[Corticosteroid withdrawal therapy in patients with chronic hepatitis B virus infection].
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Alanine Transaminase↗
Biomedical subjects
Hiromitsu Kumada
Publications and source records attributed to Hiromitsu Kumada.
Association of amino acid substitution pattern in nonstructural protein 5A of hepatitis C virus genotype2a low viral load and response to interferon monotherapy.
Patients with low titer (<0.5 mEq/ml) of hepatitis C virus (HCV) genotype 2a achieve high and sustained response (SR) rates to interferon (IFN) monotherapy, but we also encounter patients who are resistant to therapy. We explored the relationship between response to IFN and virological differences in such patients. We evaluated 159 consecutive naive patients with low titer of HCV genotype 2a who received IFN monotherapy. A case-control study matched for age, sex, and viral load was conducted to examine the substitution patterns in amino acid positions (amino acids) 2163-2254 of nonstructural (NS) 5A between nonresponders to ideal IFN dose (>/=500 million units) (nonresponders; NR) and responder to less than ideal dose. Overall, 82.4% achieved SR. The substitution numbers in amino acids 2193-2254 were higher in SR than NR patients (P < 0.05). High proportions of patients with substitution at amino acid 2205 (mainly threonine [T] instead of alanine [A]), dual amino acids 2169 and 2205 (mainly A-T instead of T-A), and those without substitution at amino acids 2227 were NR (P < 0.05). Four of 7 NR patients achieved SR after receiving a second course of IFN. Their amino acids patterns at positions probably associated with sensitivity to IFN did not change at the start of initial and second therapies except for one patient, and they had lower viral load and were treated with higher IFN dose in the second course compared with the initial course. Our results suggest that substitution patterns in NS5A in patients with low titer of HCV genotype 2a may affect their response to IFN, but the response to therapy may be affected by mechanisms other than substitutions in this region.
Adult↗
HBe antigen loss during lamivudine therapy is not caused by mutations in precore and core promoter genes in patients with chronic hepatitis B.
HBe antigen (HBeAg) loss or seroconversion can occur during lamivudine therapy. The purpose of this study was to analyze nucleotide sequences in precore and core promoter regions, and examine the influence of mutations in these regions on the disappearance of HBeAg during lamivudine therapy. Serial serum samples were obtained from 51 patients (HBeAg loss in 26 patients) at commencement of therapy (baseline) and after 1 year of lamivudine therapy. Serum samples were amplified with PCR and nucleotide sequences of HBV were analyzed. At baseline, a precore stop codon mutation (A1896) was identified in 8 of 26 HBeAg loss patients and in 8 of 25 HBeAg non-loss patients. At 1 year, precore mutation was observed in 4 of 14 patients analyzed who showed HBeAg loss. At 1 year, however, a precore mutation was observed also in 3 of 9 analyzed patients who showed no HBeAg loss. Core promoter mutations were noted in 21 of 26 HBeAg loss patients and in 20 of 25 HBeAg non-loss patients. At 1 year, core promoter mutations were noted in 11 of 14 HBeAg loss patients and in 8 of 9 HBeAg non-loss patients. Our data suggested that during lamivudine therapy, core promoter and precore mutations do not influence HBeAg loss or seroconversion but may reduce the viral level upon HBeAg loss or seroconversion.
Adult↗
Natural histories of hepatitis C virus infection in men and women simulated by the Markov model.
The Markov model was introduced to simulate natural histories of hepatitis C virus (HCV) infection in men and women. The data set was constructed on 942 HCV carriers who were examined at least once a year without receiving antiviral therapies. Based on 2,251 patient-year data, the probabilities of transition between any two of the four clinical states, i.e., asymptomatic carrier state, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in 1 year were calculated. Hepatocellular carcinoma was defined as the absorbing state from where no transitions occur. Probability matrices thus obtained on six each subsets of HCV infection (asymptomatic carrier state, chronic hepatitis and liver cirrhosis in men and women) in their forties, fifties, and sixties, were used to simulate long-term outcomes of HCV infection. Male asymptomatic carriers aged 40 years were expected to retain the asymptomatic carrier state in 2.6%, evolve into chronic hepatitis in 48.4%, liver cirrhosis in 14.6% and hepatocellular carcinoma in 34.4% after 30 years when they reached 70 years of age, in contrast to 1.9%, 45.3%, 32.8% and 20.0%, respectively, of female asymptomatic carriers. Likewise, male patients with chronic hepatitis aged 40 years were expected to remain with chronic hepatitis in 43.8%, evolve into liver cirrhosis in 15.0% and hepatocellular carcinoma in 41.1%, contrasting with 38.9%, 32.7% and 22.0%, respectively, of female patients during 30 years. The Markov model could simulate the outcomes of 153 HCV carriers identified among blood donors after 5 years. The Markov simulation would help in assessing the long-term outcome of HCV infection and making decisions in the management of HCV carriers toward prevention of hepatocellular carcinoma.
