Complication Of End-stage Liver Disease Research Articles

Critical care management of patients with end-stage liver disease

To review the management of complications related to end-stage liver disease in the intensive care unit. The goal of this review is to address topics important to the practicing physician. We performed an organ system-based PubMed literature review focusing on the diagnosis and treatment of critical complications of end-stage liver disease. DATA SYNTHESIS AND FINDINGS: When available, preferential consideration was given to randomized controlled trials. In the absence of trials, observational and retrospective studies and consensus opinions were included. We present our recommendations for the neurologic, cardiovascular, pulmonary, gastrointestinal, renal, and infectious complications of end-stage liver disease. Complications related to end-stage liver disease have significant morbidity and mortality. Management of these complications in the intensive care unit requires awareness and expertise among physicians from a wide variety of fields.

The Management of Hospitalized Patients with Cirrhosis: The Mount Sinai Experience and a Guide for Hospitalists

Cirrhosis and chronic liver disease carry appreciable morbidity and mortality. Cirrhotic patients frequently require hospitalization and their care is both extremely complex and labor-intensive. We seek to provide a review for gastroenterologists, hepatologists, internists, and hospitalists on the approach to care in patients hospitalized for complications related to end-stage liver disease. The Mount Sinai Medical Center's inpatient liver service has developed an integrated team approach for cirrhotic patients and throughout the years has educated fellows-in-training and medical house staff on both the treatment principles and "pearls" in managing the hospitalized cirrhotic patient. We reviewed the literature and provide recommendations on the management of complications of end-stage liver disease. Additionally, we provide a review of the protocols used at our institution in the care for cirrhotic patients. Major complications of advanced liver disease include infection, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, portal hypertension, variceal hemorrhage, hepatorenal syndrome, and hepatocellular carcinoma. Management of these complications involves selecting the appropriate diagnostic studies and prompt administration of therapy. There are many complications of cirrhosis. Management of these complications can be complex and are targeted at stabilizing the patient's clinical condition. Liver transplantation remains the only definitive treatment.

Pediatric living donor liver transplantation for biliary atresia with hepatopulmonary syndrome: the gift of a second wind

Hepatopulmonary syndrome (HPS) is a progressive, deteriorating complication of end-stage liver disease (ESLD) that occurs in 13-47% of liver transplant candidates. Although LT is the only therapeutic option for HPS, it has a high morbidity and mortality, especially in patients with severe hypoxemia before transplantation, but the course of HPS after living donor liver transplantation (LDLT), especially for biliary atresia (BA) patients is not well established. The present study evaluated 122 patients who received an LDLT for BA and of these, 3 patients had HPS at the time of LDLT in a single-center series. Two patients of the HPS patients them had biliary and/or vascular complications, but they recovered uneventfully with interventional treatment. None of the patients required supplemental oxygen and had no residual cardiopulmonary abnormalities at a follow-up of more than 24 months. Although a series of three patients is too small for definitive conclusion and further investigations must be conducted, pediatric LDLT can be a favorable therapeutic option for HPS.

Antiviral Treatment for Hepatitis C Virus Infection after Liver Transplantation

A significant proportion of patients with chronic hepatitis C virus (HCV) infection develop liver cirrhosis and complications of end-stage liver disease over two to three decades and require liver transplantation, however, reinfection is common and leads to further adverse events under immunosuppression. Pretransplant antiviral or preemptive therapy is limited to mildly decompensated patients due to poor tolerance. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic hepatitis C. Combined pegylated interferon and ribavirin therapy is the current standard treatment with sustained viral response rates of 25% to 45%. The rate is lower than that in the immunocompetent population, partly due to the high prevalence of intolerability. To date, there is no general consensus regarding the antiviral treatment modality, timing, or dosing for HCV in patients with advanced liver disease and after liver transplantation. New anti-HCV drugs to delay disease progression or to enhance viral clearance are necessary.

