Pharmacotherapy for primary biliary cholangitis: an assessment of medication candidacy and rates of treatment.

BACKGROUND: Ursodeoxycholic acid is the preferred first-line therapy for primary biliary cholangitis. Alternative therapies, such as obeticholic acid, are recommended for patients who cannot tolerate ursodeoxycholic acid or who have an inadequate response to ursodeoxycholic acid monotherapy. Prior investigations have suggested that as many as 30% of patients with primary biliary cholangitis may have never received treatment with ursodeoxycholic acid. No prior investigations have examined usage rates of obeticholic acid in the treatment of primary biliary cholangitis. METHODS: All patients with an ICD-10 diagnosis of primary biliary cholangitis who had any records within the health system were included. A review of medical records was performed to confirm the diagnosis of primary biliary cholangitis and determine which medications had been prescribed for treatment, as well as candidacy for second-line therapies. RESULTS: A total of 495 patients met inclusion criteria. Notably, 95% of patients were taking ursodeoxycholic acid for treatment of their primary biliary cholangitis, with 67% of patients having disease that was well-controlled on ursodeoxycholic acid monotherapy. In total, 8% of patients were taking obeticholic acid (either as combination or monotherapy). Only 3% would benefit from the addition of a second line therapy but had not yet been offered medication. Only 3% of patients were not on any medication for management of their primary biliary cholangitis. CONCLUSIONS: Ursodeoxycholic acid is a readily available and generally well-tolerated medication that should be offered to all patients with primary biliary cholangitis as first-line therapy. While prior investigations have suggested that up to 30% of patients with primary biliary cholangitis may never have received treatment for the disorder, the present study suggests that patients are generally being managed according to guidelines. Moreover, a significant proportion of patients with primary biliary cholangitis will qualify for second line therapies and prescribers should be aware of the indications to use these medications.

Ultrasound Pressure Estimation for Diagnosing Portal Hypertension in Patients Undergoing Dialysis for Chronic Kidney Disease.

OBJECTIVES: Hepatic venous pressure gradient (HVPG) is considered the standard in quantifying portal hypertension, but can be unreliable in dialysis patients. A noninvasive ultrasound technique, subharmonic-aided pressure estimation (SHAPE), may be a valuable surrogate of these pressure estimates. This study compared SHAPE and HVPG with pathology findings for fibrosis in dialysis patients. METHODS: This was a subgroup study from an IRB-approved trial that included 20 patients on dialysis undergoing SHAPE examinations of portal and hepatic veins using a modified Logiq 9 scanner (GE, Waukesha, WI), during infusion of Sonazoid (GE Healthcare, Oslo, Norway). SHAPE was compared to HVPG and pathology findings using the Ludwig-Batts scoring system for fibrosis. Logistic regression, ROC analysis, and t-tests were used to compare HVPG and SHAPE with pathological findings of fibrosis. RESULTS: Of 20 cases, 5 had HVPG values corresponding to subclinical and clinical portal hypertension (≥6 and ≥10 mmHg, respectively) while 15 had normal HVPG values (≤5 mmHg). SHAPE and HVPG correlated moderately (r = 0.45; P = .047). SHAPE showed a trend toward correlating with fibrosis (r = 0.42; P = .068), while HVPG did not (r = 0.18; P = .45). SHAPE could differentiate between mild (stage 0-1) and moderate to severe (stage 2-4) fibrosis (-10.4 ± 4.9 dB versus -5.4 ± 3.2 dB; P = .035), HVPG could not (3.0 ± 0.6 mmHg versus 4.8 ± 0.7 mmHg; P = .30). ROC curves showed a diagnostic accuracy for SHAPE of 80%, while HVPG reached 76%. CONCLUSION: Liver fibrosis staging in dialysis patients evaluated for portal hypertension appears to be more accurately predicted by SHAPE than by HVPG; albeit in a small sample size.

Diagnosing Portal Hypertension with Noninvasive Subharmonic Pressure Estimates from a US Contrast Agent.