Adult↗
Virological and biochemical relapse according to YMDD motif mutant type during long-term lamivudine monotherapy.
Whether the type of lamivudine-resistant virus in hepatitis B virus (HBV) influences the clinical outcome, it is not completely understood. We evaluated the serial changes in YMDD motif mutant in 60 Japanese genotype C-HBV patients who received long-term lamivudine monotherapy. YIDD or YVDD alone tended to stop shifting to the mixed type (YVDD and YIDD) within 12 months after the detection of mutant virus. Hence, the characteristics, virological relapse (DNA breakthrough) and biochemical relapse (breakthrough hepatitis) of 49 patients, who could be classified into three types (continuous YVDD, continuous YIDD, and the mixed type), were investigated. YVDD and YIDD type tended to have the opposite background with regard to age, histology, and viral load. The mixed and YIDD types tended to have similar backgrounds, except for viral load. In the mixed type, both the HBeAg-positive rate and viral load as risk factors for emergence of the mutant tended to be high. Mutant virus, DNA breakthrough and breakthrough hepatitis emerged significantly earlier in the mixed type than the two other types. The incidence of severe breakthrough hepatitis accompanied by icteric flare-up tended to be higher in the mixed type than the other types. Our results suggest that the YMDD motif mutant type might emerge from different backgrounds and modulate the virological and biochemical relapse after the emergence. Large-scale studies of each mutant type should be conducted in the future to confirm these findings.
Adult↗
Type C-chronic hepatitis patients who had autoimmune phenomenon and developed jaundice during interferon therapy.
Of a total of 2342 patients with type-C chronic hepatitis treated with interferon (IFN) at this hospital, 3 patients developed jaundice during the course of IFN therapy, but all 3 of them exhibited negative conversion of hepatitis C virus (HCV)-RNA following readministration of IFN. All 3 patients were assessed as having "probable autoimmune hepatitis (AIH)" in accordance with the AIH scoring system, indicating association with an "autoimmune phenomenon". Readministration of IFN at a low-dose induced activation of the autoimmune phenomenon, leading to fulminant hepatocellular impairment. As a result, HCV-RNA content dropped dramatically, possibly contributing to the negative conversion of HCV-RNA noted following the readministration of IFN. At present, no adequate therapy has been established for type-C chronic hepatitis with autoimmune manifestations. However, in conclusion, our findings suggested that: IFN should be a frontline regiment: (1). if autoantibody titers are low or patients are rated as having "probable AIH" or lower in accordance with the AIH scoring system, indicating a strong link to chronic hepatitis or (2). if IFN is expected to be efficacious on the basis of genotype of HCV-RNA level; even if there is acute exacerbation of type-C chronic hepatitis, IFN should be re-administered in the HCV-RNA level has dropped subsequently.
Adult↗
Clinical features of hepatitis B virus genotype A in Japanese patients.
BACKGROUND: Hepatitis B virus (HBV) genotype A is predominant in northern Europe and central Africa. In the present study, we examined the clinical features associated with HBV genotype A disease in the Tokyo metropolitan area. METHODS: We investigated 53 cases of HBV surface antigen (HBsAg)-positive Japanese patients with HBV genotype A. The 53 cases were further classified as to their serum alanine aminotransferase (ALT) status being within the normal range (asymptomatic carriers, n = 17), chronic hepatitis (n = 15), liver cirrhosis (n = 4), and acute hepatitis (n = 17). RESULTS: Chronic hepatitis patients had significantly higher HBV DNA levels (P = 0.003) and hepatitis B e antigen (HBeAg) positivity rates at the initial visit than did asymptomatic carriers or patients with liver cirrhosis (P = 0.003 and P = 0.054, respectively). The efficacy of treatment (HBeAg seroconversion rate) was 75% in 12 chronic hepatitis patients, which was excellent. A family history of HBsAg positivity was identified in eight (15%) families (five asymptomatic carriers, three with chronic hepatitis). However, none of the mothers in the study was positive for HBV genotype A. CONCLUSIONS: Maternal transmission of HBV has often been reported in Japan, but our present findings suggest that horizontal infection of HBV genotype A is more prevalent in the Tokyo metropolitan area. Our data indicate that HBV genotype A exhibits a mode of infection different from that of conventional HBV previously seen in Japan.
