Antibiotics in the management of hepatic encephalopathy: an evidence-based review

Hepatic encephalopathy (HE) is an increasingly prevalent and debilitating condition that occurs in functional hepatic insufficiency. It is marked by fluctuating neuropsychiatric and cognitive impairment, which can be severe and life threatening. Hepatic encephalopathy is a diagnosis of exclusion; thus, it is challenging to diagnose definitively and to investigate in clinical trials. High response rates in the placebo arms of well-conducted studies demonstrate that the most effective treatment for HE is the correction of known precipitating triggers. However, pharmacological therapies may also be helpful. Although the precise pathogenesis remains unknown, bacterially derived neurotoxins from enteric flora likely play an important role. Based on this hypothesis and on accumulating clinical experience documented in randomized trials, oral antibiotics have emerged as an important treatment adjunct. This article addresses the qualities of an ideal antibiotic and reviews the literature on 4 antibiotics used to treat HE: neomycin, metronidazole, vancomycin, and rifaximin, with the most promising of these drugs appearing to be rifaximin. Unfortunately, most studies of the treatment of HE are difficult to interpret due to small sample sizes, methodological flaws, vulnerability to bias, and the intrinsic challenges of studying HE. Many studies have erroneously concluded that treatments are equivalent simply because no significant difference between treatment arms was detected. Consequently, the literature generally lacks definitive data from large, randomized, placebo-controlled trials. Nevertheless, the data suggest that minimally absorbed antibiotics are emerging as a safe and effective approach for the treatment of HE.     

Role of liver biopsy in the management of chronic liver disease: selective rather than routine

Liver biopsy has historically played a central role in the diagnosis and management of a variety of chronic liver diseases. However, as the understanding of disease pathology has progressed, and laboratory diagnostics, imaging technology, and clinical algorithms to determine both the etiology and presence of fibrosis have advanced, the role of liver biopsy has become more circumscribed. In chronic liver disease, liver biopsy is now more often used selectively, rather than routinely, for diagnostic purposes. Newer treatment of chronic hepatitis B and C has become more effective and thus reduced the routine need to acquire tissue. Risk factors for nonalcoholic fatty liver disease are readily identified and suggest the diagnosis after exclusion of alternative considerations, and there is no specific treatment for this condition; thus there is little role for the routine use of liver biopsy to guide treatment. Only in select cases of chronic hepatitis C, especially in patients with genotype 1, an indeterminate stage and grade of disease on noninvasive evaluation, or in those with human immunodeficiency virus coinfection, for whom the risks and benefits of treatment are less clear, is there a role for routine pretreatment biopsy.     

Cost-effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C

BACKGROUND: Screening for hepatocellular carcinoma in cirrhotic patients using abdominal ultrasonography and alpha-foetoprotein levels is widely practiced. AIM: To evaluate its cost-effectiveness using a Markov decision model. METHODS: Several screening strategies with abdominal ultrasonography or computerized tomography and serum alpha-foetoprotein at 6-12-month intervals in 40-year-old patients with chronic hepatitis C and compensated cirrhosis were simulated from a societal perspective, resulting in discounted costs per quality-adjusted life-year saved. Extensive sensitivity analysis was performed. RESULTS: For the least efficacious strategy, annual alpha-foetoprotein/ultrasonography, the incremental cost-effectiveness ratio (vs. no screening) was $23 043/quality-adjusted life-year. Biannual alpha-foetoprotein/annual ultrasonography, the most commonly used strategy in the United States, was more efficacious, with a cost-effectiveness ratio of $33 083/quality-adjusted life-year vs. annual alpha-foetoprotein/ultrasonography. The most efficacious strategy, biannual alpha-foetoprotein/ultrasonography, resulted in a cost-effectiveness ratio of $73 789/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual ultrasonography. Biannual alpha-foetoprotein/annual computerized tomography screening resulted in a cost-effectiveness ratio of $51 750/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual ultrasonography screening. CONCLUSIONS: Screening for hepatocellular carcinoma is as cost-effective as other accepted screening protocols. Of the strategies evaluated, biannual alpha-foetoprotein/annual ultrasonography gives the most quality-adjusted life-year gain while still maintaining a cost-effectiveness ratio <$50 000/quality-adjusted life-year. Biannual alpha-foetoprotein/annual computerized tomography screening may be cost-effective.     

