Heat-killed Lactobacillus helveticus improves mood states: a randomised, double-blind, placebo-controlled study.

We investigated the effects of heat-killed Lactobacillus helveticus MCC1848 on daily mood states in healthy young adults. Participants (n=58) were randomised to receive heat-killed L. helveticus MCC1848 powder or placebo powder for 4 weeks. During the study period, adverse events were recorded in the participant diary. Mood states were assessed before and 2 and 4 weeks after initiation of the intervention. The primary outcomes were the shortened version of the Profile of Mood States 2 (POMS 2) scores. Secondary outcomes included other mood state (State-Trait Anxiety Inventory (STAI); visual analogue scale (VAS)), quality of life (acute form of the SF-36v2), sleep (Athens Insomnia Scale (AIS)) and fatigue (Chalder Fatigue Scale (CFS)) scores. Four weeks of heat-killed L. helveticus MCC1848 intake, compared to placebo, significantly improved the shortened version of the POMS 2 'friendliness' and the VAS 'relaxed' scores, which are two indicators of positive mood states. On the other hand, heat-killed L. helveticus MCC1848 intake had no significant effects on negative mood state items (e.g. anger, nervousness, confusion) assessed by the shortened version of the POMS 2, STAI and VAS. AIS and CFS scores also showed no significant differences. No adverse effects were observed with 4 weeks of heat-killed L. helveticus MCC1848 intake. These results suggest that daily consumption of heat-killed L. helveticus MCC1848 is safe and has the potential to improve positive mood states. UMIN Clinical Trial Registry: UMIN000043697.

Deciphering the influence of paraimmunobiotic bifidobacteria on the innate antiviral immune response of bovine intestinal epitheliocytes by transcriptomic analysis.

Previously, we reported that the non-viable immunomodulatory Bifidobacterium infantis MCC12 and Bifidobacterium breve MCC1274 strains (paraimmunobiotic bifidobacteria) were able to increase the protection against rotavirus infection in bovine intestinal epithelial (BIE) cells. In order to gain insight into the influence of paraimmunobiotic bifidobacteria on the innate antiviral immune response of BIE cells, their effect on the transcriptomic response triggered by Toll-like receptor 3 (TLR3) activation was investigated. By using microarray technology and qPCR analysis, we obtained a global overview of the immune genes involved in the innate antiviral immune response in BIE cells. Activation of TLR3 by poly(I:C) in BIE cells significantly increased the expression of interferon (IFN)-α and IFN-ß, several interferon-stimulated genes, cytokines, and chemokines. It was also observed that both paraimmunobiotic bifidobacteria differently modulated immune genes expression in poly(I:C)-challenged BIE cells. Most notable changes were found in genes involved in antiviral defence (IFN-ß, MX1, OAS1X, MDA5, TLR3, STAT2, STAT3), cytokines (interleukin (IL)-6), and chemokines (CCL2, CXCL2, CXCL6) that were significantly increased in bifidobacteria-treated BIE cells. B. infantis MCC12 and B. breve MCC1274 showed quantitative and qualitative differences in their capacities to modulate the innate antiviral immune response in BIE cells. B. breve MCC1274 was more efficient than the MCC12 strain to improve the production of type I IFNs and antiviral factors, an effect that could be related to its higher ability to protect against rotavirus replication in BIE cells. Interestingly, B. infantis MCC12 showed a remarkable anti-inflammatory effect. The MCC12 strain was more efficient to reduce the expression of inflammatory cytokines and chemokines (IL-16, IL-20, CX3CL1) when compared with B. breve MCC1274. These results provided valuable information for the deeper understanding of the antiviral immune response of intestinal epithelial cells as well as the host-paraimmunobiotic interaction in the bovine host.

Bioactive factors secreted by Bifidobacterium breve B-3 enhance barrier function in human intestinal Caco-2 cells.