Elevated Myostatin Levels in Patients with Liver Disease

Loss of skeletal muscle mass is a poorly understood complication of end-stage liver disease (ESLD). Based on recent stem cell literature, we hypothesized that the potent negative regulator of muscle mass, myostatin, could play a role in the muscle loss associated with ESLD. In this preliminary investigation, we measured myostatin levels in patients undergoing liver transplant evaluation, using a novel enzyme-linked immunosensitivity assay. Myostatin levels were significantly elevated in patients with ESLD compared with healthy controls. These data suggest that myostatin deserves further investigation as a target for therapies designed to preserve muscle mass in patients with ESLD.

Hepatorenal Syndrome

Acute kidney injury (AKI) secondary to hepatorenal syndrome (HRS) is an ominous complication of end-stage liver disease (ESLD). In HRS, splanchnic and peripheral vasodilatation with reduction in effective arterial volume causes activation of mechanisms leading to intense renal vasoconstriction and functional AKI. HRS is a diagnosis of exclusion and all other causes of AKI (especially prerenal azotemia) have to be considered and excluded. Spontaneous bacterial peritonitis (SBP) frequently precipitates HRS and should be ruled out in all ESLD patients presenting with AKI. Prompt therapy of SBP with intravenous antibiotics and albumin lessens the risk of developing HRS. Combined use of intravenous albumin, splanchnic and/or peripheral vasoconstrictors, and renal replacement therapy (RRT) are only bridges to early liver transplantation (or combined liver-kidney transplantation in selected patients). Transplantation is the only definitive way of improving the long-term prognosis. Close collaboration between hospitalists/internists managing HRS patients and hepatology and nephrology consultants is critically important.

Survival of HIV-infected patients with compensated liver cirrhosis

Since the advent of HAART, liver-related mortality has become the leading cause of non-AIDS deaths in HIV-infected patients in western countries, complications of end-stage liver disease due to chronic hepatitis B, chronic hepatitis C or both being mainly responsible. The incidence and predictors of mortality were examined in HIV-infected patients with compensated liver cirrhosis. The accuracy of three different methods (elastometry, Child-Pugh and Model for End-Stage Liver Disease scores) to predict mortality was further examined. Cirrhosis was defined for hepatic elastometry values above 14.5 kPa. A total of 194 (11.4%) out of 1706 HIV-positive individuals were cirrhotic and were prospectively followed since October 2004 until December 2008. Overall, 89% of cirrhotic individuals had chronic hepatitis C, 10.3% chronic hepatitis B, 4.6% hepatitis delta and 4.1% liver disease of other causes or unknown cause. The overall mortality rate was 5.8 deaths per 100 patient-years. Multivariate analyses showed that age of at least 50 years (hazard ratio 4.76, 95% confidence interval 1.66-13.59, P = 0.004), CD4 cell counts below 200 cells/microl (hazard ratio 3.01, 95% confidence interval 1.26-7.23, P = 0.03) and detectable plasma HIV-RNA (hazard ratio 3.97, 95% CI, 1.53-10.27, P = 0.005) were associated with mortality. A baseline Model for End-stage Liver Disease score of at least 11 (P = 0.03) and hepatic elastometry values above 28.75 kPa (P = 0.001) were independent predictors of mortality. The death rate in HIV-infected patients with compensated liver cirrhosis in the HAART era is 5.8% yearly, higher than mortality previously reported for either HIV-uninfected individuals with cirrhosis or noncirrhotic HIV-positive patients. Factors associated with mortality were older age, low CD4 cell counts and detectable plasma HIV-RNA. Both Model for End-Stage Liver Disease and especially hepatic elastometry accurately predicted mortality in this population.