The need for routine eye examinations

PURPOSE: To determine the incidence and causes of vision loss to assist in the objective determination of the preferred frequency of routine screening for those with normal vision. METHODS: A prospective, population-based study of people aged 40 or more years. Standardized examination protocols were used that included presenting and best corrected visual acuity, visual field testing, and comprehensive eye examination with dilation. RESULTS: There were 2529 people with a full data set, including 1590 with a normal baseline examination. The 5-year incidence of vision loss (<6/12 presenting acuity in the worse eye) was 2.39%. Overall, 24 (63%) of 38 of those with vision loss had noticed a change in their vision, and 18 (75%) of these 24 had attended an eye examination. This left only 14 (0.88%) people who had had normal baseline examination results and had asymptomatic vision loss develop over this 5-year period. CONCLUSIONS: Frequent routine eye examinations of those with normal examination results will have a low yield and may not be cost effective. Health promotion messages should target those who notice a change in vision and those at higher risk such as those with diabetes or a family history of eye disease.     

Measurement of indirect costs for people with vision impairment

From a societal perspective, chronic eye diseases can affect not only the person who has vision impairment but also the economics of that society. To obtain comprehensive medical and non-medical expenditures for people with impaired vision, direct and indirect costs should be collected. Indirect costs are usually not included in cost evaluation in health economics due to the difficulty of the data collection and analysis. Questionnaires and cost diaries have been developed in this study to estimate total resource use, expenses, and lost production from the participants or their caregivers due to the participants' vision loss. Pilot testing was conducted to verify the format, clarity of instructions, relevance of content and completeness of the questionnaires and diary. Modifications were then made to the format from feedback from the participants. Diaries using large print, audio and Braille facilitate data collection for people with impaired vision.     

Associations between glaucomatous visual field loss and participation in activities of daily living

Purpose: This study investigated the association between visual field loss and participation in daily activities in individuals with glaucoma. Methods: Seventy‐nine patients were recruited from the Royal Victorian Eye and Ear Hospital. Visual fields were assessed using the Esterman binocular visual field tests and participation in daily activities was assessed using the Impact of Vision Impairment (IVI) questionnaire. Visual acuity and contrast sensitivity were also measured. Results: There was no independent relationship between visual field loss and IVI score (r = ?0.20; P = 0.09), except for the mobility domain (r = 0.25; P = 0.03). Mobility was the most affected domain of the IVI (mean = 1.2). Over a quarter of the patients reported experiencing moderate to severe restriction with mobility activities despite relatively minor binocular field loss. Conclusion: Mobility is the area in which glaucoma patients encounter difficulties even when the visual field and visual acuity are relatively good. Questions related to mobility could be asked to identify those patients who need rehabilitation.     

Systematic review: peginterferon vs. standard interferon in the treatment of chronic hepatitis C

BACKGROUND: Randomized controlled trials over the last decade have demonstrated incremental improvement in the treatment efficacy of chronic hepatitis C with combination interferon and ribavirin therapy when compared with interferon monotherapy. AIM: To perform a systematic review of clinical trials directly comparing interferon formulations to test the hypothesis that a true difference in terms of efficacy exists between standard interferon (with and without ribavirin) and peginterferon (with and without ribavirin). METHODS: A search of the on-line bibliographic databases MEDLINE and PUBMED was performed independently by two authors to identify all relevant articles. In addition, the reference sections of all relevant articles were manually searched to identify any missed articles. Quality was assessed using the Jadad scale, which is an accepted scale specific for randomized controlled trials. A priori, it was decided to include only articles with a Jadad score of three or higher in the final analysis. Data were abstracted on to pre-determined abstraction sheets. The inclusion of articles, the data abstracted and the methodological score differences were adjudicated by consensus with agreement of the authors performing the search. RESULTS: Seven citations of randomized controlled trials, comparing at least two different interferon formulations and evaluating the sustained virological response as a primary end-point, were identified. These relevant articles were abstracted, and five of the seven were found to have a Jadad score of three or higher and comprised the final set of citations reviewed. The studies consistently demonstrated that peginterferon monotherapy was superior to standard interferon, even in patients with advanced fibrosis. With regard to combination interferon therapy, only two high-quality articles compared peginterferon plus ribavirin with standard interferon plus ribavirin. Both studies demonstrated that the overall sustained virological response was statistically better with peginterferon plus ribavirin. CONCLUSIONS: On the basis of this systematic review, peginterferon-based regimens are superior to standard interferon-based regimens for the treatment of chronic hepatitis C.     

