Risk Prediction Models for Post-Operative Mortality in Patients With Cirrhosis.

BACKGROUND AND AIMS: Patients with cirrhosis are at increased risk of postoperative mortality. Currently available tools to predict postoperative risk are suboptimally calibrated and do not account for surgery type. Our objective was to use population-level data to derive and internally validate cirrhosis surgical risk models. APPROACH AND RESULTS: We conducted a retrospective cohort study using data from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) cohort, which contains granular data on patients with cirrhosis from 128 U.S. medical centers, merged with the Veterans Affairs Surgical Quality Improvement Program (VASQIP) to identify surgical procedures. We categorized surgeries as abdominal wall, vascular, abdominal, cardiac, chest, or orthopedic and used multivariable logistic regression to model 30-, 90-, and 180-day postoperative mortality (VOCAL-Penn models). We compared model discrimination and calibration of VOCAL-Penn to the Mayo Risk Score (MRS), Model for End-Stage Liver Disease (MELD), Model for End-Stage Liver Disease-Sodium MELD-Na, and Child-Turcotte-Pugh (CTP) scores. We identified 4,712 surgical procedures in 3,785 patients with cirrhosis. The VOCAL-Penn models were derived and internally validated with excellent discrimination (30-day postoperative mortality C-statistic = 0.859; 95% confidence interval [CI], 0.809-0.909). Predictors included age, preoperative albumin, platelet count, bilirubin, surgery category, emergency indication, fatty liver disease, American Society of Anesthesiologists classification, and obesity. Model performance was superior to MELD, MELD-Na, CTP, and MRS at all time points (e.g., 30-day postoperative mortality C-statistic for MRS = 0.766; 95% CI, 0.676-0.855) in terms of discrimination and calibration. CONCLUSIONS: The VOCAL-Penn models substantially improve postoperative mortality predictions in patients with cirrhosis. These models may be applied in practice to improve preoperative risk stratification and optimize patient selection for surgical procedures (www.vocalpennscore.com).

In-Hospital mortality varies by procedure type among cirrhosis surgery admissions.

BACKGROUND: Patients with cirrhosis have increased peri-operative mortality risk relative to non-cirrhotic patients, however, the impact of surgical procedure category on this risk is poorly understood. METHODS: We performed a retrospective cohort study of cirrhosis surgery admissions using the National Inpatient Sample between 2012 and 2014 to estimate the adjusted odds of in-hospital mortality by surgical procedure category. RESULTS: In-hospital mortality differed by surgical procedure category. Relative to major orthopedic surgeries, major abdominal surgeries had the highest odds of in-hospital mortality (odds ratio [OR] 8.27, 95% confidence interval [CI] 5.96-11.49), followed by major cardiovascular surgeries (OR 3.45, 95% CI 2.33-5.09). There was also a significant interaction term, whereby elective/non-elective admission status impacted in-hospital mortality risk differently for each surgical procedure category (P < 0.001). CONCLUSION: In-hospital mortality varies substantially by surgical procedure type. Accounting for procedure type in models may improve risk prediction for peri-operative mortality in patients with cirrhosis.

A Head CT is Unnecessary in the Initial Evaluation of A Cirrhotic Patient with Recurrent Hepatic Encephalopathy.