Intestinal barrier function is closely related to intestinal health and diseases. Recent studies demonstrate that some probiotic and commensal bacteria secrete metabolites that are capable of affecting the intestinal functions. The present study examined an enhancing effect of bioactive factors secreted by Bifidobacterium breve strain B-3 on the intestinal tight junction (TJ) barrier integrity in human intestinal Caco-2 cells. Administration of conditioned medium obtained from B. breve strain B-3 (B3CM) to Caco-2 cells for 24 h increased trans-epithelial electrical resistance (TER), a TJ barrier indicator, across their monolayers. Immunoblot, immunofluorescence, and qPCR analyses demonstrated that B3CM increased an integral TJ protein, claudin-4 expression. In luciferase reporter assay, the administration of B3CM enhanced the claudin-4 promoter activity, indicating the transcriptional upregulation of claudin-4. Site-directed mutation of specificity protein 1 (Sp1) binding sites in the claudin-4 promoter sequence and suppression of Sp1 expression by siRNA technology clearly reduced the enhancing effect of B3CM on claudin-4 promoter activity. Liquid chromatography/mass spectrometry detected a significant amount of acetic acid in B3CM (28.3 mM). The administration of acetic acid to Caco-2 cells partially mimicked a B3CM-mediated increase in TER, but failed to increase claudin-4 expression. Taken together, bioactive factors secreted by B. breve B-3 enhanced the TJ barrier integrity in intestinal Caco-2 cells. Transcriptional regulation of claudin-4 through Sp1 is at least in part one of the underlying molecular mechanisms. In addition, acetic acid contributes to the B3CM-mediated barrier effect independently of claudin-4 expression.

Effects of paraprobiotic Lactobacillus paracasei MCC1849 supplementation on symptoms of the common cold and mood states in healthy adults.

We investigated the effects of paraprobiotic Lactobacillus paracasei MCC1849 (LAC-Shield™) on symptoms of the common cold and mood states in healthy young adults. A total of 241 participants were randomised to receive 1×1010 heat-killed L. paracasei MCC1849 cell powder (10LP), 3×1010 heat-killed L. paracasei MCC1849 cell powder (30LP), or placebo powder without any L. paracasei cells once daily for 12 weeks based on the incidence of the common cold in the previous year, so that the risk of the incidence was equal among the groups. The incidence and severity of common cold symptoms were rated daily in a subject diary. Salivary secretory immunoglobulin A concentrations and saliva flow rates were analysed at 0 and 6 weeks. The Profile of Mood States (POMS) was assessed using POMS 2 0, 6, and 12 weeks after the intervention. No significant differences were observed in the incidence of the common cold among the groups. In a prespecified subgroup of subjects who had the common cold in the previous year, the incidence, total number of days of symptoms, and symptom scores of the common cold significantly improved in the 10LP-intake group, and were slightly lower in the 30LP-intake group than in the placebo group. The level of deterioration in the positive mood state caused by stress was less in the MCC1849-intake group than in the placebo group. These results indicate that L. paracasei MCC1849 has the potential to improve resistance to common cold infections in susceptible subjects and maintain a desirable mood state, even under mental stress conditions. Further randomised controlled trials are needed in order to investigate the possible beneficial effects of paraprobiotic L. paracasei MCC1849 on the common cold in susceptible populations.

Development of an in vitro immunobiotic evaluation system against rotavirus infection in bovine intestinal epitheliocytes.

The bovine intestinal epithelial cell line (BIE cells) expresses the Toll-like receptor (TLR)3 and is able to mount an antiviral immune response after the stimulation with poly(I:C). In the present study, we aimed to further characterise the antiviral defence mechanisms in BIE cells by evaluating the innate immune response triggered by rotavirus (RV) infection. In addition, we attempted to determine whether immunobiotic bifidobacteria are able to confer protection of BIE cells against RV infection by beneficially modulating the antiviral immune response. RV OSU (porcine) and UK (bovine) effectively infected BIE cells, while a significant lower capacity to infect BIE cells was observed for human (Wa) and murine (EW) RV. We observed that viral infection in BIE cells triggered TLR3/RIG-I-mediated immune responses with activation of IRF3 and TRAF3, induction of interferon beta (IFN-ß) and up-regulation of inflammatory cytokines. Our results also demonstrated that preventive treatments with Bifidobacterium infantis MCC12 or Bifidobacterium breve MCC1274 significantly reduced RV titres in infected BIE cells and differentially modulated the innate immune response. Of note, both strains significantly improved the production of the antiviral factor IFN-ß in RV-infected BIE cells. In conclusion, this work provides comprehensive information on the antiviral immune response of BIE cells against RV, that can be further studied for the development of strategies aimed to improve antiviral defences in bovine intestinal epithelial cells. Our results also demonstrate that BIE cells could be used as a newly immunobiotic evaluation system against RV infection for application in the bovine host.

Bifidobacterium breve prevents necrotising enterocolitis by suppressing inflammatory responses in a preterm rat model.

