In patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon-alpha therapy, a long-term sustained biochemical and virologic response is generally seen. This response is associated with an absence of detectable intrahepatic HCV RNA and marked histologic improvement.

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C hronic hepatitis B is a significant global health care problem that affects more than 350 million people worldwide, resulting in approximately 1 million deaths each year. 1 Despite the widespread availability of an effective vaccine, large numbers of children are infected. People infected early in life who have evidence of ongoing viral replication are at the highest risk for development of progressive liver disease and are a major source of infection in others. 2 Treatment options for children are limited. The goal of treatment is to prevent the progression of chronic hepatitis B to long-term complications, such as cirrhosis and hepatocellular carcinoma, that can result in premature death. 3 Interferon ␣ has demonstrated efficacy in achieving hepatitis B e antigen (HBeAg) loss and seroconversion with HBV DNA suppression in children over 1 year old with active hepatitis B. However, only one third of treated patients will respond, and there are significant side effects associated with interferon therapy, including influenzalike symptoms, gastrointestinal disorders, nausea and vomiting, neutropenia, thrombocytopenia, and transient impairment of growth. 4,5 Treatment with lamivudine, an oral nucleoside analog, has been shown to result in similar response rates as interferon in both adults and children. [6][7][8][9] The drug is well tolerated, but long-term efficacy can be compromised by the emergence of resistance. 10 Treatment with lamivu-

SUMMARY BackgroundFirst-degree relatives (FDRs) of early-onset gastric carcinoma (EOGC) patients are at increased risk of cancer development. OLGA/OLGIM (Operative Link on Gastritis/Intestinal Metaplasia Assessment) classifications have been proposed for the identification of individuals at high risk of gastric cancer development.

SUMMARY. Lamivudine has been demonstrated safe and efficacious in the short term in a large cohort of children with chronic hepatitis B (CHB), but optimal duration of treatment has not been elucidated and limited data on the safety of long-term lamivudine administration have been reported. In addition, the durability of favourable therapeutic outcomes after lamivudine therapy in children has not been well characterized. The aim of this study was to examine the safety of lamivudine and the durability of clinical responses in a group of children who received up to 3 years of treatment for CHB. One hundred and fiftyone children from centres in nine countries who had previously received lamivudine in a large prospective trial were enrolled. During the first year, children had been randomized to either lamivudine or placebo treatment. Subsequently, in a separate extension study, those who remained hepatitis B e antigen (HBeAg) positive were given lamivudine for up to 2 years and those who were HBeAg negative were observed for additional 2 years. Results of these studies have been previously reported. In this study, these children were followed for 2 additional years. Data gathered from medical record review included weight, height, signs and symptoms of hepatitis, alanine aminotransferase (ALT) levels, serologic markers, hepatitis B virus (HBV) DNA levels and serious adverse events (SAEs). Other pharmacological treatments for CHB were allowed according to the practices of individual investigators and were documented. Subjects were divided into two groups for analysis, those who had achieved virological response (VR), defined as HBeAg negative and undetectable HBV DNA by the bDNA assay by the end of the extension study at 3 years, and those who had not. In those who had achieved VR by the end of the extension study, long-term durability of HBeAg seroconversion was 82% and >90% in those who had received lamivudine for 52 weeks and at least 2 years respectively. This compares to 75% for those who had achieved seroconversion after placebo. In those who had not achieved VR by the end of the extension study, an additional 11% did so by the end of the study; they had all received lamivudine in the previous trial, and none had received further treatment during the study. Eight children lost hepatitis B surface antigen during the study and all had received lamivudine at some point during the previous trials. Evaluation of safety data revealed no SAEs related to lamivudine. There was no effect of treatment on weight or height z scores. Clinically benign ALT flares (>10 times normal) were seen in 2% of children. Favourable outcomes from lamivudine treatment of CHB in children are maintained for at least several years after completion of treatment. Up to 3 years of lamivudine treatment is safe in children.

To identify a new marker of expression of disease, independent of HFE genotype in patients with hereditary haemochromatosis (HHC), the total peripheral blood lymphocyte counts were analysed according to iron status in two groups of subjects with HFE mutations. The groups consisted of 38 homozygotes for C282Y, and 107 heterozygotes for the C282Y or compound heterozygotes for C282Y and H63D. For control purposes, totallymphocyte counts and iron status were also examined in 20 index patients with African dietary iron overload, a condition not associated with HFE mutations, and in 144 members of their families and communities. Mean lymphocyte numbers were lower in C282Y homozygous HHC index subjects with cirrhosis and higher iron stores than in those without cirrhosis and with lower iron burdens [(1.65 +/-0.43) x 10(6)/mL vs. (2.27 +/-0.49) x 10(6)/mL; p = 0.008]. Similarly, mean lymphocyte counts were significantly lower in C282Y heterozygotes and C282Y/H63D compound heterozygotes with iron overload and increased serum ferritin concentrations compared to those with normal serum ferritin concentrations (p < 0.05). Statistically significant negative correlations were found, in males, between lymphocyte counts and the total body iron stores, either in C282Y homozygous HHC patients (p = 0.031 in a multiple regression model dependent on age) and in C282Y heterozygotes or C282Y/H63D compound heterozygotes with iron overload (p = 0.029 in a simple linear model). In contrast, lymphocyte counts increased with increasing serum ferritin concentrations among the index subjects with African iron overload (r = 0.324, not statistically significant) and among the members of their families and communities (r = 0.170, p = 0.042). These results suggest that a lower peripheral blood lymphocyte count is associated with a greater degree ofiron loading in HFE haemochromatosis but not in African iron overload, and they support the notion that the lymphocyte count may serve as a marker of a non-HFE gene that influences the clinical expression of HFE haemochromatosis.

Orthotopic liver transplantation in patients with hepatitis B-related cirrhosis is commonly complicated by reinfection with the hepatitis B virus, with rapidly progressive liver disease and poor survival rate. We assessed the efficacy of prior therapy with recombinant interferon-alpha on the prevention of posttransplantation hepatitis B virus reinfection. Twenty-two patients with hepatitis B-related cirrhosis waiting for liver transplantation received 3 MU (decreased to 1.5 MU in cases of intolerance) of recombinant interferon-alpha until transplantation. The rates of posttransplantation hepatitis B virus reinfection and survival in this group were compared with those in a group of 26 patients previously given transplants for the same disease but not given interferon therapy. The same protocol of HBs antibody passive immunoprophylaxis was applied after transplantation in both groups. Recombinant interferon-alpha was administered for 14 +/- 7 wk. The treatment had an antiviral effect, with disappearance of serum hepatitis B virus DNA in seven of the eight patients initially positive for hepatitis B virus DNA and disappearance of HBeAg in two of the three patients initially positive for HBeAg. Serum hepatitis B virus DNA remained detectable with polymerase chain reaction at transplantation in 56% of the interferon-treated patients. After transplantation, hepatitis B virus reinfection was more frequent in polymerase chain reaction-positive than in polymerase chain reaction-negative patients (78% vs. 17%, p < 0.05). One patient's condition deteriorated during interferon treatment; this patient was not given a transplant. Two patients (in whom hepatitis B virus DNA disappeared from serum) improved so markedly during treatment that they were not given transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

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