THE HEPATOPULMONARY SYNDROME

Introduction

The hepatopulmonary syndrome has been acknowledged as an important vascular complication in lungs developing systemic hypoxemia in patients with cirrhosis and portal hypertension. Is formed by arterial oxygenation abnormalities induced from intrapulmonary vascular dilatations with liver disease. It is present in 4-32% of patients with cirrhosis. It increases mortality in the setting of cirrhosis and may influence the frequency and severity. Initially the hypoxemia responds to low-flow supplemental oxygen, but over time, the need for oxygen supplementation is necessary. The liver transplantation is the only effective therapeutic option for its resolution.

Aim

To update clinical manifestation, diagnosis and treatment of this entity.

Method

A literature review was performed on management of hepatopulmonary syndrome. The electronic search was held of the Medline-PubMed, in English crossing the headings "hepatopulmonary syndrome", "liver transplantation" and "surgery". The search was completed in September 2013.

Results

Hepatopulmonary syndrome is classically defined by a widened alveolar-arterial oxygen gradient (AaPO2) on room air (>15 mmHg, or >20 mmHg in patients >64 years of age) with or without hypoxemia resulting from intrapulmonary vasodilatation in the presence of hepatic dysfunction or portal hypertension. Clinical manifestation, diagnosis, classification, treatments and outcomes are varied.

Conclusion

The severity of hepatopulmonary syndrome is an important survival predictor and determine the improvement, the time and risks for liver transplantation. The liver transplantation still remains the only effective therapeutic.     

Liver transplant offers a survival benefit over margin negative resection in patients with small unifocal hepatocellular carcinoma and preserved liver function

Background

Studies comparing orthotopic liver transplantation to margin negative resection for patients with small unifocal hepatocellular carcinoma have not controlled for degree of cirrhosis.

N-Terminal Brain Natriuretic Peptide as a Diagnostic Test in Cirrhotic Patients With Pulmonary Arterial Hypertension

Background

The aim of this study was to assessed the correlation of N-terminal natriuretic peptide type B (NT-proBNP) with echocardiographic and hemodynamic indexes of right ventricular (RV) function and to evaluate the sensitivity and specificity of Doppler echocardiography in the diagnosis of portopulmonary hypertension.

Methods

All patients underwent liver transplantation for cirrhosis. We obtained clinical data, NT-proBNP levels, echocardiography, and right heart hemodynamic measurements before transplantation.

Results

Patients with pulmonary hypertension displayed significantly higher levels of NT-proBNP. They also showed higher model for End-stage Liver Disease scores and higher indices of RV overload on cardiac hemodynamics. The negative predictive value of echocardiography to identify pulmonary hypertension was 83%. A correlation was not observed between systolic pulmonary artery pressures measured by the two methods; however, NTproBNP showed a trend toward a significant correlation with mean pulmonary pressure as determined by hemodynamics (r = .3; P < .01).

Conclusion

We concluded that NT-proBNP values showed significant correlations with pulmonary hypertension that could assist in a noninvasive diagnoseis for this group of patients.     

Incidence of heparin-induced thrombocytopenia type II and postoperative recovery of platelet count in liver graft recipients: a retrospective cohort analysis

Background

Thrombocytopenia in patients with end-stage liver disease is a common disorder caused mainly by portal hypertension, low levels of thrombopoetin, and endotoxemia. The impact of immune-mediated heparin-induced thrombocytopenia type II (HIT type II) as a cause of thrombocytopenia after liver transplantation is not yet understood, with few literature citations reporting contradictory results. The aim of our study was to demonstrate the perioperative course of thrombocytopenia after liver transplantation and determine the occurrence of clinical HIT type II.

Method

We retrospectively evaluated the medical records of 205 consecutive adult patients who underwent full-size liver transplantation between January 2006 and December 2010 due to end-stage or malignant liver disease. Preoperative platelet count, postoperative course of platelets, and clinical signs of HIT type II were analyzed.

