Higher ALT Levels Research Articles

Recombinant interferon-α2a hastens the rate of HBeAg clearance in children with chronic hepatitis B

We conducted a prospective controlled study of the efficacy of recombinant interferon-α2a in 77 children (44 boys, 33 girls, mean age 8 yr) with chronic hepatitis B. All patients had seropositive results for HBeAg and hepatitis B virus DNA; 52 had chronic persistent or nonspecific reactive hepatitis, and 25 had mild active hepatitis. Twenty-one children (group 1) received recombinant interferon-α2a 7.5 megaunits/m2 three times weekly for 6 mo, 19 children (group 2) received mega-units/m2 on the same schedule and 37 (group 3) remained untreated. At 6 mo, HBe antigen-to-antibody seroconversion associated with biochemical remission was seen in 24% of patients in group 1, 5% in group 2 and 3% in group 3 (p<0.05 vs. group 1). At 18 mo, seroconversion rates were 30% in group 1, 21% in group 2 and 13.5% in group 3. These results suggest that a course of recombinant interferon-α2a accelerates HBeAg—HBe antibody seroconversion in children. High baseline ALT levels were sensitive predictors of seroconversion in both treated and untreated patients. In contrast, baseline IgM HBc antibody levels influenced the rate of anti-HBe seroconversion only in untreated patients. These findings suggest that, in children as well as in adults, recombinant interferon-α2a favors the clearance of hepatitis B virus replication, enhancing the host antiviral immunoresponse. (Hepatology 1994;20:287-290.)

Recombinant interferon-α2a hastens the rate of HBeAg clearance in children with chronic hepatitis B

We conducted a prospective controlled study of the efficacy of recombinant interferon-alpha 2a in 77 children (44 boys, 33 girls, mean age 8 yr) with chronic hepatitis B. All patients had seropositive results for HBeAg and hepatitis B virus DNA; 52 had chronic persistent or nonspecific reactive hepatitis, and 25 had mild active hepatitis. Twenty-one children (group 1) received recombinant interferon-alpha 2a 7.5 megaunits/m2 three times weekly for 6 mo, 19 children (group 2) received megaunits/m2 on the same schedule and 37 (group 3) remained untreated. At 6 mo, HBe antigen-to-antibody seroconversion associated with biochemical remission was seen in 24% of patients in group 1, 5% in group 2 and 3% in group 3 (p < 0.05 vs. group 1). At 18 mo, seroconversion rates were 30% in group 1, 21% in group 2 and 13.5% in group 3. These results suggest that a course of recombinant interferon-alpha 2a accelerates HBeAg-HBe antibody seroconversion in children. High baseline ALT levels were sensitive predictors of seroconversion in both treated and untreated patients. In contrast, baseline IgM HBc antibody levels influenced the rate of anti-HBe seroconversion only in untreated patients. These findings suggest that, in children as well as in adults, recombinant interferon-alpha 2a favors the clearance of hepatitis B virus replication, enhancing the host antiviral immunoresponse.

Prevalence of hepatitis-C virus RNA in serum and throat washings of children with chronic hepatitis.

Serum samples from 46 children with chronic and probably transfusion acquired hepatitis were tested for the presence of hepatitis C virus (HCV) RNA by a "nested" polymerase chain reaction (PCR) assay, to judge a possible risk of HCV transmission from these patients. In 73% of the samples, viral RNA was detected, indicating a high virus prevalence in this patient group. High titers of HCV-RNA were observed in some sera as shown by the detection of virus in some samples even at dilutions of 10(-3). Comparison of simultaneously obtained PCR results and ALT values revealed no significant correlation between virus presence in serum and higher ALT levels. It was, however, shown that unusually high ALT values may reflect a high titer of viral RNA in serum. To investigate the prevalence of viral RNA in saliva, which could be a vehicle of virus transmission, 35 throat washing samples from the HCV-infected children were screened by PCR. Using three different sample preparation procedures, 20% of the throat washings were found to be positive for HCV-RNA. This indicates a prevalence of virus in this fluid lower than that reported previously.

輸血用血液におけるＨＣＶ（Ｃ１００‐３）抗体スクリーニングの効果 第二世代検査法とＨＣＶ‐ＲＮＡ測定による評価

The incidence of anti-HCV (C100-3) in suitable and unsuitable blood for transfusion according to the criteria of the Japanese Red Cross Society Blood Centers in 1985 were 1.0% and 3.4%, respectively, and that in donor blood with high ALT level was 5.6%. The incidence of HCV-RNA was 4.5% in donor blood with anti-HCV positive by one method (C100-3, GOR, 2nd), and 58% in donor blood with anti-HCV positive by two or three methods (C100-3 and 2nd, GOR and 2nd, C100-3 and GOR and 2nd). The application of multiple anti-HCV assays of donor blood that might increase the HCV screening effect would result in more false positivity and waste of donor blood. More than 3.0 of optical density of anti-HCV (C100-3 and 2nd generation) were useful for clinical evaluation since 1989.

