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Background: Anorexia nervosa (AN) is a serious mental illness with high rates of relapse and mortality. Psychiatric comorbidities are common but their impact on the prognosis is largely unknown., Objective: The aim was to investigate the influence of psychiatric comorbidity on weight gain during treatment of AN., Methods: A systematic search was performed in PubMed/MEDLINE, EMBASE and PsycINFO. Studies evaluating psychiatric comorbidity as a predictor for treatment outcome (weight gain) were included, however, comorbid alcohol/drug addiction was excluded from this review., Results: Four thousand five hundred and twenty six publications were identified from which 15 were included. The majority of the included studies had a prospective open naturalistic study design, a short-term follow-up period, and were based on small populations of primarily adolescent and adult women. Four studies indicate depression, and two obsessiveness as negative prognostic factors, whilst one study indicated moderate depression and yet another, neuroticism, as positive predictors for weight gain., Discussion: The systematic scoping review found a large number of publications whereof only a few directly described the influence of psychiatric comorbidity on weight gain in AN. Overall, studies were heterogeneous in design, purpose and outcome making comparisons difficult. Findings were divergent but depression had a negative influence on weight gain in four studies., (© 2020 Eating Disorders Association and John Wiley & Sons Ltd.)

Aim: To assess the effect of sofosbuvir (SOF) based regimens on glycemic and lipid control., Methods: This is a retrospective analysis of hepatitis C virus (HCV)-infected patients treated and cured with a SOF regimen [SOF/ribavirin/interferon, SOF/simeprevir, or SOF/ledipasvir (LDV) ± ribavirin] from January 2014 to March 2015. Patients with hemoglobin A1C (HbA1C) and lipid panels within six months before and six months after therapy were identified and included in our study. Due to the known hemolytic effect of ribavirin, HbA1C was obtained a minimum of three months post-treatment for the patients treated with a ribavirin regimen. Medical history, demographics, HCV genotype, pre-therapy RNA, and liver biopsies were included in our analysis. The patients who started a new medication or had an adjustment of baseline medical management for hyperlipidemia or diabetes mellitus (DM) were excluded from our analysis., Results: Two hundred and thirty-four patients were reviewed, of which 60 patients met inclusion criteria. Sixty-three point three percent were male, 26.7% were Caucasian, 41.7% were African American and 91.7% were infected with hepatitis C genotype 1. Mean age was 60.6 ± 6.7 years. Thirty-nine patients had HbA1C checked before and after treatment, of which 22 had the diagnosis of DM type 2. HbA1C significantly decreased with treatment of HCV (pretreatment 6.66% ± 0.95% vs post-treatment 6.14% ± 0.65%, P < 0.005). Those treated with SOF/LDV had a lower HbA1C response than those treated with other regimens (0.26% ± 0.53% vs 0.71% ± 0.83%, P = 0.070). Fifty-two patients had pre- and post-treatment lipid panels; there was a significant increase in low-density lipoprotein (LDL) and total cholesterol (TC) after treatment (LDL: 99.5 ± 28.9 mg/dL vs 128.3 ± 34.9 mg/dL, P < 0.001; TC: 171.6 ± 32.5 mg/dL vs 199.7 ± 40.0 mg/dL, P < 0.001). Pre-treatment body-mass index (BMI) did not differ from post-treatment BMI ( P = 0.684)., Conclusion: Eradication of HCV with a SOF regimen resulted in a significant drop in HbA1C and an increase in LDL and TC post therapy., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest to report.

Objective: Cognitive impairment is integral to many neurological illnesses. Specific enhancement of glutamatergic transmission may improve memory and learning. Org 25935 increases the synaptic availability of glycine, an obligate co-agonist with glutamate at N-methyl-D-aspartate receptors. We hypothesised that Org 25935 would acutely improve the learning and memory of healthy volunteers., Methods: A randomised, double-blind, parallel-group, single-dose study of Org 25935 and placebo was carried out. Thirty-two healthy male volunteers took either 12-mg Org 25935 or matching placebo and were later assessed with the manikin task, digit span and verbal memory tests. Systematic assessments of cardiovascular and adverse events were also taken., Results: There was no effect of Org 25935 on reaction time, number of correct responses or learning (greater or slower improvement over successive tasks) compared with placebo. Org 25935 caused significantly more dizziness and drowsiness compared with placebo; these side effects were mainly mild., Conclusions: A single dose of Org 25935 does not improve learning or memory in healthy male individuals. However, the drug was well tolerated, and it remains to be seen whether it would have a positive effect on cognition in patient groups with pre-existing cognitive deficits.

