Frequency and Type of Renal and Electrolyte Disorders in Fulminant Hepatic Failure

Of 48 patients with fulminant hepatic failure who progressed to grade III or IV encephalopathy 38 showed evidence of renal impairment. In 32 of these patients the underlying cause could be placed initially into one of three categories—prerenal uraemia (4 patients), acute tubular necrosis (16), and “functional renal failure” (12). The latter differed in several respects from that seen with liver failure secondary to cirrhosis. The frequency and type of renal impairment was the same in those patients in whom the fulminant hepatic failure had resulted from an overdose of paracetamol as in the other aetiological groups.Abnormalities in plasma electrolytes were common—in particular hypernatraemia occurred in 11 patients from an osmotic diuresis precipitated by hypertonic dextrose or fructose given intravenously, and from the sodium in the fresh frozen plasma used to correct the coagulation disturbance when renal excretion of this ion was inappropriately low.     

Factors contributing to mortality in paracetamol-induced hepatic failure.

Fifty patients with fulminant hepatic failure from paracetamol overdose were reviewed retrospectively to determine whether there had been any avoidable delays in treatment with protective agents, or other preventable factors which could contribute to the high mortality. Only nine were admitted to the local hospital early enough (within 12 hours) to benefit from protective agents, and only three of these were treated. Treatment was delayed in two patients while the results of plasma paracetamol concentrations were awaited. Signs of grade 3 hepatic encephalopathy were never found until 72 hours after the overdose, and sudden deterioration in consciousness at an earlier stage was due either to the sedative effects of drugs or to hypoglycaemia, which in one patient went unrecognised for 24 hours. A rapid deterioration in prothrombin time, which became prolonged by at least 25 seconds at 48 hours, preceded the onset of grade 3 encephalopathy, and this is the time at which transfer should be arranged to avoid the danger of brain-stem coning. This occurred more rapidly in those transferred at a later stage of their illness.     

Adverse reactions to acetylcysteine and effects of overdose.

Since the introduction in 1979 of intravenous acetylcysteine (Parvolex) as an antidote for overdosage of paracetamol the National Poisons Information Service and the manufacturer have been notified of 38 adverse reactions that were anaphylactoid in nature and 19 accidental overdoses. The most common feature of the anaphylactoid reaction to normal dosage was rash; other features reported included angioedema, hypotension, and bronchospasm; all the patients recovered. The features associated with an overdose of acetylcysteine were similar but more severe; two patients died, but the extent to which the overdose of acetylcysteine may have been implicated was not clear in either case.     

The Relationship Between Plasma and Brain Quinolinic Acid Levels and the Severity of Hepatic Encephalopathy in Animal Models of Fulminant Hepatic Failure

Abstract: Quinolinic acid is an excitatory, neurotoxic tryptophan metabolite proposed to play a role in the pathogenesis of hepatic encephalopathy. This involvement was investigated in rat and rabbit models of fulminant hepatic failure at different stages of hepatic encephalopathy. Although plasma and brain tryptophan levels were significantly increased in all stages of hepatic encephalopathy, quinolinic acid levels increased three- to sevenfold only in the plasma, CSF, and brain regions of animals in stage IV hepatic encephalopathy. Plasma-CSF and plasma-brain quinolinic acid levels in rats and rabbits with fulminant hepatic failure were strongly correlated, with CSF and brain concentrations ∼10% those of plasma levels. Moreover, there was no significant regional difference in brain quinolinic acid concentrations in either model. Extrahepatic indoleamine-2,3-dioxygenase activity was not altered in rats in stage IV hepatic encephalopathy, but hepatic l -tryptophan-2,3-dioxygenase activity was increased. These results suggest that quinolinic acid synthesized in the liver enters the plasma and then accumulates in the CNS after crossing a permeabilized blood-brain barrier in the end stages of liver failure. Furthermore, the observation of low brain concentrations of quinolinic acid only in stage IV encephalopathy suggests that the contribution of quinolinic acid to the pathogenesis of hepatic encephalopathy in these animal models is minor.     

Short term effect of withdrawal of diuretic drugs prescribed for ankle oedema.

