hepatitis C virus (HCV) related disease follows a long, benign course and most affected patients have mild disease. Liver biopsy is mandatory to grade and stage the disease. Characteristic, though non-specific, HCV histological lesions such as bile duct damage and steatosis have been singled out but their association with non-histological parameters has not been completely defined. Our aim was to study the relationships among these histological lesions and clinical, biochemical, functional and virological characteristics in a group of Northern Italian patients with chronic hepatitis. Methods: We studied 172 patients with HCV-related chronic hepatitis. Patients were divided into groups on the basis of histology including bile duct damage and steatosis. Clinical, biochemical, functional and virological profiles were related to histological findings. Results: Histological grading and staging of disease increased as the age of patients increased. Steatosis was present in 70% of our patients and was related to a higher degree of fibrosis and to decreased functional activity. The prevalence of bile duct damage was 20%. This lesion was present in older patients with higher staging and impaired liver function. Biochemically it was associated with an increase in aspartate aminotransferase, gammaglutamyltranspeptidase, alkaline phosphatase, and total bilirubin. Conclusions: In the population we studied, HCV chronic hepatitis was predominantly a mild disease. Moreover both steatosis and bile duct damage were also mild. Steatosis was associated with fibrosis and this might influence liver metabolic function. Bile duct lesions were found in older patients with advanced disease showing biochemical evidence of cholestasis. The molecular role HCV might play in the pathogenesis of these histological features should be addressed in further studies.     

486例慢性乙型肝炎患者肝组织病理学变化与肝功能指标的相关性研究*

目的 了解慢性乙型肝炎患者常见的肝功能指标与肝组织学之间的关系。方法 在486例慢性乙型肝炎患者,行一秒钟快速肝穿刺活检,对病理标本进行组织炎症活动度分级（G）和纤维化程度分期（S）,并分别与同期检测的血清肝功能指标和患者的性别、年龄等指标进行统计学分析。对非正态分布的计量资料采用Mann-Whitney U检验,对正态分布的计量资料采用t检验,相关分析采用Spearman’s或Pearson’s双侧检验。结果 在486例慢性乙型肝炎患者中,肝组织≥G2者63例（12.96%）,≥S2者231例（47.5%）;248例HBeAg阳性患者的年龄为（32.9±10.5）岁,明显低于238例HBeAg阴性患者[（40.6±9.5）岁,P＜0.05],AKP水平为（88.2±37.1）U/L,明显高于HBeAg阴性患者[（76.4+27.6）U/L,P＜0.05];231例肝组织≥S2组年龄、谷草转氨酶（AST）、碱性磷酸酶（AKP）、γ-谷氨酰转肽酶（GGT）和≥G2比例要明显高于245例相似文献   

Histological features and HLA class II alleles in hepatitis C virus chronically infected patients with persistently normal alanine aminotransferase levels

OBJECTIVE: A significant proportion of individuals with chronic hepatitis C virus (HCV) infection have persistently normal alanine aminotransferase (ALT) levels. Although data are controversial, such patients usually have weaker histological damage and a lower progression rate of fibrosis. The aims of this study were: (1) to compare demographic, virological, and histological parameters of HCV patients with normal ALT values with those of HCV patients with elevated ALT levels; and (2) to determine whether HLA class II alleles contribute to the persistence of normal ALT levels in HCV patients. PATIENTS AND METHODS: Eighty three patients with chronic HCV infection and persistently normal ALT values (group 1) and 233 patients with chronic HCV infection and elevated ALT levels (group 2) were studied. Histological features were expressed using Knodell and Metavir scores. HLA DRB1* and DQB1* genotyping was performed using hybridisation with sequence specific oligonucleotides after genomic amplification. The kappa2 and Fisher's exact tests were used to compare discrete variables and phenotype frequencies between the two groups, and Wilcoxon's test was used for continuous variables. A multivariate logistic regression model was used to determine which variables predicted normal ALT values. RESULTS: ALT levels were correlated with the severity of liver damage. In group 1, 93% of patients had an F0 or F1 Metavir index of fibrosis compared with 47% of patients in group 2 (p<0.001). A longer duration of infection (p<0.001) and increased DRB1*11 phenotype frequency (pc=0.03) were observed among patients with normal ALT. The two groups did not differ with regard to the mode of contamination or viral genotype. After logistic regression, young age (p=0.0008), female sex (p=0.01), long duration of infection (p=0.0001), and HLA DRB1*11 (p=0.050) were more strongly associated with persistence of normal ALT. CONCLUSIONS: Our study confirms that patients with chronic hepatitis C and normal ALT levels have less severe liver disease than those with elevated ALT levels. This particular biochemical outcome may be explained, at least in part, by host immunogenetic factors such as the presence of HLA-DRB1*11.     