Background: Limited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease., Methods: We determined genomewide associations with the presence of aortic-valve calcification (among 6942 participants) and mitral annular calcification (among 3795 participants), as detected by computed tomographic (CT) scanning; the study population for this analysis included persons of white European ancestry from three cohorts participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (discovery population). Findings were replicated in independent cohorts of persons with either CT-detected valvular calcification or clinical aortic stenosis., Results: One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance for the presence of aortic-valve calcification (odds ratio per allele, 2.05; P=9.0×10(-10)), a finding that was replicated in additional white European, African-American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically determined Lp(a) levels, as predicted by LPA genotype, were also associated with aortic-valve calcification, supporting a causal role for Lp(a). In prospective analyses, LPA genotype was associated with incident aortic stenosis (hazard ratio per allele, 1.68; 95% confidence interval [CI], 1.32 to 2.15) and aortic-valve replacement (hazard ratio, 1.54; 95% CI, 1.05 to 2.27) in a large Swedish cohort; the association with incident aortic stenosis was also replicated in an independent Danish cohort. Two SNPs (rs17659543 and rs13415097) near the proinflammatory gene IL1F9 achieved genomewide significance for mitral annular calcification (P=1.5×10(-8) and P=1.8×10(-8), respectively), but the findings were not replicated consistently., Conclusions: Genetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aortic-valve calcification across multiple ethnic groups and with incident clinical aortic stenosis. (Funded by the National Heart, Lung, and Blood Institute and others.).

Objective: A growing body of evidence supports the efficacy of D-cycloserine (DCS), a partial agonist at the N-methyl-D-aspartate (NMDA) glutamate receptor, as augmentation to cognitive-behavioral therapy (CBT) in the treatment of anxiety disorders. Org 25935 is a glycine transporter 1 inhibitor that acts to increase synaptic glycine levels and enhance NMDA-mediated glutamatergic activity. The aim of this study was to examine the efficacy of a glutamatergic compound other than DCS in a CBT augmentation paradigm., Method: This was a randomized, double-blind, placebo-controlled, parallel-group clinical trial for which participants were recruited from November 2008 through February 2010. Eligible adult patients diagnosed (DSM-IV) with panic disorder with or without agoraphobia (N = 40) were scheduled to receive 5 manualized CBT treatment sessions. Participants were randomly assigned to receive either a dose of Org 25935 (4 mg or 12 mg) or placebo 2 hours prior to the start of CBT sessions 3, 4, and 5. The primary endpoint was symptomatic change as measured by the Panic Disorder Severity Scale (PDSS) 1 week following the last CBT session., Results: Although mean PDSS total scores decreased significantly from baseline to end of treatment in every group, no statistically significant benefit was observed for Org 25935 (4 or 12 mg) over placebo on the primary endpoint or on any secondary efficacy endpoint. Org 25935 showed no safety issues at either dose but was much better tolerated at the 4-mg dose level than at the 12-mg dose level., Conclusions: Org 25935 demonstrated no benefit over placebo in augmenting CBT for panic disorder. Study limitations and implications are discussed., Trial Registration: clinicaltrials.gov Identifier: NCT00725725., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Enhancing glutamate function by stimulating the glycine site of the NMDA receptor with glycine, D-serine, or with drugs that inhibit glycine reuptake may have therapeutic potential in schizophrenia. The effects of a single oral dose of cis-N-methyl-N-(6-methoxy-1-phenyl-1,2,3,4-tetrahydronaphthalen-2-ylmethyl) amino-methylcarboxylic acid hydrochloride (Org 25935), a glycine transporter-1 (GlyT1) inhibitor, and placebo pretreatment on ketamine-induced schizophrenia-like psychotic symptoms, perceptual alterations, and subjective effects were evaluated in 12 healthy male subjects in a randomized, counter-balanced, within-subjects, crossover design. At 2.5 h after administration of the Org 25935 or placebo, subjects received a ketamine bolus and constant infusion lasting 100 min. Psychotic symptoms, perceptual, and a number of subjective effects were assessed repeatedly before, several times during, and after completion of ketamine administration. A cognitive battery was administered once per test day. Ketamine produced behavioral, subjective, and cognitive effects consistent with its known effects. Org 25935 reduced the ketamine-induced increases in measures of psychosis (Positive and Negative Syndrome Scale (PANSS)) and perceptual alterations (Clinician Administered Dissociative Symptoms Scale (CADSS)). The magnitude of the effect of Org 25935 on ketamine-induced increases in Total PANSS and CADSS Clinician-rated scores was 0.71 and 0.98 (SD units), respectively. None of the behavioral effects of ketamine were increased by Org 25935 pretreatment. Org 25935 worsened some aspects of learning and delayed recall, and trended to improve choice reaction time. This study demonstrates for the first time in humans that a GlyT1 inhibitor reduces the effects induced by NMDA receptor antagonism. These findings provide preliminary support for further study of the antipsychotic potential of GlyT1 inhibitors.

