Management of patients with cirrhosis awaiting liver transplantation

The demand for OLT continues to be on the rise with patients spending a long time on the waiting list; this not only increases the risk of developing further decompensation but also mortality. The complications discussed above may not only lead to removal from the waiting list in some cases but also a poorer outcome following transplantation. Therefore the appropriate prevention, recognition and treatment of the above-mentioned complications of cirrhosis will have a positive impact on the outcome before and after liver transplantation.     

Referral of patients with primary biliary cirrhosis for liver transplantation.

All patients with primary biliary cirrhosis referred to this unit for consideration for transplantation between April 1981 and January 1989 were analysed retrospectively to assess whether disease stage at referral affects the outcome after grafting and whether greater awareness of the benefits of the procedure means that patients are now being referred at an earlier stage. Seventy of the 107 patients have been grafted, with an overall one year actuarial survival of 62%. A better prognosis at the time of referral, as assessed by both serum bilirubin concentration and a mathematically derived prognostic index, was associated with a greater probability of survival after grafting. Patients in the tertile with the best prognosis (median serum bilirubin concentration at referral 84 mumol/l and estimated survival in the absence of transplantation of more than nine months) had a 78% one year actuarial survival after transplantation, whereas those in the tertile with the worst prognosis (median serum bilirubin concentration 467 mumol/l and estimated survival of less than four months) had a one year actuarial survival of only 50%. No trend towards earlier referral of patients, however, was shown using either of these two markers. This retrospective analysis suggests that many patients are being referred too late for an optimal outcome. We recommend that patients with primary biliary cirrhosis who are potential candidates for liver grafting should be referred to a transplant centre before the serum bilirubin concentration approaches 150 mumol/l.     

Special aspects of timing of liver transplantation in patients with liver cirrhosis

The introduction of liver transplantation as a therapeutic procedure in the treatment of chronic liver disease has accelerated efforts to establish objective criteria in the evaluation of the prognosis of chronic liver disease. Evaluation of the optimum time for liver replacement involves the estimation of the spontaneous prognosis and the possible prognosis after transplantation. Because both items develop dynamically in different directions, criteria for the best time for the indication of liver transplantation are controversial; clinical deterioration of the patient seems to mark the beginning of this time even if the dynamic process of the evolution of clinical complications are taken into account. The change in biochemical parameters is more likely to define the end-point of this period when transplantation could be performed with reasonable success. The development of scores from multivariate statistical analyses has to include the aetiology of the underlying liver disease, but also the specific dynamics of the course of the disease. If these presumptions are fulfilled, the use of such scores seems to be a great step forward to the goal of objective criteria to define the optimum time for liver transplantation.     

Indications of liver transplantation in patients with complications of cirrhosis

Transplantation is the only option for reversing liver insufficiency and its complications in patients with end-stage cirrhosis. Transplantation is generally considered after the first episode of decompensation of cirrhosis, provided no specific intervention can result in a longstanding return to the compensated state. Alcohol abuse and hepatitis C virus infection are the predominant causes leading to transplantation in Western countries. In cases of alcoholic cirrhosis, a 6-month period of abstinence is needed before transplantation. Patients with hepatitis C virus infection are considered independent of viral replication, even if post-transplantation recurrence is almost constant. Conversely, in cases of hepatitis B infection, only patients without viral replication (or with extremely low viral load) are suitable candidates. Hepatocellular carcinoma represents an increasing proportion of the indications and offers excellent long-term survival. However, transplantation should be limited to patients with small tumours. HIV infection no longer represents a definitive contraindication.     

Fiberoptic bronchoscopy in bronchial asthma. A word of caution.

Three instances of intense laryngospasm and bronchospasm occurred as a result of fiberoptic bronchoscopic examination in three patients with quiescent bronchial asthma. The indications for the procedure were hemoptysis in one patient and lobar collapse in two. It is likely that vagally mediated reflex laryngospasm and bronchoconstriction occur when irritant receptors are mechanically stimulated by the bronchoscope. Therefore, in the asthmatic population with its increased airway reactivity, indications for fiberoptic bronchoscopy should be absolute, and the procedure should be performed under optimal conditions. A rationale for minimizing the risk of this procedure in patients with bronchial asthma is discussed.     

