Effect of interferon-alpha induction therapy on genotype 2b/3a and low viral load hepatitis C virus infection. A randomized multicentre study.

BACKGROUND: Interferon monotherapy for chronic hepatitis C virus (HCV) infection leads to sustained viral eradication in a minority of patients. However, in selected groups of patients, sustained virological response is observed in as many as 50% of patients. High initial interferon dose (induction therapy) has been reported to increase the initial response rate. We have studied the effect of interferon induction therapy in patients infected with HCV genotype 2b/3a, low viral load and no cirrhosis. METHODS: A total of 71 treatment-naive HCV RNA-positive patients with biopsy-confirmed chronic hepatitis, with genotype 2b or 3a, viral load < or = 3 million copies per ml and no cirrhosis were randomized to receive either standard interferon therapy (3 MIU interferon-alpha-2a thrice weekly) for 26 weeks or 6 MIU interferon-alpha-2a daily for 4 weeks (induction group) followed by the standard dose (3 MIU thrice weekly) for 22 weeks. Those with persistent HCV RNA at 4 weeks stopped treatment. Patients were monitored for HCV RNA during and following treatment, and data were interpreted according to intention-to-treat analysis. RESULTS: Viral clearance occurred more rapidly (after 4 weeks) in the induction group (33/36 = 92%) compared to the standard interferon group (21/35 = 60%) (P = 0.01). Among the initial responders, 23/33 (induction group) compared to 16/21 (standard group) were persistently HCV RNA-negative at the end of treatment. At 52 weeks (6 months' follow-up), 22/36 (61%) (induction group) compared to 10/35 (29%) (standard group) were HCV RNA-negative. Among initial responders, 22/33 (induction group) and 10/21 (standard group) achieved a sustained virological response. Among end-of-treatment responders, 22/24 (induction group) and 10/16 (standard group) were HCV RNA-negative at 6 months' follow-up (P = 0.013). CONCLUSIONS: In patients infected with HCV genotype 2b/3a, low viral load and without cirrhosis, IFN induction therapy increases the initial viral clearance and reduces the risk of relapse in end-of-treatment responders. A sustained virological response was achieved in 61% of the patients receiving IFN induction therapy.

Effect of combined interferon-alpha induction therapy and ribavirin on chronic hepatitis C virus infection: a randomized multicentre study.

BACKGROUND: The efficacy of interferon-alpha (IFN) induction in combination with ribavirin for chronic hepatitis C virus (HCV) infection is not known. METHODS: A total of 256 treatment-naive HCV RNA-positive patients with biopsy-confirmed chronic hepatitis were enrolled in a randomized multicentre study. The patients received either standard combination therapy with 3 MIU interferon-alpha2b thrice weekly for 26 weeks or 6 MIU interferon-alpha2b daily for 4 weeks and 3 MIU 3/7 days for 22 weeks. All patients received ribavirin 1000 mg or 1200 mg (weight dependent) daily during the 26-week treatment period. Patients were monitored for HCV RNA during and following treatment. RESULTS: The sustained virological response rates (26 weeks after end of treatment) were 54% and 47% for patients receiving IFN induction/ribavirin and standard IFN/ribavirin, respectively (P = 0.35). Among patients infected with genotype 1a/1b, the sustained response rates were 32% and 35%. In patients infected with genotype 2b/3a IFN induction/ribavirin led to a sustained response rate of 80% as compared to 65% in the standard combination therapy group (P = 0.073). Steatosis was more frequently seen in liver biopsies from patients infected with genotype 3a as compared to genotypes la/lb. Among genotype 1a/1b infected patients. steatosis was a highly significant predictor of failure to achieve sustained virological response. Logistic regression analysis (multivariate analysis) showed that independent predictors of sustained virological response were low age, female gender, genotype 2b/3a and HCV RNA negativity at 2 weeks. CONCLUSIONS: IFN induction in combination with ribavirin does not increase the sustained virological response rate among patients infected with HCV. Absence of steatosis is an independent predictor of sustained virological response in patients infected with genotypes 1a/1b.

The effect of faecal enema on five microflora-associated characteristics in patients with antibiotic-associated diarrhoea.

BACKGROUND: Patients with antibiotic-associated diarrhoea (AAD) show significant disturbances in short-chain fatty acid pattern. In the present study five more microflora-associated characteristics (MACs) were investigated before and after administration of an enema containing faecal microflora from a healthy person on a Western diet. METHODS: The functions of the microflora were determined with gas chromatography, electrophoresis, and spectrophotometry. RESULTS: The conversion of cholesterol to coprostanol and the concentration of urobilinogen and trypsin were significantly reduced in comparison with healthy persons. The pattern of mucin was altered, but beta-aspartylglycine remained the same as in healthy persons. Enema treatment influenced these functions to different extents. CONCLUSION: Most MACs were significantly disturbed in patients with AAD. Administration of a human faecal enema modified these changes and relieved diarrhoea, usually within 4 days.