Background The current standard for assessing the severity of portal hypertension is the invasive acquisition of hepatic venous pressure gradient (HVPG). A noninvasive US-based technique called subharmonic-aided pressure estimation (SHAPE) could reduce risk and enable routine acquisition of these pressure estimates. Purpose To compare quantitative SHAPE to HVPG measurements to diagnose portal hypertension in participants undergoing a transjugular liver biopsy. Materials and Methods This was a prospective cross-sectional trial conducted at two hospitals between April 2015 and March 2019 (ClinicalTrials.gov identifier, NCT02489045). This trial enrolled participants who were scheduled for transjugular liver biopsy. After standard-of-care transjugular liver biopsy and HVPG pressure measurements, participants received an infusion of a US contrast agent and saline. During infusion, SHAPE data were collected from a portal vein and a hepatic vein, and the difference was compared with HVPG measurements. Correlations between data sets were determined by using the Pearson correlation coefficient, and statistical significance between groups was determined by using the Student t test. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity of SHAPE. Results A total of 125 participants (mean age ± standard deviation, 59 years ± 12; 80 men) with complete data were included. Participants at increased risk for variceal hemorrhage (HVPG ≥12 mm Hg) had a higher mean SHAPE gradient compared with participants with lower HVPGs (0.79 dB ± 2.53 vs -4.95 dB ± 3.44; P < .001), which is equivalent to a sensitivity of 90% (13 of 14; 95% CI: 88, 94) and a specificity of 80% (79 of 99; 95% CI: 76, 84). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the HVPG measurements (r = 0.68). Conclusion Subharmonic-aided pressure estimation is an accurate noninvasive technique for detecting clinically significant portal hypertension. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kiessling in this issue.

Hepatic Vein Contrast-Enhanced Ultrasound Subharmonic Imaging Signal as a Screening Test for Portal Hypertension.

BACKGROUND: Portal hypertension is the underlying cause of most complications associated with cirrhosis, with the hepatic venous pressure gradient (HVPG) used for diagnosis and disease progression. Subharmonic imaging (SHI) is a contrast-specific imaging technique receiving at half the transmit frequency resulting in better tissue suppression. AIMS: To determine whether the presence of optimized SHI signals inside the hepatic vein can be used as a screening test for portal hypertension. METHODS: This prospective trial had 131 patients undergoing SHI examination of portal and hepatic veins using a modified Logiq 9 scanner (GE, Waukesha, WI). Images acquired after infusion of the ultrasound contrast agent Sonazoid (GE Healthcare, Oslo, Norway) were assessed for the presence of optimized SHI signals in the hepatic vein and compared to the HVPG values obtained as standard of care. RESULTS: Of 131 cases, 64 had increased HVPG values corresponding to subclinical (n = 31) and clinical (n = 33) portal hypertension (> 5 and > 10 mmHg, respectively), and 67 had normal HVPG values (< 5 mmHg). Two readers performed independent, binary qualitative assessments of the acquired digital clips. Reader one (experienced radiologist) achieved for the subclinical subgroup sensitivity of 98%, specificity of 88%, and ROC area of 0.93 and for the clinical subgroup sensitivity of 100% and specificity of 61%, with an ROC area of 0.74. Reader two (less experienced radiologist) achieved for the subclinical subgroup sensitivity of 77%, specificity of 76%, and ROC area of 0.76 and for the clinical subgroup sensitivity of 88% and specificity of 63%, with an ROC area of 0.70. Readers agreement was of 83% with kappa value of 0.66. CONCLUSION: The presence of optimized SHI signals inside the hepatic vein can be a qualitative screening test for portal hypertension, which could reduce the need for invasive diagnostic procedures.

Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis.

BACKGROUND: As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase. METHODS: We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir-velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: Of the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir-velpatasvir, 94% (95% CI, 87 to 98) among those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir-velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19% of patients who received 12 weeks of sofosbuvir-velpatasvir, 16% of those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 18% of those who received 24 weeks of sofosbuvir-velpatasvir. The most common adverse events were fatigue (29%), nausea (23%), and headache (22%) in all patients and anemia (31%) in the patients receiving ribavirin. CONCLUSIONS: Treatment with sofosbuvir-velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir-velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis. (Funded by Gilead Sciences; ASTRAL-4 ClinicalTrials.gov number, NCT02201901.).