INTRODUCTION AND AIM: The evaluation to determine the cause of hepatic encephalopathy consists primarily of laboratory testing to rule out infections and metabolic causes. Despite lack of evidence, it is a common practice amongst clinicians to obtain a head CT as part of their initial evaluation in a cirrhotic presenting with recurrent episodes of hepatic encephalopathy. MATERIAL AND METHODS: Medical records of all cirrhotic adults admitted to a tertiary care hospital from 2007 to 2010 with hepatic encephalopathy were reviewed. RESULTS: In 67 patients, there were 147 episodes of hepatic encephalopathy where a head CT was performed. Six CTs had intracranial findings explaining hepatic encephalopathy. Two patients had focal neurologic findings on physical exam with no history of trauma, one had a history of trauma with no focal neurologic deficits and two had both a history of trauma and focal neurologic findings. Only one case revealed an intracranial hemorrhage with neither a preceding history of trauma nor positive neurological signs. The overall prevalence of intracranial findings in hepatic encephalopathy was 4% (6/147) and 0.6% (1/142) in the absence of trauma or focal neurologic findings. Laboratory and clinical variables including mean levels of ammonia, sodium, creatinine, bilirubin, albumin, platelet count, INR, encephalopathy grade and MELD score did not have a statistically significant impact on head CT findings (P > .05). CONCLUSION: In conclusion, the yield of a head CT in determining the cause of change in mental status is extremely low in patients with cirrhosis who present with recurrent hepatic encephalopathy.

Liver transplantation using an organ donor with HELLP syndrome.

BACKGROUND: The shortage of organs for liver transplantation has forced transplant centers to expand the donor pool by using donors traditionally labeled as marginal. One such example is liver transplantation using a donor with HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), a disorder of late pregnancy that involves the liver as one of the target organs. METHODS: Two patients who died from complications of HELLP syndrome were evaluated for attempted multi-organ procurement. Donor characteristics, gross and microscopic liver findings, and procurement and transplant outcomes were reviewed. RESULTS: One of the liver allografts was successfully transplanted; the other was not procured because of poor macroscopic appearance. CONCLUSION: It is possible to successfully transplant the liver from a donor that succumbs to HELLP syndrome, provided there is adequate recovery of liver function before procurement.

Long-term outcome of controlled, non-heart-beating donor liver transplantation.

BACKGROUND: Previous reports have established the feasibility of using livers from controlled, non-heart-beating donors (CNHBD) with good immediate graft function. This has been largely borne out of necessity because of the donor shortage. METHODS: Retrospective database review for the last 7 years (1995-2002), encompassing 19 patients receiving CNHBD, with follow-up period of 1,000 +/- 694 days, median 762 days. Detailed review of recipient characteristics, operative and clinical course, immunosuppression, complications, survival rates, and comparison with the results obtained in patients receiving transplants of allografts procured in standard fashion, from heart-beating donors RESULTS: Kaplan-Meier patient survival rates were 100%, 89.5%, and 83.5% at 30 days, 1, and 2 years, respectively, which is not different from recipients of livers procured from heart-beating cadaveric donors (P=0.74, log-rank test). Five patients died at a mean follow-up time of 492 (range 46-1,103) days. The causes of death were related to secondary sclerosing cholangitis (n=1), cardiac failure (n=1), and sepsis (n=3). Two (10.5%) recipients underwent retransplantation, one for primary graft nonfunction and one because of biliary cast syndrome with cholangitis. Significant preservation damage (ALT>2,000) developed in five patients, but this did not affect survival. The incidence of vascular (15.6% vs. 9.6%, P=0.34) and biliary complications (10.55 vs. 13.8%, P=0.68) was no different than for those recipients receiving standard cadaveric donors. CONCLUSIONS: CNHBD safely expands the donor pool with similar long-term results as those obtained in patients receiving organs from brain-dead donors under standard procurement techniques.

Primary biliary cirrhosis.

Primary biliary cirrhosis is a chronic autoimmune inflammatory disease of the liver with a striking female preponderance. It has an insidious onset and typically affects middle-aged women. The disease manifests gradually with symptoms of fatigue, pruritis, and increased alkaline phosphatase levels on laboratory evaluation. The hallmark of the disease is the circulating antimitochondrial antibody. Histology is characterized by inflammation of the bile ducts, destruction of cholangiocytes, and subsequent cholestasis, progressing to biliary cirrhosis. The standard treatment for primary biliary cirrhosis is ursodeoxycholic acid, which improves survival, but the disease can still lead to cirrhosis and liver failure over decades.

