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.     

Natural history of initially mild chronic hepatitis C

The hepatitis C virus is a leading cause of chronic liver disease, cirrhosis and hepatocellular carcinoma in western countries. Chronic hepatitis C is highly heterogeneous and many patients present with a mild form of liver disease. Population-based studies have indeed demonstrated that around 50% of hepatitis C virus carriers have persistently normal ALT and two-third have mild histological liver lesions. Studies on the natural history of initially mild chronic disease indicate that the short-term outcome is always benign. However, progression of liver fibrosis can be observed at long-term (>5-7 years) follow-up, particularly in those cases who have elevated and/or fluctuating transaminase levels. Observational prospective studies and outcome modelling projections indicate that the risk of liver disease progression towards severe fibrosis/cirrhosis is minimal at 10-15 years in hepatitis C virus carriers with persistently normal ALT, around 5-10% in patients with elevated ALT and F0 (no fibrosis) in the initial biopsy but >30-40% in chronic carriers with elevated ALT and F1 (portal fibrosis) in the initial biopsy. Cofactors like age at infection, alcohol, coinfections and liver steatosis accelerate disease progression. On the basis of these findings, patients with initially mild chronic hepatitis C and elevated ALT should be proposed for antiviral therapy in the absence of contraindications.     

Pathological and virological findings in patients with persistent hypertransaminasaemia of unknown aetiology

BACKGROUND: The histopathological spectrum and role of hepatitis viruses in cases of hypertransaminasaemia of unknown aetiology have not been correctly analysed in a sufficiently large number of patients. METHODS: We studied 1075 consecutive patients referred for liver biopsy because of elevation of alanine aminotransferase (ALT) levels for more than six months. From this population we selected those cases in whom the aetiology could not be defined from clinical, biochemical, and serological data obtained before biopsy. In these patients liver biopsies were reviewed, and hepatitis B virus (HBV)-DNA and hepatitis C virus (HCV)-RNA were assayed in serum by polymerase chain reaction (PCR). Serum hepatitis G virus (HGV)-RNA was determined by PCR in 74 patients. RESULTS: Of 1075 patients studied, the cause of the increased serum ALT levels remained elusive after appropriate testing in 109 patients (10.1%). Liver biopsies from these patients showed non-specific changes in 32.7% of cases, non-alcoholic steatohepatitis (NASH) in 15.8%, and chronic hepatitis or cirrhosis in 51.5%. HBV-DNA and/or HCV-RNA was detected more frequently in cryptogenic liver disease than in healthy blood donors (26.7% v 3.4%; p<0.001). HGV-RNA was found in only one patient. The proportion of cases with detectable HBV-DNA or HCV-RNA was 14.3% in patients with non-specific changes or NASH, 30.7% in patients with chronic hepatitis, and 61.5% in patients with cirrhosis. Cirrhosis was found more frequently in patients with positive HBV-DNA and/or HCV-RNA in serum than in those who tested negatively (p=0.005). CONCLUSIONS: In our series, patients in whom biochemical and serological data did not determine the aetiology of the disease represented 10% of all cases referred for liver biopsy for persistent elevation of serum transaminases. Approximately 50% of patients had chronic hepatitis or cirrhosis and the remainder had NASH or non-specific changes. Occult viral infections were found in a high proportion of cases in the first group and in a low percentage of patients in the second.     

Stability of HCV-RNA level and its lack of correlation with disease severity in asymptomatic chronic hepatitis C virus carriers