Results

A total of 155 (75.6%) of 205 patients had thrombocytopenia before transplantation, significantly influenced by Model of End-Stage Liver Disease score and liver cirrhosis. The platelet count exceeded 100,000/μL in most of the patients (n = 193) at a medium of 7 d. Regarding HIT II, there were four (1.95%) patients with a background of HIT type II.

Conclusions

The incidence of HIT in patients with end-stage hepatic failure is, with about 1.95%, rare. For further reduction of HIT type II, the use of intravenous heparin should be avoided and the prophylactic anticoagulation should be performed with low-molecular-weight heparin after normalization of platelet count.     

Outcome of Combined Liver and Kidney Transplantation in Hepatitis C: A Single-Center Long-Term Follow-up Experience

Introduction

Hepatitis C (HCV) cirrhosis is the prevalent liver disease requiring liver transplantation in the United States. Candidates who also have end-stage renal disease, chronic renal disease stage 4, or prolonged hepatorenal syndrome are considered for combined liver and kidney transplantation (CLKT).

Materials and methods

We performed a retrospective study of HCV(+) and HCV(−) CLKT patients with more than 12 months of follow-up and HCV(+) patients with isolated liver transplant (OLT) to compare the outcomes of various groups.

Results

Since 1988, 2983 OLTs were performed at our institution including 58 CLKTs. Of these, 23 were HCV(+) subjects who were significantly older than HCV(−) CLKT patients. Race, pretransplant dialysis time, renal indication for CLKT, Model for End-stage Liver Disease score, donor age, liver and kidney rejection as well as occurrence of posttransplant hypertension were similar among HCV(+) and HCV(−) CLKT patients. Posttransplant diabetes was observed in 80% of the HCV(+) group and 30% of the HCV(−) group (P = .01). Renal function seemed to be better in HCV(−) when compared with HCV(+) subjects at 5 years (P = .09). Overall patient survival for HCV(+) CLKT, HCV(−) CLKT, and HCV(+) OLT groups at 1, 2, and 5 years were not significantly different (P = .6).

Conclusion

HCV positivity should not exclude appropriate candidates for CLKT.     

Association Between Readmission After Liver Transplant and Adverse Immunosuppressant Reactions: A Prospective Cohort With a 1-Year Follow-up

Objective

To measure the association between readmission after liver transplantation and corresponding adverse drug reactions.

The comparison of the perioperative changes in lactate and prothrombin time between deceased versus living donor liver transplantation

Introduction

The present study compared the functional capacity of the grafts by evaluating changes in lactate and PT after reperfusion among deceased donor liver transplantation (DDLT) versus living donor liver transplantation (LDLT).

Methods

We performed a retrospective analysis of primary adult liver transplantations (45 and 77 recipients in DDLT and LDLT, respectively) between January 2007 and December 2009. Lactate was recorded from 5 minutes after reperfusion of graft (R0) to intensive care unit admission (P0). PT expressed in international normalized ratio (INR) was recorded from R0 to postoperative day (POD) 5. These values were compared between two groups.

Results

The cold ischemia time (CIT), Child-Turcotte-Pugh score, Model for End-stage Liver Disease score, INR, and graft-to-recipient weight ratio were greater in the recipients of DDLT versus LDLT. Lactate and INR at R0 were similar between the two groups, but, the values showed a faster recovery from 1 hour after reperfusion until P0 for lactate and until POD 5 for INR among DDLT recipients. The fresh frozen plasma requirements during corresponding periods were similar between the two groups.

Conclusion

The functional capacity of the graft measured by changes in lactate and PT after reperfusion showed faster recovery among DDLT versus LDLT recipients despite poorer graft quality (longer CIT) and the recipients' preoperative medical conditions-higher MELD and CTP scores.     

Survival Rates Among Patients Awaiting Deceased Donor Liver Transplants at a Single High-Volume Korean Center

Background

Since the establishment of the Korean Network for Organ Sharing (KONOS) in 2000, thousands of patients have been enrolled on the waiting list, but only a small proportion have received a deceased donor liver transplantation. This report on waiting list mortality in Korea based on data from a single institution.

