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.

A randomized trial of mailed outreach with behavioral economic interventions to improve liver cancer surveillance.

BACKGROUND: Surveillance rates for HCC remain limited in patients with cirrhosis. We evaluated whether opt-out mailed outreach increased uptake with or without a $20 unconditional incentive. METHODS: This was a pragmatic randomized controlled trial in an urban academic health system including adult patients with cirrhosis or advanced fibrosis, at least 1 visit to a specialty practice in the past 2 years and no surveillance in the last 7 months. Patients were randomized in a 1:2:2 ratio to (1) usual care, (2) a mailed letter with a signed order for an ultrasound, or (3) a mailed letter with an order and a $20 unconditional incentive. The main outcome was the proportion with completion of ultrasound within 6 months. RESULTS: Among the 562 patients included, the mean age was 62.1 (SD 11.1); 56.8% were male, 51.1% had Medicare, and 40.6% were Black. At 6 months, 27.6% (95% CI: 19.5-35.7) completed ultrasound in the Usual care arm, 54.5% (95% CI: 47.9-61.0) in the Letter + Order arm, and 54.1% (95% CI: 47.5-60.6) in the Letter + Order + Incentive arm. There was a significant increase in the Letter + Order arm compared to Usual care (absolute difference of 26.9%; 95% CI: 16.5-37.3; p<0.001), but no significant increase in the Letter + Order + Incentive arm compared to Letter + Order (absolute difference of -0.4; 95% CI: -9.7 to 8.8; p=0.93). CONCLUSIONS: There was an increase in HCC surveillance from mailed outreach with opt-out framing and a signed order slip, but no increase in response to the financial incentive.

The importance of triple panel testing for hepatitis B and the burden of isolated anti-hepatitis B core antibodies within a community sample.

Within the United States (US), 2.4 million individuals are living with chronic hepatitis B, but less than 20% are diagnosed. Isolated anti-hepatitis B core (iAHBc) antibodies indicate serology in an individual that is positive for anti-HBc antibodies, while negative for surface antigen (HBsAg) and surface antibodies (anti-HBs). A result of iAHBc could indicate a chronic occult bloodstream infection, necessitating further testing. This study assesses the prevalence and risk factors associated with anti-HBc and iAHBc within community high-risk screening in Greater Philadelphia. Participants (n = 177) were screened for HBsAg, anti-HBs, and anti-HBc during community screening events in 2022. Chi-square tables and Firth logistic regression were used to describe the data and to assess the odds of iAHBc. The findings indicate that there was an iAHBc prevalence of 7.3% (n = 13) within our study. The odds of anti-HBc were increased for immigrants from the Western Pacific (4.5%) and Africa (11.9%). Individuals born in Africa had 7.93 greater odds for iAHBc than those born in the Americas, and these odds are multiplied by 1.01 for every 1-year increase in age. Our data show a high burden of iAHBc within high-risk and often hard-to-reach communities. Triple panel screening should be incorporated into all HBV screening programs, in accordance with current Centers for Disease Control and Prevention (CDC) universal screening recommendations, to ensure a comprehensive picture of the disease burden and reduce the risk of missing people with occult hepatitis B and those at risk for viral reactivation or liver complications.

Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results.

UNLABELLED: Up to 50% of patients with chronic hepatitis C fail to respond to initial therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV). With unsuccessful viral eradication, these patients remain at risk for developing progression of their liver disease. Retreatment with PEG-IFN/RBV yields sustained virologic response (SVR) rates that are under 10%. A wholly synthetic interferon, interferon alfacon-1 or consensus interferon (CIFN) given with RBV, was evaluated in patients who failed initial PEG-IFN/RBV therapy. The intent-to-treat analysis included 487 patients; 245 received CIFN 9 microg/day and RBV, and 242 received CIFN 15 microg/day and RBV. Within this group of patients, 59.3% had documented advanced fibrosis at baseline liver biopsy (stage F3 or F4). SVR rates were 6.9% (17/245 patients) in the 9 microg group and 10.7% (26/242) in the 15 microg group. In the intent-to-treat analysis, SVR rates were higher among patients with a >2-log(10) decrease in hepatitis C virus RNA during prior PEG-IFN/RBV therapy: 11% (4/38) in the 9 mug group and 23% (7/31) in the 15 microg group. Among patients with lower baseline fibrosis scores (F0-F3), SVR rates were 7.8% (15/192) in the 9 microg group and 13.1% (23/175) in the 15 microg group. In this same group of patients (F0-F3), if a >2-log(10) decrease in hepatitis C virus RNA with previous PEG-IFN/RBV treatment was achieved, SVR rates improved to 10.7% and 31.6% in the 9 microg and 15 microg groups, respectively. CIFN/RBV combination retreatment was safe and well tolerated. CONCLUSION: Retreatment of PEG-IFN and RBV nonresponders with CIFN and RBV is safe and efficacious and can be considered a retreatment strategy for patients failing previous therapy with PEG-IFN/RBV, especially in interferon-sensitive patients with lower baseline fibrosis scores.

Yogi Detox Tea: A Potential Cause of Acute Liver Failure.

We present a case of acute fulminant liver failure from a liver detoxification tea. We present a 60-year-old female with weakness, lethargy, scleral icterus, jaundice, and worsening mental status. She drank herbal tea three times a day for 14 days prior to symptom development. Liver tests were elevated. Remaining laboratory tests and imaging were negative for other etiologies. An ultrasound-guided liver biopsy showed submassive necrosis. A literature search on the ingredients shows six ingredients as having hepatotoxic effects and remaining ingredients as having very sparse hepatoprotective data. Healthcare professionals should discuss herbal medication and tea use and report adverse effects.

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.

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.

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.

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.

Inducible left ventricular outflow tract gradient during dobutamine stress echocardiography: an association with intraoperative hypotension but not a contraindication to liver transplantation.

BACKGROUND: Dobutamine stress echocardiography (DSE) is frequently used in the evaluation of cardiac risk prior to orthotopic liver transplantation (OLT). In the general cardiac population, an inducible left ventricular outflow tract gradient (LVOT Delta) during DSE has variable prognostic importance. The purpose of this study was to determine the prevalence and clinical significance of LVOT Delta in patients undergoing OLT during DSE. METHODS: Consecutive medical records of 106 patients who had undergone OLT at our institution from January 1997 until January 2002 were retrospectively analyzed and divided into two groups based on the presence (Group I, LVOT Delta >36 mmHg) or absence (Group II, LVOT Delta< or = 36 mmHg) of a significant LVOT Delta measured during DSE. We determined any outcome differences between these two groups with regard to intraoperative hypotension, cardiac mortality, length of hospital stay, graft function, and renal function post-OLT. RESULTS: Forty-six patients had an LVOT Delta > 36 mmHg (Group I) and 60 patients had LVOT Delta< or = 36 mmHg (Group II). Baseline demographics were similar in both groups. There was no significant overall difference in cardiac mortality between Group I versus Group II patients (0 versus 1 patient, respectively, P=0.57). Intraoperative hypotension occurred in 4 patients in Group I versus 0 patient in Group II (P=0.03). Length of stay, graft function, and postoperative renal function were similar in both groups. CONCLUSION: A significant LVOT Delta >36 mmHg is a frequent finding occurring in 46/106 (43%) of patients who have DSE pre-OLT. Intraoperative hypotension is associated with patients having an LVOT Delta. However, post-OLT patients with significant LVOT Delta have a similar in-hospital outcome compared to patients without significant LVOT Delta.

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.

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.