Hepatitis C infection in Alaska Natives with persistently normal, persistently elevated or fluctuating alanine aminotransferase levels.

BACKGROUND/AIMS: An estimated one-third of patients with chronic hepatitis C virus (HCV) infection have persistently normal alanine transaminase (PNALT); however, in many previous studies alanine aminotransferase (ALT) levels were followed for < or = 12 months. METHODS: We analyzed data from a population-based cohort of 935 Alaska Natives with HCV, recruited from 1994 to 2005, to determine the proportion of persons with PNALT, persistently elevated ALT (PEALT), and fluctuating ALT (FLUXALT) to determine factors for each ALT state. We selected persons with two positive HCV RNA results > or = 1 year apart and > or = 6 ALT levels measured over the subsequent 3 years with at least 1 month between ALT measurements (n = 265). We defined a person as having PNALT, PEALT, or FLUXALT when all six ALT levels were normal, elevated, or did not fit either of the above two categories, respectively, during the 3-year follow-up period. RESULTS: Among 208 persistently HCV RNA-positive persons, 13 had PNALT, 121 PEALT, 74 FLUXALT. Among 77 persons who underwent liver biopsy, those with PEALT were more likely to have Ishak fibrosis scores > 2 compared with persons with FLUXALT (44% vs. 10%, OR 7.0, 95% CI: 1.5-33.2). No statistically significant differences were found in ALT classification by age, gender, infection duration, median body mass index, alcohol consumption, residence, risk behavior, RNA level, or genotype. CONCLUSIONS: Only 6% of persons with chronic HCV had PNALT. Persons with PEALT were significantly more likely to have higher fibrosis scores on liver biopsy than those with FLUXALT. Previous studies with short follow-up periods may have overestimated the proportion of persons with normal ALT levels.     

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.     

A 24-week course of high-dose interferon-alpha plus ribavirin for Taiwanese chronic hepatitis C patients with persistently normal or near-normal alanine aminotransferase levels.

BACKGROUND/AIMS: We aimed to evaluate the efficacy, advantage, and safety of a 24-week regimen with high-dose interferon-alpha (INF-alpha; 6 million units thrice weekly) plus ribavirin (1000-1200 mg/day) combination therapy for 46 Taiwanese chronic hepatitis C (CHC) patients with persistently normal or near-normal alanine aminotransferase (PNALT) levels. METHODS: Ninety-two age- and sex-matched CHC patients with elevated ALT levels (> 2 times the upper limit of normal range) with a ratio of 1:2, treated with the same regimen, served as a control. RESULTS: The sustained virologic response (SVR) rate was comparable between PNALT (67.4%) and elevated ALT (65.2%) groups (intention-to-treat analysis). The two groups had similar rates of discontinuation and incidence of adverse effects. Viral genotype 1b, baseline viral loads, body mass index, and age were significant factors negatively associated with SVR. Further decline of ALT levels throughout the follow-up period was observed in sustained responders of the PNALT group. None of the eight patients with ALT flares developed icteric hepatitis. The virologic efficacy was sustained in a 3-year extended follow-up period. CONCLUSION: high-dose INF-alpha with ribavirin combination therapy is effective, safe, and well tolerated in CHC patients with PNALT levels. The ALT assay might not be used as a single biochemical marker for determination of treatment consideration.     

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.     

Clinical features of hepatitis C virus carriers with persistently normal alanine aminotransferase levels

Hepatitis C virus (HCV) infection causes chronic hepatitis, which frequently leads to hepatic fibrosis and hepatocellular carcinoma (HCC). Alanine aminotransferase (ALT) is a biomarker of hepatocyte injury and is associated with the progression of hepatic fibrosis. Advanced hepatic fibrosis also predisposes HCV carriers to a risk of HCC. In contrast, some cases with persistent HCV infection have normal ALT levels that persist for a long time, and these HCV carriers have no or mild hepatitis and hepatic fibrosis. These HCV carriers are defined as persistent normal ALT (PNALT) cases and their risk of HCC is low compared to HCV carriers with abnormal ALT. However, there are various definitions of normal ALT and PNALT, and advanced hepatic fibrosis may be missed without a liver biopsy. In addition, there is also a risk of ALT elevation in HCV carriers with PNALT, which increases the risk of progression to hepatic fibrosis and HCC. Most HCV carriers with PNALT have asymptomatic or nonspecific symptoms. HCV carriers with PNALT are also considered to be responsive to interferon-based treatment. Thus, assessment of hepatic fibrosis is important in HCV carriers, and the eradication of HCV infection is more likely in HCV carriers with evidence of hepatic fibrosis, regardless of their ALT levels.     

