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Biomedical subjects

A Tsubota

Publications and source records attributed to A Tsubota.

At least 19 recordsLinked to original sources
PubMed1998

Interferon decreases hepatocellular carcinogenesis in patients with cirrhosis caused by the hepatitis B virus: a pilot study.

BACKGROUND: To elucidate the influence of long term interferon administration on the rate of occurrence of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-related cirrhosis, the authors analyzed 313 consecutive patients with cirrhosis. METHODS: Of the 313 patients, 94 underwent long term intermittent administration of interferon for > or = 6 months, and the remaining 219 patients received no interferon or other antiviral drug. RESULTS: Cumulative occurrence rates of HCC in the group treated with interferon and the untreated group were 4.5% and 13.3%, respectively, at the end of 3 years; 7.0% and 19.6%, respectively at the end of 5 years; and 17.0% and 30.8%, respectively, at the end of 10 years. The rate of HCC development in the treated group was significantly lower than that of the untreated group (P = 0.0124). The Cox proportional hazard model revealed that interferon treatment was an independent contributing factor in lowering the rate of carcinogenesis (odds ratio = 0.39; P = 0.031) even after correction by significant covariates in multivariate analysis. The virologic study showed that the role of interferon therapy from the viewpoint of cancer prevention was much more significant in patients with a HBV DNA concentration of > or = 10 milliequivalents. CONCLUSIONS: Interferon therapy for patients with HBV-related cirrhosis significantly decreased the HCC rate, especially in patients with a larger amount of serum HBV DNA. If interferon is administered properly for a selected group of patients, an effective strategy of cancer prevention can be achieved, even in patients with cirrhosis.

Adult↗
PubMed1998

Deletions in the hepatitis B virus core gene may influence the clinical outcome in hepatitis B e antigen-positive asymptomatic healthy carriers.

To address the significance of mutations within the hepatitis B virus (HBV) core gene in chronic HBV infection, we followed prospectively HBe-antigen-positive asymptomatic healthy carriers, documented the onset of their disease based on serum alanine transaminase (ALT) concentrations, and analyzed sequentially serum samples from a quiescent phase through to an active phase of the chronic infection. In three female carriers, the first flare-up was documented during the follow-up period. Serial analysis by polymerase chain reaction, cloning, and sequencing of the HBV precore/core open reading frame genome demonstrated that clones with core gene deletions emerged during the quiescent phase and persisted subsequently during the active phase in two patients, who failed to seroconvert to anti-HBe and had persistently increased ALT levels despite interferon (IFN) therapy. The deletions were various, overlapping, and located in the mid-core region ranging from amino acid (aa) position 64 to 128. The remaining patient, who seroconverted with IFN therapy, did not have a core-gene-deletion HBV variant during follow-up, but had aa substitutions clustered in some restricted core regions. Two control asymptomatic carriers, who had no change in biochemical or virologic markers over a 15- to 19-year period, had no core-gene-deletion variants and few aa changes. These findings indicate that the mid-portion of the core gene is subject to deletion even during the quiescent phase. Thus, the immunologic interaction between the host and virus may occur insidiously, and the emergence of a core-gene-deletion HBV variant during the quiescent phase may be involved in the onset of hepatitis and the subsequent outcome of chronic infection.

Amino Acid Sequence↗
PubMed1998

Emergence and takeover of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy and re-takeover by wild type after cessation of therapy.

Treatment of hepatitis B virus (HBV) with lamivudine is effective in suppressing virus replication and results in reduced inflammatory activity. However, the emergence of lamivudine-resistant mutant virus, with amino acid substitution in the YMDD motif of DNA polymerase, has been reported. We report the emergence and takeover of YMDD mutant and re-takeover by wild type during and after long-term lamivudine therapy. YMDD mutants were detected in five patients who showed DNA breakthrough (HBV DNA becoming detectable after a period of DNA negativity), which occurred after 9 to 14 months of lamivudine therapy. Four of five mutants had amino acid sequence YIDD, and the remaining mutant had YVDD. Patients with high HBV-DNA titer and/or hepatitis B e antigen tended to develop breakthrough (P = .038). Using a sensitive and specific polymerase chain reaction (PCR)-based method developed in this study, the emergence of YMDD mutants was detected 1 to 4 months before DNA breakthrough, but not detected in any of the pretreatment sera. The mutants were predominant at breakthrough, but were replaced by wild-type virus 3 to 4 months after cessation of therapy in the two patients who discontinued therapy. One of these patients had a relapse of hepatitis. Mutant continued to replicate in the remaining three patients who continued to receive treatment, and relapse occurred in only one of these patients. Our results suggest that the replication of YMDD mutant viruses is less than wild type and is re-overtaken by wild type after cessation of therapy. Re-administration of lamivudine, possibly combined with other antiviral therapy, might be useful in some patients experiencing hepatitis with lamivudine-resistant variants.