Dose reductions of pegylated interferon alpha and ribavirin may be avoided by using growth factors. This phase II clinical trial assesses the dose, efficacy and safety of darbepoetin alpha and filgrastim for treatment of anaemia and neutropenia associated with combination therapy for hepatitis C virus (HCV). Chronic hepatitis C patients (n = 101) received pegylated interferon alpha-2b (1.5 mug/kg once weekly) and ribavirin (800-1400 mg once daily). Patients with anaemia [haemoglobin (Hb) /= 0.75 x 10(9)/L and <10 x 10(9)/L. During antiviral therapy, 52% of patients required darbepoetin alpha, filgrastim or both. Hb at the time of darbepoetin alpha initiation was 10.2 +/- 0.4 g/dL. After 81 days of darbepoetin alpha, Hb increased by 1.9 +/- 1.0 g/dL to 12.1 +/- 1.1 g/dL (P < 0.0001). Filgrastim resulted in a significant increase in ANC [0.75 +/- 0.16 x 109/L to 8.28 +/- 5.67 x 10(9)/L (P < 0.0001)]. In treatment-naïve patients, 48% achieved sustained virological response (SVR), whereas 27% of patients previously treated with a course of pegylated interferon alpha achieved SVR. Low viral load, nongenotype 1 and treatment with growth factors were independently associated with SVR. Mild and severe anaemia were associated with quality of life impairments. Darbepoetin alpha resulted in an improvement in the Vitality domain of Short Form-36. No significant adverse events were related to growth factors. During anti-HCV therapy, filgrastim improved neutropenia and darbepoetin alpha improved both anaemia and quality of life. Future randomized clinical trials are needed to establish the impact of growth factors in improving sustained virological response.

Maturation is a critical process for dendritic cells (DC) to gain or enhance their functions in antigen presentation and T-cell activation. In this study, we investigated the effect of hepatitis C virus (HCV) envelope protein E2 on DC maturation and related functions. We show that binding of E2 protein to DC leads to a change from immature to mature phenotype as detected by an increased expression of cell surface molecules including CD83, CD80, CD86, CD11c and MHC class II. The E2-matured DC showed higher capacity to stimulate T-cell proliferation and interferon-gamma production and displayed higher levels of interleukin-12 production when compared with immature DC. The induction of DC maturation by E2 is both time- and dose-dependent and can be inhibited by anti-E2 antibodies. In addition, DC matured by E2 showed decreased uptake of bovine serum albumin and latex beads, indicating their decreased activities of endocytosis and phagocytosis upon maturation. Taken together, our results demonstrated that E2 protein is able to induce dendritic cell maturation and suggested that E2 protein may play an important role in regulation of immune responses during HCV infection.