Methods

The 1772 patients enrolled on the waiting list between February 2000 and December 2011 either have not yet received at the time of analysis or have died before receiving an organ. Survival information was obtained in February 2012 by reviewing medical records or by telephone. We excluded patients who died immediately after enrollment or after retransplantation.

Results

Primary diagnoses of those awaiting transplantation were hepatitis B virus-associated cirrhosis (63.7%), alcoholic liver disease (14.3%), hepatitis C virus-associated cirrhosis (13.8%), and acute liver failure due to other causes (8.1%). The priority status of patients on the waiting list was KONOS status 1 (highest priority) in 3.8%, status 2A in 3.9%, status 2B in 41.9%, status 3 to 7 (lowest priority) in 50.5%. Their median survival periods were 1, 1, 18, and 59 months, respectively. The mean Child-Pugh score was 8.5 ± 2.5 and Model for End-stage Liver Disease (MELD) score 18.1 ± 9.8.

Conclusions

Patients with high MELD scores or hepatocellular carcinoma succumbed soon after being entered on to the waiting list. By increasing organ donation rates and developing a risk-based allocation system, it should be possible to reduce mortality among patients on organ waiting lists.     

Bone Disorders in Patients With Chronic Liver Disease Awaiting Liver Transplantation

Background

An important complication of chronic liver disease is osteodystrophy, which includes osteoporosis and the much rarer osteomalacia. Both conditions are associated with significant morbidity through fractures resulting in pain, deformity, and immobility. Liver transplantation may further deteriorate bone metabolism. The aim of the present study was to investigate the frequency and severity of hepatic osteodystrophy among patients with liver cirrhosis who were referred for liver transplantation. We also evaluated modifications in bone metabolism after liver transplantation.

Materials and methods

We recruited 35 consecutive patients with chronic liver disease who were undergoing assessment for transplantation over a 1-year period. Bone mass in the total skeleton and proximal hip was evaluated using a dual-energy X-ray absorptiometry device (Lunar Prodigy Advance, GE Healthcare, USA). According to World Health Organization recommendations, osteoporosis was defined as a T score < −2.5 and osteopenia as T score between −1 and −2.5.

Results

We enrolled in the study 35 patients, including 8 females and 27 males of overall mean age of 57 ± 7, who showed a viral etiology (57%) or alcohol etiology (28%), Child-Pugh 8.7 ± 2.3. The overall prevalence of osteodystrophy was 40% (26% osteopenia and 14% osteoporosis). No difference was evident according to gender, severity of liver disease (Child-Pugh, Model for End-stage Liver Disease), or origin of liver disease. A subgroup of 10 transplanted patients reached 3-month follow-up, showing total body T score with a significant decrease after 3 months while femoral T scores tended to decrease insignificantly.

Conclusions

This study revealed a high prevalence of low bone mineral density among cirrhotic patients before liver transplantation. We suggest that both bone mineral density and biochemical examinations should be considered to be routine tests to identify the status of bone mass and bone metabolism among recipients prior to liver transplantation.     

Living Donor Liver Transplantation for Progressive Familial Intrahepatic Cholestasis Type 1: Two Reported Cases

Background

Progressive familial intrahepatic cholestasis type 1 (PFIC1) is an inherited disease characterized by cholestatic features. We report two patients with PFIC1 who underwent liver retransplantation.

Diaphragm Muscle Surface Electromyography in Patients Submitted to Liver Transplant and Eligible for Extubation

Introduction

Liver disease induces many organic and metabolic changes, leading to malnutrition and weight and muscular function loss. Surface electromyography is an easily applicable, noninvasive study, through which the magnitudes of the peaks on the charts depict voluntary muscle activity.