Inadequate use of proton-pump inhibitors in patients with liver cirrhosis

OBJECTIVES: Patients with liver cirrhosis have a high prevalence of gastrointestinal symptoms. The use of antiacid therapy (AAT) in these patients is unexplored. We aimed to assess the use of AAT in cirrhotic patients. METHODS: A total of 128 consecutive cirrhotic patients were evaluated for the use of and indications for acid-suppressive agents. Upper endoscopy findings and concomitant medications were registered. A validated questionnaire was used to measure the gastrointestinal symptom burden. Adequate indications for AAT were those strongly supported by the medical literature. RESULTS: Forty percent (n=51) of patients with cirrhosis were on AAT. Thirty-seven percent (n=19) of these had adequate and 63% (n=32) inadequate indications for AAT. The major inadequate indication was previous variceal bleeding (34%). Patients with inadequate indications for AAT had increased severity of symptoms of indigestion compared with patients without AAT (P<0.05). Multivariate analysis revealed that inadequate use of AAT was independently related only to previous variceal bleeding and the number of concomitant medications. CONCLUSION: AAT is used by a large proportion of patients with cirrhosis. In the majority, therapy is based on inadequate indications, mainly continuous long-term therapy after previous variceal bleeding. Patients with an inadequate indication for acid-suppressive medications have increased severity of symptoms of indigestion, indicating that gastrointestinal symptoms might be a factor contributing to proton-pump inhibitor consumption in these patients.     

Optimal timing of liver transplantation for patients with primary biliary cirrhosis: use of prognostic modelling

BACKGROUND/AIMS: Liver transplantation remains the only definitive treatment for patients with end-stage primary biliary cirrhosis, although the optimal timing of the procedure remains uncertain. The aim of the study was to use prognostic modelling to determine the optimal timing of transplantation for patients with primary biliary cirrhosis. METHODS: A prognostic model for predicting the survival of patients after transplantation was generated using the Cox regression model with data from 312 patients transplanted for primary biliary cirrhosis at the Queen Elizabeth Hospital, Birmingham. The prognosis after transplantation was compared to that without transplantation (using a previously published prognostic index for non-transplantation) both in these patients and in 98 non-transplanted primary biliary cirrhosis patients dying from the liver disease, in order to establish at what stage the prognosis with transplantation was better than without transplantation. RESULTS: The prognostic index for transplantation included the following significant prognostic variables: serum bilirubin, serum albumin, age, year of transplantation, and the presence of ascites or treatment with diuretics. Comparison of prognosis with and without transplantation showed that the predicted gain in survival after transplantation becomes increasingly positive when the 6-month survival probability in the absence of transplantation falls below 0.85. In the non-transplanted patients this occurs on average about 8 months before death. CONCLUSIONS: Comparison of the prognosis with and without transplantation provides a rational method for determining the optimum timing of the procedure which occurs approximately when the predicted 6-month survival probability without transplantation falls below 0.85.     

Bacteremia in patients with cirrhosis of the liver.

Infections are frequent in patients with liver cirrhosis, as their defenses against infectious agents are altered. But bacteremia occurring in cirrhotic patients has seldom been reported in the literature. From 1981 to 1986, we collected 197 cases with 228 episodes of bacteremia for this retrospective study. The incidence of bacteremia in cirrhotic patients was 8.8%; no significant difference was noted between cirrhotic patients with variant etiologies of HBV(+), HBV(-) and alcohol. But the incidence increased with the severity of the disease (1%, 4.8%, 17.1% in Child's A, B, C groups, respectively). Gram-negative bacteria were the predominant microorganisms of bacteremia (75.6%). Among them, Escherichia coli, Klebsiella pneumoniae and Aeromonas hydrophilia were the three most commonly detected microorganisms. Gram-positive bacterias were detected in 21.2% of patients with bacteremia, with predominance of the Streptococcus group and Staphylococcus aureus. In about 26.3% of cases the infectious sources were the same by bacteria cultures as from blood. The most common sources were spontaneous bacterial peritonitis, urinary tract infection, pneumonia and biliary tree infection. In cirrhotic patients with and without bacteremia, the mortality rate increased significantly in the bacteremia group (54.8% vs 23.2%, P less than 0.05). By Child's classification, the mortality of patients with classes B and C increased significantly after onset of bacteremia. There was no significant difference in mortality between bacteremic patients in the HBV(+), HBV(-) and alcohol groups. In conclusion, bacteremia is a severe complication of liver cirrhosis and a sign of a poor prognosis.     

Response to exercise in patients with liver cirrhosis: Implications for liver transplantation

End-stage liver cirrhosis is a systemic disease carrying a short-term desperate prognosis without liver transplantation. Given the discrepancy between the growing number of candidates and the limited available liver grafts, the pre-transplantation screening process has become a challenging task. Cardiopulmonary exercise testing, by measuring maximal oxygen consumption at peak exercise, provides a global integrative approach of the health status of an individual. In the setting of liver cirrhosis, decreased oxygen consumption at peak exercise may result from a combination of multiple extra-hepatic complications, including deconditioning, malnutrition-associated muscle weakness, anaemia, cirrhotic cardiomyopathy, and hepato-pulmonary syndrome for instance. In addition, oxygen consumption at peak exercise not only correlated with the severity of the liver disease, but it is also independently associated with survival following liver transplantation. The present article aims to review the numerous determinants of impaired aerobic capacity in patients with severe liver disease, and to discuss how useful is cardiopulmonary exercise testing as a critical tool in the pre-transplantation assessment of these patients.     

