Clinical course and predictive factors of virological response in long-term lamivudine plus adefovir dipivoxil combination therapy for lamivudine-resistant chronic hepatitis B patients.

The aims of this study were to assess the long-term efficacy of lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy in patients with chronic hepatitis B resistant to LAM, to identify predictive factors of complete viral response (HBV-DNA <2.6 log copies/ml at 12 months of combination therapy), and to analyze amino acid substitutions associated with treatment resistance in the hepatitis B virus (HBV) genome. Seventy-two patients who received ADV in addition to LAM for breakthrough hepatitis were enrolled. Undetectable HBV-DNA was observed in 61%, 74%, 81%, 84%, and 85% at 12, 24, 36, 48, and 60 months of combination therapy, respectively. On multivariate analysis, undetectable HBV-DNA during the preceding LAM monotherapy (P < 0.0001), alanine aminotransferase value ≥ the upper limit of normal × 6 (P = 0.006) and HBV-DNA level < 6.0 log copies/ml at the initiation of combination therapy (P = 0.007) were independent significant predictors of complete viral response. The cumulative rate of undetectable HBV-DNA was significantly higher in patients with response to the preceding LAM monotherapy than in those with poor response to it. Breakthrough hepatitis occurred in three patients without complete viral response and with poor response to the preceding LAM monotherapy, and rtA181A/V substitution was detected in one of the three patients. In conclusion, undetectable HBV-DNA during the LAM monotherapy was the strongest independent predictor of complete viral response to the following combination therapy. The efficacy of LAM plus ADV combination therapy may be determined by viral response to the preceding LAM monotherapy.

Overlap/switch to adefovir monotherapy for lamivudine-resistant patients who responded to combination therapy: a pilot controlled study.

OBJECTIVE: The aim of this study was to investigate the outcome of overlap/switch to adefovir dipivoxil (ADV) monotherapy for chronic hepatitis B (CHB) patients with lamivudine (LAM)-resistant HBV, who responded to LAM plus ADV combination therapy. METHODS: In 29 of 35 LAM-resistant CHB patients, serum HBV-DNA levels decreased to <3.7 log genome equivalent (LGE)/mL at 12 months after LAM plus ADV combination therapy, defined as complete virological response (CVR). The 29 CVR patients were randomly allocated to continuation of combination therapy or switch to ADV monotherapy within 12 months. The cumulative rates of sustained CVR were compared between the two groups. RESULTS: The follow-up duration after randomization was 19.3-36.7 months (median, 28.2 months) for the combination group and 21.0-36.4 months (29.0 months) for the overlap/switch group. The cumulative rate of sustained CVR during the follow-up period was 100% in all patients of both groups. The total medical expenses during follow-up after randomization were median US$20,949 for the combination group and US$16,107 for the overlap/switch group (p=0.012). Overlap/switch to ADV monotherapy sufficiently repressed the replication of LAM-resistant mutants without the development of ADV-resistant mutants. The rate of sustained CVR was not influenced by treatment regimen (continuation of combination therapy or switching to ADV monotherapy), the duration of the overlap period, or patient and virological characteristics. CONCLUSION: In LAM-resistant CHB patients who achieved CVR to LAM plus ADV combination therapy, CVR was maintained after overlap/switch to ADV monotherapy, suggesting that it could be a useful regimen for such patients.

Highly active antiretroviral therapy improved persistent lamivudine-resistant viremia in acute hepatitis B virus genotype Ae infection with coinfection of human immunodeficiency virus.

A 57-year-old man developed acute hepatitis B virus (AHB), caused by HBV genotype Ae. Lamivudine (LAM) therapy was started at 8 months after the disease onset, because the infection was persistent, but not self-limited. Despite LAM therapy, the hepatitis became chronic. Further, virological breakthrough developed due to the emergence of LAM-resistant YMDD mutants at 11 months after LAM therapy. Adefovir dipivoxil (ADV) was combined with LAM against breakthrough hepatitis at 28 months after LAM therapy. Sequential genetic analysis revealed that rtL217R, a mutation potentially diminishing the ADV efficacy, was detected before and after the combination therapy. During the follow-up period, the patient unexpectedly turned out coinfected with human immunodeficiency virus (HIV) by measuring anti-HIV-1 antibody. At that time, LAM-resistant HIV mutation, M184V, had been already detected. We switched from the combination therapy with LAM plus ADV to highly active antiretroviral therapy (HAART), which included tenofovir disoproxil fumarate. HAART drastically improved LAM-resistant viremia and breakthrough hepatitis as well as HIV viremia and CD4 counts. Even in Japan, HBV genotype and HIV coinfection should be determined early in the treatment of AHB, and early induction of nucleotide analogs should be taken into consideration, because the proportion of AHB patients with HBV genotype A and the number of patients horizontally coinfected with HBV and HIV are increasing.

[Diagnosis of Helicobacter pylori infection: comparison with gold standard].

Marshall and Warren were the first to succeed in culturing Helicobacter pylori (H. pylori) from the gastric mucosa of patients with gastritis in 1983. H. pylori is a spiral-shaped bacterium that resides in the gastric mucosa and is one of the most common infections worldwide. H. pylori infection causes gastritis and peptic ulcers and is associated with the development of gastric cancer and MALT lymphoma. Now, a variety of accurate diagnostic tests are widely available. Both invasive tests (bacterial culture, histopathology, and RUT) and non-invasive tests (UBT and serological test) are conducted for the diagnosis of H. pylori infection. This review provides a general overview of the diagnostic methods and tests the characteristics (sensitivity and specificity) for H. pylori infection.

Four-week pegylated interferon alpha-2a monotherapy for chronic hepatitis C with genotype 2 and low viral load: a pilot, randomized study.

AIM: To assess the efficacy and advantages of 4-wk pegylated interferon alpha-2a (peg-IFN-alpha 2a) monotherapy for chronic hepatitis C patients with strong predictors of sustained virologic response (SVR). METHODS: Patients (n = 33) with genotype 2 and low viral load (< 100 KIU/mL), who became HCV RNA negative after 1 wk of IFN treatment, were randomly allocated to receive a 4- or 12-wk treatment course at a ratio of 2:1, respectively, with a subsequent 24-wk follow-up period. Peg-IFN-alpha 2a was administered subcutaneously at a dose of 180 microg or 90 microg once weekly. SVR was defined as absence of serum HCV RNA at the end of the follow-up period. RESULTS: All patients completed the treatment schedule, and more than half were symptom-free during the treatment. In the 4-wk treatment group, 20 of 22 (91%) patients achieved SVR. Two patients relapsed, but achieved SVR following re-treatment with peg-IFN-alpha 2a alone. In the 12-wk treatment group, 11 of 11 (100%) patients attained SVR. CONCLUSION: Our results show that a 4-wk course of peg-IFN-alpha 2a monotherapy can achieve a high SVR rate in "IFN-sensitive" patients, without negatively affecting outcome.