Acute Exacerbation Of Hepatitis Research Articles

Acute exacerbation of hepatitis B with hepatic failure during the first trimester of pregnancy: Delivery of a healthy term baby after liver transplantation

The severe form of acute exacerbation of hepatitis B during pregnancy is a rare but life-threatening condition for both the mother and the fetus. A 32-year-old pregnant woman at 10weeks of gestation was diagnosed with acute decompensated liver failure due to acute exacerbation of hepatitis B. The Model for End-stage Liver Disease score was up to 37. The patient was managed carefully with antiviral treatment, fluid resuscitation, correction of coagulopathy, close monitoring of hepatic function, and regular assessment of the fetus. She was transplanted with a deceased liver at 14weeks and 1day of gestation. With careful post-transplant care and avoidance of medication with risk of miscarriage and teratogenicity, a healthy baby was delivered at 39weeks and 1day of gestation. Herein, we report this critical condition of pregnancy that was complicated with liver failure due to acute exacerbation of hepatitis B, but had favorable outcomes for both the mother and the baby after liver transplantation.

A Case of Acute Exacerbation of Hepatitis B by Pembrolizumab for a Lung Adenocarcinoma Patient with Hepatitis B Surface Antigen

A Case of Acute Exacerbation of Hepatitis B by Pembrolizumab for a Lung Adenocarcinoma Patient with Hepatitis B Surface Antigen

Unfavorable prognosis of patients with acute liver injury due to drug-induced liver injury and acute exacerbation of hepatitisB virus infection.

Acute liver injury (ALI) has a favorable prognosis, whereas acute liver failure (ALF) leads to organ failure and thus has an unfavorable prognosis. The effect of each etiology on the clinical course of ALI remains unclear. This study aimed to determine how each etiology and glucocorticoid on the unfavorable etiology affects the clinical course of ALI. This prospective observational study enrolled 522 patients with ALI/ALF from 2004 and 2017. To evaluate the influence of etiology on prognosis, decision tree analysis was carried out using age, disease type, etiology, and the presence of hepatic encephalopathy. Of 522 patients, 398 patients satisfied the ALI criteria at registration in this study. The ALI etiologies were as follows: viral hepatitis through oral infection (n = 54), acute hepatitisB virus (HBV) infection (n = 24), acute exacerbation of HBV infection (n = 30), de novo hepatitis due to HBV (n = 5), autoimmune hepatitis (n = 59), drug-induced liver injury (DILI; n = 85), other viruses (n = 12), and undetermined (n = 129). ALI in 46 patients progressed to ALF after registration. Of 11 patients (age >52years) with ALF due to acute exacerbation of HBV infection or DILI, seven patients (63.6%) died. Whether glucocorticoid affected the clinical course of ALI due to acute exacerbation of HBV infection or DILI was evaluated using propensity score matching (age, sex, alanine aminotransferase, total bilirubin, and prothrombin time-international normalized ratio). Glucocorticoid did not improve the prognosis of ALI patients due to the two etiologies. Progression of ALI due to DILI or acute exacerbation of HBV infection to ALF showed a poor prognosis.

Chinese herbal medicine reduces acute hepatitis exacerbation in patients with hepatitis B virus infection: A case-control study in Taiwan

ObjectivesLittle information is available about the impact of Chinese herbal medicine (CHM) treatment on acute exacerbation of hepatitis. This study aimed to assess the risk of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma in HBV patients with and without CHM use. Design and settingThis population-based case-control study used data from the Taiwan Longitudinal Health Insurance Database from 2000 to 2013. Newly diagnosed HBV patients had acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma as the case group, while another patients had no acute exacerbation of hepatitis and cirrhosis and hepatoma as the control group. To correct the differences in sociodemographic factors and Western medication use between the two groups, propensity score matching was used at a 1:1 ratio, and resulted in a comparison of 1306 and 805 patients per group, respectively. Main outcome measuresOccurrence of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma. ResultsOverall rate of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma was 7.9% and 4.8%, respectively. Patients receiving CHM had a significantly lower risk of acute exacerbation of hepatitis (adjusted odds ratio [aOR] =0.20, 95% confidence interval [95%CI]: 0.13–0.31) and subsequent cirrhosis and hepatoma (aOR = 0.29, 95%CI: 0.18–0.49) than those not receiving CHM after adjusting for relevant covariates. However, no dose-dependent relationship was exhibited for either incidence of acute exacerbation of hepatitis and cirrhosis and hepatoma. ConclusionThese findings highlight that the use of CHM was associated with a significantly reduced risk of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma in patients with HBV. Future research could further explore the benefit of CHM therapies for treatment of acute hepatitis exacerbation.