During the last years, several clinical studies have been published trying to elucidate the effect of statin treatment on amyloid precursor protein (APP) processing and metabolism of brain cholesterol in Alzheimer's disease (AD) in humans. We present an open biochemical study where 19 patients with AD have been treated with simvastatin (20 mg/day) for 12 months. The aim was to further investigate the effect of simvastatin treatment on cerebrospinal fluid (CSF) biomarkers of APP processing, AD biomarkers as total tau and tau phosphorylated at threonine 181, brain cholesterol metabolism as well as on cognitive decline in patients with AD. Despite biochemical data suggesting that treatment with 20 mg/day of simvastatin for 12 months does affect the brain cholesterol metabolism, we did not find any change in CSF or plasma levels of beta-amyloid (Abeta)(1-42). However, by analysis of APP isoforms, we found that statin treatment may favor the nonamyloidogenic pathway of APP processing. The relevance and mechanism between statin treatment and AD has to be further elucidated by using statins of different lipophility in different dosages over a longer period of time.

Background: The role of various proteases in the pathogenesis of Alzheimer's disease is well documented. Recently, many members of the human tissue kallikrein family, a group of 15 secreted serine proteases, were found to be highly expressed in the central nervous system (CNS). Some of these enzymes can be measured in cerebrospinal fluid (CSF) by using ELISA-type methodologies., Methods: We quantified various kallikreins in CSF of 20 patients with Alzheimer's disease (AD), 16 patients with frontotemporal dementia (FTD), and 15 controls. We then correlated the levels of various kallikreins with presence of AD or FTD. Among all kallikreins measured, detectable levels in CSF were identified for kallikreins hK6, hK7, and hK10. Other tested kallikreins (hK5, hK8, hK11, and hK13) were unmeasurable. The most notable differences between kallikrein levels in CSF and the three groups of subjects were seen between controls and FTD patients for hK6 (decrease in FTD; P = 0.017), controls and FTD patients for hK7 (decrease in FTD; P < 0.001), and controls and AD patients for hK7 (decrease in AD; P = 0.019). In addition, significant differences were seen between FTD patients or control subjects and patients with AD patients for hK10 (increase in AD; P < 0.02). Approximately half of the AD patients had CSF hK10 levels that were higher than all patients with FTD except one and all control subjects except two. Various kallikrein concentrations in CSF were correlated, the strongest correlation seen between hK6 and hK7 (r(s) = 0.58). We also observed a statistically significant association between decreasing hK7 concentration in CSF and possession of one or two ApoE4 alleles (P = 0.014)., Conclusions: We demonstrate for the first time significant alterations of hK6, hK7, and hK10 concentration in CSF of patients with AD and FTD. Notably, all three kallikreins (hK6, hK7, and hK10) are decreased in CSF of FTD patients and hK10 is increased in CSF of AD patients, in comparison to control subjects. The possible connection between these enzymes and the pathogenesis and progression of AD and FTD needs to be further investigated.

Recently, biochemical criteria were proposed to complement histological criteria for the diagnosis of dementia lacking distinctive histopathology (DLDH), the most common pathological variant of frontotemporal dementias (FTDs), based on evidence of a selective reduction of soluble tau proteins in brains from a large cohort of sporadic DLDH and hereditary FTD (HDDD2 family) patients. To ensure that these findings are not unique to the populations included in the initial report, we extended the previous work by analyzing 22 additional DLDH brains from the United States and international centers. Our biochemical analyses here confirmed the previous findings by demonstrating substantial reductions in soluble brain tau in gray and white matter of 14 cases and moderate reductions in 6 cases of DLDH. We also analyzed brain samples from an additional affected HDDD2 family member, and remarkably, unlike other previously studied members of this kindred, this patient's brain contained substantial amounts of pathological or insoluble tau. These findings confirm and extend the definition of DLDH as a sporadic or familial "tau-less" tauopathy with reduced levels of soluble brain tau and no insoluble tau or fibrillary tau inclusions, and the data also underline the phenotypic heterogeneity of HDDD2, which parallels the phenotypic heterogeneity of other hereditary neurodegenerative FTD tauopathies caused by tau gene mutations.