OBJECTIVE--To determine the effect of withdrawing diuretic drugs on oedema in patients prescribed them for only ankle oedema, excluding patients with cardiac, hepatic, or renal failure. DESIGN--Randomised controlled trial. SETTING--15 general practices in the Netherlands. PATIENTS--1202 patients aged 65 years or older and taking diuretic drugs, 63 of whom were eligible for the trial. MAIN OUTCOME MEASURE--Change in volumetrically determined ankle oedema (oedema index) over six weeks. RESULTS--34 patients were randomised to stop diuretics and 29 to the control group. In eight patients diuretics had to be restarted. Among patients who had diuretics withdrawn successfully, rebound oedema caused a temporary increase in mean oedema index. The peak level (3.5% (95% confidence interval 1.5% to 5.2%) was reached in the third week, after which the oedema seemed to be returning to the baseline level. CONCLUSION--Few patients who have been prescribed diuretics for only ankle oedema clearly have no contraindications to withdrawing diuretics. If patients are unlikely to have cardiac insufficiency and careful monitoring is provided, withdrawal of diuretics seems to be feasible, though moderate rebound oedema may occur for a short time.     

UK legislation on analgesic packs: before and after study of long term effect on poisonings

Objective To evaluate the long term effect of legislation limiting the size of packs of analgesics sold over the counter.Design Before and after study.Setting Suicides in England and Wales, data from six liver units in England and Scotland and five general hospitals in England, and UK data on sales of analgesics, between September 1993 and September 2002.Data sources Office for National Statistics; six liver units in England and Scotland; monitoring systems in general hospitals in Oxford, Manchester, and Derby; and Intercontinental Medical Statistics Health UK.Main outcome measures Deaths by suicidal overdose with paracetamol, salicylates, or ibuprofen; numbers of patients admitted to liver units, listed for liver transplant, and undergoing transplantations for paracetamol induced hepatotoxicity; non-fatal self poisonings with analgesics and numbers of tablets taken; and sales figures for analgesics.Results Suicidal deaths from paracetamol and salicylates were reduced by 22% (95% confidence interval 11% to 32%) in the year after the change in legislation on 16 September 1998, and this reduction persisted in the next two years. Liver unit admissions and liver transplants for paracetamol induced hepatotoxicity were reduced by around 30% in the four years after the legislation. Numbers of paracetamol and salicylate tablets in non-fatal overdoses were reduced in the three years after the legislation. Large overdoses were reduced by 20% (9% to 29%) for paracetamol and by 39% (14% to 57%) for salicylates in the second and third years after the legislation. Ibuprofen overdoses increased after the legislation, but with little or no effect on deaths.Conclusion Legislation restricting pack sizes of analgesics in the United Kingdom has been beneficial. A further reduction in pack sizes could prevent more deaths.     

Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning.

One hundred cases of severe paracetamol poisoning were treated with intravenous N-acetylcysteine (acetyl-cysteine). There was virtually complete protection against liver damage in 40 patients treated within eight hours after ingestion (mean maximum serum alanine transaminase activity 27 IU/1). Only one out of 62 patients treated within 10 hours developed severe liver damage compared with 33 out of 57 patients (58%) studied retrospectively who received supportive treatment alone. Early treatment and acetylcysteine also prevented renal impairment and death. The critical ingestion-treatment interval for complete protection against severe liver damage was eight hours. Efficacy diminished progressively thereafter, and treatment after 15 hours was completely ineffective. Intravenous acetylcysteine was more effective than cysteamine and methionine and noticeably free of adverse effects. It is the treatment of choice for paracetamol poisoning.     

Acute red ear in children: controlled trial of non-antibiotic treatment in general practice.

OBJECTIVE--To examine the efficacy and safety of conservative management of mild otitis media ("the acute red ear") in children. DESIGN--Double blind placebo controlled trial. SETTING--17 group general practices (48 general practitioners) in Southampton, Bristol, and Portsmouth. PATIENTS--232 children aged 3-10 years with acute earache and at least one abnormal eardrum (114 allocated to receive antibiotic, 118 placebo). INTERVENTIONS--Amoxycillin 125 mg three times a day for seven days or matching placebo; 100 ml paracetamol 120 mg/5 ml. MAIN OUTCOME MEASURES--Diary records of pain and crying, use of analgesic, eardrum signs, failure of treatment, tympanometry at one and three months, recurrence rate, and ear, nose, and throat referral rate over one year. RESULTS--Treatment failure was eight times more likely in the placebo than the antibiotic group (14.4% v 1.7%, odds ratio 8.21, 95% confidence interval 1.94 to 34.7). Children in the placebo group showed a significantly higher incidence of fever on the day after entry (20% v 8%, p less than 0.05), mean analgesic consumption (0.36 ml/h v 0.21 ml/h, difference 0.14, 95% confidence interval 0.07 to 0.23; p = 0.0022), mean duration of crying (1.44 days v 0.50 days, 0.94; 0.50 to 1.38; p less than 0.001), and mean absence from school (1.96 days v 0.52 days, 1.45; 0.46 to 2.42; p = 0.0132). Differences in recorded pain were not significant. The prevalence of middle ear effusion at one or three months, as defined by tympanometry, was not significantly different, nor was there any difference in recurrence rate or in ear, nose, and throat referral rate in the follow up year. No characteristics could be identified which predicted an adverse outcome. CONCLUSIONS--Use of antibiotic improves short term outcome substantially and therefore continues to be an appropriate management policy.     

