A Case of Progressive Cholestatic Drug-Induced Liver Injury Due to Terbinafine.

INTRODUCTION: Terbinafine is commonly prescribed for onychomycosis. It rarely leads to severe, prolonged cholestatic drug-induced liver injury. Clinicians should remain vigilant for this complication. CASE PRESENTATION: A 62-year-old woman was started on terbinafine and developed mixed hepatocellular and cholestatic drug-induced liver injury, confirmed on liver biopsy. The injury became predominantly cholestatic. Unfortunately, she developed coagulopathy with elevated international normalized ratio and progressive drug-induced liver injury with severely elevated alkaline phosphatase and total bilirubin, requiring repeat liver biopsy. Fortunately, she did not develop acute liver failure. DISCUSSION: Prior case reports and series have documented severe cholestatic drug-induced liver injury (although with lesser degree of bilirubin elevation) due to terbinafine, which has very rarely been associated with acute liver failure, need for liver transplantation, and/or death. CONCLUSIONS: Non-acetaminophen drug-induced liver injury is idiosyncratic. Complications including acute liver failure and vanishing bile duct syndrome can be slow to develop, so monitoring for them is important over longitudinal follow-up.

Psychosocial Barriers and Their Impact on Hepatocellular Carcinoma Care in US Veterans: Tumor Board Model of Care.

Background: Psychosocial barriers, including low socioeconomic status, homelessness, alcohol and substance use disorders, and psychiatric disorders are prevalent in US veterans. Our study aims to identify the prevalence of psychosocial barriers in veterans diagnosed with hepatocellular carcinoma (HCC), and their impact on receipt of cancer care. Methods: A retrospective cohort study was performed of all veterans diagnosed with HCC at the William S. Middleton Memorial Veterans' Hospital in Madison, Wisconsin, whose tumor care was coordinated through a multidisciplinary tumor board. Outcomes included receipt of any HCC-specific therapy and overall survival. Results: From January 1, 2007, through December 31, 2016, 149 veterans were diagnosed with HCC. Substance use disorders were reported in 124 (83%) patients, psychiatric illness was documented in 55 (37%) patients, 23 (15%) patients had incomes below the poverty threshold, and 7 (5%) were experiencing homelessness. The mean (SD) distance traveled for care was 207.1 (277.9) km; travel and lodging assistance were accessed by 50 (34%) and 33 (22%) veterans, respectively. Seventy-one patients (48%) had HCC exceeding T2 stage at diagnosis. Curative treatment was offered to 78 (52%) patients, with 127 (85%) receiving any HCC-specific care. Median survival from diagnosis was 727 days (95% CI, 488-966). Conclusions: Psychosocial barriers were common in our veteran cohort. Individualizing care, and coordination of travel and lodging, assisted in enabling high rates of receipt of HCC-specific therapy and improving patient survival.

Gut microbiome in non-alcoholic fatty liver disease associated hepatocellular carcinoma: Current knowledge and potential for therapeutics.

Metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) are rising in incidence and are an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). The gut microbiome is closely connected to the liver via the portal vein, and has recently been identified as a predictor of liver disease state. Studies in NAFLD, cirrhosis and HCC have identified certain microbial signatures associated with these diseases, with the disease-associated microbiome changes collectively referred to as dysbiosis. The pathophysiologic underpinnings of these observations are an area of ongoing investigation, with current evidence demonstrating that the gut microbiome can influence liver disease and carcinogenesis via effects on intestinal permeability (leaky gut) and activation of the innate immune system. In the innate immune system, pathogen recognition receptors (Toll like receptors) on resident liver cells and macrophages cause liver inflammation, fibrosis, hepatocyte proliferation and reduced antitumor immunity, leading to chronic liver disease and carcinogenesis. Dysbiosis-associated changes include increase in secondary bile acids and reduced expression of FXR (nuclear receptor), which have also been associated with deleterious effects on lipid and carbohydrate metabolism associated with progressive liver disease. Longitudinal experimental and clinical studies are needed in different populations to examine these questions further. The role of therapeutics that modulate the microbiome is an emerging field with experimental studies showing the potential of diet, probiotics, fecal microbiota transplantation and prebiotics in improving liver disease in experimental models. Clinical studies are ongoing with preliminary evidence showing improvement in liver enzymes and steatosis. The microbial profile is different in responders to cancer immunotherapy including liver cancer, but whether or not manipulation of the microbiome can be utilized to affect response is being investigated.

