Differential Effects of Ascites and Hepatic Encephalopathy on Waitlist Mortality in Liver Transplantation by MELD 3.0.

Background: MELD 3.0 introduces changes to address waitlist disparities for liver transplant (LT) candidates. Ascites and hepatic encephalopathy (HE) are important milestones in the natural history of cirrhosis regardless of the Model for End-Stage Liver Disease (MELD) score. We aim to assess the impact of ascites and HE and its interaction with MELD 3.0 on waitlist mortality. Methods: This is a retrospective study of patients listed for LT in the Organ Procurement and Transplantation Network database from 2016 to 2021. The primary outcome was waitlist mortality (death/delisting for too sick to LT). Ascites/HE were classified as moderate ascites without moderate HE (mAscites), moderate HE without moderate ascites (mHE), both moderate ascites/HE (mBoth), and neither. MELD 3.0 scores were categorized as <20, 20-29, 30-39, and ≥40. Results: Of 39 025 candidates, 29% had mAscites, 3% mHE, and 8% mBoth. One-year waitlist mortality was 30%, 38%, and 47%, respectively, compared with 17% (all P < 0.001) for those with neither. In multivariable Cox regression, the adjusted risk of waitlist mortality associated with mAscites (versus neither) was a hazard ratio (HR) of 1.76 (95% confidence interval [CI], 1.55-2.00) when the MELD 3.0 score was <20, significantly higher than when the MELD 3.0 score was 20-29 (HR 1.40; 95% CI, 1.27-1.54), 30-39 (HR 1.19; 95% CI, 1.04-1.35), and ≥40 (HR 1.14; 95% CI, 0.91-1.43, interaction P < 0.05 for all). A similar pattern was observed by MELD 3.0 for both moderate ascites/HE. Conclusions: The presence of moderate ascites alone, or combined with moderate HE, not only increases the risk of waitlist mortality but also has a differential effect by MELD 3.0, especially at lower MELD scores. Earlier strategies addressing this group and improving treatment plans or access to LT regardless of MELD remain needed.

Pseudocirrhosis: A Case Series with Clinical and Radiographic Correlation and Review of the Literature.

BACKGROUND AND AIMS: Pseudocirrhosis is a poorly understood acquired morphologic change of the liver that occurs in the setting of metastatic malignancy and radiographically resembles cirrhosis. Pseudocirrhosis has been primarily described in metastatic breast carcinoma, with few case reports arising from other primary malignancies. We present 29 cases of pseudocirrhosis, including several cases from primary malignancies not previously described. METHODS: Radiologic, clinical, demographic, and biomedical data were collected retrospectively and analyzed. We compared clinical and radiologic characteristics and outcomes between patients with pseudocirrhosis arising in metastatic breast cancer and non-breast primary malignancies. RESULTS: Among the 29 patients, 14 had breast cancer and 15 had non-breast primaries including previously never reported primaries associated with pseudocirrhosis, melanoma, renal cell carcinoma, appendiceal carcinoid, and cholangiocarcinoma. Median time from cancer diagnosis to development of pseudocirrhosis was 80.8 months for patients with primary breast cancer and 29.8 months for non-breast primary (p = 0.02). Among all patients, 15 (52%) had radiographic features of portal hypertension. Radiographic evidence of portal hypertension was identified in 28.6% of breast cancer patients, compared to 73.3% of those with non-breast malignancies (p = 0.03). CONCLUSION: Pseudocirrhosis has most commonly been described in the setting of metastatic breast cancer but occurs in any metastatic disease to the liver. Our study suggests that portal hypertensive complications are more common in the setting of non-breast primary cancers than in metastatic breast cancer. Prior exposure to multiple chemotherapeutic agents, and agents known to cause sinusoidal injury, is a common feature but not essential for the development of pseudocirrhosis.

Combination vardenifil and tadalifil drug induced liver injury; case report and review of the literature of liver injury associated with phosphodiesterase type 5 inhibitors.