Hepatopulmonary syndrome and portopulmonary hypertension

The pulmonary complications of end-stage liver disease include hepatopulmonary syndrome and portopulmonary hypertension. The etio-pathogenesis of these conditions is as yet unclear. Hepatopulmonary syndrome is a gas exchange abnormality and usually manifests as hypoxemia secondary to intra-pulmonary vascular shunts. These shunts can be demonstrated by echocardiography using agitated saline injections, and quantitated by lung perfusion scans. Liver transplantation is the treatment of choice for hepatopulmonary syndrome, and there are no effective pharmacological therapies. Portopulmonary hypertension is a hemodynamic problem which manifests as fatigue and right sided cardiac failure. Several vasoactive agents have been used to lower mean pulmonary arterial pressures. Portopulmonary hypertension is a relative contraindication to liver transplantation.

Proteomics and liver fibrosis: identifying markers of fibrogenesis

Chronic hepatic disease damages the liver and the resulting wound-healing process might lead to liver fibrosis and subsequent cirrhosis development. Fibrosis is the excessive deposition of extracellular matrix (ECM) in the tissue as consequence of chronic liver damage. The fibrotic response triggers almost all of the complications of end-stage liver disease, including portal hypertension, ascites, encephalopathy, synthetic dysfunction and impaired metabolic capacity. Thus, efforts to understand and attenuate fibrosis have direct clinical implications. Reliable, accurate, disease-specific, noninvasive biomarkers of fibrosis and fibrogenesis in order to prevent or minimize the impact of the chronic liver disease progression are a critical need. This review aims to provide an overview of the possibilities that proteome technology can offer to the knowledge, diagnosis and prognosis of liver fibrosis.

Rapid Normalization of Portopulmonary Hypertension After Living Donor Liver Transplantation

Portopulmonary hypertension (PPHTN) is a relatively rare complication of end-stage liver disease, and a serious problem in the context of liver transplantation. Herein we have reported a case of decompensated liver cirrhosis with PPHTN, which rapidly resolved after adult-to-adult living donor liver transplantation (LDLT). A 54-year-old man was referred to our hospital with end-stage liver cirrhosis owing to chronic hepatitis C. Preoperative mean pulmonary artery pressure (mPAP), as assessed by right heart catheterization, was 38 mm Hg. Continuous infusion of epoprostenol decreased the mPAP to 24 mm Hg over 44 days. He underwent LDLT using a right hepatic lobe graft donated by his son. The postoperative course was uneventful, epoprostenol was weaned by postoperative day (POD) 21, and the mPAP normalized to 21 mm Hg on POD 28. The patient was discharged on POD 31 without any vasodilators. Our case revealed that liver transplantation can rapidly resolve PPTHN.

Portopulmonary Hypertension: Imatinib as a Novel Treatment and the Emory Experience With this Condition

Portopulmonary hypertension (PoPH) is a common and feared complication of end-stage liver disease, and imposes increased risk of perioperative morbidity in the liver transplant patient. Herein, we present the first successful use of Imatinib in the perioperative management of a patient who was not responding to conventional treatments as well as our institution's experience with this devastating complication. Of patients evaluated for transplant, 4.1% were identified with PoPH, half of which were listed, and one quarter of which were transplanted. Patients with PoPH were twice as likely to be transplanted than all other candidates (48% vs 25%), though less likely to survive their first year (69% vs 86.4%).

Editorial: Hyponatremia in Hepatic Encephalopathy:

Hyponatremia, a common complication inpatients with advanced liver disease and impaired free water clearance, has been shown to be an important predictor of short-term mortality. Hepatic encephalopathy, also a late complication of end-stage liver disease, has been associated with low-grade cerebral edema as a result of swelling of astrocytes. Guevara et al. hypothesized that hyponatremia and the resultant depletion of organic osmolytes (e.g.,myo-inositol) from brain cells contribute to brain edema, playing an important role in the pathogenesis of hepatic encephalopathy. Using a multivariable analysis, they demonstrated that hyponatremia increased the risk of hepatic encephalopathy more than eightfold, after adjustment for serum bilirubin and creatinine concentrations and previous history of encephalopathy. Their magnetic resonance spectroscopy data correlated low brain concentrations of myoinositol with hepatic encephalopathy. As both hyponatremia and encephalopathy occur in patients with advanced liver disease, it has been difficult to implicate hyponatremia independently in the pathogenesis of hepatic encephalopathy. Guevara's data do suggest that hyponatremia is more likely an accomplice than an innocent bystander.