Serum alpha-fetoprotein in fulminant hepatitis and hepatic regeneration following partial hepatectomy

The pleomorphism of hepatic regeneration was studied in 10 patients with fulminant hepatitis and 7 with hepatocellular carcinoma, liver cyst, and abscess who underwent partial hepatectomy. Serum AFP levels did not increase significantly following partial hepatectomy. All of four patients who survived fulminant hepatitis had high serum AFP levels with a peak either during or before hepatic encephalopathy. Serum AFP levels decreased rather gradually during the enlargement of the atrophic liver. The observations proposed two kinds of hepatic regeneration, hepatic regeneration following surgical removal of liver and repair of liver damage following virally and probably chemically induced liver deficiency.     

Metformin Inhibits Glutaminase Activity and Protects against Hepatic Encephalopathy

Aim

To investigate the influence of metformin use on liver dysfunction and hepatic encephalopathy in a retrospective cohort of diabetic cirrhotic patients. To analyze the impact of metformin on glutaminase activity and ammonia production in vitro.

Methods

Eighty-two cirrhotic patients with type 2 diabetes were included. Forty-one patients were classified as insulin sensitizers experienced (metformin) and 41 as controls (cirrhotic patients with type 2 diabetes mellitus without metformin treatment). Baseline analysis included: insulin, glucose, glucagon, leptin, adiponectin, TNFr2, AST, ALT. HOMA-IR was calculated. Baseline HE risk was calculated according to minimal hepatic encephalopathy, oral glutamine challenge and mutations in glutaminase gene. We performed an experimental study in vitro including an enzymatic activity assay where glutaminase inhibition was measured according to different metformin concentrations. In Caco2 cells, glutaminase activity inhibition was evaluated by ammonia production at 24, 48 and 72 hours after metformina treatment.

Results

Hepatic encephalopathy was diagnosed during follow-up in 23.2% (19/82): 4.9% (2/41) in patients receiving metformin and 41.5% (17/41) in patients without metformin treatment (logRank 9.81; p = 0.002). In multivariate analysis, metformin use [H.R.11.4 (95% CI: 1.2–108.8); p = 0.034], age at diagnosis [H.R.1.12 (95% CI: 1.04–1.2); p = 0.002], female sex [H.R.10.4 (95% CI: 1.5–71.6); p = 0.017] and HE risk [H.R.21.3 (95% CI: 2.8–163.4); p = 0.003] were found independently associated with hepatic encephalopathy. In the enzymatic assay, glutaminase activity inhibition reached 68% with metformin 100 mM. In Caco2 cells, metformin (20 mM) decreased glutaminase activity up to 24% at 72 hours post-treatment (p<0.05).

Conclusions

Metformin was found independently related to overt hepatic encephalopathy in patients with type 2 diabetes mellitus and high risk of hepatic encephalopathy. Metformin inhibits glutaminase activity in vitro. Therefore, metformin use seems to be protective against hepatic encephalopathy in diabetic cirrhotic patients.     

Endogenous Benzodiazepine Receptor Ligands in Human and Animal Hepatic Encephalopathy

The role of endogenous benzodiazepine receptor ligands in the pathogenesis of hepatic encephalopathy was studied in humans and in rat models of hepatic encephalopathy. Endogenous benzodiazepine ligands were extracted from rat brain and human CSF by acid treatment and purification by HPLC. Detection and partial characterization of these endogenous benzodiazepine ligands were carried out using both radioreceptor binding assays and radioimmunoassays with anti-benzodiazepine antibodies. Four different benzodiazepine receptor ligands were identified in human and rat tissue, two of which may be diazepam and desmethyldiazepam, based on elution profiles and anti-benzo-diazepine antibody reactivity. Human CSF and serum from patients with hepatic encephalopathy contained approximately 10 times more endogenous benzodiazepine receptor ligand than CSF from controls or nonencephalopathic patients with liver disease. The levels of brain benzodiazepine receptor ligand compounds were also increased approximately 10-fold in rats suffering from fulminant hepatic failure, but not in rats with portacaval shunts, a model of chronic hepatic disease. The increased concentrations of these substances could be behaviorally significant and may contribute to the pathogenesis of hepatic encephalopathy.     