Microwave Ablation as Bridging to Liver Transplant for Patients with Hepatocellular Carcinoma: A Single-Center Retrospective Analysis.

PURPOSE: To evaluate the efficacy and safety of microwave (MW) ablation as first-line locoregional therapy (LRT) for bridging patients with hepatocellular carcinoma (HCC) to liver transplant. MATERIALS AND METHODS: This retrospective study evaluated 88 patients who received percutaneous MW ablation for 141 tumors as first-line LRT for HCC and who were listed for liver transplantation at a single medical center between 2011 and 2019. The overall survival (OS) rate statuses after liver transplant, waitlist retention, and disease progression were evaluated using the Kaplan-Meier techniques. RESULTS: Among the 88 patients (72 men and 16 women; mean age, 60 years; Model for End-Stage Liver Disease score, 11.2) who were listed for transplant, the median waitlist time was 9.4 months (interquartile range, 5.5-18.9). Seventy-one (80.7%) patients received transplant after a median waitlist time of 8.5 months. Seventeen (19.3%) patients were removed from the waitlist; of these, 4 (4.5%) were removed because of tumors outside of the Milan criteria (HCC-specific dropout). No difference in tumor size or alpha-fetoprotein was observed in the transplanted versus nontransplanted patients at the time of ablation (2.1 vs 2.1 cm and 34.4 vs 34.7 ng/mL for transplanted vs nontransplanted, respectively; P > .05). Five (5.1%) of the 88 patients experienced adverse events after ablation; however, they all recovered. There were no cases of tract seeding. The local tumor progression (LTP) rate was 7.2%. The OS status after liver transplant at 5 years was 76.7%, and the disease-specific survival after LTP was 89.6%, with a median follow-up of 61 months for all patients. CONCLUSIONS: MW ablation appears to be safe and effective for bridging patients with HCC to liver transplant without waitlist removal from seeding, adverse events, or LTP.

Optimizing Immunization Strategies in Adult Patients With Chronic Liver Disease and Liver Transplant Recipients.

Patients with chronic liver disease (CLD) and liver transplant recipients are at increased risk for infections from vaccine-preventable diseases. Gastroenterologists and hepatologists should assess patient immunization history, and necessary vaccinations should be given as soon as possible. Vaccines demonstrate superior immunogenicity when given earlier in the course of liver disease and prior to transplant. This article summarizes recommendations from the Advisory Committee on Immunization Practices for vaccinations in patients with CLD and liver transplant recipients, and includes a discussion of the influenza, herpes zoster, hepatitis A, hepatitis B, pneumococcal, human papillomavirus, and COVID-19 vaccines.

Staging Liver Fibrosis by Fibroblast Activation Protein Inhibitor PET in a Human-Sized Swine Model.