Adult↗
PubMed1998

Usefulness of hepatitis C virus RNA counts by second generation HCV bDNA-probe in chronic hepatitis C based on the HCV genotype.

Detection of hepatitis C virus (HCV) RNA by a second generation (ver 2) HCV bDNA-probe method (bDNA-probe) was compared with detection by the first generation (ver 1) assay. The two assays were performed simultaneously with the same serum samples of HCV genotypes 1b, 2a, 2b, 3a, and 3b. The positive rates with ver 1 were 82% for HCV genotype 1b (type 1b), 57.6% for HCV genotype 2a (type 2a), 75.0% for HCV genotype 2b (type 2b), 55.6% for HCV genotype 3a (type 3a), and 93.8% for HCV genotype 3b (type 3b). The positive rates with ver 2 were 95.0% for type 1b, 93.9% for type 2a, 83.3% for type 2b, 100% for type 3a, and 93.8% for type 3b. With Fisher's exact test, the detection rate for type 2a was significantly higher (P = 0.001) with ver 2 than with ver 1. We obtained regression lines using the HCV counts measured by bDNA-probe on the y axis and the HCV counts obtained by an HCV reverse transcriptase (RT)-competitive polymerase chain reaction method (competitive PCR) on the x axis. The gradients for types 1b, 2a, and 3b were greater with ver 2 compared to ver 1. The gradients for types 2a and 3b were the highest: for type 2a, y = 0.135x + 0.6 with ver 1 and y = 0.248x + 0.1 with ver 2; for type 3b, y = 0.366x + 0.1 with ver 1 and y = 0.727x + 0.3 for ver 2. In addition, HCV-RNA counts for all the genotypes tested in this study were significantly higher with ver 2 than with ver 1. Hence, we conclude that ver 2 of the bDNA-probe measures HCV-RNA counts closer to those obtained with competitive PCR than the ver 1 assay.

DNA Probes↗
PubMed1998

Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients.

BACKGROUND/AIMS/METHODS: The aim of this study was to elucidate the rate of development to cirrhosis and the rate of appearance of hepatocellular carcinoma in chronic viral hepatitis and to assess the risk factors for the development of disease in 2215 consecutive patients with viral hepatitis who were prospectively studied for a median observation period of 4.1 years. RESULTS: The rates of development to cirrhosis were 7.6%, 21.7%, and 32.2%, at the 5th, 10th, and 15th year, respectively. The carcinogenesis rates were 3.4%, 10.5%, and 22.4% at the 5th, 10th, and 15th year, respectively. The appearance rates of cancer in 645 patients with only hepatitis B surface antigen and in 1500 patients with only anti-hepatitis C virus antibodies were 2.1% and 4.8% at the 5th year, 4.9% and 13.6% at the 10th year, and 18.8% and 26.0% at the 15th year, respectively. The proportional hazard model identified that the amount of alcohol intake (p= 0.0002) and the indocyanine green retention rate (p= 0.022) were independently associated with carcinogenesis in hepatitis type B; and stage of hepatitis (p<0.0001), gamma-glutamyl transpeptidase (p= 0.0046), history of blood transfusion (p=0.0093), albumin (p=0.012), and amount of alcohol intake (p= 0.031) were independently associated with the carcinogenesis rate in hepatitis type C. Although the severity of portal fibrosis was closely correlated with the future disease development and carcinogenesis in chronic hepatitis C, it was not a good predictor in chronic hepatitis B. CONCLUSION: These epidemiological results suggest that there are some differences in the activity and modes of disease progression and cancer promotion between hepatitis B virus infection and hepatitis C virus infection.

Adolescent↗
PubMed1998

Predictive factors in eradicating hepatitis C virus using a relatively small dose of interferon.