Effects of a drug overdose in a television drama on presentations to hospital for self poisoning: time series and questionnaire study

ObjectivesTo determine whether a serious paracetamol overdose in the medical television drama Casualty altered the incidence and nature of general hospital presentations for deliberate self poisoning.DesignInterrupted time series analysis of presentations for self poisoning at accident and emergency departments during three week periods before and after the broadcast. Questionnaire responses collected from self poisoning patients during the same periods.Setting49 accident and emergency departments and psychiatric services in United Kingdom collected incidence data; 25 services collected questionnaire data.Subjects4403 self poisoning patients; questionnaires completed for 1047.ResultsPresentations for self poisoning increased by 17% (95% confidence interval 7% to 28%) in the week after the broadcast and by 9% (0 to 19%) in the second week. Increases in paracetamol overdoses were more marked than increases in non-paracetamol overdoses. Thirty two patients who presented in the week after the broadcast and were interviewed had seen the episode—20% said that it had influenced their decision to take an overdose, and 17% said it had influenced their choice of drug. The use of paracetamol for overdose doubled among viewers of Casualty after the episode (rise of 106%; 28% to 232%).ConclusionsBroadcast of popular television dramas depicting self poisoning may have a short term influence in terms of increases in hospital presentation for overdose and changes in the choice of drug taken. This raises serious questions about the advisability of the media portraying suicidal behaviour.

Key messages

• This study found that portrayal of self poisoning in a popular television drama was associated with a short lived increase in presentation of self poisoning patients to general hospitals
• Choice of substance taken in overdose was also influenced by the broadcast
• Extreme caution should be exercised about portraying suicidal behaviour on television, and especially about giving details of the method used
• The potential role of television in preventing suicidal behaviour requires investigation

     

Treatment of acetaminophen poisoning.

Acetaminophen is an analgesic that is frequently used in Canada, and the occurrence of overdoses with this drug seems to be increasing. The most serious complication of acetaminophen overdose is hepatic failure. Because of pathophysiologic effects of acetaminophen poisoning and the mechanisms of its toxic effects are now better understood, a rational approach to treatment is possible. Several precursors of glutathione, acetylcysteine in particular, are effective in preventing liver damage if administered within 10 hours of acetaminophen ingestion. Plasma acetaminophen levels are a helpful guide to therapy.     

分子吸附再循环系统治疗肝功能衰竭合并肝性脑病的临床效果观察

目的探讨分子吸附再循环系统在肝功能衰竭合并肝性脑病治疗中的临床应用效果。方法将我院2015年1月~2016年1月收治的肝功能衰竭合并肝性脑病患者100例,根据治疗方式的不同分为观察组和对照组,每组50例。对照组50例患者接受保肝、维持水电解质平衡以及营养支持等综合治疗,观察组50例患者在综合治疗基础之上接受分子吸附再循环系统治疗,并对两组患者的治疗效果,治疗前后肝功能改善情况、不良反应进行统计分析。结果两组患者治疗前的总胆红素、凝血酶原活动度、血氨以及Glasgow昏迷评分比较差异无统计学意义(P0.05)。观察组患者治疗3天后的总胆红素以及血氨明显低于对照组,两组比较差异有统计学意义(P0.05);而且治疗有效率明显高于对照组(P0.05),治疗后肝性脑病清醒率高于对照组(P0.05)。两组患者治疗期间均无严重不良反应。结论肝功能衰竭合并肝性脑病患者在综合治疗上采取分子吸附再循环系统治疗的效果显著,可明显改善患者肝功能,提高肝性脑病清醒率,且不良反应少,值得临床推广使用。     