This study examines the relationship between HCV-RNA levels and disease severity in 60 individuals with chronic hepatitis C virus infection. HCV-RNA levels were quantified by the branched DNA (bDNA) assay in 445 samples (median: eight samples per patient) obtained over a median of 40.4 months (95% confidence interval (CI): 37.0–42.5). The median log HCV-RNA level was 6.77 (95% CI: 6.62–6.92) molecular equivalents/mL (MEQ/mL). The median log range of HCV-RNA levels in individual patients over the course of the study was 0.89 (95% CI: 0.69–1.16). HCV-RNA level varied over time by less than one log in 62% of patients, by 1–1.5 logs in 22% and by greater than 1.5 logs in only 17%. Univariate analysis, revealed an inverse association between HCV-RNA levels and ALT levels ( P =0.037). Univariate and logistic regression analysis showed no significant association between HCV-RNA levels and either the degree of inflammation or fibrosis. In contrast, there was a significant positive association between alanine aminotransferase (ALT) levels and histological activity especially in individuals with ALTs>  100 IU/L. Hence, HCV-RNA levels: (i) almost always fell within the dynamic range of the bDNA assay; (ii) were stable in asymptomatic chronically infected patients, with only a small proportion of patients exceeding a range of 1.5 logs; (iii) did not correlate with either the extent of inflammation or degree of fibrosis. In contrast, there was a strong association between ALT level and the histological severity of liver disease.     

Persistently normal alanine transaminase levels in chronic C hepatitis: what does it tell us?

BACKGROUND/AIMS: We evaluated the demographic, clinical, histological and serological characteristics of chronic hepatitis C infection with persistently normal serum alanine transaminase levels and compared the results with those obtained in a group of chronic hepatitis C infection with serum alanine transaminase levels above normal. METHODOLOGY: Twenty-one patients who had chronic hepatitis C infection with normal alanine transaminase during the follow-up period and 34 patients who had chronic C infection with serum alanine transaminase levels above normal were included in this study. Demographic, clinical, histological and serological parameters of these two groups were evaluated. RESULTS: There were no significant differences in age, gender, known route of infection, viral load and genotype distribution between the two groups (P > 0.05). The gamma-glutamyltransferase and gamma-globulin levels were significantly higher in the serum alanine transaminase levels above normal group (P < 0.01 and P < 0.05). Among the patients with normal alanine transaminase, liver biopsy findings were normal in eight patients (38%). None of the patients with serum alanine transaminase levels above normal had normal liver biopsy findings. Histologic activity index was significantly higher in serum alanine transaminase levels above normal group (9.7 +/- 2.2 vs. 6.4 +/- 1.9; P < 0.001). Histologic activity index and alanine transaminase levels correlate with the stage of the disease (P < 0.05). CONCLUSIONS: For a definite diagnosis in patients with HCV-RNA+ and normal alanine transaminase liver biopsy is necessary and significant liver disease may be present in such patients irrespective of viral load, genotype and alanine transaminase levels.     

CASE REPORT: Alanine aminotransferase deficiency detected in a patient with chronic hepatitis C

We report a case of alanine aminotransferase (ALT) deficiency in a 68-year-old Japanese female with chronic hepatitis C. The serum was positive for antibody to hepatitis C virus (HCV) and HCV-RNA. Liver biopsy showed histological evidence of chronic active hepatitis. The level of serum aspartate aminotransferase (sAST) was elevated, but sALT was extremely low. The patient was followed up for her serum aminotransferase levels for 1.5 years under the treatment with ursodeoxycholic acid. The low sALT level persisted during all the follow-up period. The ALT activity in liver tissue was also decreased. Based on these findings, ALT deficiency was suspected. sALT activity was also found to be low in her two sons. This latter finding suggests the hereditary character of this abnormality.     

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.     