Adolescent↗
Significance of multicentric cancer recurrence after potentially curative ablation of hepatocellular carcinoma: a longterm cohort study of 892 patients with viral cirrhosis.
BACKGROUND: Tumor recurrence is common after potentially curative ablation of hepatocellular carcinoma; therefore, the incidence of intrahepatic metastasis and multicentric carcinogenesis was evaluated. METHODS: A cohort of 892 patients with cirrhosis caused by either hepatitis B virus (n=246) or hepatitis C virus (n=646) was followed up without interferon administration. RESULTS: Hepatocellular carcinogenesis rates were 28.0% at the end of the fifth year, 49.2% at the tenth year, and 61.3% at the fifteenth year. Sex, hepatitis virus, alpha-fetoprotein, platelet count, age, and indocyanine green retention test value significantly affected the carcinogenesis rate. Of 372 patients with tumor development, 162 (43.5%) received surgical or radical locoregional therapy. On the assumption that a second carcinogenesis after sufficient ablation of well-differentiated cancer was attributable to multicentric carcinogenesis, recurrence rates after curative therapy in all the 162 patients, and the recurrence rates in 39 patients with solitary, small, and well-differentiated histology were analyzed: the rates were 58.2% and 30.9% at the third year, 75.9% and 53.4% at the fifth year, and 89.6% and 79.9% at the tenth year, respectively. The estimated incidence of multicentric recurrence was, therefore, 31% or higher at the third year and 53% or higher at the fifth year. The actual second carcinogenesis rates (multicentric recurrence) were approximately 1.6 times as high as those of the virtual second carcinogenesis rates calculated from statistical simulation. CONCLUSIONS: A longterm cohort study disclosed that multicentric carcinogenesis was the principal mechanism of recurrence after curative ablation of hepatocellular carcinoma and that the concept of "carcinogenic stage" should be introduced to improve the understanding of carcinogenic events in viral cirrhosis.
Adult↗
Efficacy of prolonged interferon therapy for patients with chronic hepatitis C with HCV-genotype 1b and high virus load.
BACKGROUND: In patients with hepatitis C virus (HCV)-genotype 1b and a high virus load, of more than 1 Meq/ml by the DNA probe assay, the clearance of HCV-RNA was achieved in only 10% with a 6-month interferon (IFN) course. We therefore assessed the efficacy of prolonged IFN therapy in patients with HCV-genotype 1b and a high virus load. METHODS: A total of 51 patients with HCV genotype 1b who were given 6 million units (MU) of natural IFN-alpha daily for 8 weeks followed by three-times-weekly treatment with natural IFN-alpha for 16 weeks, were enrolled in this trial. These 51 patients were randomly assigned to one of two schedule groups at the time of termination of the first IFN therapy. The 48-week-group patients (n = 25) were given 6 MU of natural IFN-alpha by intramuscular injection three times weekly for 24 weeks, beginning within a week after the termination of the first IFN therapy. The 72-week-group patients (n = 26) were given 6 MU of IFN-alpha by intramuscular injection three times a week for 48 weeks, beginning within a week after the termination of the first IFN therapy. The therapeutic efficacy was evaluated 24 and 30 months after the initiation of the first IFN treatment. A virological response (VR) to IFN therapy was defined as the normalization of serum alanime amino transferase (ALT) level (ALT less, similar 50 IU) and HCV-RNA negativity at the two time points. Biochemical response (BR) was defined as the normalization of serum ALT, but positivity for HCV-RNA, assessed by commercial Amplicor HCV qualitative assays, at the two time points. RESULTS: The efficacy of IFN treatment was assessed in relation to the IFN administration schedule by intention-to-treat (ITT) analysis and per-protocol analysis. With respect to the IFN regimen, VR occurred in 16.6% (4/24) of the patients in the 48-week-group with additional IFN and in 20% (5/25) in the 72-week-group with additional IFN by ITT analysis. The BR rate was 33.3% (8/24) in the 48-week group and 48% (12/25) in the 72-week group. CONCLUSIONS: We found that prolonged IFN therapy could be a worthwhile treatment strategy for patients with HCV genotype 1b and a high serum virus load.