Significance of hepatitis C virus coinfection with persistently normal alanine aminotransferase levels in HIV-1-infected patients

ObJECTIVES: To assess the prevalence of chronic hepatitis C virus (HCV) infection with persistently normal alanine aminotransferase (ALT) levels in HIV-1-infected patients, together with its clinical, biological and histological characteristics and predictive factors. METHODS: We retrospectively studied all HCV/HIV-coinfected patients treated in our Infectious Diseases Department, for whom data on both HIV and HCV infection were available. We compared the demographic characteristics and parameters of HIV and HCV infection between cases, defined by persistently normal ALT levels (<45 IU/L) and detectable serum HCV-RNA (determined by PCR), and controls with high ALT levels and HCV PCR positivity during the previous 3 years. RESULTS: Among the 815 HIV-infected patients assessed for this study, 179 (22%) were HCV-coinfected, of whom 155 were eligible for this analysis. Of these 155 HCV-coinfected patients, 137 (88%) were HCV-PCR-positive, of whom 39 (28.5%) had persistently normal ALT levels (cases) and 98 (71.5%) had high ALT levels (controls). Relative to controls, cases had a significantly lower fibrosis score and a lower fibrosis progression rate (2.2 vs. 1.3, P=0.004; 0.3 vs. 0.2, P=0.006, respectively). Three factors associated with persistently normal ALT levels were identified, namely: HBsAg negativity (P=0.003), HCV genotype 4 (P=0.01) and female sex (P=0.05). CONCLUSION: Persistently normal ALT levels may be considered as a marker of slow HCV disease progression in HIV-coinfected patients, with significantly less severe hepatic lesions.     

Clinical significance of activity of ALT enzyme in patients with hepatitis C virus

AIM： TO investigate serum alanine aminotransferase （ALT） levels in relation to the clinical, biochemical, ultrasonographic and histological characteristics of patients with hepatitis C virus.
METHODS： Duration of disease, HCV-RNA, liver steatosis, and the hepatitis activity index （HAI） were correlated with serum ALT in 36 patients with HCV. ALT values were also investigated in 16 control subjects without any liver diseases.
RESULTS： In bivariate analyses, ALT levels correlated with duration of HCV infection （P 〈 0.01）, HCV-RNA （P 〈 0.05）, and the HAI （P 〈 0.01）. Among the components of the HAI, ALT concentrations were significantly associated with periportal bridging/necrosis （P 〈 0.01） and fibrosis （P 〈 0.05）. In multivariate analysis, periportal bridging/ necrosis （β = 0.508; P 〈 0.01）, duration of HCV infection （β = 0.413; P 〈 0.01）, and HCV-RNA （β = 0.253; P 〈 0.05） were independently associated with ALT activity. The normal ALT activity for men and women was 〈 23 IU/L and 〈 22 IU/L, respectively.
CONCLUSION： In patients with HCV, alterations in the liver tissue as reflected by ALT elevation are mainly associated with periportal bridging/necrosis, viral load and duration of disease. A cut-off value 〈 23 IU/L distinguished with high diagnostic accuracy healthy controls from patients with HCV.     