Interferon (IFN) can reduce hepatitis C virus load and even eliminate the virus in 30-40% of patients. Several predictive factors for eradication of the virus have been reported and a higher dose of IFN tends to result in elimination of the virus. However, a small dose of IFN sometimes is as effective as a large dose in eradicating the virus. The predictive factors for such a response are not well established. We retrospectively analysed 50 patients with chronic hepatitis C who were treated with relatively small amounts of IFN (equal or less than 252 million units). Eleven patients were responders (elimination of hepatitis C virus (HCV) and normalization of alanine amino transferase (ALT) for at least 6 months), but the remaining 39 were non-responders. Multivariate analysis showed that the pretreatment viral load and total dose of IFN per kilogram of bodyweight were significant predictive factors of response to therapy. We also assessed the amino acid substitutions in the IFN sensitivity determining region (ISDR), NS5A codon 2209-2248, of HCV in serum samples obtained from 31 patients with HCV genotype 1b. The presence of more than one amino acid substitution in the ISDR tended to correlate with HCV genotype 1b elimination. As IFN is expensive and has a number of serious side effects, our study suggests that the optimal dose of IFN may vary from one patient to another and that more stringent criteria should be used to select the optimal dose for therapy.

Adult↗
PubMed1998

Biochemical and histological features of hepatitis G virus infection.

To assess the biochemical and histological characteristics of hepatitis G virus (HGV) infection, we examined four patients who were infected with HGV only (HGV group), and compared them with 16 patients infected with both HGV and hepatitis C virus (HCV; HGV + HCV group) and 18 patients infected with HCV only (HCV group). Biochemical examination showed a significantly low level of serum alanine aminotransferase (ALT) in the HGV group, and that the gamma-glutamyl transpeptidase (gamma-GTP)/ALT ratio in the same group was significantly higher than in the other two groups. Although all three patient groups had a similar degree of liver fibrosis, both the degree of periportal inflammation and total histological activity index were significantly lower in the HGV group than in the other two groups. Fibrous enlargement of the portal tract without lymphoid infiltration and thin fibrous septa was characteristically observed in the HGV group. No significant difference was found between the HGV + HCV group and HCV group. Our results suggest that biochemical and histological changes in HGV infection are very mild and quite different from those of HCV infection.

Adult↗
PubMed1998

Glomerulonephritis in autopsy cases with hepatitis C virus infection.

The glomerular changes of 188 consecutive autopsy cases with hepatitis C virus (HCV) infection were studied. The glomerular changes were classified as follows: Category I: membranoproliferative glomerulonephritis (MPGN; 21 cases, 11.2%), 2) Category II: membranous nephropathy (MN; 5 cases, 2.7%), 3) Category III: mesangial proliferative glomerulonephritis (MesGN; 33 cases, 17.6%), 4) Category IV: mesangial thickening type without proliferative mesangial cell (MT; 44 cases, 23.4%), and 5) Category V: almost normal glomeruli (85 cases, 45.2%). Glomerulonephritis was defined as glomeruli with an increase in mesangial matrix or a thickening of the capillary walls in the glomeruli; categories I-IV corresponded to glomerulonephritis in this study. Multivariate analysis, using a multiple logistic model, indicated that glomerulonephritis with HCV infection was the most strongly correlated to the existence of esophagogastric varices. Abnormal urinalysis, that is transient or continuous microhematuria or proteinuria, was observed in only 23 (12.2%) cases. These results showed that in HCV-RNA positive patients with esophagogastric varices the possibility of glomerulonephritis should be considered.

Adult↗
PubMed1998

Relationship of angiographic finding with neovascular structure detected by immunohistochemical staining of alpha-smooth muscle actin in small hepatocellular carcinoma.