Current methods of staging liver fibrosis have notable limitations. We investigated the utility of PET in staging liver fibrosis by correlating liver uptake of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) with histology in a human-sized swine model. Methods: Five pigs underwent baseline 68Ga-FAPI-46 (68Ga-FAPI) PET/MRI and liver biopsy, followed by liver parenchymal embolization, 8 wk of oral alcohol intake, endpoint 68Ga-FAPI PET/MRI, and necropsy. Regions of interest were drawn on baseline and endpoint PET images, and SUVmean was recorded. At the endpoint, liver sections corresponding to regions of interest were identified and cut out. Fibrosis was histologically evaluated using a modified METAVIR score for swine liver and quantitatively using collagen proportionate area (CPA). Box-and-whisker plots and linear regression were used to correlate SUVmean with METAVIR score and CPA, respectively. Results: Liver 68Ga-FAPI uptake strongly correlated with CPA (r = 0.89, P < 0.001). 68Ga-FAPI uptake was significantly and progressively higher across F2 and F3/F4 fibrosis stages, with a respective median SUVmean of 2.9 (interquartile range [IQR], 2.7-3.8) and 7.6 (IQR, 6.7-10.2) (P < 0.001). There was no significant difference between 68Ga-FAPI uptake of baseline liver and endpoint liver sections staged as F0/F1, with a respective median SUVmean of 1.7 (IQR, 1.3-2.0) and 1.7 (IQR, 1.5-1.8) (P = 0.338). Conclusion: The strong correlation between liver 68Ga-FAPI uptake and the histologic stage of liver fibrosis suggests that 68Ga-FAPI PET can play an impactful role in noninvasive staging of liver fibrosis, pending validation in patients.

Characterization of mesenteric and portal hemodynamics using 4D flow MRI: the effects of meals and diurnal variation.

PURPOSE: To determine the variability of blood flow measurements using 4D flow MRI in the portal and mesenteric circulations and to characterize the effects of meal ingestion, time of day, and between-day (diurnal) variations on portal and mesenteric hemodynamics. METHODS: In this IRB-approved and HIPAA-compliant study, 7 healthy and 7 portal hypertension patients imaged. MRI exams were conducted at 3 T using a 32-channel body coil with large volumetric coverage and 1.25-mm isotropic true spatial resolution. Blood flow was quantified (L/min) in the hepatic and splanchnic vasculature. The first MR scan was performed after at least 8 h of fasting. Subsequently, subjects ingested 574 mL EnSure Plus® orally. A second acquisition was started 20 min after the meal ingestion. A third scan was performed before lunch and a fourth acquisition took place 20 min after lunch. A fifth scan was performed around 4 pm. Finally, subjects returned one week later for a repeat morning visit, with identical conditions as the first visit. RESULTS: In healthy controls significant increase in blood flow was seen in the PV, SMV, SMA, HA, and SCAo in response to breakfast but only the SCAo, SMA, SMV, and PV had a significant response to lunch. In general, patients with cirrhosis showed reduced response to meals compared to that in healthy controls. Additionally, PV flow in patients had the highest value in the afternoon. CONCLUSION: Effects of meal ingestion, time of day, and between-day variations were characterized using Radial 4D flow MRI in patients with cirrhosis and healthy controls.

Utility of Multiparametric CT for Identification of High-Risk NAFLD.

OBJECTIVE. The purpose of this study was to evaluate the utility of laboratory and CT metrics in identifying patients with high-risk nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS. Patients with biopsy-proven NAFLD who underwent CT within 1 year of biopsy were included. Histopathologic review was performed by an experienced gastrointestinal pathologist to determine steatosis, inflammation, and fibrosis. The presence of any lobular inflammation and hepatocyte ballooning was categorized as nonalcoholic steatohepatitis (NASH). Patients with NAFLD and advanced fibrosis (stage F3 or higher) were categorized as having high-risk NAFLD. Aspartate transaminase to platelet ratio index and Fibrosis-4 (FIB-4) laboratory scores were calculated. CT metrics included hepatic attenuation, liver segmental volume ratio (LSVR), splenic volume, liver surface nodularity score, and selected texture features. In addition, two readers subjectively assessed the presence of NASH (present or not present) and fibrosis (stages F0-F4). RESULTS. A total of 186 patients with NAFLD (mean age, 49 years; 74 men and 112 women) were included. Of these, 87 (47%) had NASH and 112 (60%) had moderate to severe steatosis. A total of 51 patients were classified as fibrosis stage F0, 42 as F1, 23 as F2, 37 as F3, and 33 as F4. Additionally, 70 (38%) had advanced fibrosis (stage F3 or F4) and were considered to have high-risk NAFLD. FIB-4 score correlated with fibrosis (ROC AUC of 0.75 for identifying high-risk NAFLD). Of the individual CT parameters, LSVR and splenic volume performed best (AUC of 0.69 for both for detecting high-risk NAFLD). Subjective reader assessment performed best among all parameters (AUCs of 0.78 for reader 1 and 0.79 for reader 2 for detecting high-risk NAFLD). FIB-4 and subjective scores were complementary (combined AUC of 0.82 for detecting high-risk NAFLD). For NASH assessment, FIB-4 performed best (AUC of 0.68), whereas the AUCs were less than 0.60 for all individual CT features and subjective assessments. CONCLUSION. FIB-4 and multiple CT findings can identify patients with high-risk NAFLD (advanced fibrosis or cirrhosis). However, the presence of NASH is elusive on CT.

