Maria H. Sjogren

Small bile duct abnormalities in sarcoidosis.

We report four patients with hepatic involvement of sarcoidosis manifested primarily by bile duct depletion. The patients developed fever, weight loss, anorexia, a markedly elevated alkaline phosphatase, and mildly abnormal serum levels of aspartate aminotransferase. Endoscopic retrograde cholangiopancreatography showed slight intrahepatic irregularities but were not diagnostic of sclerosing cholangitis. Liver biopsy showed predominantly bile duct depletion, ranging from an estimated 10–100% absence of bile ducts in portal areas, which correlated with the degree of fibrosis. The degree of bile duct depletion is useful as a histological marker in patients with sarcoid liver disease. Steroids improve symptoms, but do not inhibit the development of “ductopenia.”

Interferon alfacon-1 and ribavirin versus interferon alpha-2b and ribavirin in the treatment of chronic hepatitis C.

Despite advances in the therapy of chronic hepatitis C, a large number of patients do not respond to current therapies. The study objective was to assess whether a combination of interferon (IFN) alfacon-1 and ribavirin improves the response rate compared with a combination of INF α-2b and ribavirin in chronic hepatitis C subjects. The study was designed as an open-label, prospective, randomized, controlled study; 128 subjects with chronic hepatitis C were randomized to INF alfacon-1, 15 μg three times per week, plus ribavirin, 1 g/day, or IFN-α2b, 3 million units three times per week, plus ribavirin, 1 g/day for 48 weeks. The end point of the study was a sustained viral response, defined as undetectable HCV RNA at 24 weeks post 48 weeks of treatment. Overall, 57% of subjects in the INF alfacon-1/ribavirin group achieved a sustained antiviral response, compared with 40% of subjects in the IFN-α2b/ribavirin group (P = 0.052). In the subset of subjects with a high viral load, HCV RNA was successfully eradicated in more individuals who received INF alfacon-1/ribavirin than subjects who received IFN-α2b/ribavirin (57 versus 31%; P = 0.025). Among individuals with genotype 1 and a high viral load, the sustained antiviral response was significantly higher with INF alfacon-1/ribavirin than with IFN-α2b/ribavirin (46 versus 14%; P = 0.019). Adverse events were similar in both treatment groups. In conclusion, this study demonstrated that the combination of INF alfacon-1 and ribavirin provides a significantly better treatment response compared with the combination of IFN-α 2b and ribavirin in chronic HCV subjects infected with genotype 1 and a high viral RNA load.

Antibody response to a delayed booster dose of anthrax vaccine and botulinum toxoid

We evaluated the prevalence and concentration of serum antibodies 18-24 months after primary inoculation with anthrax and botulinum vaccines, and assessed the reactogenicity and immunogenicity of a significantly delayed booster dose of these vaccines. Five hundred and eight male active-duty military personnel received one, two or three inoculations with anthrax vaccine and/or botulinum toxoid in 1990/1991 in preparation for Operations Desert Shield/Desert Storm. Subjects were vaccinated with the licensed anthrax vaccine, adsorbed (AVA) and pentavalent (ABCDE) botulinum toxoid (PBT) BB-IND 3723. Anthrax protective antigen (PA) IgG antibody was measured in serum using an immunocapture enzyme-linked immunosorbent assay (ELISA). A mouse neutralization test was used to determine the titer of Clostridium botulinum type A antitoxin in serum samples. The prevalence of anti-PA IgG was 30% in individuals 18-24 months after priming with one, two or three doses of AVA. After boosting, 99% of volunteers had detectable anti-PA IgG; only two individuals failed to respond. The prevalence of antibodies against botulinum toxin type A was 28% 18-24 months after initial priming. Following boosting, 99% of volunteers had serum titers >0.02IU/ml, and 97% responded with titers > or =0.25IU/ml. Systemic reactions to booster vaccinations could not be specifically ascribed to one or the other vaccine, but were generally mild and of brief duration. Forty-five percent of volunteers reported one or more systemic reactions over the course of 7 days. Injection site reactions of any kind occurred in 25% of AVA recipients and in 16% of PBT recipients; persistence of local reactions beyond 7 days was infrequent. While the kinetics and durability of immune responses must be studied, these findings suggest that booster doses of anthrax vaccine and botulinum toxoid sufficient to stimulate a robust anamnestic response may be given at times distant from receipt of the primary inoculations.