To elucidate the relationship between angiographic features and histological findings, an immunohistological study of alpha-smooth muscle actin was performed in 106 patients with small hepatocellular carcinoma. Arterial dominance or portal blood paucity were found in 73 patients (68.9%) on digital subtraction angiography, 88 (83.0%) on computerized tomographic arterial portography and 87 (82.1%) on carbon dioxide-enhanced ultrasonography. Among 73 patients with hypervascularity on angiography, 57 (78.1%) had thick-walled, nuclei-rich and slender-shaped vessels (type II), eight (11.0%) had thin-walled, nuclei-poor and oval-shaped vessels (type I) and the remaining eight had a mixed type of II and I. Conversely, among 33 patients without hypervascularity, five (15.2%) had a type II, 21 (63.6%) had a type I, five had a mixed type and two had no positive vessel. Tumour size, histological classification and amount of non-triadal vessels were also associated with the angiographic appearance of the tumours. Among varied aspects of the cancer including tumour size, tumour multiplicity, microscopic portal invasion, histological classification, amount of alpha-smooth muscle actin-positive vessels and shape of alpha-smooth muscle actin-positive vessels, multivariate logistic regression analysis demonstrated that the shape of alpha-smooth muscle actin-positive vessels was solely associated with angiographic hypervascularity independently (P<0.0001). Although the existence of non-triadal vessels characterized hepatocellular carcinoma, angiographic hypervascularity was closely associated with the type II vessel. A morphological change of non-triadal vessel from type I to type II was considered to occur in an early stage of hepatocellular carcinoma.

Actins↗
PubMed1997

The long term efficacy of glycyrrhizin in chronic hepatitis C patients.

BACKGROUND: Hepatocellular carcinoma (HCC) occurs in patients with hepatitis C virus-RNA positive chronic liver disease. It is important to prevent HCC with drug administration. METHODS: A retrospective study was undertaken to evaluate the long term preventive effect of Stronger Neo-Minophagen C (SNMC) on HCC development. SNMC is a Japanese medicine that is commonly administered to patients with chronic hepatitis C to improve the serum alanine aminotransferase (ALT) level. Of 453 patients diagnosed with chronic hepatitis C retrospectively in the study hospital between January 1979 and April 1984, 84 patients (Group A) had been treated with SNMC; SNMC was given at a dose of 100 mL daily for 8 weeks, then 2-7 times a week for 2-16 years (median, 10.1 years). Another group of 109 patients (Group B) could not be treated with SNMC or interferon for a long period of time (median, 9.2 years) and were given other herbal medicine (such as vitamin K). The patients were retrospectively monitored, and the cumulative incidence of HCC and risk factors for HCC were examined. RESULTS: The 10th-year rates of cumulative HCC incidence for Groups A and B were 7% and 12%, respectively, and the 15th-year rates were 12% and 25%. By Cox regression analysis, the relative risk of HCC incidence in patients not treated with SNMC (Group B) was 2.49 compared with that of patients treated with SNMC (Group A). CONCLUSIONS: In this study, long term administration of SNMC in the treatment of chronic hepatitis C was effective in preventing liver carcinogenesis.

Adult↗
PubMed1997

Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity-determining region predict the outcome of interferon treatment in patients with chronic genotype 1b hepatitis C virus infection.

Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are predictive factors of poor response to interferon therapy in patients with chronic hepatitis C. To further examine the factors predicting the response to interferon in patients with genotype 1b infection, we analyzed 110 consecutive patients with HCV who were treated with a total of 624 million units of lymphoblastoid interferon alfa. Thirty-six patients (33%) were responders, while the remaining 74 patients (67%) were nonresponders. Multivariate analysis showed that a high virus titer (assessed by serum core protein level, P = .0021) and the presence of more than two amino acid substitutions in the interferon sensitivity-determining region (ISDR) (P = .0036) correlated significantly with the response to interferon therapy. Because mutations analyzed by direct sequencing of polymerase chain reaction (PCR) products may reflect artifacts of direct sequencing, we further analyzed quasispecies of HCV in this region by cloning and sequencing. Although PCR-based analysis of responders with multiple amino acid substitutions in the ISDR showed the presence of a small amount of wild-type strain in their serum, the results obtained by direct sequencing and cloning were essentially the same. A longitudinal study of quasispecies in 2 patients who showed a dramatic change in the virus titer showed no conversion from wild type to mutant or vice versa. Our results indicate that amino acid substitutions and virus load are independent predictors of the response to interferon therapy. The ability of some patients with no mutation in the ISDR or high virus load to eliminate the virus suggests the presence of other unidentified factors, host or viral, that influence the response to interferon therapy.

Adult↗
PubMed1997

Effect of arterial administration of a high molecular weight anti-tumor agent, styrene maleic acid neocarzinostatin, for multiple small liver cancer--a pilot study.