Nonalcoholic Fatty Liver Disease and Diabetes Mellitus Are Associated With Post-Transjugular Intrahepatic Portosystemic Shunt Renal Dysfunction: An Advancing Liver Therapeutic Approaches Group Study.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well characterized. Here we describe renal function and characteristics associated with renal dysfunction at 30 days post-TIPS. Adults with cirrhosis who underwent TIPS at 9 hospitals in the United States from 2010 to 2015 were included. We defined "post-TIPS renal dysfunction" as a change in estimated glomerular filtration rate (ΔeGFR) ≤-15 and eGFR ≤ 60 mL/min/1.73 m2 or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post-TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions. Of the 673 patients, the median age was 57 years, 38% of the patients were female, 26% had diabetes mellitus, and the median MELD-Na was 17. After 30 days post-TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post-TIPS renal dysfunction, compared with those with stable renal function, were more likely to have nonalcoholic fatty liver disease (NAFLD; 33% versus 17%; P = 0.01) and comorbid diabetes mellitus (42% versus 24%; P = 0.001). Multivariate logistic regressions showed NAFLD (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.00-4.17; P = 0.05), serum sodium (Na; OR, 1.06 per mEq/L; 95% CI, 1.01-1.12; P = 0.03), and diabetes mellitus (OR, 2.04; 95% CI, 1.16-3.61; P = 0.01) were associated with post-TIPS renal dysfunction. Competing risk regressions showed that those with post-TIPS renal dysfunction were at a higher subhazard of death (subhazard ratio, 1.74; 95% CI, 1.18-2.56; P = 0.01). In this large, multicenter cohort, we found NAFLD, diabetes mellitus, and baseline Na associated with post-TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes mellitus undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities before proceeding with the procedure.

Provider Attitudes and Practice Patterns for Direct-Acting Antiviral Therapy for Patients With Hepatocellular Carcinoma.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC. METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses (58.6%). RESULTS: Provider beliefs about risk of HCC recurrence after DAA therapy varied: 48% responded that DAAs reduce risk, 36% responded that DAAs do not change risk, and 16% responded that DAAs increase risk of HCC recurrence. However, most providers believed DAAs to be beneficial to and reduce mortality of patients with complete response to HCC treatment. Accordingly, nearly all providers (94.9%) reported recommending DAA therapy to patients with early-stage HCC who received curative treatment. However, fewer providers recommended DAA therapy for patients with intermediate (72.9%) or advanced (57.5%) HCC undergoing palliative therapies. Timing of DAA initiation varied among providers based on HCC treatment modality: 49.1% of providers reported they would initiate DAA therapy within 3 months of surgical resection whereas 45.9% and 5.0% would delay DAA initiation for 3-12 months and >1 year post-surgery, respectively. For patients undergoing transarterial chemoembolization (TACE), 42.0% of providers would provide DAAs within 3 months of the procedure, 46.7% would delay DAAs until 3-12 months afterward, and 11.3% would delay DAAs more than 1 year after TACE. CONCLUSIONS: Based on a survey sent to hepatology providers, there is variation in provider attitudes and practice patterns regarding use and timing of DAAs for patients with HCC. Further studies are needed to characterize the risks and benefits of DAA therapy in this patient population.