Aspartate aminotransferase (AST) more than alanine aminotransferase (ALT) levels predict the progression of liver fibrosis in chronic HCV infection

The development and severity of liver fibrosis in patients with chronic HCV infection can be evaluated best according to the staging of fibrosis in blind liver biopsy. So far there is however no biochemical indicator suggesting advanced fibrosis or progression of fibrosis in chronic HCV infection. In 1997 - 1999 60 adult out-patients (32 women) with chronic HCV infection were examined by blind liver biopsy. The grading of hepatitis was scored according to Knodell and staging of fibrosis according to Desmet. All patients were anti-HCV positive, assessed by the ELISA-3 method and 48/60 had positive HCV RNA in serum. The main risk factor of HCV infection was blood transfusion (67%). Of 27 examined patients 20 (74%) had serotype HCV 1. Staging of fibrosis: histologically confirmed fibrosis was not recorded in 11 patients (18.3%), mild and medium fibrosis was recorded in 25 (42%), severe fibrosis in 14 (23%) and cirrhosis in 10 (17%). With confirmed fibrosis correlated more closely AST serum activity (p < 0.002) than ALT activity (p < 0.03). Steatosis of the liver was found in 25 (42%) patients. The mean age of patients with steatosis was significantly higher than that of patients without steatosis (p < 0.0008). Steatosis was more frequent in patients with fibrosis (p < 0.04), in particularin the age group above 60 years. The development of fibrosis in patients with chronic HCV infection is suggested by permanently elevated activity of both transaminases whereby AST has a higher predictive value than ALT activity. A total of 40% histologically tested patients had the highest staging of fibrosis (3 - 4). Steatosis is in chronic HCV infection a very frequent finding (42%), in particular in patients above 60 years and those with serious fibrosis. The finding of fibrosis should stimulate the initiation of antiviral treatment which can lead to regression of fibrosis and improvement of the histological finding.     

Clinical, virological, and pathological significance of hepatic bile duct injuries in Chinese patients with chronic hepatitis C

Purpose. Hepatic bile duct injuries are characteristic histological findings in patients with chronic hepatitis C virus (HCV) infection. However, the pathogenesis and clinical significance of this phenomenon remain unclear. The aims of this study were to evaluate the prevalence and clinical significance of hepatic bile duct injuries in Chinese patients with chronic hepatitis C. Methods. One hundred and seventeen Chinese patients with chronic hepatitis C were enrolled. Clinical, biochemical, immunological (serum autoantibodies and cryoglobulinemia), histological, and virological data (serum HCV RNA titer and HCV genotype) were compared between patients with and without hepatic bile duct injuries. Results. Eighty-three (71%) of the 117 patients with chronic hepatitis C had hepatic bile duct injuries. Patients with hepatic bile duct injuries had a significantly higher frequency of HCV genotype 1b; a higher mean serum globulin level; significantly higher mean scores for histological periportal necro-inflammation, portal inflammation, and fibrosis; and more severe portal lymphoid aggregation/follicles when compared with patients without hepatic bile duct injuries (P < 0.05, all). No significant differences in the presence of serum autoantibodies, cryoglobulinemia, mean serum HCV RNA titer, or response to interferon treatment were noted between the two groups. Multivariate logistic regression analysis showed that HCV genotype 1b infection, portal inflammation, and lymphoid aggregation/follicles were significant independent predictors associated with hepatic bile duct injuries. Conclusions. The presence of hepatic bile duct injuries in Chinese patients with chronic hepatitis C was significantly correlated with HCV genotype 1b infection, and the patients with these injuries had more severe portal inflammation and formation of lymphoid aggregates/follicles. Received: September 8, 2000 / Accepted: January 26, 2001     

Comparison of assays for N-amino terminal propeptide of type III procollagen in chronic hepatitis C by using receiver operating characteristic analysis.