Outcome after orthotopic liver transplantation in five HIV-infected patients with virus hepatitis-induced cirrhosis.

BACKGROUND: We report on our experiences with orthotopic liver transplantation (OLT) in HIV-infected patients. Between July 1998 and October 2001, five HIV-infected patients underwent OLT because of virus-induced liver cirrhosis. One patient suffered from hepatitis B virus (HBV)-, three patients from hepatitis C virus (HCV)- and one patient from HCV/HBV/HDV-related cirrhosis (HDV, hepatitis D virus). The mean duration of HIV infection was 15 years. Patients were prospectively followed up with a mean duration of 25.6 months. RESULTS: Three patients died 3, 10 and 31 months after OLT, respectively, due to graft failure. The causes of graft failure were: recurrent thrombosis of the hepatic artery, HCV-associated cholestatic hepatitis and chemotherapy-induced liver damage due to Hodgkin's disease, which was diagnosed 17 months after OLT, in addition to chronic HCV disease. The two survivors show a stable liver function and non-progredient HIV infection under antiretroviral therapy 61 and 23 months after OLT, respectively. CONCLUSIONS: A medium- or even long-term survival after OLT can be achieved in HIV-infected patients without progression of HIV disease under antiretroviral therapy. However, in our study three out of five patients died due to graft failure. Therefore, prognostic criteria have to be defined for the selection of HIV-infected patients, who may benefit from OLT.     

脐血干细胞移植治疗肝硬化的疗效观察

我科对失代偿期肝硬化患者进行脐血干细胞移植治疗,现报道如下. 一、资料与方法 1.一般资料:本研究经有关主管部门批准,医院伦理委员会审核通过,并由患者签字同意.     

Hyponatremia impairs early posttransplantation outcome in patients with cirrhosis undergoing liver transplantation

BACKGROUND & AIMS: Hyponatremia is associated with reduced survival in patients with cirrhosis awaiting liver transplantation. However, it is not known whether hyponatremia also represents a risk factor of poor outcome after transplantation. We aimed to assess the effects of hyponatremia at the time of transplantation on posttransplantation outcome in patients with cirrhosis. METHODS: Two-hundred forty-one consecutive patients with cirrhosis submitted to liver transplantation during a 4-year period (January 2000-December 2003) were included in the study. The main end point was survival at 3 months after transplantation. Secondary end points were complications within the first month after transplantation. RESULTS: Patients with hyponatremia (serum sodium lower than 130 mEq/L) had a greater incidence of neurologic disorders, renal failure, and infectious complications than patients without hyponatremia (odds ratio; 4.6, 3.4 and 2.7, respectively) within the first month after transplantation. By contrast, hyponatremia was not associated with an increased incidence of severe intra-abdominal bleeding, acute rejection, or vascular and biliary complications. Hyponatremia was an independent predictive factor of early posttransplantation survival. Three-month survival of patients with hyponatremia was 84% compared with 95% of patients without hyponatremia (P < .05). Survival was similar after 3 months. CONCLUSIONS: In patients with cirrhosis, the presence of hyponatremia is associated with a high rate of neurologic disorders, infectious complications, and renal failure during the first month after transplantation and reduced 3-month survival. In cirrhosis, hyponatremia should be considered not only a risk factor of death before transplantation but also a risk factor of impaired early posttransplantation outcome.     

Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial

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Pharmacokinetics of ciprofloxacin in patients with liver cirrhosis.

BACKGROUND: Bacterial infections are common in patients with cirrhosis of liver and are frequently treated with ciprofloxacin. Literature on pharmacokinetics of ciprofloxacin in patients with cirrhosis of the liver is scanty. The present study compared the pharmacokinetics of ciprofloxacin in cirrhotic patients with that in healthy volunteers. METHODS: In 20 patients with cirrhosis of liver (all Child-Pugh class B) and 10 healthy volunteers, plasma levels of ciprofloxacin were measured using high-performance liquid chromatography at several time points after a 500-mg oral dose. Various pharmacokinetic parameters were calculated. RESULTS: No significant differences were observed in maximum plasma levels reached (mean [SD] 2.6 [0.6] vs 2.6 [1.3] microg/ml), time taken for maximum plasma levels to be reached (1.3 [0.6] vs 1.5 [0.9] h), t1/2a (0.7 [0.3] vs 0.4 [0.9] h), elimination half-life (3.6 [1.2] vs 3.2 [1.8] h), and area under the curve (19.3 [3.8] vs 21.9 [4.5] microg/mL x h) in healthy volunteers and cirrhotic patients, respectively. CONCLUSIONS: Pharmacokinetics of ciprofloxacin is unaltered in patients with liver cirrhosis. Ciprofloxacin can be safely administered in the usual doses in such patients.