Human T-cell lymphotropic virus-1-associated renal disease in Jamaican children.

This report documents the clinicopathological features in two Jamaican children who presented with infective dermatitis, glomerulonephritis, renal failure and human T-cell lymphotropic virus (HTLV-1) seropositivity. Severe hypertension with hypertensive encephalopathy was the most impressive clinical feature. Histological findings from renal biopsy specimens in both cases revealed significant glomerulosclerosis with fibrosis, chronic inflammatory cell infiltrates in the interstitium, and arteriolar hypertensive changes. Membranoproliferative glomerulonephritis (MPGN) was demonstrable in case 1 and marked focal glomerulosclerosis in case 2. Case 1 developed end stage renal failure and died within 3 years of diagnosis. Case 2 remains hypertensive and in chronic renal failure. Although a causal relationship between HTLV-1 infection and renal disease cannot be proven by these two cases, it appears that renal involvement in children with HTLV-1 infection is severe, with the potential for chronic renal failure and malignant hypertension. HTLV-1 nephropathy should be suspected in children with infective dermatitis and renal disease.

Variations of hepatitis B virus core gene sequence in Western patients with chronic hepatitis B virus infection.

Heterogeneity of the hepatitis B virus (HBV) core gene has been reported to be associated with the presence of active liver disease in Japanese patients with chronic HBV infection. This study evaluated the significance of HBV core gene heterogeneity in Western patients with chronic HBV infection. The hepatitis B virus precore/core gene from 45 patients (inactive:active liver disease ratio 16:29) was amplified from serum by polymerase chain reaction (PCR). Gel electrophoresis was employed to detect large deletions. The PCR amplicons from 13 patients (all HBV serotype adw but with a different spectrum of liver disease) were cloned and sequenced. Hepatitis B surface antigen (HBsAg) serotypes were tested by enzyme immunoassay (EIA) and hepatic expression of HBV antigens was assessed by immunohistochemistry. The HBV core gene was amplified from the serum of all 45 patients. Three patients had mixed infection with both precore mutant and wild-type HBV and all three had active liver disease. No patient had a large deletion of the HBV core gene. Hepatitis B virus core gene sequence variations were more common in the midcore region and there was no difference in the number of silent and missense substitutions between those with inactive and active liver disease. There was no correlation between the nucleotide or encoded amino acid substitutions and the clinical and biochemical parameters, including the subsequent response to interferon-alpha therapy (n = 37) or hepatic HBV antigen expression. Variation of the HBV core gene was not found to be preferentially associated with active liver disease in Western patients with chronic HBV infection. The pattern of hepatitis B core gene variation is in accord with the genomic organization of HBV.

Variations of hepatitis C virus NS5B sequence (nucleotides 8261-8566) do not correlate with response to interferon-alpha therapy.

Hepatitis C virus (HCV) is an RNA virus with the NS5B gene encoding an RNA-dependent RNA polymerase. Interferon-alpha (IFN-alpha) is effective against HCV and its effect is believed to be related to its antiviral activity. To determine whether sequence variations of the HCV NS5B region correlate with response to IFN therapy, pretreatment serum samples from 40 patients with chronic HCV infection who were subsequently treated with IFN (> or = 3 MU thrice weekly for 24 weeks) and had well-characterized biochemical responses were studied. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to generate an approximately 365-bp fragment from which nucleotide sequence and genotypes were determined. By comparing the nucleotide sequences and the encoded amino acid sequences of samples from each group, no response group-specific nucleotide or encoded amino acid substitution was identified. Most of the substitutions identified were synonymous (usually by changes at the third position of the codon). These data suggest that these substitutions were selective rather than spontaneous events. Of the few non-synonymous substitutions identified, none was correlated with subsequent response to IFN, either within or across genotypes.