Hepatitis C in injecting drug-using women during and after pregnancy

BACKGROUND: A high proportion of female injecting drug users (IDU) have evidence of hepatitis C virus (HCV) infection. We undertook a prospective study of patients attending a clinic for pregnant IDU to determine the impact of pregnancy on the course of HCV infection and whether pregnancy is affected by HCV infection. METHODS: One hundred and thirty-one IDU were recruited and followed up with liver function tests, HCV serology and HCV-RNA tests. RESULTS: Of 131 patients, 125 had HCV antibodies (anti-HCV positive) at delivery, and of these 62% were HCV-RNA positive. The anti-HCV-negative women were younger and had a shorter duration of drug use than the anti-HCV-positive women. There were no differences between viraemic and non-viraemic women with respect to age, ethnicity, duration of injecting drug use, methadone maintenance dose, hepatitis B exposure or reported high-risk behaviour. Alanine aminotransferase (ALT) levels were higher and the proportion with ALT > 55 IU/L higher in viraemic women. Viraemia persisted in all 55 women who were viraemic at term. Eleven had an ALT flare post-partum that was unrelated to viral load and was clinically unsuspected. Four had concurrent elevated gamma-glutamyltranspeptidase and were considered to be drinking alcohol at hazardous levels. Four of 23 women who were HCV-RNA negative at term became positive during follow up. CONCLUSIONS: Pregnancy does not adversely affect the course of hepatitis C. A modest rebound in ALT levels, but not HCV-RNA, occurs after delivery in some viraemic women. This supports the theory that immune mechanisms rather than direct viral cytopathology are involved in hepatocyte injury during HCV infection. Hepatitis C infection did not influence pregnancy complications and outcomes.     

Long-term histological prognosis and serum fibrosis markers in chronic hepatitis C patients treated with interferon

BACKGROUND: Interferon (IFN) therapy is effective in 20-40% of patients with chronic hepatitis C, but the relationship between histological changes and the response to interferon is still unclear. We investigated the long-term histological prognosis and the changes of serum fibrosis markers after interferon therapy relation to the response. METHODS AND RESULTS: One hundred and eighteen patients with chronic hepatitis C who received interferon therapy were divided into four groups based on the detection of viremia and the serum alanine aminotransferase (ALT) level after treatment. A histological examination was performed by using the histological activity index and the criteria of the METAVIR score. Serum fibrosis markers were used to measure the levels of hyaluronic acid and type IV collagen 7s. Responders, whose serum ALT levels became normal after treatment, demonstrated histological improvement. Histological improvement was more rapid in sustained virological responders with hepatitis C virus (HCV) RNA seronegativity than in biochemical responders with HCV-RNA seropositivity. Only sustained virological responders exhibited histological cure. In partial responders, whose serum ALT levels decreased to less than twice the upper of normal, and non-responders whose serum ALT levels were not reduced, liver fibrosis was unchanged or showed progression. Serum fibrosis markers increased with progression of the histological stage and varied depending on the response to interferon. CONCLUSION: Normalization of serum ALT levels after interferon therapy led to a histological improvement, and that with viral clearance achieved histological cure. Serum fibrosis markers were useful indicators for long-term according to the response of IFN therapy.     

Interferon monotherapy for patients with chronic hepatitis C and normal serum aminotransferase levels at commencement of treatment

Background Approximately 30% of patients with chronic hepatitis C have normal serum alanine amino transferase (ALT) levels. While interferon (IFN) monotherapy is approved for patients with chronic hepatitis C infection, the effectiveness of such therapy for chronic hepatitis C patients with normal ALT levels at commencement of treatment remains poorly understood.Methods Ninety-four individuals (M/F, 54:40; median age, 46 years) with normal ALT levels (<50IU/l) at the commencement of treatment who were positive for both anti-hepatitis C virus (HCV) and serum HCV-RNA were studied. Among this group, 18 individuals (M/F, 9:9; median age, 50 years) had had persistently normal ALT levels for at least 3 months prior to treatment. All patients received their first course of IFN therapy in this study.Results Forty-three (45.7%) of 94 individuals had lost serum HCV-RNA at 6 months after cessation of therapy (complete response; CR). The proportion of patients with genotype 2a and HCV-RNA level over 1Meq/ml who showed CR was significantly lower in those with normal ALT levels than in those with elevated ALT levels (23.8% vs 55.6%; P = 0.0189). Two patients who had persistently normal ALT levels and HCV-RNA level over 1Meq/ml were nonresponders (NR) and had ALT flare-ups after IFN therapy. Patients with HCV-RNA levels of less than 1Meq/ml did not show differential responses based on ALT levels.Conclusions Our data suggest that IFN therapy is effective for patients with normal ALT levels and less than 1Meq/ml HCV-RNA. Thus, such patients should be considered for curative IFN therapy.     

