Midori Kono

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. J. Med. Virol. 83:953–961, 2011.

Malakoplakia of the Kidney

b alakoplakia is a rare inflammatory disease associated with Escherichia coli nfection. Despite some characteristic histoogical features, including the presence of large istiocytes with clusters of Michaelis-Gutann (MG) bodies, malakoplakia of the kidey is difficult to diagnose because of its rarity nd varying histological picture. We report the ase of a 57-year-old man who had granulomaous interstitial nephritis caused by kidney arenchymal malakoplakia. Of note, using olymerase chain reaction (PCR), we were ble to site-specifically amplify E coli DNA rom his kidney biopsy specimens. Malakoplaia of the kidney should be considered in the ifferential diagnosis of granulomatous intertitial nephritis, and application of molecular iological approaches to the analysis of kidney issues may be useful in the diagnosis of this isease.

Fungal granulomatous interstitial nephritis presenting as acute kidney injury diagnosed by renal histology including PCR assay

We describe two cases of fungal granulomatous interstitial nephritis (GIN) presenting as acute kidney injury (AKI). Increased serum creatinine was detected in Patient 1 after chemotherapy for pharyngeal cancer and in Patient 2 after steroid pulse therapy for bronchial asthma. Renal histology of both patients revealed GIN. Polymerase chain reaction (PCR)-based detection of fungal DNA sequences from kidney tissue demonstrated Trichosporon laibachii and Candida albicans, respectively. When AKI occurs in an immunocompromised host, differential diagnosis of fungal interstitial nephritis should be considered. Furthermore, PCR-based detection of fungal DNA sequences from renal specimens can be useful for rapid diagnosis.

A mutation of the start codon in the X region of hepatitis B virus DNA in a patient with non-B, non-C chronic hepatitis.

There are cases of hepatitis involving occult hepatitis B virus (HBV) infection in which, even though the HB surface antigen (HBsAg) is negative, HBV-DNA is detected by a polymerase chain reaction (PCR). We conducted a sequence analysis of the entire HBV region in a case of non-B non-C chronic hepatitis in a 46-year-old female. A diagnosis of non-B non-C chronic hepatitis was made. Although HBV markers, such as HBs antibody (anti-HBs), anti-HBc, HBeAg and anti-HBe, were negative, HBV-DNA was positive. Nested PCR was performed to amplify the precore region of HBV-DNA and all remaining regions by long nested PCR. Sequence analysis of the two obtained bands was conducted by direct sequencing. Compared with the control strains, the ATG (Methionine) start codon in the X region had mutated to GTG (Valine). It is assumed that a mutation at the start codon in the X region may be the reason why HBV markers are negative in some cases of hepatitis that involve occult HBV infection.

Hepatitis B virus variants in carriers with hematologic malignancies in whom fulminant hepatic failure develops after chemotherapy

Abstract Three patients who were carriers of hepatitis B virus (HBV) and had hematologic malignancies, experienced fulminant hepatic failure after withdrawal of chemotherapy. Before treatment, each patient had inactive HBV infection with undetectable viral DNA polymerase; two patients were negative for hepatitis B e antigen. After chemotherapy, DNA polymerase increased and HBV variants with mutations in the precore region prevailed in their sera. These results implicate precore mutants thriving after chemotherapy and restored immune responses of patients in the pathogenesis of severe hepatic failure.