Adult↗
Long-term prognosis by lamivudine monotherapy for severe acute exacerbation in chronic hepatitis B infection: emergence of YMDD motif mutant and risk of breakthrough hepatitis -- an open-cohort study.
BACKGROUND/AIMS: Comparison of long-term prognosis in patients with chronic hepatitis B treated with lamivudine, with or without severe acute exacerbation (SAE). METHODS: In chronic hepatitis B HBeAg-positive patients on lamivudine monotherapy, 21 patients with SAE were retrospectively compared with 63 patients without SAE. Both groups were matched for age and sex. We investigated the efficacy and problems associated with monotherapy with respect to SAE. RESULTS: In SAE and non-SAE, HBeAg seroconversion rates were 21.1 vs. 27.6%, 20.0 vs. 50.0%, and 14.3 vs. 66.7% at 1, 2, and 3 years, respectively. YMDD mutant emerged later in SAE than in non-SAE, but the emergence rates in SAE almost exceeded those of non-SAE from 2 years (rates of about 35%). DNA breakthrough (hepatitis B virus DNA becoming detectable after a period of negativity, accompanied by emergence of YMDD mutant) and breakthrough hepatitis (alanine aminotransferase becoming abnormal after a period of normalization, accompanied by DNA breakthrough) also appeared later in SAE than in non-SAE, but the rates in SAE exceeded those of non-SAE at 3 years. CONCLUSIONS: Our results suggest that Japanese genotype C-dominant hepatitis B patients with SAE seem to be at greater risk of re-exacerbation after temporary relief of the initial SAE by long-term lamivudine monotherapy, compared with those without SAE.
Adult↗
The influence of hepatitis B virus genotype on the development of lamivudine resistance during long-term treatment.
BACKGROUND/AIMS: Genotype-dependent development of lamivudine resistance in hepatitis B virus (HBV) has not been reported. METHODS: We determined the cumulative rate of emergence of YMDD motif mutant in 213 Japanese patients with chronic hepatitis B infected with genotype A, B, or C and treated with lamivudine for more than 1 year. RESULTS: The emergence rate of lamivudine resistance was independent of the genotype (A, B, and C). In contrast, the emergence rate was significantly higher in the Ba ("a" stands for Asia) subgroup of HBV than in Bj ("j" for Japan) subgroup (P<0.05). For genotype C (HBV/C), the emergence rate in hepatitis B e antigen (HBeAg)-positive was significantly higher than in HBV/C-HBeAg-negative (P<0.05), but the rate in HBV/B-HBeAg-positive was similar to HBV/B-HBeAg-negative. Only four patients with HBV/C developed severe acute exacerbation of hepatitis accompanied by emergence of YMDD mutant, but none of the patients with other genotypes developed such complication. CONCLUSIONS: Our results suggest that lamivudine resistance in HBV does not seem to depend on the genotype but rather on the subgroup of HBV/B. The results also suggest that lamivudine resistance according to HBeAg state might be different between HBV/B and HBV/C. Large-scale prospective studies of each genotype should be conducted in the future to confirm these findings.
Adult↗
Serum levels of gamma-globulin and total bilirubin influence the prevalence of multiple extrahepatic complication in patients with hepatitis C virus infection.
Patients with chronic hepatitis C virus (HCV) infection develop various extrahepatic complications. In this study, we analyzed as following. (1) The prevalence and interrelation of multiple extrahepatic manifestations. (2) Exact factors that are related to multiple extrahepatic manifestations. Consecutive autopsies of 261 cases with HCV infection that had undergone autopsy in 1988-1998 were enrolled. One hundred and forty consecutive patients who had gastro enteric carcinoma and underwent autopsy after death in our institution during the same period were used as controls. These 140 patients did not have hepatitis virus and chronic hepatitis or liver cirrhosis histologically. The prevalence of glomerulonephritis (GN), sialadenitis, thyroiditis, and idiopathic pulmonary fibrosis (IPF) was determined histologically. 'Multiple extrahepatic complications' was defined as the presence of two or more of the above four extrahepatic complications. Multiple logistic regression analyses of the risk for the multiple extrahepatic manifestations were performed. GN was present in 58.6% (153 cases), sialadenitis in 16.1% (42 cases), thyroiditis in 7.7% (20 cases), and IPF in 5% (13 cases) in cases of HCV infection. In addition, 37 out of 261 (14.2%) and seven (2.7%) cases had two and three extrahepatic complications, respectively. Multivariate analysis showed that multiple extrahepatic complications correlated with high serum gamma-globulin levels (>/=2.5 g/dl) and high serum total bilirubin levels (>/=1.2 mg/dl) about 1 year before death. Moreover, about 70-80% of patients with sialadenitis, IPF, or thyroiditis had other extrahepatic manifestations. HCV-positive patients with high serum gamma-globulin or high total bilirubin are at high risk of multiple extrahepatic complications.
