The beneficial role of statins in primary and secondary prevention of coronary heart disease has resulted in their frequent use in clinical practice. However, safety concerns, especially regarding ...hepatotoxicity, have driven multiple trials, which have demonstrated the low incidence of statin-related hepatic adverse effects. The most commonly reported hepatic adverse effect is the phenomenon known as transaminitis , in which liver enzyme levels are elevated in the absence of proven hepatotoxicity. This class effect is usually asymptomatic, reversible, and dose-related. However, the increasing incidence of chronic liver diseases, including nonalcoholic fatty liver disease and hepatitis C, has created a new challenge when initiating statin treatment in patients with high cardiovascular risk. These diseases result in abnormally high liver biochemistry values, discouraging statin use by clinicians, fostering treatment discontinuation, and leaving a large number of at-risk patients untreated. A PubMed/MEDLINE search of the literature regarding statin safety (January 1, 1994-December 31, 2008) was performed, using the following search terms: statin safety , statin-related hepatotoxicity , and chronic liver disease and statin use , as well as the specific names of different statins and different liver diseases. Relevant clinical trials, review articles, panel discussions, and guideline recommendations were selected. This review supports the use of statin treatment in patients with high cardiovascular risk whose elevated aminotransferase levels have no clinical relevance or are attributable to known stable chronic liver conditions. For each patient, the decision should be based on an individual assessment of risks and benefits.
Summary Background Peginterferon plus ribavirin achieves sustained virological response (SVR) in fewer than half of patients with genotype 1 chronic hepatitis C virus infection treated for 48 weeks. ...We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b and ribavirin. Methods In part 1 of this trial, undertaken in 67 sites in the USA, Canada, and Europe, 520 treatment-naive patients with genotype 1 hepatitis C virus infection were randomly assigned to receive peginterferon alfa-2b 1·5 μg/kg plus ribavirin 800–1400 mg daily for 48 weeks (PR48; n=104); peginterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PRB24; n=103) or 44 weeks (PR4/PRB44; n=103); or peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 28 weeks (PRB28; n=107) or 48 weeks (PRB48; n=103). In part 2, 75 patients were randomly assigned to receive either PRB48 (n=16) or low-dose ribavirin (400–1000 mg) plus peginterferon alfa-2b and boceprevir three times a day for 48 weeks (low-dose PRB48; n=59). Randomisation was by computer-generated code, and study personnel and patients were not masked to group assignment. The primary endpoint was SVR 24 weeks after treatment. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00423670. Findings Patients in all four boceprevir groups had higher rates of SVR than did the control group (58/107 54%, 95% CI 44–64, p=0·013 for PRB28; 58/103 56%, 44–66, p=0·005 for PR4/PRB24; 69/103 67%, 57–76, p<0·0001 for PRB48; and 77/103 75%, 65–83, p<0·0001 for PR4/PRB44; vs 39/104 38%, 28–48 for PR48 control). Low-dose ribavirin was associated with a high rate of viral breakthrough (16/59 27%), and a rate of relapse (six of 27 22%) similar to control (12/51 24%). Boceprevir-based groups had higher rates of anaemia (227/416 55% vs 35/104 34%) and dysgeusia (111/416 27% vs nine of 104 9%) than did the control group. Interpretation In patients with untreated genotype 1 chronic hepatitis C infection, the addition of the direct-acting antiviral agent boceprevir to standard treatment with peginterferon and ribavirin after a 4-week lead-in seems to have the potential to double the sustained response rate compared with that recorded with standard treatment alone. Funding Merck.
Summary The SPine response assessment In Neuro-Oncology (SPINO) group is a committee of the Response Assessment in Neuro-Oncology working group and comprises a panel of international experts in spine ...stereotactic body radiotherapy (SBRT). Here, we present the group's first report on the challenges in standardising imaging-based assessment of local control and pain for spinal metastases. We review current imaging modalities used in SBRT treatment planning and tumour assessment and review the criteria for pain and local control in registered clinical trials specific to spine SBRT. We summarise the results of an international survey of the panel to establish the range of current practices in assessing tumour response to spine SBRT. The ultimate goal of the SPINO group is to report consensus criteria for tumour imaging, clinical assessment, and symptom-based response criteria to help standardise future clinical trials.