Acute exacerbation of hepatitis C in hepatocellular carcinoma patients receiving chemotherapy.

Acute hepatitis C exacerbations can occur in cancer patients carrying hepatitis C virus (HCV) when receiving systemic chemotherapy. However, clinical studies evaluating these complications remain rare due to the lack of clinically proven effective and tolerable anti-HCV treatments at late cancer stages. Furthermore, no data were available regarding hepatitis C exacerbation in advanced hepatocellular carcinoma (HCC) patients receiving chemotherapy. To address this issue, 48 patients with HCV-related advanced HCC, who underwent systemic chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone from 2008 to 2014 were analyzed. Nine patients developed acute hepatitis exacerbations defined by HCV-RNA elevation ≥10-fold and alanine transaminase (ALT) elevation ≥5-fold of the upper normal limit. Six were genotype 1b and 3 were genotype 2. Three patterns of clinical courses were observed including single episode of exacerbation (n = 5), fluctuated flares (n = 3), and delayed exacerbation (n = 1). Hepatic failure developed in five patients. Patients with acute exacerbations were less likely to have pretreatment ascites (11.1% vs. 53.8%; P = 0.028) and displayed a lower baseline ALT (44.1 ± 28.5 U/L vs. 72.6 ± 19.2 U/L; P = 0.007). Paradoxically, despite a high risk of hepatic failure, occurrence of hepatitis C exacerbation was associated with a favorable overall survival (P = 0.027; 22.8 vs. 5.4 months). In conclusion, hepatitis C exacerbation can occur in HCC patients receiving chemotherapy, leading to liver failure. However, the flare was associated with a better overall survival, possibly due to its association with a better baseline liver function. J. Med. Virol. 89:153-160, 2017. © 2016 Wiley Periodicals, Inc.

Interferon‐beta, prednisolone and lamivudine combination in acute exacerbation of chronic hepatitisBduring pregnancy

Dear Editor, We read with great interest the recently published case report by Koh et al. describing acute exacerbation of hepatitis B in a pregnant woman who was treated with lamivudine (LAM), interferon (IFN)-b and steroids early in the second trimester. Antiviral treatment is advised for pregnant women at risk of hepatic decompensation. In order to reduce the risk of hepatic destruction, antiviral therapy should be continued during pregnancy when there is clear hepatic fibrosis. LAM, adefovir and entecavir are listed by the US Food and Drug Administration as pregnancy category C drugs, and telbivudine and tenofovir are listed as category B drugs. However, in experiences with HIV positive women, use of LAM in pregnant women with hepatitis B virus has yielded much data regarding its safety. Therefore, based on these data, tenofovir, LAM or telbivudine could be considered to be safe in the pregnancy. However, adefovir and entecavir were not suggested to be used during pregnancy. Moreover, IFN and pegylated IFN are contraindicated in pregnancy. Also, the use of steroids in acute exacerbation of hepatitis B is not indicated because they have no effect on the resolution of chronic hepatitis B, and steroids may increase the rate of relapse due to immune suppression. IFN-b has been demonstrated to be useful in patients with multiple sclerosis. But, according to our knowledge, IFN-1-b treatment is recommended to be stopped during pregnancy. Moreover, IFN treatment during pregnancy may be harmful by causing spontaneous abortion or congenital defects. So, only LAM monotherapy was sufficient for acute exacerbation of hepatitis B in this case, and the reason was not clear why they used LAM, steroid and IFN-b combination for treatment of their case.