Statin Use is Protective Against Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: A Case-control Study.

BACKGROUND AND GOAL: The incidence of nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is rising. We aimed to characterize risk factors for NAFLD-HCC development. METHODS: We performed a retrospective case-control study of HCC cases from a cohort of NAFLD patients who underwent at least 2 computed tomography scans. NAFLD-HCC cases confirmed on contrast imaging and/or biopsy were included. Controls were NAFLD patients without HCC matched by sex and age. Clinical variables were assessed. Visceral adipose tissue and subcutaneous adipose tissue were measured by computed tomography at 2 timepoints: before HCC diagnosis and at diagnosis. RESULTS: We identified 102 subjects [34 HCC cases, 68 controls, 65% (n=66) males, mean age: 69 y] from 2002 to 2016. Cirrhosis was present in 91%. In multivariate analysis, statin use was protective against HCC [odds ratio (OR)=0.20, 95% confidence interval (CI): 0.07-0.60, P=0.004], while hypertension was a risk factor for HCC (OR=5.80, 95% CI: 2.01-16.75, P=0.001). In multivariate analysis, visceral adipose tissue in males was higher before HCC diagnosis and declined by HCC diagnosis in 86%, which was a significant difference compared with controls (OR=2.78, 95% CI: 1.10-7.44, P=0.04). CONCLUSIONS: In a cohort of NAFLD-HCC patients, statin use was protective against HCC, while hypertension conferred an increased risk. Visceral adiposity at baseline was not a risk factor, but was higher in male patients before HCC development, declining in the majority by HCC diagnosis.

Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection Is Associated With Increased Survival in Patients With a History of Hepatocellular Carcinoma.

BACKGROUND & AIMS: There is controversy regarding the benefits of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection for patients with a history of hepatocellular carcinoma (HCC). We performed a multicenter cohort study to compare overall survival between patients with HCV infection treated with DAAs and patients who did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy. METHODS: We conducted a retrospective cohort study of patients with HCV-related HCC who achieved a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy, from January 2013 through December 2017 at 31 health care systems throughout the United States and Canada. We used Cox proportional hazards regression to determine the association between receipt of DAA therapy, modeled as a time-varying covariate, and all-cause mortality, accounting for informative censoring and confounding using inverse probability weighting. RESULTS: Of 797 patients with HCV-related HCC, 383 (48.1%) received DAA therapy and 414 (51.9%) did not receive treatment for their HCV infection after complete response to prior HCC therapy. Among DAA-treated patients, 43 deaths occurred during 941 person-years of follow-up, compared with 103 deaths during 526.6 person-years of follow-up among patients who did not receive DAA therapy (crude rate ratio, 0.23; 95% confidence interval [CI], 0.16-0.33). In inverse probability-weighted analyses, DAA therapy was associated with a significant reduction in risk of death (hazard ratio, 0.54; 95% CI, 0.33-0.90). This association differed by sustained virologic response to DAA therapy; risk of death was reduced in patients with sustained virologic response to DAA therapy (hazard ratio, 0.29; 95% CI, 0.18-0.47), but not in patients without a sustained virologic response (hazard ratio, 1.13; 95% CI, 0.55-2.33). CONCLUSIONS: In an analysis of nearly 800 patients with complete response to HCC treatment, DAA therapy was associated with a significant reduction in risk of death.

Direct-Acting Antiviral Therapy Not Associated With Recurrence of Hepatocellular Carcinoma in a Multicenter North American Cohort Study.

