Alanine Aminotransferase Normalization Rate Research Articles

Evaluation of long‐term biochemical responses to combination therapy of interferon plus ribavirin in those infected with hepatitis C virus genotype 1b and high baseline viral load

The aim of this study was to determine the long-term effects in non-responders (NRs) to 48-week interferon (IFN) and ribavirin combination treatment in patients infected with hepatitis C virus (HCV) genotype 1b and high baseline viral loads. We measured serum alanine aminotransferase (ALT) and HCV-RNA levels in 52 consecutive patients infected with HCV genotype 1b and high viral loads who received combination therapy for 48 weeks. Sustained virologic response (SVR) was noted in 30 patients (57.7%). Virologic response (VR), that is serum HCV-RNA negativity by the end of treatment and positivity during follow-up, was noted in nine patients (17.3%). Thirteen (25.0%) patients were NRs. Significantly lower serum albumin (P = 0.007) and ribavirin doses according to body weight (P = 0.021) and higher gamma glutamyl transpeptidase (GGT,P = 0.038) were noted at baseline in the NR group than in the SVR and VR groups. ALT normalization rates at six months after the completion of treatment were 55.6% (5/9) in VR and 61.5% (8/13) in NRs. Sustained ALT normalization at two years after the completion of treatment was noted in 55.6% (5/9) and 58.3% (7/12), respectively. Our study indicates a high rate of ALT normalization in patients infected with HCV genotype 1b and high baseline viral loads who received combination therapy and that such a rate could be maintained after the completion of therapy, even in NRs. Our results suggest that combination therapy should be continued in NRs who show ALT normalization in order to prevent potential hepatocarcinogenesis.

Efficacy of adefovir dipivoxil in the treatment of lamivudine‐resistant hepatitis B virus genotype C infection

Adefovir dipivoxil (ADV) is a nucleotide analogue that is known to be effective for lamivudine-resistant hepatitis B virus (HBV) mutants as well as wild-type HBV. The aim of this study is to assess the efficacy of ADV against lamivudine-resistant genotype C HBV mutants. Thirty-five patients with breakthrough hepatitis due to lamivudine-resistant HBV received ADV 10 mg daily with discontinuation of lamivudine. Quantitative HBV DNA, HBeAg, liver function test including alanine aminotransferase (ALT) was checked every 4-12 weeks to evaluate the efficacy of ADV. ADV was administered for a median of 48 weeks (range: 24-120 weeks). The rate of serum HBV DNA loss was 68.6%, 80.0%, 84.0%, and 88.2% at weeks 12, 24, 36, and 48, respectively. The rate of serum HBeAg seroconversion was 8.3% and 14.3% at weeks 24 and 48, respectively. The rate of serum ALT normalization at week 48 was 70.6%. Within 32 weeks after stopping ADV therapy, serum HBV DNA levels increased to a median of 378.9 pg/ml in 88.9% of patients, who were treated for a median of 40 weeks. Moreover, in some patients, the ALT level increased to more than five times the upper limit of normal. Administration of ADV is an effective option for the treatment of patients with lamivudine-resistant genotype C HBV infection.

Lamivudine Therapy for Korean Children with Chronic Hepatitis B

PurposeLamivudine is known to be very effective in suppressing hepatitis B virus replication and virus induced necroinflammation. The aim of this study was to evaluate lamivudine therapy efficacy, predictive factors, breakthrough, prevalence of YMDD mutation, and relapse rate in Korean children with chronic hepatitis B.Materials and MethodsBetween August 1999 and February 2005, 60 children on lamivudine therapy for chronic hepatitis B were enrolled. Treatment response was defined as alanine aminotransferase (ALT) normalization, and HBeAg and HBV-DNA disappearance.ResultsSeroconversion rates of HBeAg and HBV-DNA were 42% and 53%, respectively, and ALT normalization rate was 88%. Seroconversion rates of HBeAg (60.0%) and anti-HBe (60.0%) were higher in patients younger than 6 years. Seroconversion rate of HBV-DNA (68.4%) and normalization rate of serum ALT (94.7%) were highest in patients between 6 and 12 years. Seroconversion rates of all HBV markers were lowest in patients older than 12 years. Predicted 3 year cumulative seroconversion rates, were 70%, 68% for HBeAg, HBV-DNA, respectively. These were calculated by Kaplan-Meier method. Cox proportional hazard regression model showed that pre-treatment ALT was a positive predictive factor for seroconversion of HBeAg and HBV-DNA. Breakthrough phenomenon was noted in 6 patients, and 3 had a YMDD mutation.ConclusionLamivudine therapy had a significant effect on HBeAg seroconversion and HBV-DNA disappearance, and ALT normalization for Korean children with chronic hepatitis B.