Living donor liver transplantation for Dorfman-Chanarin syndrome with 1 year follow-up: case report

A 27-year-old Japanese man underwent liver transplantation because of uncompensated cirrhosis due to Dorfman-Chanarin syndrome (DCS). At birth, the patient displayed ichthyosis and liver dysfunction. Moreover, mental retardation appeared and intracytoplasmic vacuoles were observed within peripheral blood neutrophils. A fatty liver was also noticed, leading to the diagnosis of DCS. When he was referred to our hospital, his American Society of Anesthesiologists score was 3. The findings of computed tomography showed liver atrophy, splenomegaly, and ascites. The Child-Pugh score was B, and the Model for End-stage Liver Disease score was 14. The pathophysiology was DCS with uncompensated liver cirrhosis. Therefore, living donor liver transplantation (LDLT) was performed from the patient's brother. The histological appearance of the resected liver revealed macrovesicular steatosis in most hepatocytes with excess fibrous tissue in the portal areas. These findings were compatible with nonalcoholic steatohepatitis. Although the patient's mental retardation and characteristic appearance have not improved, good liver function has been maintained since LDLT. An outpatient protocol liver biopsy performed at 12 months after LDLT did not show recurrence of macrovesicular steatosis.     

Liver transplantation in patients with cryptogenic cirrhosis: long-term follow-up

Objective

The objective of this study was to evaluate long-term survival, histological diagnoses, and mobility of patients with cryptogenic cirrhosis (CC) treated with orthotopic liver transplantation (OLT).

Patients and Methods

We performed a retrospective analysis of 35 patients who underwent transplantation with CC among 800 OLT patients. There were no differences in gender, mean age of 47 years, average MELD (Model for End-stage Liver Disease) of 16, and hepatocellular carcinoma incidence (8%).

Results

In 28.6% of patients, the diagnosis of CC was wrong. There was no incidence of an acute rejection episode and a low incidence of complications, although the postoperative mortality rate was 20%, of chronic rejection was 25%, and recurrence of disease was 4%. Cumulative at 3-, 5-, and 10-year survivals were lower than the other OLT. Survival was lower in patients receiving suboptimal grafts.

Conclusions

One of 3 patients who underwent transplantation for CC had a specific etiologic diagnosis. The chronic rejection rate and postoperative mortality rate were higher than other etiologies, and survivals at 5, 10, and 15 years were lower than other OLT.     

Outcomes of liver transplantation in candidates with portal vein thrombosis

Objective

The objective of the present study was to analyze the incidence of portal vein thrombosis (PVT), comparing morbidity and mortality rates among those affected with and those free of this complication. In the PVT group, we also analyzed mortality related to partial (PPVT) and total (TPVT) thrombosis.

Methods

We undertook a retrospective study of orthotopic liver transplantations from deceased donors in 617 recipients from January 1991 until October 2008. Recipients were classified according to whether they had PVT. In all cases, we considered age, sex, Model for End-stage Liver Disease score, Child-Pugh score, indication for transplantation, type of thrombosis, surgical technique blood product transfusion, and survival rate.

Results

There were 48 patients with PVT (7.78%) among 670 transplantations in 617 recipients in our institution. Concerning the type of thrombosis, 28 (58.3%) were partial and 20 (41.7%) total with complete occlusion of the portal vein lumen.

Conclusion

PVT in liver transplant candidates is a rare event (7.8%) that entails greater difficulty in the procedure, expressed as a longer operative time, greater consumption of blood products, and complex surgical techniques. The prognosis for these patients depends on the type of thrombosis: patients with TPVT showed a higher mortality, whereas those with PPVT had survival rates comparable to those of candidates with a permeable portal vein.     

Impact of Tumor Characteristic on the Outcome of Liver Transplantation in Patients With Hepatocellular Carcinoma

Introduction

Orthotopic liver transplantation (OLT) is a well-established treatment for cirrhotic patients with hepatocellular carcinoma (HCC) who meet the Milan criteria. The aim of this study was to identify predictors of survival among 65 patients with HCC in cirrhotic livers who underwent liver transplantation (OLT).