Successful treatment of donor-derived hepatitis C viral infection in three transplant recipients from a donor at increased risk for bloodborne pathogens.

We report here the successful treatment of hepatitis C virus (HCV) transmitted from a nucleic acid testing (NAT)-negative donor to three HCV-negative recipients-two renal transplants and one liver. Both renal recipients underwent standard deceased-donor renal transplantation with immediate graft function. The liver recipient underwent standard orthotopic liver transplantation and recovered uneventfully. The donor was a 39-year-old woman with a terminal serum creatinine of 0.7 mg/dL. She was high risk for bloodborne pathogens, based upon a history of sexual contact with an HCV-infected male partner. Recipient 1 was a 45-year-old man with a history of end-stage renal disease from systemic lupus erythematosus. Recipient 2 was a 62-year-old woman with a history of end-stage renal disease caused by hypertension and insulin-dependent diabetes. Recipient 3 was a 42-year-old man with acute liver failure from acetaminophen ingestion. All recipients became HCV polymerase chain reaction positive on post-transplant follow-up. Both kidney recipients were treated with ledipasvir/sofosbuvir combination therapy for 12 weeks without side effects or rejection episodes. Recipient 3 was treated with ledipasvir/sofosbuvir in combination with ribavirin for 12 weeks without side effects. All patients achieved a sustained viral response at 12 weeks and are considered cured of HCV. The kidney recipients maintained good allograft function with a serum creatinine of 1.4 mg/dL and 1.0 mg/dL, respectively. Both renal recipients maintained normal liver function post treatment and did not develop any evidence of fibrosis. The liver recipient's liver function tests returned to normal without further incident. This case report provides evidence for the successful treatment of donor-derived HCV in transplant recipients.

Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study.

BACKGROUND & AIMS: Patients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward. METHODS: In a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child-Turcotte-Pugh score, ≤7) who were on waitlists for liver transplantation for hepatocellular carcinoma, received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary end point was the proportion of patients with HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients with this HCV-RNA level at their last measurement before transplantation. RESULTS: Sixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per-protocol efficacy population consisted of 43 patients who had HCV-RNA level less than 25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had a post-transplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died (2 from nonfunction of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a post-transplantation virologic response. Recurrence was related inversely to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%). CONCLUSIONS: Administration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence. ClinicalTrials.gov: NCT01559844.

Pregnancy as an Opportunity for Hepatitis C Virus Elimination and Eradication.

Since the development of highly effective direct-acting antivirals, the WHO has set a goal of hepatitis C virus (HCV) elimination by 2030. Key to this strategy is increased screening and treatment. Pregnancy and the postpartum period represent a unique time when underserved populations have increased contact with the healthcare system. We propose using antenatal care to maximize case identification, treatment, and prevention. Pregnant individuals are an ideal sentinel population for HCV surveillance. Universal screening in pregnancy can provide population-level data. Once cases are identified, pregnancy presents an opportunity for intervention. Although not currently WHO approved, clinical trials are examining treatment during pregnancy. In the interim, identification of infection during pregnancy allows for optimization of the treatment cascade postpartum. Pregnancy can be used as a time for prevention. Taking advantage of patient engagement and existing infrastructure, pregnancy presents an opportunity to intervene in the fight for HCV eradication.

Single-center comparison of three chemoembolization regimens for hepatocellular carcinoma.