Case treated with triple therapy of lamivudine, interferon‐β and prednisolone for acute exacerbation of chronic hepatitis B during pregnancy

We herein report a case of a pregnant Chinese woman who suffered an acute exacerbation of hepatitis B. The patient's liver enzymes became elevated toward the end of the first trimester. She was treated with lamivudine, interferon (IFN)-β and steroids early in the second trimester. After this treatment regimen was initiated, aminotransferase levels rapidly normalized within 4 weeks. IFN-β and steroids were administrated for 2 weeks in the second trimester, while the administration of lamivudine continued until delivery. The spontaneous delivery of a female baby weighing 2984 g occurred at 37 weeks of gestation. A neonatal examination revealed no congenital anomalies, and fetal growth was found to be within normal reference ranges. The infant received simultaneous active and passive hepatitis B virus immunization within 12 h of delivery and completed the hepatitis B vaccine schedule at 2, 3 and 5 months of age. The infant was successfully prevented from contracting hepatitis B virus. This case suggests that combination therapy with lamivudine, IFN-β and steroids may be safely used during the second trimester to treat acute exacerbations of hepatitis B.

Aflatoxin M1 in the urine of non-carriers and chronic carriers of hepatitis B virus in Maringa, Brazil

Exposure to aflatoxins (AFs) in the diet may favour the development of hepatocellular carcinoma (HCC) and the acute exacerbation of hepatitis in chronic hepatitis B virus (HBV) carriers. Measurement of biomarkers such as aflatoxin M1 (AFM1), a metabolite of aflatoxin B1 (AFB1), in urine allows for the assessment of populations exposed to aflatoxins. The aim of this study was to investigate the occurrence of aflatoxin M1 in the urine of HBV carrier and non-carrier patients. One group included 43 randomly selected HBV carriers treated at two hospitals in the city of Maringa, Brazil, from March to June 2008. Control group consisted of 29 healthy adult volunteers with anti-HBs positive and HBsAg negative test results. Detection of AFM1 was performed by fluorescence using high performance liquid chromatography (HPLC) and post-column derivation with the Kobra Cell®. Of the 72 samples analysed, 05/29 (17.2%) AFM1 positive samples were from HBV non-carriers, and 16/43 (37.2%) of samples were from chronic HBV carriers. This study showed AFM1 in the urine of the two surveyed population. However, there is evidence that the chronic HBV carriers have a higher risk of developing HCC due to additive interaction between AFs and HBV.

A patient with rheumatoid arthritis treated with tocilizumab together with lamivudine prophylaxis after remission of infliximab-reactivated hepatitis B

A 59-year-old woman with rheumatoid arthritis was treated quite successfully with infliximab, but her serum aminotransferase levels were markedly elevated; this was diagnosed as acute exacerbation of hepatitis B and she was treated with lamivudine, and infliximab was discontinued. The rheumatoid arthritis disease activity was uncontrollable after the discontinuation of infliximab, and we therefore initiated tocilizumab treatment (after obtaining the patient's informed consent) together with lamivudine prophylaxis. After tocilizumab administration her rheumatoid arthritis disease activity was significantly attenuated, and the activity has remained low, without re-exacerbation of the hepatitis, for more than 2 years since the initiation of the tocilizumab.

The effect of transcatheter arterial chemoembolization on hepatitis C virus (HCV) kinetics in patients with HCV-associated hepatocellular carcinoma.