Neuromonitoring in a porcine model of acute hepatic failure

Cerebral oedema has been noted to occur frequently in patients dying of fulminant hepatic failure. Therefore, in the present study, multimodal neuromonitoring was evaluated in an animal model of hepatectomy. Acute liver failure was surgically induced in swine by complete hepatectomy (n = 8). Intracranial pressure monitoring via a ventricular drainage system, electroencephalogram and recording of visually evoked potentials were used to establish a continuous neuromonitoring system. Measurements of liquor and serum ammonia (NH(3)) levels were taken at later stages of the trial in an approach to widen monitoring. Serial monitoring of the electroencephalogram revealed progressive slowing of the frequency with decreasing amplitude. Monitoring of the intracranial pressure with a subdural pressure transducer demonstrated a progressive and reproducible elevation. Increase in blood NH(3) was observed. Anaesthesia was terminal. In all cases death was caused by cardiocirculatory insufficiency, confirmed by autopsy. At autopsy, brain tissue of the animals was found to be swollen showing flattened cortical gyri. In conclusion, the technique of extended neuromonitoring offers an advanced option for monitoring animal models of fulminant hepatic failure for further developments and investigations.     

Association of healthy lifestyle including a healthy sleep pattern with incident type 2 diabetes mellitus among individuals with hypertension

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic disease and independently affects the development of cardiovascular (CV) disease. We investigated whether hepatic steatosis and/or fibrosis are associated with the development of incident heart failure (iHF), hospitalized HF (hHF), mortality, and CV death in both the general population and HF patients. We analyzed 778,739 individuals without HF and 7445 patients with pre-existing HF aged 40 to 80 years who underwent a national health check-up from January 2009 to December 2012. The presence of hepatic steatosis and advanced hepatic fibrosis was determined using cutoff values for fatty liver index (FLI) and BARD score. We evaluated the association of FLI or BARD score with the development of iHF, hHF, mortality and CV death using multivariable-adjusted Cox regression models. A total of 28,524 (3.7%) individuals in the general population and 1422 (19.1%) pre-existing HF patients developed iHF and hHF respectively. In the multivariable-adjusted model, participants with an FLI ≥ 60 were at increased risk for iHF (hazard ratio [HR], 95% confidence interval [CI], 1.30, 1.24–1.36), hHF (HR 1.54, 95% CI 1.44–1.66), all-cause mortality (HR 1.62, 95% CI 1.54–1.70), and CV mortality (HR 1.41 95% CI 1.22–1.63) in the general population and hHF (HR 1.26, 95% CI 1.21–1.54) and all-cause mortality (HR 1.54 95% CI 1.24–1.92) in the HF patient group compared with an FLI < 20. Among participants with NAFLD, advanced liver fibrosis was associated with increased risk for iHF, hHF, and all-cause mortality in the general population and all-cause mortality and CV mortality in the HF patient group (all p < 0.05). Hepatic steatosis and/or advanced fibrosis as assessed by FLI and BARD score was significantly associated with the risk of HF and mortality.     

Predicting outcome of paracetamol poisoning by use 14C-aminopyrine breath test.

The 14C-aminopyrine (14C-amidopyrine) breath test, carried out within 24-36 hours of an overdosage of paracetamol, was used to predict the extent of liver damage in 30 seriously poisoned patients. Mean 14CO2 excretion was 4.4% in 20 healthy control subjects; 5.5% in six patients who escaped injury; and 2.9%, 1.5%, and 0.2% in those with mild to moderate (12 patients), severe (eight patients), and fatal (four patients) liver damage respectively. This test proved to be a more reliable predictor of the extent of liver damage than plasma paracetamol concentration or half life or the results of conventional liver function tests and may enable treatment of hepatic failure to be started at an early stage.     

Propofol versus Midazolam for Upper Gastrointestinal Endoscopy in Cirrhotic Patients: A Meta-Analysis of Randomized Controlled Trials

BackgroundSedation during gastrointestinal endoscopy is often achieved using propofol or midazolam in general population. However, impaired protein synthesis, altered drug metabolism, and compromised hepatic blood flow in patients with liver cirrhosis might affect the pharmacokinetics of sedatives, placing cirrhotic patients undergoing endoscopy at a greater risk of adverse events. The objective of this study was to assess comparative efficacies and safety of propofol and midazolam in cirrhotic patients undergoing endoscopy.MethodsRandomized, controlled trials comparing propofol with midazolam in cirrhotic patients undergoing gastrointestinal endoscopy were selected. We performed the meta-analysis, using a random-effect model, the Review Manager, Version 5.2, statistical software package (Cochrane Collaboration, Oxford, UK) according to the PRISMA guidelines.ResultsFive studies between 2003 and 2012, including 433 patients, were included. Propofol provided a shorter time to sedation (weight mean difference: -2.76 min, 95% confidence interval: -3.00 to -2.51) and a shorter recovery time (weight mean difference -6.17 min, 95% confidence interval: -6.81 to -5.54) than midazolam did. No intergroup difference in the incidence of hypotension, bradycardia, or hypoxemia was observed. Midazolam was associated with the deterioration of psychometric scores for a longer period than propofol.ConclusionThis meta-analysis suggests that Propofol sedation for endoscopy provides more rapid sedation and recovery than midazolam does. The risk of sedation-related side effects for propofol does not differ significantly from that of midazolam. The efficacy of propofol in cirrhotic patients undergoing endoscopy is superior to those of midazolam.     