We report a prospective, randomized, single-blinded trial comparing immunogenicity of rapid (0, 1, and 2 months) versus standard schedule (0, 1, 6 months) hepatitis B vaccinations of healthy adults ...with recombinant hepatitis B vaccine (Engerix-B, 20 micrograms i.m.) (230 of 234) negative to hepatitis B were randomized and completed the study. Groups were similar in age, weight, race, and obesity rate, but the rapid schedule group had more women. Both groups reached > or = 100 mIU/mL at a similar rate, but a higher seroprotection rate at > or = 500 mIU/mL was reached by the standard schedule. No demographic variables influenced the effect of dose schedule on anti-hepatitis B titer. We conclude that rapid schedule vaccination gives a rate that is quicker than, and identical to, the rate of seroprotection of the standard schedule vaccination.
An outbreak of hepatitis B in a residential institution for the mentally retarded was studied. Initially one overt case of hepatitis was noted. A serologic screen of students and employees revealed a ...total of 12 individuals positive for hepatitis B surface antigen (HBsAg). Subtyping by radioimmunoassay subsequently demonstrated that the population of HBsAg-positive individuals could be subdivided into two groups, based on the HBsAg subtype: adw2 or ayw3. The five individuals with subtype adw2 all were carriers. The ayw3 group, in contrast, were acutely infected except for one carrier with persistent hepatitis B e antigen. Both the ayw3 carrier and several of the acutely infected individuals were aggressive biters. Human biting, a frequent occurrence in the classroom studied, was one probable mode of transmission in this outbreak. The resolution of the outbreak was achieved by rapid screening for HBsAg with subtyping of positive patients and careful observation of the setting for putative modes of transmission.
Medical personnel accidentally exposed to blood from patients who had acute hepatitis or carried hepatitis B surface antigen (HBsAg) were assigned randomly to receive two injections one month apart ...of immune serum globulin containing a high titer of antibody to HBsAg (anti-HBs) (269 subjects), an intermediate titer (223 subjects), or a normal titer (265 subjects). Four months after exposure nearly 7% of recipients of normal-titer globulin or intermediate-titer globulin had developed hepatitis B, whereas no cases had appeared among recipients of high-titer globulin (P < 0.01). However, an excess of late-onset cases in recipients of high-titer globulin nullified initial evidence of protection; at follow-up at nine months, the cumulative incidence of hepatitis B had reached 8.7%, 7.3%, and 7.2%, respectively, in the three groups (P > 0.30). Intercurrent infection was estimated to have accounted for only 20% of late-onset cases; 80% were thought to reflect an effect of high-titer globulin which was sufficient to delay onset but insufficient to reduce clinical severity. Many of these cases emerged in the presence of anti-HBs residual from administration of hightiter globulin, whereas no cases occurred in individuals who already possessed minimal amounts of anti-HBs at the time of exposure. The high-titer globulin was found to contain fragmented anti-HBs which may have interfered with the neutralizing activity of the large amount of unfragmented anti-HBs also present in the high-titer globulin. In any event, the lack of significant protection in the current trial means that a decision to use high-titer globulin as postexposure prophylaxis will have to rest upon the evidence of protection that has been obtained by others.
Personnel in the VA dental facilities were screened for the detection of viral hepatitis and identification of factors implicating infectivity. A total of 963 personnel from 126 dental facilities ...throughout the United States voluntarily participated in the study. The rate of seroconversion for any hepatitis B markers was approximately 1% per year. Serial positive tests for antibody to hepatitis B core antigen or antibody to hepatitis B surface antigen (or both) were present in 16.2% of dentists and 13.0% of dental auxiliary personnel. Oral and maxillofacial surgeons composed the highest prevalence occupation (24.0%), and clinical personnel composed the lowest prevalence occupation (8.9%). There was a significant association between years in dental environment and serological positivity for viral B infection. The dentists and dental auxiliary personnel had significant linear trends of increasing serological positivity with years in the dental environment. Although a majority of personnel reported wearing gloves while treating high-risk patients or performing invasive procedures, inadequate prophylactic measures were exercised for most patients undergoing a variety of less invasive procedures. The results of the study show the need for an active immunization program against type B viral infection for dental and dental auxiliary personnel, preferably before the initial exposure to the professional environment.
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