Nonabsorbable Disaccharides Research Articles

Rifaximin therapy and hepatic encephalopathy: Pros and cons

Hepatic encephalopathy (HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life. Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy. Non-absorbable antibiotics, such as neomycin and paramomycin, are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects. To overcome these limitations, rifaximin use has been proposed. Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention, with a similar incidence of side-effects. Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern. Following long-term rifaximin therapy, Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients. In addition, selection of resistant mutants of both Gram-negative and -positive bacteria in the gastrointestinal tract cannot be definitely ruled out. Electrolyte alterations (sodium and potassium) have been reported during rifaximin therapy, a warning for its long-term use in cirrhotics. Moreover, a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients. The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides. While waiting for further safety data, caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to non-absorbable disaccharides.

Pharmacotherapy for Hepatic encephalopathy: view of Evidence-Based Medicine

Hepatic encephalopathy (HE) refers to a complex and reversible neuro-psychiatric syndrome that results from complications of acute or chronic hepatic failure, particularly alcoholic cirrhosis. It will lead to frequent life disruptions, poor quality of life and extensive use of health care resources. We conducted the review of several agents based on randomized controlled trials (RCTs) of high-quality Jadad scores (≥3) to provide effective information for clinical practice. Rifaximin appears at least to be as effective as conventional treatments, but not superior to them. L-Ornithine-L-aspartate appears to be a safe and effective treatment of chronic HE when compared with a placebo regime. Other treatments include non-absorbable disaccharides (NAD) and benzodiazepine receptor antagonists. In spite of the variability in the improvement of HE, NAD and non-absorbed antibiotics such as rifaximin offer a favorable benefit–risk ratio in the improvement of HE. Further RCTs with power calculation and a multi-centre approach with adequate population number are needed to resolve the heterogeneous results

What improves minimal hepatic encephalopathy: Probiotic yogurt, protein restriction or nonabsorbable disaccharides?

What improves minimal hepatic encephalopathy: Probiotic yogurt, protein restriction or nonabsorbable disaccharides?

P2-76 Antibiotics for hepatic encephalopathy: systematic review of randomised controlled trials

ObjectiveTo assess the effectiveness of antibiotics in the treatment of hepatic encephalopathy (HE).Data sourcesCochrane Hepato-Biliary Group controlled trials register, Cochrane Controlled Trials Register, MEDLINE, LILACS, SCI Expanded, Embase and http://clinicaltrials.gov/...

Non-absorbable disaccharides and antibacterials are the treatment of choice for hepatic encephalopathy

Non-absorbable disaccharides and antibacterials are the treatment of choice for hepatic encephalopathy