Background: Phosphodiesterase type 5 inhibitors (PDE5I) are prescribed for erectile dysfunction and pulmonary hypertension. Despite its widespread use, there are only seven cases of drug-induced liver injury (DILI) associated with PDE5I, none associated with vardenafil or avanafil. We report a patient who had taken vardenafil and tadalafil individually for several years without developing symptoms of liver injury. However, after taking vardenafil and tadalafil together on 2 consecutive days, he developed severe cholestasis. Methods: Causality was determined using Roussel Uclaf causality assessment method (RUCAM). Results: The patient is a 72-year-old White man in excellent health who drank 2 units of alcohol, three times/week. Previously, he had used vardenafil for more than 2 years and tadalafil for 3 months as single agent for erectile dysfunction without any complications. He took vardenafil and tadalafil for 2 consecutive days and 5 days later, he developed dyspepsia, loss of appetite, jaundice, and intense itching. Liver tests showed mixed cholestatic/hepatocellular pattern of injury. Histology showed marked cholestasis with minimal inflammation. He remained cholestatic for 5 weeks before a full recovery 2 months later. The patient then resumed vardenafil monotherapy with no recurrent liver dysfunction. RUCAM causality score 7 indicates that the combination of PDE5I is probable cause of liver injury. The similarities among the eight cases of PDE5I DILI include a relatively short latency, cholestatic histological features, and complete recovery. Biochemical pattern of liver injury is variable. Conclusions: PDE5I DILI is a rare event that can result in severe acute liver injury.

Disparities in presentation and management of chronic hepatitis B among Hispanics in a diverse safety net system.

BACKGROUND: Chronic hepatitis B (HBV) prevalence is highest in foreign-born Asian and African individuals in the US, though Hispanics make up the largest proportion of the immigrant population. Differences in the diagnosis and management of chronic HBV in Hispanics might exist due to the lower awareness of risk. We aim to examine racial/ethnic disparities in the diagnosis, presentation, and immediate management of chronic HBV in a diverse safety net system enriched for Hispanics. METHODS: In a large urban safety-net hospital system, we retrospectively identified patients with chronic HBV by serological data and categorized them into mutually exclusive self-identified racial/ethnic groups: Hispanics, Asians, Blacks, and Whites. We then examined differences in screening, disease phenotype and severity, follow-up testing, and referral by race/ethnicity. RESULTS: Among 1063 patients, 302 (28%) were Hispanics, 569 (54%) Asians, 161 (15%) Blacks, and 31 (3%) Whites. More Hispanics (30%) were screened in the acute setting (defined as inpatient or emergency department encounters) than Asians (13%), Blacks (17%), or Whites (23%) (p<0.01). Hispanics also had lower rates of follow-up testing after HBV diagnosis than Asians including HBeAg status (43% vs. 60%, p<0.01) and HBV DNA levels (42% vs. 58%, p<0.01) and lower rates of linkage to specialty care (32% vs. 55%, p<0.01). Among those with available testing, however, the presence of immune-active chronic HBV was infrequent and similar across racial/ethnic groups. 25% of Hispanics had cirrhosis at initial presentation, proportionally higher than other groups (p<0.01). CONCLUSION: Our results underscore the importance of raising chronic HBV awareness and increasing both screening and linkage to care among Hispanic immigrants in addition to the existing risk groups, with the goal of mitigating downstream liver-related complications.

Mifepristone induced liver injury in a patient with Cushing syndrome: a case report and review of the literature.

BACKGROUND: Mifepristone, also known as RU-486, is an anti-progestational steroid with similar chemical structure to anabolic steroids. Given as a single dose in conjunction with misoprostol, mifepristone is used to induce medical abortion. Mifepristone administered chronically at a higher dose is also approved for the management of hypercortisolism. There have been only 2 reported cases of mifepristone associated liver injury, in both cases, in the setting of Cushing syndrome. We report a third patient with Cushing syndrome with mifepristone induced liver injury with unique histological findings that provide insight to the pathophysiology of liver injury in mifepristone and anabolic steroids. CASE PRESENTATION: Patient is a 63-year-old Caucasian female Cushing disease with no prior history of liver disease. She was started on mifepristone and semaglutide. Ninety days after initiating mifepristone, she developed deep jaundice, severe pruritus, fatigue, and nausea. Liver tests revealed a mixed hepatocellular/cholestatic pattern. Viral and autoimmune serologies were negative and there was no biliary dilatation on imaging. Liver biopsy showed severe cholestasis but no bile duct injury. Focal endothelialitis was present within a central venule. Cholestatic symptoms persisted for one month after presentation before slowly subsiding. Four months after stopping mifepristone, the patient's symptoms completely resolved, and liver tests became normal. Compilation of Roussell Uclaf Causality Assessment Method score indicated probable causality. CONCLUSIONS: Mifepristone shares a similar chemical structure as synthetic anabolic/androgenic steroids and there are many similarities in the clinical presentation of liver injury. This case and the 2 other reported cases share similar clinical characteristics. The observation of endothelialitis in our patient may provide a mechanistic link between mifepristone, or anabolic steroids in general, and the development of vascular complications such as peliosis.