Journal Article↗
Randomized trial of prolonged interferon retreatment for chronic hepatitis C patients with HCV-genotype 1b and high virus load.
The aim of this study was to examine whether 78 week course of interferon (IFN) retreatment could improve the beneficial effect of IFN in chronic hepatitis C patients compared with 52 week course of IFN retreatment. Inclusion criteria were biopsy-proven chronic hepatitis, serum HCV-RNA level of more than 1 Meq/ml, HCV-genotype 1b, abnormal serum alanine aminotransferase (ALT), and transient negative conversion for HCV-RNA during the initial course of IFN therapy. Forty-one patients were randomly assigned to two groups, receiving total doses of: 1410 MU for 52 weeks (a 52 week-group: n=20), or 1995 MIU for 78 weeks (a 78 week-group: n=21). But three patients (one in the 52 week-group and two in the 78 week-group) were withdrawn from the study due to a transfer, refusal after randomization, and occurrence of malignant lymphoma before IFN retreatment, respectively. Therefore remainder 38 patients were studied about efficacy of IFN administration. A virological response (VR) to IFN therapy was defined as HCV-RNA negativity by the reverse transcription nested polymerase chain reaction both 3 and 6 months after the completion of IFN retreatment. A biochemical response (BR) was defined as normalization of ALT but positive HCV-RNA both 3 and 6 months after the cessation of IFN therapy. According to these criteria, VR was 36.8% (7/19) in the 52 week-group and 21.1% (4/19) in the 78 week-group. BR was 5.3%(1/19) in the 52 week-group and 21.1% (4/19) in the 78 week-group. There was no significant difference between the 52 week-group and the 78 week-group with respect to the effect of IFN. We conclude that 52 week course of IFN retreatment may be a sufficient strategy if patients, who have HCV-genotype 1b and high virus load, show negative HCV-RNA and normal ALT level during the first IFN therapy.
Journal Article↗
Usefulness of serum KL-6 for early diagnosis of idiopathic pulmonary fibrosis in patients with hepatitis C virus.
The aim of this study was to evaluate when the serum level of KL-6, a sensitive marker for idiopathic pulmonary fibrosis (IPF), rise prior to clinical onset of IPF. Eight hepatitis C virus (HCV)-positive patients with IPF were enrolled in this trial. The serum samples of these eight patients were stored -80 degrees C every 1-3 month during a follow-up period and enzyme-linked immunosorbent assay (ELISA) for KL-6 was done at the same time. Diagnosis of IPF was based on computed tomography and/or histology. Diagnosis of clinical onset of IPF was based on presence of dyspnea, dry cough, and audible fine crackles. At 1 year before clinical onset of IPF, the sensitivities of serum marker for IPF were 75% (6/8) for KL-6, 25% (2/8) for each of lactic acid dehydrogenase (LDH) and C-reactive protein (CRP). At 2 years before clinical onset of IPF, the sensitivities of the same serum markers were 62.5% (5/8), 12.5% (1/8) and 0% (0/8), respectively. The sensitivity of KL-6 at 1 and 2 year before clinical onset of IPF was significantly higher compared with LDH and CRP. Our results indicate that many future patients with IPF may have high levels of serum KL-6 at 1 or 2 years before clinical onset of IPF, suggesting that changes in serum KL-6 level can provide useful information for the early diagnosis of IPF in patients with HCV.
Journal Article↗
Interferon-alpha for reinfection with hepatitis C virus in two patients with chronic hepatitis C who had responded to previous therapies.
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Acute Disease↗
Pharmacokinetics of ribavirin in combined interferon-alpha 2b and ribavirin therapy for chronic hepatitis C virus infection.