Necrotising enterocolitis (NEC) is associated with inflammatory responses and barrier dysfunction in the gut. In this study, we investigated the effect of Bifidobacterium breve M-16V on factors related to NEC development using an experimental rat model. Caesarean-sectioned rats were given formula milk with or without B. breve M-16V by oral gavage thrice daily, and experimental NEC was induced by exposing the rats to hypoxic conditions. Naturally delivered rats that were reared by their mother were used as healthy controls. The pathological score of NEC and the expression of molecules related to inflammatory responses and the barrier function were assessed in the ileum. B. breve M-16V reduced the pathological scores of NEC and resulted in some improvement in survivability. B. breve M-16V suppressed the increased expression of molecules related to inflammation and barrier function that resulted from NEC induction. B. breve M-16V normalised Toll-like receptor (TRL)4 expression and enhanced TLR2 expression. Our data suggest that B. breve M-16V prevents NEC development by modulating TLR expressions and suppressing inflammatory responses in a rat model.

Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice.

Probiotics have been shown to have a preventative effect on skin photoaging induced by short term UV irradiation, however, the underlying mechanisms and the effect of probiotics on skin photoaging induced by chronic UV irradiation remain unclear. In this study, we investigated the effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in hairless mice. Mice were irradiated with UVB three times weekly and orally administered B. breve B-3 (2×10(9) cfu/mouse /day) for 7 weeks. Nonirradiated mice and UVB-irradiated mice without probiotic treatment were used as controls. B. breve B-3 significantly suppressed the changes of transepidermal water loss, skin hydration, epidermal thickening and attenuated the damage to the tight junction structure and basement membrane induced by chronic UVB irradiation. Administration of B. breve B-3 tended to suppress the UV-induced interleukin-1ß production in skin (P=0.09). These results suggest that B. breve B-3 could potentially be used to prevent photoaging induced by chronic UV irradiation.

Fluctuation of fecal microbiota in individuals with Japanese cedar pollinosis during the pollen season and influence of probiotic intake.

BACKGROUND: We have previously reported the results of a randomized, double-blind, placebo-controlled trial that found the intake of yogurt supplemented with a probiotic strain, Bifidobacterium longum BB536, alleviates symptoms and affects blood parameters in individuals with Japanese cedar pollinosis (JCPsis) during the pollen season. OBJECTIVE: In the present study, fecal microbiota were investigated to examine whether any changes occur during the pollen season and whether any influence is exerted by probiotic intake. METHODS: Yogurt either with BB536 (BB536 yogurt) or without BB536 (placebo yogurt) was administered for 14 weeks at 2 x 100 g per day to 40 subjects (17 men, 23 women) with a clinical history of JCPsis. Fecal samples were obtained from 23 subjects (placebo group, n=13; BB536 group, n=10) before and during the intervention (weeks 4, 9 and 13) and fecal microbiota were analyzed using terminal-restriction fragment length polymorphism and real-time polymerase chain reaction (PCR) methods. RESULTS: From the fluctuation patterns of terminal-restriction fragments, the Bacteroides fragilis group and bifidobacteria were among the species that changed most with pollen dispersion. Real-time PCR analyses indicated that the cell numbers of the B fragilis group increased significantly along with pollen dispersion in both BB536 and placebo groups. Cell numbers of bifidobacteria were significantly higher in the BB536 group compared with the placebo group (P < .05 at weeks 4 and 9). The ratio of cell numbers of the B fragilis group to bifidobacteria increased significantly during the pollen season in the placebo group (P < .01 at weeks 9 and 14), but not in the BB536 group. An in vitro study using peripheral blood mononuclear cells from JCPsis subjects indicated that strains of the B fragilis group induced significantly more helper T cell (T(H)) type2 cytokines (interleukin [IL]-6) but fewer T(H)1 cytokines (IL-12 and interferon) compared with those of bifidobacteria. CONCLUSIONS: These results suggest a relationship between fluctuation in intestinal microbiota and pollinosis allergy. Furthermore, intake of BB536 yogurt appears to exert positive ihfluences on the formation of anti-allergic microbiota.

Probiotics in the treatment of Japanese cedar pollinosis: a double-blind placebo-controlled trial.