The Conundrum of Patients With Compensated Cirrhosis Requiring Kidney Transplantation; Kidney Alone or Simultaneous Liver Kidney Transplantation.

BACKGROUND: Patients with compensated cirrhosis and chronic kidney disease are increasing along with demand for simultaneous liver kidney transplant (SLKT) and shortages of organs for transplantation. Although these well-compensated patients may not need a liver organ, the alternative of kidney transplant alone (KTA) poses the risk of liver decompensation. Therefore, we aim to characterize outcomes among patients with compensated cirrhosis and chronic kidney disease listed for SLKT or receiving KTA to inform clinical decisions. METHODS: The 2-part retrospective study included a national cohort of patients listed for SLKT in United Network for Organ Sharing from January 2003 to June 2019 with Child A cirrhosis, with model for end-stage liver disease <25, and receiving dialysis; and a cohort of patients who underwent KTA from 2004 to 2019 with Child A cirrhosis identified through a 4-center chart review. Waitlist outcomes (SLKT, death, and clinical improvement) and post-KTA liver decompensation and survival were evaluated in the cohorts, respectively. RESULTS: In the national SLKT cohort (N = 705, median age 56 y, 68.8% male), 5-y cumulative incidence of SLKT was 43.1%, death 32.1%, and clinical improvement 9.1%. Among SLKT recipients, 36.3% remained Child A without ascites or encephalopathy at transplant. In the local KTA cohort (N = 34, median age 54 y, 79.4% male), none had ascites or hepatic encephalopathy before KTA, but 15 had clinical portal hypertension. Five-y post-KTA incidence of liver decompensation was 36.8%, and survival was 89.2%. CONCLUSIONS: SLKT may not be necessary for some patients with compensated cirrhosis needing kidney transplant. KTA is safe for selected patients with intact liver biochemical function, even with portal hypertension but without hepatic encephalopathy or ascites.

Incidence, Risk Factors, and Outcomes of COVID-19 Infection in a Large Cohort of Solid Organ Transplant Recipients.

BACKGROUND: Solid organ transplant recipients (SOTr) are at increased risk for severe disease from coronavirus disease 2019 (COVID-19) compared with non-SOTr. METHODS: We performed a retrospective cohort study between March 1, 2020, and March, 30, 2021, in an integrated healthcare system with 4.3 million members aged ≥18 y including 5126 SOTr. Comparisons in COVID-19 mortality, hospitalization, and incidence were made between SOTr and non-SOTr, and between different SOTr organs. Multivariate analysis was performed to identify risk factors for COVID-19 mortality and hospitalization. RESULTS: There were 600 SOTr (kidney, liver, heart, and lung) with COVID-19. Per person-year incidence of COVID-19 among SOTr was 10.0% versus 7.6% among non-SOTr (P < 0.0001). Compared with uninfected SOTr, infected SOTr were older (57.1 ± 14.0 versus 45.7 ± 17.9 y, P < 0.001), predominantly Hispanic/Latino (58.8% versus 38.6%, P < 0.0001), hypertensive (77.0% versus 23.8%; P < 0.0001), and diabetic (49.6% versus 13.0%; P = 0.0009). Compared with non-SOTr, infected SOTr had higher hospitalization (39.5% versus 6.0%; P < 0.0001), intensive care unit admission (29.1% versus 15.5%; P < 0.0001), and mortality (14.7% versus 1.8%; P < 0.0001) from COVID-19. Older age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.05-1.10), male gender (HR, 1.79; 95% CI, 1.11-2.86), and higher body mass index (HR, 1.04; 95% CI, 1.00-1.09; P = 0.047) were associated with increased mortality from COVID-19, whereas race, diabetes, and number/type of immunosuppressive medications were not. Among the different SOTr, COVID-19 mortality risk was lowest in liver recipients (HR, 0.34; 95% CI, 0.16-0.73) and highest in lung recipients (HR, 1.74; 95% CI, 0.68-4.42). CONCLUSIONS: SOTr have higher rates of hospitalization and mortality from COVID-19 compared with the general population. Among the SOTr, the incidence and outcomes were distinct among different transplantation types.