To assess the efficacy of the zinostatin derivative, the anti-tumor agent, styrene-maleic acid neocarzinostatin, in treating multiple small liver cancers, 29 patients with multiple hepatocellular carcinoma of 3 cm or less in diameter were treated with intraarterial injections of this high molecular weight agent, mixed with Lipiodol. Computed tomography 3 months after the first therapy showed complete deposition of Lipiodol in the entire area of the original tumor in 8 patients (27.6%), 50%-99% deposition in 4 (13.8%), 10%-49% in 10 (34.5%), and less than 10% in 7 (24.1%). After repeated injections, Lipiodol deposition in the entire area of the original tumor was found in 11 patients (37.9%). The degree of Lipiodol deposition depended on the angiographic vascularity of the tumor and on the images of the computed tomogram during arterial portography. Although complete deposition of Lipiodol was found in all tumors in 10 (58.8%) of the 17 patients with well demarcated round hypervascularity, only 1 (8.3%) of 12 patients with ill demarcated tumors showed complete deposition of Lipiodol in the tumors. Taking into account that hypervascularity on angiograms was closely correlated with the degree of Lipiodol accumulation on computed tomograms taken later, it appears that well demarcated round-shaped liver cancer is the best candidate for styrene-maleic acid neocarzinostatin therapy.

Adult↗
PubMed1997

Time course of histological changes in patients with a sustained biochemical and virological response to interferon-alpha therapy for chronic hepatitis C virus infection.

BACKGROUND/AIMS: Although biochemical and virological responses to interferon-alpha therapy for chronic hepatitis C virus infection have been extensively studied, long-term changes in liver histology have not been well documented. METHODS: We retrospectively analyzed 105 paired liver biopsy specimens taken before and after treatment from 93 patients who persistently showed biochemical remission and an absence of viremia for up to 68 months. RESULTS: The grading scores for necroinflammatory and fibrotic activity in the liver biopsy specimens decreased significantly after interferon-alpha therapy. Histological scores graded according to Knodell's components improved significantly in every category after interferon-alpha therapy. However, inflammatory cell infiltrates remained within the portal tracts for long periods; necroinflammation in the periportal and lobular regions were absent in most of the post-therapy specimens. The cumulative disappearance rate, calculated using the Kaplan-Meier method, was significantly lower for portal inflammation than for periportal or lobular necroinflammation but was equivalent to that for histological disease activity. On univariate analysis, age and fibrosis at the onset of treatment were significant factors influencing the response of histological disease activity to interferon-alpha therapy (p=0.025 and 0.049, respectively). Using Cox's proportional hazard analysis, age was the only significant independent predictor of histological response to treatment (p=0.035). CONCLUSIONS: Clinical remission of chronic hepatitis C virus infection is associated with histological resolution of necroinflammation in the periportal and lobular regions. Host-related factors are likely to influence whether early remission of inflammation after interferon-alpha therapy occurs.

Adult↗
PubMed1997

A prospective randomized administration of 5'-deoxy-5-fluorouridine as adjuvant chemotherapy for hepatocellular carcinoma treated with transcatheter arterial chemoembolization.

A prospective randomized trial was conducted to evaluate the efficacy of long-term oral administration of low-dose 5'-deoxy-5-fluorouridine (5'-DFUR) as an adjuvant chemotherapy, following transcatheter arterial embolization (TAE) in 40 patients with hepatocellular carcinoma (HCC). Forty eligible patients were randomized into two groups: 20 with TAE plus 5'-DFUR (400 mg/day) and 20 with TAE alone. A good necrosis rate or decrease in size of more than 70% of the original tumor mass was attained in 14 by the TAE plus 5'-DFUR arm, and in 12 by the TAE arm at 3 months after the first TAE. Although all five patients with HCC and 70-99% necrosis rate after the first TAE in the TAE alone arm showed a less than 70% necrosis rate at 12 months, four of the seven patients with a 70-99% necrosis in the TAE plus 5'-DFUR arm retained a necrosis of more than 70% at 12 months after the first TAE. The appearance rate of ascites and/or encephalopathy in patients with chemotherapy was not different from that of patients with TAE alone. One-year survival rates in the TAE plus 5'-DFUR arm and the TAE alone arm were 75.0% and 85.0%, 2-year rates were 64.2% and 66.2%, and 3-year rates were 64.6% and 49.7%, respectively. There was no significant difference in the survival curves. In conclusion, adjuvant therapy with 5'-DFUR was well tolerated without significant side effects, and it might maintain a good necrosis state of HCC after TAE. In order to confirm a beneficial effect of the chemotherapy on the survival period, a study using more patients and longer observation periods will be required.