BACKGROUND: Probiotic bacteria may be effective in the treatment of allergic inflammation and food allergy, but efficacy and underlying mechanisms remain unclear. OBJECTIVE: The present study investigated the effects of probiotic strain Bifidobacterium longum BB536 in the treatment of Japanese cedar pollinosis (JCPsis). METHODS: In a randomized, double-blind, placebo-controlled trial, 44 JCPsis subjects received BB536 or placebo for 13 weeks during the pollen season. Subjective symptoms and self-care measures were recorded daily and blood samples were taken before and during intervention to measure blood levels of parameters related to JCPsis. RESULTS: BB536 intake was associated with a significant reduction in number of subjects prematurely terminated due to severe symptoms and pollinosis medication (P=0.0057 vs. placebo group). Comparison of subjective symptom scores indicated significant decreases in rhinorrhea, nasal blockage and composite scores in the BB536 group compared with the placebo group. Comparison of medical scores showed marked improvements in all symptoms on BB536 intake. A T-helper type 2 (Th2)-skewed immune response occurring along with pollen dispersion was observed. BB536 significantly suppressed increases in plasma thymus- and activation-regulated chemokine and tended to suppress elevations of Japanese cedar pollen (JCP)-specific IgE. CONCLUSION: These results suggest the efficacy of BB536 in relieving JCPsis symptoms, probably through the modulation of Th2-skewed immune response.

Immunostimulatory oligodeoxynucleotide from Bifidobacterium longum suppresses Th2 immune responses in a murine model.

We have reported previously that novel immunostimulatory sequence (ISS) oligodeoxynucleotide (ODN) BL07S from a probiotic strain of Bifidobacterium longum inhibited immunoglobulin (Ig) E production in vitro. However, whether ISS-ODNs from probiotics regulate T helper type 2 (Th2)-polarized immune reactions in vivo remains unclear. To evaluate the inhibitory effects of ODN BL07S on type I allergic response, BALB/c mice were injected with or without ODN BL07S in the presence of ovalbumin (OVA) on days 0 and 14. Serum Ig levels (IgE, IgG1 and IgG2a) and cytokine levels (interferon (IFN)-gamma, interleukin (IL)-12, IL-4, IL-5, IL-10 and IL-13) were investigated in splenocyte cultures from days 14-28. Production of OVA-specific and total IgE were significantly suppressed by administration of ODN BL07S, but not by ODN BL06S, a non-ISS-ODN. Compared to controls, ODN BL07S induced significantly lower levels of Th2 cytokines (IL-4 and IL-5) in splenocyte cultures, and significantly higher levels of serum OVA-specific IgG2a. These effects of ODN BL07S on modulation of Th2 immune response were dose-dependent. The present results demonstrate that ODN BL07S from genomic DNA of B. longum BB536 prevents antigen-induced Th2 immune responses in vivo, suggesting that ISS-ODNs from probiotics might be useful in preventing allergic disease.

Effect of probiotic Bifidobacterium longum BB536 [corrected] in relieving clinical symptoms and modulating plasma cytokine levels of Japanese cedar pollinosis during the pollen season. A randomized double-blind, placebo-controlled trial.

Probiotic microorganisms have been shown to be effective in the treatment of allergic inflammation and food allergy, but their efficacy remains controversial. This study tested the effect of a yogurt supplemented with a probiotic strain Bifidobacterium longum BB536 in the treatment of Japanese cedar pollinosis (JCPsis). Forty subjects with a clinical history of JCPsis were given yoghurt either containing BB536 (BB536 yoghurt) or without BB536 (placebo yoghurt) at 2 X 100 g per day for 14 weeks, in a randomized, double-blind, placebo-controlled trial. Subjective symptoms and self-care measures were recorded daily and blood samples were taken before and during the intervention (at weeks 4, 9, and 14) to measure the blood parameter levels related to JCPsis. Yoghurt supplemented with BB536 significantly alleviated eye symptoms compared with placebo yoghurt (odds ratio 0.31; 95% confidence interval 0.10-0.97; p = 0.044). Although no statistically significant differences were detected, nasal symptoms such as itching, rhinorrhea, and blockage, as well as throat symptoms tended to be relieved with the BB536 yoghurt. BB536 tended to suppress the decreasing blood levels of interferon-gamma (IFN-y) and the increasing blood eosinophil rates; a significantly higher IFN-gamma level was observed for the difference from baseline at week 4. A decreased trend in the difference from baseline levels of JCP-specific IgE levels was also observed at week 4 in the BB536 group compared with the placebo group. In conclusion, these results suggest that intake of BB536-supplemented yoghurt may relieve JCPsis symptoms, probably through a modulating effect on Th balance.