HYPERAMMONEMIC ENCEPHALOPATHY DUE TO A URINARY DIVERSION: AN UNCOMMON CAUSE OF REVERSIBLE DEMENTIA

To the Editor: Patients with cognitive impairment may have potentially reversible conditions. Metabolic diseases constitute an important group of these nondegenerative etiologies. Urinary diversion has been reported to cause hyperammonemic encephalopathy (HE), even without liver disease. This letter presents the case of a patient with hyperammonemia and history of a Bricker diversion after radical cystectomy for bladder cancer previously misdiagnosed with early-onset dementia. After specific treatment for hyperammonemia, the patient's cognition improved greatly. A 74-year-old man was admitted to the acute geriatric unit of our hospital because of a 3-week history of drowsiness and general stiffness. He had a prior medical history of a Bricker uretero-ileostomy after radical cystectomy for bladder cancer performed 1 year before admission and cognitive impairment, labelled as Alzheimer's disease, detected 3 months before by his general physician, although no specific tests had been performed to evaluate it. Omeprazole and lorazepam were his regular medications. On examination, he was unaware of time and place, and he presented with signs of dehydration. Neurological findings included slurred speech, drowsiness, clumsiness, stiffness, postural instability, and bradykinesia. Symptoms were present and stable all day. Blood tests showed mildly high C-reactive protein (3.5 mg/dL), hypernatremia (156 mEq/L), and leucocytosis (18 × 109/L). Glucose, calcium, magnesium, Vitamin B12, thyroid hormone, and renal and liver function tests were normal. Urine sediment evidenced mild leukocyturia with bacteriuria. Chest radiography was normal. Initial diagnosis was hypernatremia secondary to dehydration and urinary infection, and fluid therapy and antibiotic with ceftriaxone were started. Urinary culture was negative. Natremia normalized progressively, but the patient's symptoms did not improve at all. A cranial computed tomography (CT) scan showed mild diffuse cerebral atrophy, and an electroencephalogram revealed diffuse nonspecific encephalopathy. Despite normal liver function, given the urinary diversion, blood ammonia levels were tested revealing marked hyperammonemia (122 μmol/L). An abdominal–pelvic CT scan did not evidence signs of obstruction or dilatation of the uretero-ileal anastomosis. Specific treatment with dietary protein restriction and lactulose therapy was initiated. In a few days, ammonemia became normal, and the patient quickly showed great improvement in his mental state (Mini-Mental State Examination score 29/30 at 1 month after discharge). The global prevalence of dementia in the elderly population is approximately 5%.1 Alzheimer's disease is the most common disorder, accounting for 60% to 80% of cases, followed by vascular dementia (10–20%).2 The prevalence of a potentially reversible cause (Table 1) ranges from less than 1% to 9%, being higher in younger (<60) than older adults and significantly more common in patients with only subjective symptoms than in patients with established dementia.2–4 The most common reversible causes are depression, drugs, hydrocephalus, and metabolic diseases; thyroid disease and vitamin B12 deficiency are the most frequently detected causes from metabolic diseases.2,3 HE is an uncommon reversible etiology of cognitive impairment. Liver diseases, some drugs, portosystemic shunting, congenital defects of enzymes of the urea cycle, parenteral nutrition, hematological dyscrasia, and urinary diversion have been reported as causes of hyperammonemia.5–7 Nonhepatic hyperammonemia in patients undergoing urinary diversion is due to the prolonged contact of urine and the intestinal epithelium that results in high intestinal uptake of urine-excreted products, which can overload the detoxifying capacity of the liver, leading to the download of ammonia into the blood flow.8 Furthermore, urinary tract infections with urease-producing bacteria may cause urine ammonia concentration to rise. Proteus mirabilis and Pseudomonas aeruginosa are the best-known urea-splitting bacteria.9 There are no standardized guidelines for treating acute nonhepatic hyperammonemia. The reduction of intestinal ammonia levels by limiting protein ingestion to 20 g/d and using nonabsorbable disaccharides such as lactulose and lactitol to increase intestinal ammonia elimination is encouraged. If urinary tract infection is suspected, an antibiotic should also be started.10 In conclusion, unexplained neurological or neuropsychiatric symptoms in a patient with a urinary diversion should include hyperammonemia in the differential diagnosis. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors: diagnosis and care of patients and preparation of manuscript. Sponsor's Role: None.

Comparison of Efficacy of Rifaximin and Non-Absorbable Disaccharides in Management of Hepatic Encephalopathy: A Meta-Analysis

Comparison of Efficacy of Rifaximin and Non-Absorbable Disaccharides in Management of Hepatic Encephalopathy: A Meta-Analysis

147 EXCESSIVE REDUCTION IN HVPG IS PREDICTIVE OF MORTALITY AFTER TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS)

Introduction: Hepatic Encephalopathy (HE) is a serious complication of chronic liver disease characterized by complex neuropsychiatric abnormalities that range from mild confusion to coma. Although there have been different treatment options for HE, lactulose (a nonabsorbable disaccharide, NADS) has been most commonly used and remains the mainstay of therapy. Rifaximin is a non-absorbable antibiotic and was recently approved by FDA for prevention of recurrent HE. Several small trials in the past have compared the effectiveness of rifaximin and NADS in management of HE. The results of these trials have been conflicting and limited due to small number of subjects involved. Aim: We therefore conducted a metaanalysis of Randomized controlled trials (RCT) to evaluate the efficacy of rifaximin in comparison to NADS. Methods: Two reviewers searched MEDLINE, EMBASE, CINAHL and the Cochrane Database using search terms “hepatic encephalopathy”, “rifaximin, “lactulose”, “lactitol”, “non-absorbable disaccharides”, “cirrhosis”. Inclusion criteria were:1) Studies involving patients with HE 2) study be a RCT 3) comparison of rifaximin with NADS (either lactulose or lactitol). The review was done per guidelines of PRISMA statement and methodological quality evaluated using Jadad scoring system. The results were pooled and relative risk ratio and 95% confidence interval (95% CI) derived using fixed effect estimates using STATA 10. Results: Five studies with a total of 259 patients met the pre-specified inclusion criteria. Of these 134 were randomized to rifaximin while 125 to NADS. In comparison to NADS, use of rifaximin was associated with significant reduction in risk of no improvement of HE (RR 0.57, 95% CI 0.35 0.94, p = 0.028). There was no significant heterogeneity amongst studies with Chi square statistic = 3.9, p = 0.41, I squared statistic = 0.0%. Discussion: Rifaximin is more beneficial in comparison to NADS in management of HE. Although Lactulose is used as the first line agent, frequent side effects such as bloating, flatulence, diarrhea limit tolerability. Rifaximin is not absorbed systemically and thus better tolerated. Further research should explore the optimum treatment duration for HE and costanalysis with use of rifaximin.