OBJECTIVE: During the process of liver fibrosis, type III procollagen is converted to type III collagen by cleavage of its amino terminal and carboxy terminal propeptides. Serum levels of amino terminal propeptide of type III procollagen (PIIINP) are a marker of collagen turnover in liver fibrosis. Two assays for PIIINP are available, one which measures both Col 1-3 (collagen synthesis) and Col 1 (collagen degradation) peptides, and one which measures Col 1-3 only. Using receiver operating characteristic analysis, the two PIIINP assays were compared with serum ALT as markers of liver disease in chronic hepatitis C. METHODS: Serum PIIINP was measured using both assays in 33 patients with chronic hepatitis C and five healthy controls. Liver biopsies in chronic hepatitis C patients were scored using a previously described grading and staging system. RESULTS: Serum PIIINP was significantly elevated in chronic hepatitis C compared to controls using both the combined Col 1-3 and Col 1 (median 0.61 vs 0.33 U/ml, P=0.001) and Col 1 assays (median 6.5 vs 3.5 microg/l, P=0.006). Serum PIIINP measured by the combined assay was significantly related to liver fibrosis, periportal necrosis and histological activity index (P<0.05). The area under the curve for specificity and sensitivity in detecting advanced liver disease was only significant for the combined assay (P=0.017). Serum PIIINP measured by the Col 1 assay was not related to these indices of disease severity while serum ALT was only related to portal inflammation. CONCLUSION: A serum PIIINP assay which measures both Col 1-3 and Col 1 peptides instead of Col 1-3 peptide alone is more predictive of severity of liver disease and should be used in preference as a non-invasive marker of liver injury in chronic hepatitis C.     

Viral kinetics during antiviral therapy in patients with chronic hepatitis C and persistently normal ALT levels

The aim of the present study was to compare viral kinetics between patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels and those with elevated ALT levels. Kinetic parameters were derived from nonlinear, least square fitting of serum hepatitis C virus RNA quantifications collected from patients with chronic hepatitis C and persistently normal (n = 20) and elevated (n = 19) ALT levels before and during treatment with 180 mug pegylated interferon alpha-2a once weekly plus daily ribavirin. Patients with chronic hepatitis C and persistently normal ALT levels showed a trend to lower pretreatment infected cell loss (delta) (P = .13) but no differences in efficacy of blocking virus production (epsilon) and infected cell loss during treatment (mdelta) compared with patients with elevated ALT levels. Differences were significant for epsilon (P = .02) and delta (P = .04) when applying updated "healthy" levels for ALT (0.75 times and 0.63 times upper limit of normal for male and female patients, respectively). A significant reduction of the kinetic parameters epsilon, delta, and mdelta was observed in patients with elevated gamma-glutamyltranspeptidase (GGT) levels compared with patients with normal GGT levels (P = .02, P = .005, and P = .02, respectively). In conclusion, viral kinetics are similar in patients with chronic hepatitis C and persistently normal ALT levels and those with elevated ALT levels. However, in patients with elevated GGT levels, a major association with reduced efficacy of blocking virus production and lower infected cell loss was observed. These data show that virological response in patients with chronic hepatitis C is less associated with baseline ALT than with GGT levels.     

Iron overload in patients with chronic hepatitis C virus infection: clinical and histological study