Living Liver Donation Does not Significantly Affect Long-Term Life, Disability, or Medical Insurability.

INTRODUCTION: The growing practice of living liver donation requires comprehensive understanding of the financial implications for living liver donors. While obtaining and maintaining insurance is important to financial health, little is known about the impact of liver donation on future insurability. RESEARCH QUESTIONS: The purpose of this study was to evaluate the donors' experiences with insurance following donation and identify the insurance provider-driven factors that contribute to donor insurability. DESIGN: A two center cohort of living donors with donation between January 2000 and December 2018 (N = 442) were surveyed about postdonation insurance experiences. To understand insurance provider practices towards liver donors, life (n = 11) and disability (n = 4) insurance underwriters were asked to provide policy quotes for a standardized living liver donor profile. RESULTS: Responses (N = 101) were received by August 2020 (response rate = 22.9%). Living liver donors reported owning life (58%), disability (35%), and medical (87%) insurance at rates comparable to the general population with low proportions reporting difficulty obtaining these insurance types (9%, 9%, 4%, respectively). Post-donation life insurance ownership was associated with post-donation employment (P = 0.01). Underwriter responses indicate life and disability insurability were adversely affected up to 12 months following donation. CONCLUSIONS: Living liver donors did not have difficulty maintaining insurance in the long-term but should be counseled to purchase insurance prior to surgery as short-term insurability may be affected. Perception of difficulty obtaining insurance following donation remains of significant concern among living donors. Further collaboration between the transplant community and insurance companies is warranted.

Use of liver stiffness measurements in acute decompensated heart failure: new applications of a non-invasive technique.

Heart failure (HF) is a complex disease associated with multisystem organ failure, recurrent hospital admissions, and increased mortality. Acute decompensated heart failure (ADHF) increases central venous pressure (CVP) with resultant hepatic congestion, and this relationship has prognostic significance. The gold standard method of measuring CVP, right heart catheterization, is invasive and costly, prompting further investigation into more accurate non-invasive assessments in HF patients, including liver elastography. Liver elastography relies on imaging techniques to assess liver stiffness measurements (LSM), with high values equating to increased stiffness. While this was developed to assess fibrosis in liver disease, LSM also reflect increased CVP and hepatic congestion. Multiple studies involving ADHF patients, find that increased LSM are independently predictive of increased cardiac events, all-cause mortality, and worse post-operative outcome after both acute HF exacerbation and left ventricular assist device (LVAD) placement. In this review, we discuss the role of LSM as a surrogate for CVP and their applications in determining prognosis in both the ADHF and LVAD populations.