PURPOSE: Transarterial chemoembolization regimens for hepatocellular carcinoma (HCC) vary, without a gold-standard method. The present study was performed to evaluate outcomes in patients with HCC treated with doxorubicin/ethiodized oil (DE), cisplatin/doxorubicin/mitomycin-c/ethiodized oil (CDM), or doxorubicin drug-eluting beads (DEBs). MATERIALS AND METHODS: Patients received the same regimen at all visits, without crossover. Groups were compared based on Child-Pugh disease status, tumor/node/metastasis stage, and Barcelona Clinic Liver Cancer stage. Imaging outcomes were assessed based on modified Response Evaluation Criteria in Solid Tumors to calculate tumor response (ie, sum of complete and partial response), progressive disease (PD), and time to progression (TTP). RESULTS: A total of 228 infusions were performed in 122 patients: 59 with DE, 30 with CDM, and 33 with DEBs. The groups had similar Child-Pugh status (P = .45), tumor/node/metastasis stages (P = .5), and Barcelona Clinic Liver Cancer scores (P = .22). Follow-up duration was similar among groups (P = .24). Patients treated with DE underwent significantly more treatments (2.3 ± 1.4) than those treated with CDM (1.6 ± 0.7; P = .004) or DEBs (1.4 ± 0.6; P<.0001). Compared with DE (51%), tumor response was significantly more common with CDM (84%; P = .003) or DEBs (82%; P = .004). PD was significantly more likely with DE (37%) than with CDM (13%; P = .02) or DEBs (9%; P = .004). TTP was similar between groups (P = .07). CDM and DEBs were similar in regard to disease progression (P = .6) and response (P = .83). CONCLUSIONS: During a similar follow-up period, patients treated with CDM or DEB chemoembolization showed a significantly higher response rate and a lower incidence of tumor progression, with fewer required treatment sessions, than those treated with DE chemoembolization.

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.

Hematuria Leads to a New Diagnosis of Cirrhosis.

A known consequence of portal hypertension is the development of varices, which are described as "ectopic" when located at unusual sites in the abdomen. Ectopic varices carry a mortality rate as high as 40% after initial hemorrhagic episode. We report a patient who presented with hematuria secondary to bladder varices as the presenting symptom for a new diagnosis of cirrhosis. Cross-sectional imaging, early recognition of this rare event, combined with multidisciplinary management was essential for this patient to have a successful outcome.

Durable Response to Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, and Prednisone (BV-CHP) in a Patient with CD30-Positive PTCL Arising as a Post-Transplant Lymphoproliferative Disorder (PTLD).

T-cell PTLDs are lymphoid proliferations that develop in recipients of SOT or allogeneic HSCT. They carry an extremely poor prognosis with a reported median survival of only 6 months. The infrequency with which they are encountered makes treatment a challenge due to the lack of prospective trials to guide management. The significantly higher risk of morbidity and mortality in T-cell PTLD, compared to B-cell PTLD, underscores the challenge of treating these patients and the need for new therapeutic options. Brentuximab vedotin, an ADC targeting CD30, is FDA-approved in combination with CHP as front-line treatment for patients with CD30 expressing PTCL. Herein we report a case of CD30-positive T-cell PTLD that was successfully treated with BV-CHP, suggesting the added value of the addition of BV to chemotherapy, contributing to our patient's long and ongoing progression-free survival. To our knowledge, this is the first documented case of successful treatment using BV-CHP for a CD30-positive, EBV-negative, late T-cell PTLD.

A Noninvasive Ultrasound Based Technique to Identify Treatment Responders in Patients with Portal Hypertension.

RATIONALE AND OBJECTIVE: Subharmonic aided pressure estimation (SHAPE) is based on the inverse relationship between the subharmonic amplitude of ultrasound contrast microbubbles and ambient pressure. The aim of this study was to verify if SHAPE can accurately monitor disease progression in patients identified with portal hypertension. MATERIALS & METHODS: A modified Logiq 9 scanner with a 4C curvi-linear probe (GE, Waukesha, WI) was used to acquire SHAPE data (transmitting and receiving at 2.5 and 1.25 MHz, respectively) using Sonazoid (GE Healthcare, Oslo, Norway; FDA IND 124,465). Twenty-one (median age 59 years; 12 Males) of the 178 patients enrolled in this institutional review board approved study (14F.113) were identified as having clinically significant portal hypertension based on their hepatic venous pressure gradient results ≥ 10 mmHg. Repeat SHAPE examinations were done every 6.2 months. Liver function tests and clinical indicators were used to establish treatment response. RESULTS: Of the 21 portal hypertensive subjects, 11 had successful follow up scans with an average follow up time of 6.2 months. There was a significantly larger SHAPE signal reduction in the group who were classified as treatment responders (n = 10; -4.01±3.61 dB) compared to the single nonresponder (2.33 dB; p < 0.001). Results for responders matched the corresponding clinical outcomes of improved model for end stage liver disease (MELD) scores, improvement in underlying cause of portal hypertension, improved liver function tests and reduced ascites. CONCLUSION: SHAPE can potentially monitor disease progression in portal hypertensive patients and hence, may help clinicians in patient management. A larger study would further validate this claim.