Hepatitis C virus prevalence and outcomes among injecting drug users on opioid replacement therapy

OBJECTIVES: To determine hepatitis C virus (HCV) prevalence among injecting drug users (IDUs) receiving opioid replacement therapy in a referred office setting, and assess potential needs for hepatitis C treatment and care. METHODS: Data were collected on 178 IDUs receiving opioid replacement therapy who underwent clinical assessment between January 2002 and June 2003. Standard clinic protocols included HCV and hepatitis B virus (HBV) serology, liver biochemistry and HCV RNA analysis for patients with a positive HCV antibody and normal alanine aminotransferase (ALT) levels. RESULTS: HCV prevalence was 75.3%, similar for males (75.5%) and females (74.4%), and increased with age from 60.8% for 19-30 years to 93.9% above 40 years. Among patients with HCV antibodies and no prior HCV antiviral therapy (n = 130), 53.1% had normal ALT levels and 25.4% were HCV-RNA negative. Older patients were more likely to have normal ALT levels (P = 0.02), and be HCV-RNA negative (P = 0.02). Younger patients were more likely to have been HBV vaccinated (P < 0.001), however, were less likely to have either vaccine or natural immunity (P = 0.006). Of 97 patients with probable chronic HCV infection, 58 patients met pre-liver biopsy criteria for HCV treatment, 34 had relative contraindications to treatment and 6 had been referred for treatment assessment. CONCLUSION: Clinical characterization in a setting of high HCV prevalence has enabled the differentiation of patients into groups with no evidence of HCV viraemia, with chronic HCV infection, and those most appropriate for HCV treatment referral. These clinical assessments along with appropriate referral should be instituted in drug dependency treatment settings.     

Characteristics of chronic hepatitis B patients who underwent liver biopsies

Summary. Significant liver disease has been reported in chronic hepatitis B patients with normal alanine aminotransferase (ALT) but most studies performed biopsies on selected patients only. The aims of this study were to determine the rate of liver biopsy, characteristics of patients who underwent a biopsy and factors associated with significant liver disease in a cohort of such patients. Records of patients with chronic hepatitis B during a 10‐year period were reviewed. Significant liver disease was defined as Knodell HAI ≥ 7 and/or Ishak fibrosis ≥ 3. Of 743 patients, 55.7% were Asian, 56.4% were men, and the mean age was 43.1 years. One hundred and ninety‐three (26%) had undergone a biopsy. Biopsied patients were more likely to be men, HBeAg positive, and had lower platelet and higher alkaline phosphatase, bilirubin, ALT and hepatitis B virus (HBV) DNA. Significant liver disease was observed in 20% of patients who had normal ALT at presentation, 14% of those with normal ALT at the time of biopsy and in none of the patients with persistently normal ALT. Patients with normal ALT who were biopsied had higher HBV DNA and higher ALT than those not biopsied. Multivariate analysis showed that low albumin at the time of biopsy and HBV DNA >5 log₁₀ copies/mL were predictors of significant liver disease. Significant liver disease is rare in patients with chronic HBV and persistently normal ALT and liver histology of chronic HBV infected patients with normal ALT cannot be generalized to other patients with normal ALT that were not biopsied.     

Circulating HCV-RNA,HCV genotype,and liver histology in asymptomatic individuals reactive for anti-HCV antibody and their follow-up study

