In the background of availability of better treatments for specific liver diseases and listing of nonalcoholic steatohepatitis (NASH) as an etiology for liver transplantation (LT), data are unclear ...on the impact of disease etiology on the frequency of LT and liver posttransplantation outcomes.
The United Network for Organ Sharing database (1994-2009) was queried for adults receiving first LT for primary biliary cirrhosis (PBC; n=3052), primary sclerosing cholangitis (PSC; n=3854), hepatitis C virus (HCV; n=15,147), alcoholic cirrhosis (AC; n=8940), HCV+alcohol (n=6066), NASH (n=1368), cryptogenic cirrhosis (CC; n=5856), hepatitis B virus (HBV; n=1816), and hepatocellular carcinoma (HCC; n=8588). Graft and patient survival were compared and Cox models were built to determine independent prediction of outcomes by disease etiology.
The frequency of LT increased for NASH, HCC, and HCV+alcohol, remained stable for AC, and decreased for PBC, PSC, HCV, CC, and HBV. The proportion of simultaneous liver-kidney transplants increased from approximately 3% in 2001 to 10% in 2009. Compared with PBC, 5-year graft and patient survival were (a) similar for PSC, NASH, and HBV (80-85%), (b) poorer for AC and CC (hazard ratio, 1-1.5), and (c) worst for HCV, HCV+alcohol, and HCC (hazard ratio, 1.5-2.4). Five-year outcomes for HCV-associated HCC were poorer compared with HCC due to other etiologies.
LT performed for NASH and HCC are increasing. Potent treatment options resulted in a decrease in number of transplants for HBV, HCV, and PBC. Better treatment modalities for HCV are expected to further reduce the number of LT for HCV. Excellent posttransplantation outcomes for NASH and AC are encouraging, resulting in wider acceptance of transplants for these etiologies.
The Model for End-Stage Liver Disease (MELD) uses bilirubin, the international normalized ratio for prothrombin time, and creatinine to estimate the risk of death in patients waiting for liver ...transplantation. This analysis of about 14,000 registrants on the waiting list showed that the addition of the serum sodium concentration to the MELD score improves prognostic accuracy and may reduce mortality among patients on the waiting list who have low MELD scores and serum sodium levels.
This analysis of registrants on the waiting list for liver transplantation showed that the addition of the serum sodium concentration to the Model for End-Stage Liver Disease (MELD) score improves prognostic accuracy and may reduce mortality among patients on the waiting list who have low MELD scores and serum sodium levels.
The allocation of grafts for liver transplantation from deceased donors in the United States is based on medical urgency, which is estimated according to the Model for End-Stage Liver Disease (MELD) score. The MELD score is based on the results of three readily available, objective, and reproducible laboratory tests: the total serum bilirubin concentration, the international normalized ratio (INR) for the prothrombin time, and the serum creatinine concentration.
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In the United States, the MELD score has been used in determining priorities for organ allocation in liver transplantation since 2002.
In addition to the MELD score, the serum sodium concentration . . .