Long-term management of the liver transplant recipient: pearls for the practicing gastroenterologist.

Liver transplantation is becoming more common and patients are surviving longer after transplantation. Special care must be paid to the long-term management of these patients because they are at increased risk for medical problems, malignancies, and adverse effects from immunosuppression. A stable and continuing relationship must be developed between the physician and the patient to optimize the long-term outcomes for these individuals.

Health maintenance issues in cirrhosis.

Caring for patients with cirrhosis requires special consideration. The role of the hepatologist is to assist the primary care physician in caring for such patients. This involves an active role in immunizations, lifestyle modifications, and providing instructions on when to go to the emergency room (ER). There are also specific recommendations geared toward the patient with cirrhosis relating to slowing down the disease process, maintaining quality of life, and improving survival.

Extended survival by urgent liver retransplantation after using a first graft with metastasis from initially unrecognized donor sarcoma.

A 58-year-old man underwent orthotopic liver transplantation for polycystic liver disease. Shortly after the procedure, it was discovered that the donor harbored a sarcoma of the aortic arch that had metastasized to the spleen, and bilateral renal cell carcinomas. The two sole organ recipients, our liver recipient and a lung recipient at another institution, were both listed for urgent retransplantation, which they received from the same second donor. The liver explant contained metastatic sarcoma. Twenty-four months survival following lung retransplantation has been previously reported. We report the 76-month disease-free survival in the liver recipient.

Safe use of livers from donors with positive hepatitis B core antibody.

Thirty-five patients received liver transplants using liver donors who had positive test results for the hepatitis B core antibody (HBcAb). In the same time frame, 195 patients received HBcAb-negative liver donors. Mean follow up for patients receiving HBcAb-positive donors was 25 months. All patients receiving HBcAb-positive donors were monitored for recurrence of hepatitis B (HBV) with HBV DNA assays. There was no de novo HBV in recipients of HBcAb-negative grafts. In the group of patients receiving HBcAb-positive donors, 4 of 35 patients died within 3 months after transplant with no evidence of HBV recurrence at time of death. Four patients were transplanted for HBV-related disease and were postoperatively placed on lamivudine and hepatitis B immune globulin (HBIG). HBV recurrence was seen in one of these patients. Of the remaining 27 patients, three of three mismatched patients (HBcAb-positive donor to HBcAb-negative recipient) developed de novo HBV (100%). Of 24 matched patients (HBcAb-positive donor to HBcAb-positive recipient), only two (7%) developed recurrent HBV allograft reinfection. All de novo and recurrent HBV infections were successfully managed with HBIG and lamivudine therapy. Survival for this subgroup of patients receiving HBcAb-positive donors for non-HBV-related liver disease was 100%. We conclude that the judicious use of HBcAb-positive donors is reasonably safe and associated with low morbidity and mortality, with the appropriate follow-up protocols. Additionally, lamivudine use can be reserved for those cases with de novo or recurrent HBV in the liver allograft, or, selectively, as prophylaxis in those recipients patients who are naïve to HBV and receive an HBcAb-positive donor.

Cigarette smoking is associated with an increased incidence of vascular complications after liver transplantation.

Hepatic artery thrombosis (HAT) and other vascular complications are significant causes of morbidity after liver transplantation. Although cigarette smoking increases the risk of vascular complications after renal transplantation, its impact after liver transplantation remains unknown. Between May 1995 and April 2001, 288 liver transplantations were performed in 263 patients. Vascular complications developed in 39 patients (13.5%) (arterial complications, 28 patients [9.7%]; venous complications, 11 patients [3.8%]). Patient demographics, comorbid illnesses, and risk factors were analyzed using the Mann-Whitney U test, Chi-squared test, and Fisher's exact test. In patients with a history of cigarette smoking, incidence of vascular complications was higher than in those without history of cigarette smoking (17.8% v 8%, P =.02). Having quit cigarette smoking 2 years before liver transplantation reduced the incidence of vascular complications by 58.6% (24.4% v 11.8%, P =.04). The incidence of arterial complications was also higher in patients with a history of cigarette smoking compared with those without such history (13.5% v 4.8%, P =.015). Cigarette smoking cessation for 2 years also reduced the risk of arterial complications by 77.6% (21.8% v 5.9%, P =.005). However, the incidence of venous complications was not associated with cigarette smoking. Furthermore, there was no significant association between development of vascular complications and all other characteristics studied. Cigarette smoking is associated with a higher risk for developing vascular complications, especially arterial complications after liver transplantation. Cigarette smoking cessation at least 2 years before liver transplantation can significantly reduce the risk for vascular complications. Cigarette smoking cessation should be an essential requirement for liver transplantation candidates to decrease the morbidity arising from vascular complication after liver transplantation.