This Month in Gastroenterology

Hepatic encephalopathy is a complication of chronic liver failure, with a spectrum that ranges from mild cognitive dysfunction to decreased consciousness, coma, and death. The pathogenesis is thought to involve toxins released from the gastrointestinal tract by the bacterial flora, which interfere with central nervous system functioning. Therapeutic approaches aim at modifications of the bacterial flora, through nonabsorbable disaccharides such as lactulose, or through antibiotics with low systemic absorption, such as rifaximin.

Patent Paraumbilical Vein-Induced Hepatic Encephalopathy

A 68-year-old man with hepatitis C virus–related cirrhosis was referred to our unit because of the occurrence of a depressed level of consciousness, disturbed sleep pattern, and impaired intellect. Liver failure was classified as Child–Pugh class B (score, 8). Neurologic symptoms were attributed to hepatic encephalopathy (HE), and diagnosis was confirmed by altered ammonia levels and absence of other causes responsible for his symptoms. Treatment with bowel enemas, nonabsorbable disaccharides (lactulose), intestinal antibiotics (rifaximin), and intravenous branched-chain amino acids was instituted with poor success.

Pharmacotherapy for Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a challenging clinical complication of liver dysfunction with a wide spectrum of neuropsychiatric abnormalities that range from mild disturbances in cognitive function and consciousness to coma and death. The pathogenesis of HE in cirrhosis is complex and multifactorial, but a key role is thought to be played by circulating gut-derived toxins of the nitrogenous compounds, most notably ammonia. Therapeutic treatment options for HE are currently limited and have appreciable risks and benefits associated with their use. Management of HE primarily involves avoidance of precipitating factors, limitation of dietary protein intake, and administration of various ammonia-lowering therapies such as non-absorbable disaccharides and select antimicrobial agents. Non-absorbable disaccharides, such as lactulose, have traditionally been regarded as first-line pharmacotherapy for patients with HE. However, multiple adverse events have been associated with their use. In addition, recent literature has questioned the true efficacy of the disaccharides for this indication. Neomycin, metronidazole and vancomycin may be used as alternative treatments for patients intolerant or unresponsive to non-absorbable disaccharides. Antimicrobials reduce bacterial production of ammonia and other bacteria-derived toxins through suppression of intestinal flora. Neomycin has been reported to be as effective as lactulose, and similar efficacy has been reported with vancomycin and metronidazole for the management of HE. However, the adverse effects frequently associated with these antimicrobials limit their use as first-line pharmacological agents. Neomycin is the most commonly used antimicrobial for HE and, although poorly absorbed, systemic exposure to the drug in sufficient amounts causes hearing loss and renal toxicity. Long-term neomycin therapy requires annual auditory testing and continuous monitoring of renal function. Long-term use of metronidazole has been associated with neurotoxicity in patients with cirrhosis, including dose-dependent peripheral neuropathy. Vancomycin may be a safer option for HE in patients with chronic liver disease; however, limited experience, possible bacterial overgrowth and risk for enteric bacteria resistance preclude the routine use of vancomycin for HE. Rifaximin is a novel antimicrobial agent with a wide spectrum of activity that has shown promise as an alternative antimicrobial treatment option for HE. Several clinical trials have compared rifaximin to the disaccharides, lactulose and lactitol, and the antimicrobial neomycin. Rifaximin appears to be at least as effective as conventional drug therapy and has been associated with fewer adverse effects due to its limited systemic absorption. The available clinical data appear to support a favourable benefit-risk ratio for rifaximin, which has shown efficacy with an improved tolerability profile. Future studies are needed in order to truly characterize its cost effectiveness in today's healthcare environment. Other less frequently utilized alternative treatment options include administration of benzodiazepine receptor antagonists, branched-chain amino acids, ornithine aspartate, zinc supplementation, sodium benzoate, dopamine receptor agonists, acarbose and probiotics. Presently, there is relatively limited clinical data supporting their routine use in HE.