Plasma cell free DNA methylation markers for hepatocellular carcinoma surveillance in patients with cirrhosis: a case control study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis, primarily due to failed early detection. HCC screening is recommended among individuals with cirrhosis using biannual abdominal ultrasound, for earlier tumor detection, administration of curative treatment, and improved survival. Surveillance by imaging with or without biomarkers such as alpha-fetoprotein (AFP) remains suboptimal for early stage HCC detection. Here we report on the development and assessment of methylation biomarkers from liquid biopsies for HCC surveillance in cirrhotic patients. METHODS: DNA methylation markers including the HCCBloodTest (Epigenomics AG) and a DNA-methylation panel established by next generation sequencing (NGS) were assessed using a training/testing design. The NGS panel algorithm was established in a training study (41 HCC patients; 46 cirrhotic non-HCC controls). For testing, plasma samples were obtained from cirrhotic patients (Child class A or B) with (60) or without (103) early stage HCC (BCLC stage 0, A, B). The assays were then tested using blinded sample sets and analyzed by preset algorithms. RESULTS: The HCCBloodTest and the NGS panel exhibited 76.7% and 57% sensitivities at 64.1% and 97% specificity, respectively. In a post-hoc analysis, a combination of the NGS panel with AFP (20 ng/mL) achieved 68% sensitivity at 97% specificity (AUC = 0.9). CONCLUSIONS: Methylation biomarkers in cell free plasma DNA provide a new alternative for HCC surveillance. Multiomic panels comprising DNA methylation markers with other biological markers, such as AFP, provide an option to further increase the overall clinical performance of surveillance via minimally invasive blood samples. TRIAL REGISTRATION: Test set study-ClinicalTrials.gov (NCT03804593) January 11, 2019, retrospectively registered.

Case series and review of Ayurvedic medication induced liver injury.

BACKGROUND: Complementary and alternative medicine use among Americans is prevalent. Originating in India, Ayurvedic medicine use in the United States has grown 57% since 2002. CAM accounts for a significant proportion of drug induced liver injury in India and China, but there have been only three reports of drug induced liver injury from Ayurvedic medications in the U.S. We report three cases of suspected Ayurvedic medication associated liver injury seen at a Southern California community hospital and review literature of Ayurvedic medication induced liver injury. CASE PRESENTATIONS: Three patients presented with acute hepatocellular injury and jaundice after taking Ayurvedic supplements for 90-120 days. First patient took Giloy Kwath consisting solely of Tinospora cordifolia. Second patient took Manjishthadi Kwatham and Aragwadhi Kwatham, which contained 52 and 10 individual plant extracts, respectively. Third patient took Kanchnar Guggulu, containing 10 individual plant extracts. Aminotransferase activities decreased 50% in < 30 days and all 3 patients made a full recovery. Roussel Uclaf Causality Assessment Method (RUCAM) scores were 7-8, indicating probable causality. These products all contained ingredients in other Ayurvedic and traditional Chinese medicines with previously reported associations with drug induced liver injury. CONCLUSIONS: These patients highlight the risk of drug induced liver injury from Ayurvedic medications and the complexity of determining causality. There is a need for a platform like LiverTox.gov to catalog Ayurvedic ingredients causing liver damage.

Bone and renal safety profile at 72 weeks after switching to tenofovir alafenamide in chronic hepatitis B patients.

BACKGROUND AND AIM: Tenofovir disoproxil fumarate (TDF) has been efficacious in treating chronic hepatitis B (CHB), but long-term use is accompanied by a decline in renal function and bone mineral density (BMD). Tenofovir alefanamide (TAF) is a prodrug of tenofovir, with similar efficacy in CHB but with fewer side effects than TDF. Recent studies on patients who underwent the switch from TDF to TAF have shown improved bone and renal profiles from 24 to 48 weeks of follow-up. METHODS: This study provides follow-up at 72 weeks in a real-world cohort of 61 Asian CHB patients who were switched from TDF to TAF. All patients had been treated with TDF for at least 12 months with hepatitis B virus DNA <21 IU/mL prior to switch. RESULTS: Improvements in proximal tubular function, measured by urine beta-2-microglobulin to creatinine and retinol-binding protein to creatinine ratios, were sustained at 72 weeks (P < 0.01). Renal function showed decline at 72 weeks compared to baseline (GFRCG 90.9 vs 96.3 mL/min, P < 0.01). Improvement in hip BMD was sustained at 72 weeks (mean % change of 17.7% from baseline, P < 0.01). However, spine BMD showed discordance, with initial improvement at 24 weeks (3.3% from week 0, P < 0.01) but regression at 72 weeks (-0.6% from week 0, P = NS). Interestingly, there was a slight increase in weight and BMI after 72 weeks (P < 0.01). CONCLUSIONS: CHB patients who switch from long-term TDF to TAF therapy show sustained improvement in proximal tubular function and hip BMD. Weight gain was noted, and long-term studies are needed to evaluate its effect on patient outcomes.