Determinants of serum ALT normalization after phlebotomy in patients with chronic hepatitis C infection

Phlebotomy is performed to reduce excessive iron accumulation in hepatic tissue. We studied serum alanine aminotransferase (ALT) normalization rates and 50% reduction in initial serum ALT (ALT(50%) reduction rate) in patients with hepatitis C viral (HCV) infection and investigated the factors that influenced the response to phlebotomy therapy. We evaluated 23 consecutive patients with HCV infection who underwent phlebotomy. Phlebotomy was performed a few times per week, then a few times per month, and 200-400 ml of blood was removed at each session, depending on the clinical response. During the course of therapy, hemoglobin (Hb), serum ALT, and ferritin levels were assessed monthly. In patients with Hb of less than 11 g/dl, the ALT(50%) reduction rate was 87.5%. In patients with a serum ferritin level of less than 10 g/dl the ALT(50%) reduction rate was 83.3%. In patients with Hb of less than 11 g/dl, the ALT normalization rate was 50%, and in those with a serum ferritin level of less than 10 g/dl, the ALT normalization rate was 41.7%. Multivariate analysis identified ALT less than 100 IU/l at the start of phlebotomy as an independent factor associated with ALT normalization. Of the 7 patients who showed no response to phlebotomy, 85.7% were obese (body mass index > or =25 kg/m(2)), and 40% showed more than 30% steatosis on liver histology. The cumulative ALT normalization rate in relation to the total volume of blood loss was 43.9% with a blood less or more than 3 l, and thus was optimal above 3 l. Although the sample number was relatively small, the results of our study suggest that phlebotomy is effective therapy for HCV patients who are nonobese, show little or no steatosis on liver histology, and have a baseline serum ALT level of less than 100 IU/l.

Interferon–Lamivudine Combination is No Better than Lamivudine Alone in Anti-Hbe-Positive Chronic Hepatitis B

Results of studies using lamivudine and interferon combination in the treatment of chronic hepatitis B are not consistent or conclusive. This study aimed to evaluate the efficacy of interferon plus lamivudine use versus single lamivudine in anti-HBe-positive chronic hepatitis B. Eighty patients were treated with either lamivudine or lamivudine plus simultaneously started interferon. Patients were assigned in groups according to random allocation rule. Lamivudine was given 150 mg/day for 96 weeks in each group; interferon was administered 10 MU three times a week for 24 weeks in the combination therapy group. Alanine aminotransferase (ALT) normalization was achieved earlier in patients treated with lamivudine alone. At the end of treatment, there was no difference between the groups with respect to HBV DNA negativity, ALT normalization and breakthrough rate. Histological improvement was remarkable in each group, but fibrosis score and necro-inflammatory activity were much lower in lamivudine-treated patients. Addition of interferon to the lamivudine regimen does not increase the effectiveness of the treatment. Considering the side effects of interferon treatment, this combination seems not to be convenient for anti-HBe-positive chronic hepatitis B.