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.     

Hepatocellular proliferation in patients with chronic hepatitis C and persistently normal or abnormal aminotransferase levels

BACKGROUND/AIMS: Some patients chronically infected with the hepatitis C virus (HCV) have persistently normal alanine aminotransferase (ALT) levels while progressive liver damage is observed histologically. In the present study, we compared the rate of proliferation, apoptosis, and necrosis in liver biopsy specimens of patients with persistently normal or elevated ALT levels. METHODS: Fourteen patients with persistently normal and 14 age- and sex-matched patients with elevated ALT levels were enrolled. Proliferation was detected using anti-Ki 67 in 10-microm liver biopsy specimens of the patients. Apoptosis was measured by TUNEL-assay and by monoclonal anti-M30 directed against caspase-cleaved cytokeratin 18 filaments. RESULTS: The mean number of anti-Ki 67 positive hepatocytes was lower in patients with persistently normal aminotransferases (3.1 +/- 2.8/10(3) vs 10.8 +/- 8.8/10(3) hepatocytes, p<0.0011) and was correlated with serum ALT (r=0.86, p<0.01) and aspartate aminotransferase levels (r=0.83, p<0.01). The rate of apoptosis detected by TUNEL assay was low and not different between patients with persistently normal and elevated aminotransferases. Staining with anti-M30 revealed a granular staining pattern and showed a trend towards higher cell death rates in patients with elevated aminotransferase levels (apoptotic hepatocytes with >75% staining: 3.97 +/- 6.24/10(3) hepatocytes vs 13.65 +/- 19.41/10(3) hepatocytes; p=0.08). CONCLUSIONS: Patients with chronic hepatitis C and normal aminotransferases have significantly lower hepatocyte proliferation rates and show a trend towards lower apoptosis rates compared with patients with elevated aminotransferases.     

Intrahepatic and peripheral T-cell responses in genotype 1b hepatitis C virus-infected patients with persistently normal and elevated aminotransferase levels

AIM: To evaluate whether the cytokine responses in liver and serum differ in chronic hepatitis C patients with normal and high alanine aminotransferase (ALT) levels. METHODS: Thirty-three (16 with normal ALT level as group 1 and 17 with elevated ALT level as group 2) patients infected with genotype 1b hepatitis C virus (HCV) were examined. Liver infiltrating lymphomononuclear cells (LILMCs) were isolated from liver biopsy by collagenase type 1 and stimulated with phytohemagglutinin and interleukin 2 (IL-2). IL-10, IL-12, interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) were determined in serum and LILMCs by ELISA. RESULTS: Serum cytokine levels were similar in both groups (P>0.05). Stimulated IFN-γ and TNF-α levels in LILMCs were increased in both groups. IL-12 and IL-10 levels stimulated with IL-2 were higher in group 1 than in group 2 (P = 0.023). Histological activity index (HAI) and stage had a negative correlation with TNF-α and IFN-γ levels in group 2. CONCLUSION: Increased T-helper type 2 (Th2) cytokine response may regress inflammatory and biochemical activity. Progression of histological abnormalities in persons with elevated ALT probably depends on insufficient Th2 cytokine response, which does not balance Th1 cytokine response.     

Impaired health-related quality of life in patients with chronic hepatitis C and persistently normal aminotransferase levels

A significant impact of hepatitis C virus (HCV) infection on health-related quality of life (HRQOL) has been previously described. However, comprehensive data on the quality of life in patients with chronic hepatitis C and persistently normal aminotransferase levels (PNAL) are currently not available. One hundred fifteen patients with chronic hepatitis C (45 with persistently normal aminotransferases and 70 with elevated aminotransferases) and 50 healthy subjects were enrolled. Emotional and psychological states were assessed by Profile of Mood States (POMS) scale and HRQOL was assessed by the 'Everyday Life' questionnaire (EDLQ), a validated questionnaire related to the SF-36 Health Survey. An impairment in HRQOL was observed in patients with chronic hepatitis C showing PNAL compared with healthy subjects with significant differences for the factor scores depression and anger in the POMS scale as well as for the items body, relationship to partner, self-confidence and zest of life in the EDLQ. No differences in any questionnaire were observed between patients with chronic hepatitis C showing PNAL or elevated aminotransferase levels except of a worse mean level for factor score anger in POMS scale in patients with persistently normal aminotransferases. No association of quality of life with severity of liver disease was found. Impairment of HRQOL by chronic infection with HCV is similar in patients with PNAL and those with elevated aminotransferase levels.     