Possible role of preS2 peptides presented by MHC class I antigen in the pathogensis of chronic hepatitis B

Many variations exist in the first 39 nucleotides of the preS2 (pre-S2; 1-39) region of the HBV genome. Based on the similarities of their coding amino acid sequences to those of prototype HBV, they were classified into 3 different types, adr-preS2, adw-preS2 and ayw-preS2. To clarify the meaning of these variabilities in the preS2 region, we studied the HLA class I phenotype of chronic hepatitis B patients having high levels of serum ALT. Our results indicated that in 12 of 14 chronic hepatitis patients infected with HBV type adr-preS2 had HLA-A24 phenotype whereas all of 7 patients infected with either adw- or ayw-preS2 HBV had HLA-A2 phenotype. This strong association between HLA class I phenotype and certain preS2 types of HBV infection was found only in patients with high serum ALT levels but not in patients with almost normal levels of serum ALT. Our results therefore suggest that in the generation of chronic hepatitis B a suitable combination between a fragment of preS2 antigen and HLA class I antigens of the infected host, such as adr-preS2 with HLA-A24 and either adw- or ayw-preS2 with HLA-A2, might be required.

Antibody to hepatitis C virus in acute, self-limited, type B hepatitis.

Sera from 104 patients with self-limited, acute type B hepatitis were tested for the presence of anti-HCV antibodies. The results show that especially drug users with acute type B (and occasionally coinfected with type D) hepatitis commonly are infected with HCV. Furthermore, HCV infection may have preceded infection with the other agents and may be responsible for high ALT levels.

Prevalance and significance of anti-HCV in HBsAg negative blood donors with high ALT levels

Prevalance and significance of anti-HCV in HBsAg negative blood donors with high ALT levels

Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children

During a follow-up period of 3.2 +/- 1.6 (1 to 8.6) yr, 1,087 serum specimens from 230 HBsAg carrier children were tested for hepatitis B virus markers. Dividing the serum specimens into four groups according to the status of HBeAg and hepatitis B virus DNA, the frequency of abnormally elevated ALT levels in serum was in the following order: HBeAg(+)/hepatitis B virus DNA(-) serum (60%), HBeAg(-)/hepatitis B virus DNA(+) serum (53%), HBeAg(+)/hepatitis B virus DNA(+) serum (41%), HBeAg(-)/hepatitis B virus DNA(-) serum (11%). Analysis of the data before HBeAg clearance showed that both a high serum ALT level and a low serum hepatitis B virus DNA level correlated with an imminent clearance of HBeAg. Approximately two thirds of children with serum ALT levels higher than 100 IU/L cleared HBeAg within the following year. Clearance of HBeAg occurred within the following year in 65% (13 of 20) of cases with serum hepatitis B virus DNA level less than or equal to 1,000 pg/ml, in contrast to 19% (30 of 157) of those with serum hepatitis B virus DNA level greater than 1,000 pg/ml. Among 53 children who lost HBeAg and hepatitis B virus DNA during follow-up, only nine cases did not have an identified period of abnormal serum ALT levels. For the remaining 44 children, abnormal serum ALT levels fell to normal with clearance of both HBeAg and hepatitis B virus DNA in 33 children but remained elevated in the remaining 11 cases after seroconversion.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized controlled trial of adenine arabinoside 5′-monophosphate in chronic active hepatitis B: Comparison of the efficacy in heterosexual and homosexual patients

Twenty-two heterosexuals and 21 homosexuals with chronic active hepatitis B and who had HBsAg, HBeAg and hepatitis B virus DNA in serum were randomized separately to receive adenine arabinoside monophosphate or placebo. In the 10 heterosexuals and nine homosexuals who received placebo, no change in hepatitis B virus DNA level and HBeAg was observed. Among the patients who received adenine arabinoside monophosphate, seven of the 12 heterosexuals and five of the 12 homosexuals lost hepatitis B virus DNA; five heterosexuals and three homosexuals also lost HBeAg; one homosexual lost HBsAg. There was no significant differences in response between heterosexual and homosexual patients. When results were pooled, there was a significant effect of adenine arabinoside monophosphate on hepatitis B virus replication. None of the 19 patients who received placebo but 50% of the 24 patients who received adenine arabinoside monophosphate were negative for serum hepatitis B virus DNA at 10 months after treatment (p less than 0.001) and none of the 19 patients who received placebo and 33% of the 24 patients who received adenine arabinoside monophosphate were negative for HBeAg in serum (p less than 0.005). Retrospective analysis showed that disappearance of hepatitis B virus DNA after administration of adenine arabinoside monophosphate was more common (i) in patients with a low pretreatment hepatitis B virus DNA level than in patients with a high pretreatment hepatitis B virus DNA level (8/11 vs. 4/13, p less than 0.05); (ii) in patients with a high pretreatment ALT level than in patients with a low pretreatment ALT level (10/14 vs. 2/10, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum pregnancy‐associated α2‐glycoprotein levels in the evolution of Hepatitis B virus infection