Methods

From January 2001 to December 2008, we performed 655 OLT in 615 patients. HCC was diagnosed in 58 patients before OLT and in 65 by histological examination of the explanted livers; 74% of the patients met Milan criteria by histological examination.

Results

The median follow-up was 27 months (range = 1-96). We analyzed patient age and gender, etiology of liver disease, Child score at transplantation, rejection episodes, tumor number/size, vascular invasion, and differentiation grade. There was no significant difference in survival among patients grouped according to the Model for End-stage Liver Disease staging system for HCC. The 5-year survival of patients with low differentiated (G3) HCC was significantly worse than that of those with moderately differentiated (G2) or well-differentiated (G1) HCC: 50%, 81%, and 86% respectively, (P < .01). Patients with microvascular invasion displayed a worse 5-year survival than those without vascular invasion (42% vs 80%; P < .01).

Conclusions

The analysis indicated that the histological grade of the tumors and evidences of microscopic vascular invasion were the most useful predictive factors for overall survival among patients with cirrhosis after liver transplantation for HCC.     

ADOPTION OF MELD SCORE INCREASES THE NUMBER OF LIVER TRANSPLANT

Background

Liver transplantation is performed at large transplant centers worldwide as a therapeutic intervention for patients with end-stage liver diseases.

Aim

To analyze the outcomes and incidence of liver transplantation performed at the University of São Paulo and to compare those with the State of São Paulo before and after adoption of the Model for End-Stage Liver Disease (MELD) score.

Method

Evaluation of the number of liver transplantations before and after adoption of the MELD score. Mean values and standard deviations were used to analyze normally distributed variables. The incidence results were compared with those of the State of São Paulo.

Results

There was a high prevalence of male patients, with a predominance of middle-aged. The main indication for liver transplantation was hepatitis C cirrhosis. The mean and median survival rates and overall survival over ten and five years were similar between the groups (p>0.05). The MELD score increased over the course of the study period for patients who underwent liver transplantation (p>0.05). There were an increased number of liver transplants after adoption of the MELD score at this institution and in the State of São Paulo (p<0.001).

Conclusion

The adoption of the MELD score led to increase the number of liver transplants performed in São Paulo.     

Impact of Transjugular Intrahepatic Portosystemic Shunt Creation on Intermediate-Term Model for End-Stage Liver Disease Score Progression

Purpose

To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS) creation on Model for End-stage Liver Disease (MELD) score temporal progression in patients with liver cirrhosis.

Materials and methods

In this single-institution retrospective study, 256 consecutive patients who underwent TIPS creation between 1999 and 2013 were identified for potential investigation. Inclusion criteria for analysis consisted of at least 6 months of post-TIPS clinical follow-up with available lab values at 1, 3, 6, and, if available, 12 months post-TIPS for MELD score calculation. Patients who were lost to follow-up or expired within 6 months, lacked sufficient lab follow-up, or underwent liver transplantation within 6 months of TIPS were excluded from the study cohort. Within-patient variance in MELD score was assessed using repeated-measures analysis of variance.

Results

Sixty-six patients met criteria for study inclusion. TIPS were created for variceal hemorrhage (n = 26) or ascites, hydrothorax, or portal vein thrombosis (n = 40). Hemodynamic success rate was 97% (64/66) and median portosystemic pressure gradient reduction was 13 mm Hg. Median baseline MELD score was 14 (range 7–26). Low MELD scores (≤10, n = 16) increased in sequential scores over 1-year follow-up (median increase +3.5), intermediate MELD scores (11–18, n = 34) showed general stability in successive scores over 1-year follow-up (median increase +1), and high MELD scores (≥19, n = 16) decreased in serial scores over 1-year follow-up (median decrease −4); these trends are compatible with published MELD progression tendencies in cirrhotic patients without TIPS. However, the MELD score changes were not statistically significant (P = .172) on within-subject comparison.

Conclusions

Among patients with liver cirrhosis who recover from the procedure, TIPS creation does not alter the natural MELD score evolution during intermediate term follow-up, and as such does not significantly alter liver transplant candidacy.     