Abstract: The present study was aimed to clarify the virologic status, liver histologies, and the results of follow-up liver tests in symptom-free individuals with anti-HCV antibodies and normal liver tests. Forty-nine individuals with normal liver tests and positive second generation anti-HCV antibody assay were entered into this study. Cases with hepatitis C viremia were evaluated for HCV genotype, amount of circulating HCV-RNA, and liver histology and were followed-up for more than one year. Of the forty-nine individuals, 36 had hepatitis C viremia, indicated by polymerase chain reaction (PCR) assay. Liver histology was as follows: 3 had non-specific changes, 25 had chronic persistent hepatitis (CPH), and 8 had chronic active hepatitis (CAH). Twenty-four cases with CPH and CAH developed an elevated AST and/or ALT concentration (> 30IU/1) between 12 and 32 months of follow-up. The amount of circulating HCV-RNA ranged from 10² to 10⁷ copies/50 μl serum. The distribution of HCV genotypes was nearly the same as that for symptomatic CAH. These data suggest that the histological examination and follow-up examination are very important for following symptom-free individuals with hepatitis C viremia because there are some candidates for interferon therapy among them. There are few individuals who will remain healthy among asymptomatic HCV carriers.     

Possible mechanisms of elevation of serum transaminase levels during interferon-β therapy in chronic hepatitis C patients

Background. Serum transaminase levels are frequently elevated in patients with chronic hepatitis C who are receiving interferon (IFN)-β therapy, despite hepatitis C virus (HCV)-RNA being eradicated from the serum. We examined liver histology to determine the reason for this elevation. Methods. Patients with chronic hepatitis C, diagnosed by liver histology and positive serum HCV-RNA, were given intravenous injections of IFN-β, at a daily dose of 6 MU, every day for periods of 6 to 12 weeks. When serum alanine transaminase (ALT) levels during the therapy were higher than three times the levels before the therapy, liver biopsy was performed. Histological findings on light microscopy were compared in liver biopsy specimens obtained before and during the therapy. Results. An increase in serum ALT levels was found in 19 of the 102 patients who received the IFN-β therapy. Autoimmune hepatitis was not contributory in any of these 19 patients, because serum antinuclear antigen was negative and IgG levels were not increased. Liver histology was examined in 10 of these 19 patients. The period between the start of IFN-β therapy and the biopsy during the therapy ranged from 14 to 46 days. In 2 patients, the extent of mononuclear cell infiltration in the liver and hepatocyte necrosis was less than the extent before the therapy. In the remaining 8 patients, the grade of chronic hepatitis was unchanged during the therapy, but vacuole formation and apoptotic nuclei in hepatocytes were found in 2 patients, and centrilobular necrotic areas in 1 patient. Conclusions. The elevation of serum ALT levels during IFN-β therapy in chronic hepatitis C patients was not a result of increased hepatitis activity. Degenerative, apoptotic, and necrotic changes in hepatocytes, probably a result of the cytotoxic effects of IFN-β, may have contributed to this elevation of ALT levels. However, such changes were absent in most of the patients, suggesting that decisions on the discontinuation of IFN-β therapy must be made in accordance with liver histology findings. Received: March 7, 2001 / Accepted: June 22, 2001     

Liver histology and progression of fibrosis in individuals with chronic hepatitis C and persistently normal ALT

OBJECTIVE: The natural history of hepatitis C virus (HCV) infection in patients with normal liver biochemistry remains poorly characterized. We performed a retrospective review of patients with chronic HCV infection and persistently normal ALT to compare clinical and histological features with those in patients with abnormal liver biochemistry. METHODS: Ninety-one HCV RNA-positive patients with persistently normal ALT who had a liver biopsy between 1993 and 1999 were identified. Clinical, histological, and epidemiological features in this group were compared with those found in 94 patients with abnormal ALT. Biopsies were assessed using Ishak's scoring system and fibrosis progression rate calculated from the likely time of infection. RESULTS: Although overall necroinflammatory score and fibrosis were significantly lower in those with normal ALT, none had normal liver histology, and 15 (16%) patients with normal ALT were found to have significant necroinflammation with a score of 5 or greater and/or significant fibrosis staged at 3 or 4. No clinical, epidemiological, or virological predictors of severe histological disease were found. CONCLUSIONS: One in six patients with HCV infection and persistently normal ALT will have evidence of significant, progressive liver disease that can only be identified on liver biopsy.     