Prevalence and Characteristics of Chronic Hepatitis C Among Asian Americans Are Distinct From Other Ethnic Groups.

GOAL: The goal of this study was to determine the prevalence and characteristics of chronic hepatitis C (CHC) among Asian Americans compared with other ethnicities. BACKGROUND: Chronic hepatitis C virus (HCV) affects an estimated 2.7 million in the United States, but there are limited data on HCV among Asian Americans. STUDY: A total of 3,369,881 adults over the age of 18 who were patients of the integrated health care system in Southern California and 4903 Asian participants at community hepatitis screenings were included in a cross-sectional study. Variables included HCV serology, HCV genotype, comorbidities, and coinfections. RESULTS: The prevalence of CHC was 1.3% in the general population (8271 adults) and 0.6% among Asians. The prevalence of CHC was significantly higher in the 1945-1965 birth cohort with 2.7% (5876) in the general population and 1.0% (313) among Asians (P<0.001). Asians had the highest rates of hepatitis B coinfection (2.9% vs. 0.2%, P<0.001). The distribution of genotypes among Asians differed from the general population with the most common genotype being 1b (27.5%) and a higher presence of genotype 6 (9.5%) (P<0.001). The presence of cirrhosis was 17.6% in Asians. Disaggregated Asian data showed that CHC was highest among Vietnamese and Cambodian and that genotype 6 was predominant among these 2 subgroups. CONCLUSIONS: The prevalence of chronic HCV was significantly lower in Asians compared with other ethnicities. However, disaggregated data among Asians showed the highest prevalence rates among adults from Vietnam and Cambodia.

High Prevalence of Chronic Viral Hepatitis and Liver Fibrosis Among Mongols in Southern California.

BACKGROUND: Mongolia is a highly endemic region for chronic hepatitis B (HBV), hepatitis delta (HDV), and hepatitis C (HCV) infections. Aim of this study was to comprehensively characterize chronic viral hepatitis among Mongols living in Southern California. METHODS: Three screening events were conducted between August and November 2018, with 528 adult Mongols tested for HBV and HCV. HBsAg (+) individuals (CHB) underwent additional testing for HDV RNA and anti-HDV. Liver tests, platelet count, and FibroScan™ were performed on CHB and chronic HCV (CHC) individuals. RESULTS: Fifty-one out of 534 were HBsAg reactive (9.7%), and all were foreign-born. Mean age of CHB individuals was 37.8 (range 18-69) years. Forty-six out of 51 were HBeAg (-). HBV genotypes were exclusively D2 or A1. Twenty-one out of 51 (41.2%) were anti-HDV (+) and 17/51 (33.3%) were HDV RNA (+). HDV RNA (+) individuals had significantly higher ALT, fibrosis-4 score, and liver stiffness compared to HDV RNA (-) individuals. Incidence of advanced fibrosis was higher in HDV RNA (+) individuals (57% vs. 13%, p = 0.013). Forty-eight (9.1%) individuals were anti-HCV (+) and 19 (3.6%) were HCV RNA (+). Mean age of CHC individuals was 40.2 (range 28-71) years. Prevalence of anti-HCV (+) was higher among those born between 1945 and 1965 versus those born after 1965 (18.8% vs. 7.9%, p = 0.025). Genotype 1b was predominant. Incidence of cirrhosis was 7% among all participants. CONCLUSIONS: Mongols living in the USA are at high risk for CHB and CHC infections. One-third of CHB individuals had CHD superinfection with advanced fibrosis. Universal screening for viral hepatitis in Mongols in the USA is mandatory.

Treatment and Outcomes of Early Stage Breast Cancer in Patients with Hepatic Dysfunction.