Sclerosing peritonitis and mortality after liver transplantation

Sclerosing peritonitis describes the development of a peel or rind of fibrosis that spreads over the peritoneal surface and can lead to recalcitrant ascites, bowel obstruction, and sepsis. It is well described as a complication of peritoneal dialysis, especially with episodes of bacterial peritonitis. It is also a complication of end-stage liver disease with ascites and liver transplantation. This article describes 3 cases of sclerosing peritonitis present at the time of liver transplantation or soon after. All 3 patients had massive refractory ascites with episodes of spontaneous bacterial peritonitis prior to transplantation. Two patients had evidence of a fibrous peel at the time of transplantation. Postoperatively, all 3 patients continued to have refractory ascites and episodes of peritonitis, along with partial small bowel obstructions, abdominal pain, and malnutrition. Two patients also had constriction of the graft, including biliary obstruction and inferior vena cava and outflow obstruction, which has not been previously described. All 3 patients eventually died from complications related to the sclerosing peritonitis.

Outcome of liver transplantation in hereditary hemochromatosis

Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism. It is an uncommon indication for liver transplantation (LT). It has been suggested that patients who undergo LT for cirrhosis related to HH have higher morbidity and mortality from cardiac, infectious and malignant complications. The purpose of this retrospective review was to determine whether these observations hold true in the current era. We analysed the data of 22 patients who had LT for HH from 1996 to 2007 at our center. Thirteen patients had LT for complications of end-stage liver disease, seven for hepatocellular carcinoma (HCC) and two for subacute liver failure. Cofactors promoting liver disease were identified in 15 patients. Ten patients had iron reduction with venesection before transplantation. Patient and graft survival at 1 and 5 years were 80.7%, and 74% respectively. There were seven deaths after a median follow up of 46 months either because of multiorgan failure, or caused by HCC recurrence. Bacterial infections were the commonest cause of morbidity. Patients with HH remain at a higher risk of developing HCC. Infectious complications are common. Iron reduction with preoperative venesection reduces the risk of cardiac and infection complications postoperatively. Improved survival post-LT reflects changes in selection, disease modification through venesection, and improvement in immunosuppression.

Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis

Hepatorenal syndrome (HRS) is a serious complication of end-stage liver disease, occurring mainly in patients with advanced cirrhosis and ascites, who have marked circulatory dysfunction,1 as well as in patients...

I-50 Cirrhotic cardiomyopathy: an unappreciated complication of endstage liver disease

I-50 Cirrhotic cardiomyopathy: an unappreciated complication of endstage liver disease

Prospective study of bone mineral density and metabolism in patients with chronic hepatitis C during pegylated interferon α and ribavirin therapy

The importance of osteoporosis as a complication of end-stage liver disease is well known. However, significant osteopenia may occur in earlier stages of chronic hepatitis C (CHC). Furthermore, antiviral therapy may influence bone metabolism. Thirty patients with CHC genotype 1 infection and without established cirrhosis were treated with peginterferon-alfa and ribavirin. Dual-energy x-ray absorptiometry was performed at baseline, after 48 weeks of therapy, and by the end of a 24-week follow-up period. Bone mineral density (BMD), T-scores, and Z-scores were assessed. Serum C-terminal propeptide of type I collagen (CICP) and osteocalcin levels were measured. Thirteen patients had osteopenia (43%) and osteoporosis was present in four patients (13%). Antiviral therapy led to significant on-treatment increases of lumbar spine and hip BMD (P < or = 0.05) as well as T-scores (P < or = 0.05) and Z-scores (P < or = 0.01) irrespective of subsequent treatment response. Further analyses showed that in patients with sustained virological response (n = 19) most parameters remained highly above baseline values by the end of the 24-week follow-up period, while patients with virological relapse (n = 11) had decreases of BMD, T-scores and Z-scores thereafter that did not differ from baseline. Serum CICP and osteocalcin levels decreased during therapy. Osteocalcin levels remained below baseline in sustained responder, but showed an increase in relapsers by the end of the 24-week follow-up (P < or = 0.05). Osteopenia is detectable in a substantial proportion of CHC patients without established cirrhosis. Antiviral therapy leads to an on-treatment increase of BMD, which may last in those patients who achieve a sustained virological response.