Ribavirin and interferon is effective for hepatitis C virus clearance in hepatitis B and C dually infected patients

Ribavirin and interferon (IFN) are an effective treatment in 30% to 60% of patients with chronic hepatitis C. Whether they are also effective in dually infected patients with hepatitis B and C is unknown. Twenty-four patients with chronic hepatitis seropositive for both hepatitis B surface antigen and antibody to HCV received ribavirin 1,200 mg daily for 6 months, together with 6 million units (MU) IFN-α 2a thrice weekly for 12 weeks and then 3 MU for another 12 weeks. Serum HCV RNA was positive in 21 patients (group I, serum HBV DNA positive in 17 patients) and negative in 3 patients (group II, all HBV DNA positive) by Amplicor (Cobas Amplicor Monitor, Roche Diagnostics, Branchburg, NJ). Serum alanine aminotransferase (ALT), HCV RNA, and hepatitis B virus (HBV) DNA were monitored regularly for 12 months. Another 30 patients with chronic hepatitis C alone receiving the same regimen, served as controls. The serum HCV clearance rate in group I patients (43%) was comparable with that in controls (60%, P = .63) 24 weeks posttreatment. The serum ALT normalization rate in group I and group II patients was 43% and 0%, respectively, 24 weeks posttreatment. After treatment, resurgence of HBV and HCV was encountered in 4 group I patients and 1 group II patient, respectively. In conclusion, in hepatitis B and C dually infected patients, combination of IFN with ribavirin can achieve a sustained HCV clearance rate comparable with hepatitis C alone. In dually infected patients, the treatment may alter the dominant, ruling hepatitis virus. (H EPATOLOGY 2003;37:568-576.)

Efficacy of interferon alfa and lamivudine combination therapy versus interferon alfa monotherapy in Turkish patients with chronic hepatitis B: A double-blind, randomized, comparative study

Background: Interferon (IFN) alfa and lamivudine are the most effective agents used in the treatment of chronic hepatitis B virus (HBV). Monotherapy with IFN alfa or lamivudine provides significant benefit, but the combination of these drugs is still under investigation. It has been suggested that combination therapy has some advantages over monotherapy. Objective: The purpose of this study was to evaluate the efficacy of concurrent combination therapy with lamivudine and IFN alfa versus IFN alfa monotherapy in previously untreated patients with chronic HBV. Method: Patients were randomly assigned to 6 months' therapy with IFN alfa 9 million units 3 times weekly alone or in combination with 100 mg/d oral lamivudine. Alanine aminotransferase (ALT) measurements and viral load assessments (HBV DNA level as measured by polymerase chain reaction) were performed at baseline and months 6 and 12. Levels of hepatitis B e antigen (HBeAg) and anti-HBeAg were determined at baseline and at the end of treatment (month 12). Knodell histologic activity index score was determined at baseline. Results: Fifty patients were enrolled in each group. ALT normalization rates in the monotherapy and combination therapy groups, respectively, were 56% and 86% ( P < 0.05 between groups) at month 6, and 48% and 64% at month 12 ( P < 0.05 between groups). In the monotherapy and combination groups, respectively, there were 21 (42%) and 24 (48%) complete responders ( P < 0.05); 5 (10%) and 10 (20%) partial responders ( P < 0.05); and 24 (48%) and 16 (32%) nonresponders ( P < 0.05). HBeAg seroconversion rates were 22% in the monotherapy group and 30% in the combination therapy group at the end of 12 months ( P = NS between groups). Conclusion: Concurrent combination therapy with IFN alfa and lamivudine has a more beneficial effect on biochemical parameters (ie, ALT levels) than on viral parameters (ie, HBV DNA, seroconversion to anti-HBeAg) and this effect is more pronounced after 1 year of treatment than after 6 months. Further studies are needed to determine the long-term effects of combination therapy with lamivudine and IFN alfa.

Randomized controlled clinical trial of lymphoblastoid interferon-α for chronic hepatitis C