Clostridium difficile-associated diarrhea after short term vaginal administration of clindamycin.

A 32-yr-old woman developed frequent watery diarrhea with occult blood after 3 days treatment with clindamycin vaginal cream. Clostridium difficile toxin was demonstrated in stool samples and was considered the cause of an antibiotic-associated diarrhea. No other antibiotic was used at least 3 months before the start of diarrhea. To our knowledge, antibiotic-associated diarrhea after vaginal application has previously been reported only once.

Faecal short-chain fatty acids in patients with antibiotic-associated diarrhoea, before and after faecal enema treatment.

BACKGROUND: Antibiotic-associated diarrhoea (AAD) may range from mild disturbances to severe pseudomembranous colitis. Many antibiotics affect several intestinal microflora-associated characteristics, such as short-chain fatty acid (SCFA) pattern. In the present study we investigated SCFAs in 31 patients on admittance to the hospital for severe AAD. Nine patients were followed up more extensively after they had received an enema containing faecal microflora from a healthy person on a Western diet. METHODS: Faecal SCFAs were determined by gas chromatography. The enema was characterized before use. RESULTS: AAD patients showed significant disturbances in faecal SCFA pattern. Clinically, most enema-treated patients recovered within days and had no relapses within 18 months. CONCLUSIONS: Intestinal microflora showed great disturbances, and the amounts of SCFAs were reduced, although the diarrhoea was not related to total amount SCFAs. Administration of a faecal enema resulted in the clinical recovery of most patients with severe diarrhoea within 4 days.

[Clostridium difficile-associated diarrhea treated with homologous feces]. / Clostridium difficile-assosiert diaré behandlet med homolog feces.

The incidence of Clostridium difficile-associated diarrhoea has increased during the last few years. Treatment with vankomycin or metronidazol is usually effective, but relapses are not uncommon. Some good results have been reported with faecal enemas, but it is a controversal form of treatment. 18 patients with C. difficile-associated diarrhoea were given homologous faeces from one healthy donor. In 17 patients faeces was instillated via a coloscope and in one patient via a gastrostoma. C. difficile toxin was detected in all patients. Three patients with severe colitis did not respond to the treatment. The remaining patients were clinically cured, and no relapses were observed. Treatment of C. difficile-associated diarrhoea with faeces appears to be an alternative in moderate cases. In our limited number of patients we observed a poor correlation between the clinical picture, the endoscopic findings and the histological findings in colon biopsies. The ethical aspects of treatment with faeces will continue to be subject to discussion.

[Visceral larva migrans. A rare cause of eosinophilia in adults]. / Visceral larva migrans. En sjelden arsak til eosinofili hos voksne.

Toxocariasis is a cosmopolitan infection of dogs and cats with a roundworm resembling Ascaris. Man becomes infected by ingesting eggs from the environment. The infection occurs mainly in children. There are two distinct syndromes: visceral larva migrans and ocular toxocariasis. The author describes the case of a 70 year old Norwegian female with visceral larva migrans. One month after a visit to Spain she developed fever, hepatomegaly and marked eosinophilia. Liver biopsy revealed subacute hepatitis with eosinophilic leucocyte infiltration. Toxocara ELISA was strongly positive. Treatment with albendazol 400 mg b.i.d. and prednisone 10 mg daily for three weeks was successful. A clinical relapse after three months was treated in the same way for one month. Prolonged treatment is recommended. To our knowledge, this is the first reported case of visceral larva migrans in an adult Norwegian. Epidemiology, diagnosis and treatment are discussed.

[Cerebral hemorrhage associated with phenylpropanolamine]. / Cerebral blødning assosiert med fenylpropanolamin.

In recent years, sympathomimetic drugs, including ephedrine, amphetamine and phenylpropanolamine, have been increasingly associated with cerebral haemorrhage and infarction. We report a case of intracranial bleeding in a 37 year-old woman with mononucleosis who took therapeutic doses of phenylpropanolamine. Cerebral CT on admission showed a left-sided intracerebral hematoma. Angiography was normal. Late bleeding occurred on the fourth day. She survived but developed a right-sided cerebral infarction with persistent epilepsy. Her mononucleosis was of moderate severity without bleeding diastesis. We conclude that the intracranial bleedings were secondary to taking phenylpropanolamine.