AIMS: The aim of this study was to clarify the pharmacokinetics of ribavirin and interferon-alpha (IFN-alpha) 2b when administered in combination for 24 weeks and effects of pharmacokinetics of both on treatment outcome in chronic hepatitis C with genotype 1b and high viral load. METHODS: In this multicentre open study, 27 patients received 2-week daily induction therapy followed by 22-week, three-times-a-week maintenance therapy of intramuscular IFN-alpha 2b at a dose of 6 million units and oral ribavirin at 400 mg twice daily for 24 weeks, and followed up for 24 weeks post-treatment. Single- and multiple-dose pharmacokinetic studies were assessed by serial measurements of serum concentrations of both compounds at weeks 1 and 24. RESULTS: Five patients attained sustained virological response. Serum ribavirin concentrations asymptoted after 4-8 weeks of treatment in all patients. The steady-state concentration correlated significantly with serum ribavirin clearance after multiple dosing (r = -0.875; 95% CI -0.932, -0.721; P < 0.001). Serum concentrations at weeks 4 and 8, Cmax and AUC(0,12 h) after multiple dosing and AUC(0,28 weeks) of ribavirin were significantly higher in sustained virological responders than in virological responders or nonresponders (P < 0.05, each). Increased Cmax and accumulation index of AUC(0,12 h) (median 10.5; 95% CI 6.4, 12.4), and prolonged washout half-life after multiple dosing reflected accumulation and slow clearance of ribavirin from the tissue compartments. CONCLUSIONS: Continuous exposure and accumulation of ribavirin may be necessary for sustained virological response to combination therapy in chronic hepatitis C with genotype 1b and high viral load.
Adult↗
Consistently low hepatitis B virus DNA saves patients from hepatocellular carcinogenesis in HBV-related cirrhosis. A nested case-control study using 96 untreated patients.
BACKGROUND: To elucidate the influence of serum hepatitis B virus (HBV) load on hepatocellular carcinogenesis in cirrhotic patients, HBV-DNA was sequentially measured. PATIENTS AND METHODS: Among 160 consecutive patients with HBV-related cirrhosis who received no anti-viral therapy, serial assay of HBV-DNA concentration was available in 146 (91.3%): 48 developed hepatocellular carcinoma (HCC) and 98 did not during a median of 11.7 years. HBV-DNA of 10(3.7) copies/ml or less was considered as low. RESULTS: Of the 48 cases with eventual HCC development (group A), 9 showed intermittently high HBV-DNA, and the other 39 persistently high values. Among 48 age- and sex-matched control patients (group B) selected from the 98 HCC-free patients, 9 had continuously low HBV-DNA, 13 showed a settled down course of HBV-DNA, 9 intermittently high, and the remaining 17 patients demonstrated continuously high HBV-DNA. High HBV-DNA in the last 3 years was significantly associated with carcinogenesis (group A; 0/48 vs. group B; 22/48, p < 0.0001). No patient with a continuously low HBV-DNA for the last 3 years developed HCC. CONCLUSION: Persistence of high HBV-DNA concentration suggested an increased risk of carcinogenesis. Sequential analysis of HBV-DNA is important in the assessment of the carcinogenesis risk.
Adult↗
Precore wild-type hepatitis B virus with G1896 in the resolution of persistent hepatitis B virus infection.
OBJECTIVE: Factors influencing the resolution of persistent hepatitis B virus (HBV) infection were sought for. METHODS: The loss of hepatitis B surface antigen (HBsAg) from serum was correlated with mutations in HBV DNA for a hepatitis B e antigen (HBeAg)-minus phenotype in patients infected with HBV genotype C and positive for HBeAg at presentation. RESULTS: HBeAg turned negative in all the 22 patients in whom HBV infection resolved, but only in 11 of the 25 patients with severe liver diseases (100 vs. 44%, p = 0.0001). The precore wild type (G1896) persisted significantly more frequently in the 22 patients in whom HBV infection resolved than in the 11 patients who developed decompensated liver cirrhosis or hepatocellular carcinoma (15/22 or 68% vs. 1/11 or 9%, p = 0.005). The double mutation in the core promoter (T1762/A1764) was comparably frequent in the two groups of patients at presentation (14/22 or 64% vs. 7/11 or 64%) and >15 years thereafter (18/22 or 82% vs. 10/11 or 91%). CONCLUSION: The precore wild type (G1896) would seem to facilitate the resolution of HBV infection, while the precore mutant (A1896) may induce severe liver diseases in patients with HBeAg-positive chronic hepatitis who have lost HBeAg from serum.
Adult↗