Alanine aminotransferase flare-up in hepatitis C virus carriers with persistently normal alanine aminotransferase levels in a hyperendemic area of Japan

Background The clinical features of hepatitis C virus (HCV) carriers with persistently normal alanine aminotransferase (PNALT) levels (ALT ≤ 34 IU/l) have not been fully elucidated. We investigated clinical factors associated with ALT flare-up in PNALT individuals in a HCV hyperendemic area of Japan. Methods We analyzed 101 HCV carriers who had PNALT between 1993 and 2000. The first occurrence of ALT flare-up (ALT ≥ 35 IU/l) between 2001 and 2005 was evaluated by the Kaplan-Meier method. Multivariate analysis of factors predicting ALT flare-up were conducted using Cox proportional hazards models. Results The mean follow-up period was 2.8 years, and the 5-year cumulative incidence of ALT flare-up was estimated to be 31.8%. In multivariate analysis, an ALT level of 20–34 IU/l and a high serum ferritin level (≥90 ng/ml) in the most recently available data up to the year 2000, as well as H63D heterozygosity in the HFE gene, were independently and strongly associated with the incidence of ALT flare-up (Hazard ratios = 5.6, 3.1, and 4.8, respectively). In addition, HFE H63D heterozygosity was significantly associated with higher serum ferritin levels in subjects with PNALT (153.8 ± 73.3 ng/ml in subjects with the 63HD genotype vs. 89.4 ± 51.3 ng/ml in subjects with the 63HH genotype, P = 0.043). Conclusions HCV carriers with PNALT in this population were at risk for ALT flare-up. Basal ALT levels, serum ferritin levels, and HFE polymorphism are potentially important predictors of ALT flare-up.     

丙氨酸转氨酶持续正常的HBeAg阴性慢性乙型肝炎病毒感染者肝脏组织学改变及其影响因素

目的 分析ALT持续正常的HBeAg阴性慢性HBV感染者的肝脏组织学改变及其影响因素.方法 选择2003年10月至2008年3月经皮肝组织活检的ALT持续正常的HBeAg阴性慢性HBV感染者98例,检测其ALT水平、HBV标志物、HBV DNA水平和肝脏组织学改变.均数比较采用t检验和单因素方差分析,非参数统计采用Mann-Whitney U检验和Kruskal-Wallis检验.采用Logistic模型进行独立危险因素分析,采用受试者工作特征曲线评价ALT水平对显著肝脏病理改变的诊断价值.结果 98例患者中炎症活动指数(Hal)≥4、纤维化(F)评分≥3的患者分别占22.4%与17.3%.ALT为(0.51～1.00)×正常值上限(ULN)组发生上述病理改变的比例均高于(0～0.50)×ULN组(HAI≥4:36.4%比11.1%,χ2=8.881,P=0.003;F评分≥3:27.3%比9.3%,χ2=5.487,P=0.019).年龄每增长10岁是HAI≥4分的独立危险因素(OR=2.410,P=0.023);年龄>45岁者发生HAI≥4分的比例明显高于≤45岁者(33.3%比13.4%,χ2=4.923,P=0.027).HBV DNA＜1×104拷贝/mL时,仍有14.9%的患者Hal≥4分、12.8%的患者F评分≥3分.结论 部分ALT持续正常的HBeAg阴性慢性HBV感染者在不同HBV DNA水平存在一定程度的肝脏病理改变,肝组织活检对于年龄＞45岁的患者是十分重要的.0.50×ULN有望为中国HBeAg阴性的慢性HBV感染者的临床处理提供一个恰当的ALT"正常"参考值.     

Hepatitis C virus carriers with persistently normal aminotransferase levels: healthy people or true patients?