Summary Pulmonary concerns in liver transplant candidates have intraoperative and outcome implications. Evolving MELD exception policies address transplant priority for problems such as ...hepatopulmonary syndrome, portopulmonary hypertension, and hemorrhagic hereditary telangiectasia. Other pulmonary issues such as refractory hepatic hydrothorax, advanced chronic obstructive lung disease (including alpha-1 antitrypsin deficiency) and indeterminate pulmonary nodules may affect liver transplant consideration. Herein, we discuss current pulmonary-related contraindications, indications and MELD exception policies for liver transplantation, suggesting future considerations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Few data exist concerning survival after the diagnosis of hepatopulmonary syndrome (HPS). Although orthotopic liver transplantation (OLT) frequently results in complete resolution of HPS, the ...relationship between transplantation and survival has not been described. The study rationale was to describe long-term survival in patients with HPS. Data were derived from patients diagnosed with HPS at Mayo Clinic (n = 61) between 1985 and 2002, including those undergoing OLT (n = 24) and those who did not (n = 37). A case-control, Kaplan-Meier survival analysis between HPS patients and 77 patients without HPS matched for liver disease cause, model for end-stage liver disease (MELD), severity of liver disease by the Child classification, and age was described for OLT and non-OLT groups. Patients with HPS had a mean partial pressure of arterial oxygen (PaO(2)) decline of 5.2 + 2.3 mm Hg per year awaiting OLT. For HPS patients, despite similar baseline PaO(2), brain uptake of technetium macroaggregated albumin ((99m)TcMAA), or measures of hepatic dysfunction, 5-year survival associated with OLT was 76% versus 23% who did not undergo transplantation (P < .0001). Comparing those who did not undergo transplantation, HPS patients had worse 5-year survival than matched controls (P = .0003). However, reasons to deny OLT (comorbidity) in the setting of HPS may well have contributed to observed survival differences. Baseline PaO(2) </=50 mm Hg was associated with worse survival irrespective of the decision to perform OLT. In conclusion, hypoxemia of HPS is frequently progressive. As OLT outcome relates to pretransplantation PaO(2), additional MELD points should advance the priority for OLT in HPS.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background Ambrisentan is a selective endothelin-receptor antagonist that is approved by the US Food and Drug Administration for the treatment of pulmonary arterial hypertension. We describe ...hemodynamic responses and clinical outcomes of patients with portopulmonary hypertension (POPH) treated with ambrisentan. Methods In this observational study, we prospectively identified and followed consecutive adult patients with POPH who received monotherapy with ambrisentan ≤ 10 mg daily from January 2007 until December 2009. Liver enzymes were assessed monthly. Pulmonary hemodynamic responses were assessed using echocardiograms and right-sided heart catheterizations. Results We identified 13 patients (seven men) with POPH and began monotherapy with ambrisentan. The median age was 57 (interquartile range IQR, 52-60). Patients were followed for a median of 613 days (IQR, 385-1,011). The median model for end-stage liver disease score was 10 (IQR, 8.5-15); eight patients had Child-Turcotte-Pugh A classification. Median time on ambrisentan therapy was 390 days (IQR, 363-611). Two patients died, one of advanced hepatocellular carcinoma and one of septic shock following pneumonia. The mean pulmonary artery pressure decreased from a baseline median of 58 mm Hg (IQR, 37-63) to 41 mm Hg (IQR, 27-48) ( P = .004). The pulmonary vascular resistance median was reduced from 445 dynes/s/cm5 (IQR, 329-834) to 174 dynes/s/cm5 (IQR, 121-361) ( P = .008). There was no difference in the longitudinal analysis of liver function tests (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and international normalized ratio) after 12 months of therapy. One patient underwent successful liver transplantation and normalized pulmonary hemodynamic responses after transplantation. Conclusions In this small cohort of patients with moderate to severe pulmonary hypertension in the setting of POPH, we have shown that ambrisentan monotherapy can significantly improve pulmonary hemodynamic responses without adverse effect on hepatic function.
BACKGROUNDThe frequency of simultaneous liver kidney (SLK) transplantation is increasing. Data are scanty on outcomes of SLK transplants for liver disease etiology.
METHODSOutcomes for liver and ...kidney grafts and patients survival at 5 years were compared for liver disease etiology among adults receiving SLK during 2002 and 2011 in the United States. Cox regression analysis models were built to determine the independent impact of liver disease etiology on outcomes.
RESULTSA total of 2,606 patients (mean age 53 years, 69% males, 55% Caucasians) received SLK for primary biliary cirrhosis (PBC, n=76), primary sclerosing cholangitis (n=81), hepatitis C virus (HCV) (n=945), alcoholic liver disease (n=495), alcohol and HCV (n=152), cryptogenic cirrhosis (CC, n=289), nonalcoholic steatohepatitis (NASH) (n=221), hepatitis B virus (HBV) (n=98), and hepatocellular carcinoma (HCC) (n=249). HCV and NASH+CC contributed to about 44% and 9%, respectively, of all SLK transplants in 2002. Corresponding figures in 2011 were 34% and 22%, respectively. Compared to PBC, 5-year outcomes were worse for NASH, HCV, and HCC for liver graft (72%, 66%, and 72% vs. 82%; hazard ratio, HR2.5–3.1), kidney graft (71%, 65%, and 71% vs. 80%; HR2.3–2.8), and patient survival (74%, 69%, and 69% vs. 82%; HR2.4–2.7). Follow-up renal function assessed at 1, 3, and 5 years showed poor renal function among patients receiving SLK for HCV, NASH, CC, and HBV.