BACKGROUND: There exists a dogma of surgical nihilism for patients with cirrhosis and breast cancer causing de-escalation of surgery and impacting survival. We hypothesized that breast cancer surgery would not result in a significant change in the Model for End-Stage Liver Disease-Sodium (MELD-Na) scores before and after surgery. METHODS: We performed a single institutional retrospective review of medical records between January 2013 and July 2019 of patients with concurrent cirrhosis and breast cancer. We used the nonparametric Friedman test to compare differences in MELD-Na scores. RESULTS: Eight patients with both cirrhosis and breast cancer were identified. Median follow-up was 30.5 mo. Half of the patients had Child-Pugh class A cirrhosis and half had Child-Pugh class B cirrhosis. Six (75%) patients underwent lumpectomy and two (25%) underwent mastectomy. There was no statistically significant difference (P = 0.66) in median MELD-Na score before surgery (16) and after surgery (18). Two (25%) patients experienced postoperative complications. Three patients were listed for liver transplantation. Of three listed patients, two (25%) patients underwent successful liver transplantation after breast surgery. One (12.5%) patient died without transplant. Three (37.5%) patients were alive for more than 5 y after breast cancer diagnosis without evidence of cancer recurrence. The eighth patient has remained breast cancer free for more than 6 mo since her surgery. CONCLUSIONS: Surgery for patients with Child-Pugh class A and B cirrhosis and early stage breast cancer did not result in a significant change in MELD-Na score before and after surgery, suggesting that selected patients may benefit from breast cancer surgery with curative intent.

Long-Term Financial, Psychosocial, and Overall Health-Related Quality of Life After Living Liver Donation.

BACKGROUND: To assess the impact of living liver donation (LD) in a diverse and aging population up to 20 y after donation, particularly with regard to medical, financial, psychosocial, and overall health-related quality of life (HRQOL). METHODS: Patients undergoing LD between 1999 and 2009 were recruited to respond to the Short-Form 36 and a novel Donor Quality of Life Survey at two time points (2010 and 2018). RESULTS: Sixty-eight living liver donors (LLDs) completed validated surveys, with a mean follow-up of 11.5 ± 5.1 y. Per Donor Quality of Life Survey data, physical activity or strength was not impacted by LD in most patients. All respondents returned to school or employment, and 82.4% reported that LD had no impact on school or work performance. LD did not impact health insurability in 95.6% of donors, and only one patient experienced difficulty obtaining life insurance. Overall, 97.1% of respondents did not regret LD. Short-Form 36 survey-measured outcomes were similar between LLDs and the general U.S. POPULATION: LLDs who responded in both 2010 and 2018 were followed for an overall average of 15.4 ± 2.4 y and HRQOL outcomes in these donors also remained statistically equivalent to U.S. population norms. CONCLUSIONS: This study represents the longest postdonation follow-up and offers unique insight related to HRQOL in a highly diverse patient population. Although LLDs continue to maintain excellent HRQOL outcomes up to 20 y after donation, continued lifetime follow-up is required to accurately provide young, healthy potential donors with an accurate description of the risks that they may incur on aging.

VRE in cirrhotic patients.

BACKGROUND: Vancomycin resistant enterococci (VRE) infections are of increasing concern in many hospitalized patients. Patients with cirrhosis are at added risk of infection with VRE, with associated increased risk for complications from infections. The goals of this study were to: [1] identify risk factors for VRE amongst cirrhotic patients before liver transplantation, and [2] evaluate risk of morbidity and mortality at 30-days and one-year after VRE infection. METHODS: Chart review of 533 cirrhotic patients hospitalized at a tertiary medical center was performed. Patients infected with VRE (n = 65) were separately compared to patients infected with gram-negative organisms (n = 80) and uninfected patients (n = 306). RESULTS: In multivariable logistic regression analyses, female gender (OR 3.73(95% CI1.64,8.49)), severity of liver disease measured by higher Child Pugh scores (OR 0.37(95%CI 0.16,0.84)), presence of ascites (OR 9.43(95% CI 3.22,27.65) and any type of dialysis (OR 3.31,95% CI (1.21,9.04), oral antibiotic prophylaxis for spontaneous bacterial peritonitis and rifaximin use were statistically significantly associated with VRE infection (OR 2.37 (95%CI 1.27, 4.42)). VRE-infected patients had significantly longer mean ICU and total hospital stays (both p < 0.0001), with increased one-year mortality compared to cirrhotic patients without VRE infection, adjusted for age, sex, Hispanic ethnicity, and disease severity. CONCLUSIONS: It is unclear whether VRE infection serves as an independent risk factor for increased mortality or an indicator for patients with more severe illnesses and thus a higher risk for death.