Adult↗
PubMed1997

[Cranial MRI in the patients with chronic liver disease (CLD)].

We examined cranial MRI in 62 patients with CLD. Abnormal finding that high intensity area in symmetrical bilateral basal ganglia other than globus pallidum was found on both T-1 weighted images (T1WI) and fat suppression (chemical shift selective) images. This MRI finding was observed in 32 of 41 patients with cirrhosis while 1 of 21 patients with chronic hepatitis. This MRI finding was irreversible. The incidence of this MRI finding was correlated with severity of CLD and was statistically significant between in the patients with chronic hepatitis and those with cirrhosis. The contributing factors to the incidence of this MRI finding were severity of CLD and total bilirubin level by an analysis with logistic regression model. This MRI finding was detected clearer in a fat suppression imaging than in T1WI. The cause of this MRI finding was supposed not fat related substance by the finding of fat suppression imaging. This MRI finding would be useful for prediction of severity of CLD.

Adult↗
PubMed1996

Relationship between pretreatment viremia level and response to interferon-alpha therapy in chronic hepatitis C differs in viral type 1 and 2 infections.

To determine the contribution of virus-related factors to long-term remission of chronic hepatitis C infection, we analyzed viral type and viremia level in 185 patients who had undergone a six-month course of interferon-alpha therapy. These virus-related factors were measured by an enzyme-linked immunosorbent assay with use of viral type-specific antigens and the branched DNA (bDNA) signal amplification assay, respectively. Sustained and long-term sustained responses were achieved in 55% and 50% of the patients, respectively. Transient or no responses were observed in 30% and 15% of the patients, respectively. Thirty-five percent of viral type 1 patients and 82% of viral type 2 patients had long-term sustained responses. Forty-two percent of bDNA-positive and 71% of bDNA-negative patients experienced long-term sustained responses. On multivariate analysis, viral type, Knodell's intralobular score, and viremia level were strong independent predictors of long-term sustained response (P < 0.0001, = 0.0060, and 0.037, respectively). Viremia level, however, was a significant predictor only in viral type 1, not type 2, patients. The relation between pretreatment viremia level and response to interferon-alpha therapy in chronic hepatitis C differs in viral type 1 and 2 infections.

Chronic Disease↗
PubMed1996

A randomized, double-blind, controlled trial of natural interferon-beta therapy for e-antigen-negative chronic hepatitis B patients with abnormal transaminase levels.

Intermittent interferon (IFN) therapy appears to be effective for patients with e-antigen-negative chronic hepatitis B who exhibit abnormal fluctuations of alanine aminotransferase (ALT) levels and histological evidence of disease progression. To determine the optimal dose of IFN in such patients, we studied the effects of natural IFN-beta in a prospective, randomized, double-blind, controlled trial in 36 patients with e-antigen-negative chronic hepatitis B who repeatedly demonstrated abnormal fluctuations in ALT levels. Thirty-six patients were randomly assigned to three groups, receiving doses of: 0.3 MIU IFN (group 1; n = 12), 1 MIU (group 2; n = 12), or 3 MIU (group 3; n = 12), administered twice per week for 24 weeks. Patients were regarded as responders if ALT levels remained within the normal range and HBV-DNA tested negative for 6 months after the initiation of the therapy. According to this criterion, treatment was effective in 16.7% of the patients (2/12) in group 1, 33.3% (4/12) in group 2, and 75% (9/12) in group 3, the efficacy rate in group 3 being significantly higher than that in the other two groups. However, in 12 of the 15 responders, (80%) ALT levels were frequently elevated again within 3 years of the termination of IFN therapy. Although IFN was effective in controlling the manifestations of hepatitis in terms of e-antigen-negative patients who exhibited abnormal fluctuations in ALT, it appears that continuous treatment with intermittent high-dose IFN is necessary to maintain ALT levels within the normal range.

Adult↗