CONCLUSIONSFrequency of SLK transplants is increasing among NASH patients. Overall graft and patient outcomes are good. However, SLK for NASH, HCV, and HCC do worse. Strategies are needed to improve outcomes for SLK in HCV and NASH patients.
Treatment options for refractory hepatic encephalopathy (HE) are limited. Patients who fail medical management may harbor large portosystemic shunts (PSSs) which are possible therapeutic targets. ...This study aims to describe patient selection, effectiveness, and safety of percutaneous PSS embolization in those with medically refractory HE. A retrospective evaluation of consecutive adult patients with medically refractory HE referred for PSS embolization at a tertiary center was performed (2003‐2015). Patient data collected included the type of HE, medications, Model for End‐Stage Liver Disease (MELD) score, shunt type, embolization approach, and materials used. Outcomes of interest were immediate (7 days), intermediate (1‐4 months), and longer‐term (6‐12 months) effectiveness and periprocedural safety. Effectiveness was determined based on changes in hospitalization frequency, HE medications, and symptoms. Twenty‐five patients with large PSS were evaluated for shunt embolization. Five were excluded due to high MELD scores (n = 1), comorbid conditions (n = 1), or technical considerations (n = 3). Of 20 patients who underwent embolization, 13 had persistent and 7 had recurrent HE; 100% (20/20) achieved immediate improvement. Durable benefit was achieved in 100% (18/18) and 92% (11/12) at 1‐4 and 6‐12 months, respectively. The majority (67%; 8/12) were free from HE‐related hospitalizations over 1 year; 10% developed procedural complications, and all resolved. Six developed new or worsening ascites. In conclusion, PSS embolization is a safe and effective treatment strategy that should be considered for select patients with medically refractory HE. Liver Transplantation 22 723–731 2016 AASLD.
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BACKGROUNDData on patient and liver graft survival comparing liver transplantation alone after listing for kidney with simultaneous liver kidney (SLK) transplantation are scanty.
METHODSUnited ...Network Organ Sharing network database (1994–2011) queried for liver transplantation alone after being listed for kidney and SLK transplants.
RESULTSOf 65,206 first liver transplants, 3549 were listed for simultaneous kidney. Of these, 422 (12%) received only liver (LIST) and differed from SLK recipients for the white race (64% vs. 57%; 0.005), diabetes (27% vs. 37%; P = 0.02), model for end-stage liver disease era (68% vs. 82%; P = 0.0001), serum creatinine (2.9±1.9 vs. 4.3±2.5; P < 0.0001), dialysis (35% vs. 64%; P < 0.0001), and donor risk index (1.6±0.4 vs. 1.5±0.3; P < 0.0001). Overall survival was poorer in the LIST group (55% vs. 76%; P < 0.0001). A higher proportion of patients died within 2 days of transplantation in LIST group (11% vs. 0.5%; P < 0.0001), mostly from cardiovascular causes. After excluding these patients, odds of patient mortality and liver graft loss were about 1.2-fold and twofold higher in the LIST group. A total of 103 (24%) patients needed a renal transplantation in the LIST group with 16 (4%) receiving kidney within first year after transplantation. After excluding patients receiving kidney within first year, about 33% recovered renal function to above estimated GFR of greater than 60 mL per min.
CONCLUSIONGuidelines are needed for patient selection to list for and receipt of simultaneous liver kidney transplantation.
Management strategies for patients with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) have changed, along with liver allocation policies based on model for end-stage liver ...disease score. We investigated etiologic-specific trends in liver transplantation in the United States during different time periods.