Hepatitis C is a major cause of liver disease leading to cirrhosis. Although interferon (IFN) is the only approved therapy, treatment is characterized by low response rates and dose-limiting side effects. We evaluated the addition of thymosin alpha1 (TA1), an immunomodulatory peptide, to the standard treatment regimen for hepatitis C to determine if combination therapy shows biological activity using outcome measures including normalization of alanine aminotransferase levels, histological activity, and viral load during treatment. We performed a randomized, double-blind, placebo-controlled trial to compare the biological activity of a combination TA1 and IFN with that seen for IFN alone in patients with chronic hepatitis C infection. One hundred nine patients were randomized for intention to treat and received 1.6 mg of TA1 subcutaneously twice weekly and 3 MU of IFN three times weekly; 3 MU of IFN three times weekly and placebo TA1; or placebo for both agents. All patients had chronic HCV infection with confirmation of chronic hepatitis on liver biopsy. Biochemical responders were followed up until alanine aminotransferase (ALT) levels became abnormal or for 26 weeks, and relapsers were retreated for 26 weeks in the same treatment arm. One hundred three patients completed treatment for 26 weeks, and six patients dropped out. The groups were similar with regard to sex, gender distribution, baseline histological activity index (HAI) score, risk factors, and viral titers. End-of-treatment biochemical response was seen in 37.1% of patients treated with combination therapy, 16.2% of patients treated with IFN alone, and 2.7% of untreated controls by intent-to-treat analysis (IFN/TA1 vs. IFN, chi2 = 4.05, P = .04). HCV RNA clearance was seen in 37.1% of IFN/TA1-treated patients and 18.9% of IFN-treated subjects. Mean HCV RNA titers were significantly lower than baseline at weeks 8, 16, and 24 after drug initiation among patients treated with IFN/TA1 but not in the other treatment arms. Histological improvement, as evidenced by a decrease in HAI of more than two points, occurred in the combination therapy arm more frequently than in comparison groups. Cumulative sustained biochemical responses were 14.2% and 8.1% in the IFN/TA1 and IFN arms, respectively, based on an intention-to-treat model. The combination of TA1 and standard IFN treatment for chronic hepatitis C showed evidence of biological activity at the completion of treatment by biochemical, histological, and virological outcome measures. Further research involving longer duration and varied dosing is needed.

Purified, formaldehyde-inactivated and alum-adjuvanted hepatitis A virus (HAV) vaccines have recently become available for clinical trials. The vaccine is administered intramuscularly in a schedule of 0, 1, and 6 months. The aim of the study was to evaluate the reactogenicity and immunogenicity of an inactivated hepatitis A (HA) vaccine. Three groups of volunteers comprised the study population: 28 volunteers without antibody to HAV were given HA vaccine and, for comparison, 43 subjects received hepatitis B vaccine for possible adverse reactions to the HA vaccine; 12 other subjects received immunoglobulin alone. Each 1 ml dose of HA vaccine contained 720 enzyme units or about 100 ng of antigen. Anti-HAV was determined by means of a commercial assay (Abbott Laboratories: HAV-EIA), and by a more sensitive ELISA. No significant adverse reactions were reported. In the group that received HA vaccine, 4 weeks following the first dose all had detectable antibodies (> or = 20 mIU/ml) by the sensitive ELISA. By commercial HAV-EIA, at 20 weeks following the second dose 75.0% had detectable antibodies, and after the third vaccine all had detectable antibodies. This new inactivated HA vaccine is highly immunogenic and had no significant side effects.

Inactivated hepatitis A virus (HAV) vaccine is given in a three-dose schedule. When rapid protection is needed, injection of immune globulin (IG) concomitantly with the first dose could provide passive protection until adequate active antibody response has developed. A possible effect of IG on the immune response to the vaccine was studied in healthy volunteers; 28 received vaccine alone, and 34 received the first dose simultaneously with 5 mL of IG. A control group received hepatitis B vaccine, and a fourth group received IG alone. Four weeks after the first vaccine dose, all subjects had detectable ELISA anti-HAV antibodies. Several weeks after each vaccine dose, the geometric mean titer of antibodies was significantly lower in those who received vaccine with IG but higher than in those who received IG alone. Results for neutralizing antibodies yielded a similar trend. If IG is given with HAV vaccine, a further booster vaccine dose may be required to ensure long-lasting immunity.