Acute Liver Failure Requiring Liver Transplantation due to Acute Hepatitis A Virus Infection.

INTRODUCTION: Hepatitis A infection (HAV) is generally characterized by an acute icteric illness or may have a subclinical self-limited course, although rarely, can result in fulminant hepatitis and death. In 2019, the City of Philadelphia declared a public health emergency due to an HAV outbreak. We are reporting a series of four cases of acute liver failure (ALF) requiring liver transplantation (LT) due to acute HAV. METHODS: Chart review and case descriptions of four patients with acute HAV-related ALF who were expeditiously evaluated, listed as Status 1A, and who underwent LT between August 2019 and October 2019 at Thomas Jefferson University Hospital. RESULTS: All four patients presented with acute hepatocellular jaundice and had a positive HAV IgM, and all other causes of ALF were excluded. All four cases met the American Association for the Study of Liver Diseases (AASLD) criteria for ALF. Three of the four cases met King's College Criteria of poor prognosis for nonacetaminophen-induced ALF. All four patients underwent successful LT and were discharged six to twelve days postoperatively. One patient died of disseminated Aspergillus infection five months after LT, while the others have had excellent clinical outcomes shown by one-year follow-ups. All four explants had remarkably similar histological changes, revealing acute hepatitis with massive necrosis accompanied by a prominent lymphoplasmacytic inflammatory infiltrate and bile ductular proliferation. CONCLUSION: Although rare, patients presenting with acute HAV need close monitoring as they may rapidly progress to ALF. Early referral to a transplant center afforded timely access to LT and yielded overall good one-year survival. Widespread HAV vaccination for high-risk individuals is an essential strategy for preventing disease and curbing such future outbreaks.

Over-the-counter analgesics in cirrhotic patients: a case-control study examining the risk of hospitalization for liver-associated events.

OBJECTIVE: To assess the association between over-the-counter analgesic (OTCA) use and hospitalization for liver-associated events in cirrhotic patients. MATERIAL AND METHODS: Ninety adult cirrhotics admitted with liver-associated events and 126 non-hospitalized cirrhotic controls were enrolled prospectively into a case-control study. Standardized questionnaires were used to obtain predictor variables, including detailed 30-day OTCA use. Data were analyzed via logistic regression. RESULTS: Hepatitis C (43%), alcohol (34%), and cryptogenic (13%) were the most common etiologies of cirrhosis. OTCA use was similar between cases and controls in the 30 days prior to enrollment (34% vs. 44%; odds ratio, OR = 0.66, 95% confidence interval, CI = 0.37-1.16, p = 0.148). Adjusted analyses also found no significant association between OTCA use and hospitalization for liver-associated events (OR = 0.73, 95% CI = 0.38-1.38, p = 0.330). Furosemide (p = 0.001), lactulose (p = 0.026), and number of prior liver-associated events (p = 0.002) were positively associated with hospitalization, while propranolol showed an inverse association (p = 0.008). CONCLUSION: Our data suggest that non-excessive OTCA use is not significantly associated with hospitalization for liver-associated events.

Employment and Patient Satisfaction after Liver Transplantation.