e14578 Background: Reactivation of chronic HCV infection due to systemic chemotherapy has been sporadically reported. Transcatheter arterial chemoembolization (TACE) is an important treatment modality for unresectable hepatocellular carcinoma (HCC). A previous prospective study has suggested that TACE does not aggravate hepatitis B virus infection. We retrospectively evaluated the effect of TACE on HCV kinetics and liver function in patients with HCV associated HCC. Methods: Medical records of HCV associated HCC cases seen at our institution between 01/01/2008 and 12/31/2009 were identified. Clinical and virological data were analyzed. Reactivation of HCV was defined as a > 2 log IU/mL increase in post TACE HCV RNA as compared to baseline (pre TACE) levels. Acute exacerbation of hepatitis (AcEx) was defined as a > 3-fold increase in serum alanine aminotransferase (ALT) level, in the absence of other hepatotoxic drugs, systemic infections and recent blood transfusions. Results: Out of the 84 HCV associated HCC cases identified, 24 (29%) received TACE. Three of them had pre and post TACE HCV RNA levels. TACE was conducted with cisplatin, mitomycin and doxorubicin in two patients, and only doxorubicin in one patient. They received a total of six TACE procedures. Six episodes of AcEx were noted, one after every TACE procedure, with a median ALT peak of 394 (range, 191-2,295) IU/mL at an average of 2.7 (range, 2-3) days after TACE. Viral loads were measured on an average of 80 (range, 50-125) days after TACE. Increase in the HCV RNA levels was observed in two patients, average 0.26 (0.14-0.38) log IU/mL. In the third patient, HCV RNA after TACE decreased by 0.20 log IU/ml. No cases of HCV reactivation were identified. Two cases had genotype 1a and one had genotype 2b. All three cases were naïve to HCV therapy. Conclusions: Even though we cannot rule out a transient reactivation of HCV following TACE, increase in HCV activity appears to be uncommon following this procedure. However, larger prospective series are warranted to better define this entity.

The expression of IL-2, IL-4 and interferon-gamma (IFN-gamma) mRNA using liver biopsies at different phases of acute exacerbation of chronic hepatitis B.

To investigate the hypothesis that Th1 phenotype cytokines are associated with the increasing activity of hepatitis and Th2 phenotype cytokines with decreasing activity in the liver of chronic viral hepatitis, expressions of the mRNA of the cytokines IL-2, IFN-gamma and IL-4 in the liver of 23 patients with chronic hepatitis B were investigated by reverse transcription polymerase chain reaction. Patients were divided into three groups according to the phase of acute exacerbation of hepatitis as increasing (n = 9), decreasing (n = 8), and stable phase (n = 6). Both IL-2 and IFN-gamma mRNA were preferentially expressed in increasing phase than in decreasing phase (P < 0.01, P < 0.05, respectively) and associated with the high serum alanine aminotransferase (ALT) level. On the other hand, IL-4 mRNA was detected in decreasing phase with significant frequency compared with increasing phase (P < 0.05). However, expression of IL-4 mRNA was not associated with serum ALT level. Our results suggest that Th1 phenotype cytokines up-regulate and Th2 phenotype cytokines down-regulate the liver inflammation of chronic viral hepatitis.

Long-Term follow-up of Lamivudine Treatment in Patients with Severe Acute Exacerbation of Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B

The long-term efficacy of lamivudine treatment for patients suffering from severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is unknown. Consecutive patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B were prospectively recruited from 1999 to 2004 and treated with lamivudine. All patients had alanine aminotransferase (ALT) and serum bilirubin levels 10x and 3x above the upper limit of normal, respectively. HBeAg-positive patients without severe acute exacerbation served as controls. Forty-five patients with severe acute exacerbation and 31 controls were treated with lamivudine for a median of 2.8 (range 1.0-7.1) years and 3.8 (range 3.5-8.4) years, respectively. Compared with controls, patients with severe acute exacerbation had higher HBeAg seroconversion rates (78% versus 52%; P=0.02) and lower risk of virological breakthrough. However, 33% of patients with severe acute exacerbation still developed lamivudine resistance and virological breakthrough by year 5. HBV DNA levels at week 4 and prolonged baseline prothrombin time were independent factors associated with virological breakthrough. All patients with week 4 HBV DNA <3 log10 copies/ml had maintained virological response. Among 15 patients who stopped lamivudine after sustained HBeAg seroconversion for > or =6 months, 11 (73%) had virological relapse at a median of 1.4 (0.2-3.9) years. ALT increased beyond 10x the upper limit of normal in six (38%) patients who stopped lamivudine and two (7%) patients on maintained lamivudine treatment (P=0.02). Among patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B treated with lamivudine, virological breakthrough and post-treatment relapse are common despite a high rate of HBeAg seroconversion. Severe hepatitis flare is also common particularly among patients developing virological relapse after discontinuation of lamivudine.