Considerations on the Impact of Hepatic Encephalopathy Treatments in the Pretransplant Setting

Hepatic encephalopathy (HE) is a common complication of acute and chronic liver disease associated with exposure of brain tissue to excessive levels of ammonia produced by intestinal bacteria. Clinical manifestations range from subtle neurologic abnormalities to coma. Because development of HE can reduce survival probability, guidelines for evaluating patients for liver transplantation suggest that patients who develop HE should be considered for transplantation. Various patient factors before transplantation, including the presence of HE and reduced nutritional status, may increase the risk of poor outcomes after transplantation. Therefore, effective management of HE before transplantation, while minimizing the potential impact of negative predictive factors, may improve transplantation outcomes. The most common HE treatments are directed toward reducing systemic ammonia levels, thereby reducing brain exposure to this neurotoxin. The administration of nonabsorbable disaccharides is considered as a first-line therapy for HE, and the antibiotics neomycin and metronidazole are frequently administered, despite a lack of clinical data supporting their efficacy. These agents are associated with adverse events that may reduce nutritional status in patients awaiting transplantation and could contribute to poor posttransplantation outcomes. The nonsystemic antibiotic rifaximin has demonstrated efficacy for the treatment of HE and has a favorable safety profile. Given these data, nonsystemic antibiotics may also provide a safe and effective option for treating HE in the pretransplant setting. This article reviews treatments for HE and the potential impact these treatments may have on pretransplantation status of patients awaiting liver transplantation and on posttransplantation outcomes.

Rifaximin and nonabsorbable disaccharides for hepatic encephalopathy

Rifaximin and nonabsorbable disaccharides for hepatic encephalopathy

Rifaximin for Hepatic Encephalopathy

Objective: To evaluate the efficacy of rifaximin for the treatment of hepatic encephalopathy (HE). Data Sources: All articles were accessed via PubMed (January 1960–December 2008), Cochrane Library, and Iowa Drug Information Service (1966–December 2008) using the terms rifaximin and hepatic encephalopathy. In addition, reference citations from publications identified were reviewed. Study Selection and Data Extraction: All articles in English identified from the data sources were evaluated. Fifteen studies that evaluated the efficacy, safety, and/or cost-effectiveness of rifaximin for the treatment of HE are reviewed in this article. Data Synthesis: HE is a neuropsychiatric syndrome that develops in patients with acute or chronic liver failure. There are a number of accepted theories explaining the pathophysiology of HE. Currently, pharmacologic therapies include nonabsorbable disaccharides (lactulose) and antibiotics (neomycin and metronidazole). Recent studies have shown a possible benefit with a newer, nonabsorbable rifamycin derivative, rifaximin. It has a broad spectrum of activity against aerobic and anaerobic gram-positive and gram-negative organism. Clinical trials have compared rifaximin with lactulose, neomycin, or metronidazole for the treatment of HE. There have also been review articles addressing the cost-effectiveness of rifaximin compared with lactulose, including the cost of hospitalization. To date there have been no randomized, placebo-controlled studies that have assessed the efficacy and long-term safety outcomes of rifaximin in the treatment of HE; however, rifaximin has demonstrated similar efficacy and better safety profiles compared with other therapies, in particular, neomycin and lactulose. Conclusions: Patients with HE who are refractory to lactulose therapy or who have decreased tolerability to lactulose therapy may benefit from rifaximin as either adjunct therapy or salvage therapy. ACPE Universal Program Numbers: 407-000-09-053-H01-P (Pharmacists); 407-000-09-053-H01-T (Technicians)

AASLD practice guidelines the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension update 2009