BACKGROUND & AIMS: There is controversy over the effects of direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection on hepatocellular carcinoma (HCC) recurrence and tumor aggressiveness. We compared HCC recurrence patterns between DAA-treated and untreated HCV-infected patients who had achieved a complete response to HCC treatment in a North American cohort. METHODS: We conducted a retrospective cohort study of patients with HCV-related HCC with a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy from January 2013 through December 2017 at 31 health systems throughout the United States and Canada. Cox regression was used to examine the association between DAA therapy and time to recurrence after a complete response, with DAA therapy analyzed as a time-varying exposure. We also estimated the association between DAA therapy and risk of early HCC recurrence (defined as 365 days after complete response). RESULTS: Of 793 patients with HCV-associated HCC, 304 (38.3%) received DAA therapy and 489 (61.7%) were untreated. HCC recurred in 128 DAA-treated patients (42.1%; early recurrence in 52 patients) and 288 untreated patients (58.9%; early recurrence in 227 patients). DAA therapy was not associated with HCC recurrence (hazard ratio 0.90, 95% confidence interval 0.70-1.16) or early HCC recurrence (hazard ratio 0.96, 95% confidence interval 0.70-1.34) after we adjusted for study site, age, sex, Child-Pugh score, α-fetoprotein level, tumor burden, and HCC treatment modality. In DAA-treated and untreated patients, most recurrences were within the Milan criteria (74.2% vs 78.8%; P = .23). A larger proportion of DAA-treated than untreated patients received potentially curative HCC therapy for recurrent HCC (32.0% vs 24.6%) and achieved a complete or partial response (45.3% vs 41.0%) but this did not achieve statistical significance. CONCLUSION: In a large cohort of North American patients with complete response to HCC treatment, DAA therapy was not associated with increased overall or early HCC recurrence. HCC recurrence patterns, including treatment response, were similar in DAA-treated and untreated patients.

CT texture analysis of the liver for assessing hepatic fibrosis in patients with hepatitis C virus.

OBJECTIVE: To evaluate CT texture analysis (CTTA) for non-invasively staging of hepatic fibrosis (stages F0-F4) in a cohort of patients with hepatitis C virus (HCV). METHODS: Quantitative texture analysis of the liver was performed on abdominal multidimensional CT scans. Single slice region of interest measurements of the total liver, Couinaud segments IV-VIII and segments I-III were made. CT texture parameters were tested against stage of hepatic fibrosis in segments IV-VIII on the portal venous phase. Texture parameters were correlated with biopsy performed within 1 year for all cases with intermediate fibrosis (F0-F3). RESULTS: CT scans of 556 adults (360 males, 196 females; mean age, 49.8 years), including a healthy control group (F0, n = 77) and patients with hepatitis C virus and Stage 0 disease (n = 49), and patients with increasing stages of fibrosis (F1, n = 80; F2 n = 99; F3 n = 87; F4 n = 164) were evaluated. Mean gray level intensity increased with increasing fibrosis. For significant fibrosis (≥F2), mean showed receiver operatingcharacteristic area under the curve (AUC) of 0.80 with sensitivity and specificity of 74 and 75% using a threshold of 0.44, with similar receiver operatingcharacteristic AUC and sensitivity/specificity for advanced fibrosis (≥F3). Skewness and kurtosis were inversely associated with hepatic fibrosis, most prominently in cirrhotic patients. A multivariate model combining these four texture features (mean, mpp, skewness and kurtosis) showed slightly improved performance with AUC of 0.82, 0.82 and 0.86 for any fibrosis (F0 vs F1-F4), significant fibrosis (F0-1 vs F2-4) and advanced fibrosis (F0-2 vs F3-4) respectively. CONCLUSION: CT texture features may be associated with hepatic fibrosis and have utility in staging fibrosis, particularly at advanced levels. ADVANCES IN KNOWLEDGE: CTTA may be helpful in detecting and staging hepatic fibrosis, particularly at advanced levels. CT measures like CTTA can be retrospectively evaluated without special equipment.