Short and long-term effects of interferon on serum markers of hepatitis C virus replication

Abstract Hepatitis C virus RNA (HCV-RNA) and serological markers of HCV infection were measured in 30 patients with chronic hepatitis C who had been treated with interferon (IFN). Patients were classified into four groups according to serum alanine aminotransferase (ALT) levels after treatment. These were: as complete responders (CR); partial responders (PR); transient responders (TR); and non-responders (NR). In all 11 patients in the CR group, HCV-RNA disappeared from serum for at least 24 months and anti-c100-3 decreased progressively during this time. In the PR group, four of five patients were positive for HCV-RNA in spite of the improvement of ALT levels and decline of anti-c100-3. In the TR and NR groups, HCV-RNA disappeared transiently or remained persistently positive. The results indicate that IFN-mediated improvement of ALT and decrease of anti-HCV (anti-c100-3) were not always related to the disappearance of HCV-RNA from serum. On the other hand, sustained disappearance of HCV-RNA from serum was demonstrated in the patients who did not have post-treatment ALT relapse. This indicates that IFN can eradicate HCV from serum in some patients and provide a clinical remission of chronic hepatitis C.     

Hepatitis G virus infection in Japanese haemophiliacs

The recently identified hepatitis G virus (HGV) (also known as GB virus-C) has been considered as a blood-transmissible agent. As many haemophiliacs have risk factors for infectious agents, to clarify the frequency of HGV infection is important. HGV-RNA was investigated in 77 Japanese haemophiliacs who had been treated with nonvirus-inactivated concentrates derived from pooled plasma. Detection of HGV-RNA was performed with a nested RT-PCR that recognizes the 5'-NCR of the HGV genome. HGV-RNA was detected in 19 (24.7%), including four (21.0%) infected with HGV alone, 12 (63.2%) co-infected with HCV and three (15.8%) who were HBV carriers. The patients infected with HGV alone showed a normal ALT level of 18.7 ± 4.1 IU L⁻¹. Most (36/37, 97.3%) of the patients with abnormal ALT levels had HCV-RNA. Patients infected with HCV alone or co-infected with HCV and HGV showed higher ALT levels of 108.8 ± 90.2 IU L⁻¹ ( n = 39) and 67.6 ± 62.6 IU L⁻¹ ( n = 11), respectively. However, there was no significant difference ( P = 0.16) in ALT levels between HCV infection alone and HCV/HGV co-infection. On the other hand, four of the patients who could be followed over 10 years showed HGV-RNA persistently. In two who underwent liver biopsy, the histological evidence showed no definitive fibrotic and necro-inflammatory changes. These results indicate that HGV infection has frequently occurred in haemophiliacs. It is possible that HGV infection does not cause aggressive hepatitis with elevated ALT levels, and that co-infection with HGV may not aggravate hepatitis caused by HCV.     

Assessment of histological features and outcome of interferon therapy in chronic hepatitis C

The correlation between the histological features of liver biopsy specimens before interferon (IFN) treatment and the clinical effect of IFN administration on chronic hepatitis C was investigated. A study of the relation between several histological features that were graded in 60 liver biopsy specimens from chronic hepatitis C patients before IFN treatment disclosed that the grade of portal fibrosis was positively correlated with the grade of other inflammatory features, including piecemeal necrosis and portal and lobular inflammation. The degree of portal fibrosis adversely affected the rate of normalization of ALT levels in chronic hepatitis C during and after IFN treatment. We reexamined 36 liver biopsy specimens that showed a moderate degree of portal fibrosis, and found that the degree of piecemeal necrosis was inversely correlated with the extent of lymphoid follicle formation in the portal tracts. During IFN therapy, the group of chronic hepatitis C patients who showed marked piecemeal necrosis and less lymphoid follicle formation in the liver specimens had a poor response to IFN treatment, whereas another group that showed marked lymphoid follicle formation and little piece-meal necrosis in the liver specimens had a good response to IFN. These relationships gradually disappeared after the completion of IFN treatment.