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.

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.

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.

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.

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.

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.

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.

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.

Comparison of Demographic and Clinical Characteristics of Hispanic and Asian Chronic Hepatitis B Patients in Southern California.

OBJECTIVES: There are few data regarding the clinical and serologic features of chronic hepatitis B (CHB) infection among Hispanics in the United States. The aims of this study were to compare and contrast clinical characteristics of Hispanic and Asian CHB patients. METHODS: Demographic, clinical, and laboratory data were collected from Hispanic and Asian CHB patients seen between January 2013 and May 2014 at Los Angeles County Hepatitis Clinic. RESULTS: A total of 55 Hispanic and 342 Asian CHB patients were identified. Almost all were foreign-born. Compared with Asians, Hispanics were more likely to report heterosexual transmission (P<0.0001) and blood transfusion history (P<0.0001) as risk factors. Overall, 31% of Hispanics had HBV>2000 IU/mL compared with 54% of Asians (P=0.004).Significantly more Asian HBeAg-negative/anti-HBe-positive CHB patients had high HBV DNA levels (>2000 IU/mL) with elevated ALT compared with Hispanic patients (P=0.04). Compared with Asians, Hispanic CHB patients were more likely to have elevated ALT and low HBV DNA levels (P=0.001). Among CHB patients who received antiviral therapy, response was comparable among Hispanics and Asians. There were no Hispanic CHB patients who experienced spontaneous reactivation or developed hepatocellular carcinoma. CONCLUSIONS: There were important differences in the clinical, demographic, and serologic characteristics between Hispanic and Asian CHB. Response rate to antiviral therapy was comparable. Further studies of Hispanic CHB patients in the United States are warranted.

Nucleoside-Nucleotide Analog Combination Therapy Is Effective in Preventing Recurrent Hepatitis B After Liver Transplantation.

BACKGROUND: Hepatitis B immune globulin (HBIg) in combination with a nucleos(t)ide analog is the mainstay of prophylactic regimen to prevent recurrence of hepatitis B following orthotopic liver transplantation (OLT). HBIg therapy is costly and inconvenient for the patients. There is a growing experience converting HBIg/nucleos(t)ide to combination nucleotide/nucleoside analogs from. METHODS: Twenty-six patients that underwent OLT between March 2001 and July 2011 who had received at least 12 months of HBIg and single nucleos(t)ide were enrolled. HBsAg and HBV DNA were undetectable, and anti-HBs were detectable at the time of switch. HBV DNA and HBsAg were measured every 3 months following discontinuation of HBIg and addition of nucleos(t)ide. RESULTS: Patients included 23 Asians/3 Caucasian, 21 males/5 females. Mean time of conversion from HBIg/nucleos(t)ide to nucleoside/nucleotide combination was 77.5 (range 11-132) months after OLT. Mean duration of follow-up after conversion was 31.9 (range 14-70) months. All patients had undetectable HBV DNA, and 24 patients remained HBsAg negative during follow-up. Two patients recurred 7 and 9 months later, respectively, with detectable HBsAg. Both patients continued to have undetectable HBV DNA and normal ALT. HBsAg was neutralized by reinfusion of HBIg. CONCLUSION: Nucleoside/nucleotide combination is an effective alternative to HBIg/nucleos(t)ide to prevent recurrence of hepatitis B after OLT.

Long-term treatment with tenofovir in Asian-American chronic hepatitis B patients is associated with abnormal renal phosphate handling.