Liver transplantation for pulmonary vascular complications of pediatric end-stage liver disease

Purpose Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) are poorly understood pulmonary complications of end-stage liver disease (ESLD). We present a case series of children with HPS and PPH. Methods After institutional review board approval, query of our medical database identified children 0 to 18 years of age with ESLD diagnosed with HPS or PPH. Data were collected via chart review. Results We identified 7 children with either HPS (n = 5) or PPH (n = 2). Patients with HPS presented with progressive dyspnea over a mean of 7 months (range, 4-12 months) at a mean of 13 years (range, 5-17 years) of age. Pulmonary shunting by albumin perfusion scan averaged 41% (range, 20%-66%) with an initial mean resting Sp o 2 of 88% (range, 84%-94%) and mean Sp o 2 during exertion of 79% (range, 60%-89%). Four patients required supplemental O 2 and, upon United Network for Organ Sharing (UNOS) appeal, received pediatric model for ESLD (or Child-Pugh) score exceptions, enabling them to undergo orthotopic liver transplant (OLT) within 1-2 months. The fifth patient was initially rejected by the UNOS regional review board, but 6 months of worsening hypoxemia led to OLT 2 months after successful UNOS appeal. All patients with HPS undergoing OLT experienced complete resolution of hypoxemia within 8 months. Both children with PPH were treated with intravenous epoprostenol, which lowered or stabilized mean pulmonary artery pressure and bridged them to OLT within 7 months of listing. Overall, there were no pulmonary complications; however, 1 patient with PPH expired shortly after OLT. The remaining patients are alive at a median follow-up of 27 months (range, 6-96 months). Conclusion Hepatopulmonary syndrome and PPH are uncommon complications of ESLD in children. Epoprostenol can bridge PPH patients to OLT. OLT leads to rapid resolution of HPS and PPH and currently represents the only successful treatment for these children.

Immunizations and infectious diseases in pediatric liver transplantation

Liver transplantation (LTx) is an established and effective treatment for children with end-stage and metabolic liver disease. Improved surgical techniques and immunosuppressive regimens have led to enhanced short-term and long-term survival rates, which now approach or exceed 90%. Consequently, more children are being referred for LTx, and an increasing numbers of pediatric centers routinely perform this procedure. Infectious complications are an important cause of morbidity and mortality in children undergoing LTx. However, improvements in immune suppression management along with the availability of new antimicrobial agents and diagnostic tools have resulted in improved treatment and preventative regimens, thus reducing the impact of infectious complications on these children. This review provides an overview of the infectious complications and prevention strategies for children undergoing LTx.

Critical Care Management of the Liver Transplant Recipient

Liver transplantation is an acceptable treatment modality for complications of end-stage liver disease from chronic and acute liver failure. In the United States, 16 377 people are currently awaiting liver transplant but only 6492 transplantations were performed in 2007. All options for liver transplantation including Model for End stage Liver Disease allocated, expanded criteria deceased donors, and live donor liver transplantation should be discussed with potential recipients on the waitlist to create an early access plan for safe and expeditious transplantation. After transplantation, careful management to avoid complications and intervene early is necessary. Common postoperative complications include graft dysfunction, vascular thrombosis, biliary tract complications, infection, rejection, neurologic injury, electrolyte imbalances, and drug interactions. A multidisciplinary approach to care including the critical care nurse is necessary for successful long-term outcomes.