Late onset cardiac cirrhosis and portal hypertensive ascites after atrial fibrillation ablation.

Pulmonary vein stenosis is a potential complication following catheter ablation of atrial fibrillation (AF). We report the case of a patient with refractory ascites late after multiple catheter ablation procedures for AF. This is the first case report of portal hypertensive ascites due to acquired multiple pulmonary vein stenoses resulting in pulmonary hypertension (PH) and cardiac cirrhosis late after AF ablation. Despite extensive surgical reconstruction of the affected pulmonary veins, the patient has PH and right heart failure with persistent ascites and lower extremity edema.

Improvement of bone mineral density and markers of proximal renal tubular function in chronic hepatitis B patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide.

Tenofovir alafenamide (TAF) is a novel prodrug that reduces tenofovir plasma levels by 90% compared to tenofovir disoproxil fumarate (TDF), resulting in decreased bone mineral density (BMD) loss and renal toxicity. We aimed to study changes in BMD and markers of renal function of chronic hepatitis B (CHB) patients previously treated with TDF who were switched to TAF in as early as 12 weeks. This was a prospective single-arm open-label study of 75 CHB patients treated with TDF 300 mg daily who were switched to TAF 25 mg daily and followed for 24 weeks. All patients had been treated with TDF for at least 12 months and had HBV DNA <21 IU/mL at the time of switch. BMD and markers of renal function were taken on the day of switch and repeated after 12 and 24 weeks of TAF treatment. Hip and spine bone mineral density significantly increased from baseline to week 12 (+12.9% and +2.4%, respectively, P < 0.01). There were significant decreases in urinary beta-2-microglobulin to creatinine and retinol-binding protein to creatinine ratios by week 12 (P < 0.01 for both). Mean estimated glomerular filtration rate (GFR) did not change. Tubular reabsorption of phosphate was decreased at week 24 (P < 0.05). In conclusion, CHB patients previously treated with TDF experienced significant improvement in bone density and some markers of renal tubular function and as early as 12 weeks after switching to TAF. Bone density changes associated with TDF may not be entirely related to renal handling of phosphate.

Striking Racial/Ethnic Disparities in Liver Cancer Incidence Rates and Temporal Trends in California, 1988-2012.

Background: Hepatocellular carcinoma (HCC) is characterized by disparate risk patterns by race/ethnicity. We examined HCC incidence patterns and temporal trends among detailed racial/ethnic populations, including disaggregated Asian-American subgroups. Methods: Using data from the population-based California Cancer Registry, we identified 41 929 invasive HCC cases diagnosed during 1988-2012. Patients were grouped into mutually exclusive racial/ethnic groups of non-Hispanic (NH) white, NH black, Hispanic, and NH Asian/Pacific Islander (API), as well as Asian subgroups of Chinese, Filipino, Japanese, Korean, Vietnamese, Cambodian, Laotian, and South Asian. Age-adjusted and age-specific incidence rates by sex, race/ethnicity, and time period were calculated. The average annual percent change (AAPC) in incidence rates was estimated using joinpoint regression. All estimates were provided with the 95% confidence intervals (CIs). Results: Aggregated NH API had higher HCC risk than NH whites, NH blacks, and Hispanics. When disaggregated, Southeast Asians (Vietnamese, Cambodians, and Laotians) had overall HCC incidence rates eight to nine times higher than NH whites and more than twice that of other ethnic Asians. Statistically significant rising temporal trends of HCC were found in NH whites, NH blacks, and Hispanics, especially those older than age 50 years. Overall HCC risk declined in Chinese males (AAPC = -1.3%, 95% CI = -2.0 to -0.6), but rose in Filipino (AAPC = +1.2%, 95% CI = 0.3 to 2.1) and Japanese males (AAPC = +3.0%, 95% CI = 0.4 to 5.6) and Vietnamese (AAPC = +4.5%, 95% CI = 0.7 to 8.5) and Laotian (+3.4%, 95% CI = 0.1 to 6.8) females. Conclusions: Our findings provide valuable information for the identification of at-risk ethnic subgroups of Asian Americans while underscoring the importance of disaggregating ethnic populations in cancer research.