The neurological manifestations of acute liver failure

Acute liver failure is a disorder which impacts on multiple organ systems and results from hepatocellular necrosis in a patient with no previous history of chronic liver disease. It typically culminates in the development of liver dysfunction, coagulopathy and encephalopathy, and is associated with high mortality in poor prognostic groups. In acute liver failure, some patients may develop cerebral edema and increased intracranial pressure although recent data suggest that intracranial hypertension is less frequent than previously described, complicating 29% of acute cases who have proceeded to grade 3/4 coma. Neurological manifestations are primarily underpinned by the development of brain edema. The onset of encephalopathy can be rapid and dramatic with the development of asterixis, delirium, hyperreflexia, clonus, seizures, extensor posturing and coma. Ammonia plays a definitive role in the development of cytotoxic brain edema. Patients with acute liver failure have a marked propensity to develop renal insufficiency and hence impaired ammonia excretion. The incidence of both bacterial and fungal infection occurs in approximately one third of patients. The relationship between inflammation, as opposed to infection, and progression of encephalopathy is similar to that observed in chronic liver disease. Intracranial pressure monitoring is valuable in identifying surges in intracranial hypertension requiring intervention. Insertion of an intracranial bolt should be considered only in the subgroup of patients who have progressed to grade 4 coma. Risk factors for developing intracranial hypertension are those with hyperacute and acute etiologies, progression to grade 3/4 hepatic encephalopathy, those who develop pupillary abnormalities (dilated pupils, sluggishly responsive to light) or seizures, have systemic inflammation, an arterial ammonia >150 μmol/L, hyponatremia, and those in receipt of vasopressor support. Strategies employed in patients with established encephalopathy (grade 3/4) aim to maintain freedom from infection/inflammatory milieu, provide adequate sedation, and correct hypo-osmolality.     

Liver Stiffness by Transient Elastography Predicts Liver-Related Complications and Mortality in Patients with Chronic Liver Disease

Background

Liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) is a validated method for noninvasively staging liver fibrosis. Most hepatic complications occur in patients with advanced fibrosis. Our objective was to determine the ability of LSM by TE to predict hepatic complications and mortality in a large cohort of patients with chronic liver disease.

Methods

In consecutive adults who underwent LSM by TE between July 2008 and June 2011, we used Cox regression to determine the independent association between liver stiffness and death or hepatic complications (decompensation, hepatocellular carcinoma, and liver transplantation). The performance of LSM to predict complications was determined using the c-statistic.

Results

Among 2,052 patients (median age 51 years, 65% with hepatitis B or C), 87 patients (4.2%) died or developed a hepatic complication during a median follow-up period of 15.6 months (interquartile range, 11.0–23.5 months). Patients with complications had higher median liver stiffness than those without complications (13.5 vs. 6.0 kPa; P<0.00005). The 2-year incidence rates of death or hepatic complications were 2.6%, 9%, 19%, and 34% in patients with liver stiffness <10, 10–19.9, 20–39.9, and ≥40 kPa, respectively (P<0.00005). After adjustment for potential confounders, liver stiffness by TE was an independent predictor of complications (hazard ratio [HR] 1.05 per kPa; 95% confidence interval [CI] 1.03–1.06). The c-statistic of liver-stiffness for predicting complications was 0.80 (95% CI 0.75–0.85). A liver stiffness below 20 kPa effectively excluded complications (specificity 93%, negative predictive value 97%); however, the positive predictive value of higher results was sub-optimal (20%).

Conclusions

Liver stiffness by TE accurately predicts the risk of death or hepatic complications in patients with chronic liver disease. TE may facilitate the estimation of prognosis and guide management of these patients.