Interferon Treatment Duration in Patients With Chronic Delta Hepatitis and its Effect on the Natural Course of the Disease.

Background: Interferon is the only treatment option in chronic delta hepatitis (CDH). A CDH database (333 patients, 161 with interferon treatment history) was analyzed for effects of treatment duration on virologic response and clinical outcomes. Methods: Ninety-nine CDH patients who received at least 6 months of interferon were selected. Maintained virologic response (MVR) was defined as hepatitis D virus RNA negative for 2 years after treatment discontinuation. Cumulative median interferon treatment duration was 24 months (range 6-126 months), with a median of 2 courses (range 1-8). Post-treatment median follow-up was 55 months (24-225 months). Results: Thirty-five patients achieved MVR. Cumulative probability of MVR increased with treatment duration and reached 50% at 5 years. Patients with MVR were less likely to die from liver disease or develop complications compared to patients without MVR (P = .032, P = .006, respectively). Cirrhosis at baseline and no response to therapy (odds ratio 16.1 and 5.23, respectively) predicted an adverse endpoint. Hepatitis B surface antigen clearance occurred in 37% of patients with MVR. Conclusion: Viral response to interferon increases with treatment duration and favorably affects the natural course of disease. Interferon treatment duration has to be individualized with careful post-treatment assessment.

Entecavir treatment of chronic hepatitis D.

BACKGROUND: Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) to propagate infection and cause disease. Entecavir is a nucleoside analog with potent antiviral efficacy, and in the woodchuck animal model it also decreased hepatitis B virus (HBV) cccDNA and woodchuck surface antigen. The aim of this study was to investigate the efficacy of entecavir in chronic hepatitis D (CHD). METHODS: This single-center study was conducted in patients with compensated liver disease. All patients had to have detectable hepatitis HDV RNA and elevated levels of alanine aminotransferase (ALT). Entecavir was given at a dosage of 1 mg/d for 1 year. The primary end point was achievement of undetectable HDV RNA at the end of treatment. RESULTS: Thirteen consecutive patients were assessed. All patients had detectable HDV RNA, and 8 had detectable HBV DNA at baseline. At the end of treatment, HBV DNA became undetectable in all patients (P = .001). No significant decline in HDV RNA, ALT, or quantitative HBsAg levels was observed. The primary end point of undetectable HDV RNA at the end of treatment was achieved in 3 patients who had significantly lower baseline HDV RNA levels than nonresponders (2.99 log(10) copies/mL ± .70 vs 4.68 ± .97; P = .0185). In all 3 patients, ALT levels were also normal at the end of treatment. CONCLUSIONS: One year of entecavir treatment is ineffective in CHD. Any generalized beneficial effect of nucleoside/nucleotide analog treatment may necessitate prolonged treatment. Patients with CHD with HBV dominance, which is likely to occur in the later phases of CHD, may be a reasonable patient cohort in which to target nucleoside/nucleotide analog therapy.

Fatigue of cholestasis and the serotoninergic neurotransmitter system in the rat.

Fatigue associated with cholestasis may impair health-related quality of life. The pathogenesis of this symptom is largely unknown, but it has been suggested that central serotoninergic neurotransmission may be implicated and that serotonin 1A receptor agonists may yield improvement. The aim of this study was to study the central serotoninergic system, specifically the serotonin (5-HT)(1A) receptor-mediated pathway of serotoninergic neurotransmission, in a bile duct resection rat model of cholestasis. Fatigue was assessed in the forced swim test in sham and bile duct-resected rats. The serotonin behavioral syndrome, which includes hyperlocomotion, was assessed in both groups of rats after escalating doses of the 5-HT(1A) receptor agonist 8-hydroxy(di-n-propylamine)tetralin (8-OH DPAT). 5-HT(1A) and 5-HT(2) receptor densities were explored in four brain regions using a receptor-binding assay. Extracellular 5-HT and 5-hydroxyindoleacetic acid were measured via in vivo brain dialysis. Bile duct-resected rats spent more time floating in the forced swim test, and 8-OH DPAT decreased floating time in cholestatic rats (P < .01). Dose-response curves created with 8-OH DPAT for the serotonin behavioral syndrome were similar in bile duct-resected and sham-operated rats. 5-HT(1A) and 5-HT(2) receptor densities in most brain regions and extracellular serotonin levels were similar in both groups of rats. In conclusion, 5-HT(1A) receptor agonist-induced amelioration of fatigue in cholestatic rats may be nonspecific and not linked to reversal of the pathophysiology of fatigue associated with cholestasis; however, these data do not exclude a potential role of the central serotoninergic system in the evolution of fatigue.