Pretransplant hyponatremia could be associated with a poor prognosis after liver transplantation

Introduction

Predicting the prognosis of hepatic cirrhosis is the most accurate method to achieve a fair allocation among the liver transplant waiting list thereby reducing overall mortality rates.

Aim

To study the survival rates of recipients who undergo liver transplantation in association with hyponatremia rates.

Methods

This retrospective study used a prospectively collected database. The characteristics of liver donors and recipients were: age (years), Model for End-stage Liver Disease (MELD), MELD Na score, recipient body mass index (kg/m²), warm ischemia time (minutes), cold ischemia time (minutes), intensive care unit time (days), hemocomponents transfused, recipient glycemia (mg/dL) and serum sodium (mEq/L), Child-Pugh-Turcotte classification (points), and survival time (months). We analyzed all 318 consecutive liver transplantations from February 1994 to May 2010 divided into two groups: A (Na > 130 mEq/L) and B (Na ≤ 130 mEq/L). The Kaplan-Meier method was used to evaluate survival rate and the Cox regression test to identify predictive factors.

Results

Hyponatremic patients displayed shorter survival (P = .04). The Cox regression for survival time showed that patients with low serum sodium values (group B) had: Child-Pugh scores with 1.13% plus risk of death for each point; cold ischemia time with 1.001% less risk of death for each minute; glycemia with 0.6% for each mg/dL; 0.66% use of cell-saver; plus a risk of death for each 100 mL plus 1.02% risk of death for each year of donor age.

Conclusion

Hyponatremic cirrhotic patients show more advanced stages of disease compared to normonatremic cirrhotics. They usually display metabolic or cirrhotic decompensation and comorbidities. When these symptoms were associated with the use of extended criteria donors, increased cold ischemia time, and intraoperative bleeding, we observed lower survival rates.     

Stratifying Mortality in a Model for End-Stage Liver Disease Waiting List: A Brazilian Single-Center Study

Background

The Model for End-Stage Liver Disease (MELD) system reliably predicts mortality in cirrhotic patients. However, the etiology of liver disease and presence of portal vein thrombosis are not directly taken into account in MELD score. Its impact on the outcomes of patients on the waiting list is still unclear. The aim of this study was to investigate mortality and access to transplantation regarding etiology of liver disease and portal vein thrombosis (PVT).

Assessing bone status in patients awaiting liver transplantation

Osteoporosis is common in liver transplant recipients as a result of both iatrogenic factors and preexisting hepatic osteodystrophy.

Objectives

To assess the prevalences of osteoporosis and fractures and to identify risk factors for these two abnormalities in patients awaiting liver transplantation for end-stage liver disease.

Methods

Between January 2006 and December 2007, patients on a liver transplant waiting list underwent a routine evaluation comprising the identification of risk factors for osteoporosis, radiographs of the spine, bone mineral density measurements (BMD), and laboratory tests (phosphate and calcium levels, hormone assays, liver function tests, and bone turnover markers).

Results

We studied 99 patients (70 males and 20 females; mean age, 55 ± 8 years) including 75% with alcohol-induced cirrhosis with or without hepatocarcinoma. Among them, 36% had radiographic vertebral fractures, 38% had osteoporosis, 35% had osteopenia, and 88% had vitamin D insufficiency or deficiency (25(OH)vitamin D3 < 20 ng/mL). Lower BMD values were associated with vertebral fractures; the odds ratios and 95% confidence intervals for each BMD decrease of 1 SD were as follows: spine, 1.45 (95%CI, 1.1–1.9); total hip, 2.1 (95%CI, 1.3–3.2); and femoral neck, 2 (95%CI, 1.3–3.1) (P < 0.05). Levels of bone resorption markers correlated negatively with BMD at the spine and hip. The Model for End-Stage Liver Disease score correlated negatively with hip BMD.

Conclusion

Our findings suggest high prevalences of low BMD values and vertebral fractures among patients awaiting liver transplantation. Bone status should be evaluated routinely in candidates to liver transplantation.