We performed a retrospective study, using the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry data, to identify all adult patients registered for liver transplantation in the United States from January 1, 2004, through December 31, 2015. For subjects listed with multiple diagnoses, HCC was considered the primary listing diagnosis. To determine whether availability of direct-acting antiviral agents, which began in 2011, affected pretransplant (death or drop-out) and post-transplant outcomes for patients with HCV infection, we compared data from the time periods of 2004 to 2010 and 2011 to 2014. We used competing-risk analysis to compare differences in end points between these periods. Differences between periods in pretransplantation and post-transplantation outcomes were estimated using Kaplan-Maier analysis and compared using the log-rank test. Associations between year of listing and pre-liver transplant outcome, and year of liver transplant and survival after transplant, were examined using the log-rank test. Proportional hazard regression was used to evaluate the reliability of the time period effect with potential confounders.
Among 109,018 registrants, 18.5% were registered for liver transplantation because of HCC. In 2015, HCC was the leading diagnosis among registrants (23.9% of registrations) and recipients (27.2% of recipients). Between 2004 and 2015, the ratio of registrants with vs without HCC increased 5.6-fold for patients with HCV infection, 1.9-fold for patients with hepatitis B virus (HBV) infection, 2.7-fold for patients with alcohol abuse, and 10.2-fold for patients with nonalcoholic steatohepatitis. After adjusting for covariates, we associated the period of 2011 to 2014 with a decreased probability that HCC registrants would undergo liver transplantation (hazard ratio HR, 0.62; P < .0001). The period of 2011 to 2014 also was associated with a decreased probability of drop-out owing to deterioration or death from HCV-induced (HR, 0.90; P = .0003), HBV-induced (HR, 0.71; P = .002), or alcohol-induced (HR, 0.90; P = .01) liver disease, and an increased probability of delisting as a result of clinical improvement in patients with HCV infection (HR, 3.4; P < .0001), HBV infection (HR, 2.3; P = .004), or alcohol abuse (HR, 2.2; P < .0001). The period of 2011 to 2014 was associated with a decreased risk of graft loss or death, with the largest effect seen in HCV-infected recipients (HR, 0.76; P < .0001).
HCC was the leading indication for liver transplantation in the United States in 2015. Despite this, the probability of liver transplantation decreased the most in registrants with HCC. Pretransplantation and post-transplantation outcomes have improved, particularly in patients with HCV infection.
Portopulmonary hypertension (POPH) is the elevation of pulmonary artery pressure due to increased resistance to pulmonary blood flow in the setting of portal hypertension. Increased mortality has ...occurred with attempted liver transplantation in such patients and thus, screening for POPH is advised. We examined the relationship between screening echocardiography and right heart catheterization determinations of pressure, flow, volume, and resistance. A prospective, echocardiography–catheterization algorithm was followed from 1996 to 2005. Consecutive transplantation candidates underwent Doppler echocardiography to determine right ventricular systolic pressure (RVSP). Of 1,235 patients, 101 with RVSP >50 mm Hg underwent catheterization to measure mean pulmonary artery pressure (MPAP), flow via cardiac output (CO), central volume via pulmonary artery occlusion pressure (PAOP), and resistance via calculated pulmonary vascular resistance (PVR). Bland‐Altman analysis suggested marked discordance between echocardiography‐derived RVSP and catheterization results. All‐cause pulmonary hypertension (MPAP >25 mm Hg) was documented in 90/101 (90%) patients. Using current pressure and resistance diagnostic guidelines (MPAP >25 mm Hg, PVR ≥240 dynes/s/cm−5), POPH was documented in 66/101 (65%) patients. Elevated MPAP was due to increased CO and/or PAOP in 35/101 (35%) patients with normal resistance (PVR <240 dynes/s/cm−5). The transpulmonary gradient (MPAP–PAOP) further characterized POPH in the presence of increased volume. Model for end stage liver disease (MELD) scores correlated poorly with MPAP and PVR. In conclusion, right heart catheterization is necessary to confirm POPH and frequently identifies other reasons for pulmonary hypertension (e.g., high flow and increased central volume) in liver transplantation candidates. Severity of POPH correlates poorly with MELD scores. (HEPATOLOGY 2006;44:1502–1510.)
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