The 2009 update of the American Association for the Study of Liver Diseases (AASLD) Practice Guideline “The Role of Transjugular Intrahepatic Portosystemic Shunt (TIPS) in the Management of Portal Hypertension” is now posted online at www.aasld.org. This is the first update of the original guideline published in 2005.1 DSRS, distal splenorenal shunt; TIPS, transjugular intrahepatic portosystemic shunt. The key changes in the 2009 guidelines are new recommendations on the use of covered versus bare stents in the creation of the TIPS. Use of expanded polytetrafluoroethylene (ePTFE)-covered stents is now preferred. The lower risk of shunt dysfunction and perhaps improved outcomes using covered as opposed to bare stents are the basis for this recommendation.2, 3 Creation of a TIPS increases the risk of hepatic encephalopathy but the prophylactic use of nonabsorbable disaccharides or antibiotics does not appear to reduce this risk and is not recommended.4 The value of TIPS versus a surgical shunt in the prevention of variceal rebleeding in patients who have failed medical therapy has been clarified by the publication of a controlled trial comparing TIPS to distal splenorenal shunt (DSRS).5 Both were effective in preventing rebleeding (rebleeding incidence in 5.5% of DSRS versus 10.5% of TIPS; not significant) with no difference in encephalopathy or survival. The patients in whom TIPS was performed required significantly more interventions to maintain patency because of the use of bare stents. A cost analysis showed TIPS to be slightly more cost effective than DSRS at year 5,6 and these two approaches are now considered to be of equal efficacy in the prevention of variceal rebleeding. The other significant change to the guidelines is how TIPS should be used in the management of patients with Budd-Chiari syndrome. A large (221 patients) retrospective study was published in which patients who failed to improve with use of anticoagulation had a TIPS created (133 patients). One-year and 10-year transplant-free survival was 88% and 69%, respectively, which is better than predicted.7 TIPS patency was best in those who received a covered stent. The recommendation now is for creation of a TIPS in those who fail to improve with anticoagulation.

Rifaximin for Treatment of Hepatic Encephalopathy

To review the effectiveness and safety of rifaximin in the treatment of hepatic encephalopathy (HE). MEDLINE (1990-October 2008) was searched using the terms rifaximin, rifamycins, hepatic encephalopathy, liver cirrhosis, and acute liver failure. Other sources included the bibliographies of pertinent articles as well as programs and abstracts from infectious diseases and gastrointestinal diseases meetings. All English-language articles identified from the search were evaluated. All primary literature that addressed the efficacy and safety of rifaximin in the treatment of HE was included in this review. HE is a complex neuropsychiatric syndrome seen in patients with liver failure. It is characterized by disturbances in consciousness and behavior, personality changes, fluctuating neurologic signs, asterixis, and electroencephalographic changes. Although the etiology of HE is unknown, the accumulation of several gut-derived toxins such as mercaptans, ammonia, and benzodiazepine has been implicated. Current treatment options for HE include agents that reduce the concentration of these toxins, such as nonabsorbable disaccharides and antibiotics. Several studies have evaluated the use of rifaximin in the treatment of HE. They include a dose-finding study, 9 open-label studies, and 4 double-blind studies comparing rifaximin with either nonabsorbable disaccharides or antibiotics. Commonly used outcomes in most of these studies were changes in portal systemic encephalopathy index and the improvement in HE grade. Despite various limitations of the studies, rifaximin showed superior efficacy compared with lactulose for the treatment of HE, similar efficacy to paromomycin, and similar or greater efficacy than neomycin. Rifaximin was found to be associated with fewer hospitalizations, fewer days of hospitalization, and lower hospitalization charges than were seen with lactulose. Rifaximin also had a better tolerance profile than the comparative agents. Rifaximin appears to be an effective and safe treatment option for HE. Better-designed studies are needed to characterize its efficacy in the treatment of HE.

Rifaximin versus nonabsorbable disaccharides in the management of hepatic encephalopathy: a meta-analysis

To compare the positive and negative effects of rifaximin and nonabsorbable disaccharides in patients with hepatic encephalopathy. We used the method recommended by The Cochrane Collaboration to perform a meta-analysis of comparative randomized trials of rifaximin and nonabsorbable disaccharides. Seven randomized controlled trials were identified, but only five trials involving 264 patients met all the inclusion criteria. There was no significant difference between rifaximin and nonabsorbable disaccharides on improvement in patients with hepatic encephalopathy [relative risk (RR) 1.08; 95% confidence interval (CI), 0.85-1.38; P=0.53]. RR was 0.98 (95% CI: 0.85-1.13; P=0.74) for acute hepatic encephalopathy in 157 patients and 0.87 (95% CI: 0.40-1.88; P=0.72) for chronic hepatic encephalopathy in 96 patients, respectively. There was no significant difference between rifaximin and nonabsorbable disaccharides on diarrhea (RR=0.90; 95% CI: 0.17-4.70; P=0.90). However, a significant difference in favor of rifaximin on abdominal pain (RR=0.28; 95% CI: 0.08-0.95; P=0.04) was identified. Rifaximin is not superior to nonabsorbable disaccharides for acute or chronic hepatic encephalopathy in the long-term or short-term treatment except that it may be better tolerated. Further studies on larger populations are required to provide more sufficient evidence for assessment of the use of rifaximin.