Adhesion and releasing of Poliovirus to activated sludge of wastewater purifying plants.

Pathogenic enteric viruses are released from infected persons through domestic wastewater to the environment. From that point of view, the knowledge of the viral behavior in wastewater purifying process is important: it is, however, still poorly understood. In this study, we reported the adhesion of Poliovirus to activated sludge samples taken from wastewater purifying plants by using a model system. More than 10(6) particles adhered to one gram (wet) of activated sludge, and the adhered viral particles maintained infectivity for longer period of time and showed higher thermo-resistant than the free viral particles. The adhered viral particles were released by increase of salt concentration or alkaline pH buffer as infectious particles. The data suggest that pathogenic viruses could be enriched and maintain the infectivity in the activated sludge, and released to environments under certain conditions.

Relationships between colony morphotypes and oil tolerance in Rhodococcus rhodochrous.

A mucoidal strain of Rhodococcus rhodochrous was resistant to 10% (vol/vol) n-hexadecane, while its rough derivatives were sensitive. When the extracellular polysaccharide (EPS) produced by the mucoidal strain was added to cultures of the rough strains, the rough strains gained resistance to n-hexadecane. Thus, EPS confer tolerance to n-hexadecane in members of the genus Rhodococcus.

Immunological and virological predictors of outcome during interferon-alpha therapy of chronic hepatitis C.

Results from a multicentre, clinical trial of interferon-alpha2a (IFN-alpha2a) for the treatment of chronic hepatitis C are reported. Serum hepatitis C virus (HCV) RNA levels were monitored as follows: before, and 2 days after, the first administration of IFN-alpha2a; during and at the end of treatment; and 6 months after completion of therapy. Peripheral blood lymphocyte subpopulations were measured, by two-colour flow cytometry, before and 3 h after the first intramuscular (i.m.) administration of 9 mega units (MU) of IFN-alpha2a. Virological responders had a significantly lower pretreatment level of CD11+ CD8- lymphocytes. Biochemical responders had significantly lower pretreatment levels of CD11- CD8+, human leucocyte antigen (HLA) DR- CD4- and HLA DR- CD8+ populations, and a higher pretreatment HLA DR+ CD4- population. These pretreatment differences disappeared 3 h after the first i.m. administration of IFN-alpha2a. CD11- CD8+ and HLA DR+ CD8+ cell populations became significantly lower in virological responders 3 h after the first i. m. administration of IFN-alpha2a. HLA DR+ CD4+ cell populations were increased less in biochemical responders. Thus, T-lymphocyte subpopulations were different between responders and non-responders to IFN therapy and IFN-modulated host immunity. Multivariate analysis showed that the pretreatment CD11+ CD8- cell population was an independent predictive factor of response to therapy. On the other hand, patients whose serum HCV RNA cleared or decreased within the first 2 days of IFN-alpha2a therapy were more likely to achieve a virological response. This predictive factor, however, was not an independent factor by multivariate analysis. These results suggest that host immunity is an important factor in response to IFN therapy, and HCV clearance within the first 2 days is a good predictive factor of response.

[2-5 AS activity in serum and peripheral blood mononuclear cells for chronic active hepatitis C and the relationship to clinical outcome of interferon therapy].

Of 49 patients with chronic hepatitis C treated by interferon (IFN), we measured 2'-5'-oligoadenylate synthetase (2-5 AS) activity in peripheral blood mononuclear cells (PBMC) and serum before and after the IFN therapy and studied the correlation with the clinical outcome. Before IFN therapy, the levels of 2-5 AS in PBMC and serum were significantly higher in patients with chronic hepatitis C than in healthy controls, though there was no correlation between the 2-5 AS activity and the clinical outcome. When PBMC were stimulated with IFN in vitro, the induced 2-5 AS activities in patients with chronic hepatitis C were almost same as those in healthy controls. Among patients infected with hepatitis C virus (HCV) genotype II which was considered relatively resistant to IFN, patients whose HCV was disappeared from serum by IFN therapy showed good induction of 2-5 AS activity by IFN in vitro, whereas patients in which serum HCV remained positive after the therapy showed poor response to IFN in vitro. The levels of 2-5 AS in PBMC 2 months after IFN therapy were still higher in patients whose HCV was continuously disappeared from serum by the therapy (complete remission) than in healthy controls. The in vitro induction of 2-5 AS in patients whose HCV in serum remained positive after the therapy was significantly lower than in patients with complete remission. The induction of 2-5 AS activity in patients to whom IFN therapy was ineffective, significantly decreased after the IFN therapy as compared with the activity measured before the therapy. These findings suggest that measurement of 2-5 AS activity in PBMC in vitro through IFN therapy might be useful for predicting in vivo responsibility to IFN and also knowing the change of the responsibility.