Considerations When Treating Hepatitis C in a Cirrhotic Transplant Candidate.

PURPOSE OF REVIEW: This review examines the issues in determining the decision to treat a HCV-positive patient who is a liver transplant (LT) candidate with highly effective and well-tolerated direct-acting antiviral (DAA) therapies. RECENT FINDINGS: Cure of HCV with DAA can improve liver function and allow delisting in some patients. Beyond a threshold of hepatic impairment (likely MELD score > 16 to 20), patients may experience a decline in MELD score with HCV cure without improvement in liver-related complications resulting in decreased opportunity to receive a LT. Eradicating HCV from patients who need LT regardless also deprives them of the option of receiving HCV-positive donor organs. Patients with MELD > 16 or Child-Pugh B/C may also have reduced cure rates of HCV, increased risk of hepatic decompensation, and adverse events with DAA pre-LT compared to post-LT DAA therapy. Preliminary data demonstrates increase risk of hepatocellular carcinoma (HCC) recurrence after treatment with DAA with subsequent studies raising doubts about this association. Patients with HCV cirrhosis on the LT waiting list with MELD score > 16, CTP-B/C, and HCC are best treated after LT with better response, tolerability, and the ability to receive organs from a larger donor pool that includes HCV-positive donors. Larger, prospective studies are needed to assess whether increased HCC recurrence after DAA is a true effect.

Accuracy of liver surface nodularity quantification on MDCT for staging hepatic fibrosis in patients with hepatitis C virus.

PURPOSE: To evaluate semi-automated measurement of liver surface nodularity (LSN) on MDCT in a cause-specific cohort of patients with chronic hepatitis C virus infection (HCV) for identification of hepatic fibrosis (stages F0-4). METHODS: MDCT scans in patients with known HCV were evaluated with an independently validated, semi-automated LSN measurement tool. Consecutive LSN measurements along the anterior liver surface were performed to derive mean LSN scores. Scores were compared with METAVIR fibrosis stage (F0-4). Fibrosis stages F0-3 were based on biopsy results within 1 year of CT. Most patients with cirrhosis (F4) also had biopsy within 1 year; the remaining cases had unequivocal clinical/imaging evidence of cirrhosis and biopsy was not indicated. RESULTS: 288 patients (79F/209M; mean age, 49.7 years) with known HCV were stratified based on METAVIR fibrosis stage: F0 (n = 43), F1 (n = 29), F2 (n = 53), F3 (n = 37), and F4 (n = 126). LSN scores increased with increasing fibrosis (mean: F0 = 2.3 ± 0.2, F1 = 2.4 ± 0.3, F2 = 2.6 ± 0.5, F3 = 2.9 ± 0.6, F4 = 3.8 ± 1.0; p < 0.001). For identification of significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and cirrhosis (≥ F4), the ROC AUCs were 0.88, 0.89, and 0.90, respectively. The sensitivity and specificity for significant fibrosis (≥ F2) using LSN threshold of 2.80 were 0.68 and 0.97; for advanced fibrosis (≥ F3; threshold = 2.77) were 0.83 and 0.85; and for cirrhosis (≥ F4, LSN threshold = 2.9) were 0.90 and 0.80. CONCLUSION: Liver surface nodularity assessment at MDCT allows for accurate discrimination of intermediate stages of hepatic fibrosis in a cause-specific cohort of patients with HCV, particularly at more advanced levels.

Multidisciplinary Management of Hepatocellular Carcinoma Improves Access to Therapy and Patient Survival.