Serum pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) levels were evaluated in a follow-up study of patients with hepatitis B virus (HBV) infection and compared with biochemical and virological parameters. In a study of 25 patients with acute hepatitis, an association was found between high alpha 2-PAG values, ALT levels, and HBsAg in 20 patients (80%) (P less than 0.05), 18 recovered completely, and 2 had a protracted course. In five patients serum alpha 2-PAG levels were similar to those in the control group. On the other hand, eight (100%) chronic persistent HBV patients showed high levels of alpha 2-PAG (P less than 0.05) during the study period, and these levels correlated well with inflammatory activity and failure of HBsAg elimination. There were no significant differences in alpha 2-PAG values between asymptomatic HBsAg carriers and controls. Serial analysis of alpha 2-PAG, in correlation with viral markers, biochemical parameters, and histological data, would contribute to the ability to predict the final outcome of HBV infection.

Infections after Liver Transplantation

We studied infections in 101 consecutive patients who underwent liver transplantation between July 1984 and September 1985. The mean length of follow-up was 394 days. Eighty-three percent of population had 1 or more episodes of infection and 67% of the population had severe infections. The overall mortality was 26/101 (26%) and 23 of 26 deaths (88%) were associated with infection. Seventy percent of severe infections occurred in the first 2 months after transplantation. The most frequent severe infections were abdominal abscess, bacterial pneumonia, invasive candidiasis, Pneumocystis pneumonia, and symptomatic cytomegalovirus infection. Patients with more than 12 hours of cumulative surgical time had a higher rate of severe infections (P less than 0.001), particularly fungal (P less than 0.001) and bacterial (P less than 0.01) infections. Also, the use of choledocho-jejunostomy was associated with a higher rate of infection in patients who had more than 1 transplant operation (P less than 0.02). No increase in infection was found in patients who received azathioprine, or more than the median number of steroid boluses or "recycles"; but patients who received OKT3 therapy had a higher rate of protozoal infections (P less than 0.05). A result similar to that of our previous studies was a strong relation between the number of severe fungal infections and prolonged courses of antibiotics after transplant operation (P less than 0.001). Pretransplant manifestations of severe liver disease such as ascites, encephalopathy, and gastrointestinal bleeding were not associated with higher rates of infection after transplantation, but high serum levels of ALT were. Patients with lower ratios of T-helper to T-suppressor lymphocytes had more severe viral (P less than 0.02) and fungal (P less than 0.01) infections after transplantation.

Comparison of 1.5 against 18 MU of rIFN-α treatment of chronic hepatitis B in patients with high alt levels

Comparison of 1.5 against 18 MU of rIFN-α treatment of chronic hepatitis B in patients with high alt levels

Identification of different degrees of hepatitis B virus (HBV) replication by serological (HBV-DNAp, HBcAg and HBV-DNA) and histological (HBcAg) methods.

The incidence of HBV-DNA polymerase, HBV-DNA and serum and liver HBcAg in 104 chronic HBsAg carriers was studied. HBV-DNA was the most frequently detected marker, followed by HBcAg and HBV-DNAp. According to their individual or combined presence, four different serological patterns of viral replication were discerned: 53 patients had all these markers, 30 had HBV-DNA but lacked HBV-DNAp (15 with and 15 without HBcAg) and 21 had no such markers detectable. The simultaneous positivity for all of those markers was observed only in HBeAg-positive patients. HBV-DNA alone or along with HBcAg was found in a similar incidence irrespective of the HBe system. Liver HBcAg was found in all but four patients with and in four without HBV-DNA. Viral DNA concentration was significantly (p less than 0.001) higher when HBV-DNAp tested positive. Indeed, HBeAg rather than anti-HBe patients had higher (p less than 0.005) levels of HBV-DNA. In HBeAg-positive patients, the nuclear HBcAg staining was significantly (p less than 0.05) higher when HBV-DNAp tested positive. In DNA polymerase-negative patients, but positive for HBV-DNA, those with or without HBcAg had a similar percentage of core antigen staining. The same distribution was seen in anti-HBe, HBV-DNA-positive patients. However, the mean percentage of hepatocytes displaying cytoplasmic HBcAg did not differ significantly among patients with HBV-DNA, irrespective of the HBe system and the HBV-DNAp status. Such patients had significantly (p less than 0.001) higher ALT levels than those without viral DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

The Pyrophosphate Heart Scintigram in Children with Progressive Muscular Dystrophy

A pyrophosphate heart scintigram was obtained in 16 boys with progressive muscular dystrophy Duchenne. All of them showed pathological ECG findings and high plasma levels of CK, AST, ALT and LD. In 4 patients the scintigram was distinctly positive and in further 3 it reached borderline values. The remaining 9 boys had normal scintigraphic findings. Those with a positive heart scintigram had very high plasma levels of the enzymes under study which was suggestive of current progression of the disease. There was, however, no relation between heart scintigraphy and the affliction of the skeletal muscles expressed by means of an index.