Changes in Serological Markers of Hepatitis B Virus After Renal Transplantation

An estimated 350 million persons worldwide are chronically infected with hepatitis B virus (HBV). Immunosuppression after renal transplantation seems to enhance viral replication and increase the risk of developing cirrhosis and hepatocellular carcinoma. This retrospective study was performed to assess the prevalence among and serological status of HBV infection after renal transplantation at a single university Brazilian center. Thirty six (4.2%) patients among 850 kidney recipients showed positive HBsAg for more than 6 months; 31 were hepatitis B surface antigen (HBsAg) positive at transplantation. Of the 15 hepatitis B e antigen (HbeAg) positive patients, six had spontaneous HBeAg seroconversion and three also had HBsAg clearance. An additional two showed HBeAg clearance with Lamivudine without seroconversion. Among 15 HBeAg-negative patients, three developed HBeAg reversion with no elevation of alanine transferase (ALT) levels and one had HBsAg clearance. Only one patient had acute exacerbation of hepatitis B (ALT > 20 times normal range) but remained HbeAg negative. During follow-up, five patients became HBsAg positive; two reactivations of resolved hepatitis B, two with previous anti-HBS induced by vaccination, and one with no serological marker for HBV. Lamivudine was prescribed for 16 patients, two of whom had HbeAg clearance without seroconversion and five who developed viral resistance to Lamivudine after a mean of 29.2 months. No hepatocellular carcinoma or deaths related to hepatitis B were seen in this group. In summary, prevalence of HBV in kidney transplant patients was 4.2%. Immunosuppression after renal transplantation in HBV infection led to an increased risk of liver complications and changes in HBV serological status.

Programmed death-1 expression is associated with the disease status in hepatitis B virus infection

To define the potential role of programmed death-1/programmed death-ligand (PD-1/PD-L) pathway in different hepatitis B virus (HBV) infection disease status; we examined the expression of PD-1 on antigen specific CD8+ T cells in peripheral blood of patients with chronic hepatitis B (CHB) and acute exacerbation of hepatitis B (AEHB) infection. The PD-1 level on CD8+ T lymphocytes and the number of HBV specific CD8+ T lymphocytes in patients and healthy controls (HCs) were analyzed by staining with pentameric peptide-human leukocyte antigen2 (HLA2) complexes combined with flow cytometry. Real-time quantitative polymerase chain reaction (PCR) was used to measure the serum HBV-DNA levels. The level of PD-1 expression on total CD8+ T cells in CHB patients (13.86% +/- 3.38%) was significantly higher than that in AEHB patients (6.80% +/- 2.19%, P < 0.01) and healthy individuals (4.63% +/- 1.23%, P < 0.01). Compared to AEHB patients (0.81% +/- 0.73%), lower frequency of HBV-specific CD8+ T cells was detected in chronic hepatitis B patients (0.37% +/- 0.43%, P < 0.05). There was an inverse correlation between the strength of HBV-specific CD8+ T-cell response and the level of PD-1 expression. Besides, there was a significant positive correlation between HBV viral load and the percentage of PD-1 expression on CD8+ T cells in CHB and AEHB subjects (R = 0.541, P < 0.01). However, PD-1 expression was not associated with disease flare-ups as indicated by alanine aminotransferase (ALT) levels (R = 0.066, P > 0.05). Our results confirm previous reports that HBV specific CD8+ T-cell response in the peripheral blood is more intense in patients with AEHB than in chronic hepatitis B with persistent viral infection. Moreover, there is a negative correlation between the level of PD-1 and the intensity of virus specific CD8+ T cell response.

A case for treating high hepatitis B DNA levels before starting HIV therapy

A case for treating high hepatitis B DNA levels before starting HIV therapy

Acute exacerbation of hepatitis in a boy with chronic HCV genotype-2 infection after a 9-year period of normal transaminases levels

We report on a boy with HCV genotype-2a infection who presented with a severe degree of ALTflare after 9 years of asymptomatic period and was treated with pegylated interferon and ribavirin. We suggest that children with HCV genotype-2 infection who show a significant ALT flare should be treated with anti-viral therapies in order to avoid progression of hepatic fibrosis.