Sacral glutamatergic transmission in the descending limb of the micturition reflex in the cat.

This study was undertaken to clarify the location of glutamatergic synaptic transmission in the descending pathway of the micturition reflex in decerebrate cats. Contractions of the urinary bladder evoked by stimulating the pontine micturition center were completely inhibited by the broad-spectrum excitatory amino acid antagonist, kynurenic acid (KYN) and the selective N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, that were applied intrathecally to the sacral cord, while such contractions were not attenuated by the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). An iontophoretic application of KYN remarkably inhibited discharges of the sacral parasympathetic preganglionic neurons innervating the urinary bladder (bladder motoneurons) elicited by pontine stimulation. Our results suggest that glutamatergic synaptic transmission is located at the level of the sacral cord in the descending limb of the micturition reflex and is mediated via NMDA receptor on the bladder motoneurons.

Cell-surface hydrophobicity and scum formation of Rhodococcus rhodochrous strains with different colonial morphologies.

Rhodococcus rhodochrous has been reported to be one of the micro-organisms responsible for the formation of scum which is thick and viscous biological foam in activated sludge plants. The hydrophobicity of mycolic acids present on the cell surface and the long-branched shape of the hyphae have been thought to contribute to the scum formation. Cell surface hydrophobicity and scum formation of four R. rhodochrous strains with different colony morphologies were determined, and the results showed that the two rough strains had strong cell surface hydrophobicity and produced scum, whereas the weakly hydrophobic smooth strain and the hydrophilic mucoidal strain did not. All four strains displayed long, branched hyphae, and their electrophoretic mobilities were similar, between pH 4 and 9. These data suggest that changes in the cell surface hydrophobicity of the R. rhodochrous result in changes in the culture characteristics and the formation of scum.

Expression of exogenous p59fyn modulates signaling in an immature B cell line, WEHI-231.

The WEHI-231 B lymphoma line is representative of immature B cells, which undergo growth arrest/apoptosis following cross-linking of surface immunoglobulin M (sIgM). In B cells, sIgM engagement has been shown to induce immediate (within seconds) activation of src family protein tyrosine kinases (PTKs) such as p53lyn/56lyn, p55blk, p56lck and p59fyn which are associated with B cell antigen receptor (BCR) complex. However, p59fyn expression is very low in both normal immature B cells and apoptosis-prone B cell lines, including WEHI-231. Such a finding prompted us to investigate the effects of ectopic expression of p59fyn in growth regulation of WEHI-231 cells. We have obtained WEHI-231 transfectants expressing the exogenous p59fyn by retroviral mediated gene transfer method. The transfectants demonstrated increased [Ca2+]i level in both the non-stimulated condition and sIgM cross-linking. The expression of ectopic p59fyn also increased the sensitivity of the transfectants to growth arrest signal by sIgM cross-linking. The results suggest that p59fyn can modulate signal transduction and growth regulation when expressed in the immature B cell line.

Assessment of histological features and outcome of interferon therapy in chronic hepatitis C.

The correlation between the histological features of liver biopsy specimens before interferon (IFN) treatment and the clinical effect of IFN administration on chronic hepatitis C was investigated. A study of the relation between several histological features that were graded in 60 liver biopsy specimens from chronic hepatitis C patients before IFN treatment disclosed that the grade of portal fibrosis was positively correlated with the grade of other inflammatory features, including piecemeal necrosis and portal and lobular inflammation. The degree of portal fibrosis adversely affected the rate of normalization of ALT levels in chronic hepatitis C during and after IFN treatment. We reexamined 36 liver biopsy specimens that showed a moderate degree of portal fibrosis, and found that the degree of piecemeal necrosis was inversely correlated with the extent of lymphoid follicle formation in the portal tracts. During IFN therapy, the group of chronic hepatitis C patients who showed marked piecemeal necrosis and less lymphoid follicle formation in the liver specimens had a poor response to IFN treatment, whereas another group that showed marked lymphoid follicle formation and little piecemeal necrosis in the liver specimens had a good response to IFN. These relationships gradually disappeared after the completion of IFN treatment.