Patient selection criteria for liver transplantation

The demand for liver transplantation has progressively increased in the setting of a relatively fixed cadaveric organ supply over the past 5 years. An increasing percentage of listed patients are dying waiting for an organ, with additional listed candidates being disqualified as they became too sick for transplantation. This disparity between organ demand and supply has led to continued reassessment of selection and listing criteria for transplantation as well as periodic revisions of allocation and distribution policies for cadaveric livers. The minimal listing criteria adopted in the United States in the late 1990s initially served to prevent inappropriate organ allocation to patients who had risen to high priority for a donor organ simply because they had been listed early and had a longer total waiting time. Many of these patients had lesser disease severity and immediate need for transplantation than other patients competing for the same donor organ but listed later in the natural history of their end-stage liver disease. The United Network for Organ Sharing has continuously revised organ allocation and distribution policies in an attempt to balance the ethical principles of medical justice and utility, which potentially conflict with one another. The principle of justice advocates for the sickest patient who has been waiting for the longest time, whereas that of utility favors the patient with the highest likelihood of achieving successful outcome. Throughout all of the changes in organ allocation rules, patients with fulminant hepatic failure have continued to receive the highest priority for organs. The Model for End-Stage Liver Disease (MELD) has replaced the Child-Turcotte- Pugh system for assessing disease severity and predicted mortality in patients with chronic liver failure. However, the use of MELD has favored listed candidates who have the worst post-transplant survivals. Other options that are being explored to expand the donor pool include the use of marginal donors, split liver transplants, living donors, and domino transplants, with xenotransplantation still remaining experimental.     

Update on chronic hepatitis C

Strategies for the diagnosis and treatment of chronic hepatitis C continue to evolve. Liver biopsy is now used selectively rather than routinely, and the combination peginterferon plus ribavirin is the treatment of choice for the majority of patients. Dr. Keeffe acknowledges grant support and memberships on advisory boards and speaker's bureaus of Roche Pharmaceutical and grant support and membership on the speaker' Brueau of Schering Laboratories. Dr. Ahmed acknowledges memberships on advisory boards and speakers' bureaus of Roche Pharmaceutical, Schering Laboratories, and Ortho-Biotech.     

Correction of refractive error in the Victorian population: the feasibility of "off the shelf" spectacles.

AIMS: To assess the feasibility of providing a stock of ready made spectacles for correction of refractive error in the general population. METHODS: Data were collected in the Visual Impairment Project, a population based survey of Victorian residents aged 40 years or older in randomly selected urban and rural sample areas. This included a refractive eye examination and the proportion of subjects with hypermetropia, emmetropia (defined as -1.0 to +1.0D spherical equivalent), and myopia documented in the 40-60 year age group. RESULTS: 2595 (54.8%) participants were aged between 40 and 60 years. Those with a best corrected visual acuity of less than 6/12, astigmatism of more than 1.25D, and anisometropia of more than 0.5D were excluded. 516 participants had refractive error which was deemed suitable for correction by "off the shelf" spectacles. This represents 19.9% of all participants between 40 and 60 years of age. Provision of spectacles in 0.5D increments would provide suitable stock spectacles for 85.5% of a -3.0 to +3.0D range or 89.2% of a -3.50 to +3.50D range. CONCLUSIONS: Ready made "off the shelf" spectacles could significantly alleviate visual morbidity due to refractive error in up to 20% of an urban population in Australia. This approach may also be useful in developing countries with poor access to optometric services.