BACKGROUND: Increased risk of defective urinary phosphate reabsorption and osteoporosis has been reported in HIV and chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF). AIMS: Goals of this study were to evaluate the prevalence of renal phosphate wasting and abnormal bone mineral density in CHB patients taking TDF compared to CHB patients treated with entecavir (ETV) and untreated CHB patients. METHODS: This is a cross-sectional study of 146 consecutive Asian-American CHB patients who were treatment naïve (n = 60) or treated with either TDF (n = 42) or ETV (n = 44). Proximal tubular handling of phosphate was assessed by the maximal rate of tubular reabsorption of phosphate (TmPO4) divided by glomerular filtration rate (GFR) (TmPO4/GFR). Bone mineral density (BMD) was measured using dual X-ray absorptiometry. RESULTS: TmPO4/GFR was similar among CHB patients treated with TDF compared to untreated patients and patients taking ETV. However, among patients treated with ≥18 months of TDF or ETV, prevalence of abnormal TmPO4/GFR was higher among patients treated with TDF compared to ETV (48.5 % (16/33) vs. 12.5 % (3/24), p = 0.005). Overall prevalence of osteoporosis in this cohort of CHB patients was 14 %, with no significant difference between the three groups. Renal phosphate handling did not correlate with osteoporosis. CONCLUSIONS: Chronic hepatitis B patients treated with ≥18 months of TDF experienced an increased risk of proximal tubular dysfunction. TDF did not increase the risk of osteoporosis. Longitudinal studies are needed to confirm these findings.

Durability of Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir.

INTRODUCTION: Loss of HBeAg and development of anti-HBe (seroconversion) is seen as a milestone and endpoint in the treatment of HBeAg-positive patients with chronic hepatitis B (CHB). Among patients treated with nucleos(t)ide analogs (NA), recurrent viremia is common after discontinuation of therapy. Entecavir (ETV) and tenofovir (TDF) are highly potent NA. The durability of virological response and HBeAg seroconversion in patients treated with these agents is not well studied. METHODS: We retrospectively studied the outcomes of 54 HBeAg-positive CHB patients who were treated with either ETV (n = 30) or TDF (23) or both (n = 1) that achieved virological response and underwent seroconversion and consolidation therapy before cessation of treatment. RESULTS: Only 4 (7%) patients had sustained virological, serological, and biochemical remission. Thirteen patients (24%) continued to have HBV DNA levels below 2000 IU/mL and normal alanine aminotransferase activity (ALT). Thirty-seven patients (69%) developed HBV DNA >2000 IU/mL, with 20 having elevated ALT. Among these 37 patients, 23 (62%) remained HBeAg negative/anti-HBe positive, 12 (32%) became HBeAg positive, and 2 (5%) were HBeAg and anti-HBe negative. Duration of consolidation therapy did not correlate with low versus high level of virological relapse. CONCLUSIONS: Durability of HBeAg seroconversion associated with ETV or TDF was not superior to that reported in patients treated with less potent NA. Our results, aggregated with others, suggest HBeAg seroconversion should not be considered as a treatment endpoint for most HBeAg-positive patients treated with NA. Future updates of treatment guidelines should reconsider HBeAg seroconversion as an endpoint to therapy.

Imaging appearance in acute liver failure: correlation with clinical and pathology findings.

BACKGROUND AND AIM: Acute liver failure (ALF) is characterized by sudden liver injury without underlying chronic liver disease. Excluding underlying cirrhosis in these patients is often difficult and liver biopsy may be impractical. We review the imaging appearance of acute hepatic failure in patients who underwent transplant and correlate these findings with clinical, laboratory and pathology parameters. METHODS: This is a retrospective review of 47 patients without known chronic liver disease who presented to three institutions between 2002 and 2010 with ALF, 46 of which underwent subsequent orthotopic liver transplantation. Pre-transplant ultrasound, computed tomography and magnetic resonance imaging scans were reviewed for parenchymal homogeneity, surface nodularity and evidence of portal hypertension. Explant histopathology, laboratory values and time intervals between symptom onset to initial imaging and transplant were correlated with imaging findings. RESULTS: The majority of patients with ALF had abnormal radiographic findings. Ascites was seen in 65% of patients. Splenomegaly, collateral vessel formation and hepatofugal flow in the portal vein were present in 28, 15 and 9% of patients, respectively. Nodular liver surface was noted in 23% of patients, more commonly in patients who had been ill for more than 7 days. Liver surface nodularity correlated with massive hepatic necrosis on histology and wrinkled capsule on visual inspection of explanted liver specimen. CONCLUSION: Imaging findings in ALF was variable and can resemble cirrhosis. Assessment for underlying cirrhosis in the setting of liver failure should not be based on imaging findings.

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.

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.

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.

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.