Antiviral Response of HCV Genotype 1 to Consensus Interferon and Ribavirin Versus Pegylated Interferon and Ribavirin

Achieving an antiviral response at a reasonable cost is a challenge in the treatment of patients with chronic hepatitis C. A previous study indicated that consensus interferon with ribavirin had promising activity against hepatitis C virus (HCV) genotype 1. The objective of this study was to determine the virologic response with consensus interferon or pegylated interferon α-2b plus weight-ribavirin in patients chronically infected with HCV genotype 1. Intention-to-treat analysis showed response in 37% and 41% of subjects treated with consensus interferon/ribavirin or pegylated interferon/ribavirin, respectively, with response rates of 42% and 44% observed in analysis of the per-protocol population, not a significant difference. Tolerability of the two treatment regimens was similar. In conclusion, both treatment regimens were safe and gave a similar antiviral response. It is possible that if consensus interferon is administered daily rather than three times weekly, eradication of HCV could be achieved in a larger proportion of patients infected with HCV genotype 1.

Thymosin β4 Upregulates the Expression of Hepatocyte Growth Factor and Downregulates the Expression of PDGF‐β Receptor in Human Hepatic Stellate Cells

Abstract:  Hepatic stellate cells (HSCs) are the main producers of type I collagen in the liver, and therefore are responsible, in part, for the fibrous scar observed in cirrhotic livers. Although there is no approved treatment for this deadly disease, drugs inducing HSC apoptosis in animals (gliotoxin) and hepatocyte regeneration in man (hepatocyte growth factor [HGF]), have been used successfully in ameliorating liver fibrosis. In this communication we investigated whether thymosin β4 (Tβ4), an actin‐sequestering peptide that prevents scarring of the heart after a myocardial infarction and that prevents kidney fibrosis in animals, has the potential to be used to treat liver fibrosis. To this end we studied whether the administration of Tβ4 to HSCs could alter the expression of genes encoding for extracellular matrix components, as well as those required for differentiation of HSCs. Our preliminary findings show that Tβ4 had no effect on the expression of α2 (I) collagen, tissue inhibitor of metalloproteinases‐1, and matrix metalloproteinase‐2 mRNAs. However, it upregulated the expression of HGF and downregulated the expression of platelet‐derived growth factor‐β receptor mRNAs in these cells. Overall, these findings suggest that Tβ4 has antifibrogenic potential.

Thymalfasin: an immune system enhancer for the treatment of liver disease

Abstract  Thymalfasin (thymosin‐alpha 1) is an immunomodulating agent able to enhance the Th1 immune response. It has been evaluated for its immunomodulatory activities and related therapeutic potential in several diseases, including chronic hepatitis B and C, AIDS, primary immunodeficiency diseases, depressed response to vaccination and cancer. The basis for effectiveness in these conditions is primarily through modulation of immunological responsiveness, as thymalfasin has been shown to have beneficial effects on numerous immune system parameters and to increase T‐cell differentiation and maturation.

SEROLOGIC DIAGNOSIS OF VIRAL HEPATITIS

The diagnosis of viral hepatitis is complex, particularly when the five leading causative agents belong to different virus families and evoke distinct immunologic response. This article connects known serologic markers to new methods and guides the ordering and interpretation of contemporary laboratory tests.

Hepatic decompensation associated with lamivudine : A case report and review of lamivudine-induced hepatotoxicity

We report a case of a 62-yr-old man with chronic hepatitis B virus (HBV)-related cirrhosis who developed hepatic decompensation after being started on lamivudine requiring liver transplantation. Decompensated liver disease while on lamivudine has been previously reported on two occasions, both HIV coinfected patients on a combination of nucleoside analogues. Our patient is alive and well nearly 2 yr after successful liver transplantation.

Failure of induction dosing of interferon to alter sustained response rates in patients with chronic hepatitis C

Therapeutic options to improve the rate of HCV eradication include use of induction (daily interferon) and combination therapy (interferon and ribavirin) for initial treatment of chronic hepatitis C. The aim of our study was to observe the effect of induction dose followed by either interferon alfa-2b alone or in combination therapy.

Significance of an elevated alkaline phosphatase (AP) or an AST/ALT ratio greater than one in hepatitis C (HCV) patients

Significance of an elevated alkaline phosphatase (AP) or an AST/ALT ratio greater than one in hepatitis C (HCV) patients