The immunogenicity and reactogenicity of low-dose, recombinant DNA and plasma-derived hepatitis B vaccines were investigated in a prospective, double-blind, randomized, controlled trial. Volunteers (153) received either recombinant vaccine, 10 micrograms in 1 ml intramuscularly; plasma-derived vaccine, 2 micrograms in 0.1 ml intradermally or recombinant vaccine, 1 microgram in 0.1 ml intradermally at 0, 30, and 150 days. Peak geometric mean concentrations of antibody to hepatitis B surface antigen at day 200 were 1094, 387, and 43 mIU/ml, respectively. By day 360, these concentrations had fallen to 346, 124, and 19 mIU/ml, respectively (P less than .05 between groups both dates). Number of subjects with antibody greater than or equal to 10 mIU/ml at day 200 was similar between the 10-micrograms recombinant and 2-micrograms plasma-derived groups (94% vs. 90%), while only 78% of the 1-microgram recombinant group had protective concentrations of antibodies (P less than .05). Erythema and induration occurred in most subjects in both intradermal groups, while pain was prominent at the intramuscular site especially after the second dose. Thus, plasma-derived vaccine, 2 micrograms in 0.1 ml intradermally, appears to be an acceptable cost-saving method for hepatitis B immunization, while recombinant-derived vaccine, 1 microgram in 0.1 ml intradermally, produced less satisfactory results.

Large areas of the Amazon basin in Brazil, Colombia, Ecuador, and in the nonoriental region of the peruvian jungle have been found to be hyperendemic to Hepatitis B with high prevalence of asymptomatic carriers (11 to 25%) and, in more selected areas, Hepatitis Delta has been also reported. In the present report, we have studied 108 volunteers from six different Jivaroes communities living in a hyperendemic Hepatitis B area. They received 2 doses of DNA recombinant yeast derivated HBV vaccine. All the selected persons were HBsAb negatives, but many (80%) had antibodies to HBc. Following immunization schedule, 80% responded with the formation of HBsAb; a better seroconversion was achieved in those negatives to anticore IgG compared with those having HBcAb. We obtained 90% of seroconversion in spite of the fact that our vaccination schedule was prolonged up to 10 months from the one recommended by the manufacturer. The vaccination schedule 0,4, 14 months, and the schedule 0,4 months, had 76 and 29% of seroconversion, respectively. We want to point out three observations: 1) It is quite possible that many of the Anti-core positives, that did not respond to vaccination were carriers of HBsAg undetectable by the conventional EIA test carried out; 2) The seroconversion rate in these natives was low (up to six months after the vaccination schedule); and 3) Many of the HBcAb were false positives and many of them were recently infected. We conclude: A) It is highly important to assess the anti-HBs hyperendemic areas before attempting vaccinations; B) All persons negative to anti-HBs should be vaccinated in spite to anticore antibodies; C) Areas with difficult access could be vaccinated even until 10 months without affecting good results, and D) DNA recombinant vaccine (ENGERIX B) was well tolerated. No side effects were observed.

Serum samples from 130 persons who were seropositive for hepatitis B surface antigen and who had various forms of accompanying liver disease were tested for immunoglobulin M (IgM) antibody to hepatitis B core antigen. In 99% of patients with hepatitis B antigen-positive chronic type B hepatitis, IgM antibody to hepatitis B core antigen was present. This antibody was not present in "healthy" hepatitis B surface antigen carriers and was detectable in only 30% of patients with delta hepatitis. Testing of serial sera from 38 patients with chronic type B hepatitis revealed that IgM antibody to hepatitis B core antigen persisted in patients who had evidence of persistent hepatitis B virus replication but ultimately disappeared in those patients who exhibited a sustained loss of serum markers of viral replication (hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase activity). These findings suggest that the presence of IgM antibody to hepatitis B core antigen in chronic hepatitis B surface antigen carriers indicates an active immune response to persistent viral replication.

The effect of prolonged alpha-interferon therapy on immune function was studied in patients with chronic type B hepatitis. These patients with chronic type B hepatitis have been shown to have a defect in their in vitro response to human recombinant alpha-interferon. This defect consists of a failure to augment pokeweed mitogen-stimulated immunoglobulin production at low concentrations of interferon and an increased susceptibility to the suppressive effects of interferon. After 2 weeks therapy with interferon, immunoglobulin production was further suppressed. However, after 4 months of therapy with interferon, pokeweed mitogen-stimulated immunoglobulin production partially returned towards the pretreatment values. Antibody to hepatitis B core antigen was less affected by interferon therapy. This altered response to interferon was not specific as it was seen in some patients with other forms of liver disease. The suppression of B cell differentiation appears to be separate from its antiviral and antiproliferative effects.