Determinants for the Occurrence of Acute Exacerbation of Hepatitis B Virus Infection in Chinese Patients after HBeAg Seroclearance

This study was performed to determine the factors for predicting the occurrence of acute exacerbation of hepatitis B virus infection in HBeAg-negative patients. Two hundred and sixteen patients with known times of HBeAg seroclearance were recruited. Liver biochemistry and virologic markers were monitored. Precore and core promoter mutations were determined by a line probe assay. The median age at HBeAg seroclearance was 34.5 years. The median follow-up duration was 26.4 months. Fifty-six (27.9%) patients had acute exacerbations. By Cox regression analysis, male gender, older age, and core promoter mutations at the time of HBeAg seroclearance were independently associated with the occurrence of acute exacerbation after HBeAg seroclearance (P = 0.025, 0.018, and 0.001, respectively). Fourteen (7.0%) patients had HBeAg seroreversion within a median follow-up period of 11.6 months after HBeAg seroclearance. By Cox regression analysis, older age at HBeAg seroclearance was independently associated with the chance of HBeAg seroreversion (P = 0.01). We concluded that male patients with core promoter mutations and delayed HBeAg seroclearance had a higher cumulative chance of acute exacerbation in the HBeAg-negative phase. Patients with delayed HBeAg seroclearance had a higher frequency of HBeAg seroreversion.

Adefovir Dipivoxil for Treatment of Breakthrough Hepatitis Caused by Lamivudine-Resistant Mutants of Hepatitis B Virus

Objective: Adefovir dipivoxil (ADV) is a nucleoside analogue that inhibits wild-type hepatitis B virus (HBV) and lamivudine-resistant HBV mutants in vitro and in vivo. The aim of this study was to evaluate the efficacy of ADV against lamivudine-resistant mutants and of adefovir and interferon (IFN) add-on to lamivudine for patients with severe acute exacerbation of hepatitis caused by lamivudine-resistant mutants. Methods: Fourteen patients with breakthrough hepatitis were treated with ADV. Four of the 14 patients also received IFN as combined treatment for severe acute exacerbation of hepatitis. Results: At week 24, serum HBV DNA levels had significantly decreased by a median of over 4.8 log copies/ml in the ADV group and over 5.9 log copies/ml in the ADV + IFN group compared to baseline. The median decrease in alanine aminotransferase (ALT) levels from baseline to week 24 was –1.05 times the upper limit of normal (ULN) in the ADV group [significant at week 24 compared with baseline (p = 0.012)] and –22.3 times the ULN in the ADV + IFN group. Conclusions: Administration of ADV add-on to lamivudine for patients with breakthrough hepatitis reduced HBV DNA and ALT levels. ADV and IFN add-on to lamivudine could prevent a fatal course in patients with severe acute exacerbation of hepatitis.

Continued Lamivudine Therapy in Patients with Chronic Hepatitis B

From September 1995 through April 2002, 286 patients with chronic hepatitis B were started on lamivudine at the Toranomon Hospital in Tokyo, Japan, and most of them continued with it. At present, 16 patients received lamivudine for 5 years, 7 of whom for 7 years or longer. YMDD mutants increased gradually and developed in 69% of them during the 7 years on lamivudine. Biochemical and virological responses were achieved in 9 of the 16 patients (56%) at 5 years, and in 4 of the 7 patients (57%) at 7 years. Histological assessments were performed at 3 years in the 16 patients and further at 4 and 7 years in the 7 patients. Necroinflammatory changes improved remarkably with a decrease in the total histological activity score from 11.3 ± 3.0 to 4.1 ± 1.7 (p < 0.0001) at 3 years in the 16 patients. Histological improvements continued in 4 of the 7 patients (57%) at 7 years on lamivudine, while the pathology was unchanged in 2 patients (29%) and aggravated in the remaining 1 patient (14%). Severe acute exacerbation of hepatitis developed in 1 patient, who received additional interferon-α therapy to cope with it. Based on my experience, the continuation of lamivudine in patients with chronic hepatitis B benefits approximately two thirds of them with persistent virological and biochemical responses accompanied by histological improvements. Breakthrough hepatitis induced by YMDD mutants along the way in a small number of patients needs to be diagnosed promptly by regular monitoring for transaminases and, if it develops, it can be treated with interferon or other antiviral agents.

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.