BACKGROUND: Recently it has been found that iron is an important element in the natural history of hepatitis C. Serum markers of iron stores are frequently increased in chronic hepatitis C virus (HCV)-infected carriers but the real impact of the hepatic iron overload is poorly understood. The purpose of the present paper was to determine the prevalence of iron overload and to study the relationship between hepatic iron concentration (HIC) and clinical, biochemical and histological characteristics in chronic HCV-infected carriers. METHODS: Patients presenting with anti-HCV and HCV-RNA were included. Hepatic iron concentration was determined in liver tissue by atomic absorption spectrophotometry. The association between HIC and age, gender, risk factor of transmission, duration of infection, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, iron and serum ferritin, transferrin saturation, HCV-RNA level, grading of inflammatory activity, staging of fibrosis, hepatic steatosis, and stainable iron was analyzed. Statistical analysis included the Mann-Whitney test and a multiple linear regression model. RESULTS: Ninety-six patients (58% male) with a mean age of 44 +/- 10 years were studied. Serum iron, ferritin and transferrin saturation were elevated in 28%, 27% and 12.5% of patients, respectively. Stainable iron was detected in few patients (15.6%). Higher grades of stainable iron (2 and 3) were observed in only 7%. The HIC (>30 mmol/g dry weight) was elevated in five patients (5%). Neither grading nor staging were related to HIC. Higher HIC were observed in male patients (P < 0.001), in patients with elevated serum ferritin (P = 0.001) and in patients with stainable iron (grades 2 and 3; P = 0.001). Multiple linear regression analysis showed that only stainable iron was independently correlated with HIC (P = 0.003). CONCLUSIONS: Iron overload in chronically HCV-infected patients was uncommon and hepatic iron content seemed not to be related to the liver damage process. In the eventuality of iron overload, histochemical liver iron is a useful marker to estimate HIC.     

Chronic hepatitis C in patients with persistently normal alanine transaminase levels.

BACKGROUND & AIMS: Many patients with chronic hepatitis C virus (HCV) have persistently normal serum alanine transaminase (ALT) levels. We compared characteristics of chronic hepatitis C patients with patients with normal and elevated ALT levels using data from 3 randomized phase III trials of peginterferon alfa-2a (40 kDa). METHODS: The characteristics of 480 patients with normal ALT values (on >or=3 occasions without any increases in ALT level over a 6- to 18-month period) and 1993 patients with elevated ALT levels were compared. Sixty-eight of the 480 patients with normal ALT levels were randomized to no treatment and monitored for 72 weeks. RESULTS: More patients with normal ALT levels than patients with elevated ALT levels were women (59% vs 32%; P<.01). The serum HCV RNA titer was significantly lower in patients with normal ALT levels (P<.01 vs in patients with elevated ALT levels). Patients with normal ALT levels had significantly lower inflammation and fibrosis scores on liver biopsy examination than patients with elevated ALT levels, but almost two-thirds had portal fibrosis and 10% had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA level, and liver histology was observed in patients with normal ALT levels. During the 72-week follow-up period, ALT activity elevated above the upper limit of normal in 53% of the untreated patients with normal levels of ALT. None became HCV RNA undetectable. CONCLUSIONS: Chronic hepatitis C patients with normal ALT levels should be evaluated in a similar manner as patients with elevated ALT levels because they are at risk for developing significant liver disease. The decision to treat with peginterferon alfa and ribavirin should be based on multiple factors, rather than on ALT levels alone.     

血清胆碱酯酶和总胆汁酸与慢性乙型肝炎患者肝脏病理损害的关系探讨

目的探讨血清胆碱酯酶（CHE）、总胆汁酸（TBA）与慢性乙型肝炎肝脏病理损害的关系。方法检测303例经肝穿刺活检病理证实的慢性乙型肝炎患者血清CHE和TBA，并对其与肝活检组织病理炎症分级和纤维化分期进行相关性分析。结果随着肝脏病理炎症分级和纤维化分期的加重，血清CHE逐渐下降，而血清TBA逐渐升高。血清CHE与肝脏病理分级和分期呈显著负相关（P〈0．01），血清TBA与肝脏病理分级和分期呈显著正相关（P〈0．01）。结论临床上联合测定血清CHE和TBA可在一定程度上反映慢性乙型肝炎肝组织病理损伤的程度。     

Histopathological study of chronic hepatitis B and C: a comparison of two scoring systems