Since the discovery of hepatitis C virus, the availability of serological hepatitis C virus screening has led to the identification of many subjects with normal aminotransferase levels who are chronically infected by the hepatitis C virus. To date, the epidemiology and natural history of subjects with normal aminotransferase levels are far from being clarified. Further, whether subjects with persistently normal aminotransferase levels should routinely undergo liver biopsy is still extremely controversial, and benefit from interferon treatment in this group of patients is yet to be proven. On account of the consistent normality of aminotransferases, it is not easy to calculate the rate of persons with normal aminotransferase levels among chronic hepatitis C virus carriers, nor their prevalence in the general population. It has been estimated that up to 25% of patients with chronic hepatitis C virus infection have persistently normal aminotransferase levels (10% to 40%, according to different studies). Most studies showed a clear prevalence of females, ranging from 58% to 90%. Liver biopsy shows some degree of chronic liver disease in up to 80% of these subjects, although in the majority, histological damage is mild and probably does not progress to more severe liver disease, moreover, the progression to fibrosis is slower than in patients with elevated aminotransferase levels. Virological features of these subjects (hepatitis C virus genotype distribution, viral load, quasispecies diversity) do not differ with respect to patients with elevated aminotransferase levels although a higher frequency of non 1 hepatitis C virus types has been reported. To date, no biochemical or virological tools to assess the presence and severity of liver damage exist. Antiviral treatment with interferon may induce a long-term response in only a small proportion of hepatitis C virus carriers with persistently normal aminotransferase levels, and many patients develop aminotransferase-flare-up during or shortly after treatment. Thus, interferon or combination antiviral treatment of hepatitis C virus carriers with normal aminotransferase values should be avoided in clinical practice.     

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.     

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.     

IL-28B polymorphisms and treatment response in hepatitis C virus patients with persistently normal alanine aminotransferase

AIM: To examine the association between the interleukin 28B (IL-28B) genotype and treatment response in hepatitis C virus (HCV)-infected patients with persistently normal alanine aminotransferase (PNALT).METHODS: We compared the treatment response of HCV-infected patients with PNALT to that of patients with non-PNALT. Between February 2010 and April 2013, 278 patients infected with HCV were enrolled in this study. All of the patients were treated with peginterferon-alpha 2a or 2b plus ribavirin. In addition, 180 μg of peginterferon alpha-2a or 1.5 μg/kg peginterferon alpha-2b per week plus weight-based ribavirin (600-1000 mg/d) were typically administered for 24 wk to HCV genotype 2-infected patients or for 48-72 wk to HCV genotype 1-infected patients. In all of the patients, the IL-28B rs8099917 genotype was determined using a TaqMan single-nucleotide polymorphism assay. HCV RNA was measured using the COBAS TaqMan HCV test.RESULTS: Female patients were dominant in the PNALT group (P < 0.0001). Among 72 HCV genotype 1-infected patients with PNALT, the early virologic response (EVR) rates (P < 0.01) and the sustained virologic response (SVR) rates (P < 0.01) were higher in patients with the IL-28B TT genotype than in those with the IL-28B TG/GG genotype. In HCV genotype 1-infected patients with PNALT, multivariate logistic-regression analysis showed that SVR was independently predicted by the IL-28B rs8099917 TT type (P < 0.05) and having an EVR (P < 0.01). The IL-28B rs8099917 TT genotype strongly correlated with treatment response in HCV genotype 1-infected Asian patients with PNALT.CONCLUSION: The IL-28B genotype may be useful for selecting HCV genotype 1-infected patients with PNALT who should receive interferon-based treatment.     

Natural history of hepatitis C virus carriers with persistently normal aminotransferase levels

BACKGROUND & AIMS: Some patients with serum hepatitis C virus (HCV) have persistently normal aminotransferase (ALT) levels and are affected by cirrhosis. This study prospectively evaluated progression of the disease in a group of anti-HCV-positive patients with persistently normal ALT levels. METHODS: Thirty-seven subjects were studied. Each subject underwent liver biopsy at baseline and after 5 years of follow-up. At baseline, serum samples were tested for genotypes and HCV RNA load. ALT levels and serum HCV RNA were tested every other month and every 6 months, respectively. Patients with increased ALT were discharged from the study and treated with IFN. Five years after the end of IFN therapy, a liver biopsy was performed. RESULTS: Liver biopsy at baseline showed chronic hepatitis in 34 patients and normal histology in 3 patients, 2 of whom were negative for HCV RNA and 1 positive. HCV genotypes were distributed as follows: 2a, 56%; 1b, 41%; and 1a, 3%. At the end of 7-year follow-up, 73% of the patients still had normal ALT values. Liver histology after 5 years was comparable to that observed at entry to study. CONCLUSIONS: Most patients with persistently normal ALT serum levels have very mild chronic hepatitis. However, healthy anti-HCV-positive subjects exist. In patients with HCV-related chronic hepatitis associated with persistently normal ALT levels, the grade of disease activity does not increase over years and progression to cirrhosis is slow or absent.     

关注丙氨酸氨基转移酶水平正常的慢性乙型肝炎病毒感染者

血清ALT水平升高是存在组织坏死性炎症活动的标志之一,因此ALT水平正常一般被认为预示着肝脏组织正常或肝损害处于组织学静止状态.