BACKGROUND: Given the complexity of managing hepatocellular carcinoma (HCC), it is widely accepted that a multidisciplinary team approach (tumor boards) offers the best approach to individualize therapy. The aim of this study was to determine utilization of therapies and outcomes for patients with HCC, comparing those managed through our multidisciplinary tumor board (MDTB) to those who were not. METHODS: A database analysis of all patients with HCC managed through our MDTB, from 2007 until 2011, was performed. A database of all patients with HCC from 2002 to 2011, not managed through MDTB, was similarly created. RESULTS: A total of 306 patients with HCC, from 2007 to 2011 were managed through our MDTB, in comparison with 349 patients, from 2002 to 2011 who were not. There were no significant differences in baseline demographic data or model for end-stage liver disease at presentation. Patients managed through MDTB were more likely to present at an earlier tumor stage and with lower serum alpha fetoprotein (AFP) (P=0.007). The odds of receiving any treatment for HCC was higher in patients managed through MDTB (odds ratio, 2.80; 95% confidence interval, 1.71-4.59; P<0.0001) independent of model for end-stage liver disease score, serum AFP, and tumor stage. There was significantly greater survival of patients managed through MDTB (19.1±2.5 vs. 7.6±0.9 mo, P<0.0001). Independent predictors for improved survival included management through MDTB, receipt of any HCC treatment, lower serum AFP, receipt of liver transplant, and T2 tumor stage. CONCLUSIONS: Patients with HCC managed through a MDTB had significantly higher rates of receipt of therapy and improved survival compared with those who were not.

The Utilization of Palliative Care Services in Patients with Cirrhosis who have been Denied Liver Transplantation: A Single Center Retrospective Review

ABSTRACT Introduction and aim. Utilization of palliative care services in patients dying of end-stage liver disease (ESLD) is understudied. We performed a retrospective review of palliative care services among patients with ESLD unsuitable for liver transplantation (LT) at a tertiary care center. Material and methods. Deceased ESLD patients considered unsuitable for LT from 2007-2012 were identified. Patients were excluded if they received a transplant, had an incomplete workup, were lost to follow up or whose condition improved so LT was not needed. Of the 1,175 patients reviewed, 116 met inclusion criteria. Results. Forty patients (34.4%) received an inpatient palliative care (PC) consultation and forty-one patients (35.3%) were referred directly to hospice. Thirty-three patients (28.4%) transitioned to comfort measures without PC consultation (median survival < 1 day). The median interval between LT denial and PC consultation or hospice was 28 days. Median survival after PC consult or hospice referral was 15 days. In conclusion, in a single center retrospective review of ESLD patients, palliative care services, when utilized, were for care at the very end of life. Without consultation, aggressive interventions continued until hours before death. We propose that ESLD patients could benefit from PC consultation at time of LT evaluation or based on MELD scores.

The Utilization of Palliative Care Services in Patients with Cirrhosis who have been Denied Liver Transplantation: A Single Center Retrospective Review.

INTRODUCTION AND AIM: Utilization of palliative care services in patients dying of end-stage liver disease (ESLD) is understudied. We performed a retrospective review of palliative care services among patients with ESLD unsuitable for liver transplantation (LT) at a tertiary care center. MATERIAL AND METHODS: Deceased ESLD patients considered unsuitable for LT from 2007-2012 were identified. Patients were excluded if they received a transplant, had an incomplete workup, were lost to follow up or whose condition improved so LT was not needed. Of the 1,175 patients reviewed, 116 met inclusion criteria. RESULTS: Forty patients (34.4%) received an inpatient palliative care (PC) consultation and forty-one patients (35.3%) were referred directly to hospice. Thirty-three patients (28.4%) transitioned to comfort measures without PC consultation (median survival < 1 day). The median interval between LT denial and PC consultation or hospice was 28 days. Median survival after PC consult or hospice referral was 15 days. In conclusion, in a single center retrospective review of ESLD patients, palliative care services, when utilized, were for care at the very end of life. Without consultation, aggressive interventions continued until hours before death. We propose that ESLD patients could benefit from PC consultation at time of LT evaluation or based on MELD scores.