Objective: Most of chronic hepatitis C patients with HCV-genotype 1 and a high virus load fail to eradicate the HCV-RNA by the interferon (IFN) or IFN/ribavirin therapy. But in these patients, IFN is often effective with regard to normalization of alanine aminotransferase (ALT). We had therefore the following two randomized controlled clinical trials to evaluate the effect of IFN which reduce ALT and maintain normalization of ALT. One approach (study 1) was to compare the efficacy of a 6 month course of three different dosages of recombinant IFN-α-2a in patients with chronic hepatitis C associated with HCV-genotype 1b and a high serum HCV-RNA level of more than 1 Meq/ml. Another approach (study 2) was to make clear the significance of an additional 6 month course of IFN in patients who had biochemical response during the first 6 month course of IFN (study 1). Methods: (1) Study 1; 45 patients with HCV-genotype 1b and a high serum HCV-RNA level of more than 1 Meq/ml were randomly assigned into three equal groups; group 1 was treated with 3 million units (MU), group 2 with 6 MU and group 3 with 9 MU. They were treated with IFN 3 times weekly for 6 months. Biochemical response was defined as normalization of ALT at the 6 month after initiation of IFN; (2) Study 2; Subsequently, of 23 patients with biochemical response by the first study, 22 were randomly assigned to two groups; patients in group A were continued to receive 3 MU of IFN-α-2a three times a week for an additional 6 months and patients in group B were discontinued IFN therapy. Results: (1) Study 1; One patient in group 1, three in group 2 and five in group 3 withdrew from IFN therapy because of IFN-related side-effects. Biochemical response was 10 (66.7%) patients of group 1, 8 (53.3%) of group 2 and 5 (33%) of group 3 by the intention-to-treat (ITT) analysis. The biochemical response rate in group 1 was slightly higher than that in other two groups by the Cochran Armitage two-tailed test ( P=0.066). With respect to serum HCV-RNA level, one patient in group 1, six patients in group 2 and four patients in group 3 became negative for HCV-RNA by reversed transcription nested-polymerase chain reaction (RT nested-PCR) at the end point of first 6 month course of IFN; (2) Study 2; The maintenance rate of ALT normalization was 88.9% (9/11) in group A and 11.1% (2/11) in group B. The maintenance rate of ALT normalization in group A was significantly higher than that in group B by the Fisher exact's test ( P=0.0089). With respect to serum HCV-RNA level by RT nested-PCR, four patients in group A had negative HCV-RNA at the end of an additional IFN therapy. On the other hand, all the patients in group B had positive HCV-RNA at the same time. Conclusion: Our data suggested that a prolonged IFN therapy using a dose of 3 MU of IFN-α-2a is safe strategy to reduce ALT and to maintain ALT normalization in patients with HCV-genotype 1b and a high serum HCV-RNA level of more than 1 Meq/ml.

Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa

The aim of this study was to evaluate whether interferon alfa (IFN-α) treatment-associated virological and biochemical remission improves survival in a cohort of 90 white patients with compensated cirrhosis caused by hepatitis B (Child A) followed for a mean period of 7 years. Inclusion criteria were biopsy-proven cirrhosis, hepatitis B e antigen (HBeAg) positivity, abnormal serum aminotransferase levels, exclusion of hepatitis delta virus, and absence of complications of cirrhosis. Of the 40 IFN-treated patients, 27 (67%) showed sustained HBeAg loss with alanine aminotransferase (ALT) normalization. Of the 50 untreated patients, 30 (60%) cleared HBeAg, but only 21 (42%) normalized ALT after HBeAg loss. Compared with the untreated patients, IFN-treated patients had similar cumulative rates of HBeAg clearance (P = .48), but higher rates of ALT normalization (P = .016) and of HBsAg loss (P = .028). During follow-up, liver-related death occurred in 8 treated patients, caused by liver failure in 5 and hepatocellular carcinoma (HCC) in 3; all 8 had continued to be HBeAg-positive with elevated ALT. None of the treated patients undergoing remission developed liver-related complications. At univariate analysis, life expectancy was longer in treated patients showing sustained remission than in those who did not (5-year survival: 100% vs. 81%; P = .048). Fourteen untreated patients died (from liver failure in 10 and HCC in 4); all but 3 had continued to be HBeAg-positive with elevated ALT. Cox's model identified age and ALT normalization as the only significant predictors of survival. In conclusion, in patients with HBeAg-positive compensated cirrhosis, virological and biochemical remission following IFN therapy is associated with improved survival. (Hepatology 1997 Nov;26(5):1338-42)