Development and validation of a model to diagnose cirrhosis in patients with hepatitis C.

OBJECTIVE: Although noninvasive markers predictive of cirrhosis in patients with chronic hepatitis C have been examined, none has proved sufficiently accurate for clinical use. The aim of this study was to develop an accurate model that can be easily used by clinicians to predict the probability of cirrhosis in hepatitis C patients from readily available clinical and laboratory information. METHODS: We identified 264 consecutive patients with established chronic hepatitis C infection and extracted multiple physical examination and biochemical variables (recorded before liver biopsy). Similar data were extracted from charts at another hospital. RESULTS: Logistic regression identified the following independent predictors of cirrhosis: platelet count < or = 140,000/ mm3, spider nevi, AST > 40 IU/L, and male gender. Male and female patients with normal values for platelet count and AST and no spider nevi had low probabilities of cirrhosis: 1.8% (95% CI = 0.4-7) and 0.03% (95% CI = 0.003-0.04), respectively. Male patients with abnormal values on all three other predictors had a probability of cirrhosis of 99.8% (95% CI = 98.7-100). Over 48% of study patients had a low (< or = 1.8%) or a very high (> or = 99.8%) predicted probability of cirrhosis. The model had area under the receiver operating characteristic curve of 0.938 (95% CI = 0.91-0.97) and 93.4% in an internal validation. The model accurately distinguished patients with and without cirrhosis (area under the receiver operating characteristic curve = 93.3%) in 102 hepatitis C patients from another hospital. CONCLUSIONS: In patients with hepatitis C, four readily available variables together predict cirrhosis accurately. Successful validation in hepatitis C patients at another hospital with lower prevalence of cirrhosis suggests this model's potential for broad applicability.

Liver transplantation for patients on methadone maintenance.

Most transplant programs require abstinence of at least 6 months from alcohol and illicit drugs before orthotopic liver transplantation (OLT). However, there are no published data regarding OLT outcomes in patients who are currently on methadone maintenance treatment (MMT) as part of the treatment of their heroin addiction at the time of OLT. The objective of this study is to evaluate our experience regarding the outcome of OLT in patients with end-stage liver disease (ESLD) who were on MMT at the time of OLT. Between March 1993 and May 1999, a total of 185 patients with ESLD underwent OLT at our center. Five transplant recipients (2.7%) had a history of heroin abuse and had undergone drug and alcohol rehabilitation, but could not be weaned off methadone. Pre-OLT status, drug history, perioperative course, compliance with medical therapy, post-OLT follow-up, and patient and allograft survival were analyzed in detail in these patients. All patients on MMT underwent uneventful OLTs. Their compliance with medications and follow-up was excellent. One patient was weaned completely off methadone after OLT. Post-OLT mean hospital stay in this group was 43 +/- 25 days. Although the number of patients was small, long-term outcome of liver transplant recipients on MMT appears similar to that of patients not on MMT who underwent OLT during this period. Our results suggest cirrhotic patients on MMT should be considered for OLT if they meet the same psychosocial requirements as patients with alcohol abuse. Furthermore, it is not necessary for patients to be weaned off methadone before OLT.