Rifaximin for the Treatment of Hepatic Encephalopathy

To review the effectiveness and safety of rifaximin for the treatment of hepatic encephalopathy. A literature search was conducted of MEDLINE (1966-September 2007), the Cochrane Database of Systematic Reviews (1995-2007), and the Cochrane Hepato-Biliary Group Reviews (2003-2007). English-language articles identified from the data sources were evaluated. All available studies were reviewed, including placebo-controlled, treatment comparison, and open label. Rifaximin was effective in improving behavioral, laboratory, mental status, and intellectual abnormalities associated with hepatic encephalopathy. Some studies demonstrated superior and more rapid improvement in signs or symptoms of encephalopathy during treatment with rifaximin compared with nonabsorbable disaccharides (lactulose, lactitol). Patients treated with rifaximin also required less hospitalization, had shorter duration of hospitalization, and lower hospital charges compared with lactulose-treated patients. Adverse effects of rifaximin were mostly minor gastrointestinal complaints; however, rifaximin was better tolerated than other pharmacologic treatments. Rifaximin was at least equally effective as and in some studies superior to nonabsorbable disaccharides and antimicrobials in relieving signs or symptoms observed in patients with mild-to-moderately severe hepatic encephalopathy. Future clinical trials should focus on using standardized methods of evaluating mental status and limiting enrollment to patients with mild-to-moderate, episodic, persistent, or minimal hepatic encephalopathy. Well-designed studies are needed to fully delineate the efficacy of rifaximin and other pharmacologic treatments for patients with hepatic encephalopathy.

The treatment of hepatic encephalopathy

Current recommendations for the treatment of hepatic encephalopathy are based, to a large extent, on open or uncontrolled trials, undertaken in very small numbers of patients. In consequence, there is ongoing discussion as to whether the classical approach to the treatment of this condition, which aims at reducing ammonia production and absorption using either non-absorbable disaccharides and/or antibiotics, should be revisited, modified or even abandoned. Pros and cons of present therapeutic strategies and possible future developments were discussed at the fourth International Hannover Conference on Hepatic Encephalopathy held in Dresden in June 2006. The content of this discussion is summarized.

The cost‐effectiveness and budget impact of competing therapies in hepatic encephalopathy – a decision analysis

Treatment options for hepatic encephalopathy have disparate risks and benefits. Non-absorbable disaccharides and neomycin are limited by uncertain efficacy and common dose-limiting side effects. In contrast, rifaximin is safe and effective in hepatic encephalopathy, but is more expensive. We conducted a decision analysis to calculate the cost-effectiveness of six strategies in hepatic encephalopathy: (i) no hepatic encephalopathy treatment, (ii) lactulose monotherapy, (iii) lactitol monotherapy, (iv) neomycin monotherapy, (v) rifaximin monotherapy and (vi) up-front lactulose with crossover to rifaximin if poor response or intolerance of lactulose ('rifaximin salvage'). The primary outcome was cost per quality-adjusted life-year gained. Under base-case conditions, 'do nothing' was least effective and rifaximin salvage was most effective. Lactulose monotherapy was least expensive, and rifaximin monotherapy was most expensive. When balancing cost and effectiveness, lactulose monotherapy and rifaximin salvage dominated alternative strategies. Compared to lactulose monotherapy, rifaximin salvage cost an incremental US$2315 per quality-adjusted life-year-gained. The cost of rifaximin had to fall below US$1.03/tab in order for rifaximin monotherapy to dominate lactulose monotherapy. Rifaximin monotherapy is not cost-effective in the treatment of chronic hepatic encephalopathy at current average wholesale prices. However, a hybrid salvage strategy, reserving rifaximin for lactulose-refractory patients, may be highly cost-effective.