BACKGROUND/AIMS: Several histological scoring systems are used to evaluate chronic viral hepatitis. This study was undertaken to determine the correlation between the Ishak system (modified histological activity index, HAI) and the METAVIR system, in Indian patients with chronic viral hepatitis. METHODS: Liver biopsies from 127 patients with chronic viral hepatitis B or C were examined, and scored using the Ishak and METAVIR systems, and weighted kappa analysis of correlation was done. Correlation of necroinflammatory activity with serum transaminase levels was analyzed, and prevalence of specific histological features compared in hepatitis B virus (HBV) and HCV biopsies. RESULTS: HBV infection accounted for 64.6% of cases, and HCV for 35.4%; 91.3% of patients had minimal or mild hepatitis. The necroinflammatory scores of the Ishak and METAVIR systems correlated moderately well (weighted kappa 0.627), while there was excellent correlation with regard to fibrosis (weighted kappa 0.998). Similar concordance was found when HBV and HCV cases were analyzed separately. HAI showed poor correlation with serum transaminases (weighted kappa 0.21). Micronodular cirrhosis, lymphoid aggregates, bile duct damage, bile ductular proliferation and steatosis were significantly more common in HCV biopsies compared to HBV. CONCLUSIONS: Concordance between Ishak and METAVIR scoring systems is good for necroinflammatory change, and excellent for fibrotic change.     

Virological characterization and liver histology in HCV positive subjects with normal and elevated ALT levels

Abstract: We analyzed HCV genotype and RNA titer in 36 chronically infected subjects, 20 with persistently normal or near-normal alanine aminotransferase (ALT) activity and 16 with raised ALT activity. All subjects underwent liver biopsy and evaluation of the histological activity index (HAI) by both Knodell's and Ishak's scoring systems. Genotype 2 was detected in most subjects with normal ALT activity, whereas genotype 1 was more frequent among subjects with raised ALT activity. HCV-RNA titer was higher in subjects with increased ALT. Histological evidence of chronic hepatitis was documented in all cases, but higher scores for grading and for staging were associated with increased ALT activity. HCV genotype had no statistical relationship with RNA titer or with liver histology. In logistic regression analysis, viral genotype, RNA titer and histological scores for grading and staging were correlated independently with the ALT profile. The evidence of chronic hepatitis in all subjects with persistently normal ALT activity suggests that healthy HCV carriage is a rare event.     

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.     

Endotoxin receptor CD14 gene variants and histological features in chronic HCV infection

AIM： To analyze the correlation between CD14 rs2569190/C-159T single nucleotide polymorphism （SNP） and disease progression in chronic hepatitis C. METHODS： Liver biopsy specimens from a total of 137 and 349 patients with chronic hepatitis C were separately evaluated with respect to necroinflammatory activity （grading） and architectural changes （staging）. In one group, further histological lesions characteristic for hepatitis C, hepatitis C virus subtypes, and biochemical parameters of liver disease were also investigated. Samples of genomic DNA were genotyped for the respective SNP by 5＇-nuclease assays using fluorescent dye-labeled allele-specific probes. RESULTS： Genotype distribution did not deviate from the Hardy-Weinberg equilibrium. In the first group, patients homozygous for the variant allele T were found to be younger than C allele carriers （39.6 ±12.5 vs 45.7 ± 11.5, P = 0.008）. Among the histological lesions studied, portal lymphoid aggregates were more frequently observed among TT homozygotes than among C carriers （21/37 vs 32/100, P = 0.008）. The presence of portal lymphoid aggregates was closely correlated with hepatic inflammation （P = 0.003） and with bile duct damage （P 〈 0.001）. The degree of fibrosis, in contrast, was not found to be related to the CD14 gene C-159T polymorphism.CONCLUSION： The data suggest a possible relationship between CD14 C-159T polymorphism and the formation of portal lymphoid aggregates, but not liver fibrosis progression in chronic hepatitis C.