Incidence of hepatocellular carcinoma in patients with chronic hepatitis B virus infection who have normal alanine aminotransferase values.

The importance of alanine aminotransferase (ALT) levels in the progression of hepatitis B virus (HBV) infection remains a subject of debate. This study sought to identify independent risk factors involved in development of hepatocellular carcinoma (HCC), particularly in patients with chronic HBV infection who have normal ALT values. Data from 381 consecutive hepatitis B patients were analyzed with average ALT integration values < or = 40 IU/L and follow-up periods of > 3 years. Integration values were calculated from biochemical tests, and serological markers associated with the cumulative incidence of HCC were analyzed. HCC developed in 17 of the 381 patients (4.5%) during the follow-up period. Male sex (hazard ratio, 6.011 [95% confidence interval: 1.353-26.710], P = 0.018), high HBV-DNA levels (> or = 5.0 log copies/ml; 5.125 [1.880-13.973], P = 0.001), low platelet counts (< 15.0 x 10(4)/mm(3); 4.803 [1.690-13.647], P = 0.003), and low total cholesterol levels (< 130 mg/dl; 5.983 [1.558-22.979], P = 0.009) were significantly associated with greater incidence of HCC development. High HBV-DNA levels and low platelet counts are associated with the development of HCC in patients infected with hepatitis B who have normal ALT values. Therefore, maintenance of low HBV-DNA levels is important for the prevention of HCC in patients with low platelet counts, particularly in patients whose ALT values fall within the current normal range.

Incidence of hepatocellular carcinoma in hepatitis C carriers with normal alanine aminotransferase levels.

BACKGROUND/AIMS: This study sought to identify the independent risk factors involved in the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection who have normal alanine aminotransferase (ALT) levels. METHODS: A total of 519 patients with average ALT integration values less than or equal to 40 IU/L over 10 years were included. Baseline ultrasound was done in all patients and 68 patients underwent liver biopsy at the start of this study. Factors associated with the cumulative incidence of HCC were determined. RESULTS: HCC occurred in 48 of 519 patients (9.2%). The following factors were significantly associated with the incidence of HCC: age>65 years (adjusted hazard ratio: 2.006 [95% confidence interval: 1.078-3.733]), ALT>20 IU/L (6.242 [1.499-25.987]), platelet count<15.0x10(4)/m(3) (2.675 [1.407-5.085]), total bilirubin>1.2mg/dL (2.798 [1.257-6.228]), ALP>338 IU/L (2.486 [1.327-4.657]), and total albumin<3.5g/dl (2.707 [1.177-6.223]). The 5- and 10-year cumulative incidences of HCC were 4.4% and 26.5% in patients with ALT>20 IU/L and platelet count<15.0x10(4)/m(3), respectively. CONCLUSIONS: High ALT level and low platelet count are closely associated with the development of hepatocarcinogenesis. Therefore, individuals within this group are candidates for antiviral therapy.

Differences in viral kinetics between genotypes 1 and 2 of hepatitis C virus after single administration of standard interferon-alpha.

Hepatitis C virus (HCV) kinetics were determined after a single administration of standard interferon (IFN) according to the HCV genotype that affects the response to antiviral therapy with IFN/peginterferon. A total of 208 patients were investigated. All patients received a single administration of 6 megaunits of standard IFN-alpha. HCV RNA concentration was measured before, and at 24, 48, 72, and 120 hr after administration. Changes in HCV RNA concentration were compared between genotypes. The patient group consisted of 132 patients with genotype 1B, 58 with genotype 2A, and 18 with genotype 2B. In the comparison between genotypes 1 and 2, the reduction in HCV RNA concentration after a single IFN administration was less marked in patients with genotype 1B at both 24 and 48 hr after administration (P < 0.0001). In contrast, an increase in HCV RNA concentration during 24-48 or 24-72 hr after a single administration was comparable between genotypes 1 and 2. In the comparison between genotypes 2A and 2B, the reduction in HCV RNA concentration after a single administration was more marked in patients with genotype 2A, despite the similar rate of sustained virologic response to peginterferon and ribavirin combination therapy. The results of the study indicate that the rapid decrease in HCV RNA concentration observed during IFN or peginterferon therapy in patients with genotype 2 appeared to be due to the difference in sensitivity to IFN. Within genotype 2, HCV genotype 2A was more sensitive to IFN than genotype 2B.

Long-term follow-up of patients with hepatitis C with a normal alanine aminotransferase.

An attempt was made to identify factors influencing the cumulative probability of an increased alanine aminotransferase (ALT) level and hepatocarcinogenesis in hepatitis C patients with a normal ALT level initially. A total of 398 consecutive patients with a normal ALT level initially for 6 months or more and follow-up period longer than 3 years during the period January 1995 to December 2004 were included. Patients were classified by ALT level into three groups: Group A (3-20 IU/L), Group B (21-30 IU/L), and Group C (31-35 IU/L). Factors associated with the cumulative probability of increased ALT level and hepotocarcinogenesis were evaluated. Women in groups B and C and men in Group C showed high cumulative probabilities of increased ALT levels. Factors associated with increased ALT were a high ALT level (Group B, relative risk; 1.758 [95% confidence interval: 1.290-2.392], P < 0.001, Group C, 3.328 [2.256-4.909], P < 0.001), high lactate dehydrogenase level (2.352 [1.445-3.829], P = 0.001), or low total cholesterol level (1.957 [1.330-2.882], P = 0.001). Factors associated with incidence of hepatocellular carcinoma were increased age (3.088 [1.025-9.308], P = 0.045), high ALT level (Group C, 5.803 [1.530-22.066], P = 0.010), and high total bilirubin level (8.309 [2.235-30.888], P = 0.002). In patients with hepatitis C with a normal ALT level initially, an ALT level of 21-35 IU/L is a risk factor for an increased ALT level and hepatocarcinogenesis.

Eight-week regimen of antiviral combination therapy with peginterferon and ribavirin for patients with chronic hepatitis C with hepatitis C virus genotype 2 and a rapid virological response.

BACKGROUND: It remains unclear how we can shorten the treatment duration of antiviral combination therapy with peginterferon and ribavirin for patients with chronic hepatitis C virus (HCV) genotype 2 infection who achieved a rapid virological response (RVR). AIM: We compared the efficacy of antiviral combination therapy with peginterferon and ribavirin for 8 vs. 24 weeks for the treatment of patients with HCV genotype 2 infection and with RVR. METHODS: Sixty-one patients were enrolled. Serum HCV RNA was not detected at 4 weeks after the start of treatment in 32 patients with an RVR. These 32 patients were randomly assigned to 8-week (n=15) or 24-week (n=17) treatment regimens. Patients in the 8-week group who relapsed underwent a 24-week retreatment. RESULTS: No significant difference in patient characteristics was observed between the 8- and the 24-week treatment groups. A sustained virological response (SVR) was seen in five of 15 patients (33.3%) in the 8-week treatment group and 14 of 17 (82.4%) in the 24-week treatment group; the rate was significantly higher in the 24-week treatment group (P=0.0140). Nine of 10 relapsed patients in the 8-week treatment group underwent a 24-week retreatment, and seven achieved an SVR. CONCLUSION: An 8-week regimen of combination antiviral therapy with peginterferon and ribavirin yielded an increase in the relapse rate, indicating the limitation of a reduction of treatment below 12 weeks in patients with genotype 2, after RVR.