Background and Aims: This study serves to revisit the effects of liver transplantation (LT) on employment in an era of improving survival outcomes post-transplant, and to identify areas of improvement in the transplant process to better optimize post-LT employment and patient satisfaction. Methods: Prospectively, patients who had undergone LT at a single tertiary LT center were surveyed in person and by e-mail. Primary outcomes included employment rate pre- and post-LT, annual salary, weekly hours worked, barriers to re-employment, and patient satisfaction. Results: Responses were collected and analyzed from 121 patients who underwent LT. Pre-LT, 68 (56.1%) reported full-time employment, 13 (10.7%) part-time employment, and 40 (33.1%) unemployment. Post-LT, 26 (21.4%) reported continued full-time employment, 18 (14.9%) part-time employment, and 77 (63.6%) unemployment. Average weekly work hours decreased post-LT (16.1 h/week vs. 39.9 h/week). Mean annual salaries decreased post-LT (17 earning salary ≥$40,000 vs. 56 earning salary ≥$40,000). These outcomes differed from patient pre-LT expectations, with 81.0% of previously employed patients believing they would return to employment, resulting in decreased patient satisfaction. Patients working physically demanding jobs pre-LT were less likely to return to work. Reasons cited for lack of return to full employment included early fatigue and difficulty regaining physical strength. Conclusions: Re-employment rates remain low post-LT, which is particularly true for patients working physically active jobs. Fatigue is a significant barrier to re-employment and increased physical rehabilitation post-LT may prove to be beneficial. Patients should be given realistic expectations about return to employment prior to their LT.

Timely diagnosis and staging of non-alcoholic fatty liver disease using transient elastography and clinical parameters.

BACKGROUND AND AIM: There is no standardized guideline to screen, image, or refer patients with non-alcoholic fatty liver disease (NAFLD) to a specialist. In this study, we used transient elastography (TE) to examine the fibrosis stages at which patients are first diagnosed with NAFLD. Subsequently, we analyzed metabolic markers to establish cut-offs beyond which noninvasive imaging should be considered to confirm NAFLD/non-alcoholic steatohepatitis fibrosis in patients. METHODS: Charts spanning July 2015-April 2018 for 116 NAFLD patients who had TE performed were reviewed. Univariate and multivariate analysis of metabolic markers was conducted. RESULTS: At the first hepatology visit, TE showed 73% F0-F2 and 27% F3-F4. Univariate analysis showed that high-density lipoproteins (HDL), hemoglobin A1c (A1c), aspartate transaminase (AST), and alanine transaminase (ALT) were significantly different between the F0-F2 and F3-F4 groups. Multivariate analysis showed that AST (P = 0.01) and A1c (P = 0.05) were significantly different. Optimal cut-offs for these markers to detect liver fibrosis on TE were AST >43 U/L and A1c >6.6%. The logistic regression function combining these two variables to reflect the probability (P) of the patient having advanced fibrosis (F3-F4) on TE yielded the formula: P = e R /(1 + e R ), where R = -8.56 + 0.052 * AST + 0.89 * A1c. CONCLUSIONS: Our study suggested that >25% of patients presenting to a specialist for NAFLD may have advanced fibrosis (F3-F4). Diabetes (A1c >6.6%) and AST >43 U/L were the most predictive in identifying NAFLD patients with advanced fibrosis on imaging. We proposed a formula that may be used to prioritize NAFLD patients at higher risk of having advanced fibrosis for specialist referral and imaging follow-up.

Contrast-Enhanced Subharmonic Aided Pressure Estimation (SHAPE) using Ultrasound Imaging with a Focus on Identifying Portal Hypertension.

Noninvasive, accurate measurement of pressures within the human body has long been an important but elusive clinical goal. Contrast agents for ultrasound imaging are gas-filled, encapsulated microbubbles (diameter < 10 µm) that traverse the entire vasculature and enhance signals by up to 30 dB. These microbubbles also produce nonlinear oscillations at frequencies ranging from the subharmonic (half of the transmit frequency) to higher harmonics. The subharmonic amplitude has an inverse linear relationship with the ambient hydrostatic pressure. Here an ultrasound system capable of performing real-time, subharmonic aided pressure estimation (SHAPE) is presented. During ultrasound contrast agent infusion, an algorithm for optimizing acoustic outputs is activated. Following this calibration, subharmonic microbubble signals (i.e., SHAPE) have the highest sensitivity to pressure changes and can be used to noninvasively quantify pressure. The utility of the SHAPE procedure for identifying portal hypertension in the liver is the emphasis here, but the technique has applicability across many clinical scenarios.