High sustained virologic response rates, regardless of race or socioeconomic class, in patients treated with chronic hepatitis C in community practice using a specialized pharmacy team.

Approved direct-acting antiviral (DAA) regimens against hepatitis C virus (HCV) can cure nearly all patients; however, socioeconomic disparities may impact access and outcome. This study assesses socioeconomic factors, differences in insurance coverage and the drug prior authorization process in HCV-infected patients managed in community practices partnered with a dedicated pharmacy team with expertise in liver disease. This Institutional Review Board-approved, ongoing study captures data on a cohort of 2480 patients from community practices. Patients had chronic hepatitis C and were treated with DAA regimens selected by their physician. The HCV Health Outcomes Centers Network provides comprehensive patient management including a dedicated pharmacy support team with expertise in the prior authorization process. In this cohort, 60.1% were male, 49% were Hispanic Whites (HW), 37% were Non-Hispanic Whites (NHW), and 14% were Black/African American (BAA). Eighty-seven percent of patients were treatment-naïve, 74% were infected with genotype 1 virus and 63% had advanced fibrosis/cirrhosis (F3/F4 = 68.2% HW, 65.6% BAA, 55.4% NHW). Forty percent of patients were on disability with the highest percentage in the BAA group and less than one-third were employed full time, regardless of race/ethnicity. Medicare covered 42% of BAA patients versus 32% of HW and NHW. The vast majority of HW (80%) and BAA (75%) had a median income below the median income of Texas residents. Additionally, 75% of HW and 71% of BAA had median income below the poverty level in Texas. Despite the above socioeconomic factors, 92% of all prior authorizations were approved upon first submission and patients received DAAs an average of 17 days from prescription. DAA therapy resulted in cure in 95.3% of patients (sustained virologic response = 94.8% HW, 94.0% BAA, 96.5% NHW). Despite having more advanced diseases and more negative socioeconomic factors, >94% of HW and BAA patients were cured. Continued patient education and communication with the healthcare team can lead to high adherence and > 94% HCV cure rates regardless of race/ethnicity or underlying socioeconomic factors in the community setting.

Real-world observational experience with direct-acting antivirals for hepatitis C: baseline resistance, efficacy, and need for long-term surveillance.

The aim of this study was to obtain real-world, US, observational data on the effect of baseline resistance-associated substitutions (RASs) on achieving sustained virologic response (SVR) in hepatitis C (HCV) patients treated with direct-acting antiviral (DAA) regimens; the need for long-term follow-up in post-SVR patients.It is uncertain if the presence of RASs limits efficacy to DAAs. Once SVR is achieved, society guidelines recommend long-term surveillance for hepatocellular carcinoma in certain patients. Real-world data are limited on these topics.Adult patients treated with DAAs at community hepatitis clinics between January 2015 and April 2017 were included in this study. Baseline resistance testing was performed before treatment. Per guidelines, post-SVR long-term monitoring was required in patients with F3 to F4 fibrosis before treatment or with elevated ALT levels (>19 U/L females; >30 U/L males).A total of 875 chronic, mostly GT1a (60%) HCV patients were treated with an approved DAA regimen. Average baseline AST and ALT were 75 and 67 U/L, respectively, and 47% had F3 to F4 fibrosis at baseline. SVR was achieved in 863 (98.6%) patients despite a high presence of baseline RASs (61%). Long-term monitoring was required post-SVR in 539 patients (62%).In a real-life, US cohort of HCV-infected patients, nearly all patients achieved SVR with available DAA regimens regardless of baseline RASs. Approximately two-thirds of these patients required long-term follow-up, despite viral eradication.

Ombitasvir/paritaprevir/ritonavir + dasabuvir +/- ribavirin in real world hepatitis C patients.

BACKGROUND: The hepatitis C virus (HCV) NS5A inhibitor ABT-267 (ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450 (paritaprevir, PTV), the CYP3A inhibitor ritonavir (r) and the non-nucleoside NS5B polymerase inhibitor ABT-333 (dasabuvir, DSV) (OBV/PTV/r + DSV) with or without ribavirin (RBV) is a direct-acting antiviral regimen approved in the United States and other major countries for the treatment of HCV in genotype 1 (GT1) infected patients. Patients with HCV who are considered "hard-to-cure" have generally been excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures. AIM: To investigate the efficacy of this regimen in HCV G1-infected patients historically excluded from clinical trials. METHODS: Patients were ≥ 18 years old and chronically infected with HCV GT1 (GT1a, GT1b or GT1a/1b). Patients were treatment-naïve or previously failed a regimen including pegylated interferon/RBV +/- telaprevir, boceprevir, or simeprevir. One hundred patients were treated with the study drug regimen, which was administered for 12 or 24 wk +/- RBV according to GT1 subtype and presence/absence of cirrhosis. Patients were evaluated every 4 wk from treatment day 1 and at 4 and 12 wk after end-of-treatment. RESULTS: Many of the patients studied had comorbidities (44.2% hypertensive, 33.7% obese, 20.2% cirrhotic) and 16% previously failed HCV treatment. Ninety-six patients completed study follow-up and 99% achieved 12-wk sustained virologic response. The majority (88.4%) of patients had undetectable HCV RNA by week 4. The most common adverse events were fatigue (12%), headache (10%), insomnia (9%) and diarrhea (8%); none led to treatment discontinuation. Physical and mental patient reported outcomes scores significantly improved after treatment. Almost all (98%) patients were treatment compliant. CONCLUSION: In an all-comers HCV GT1 population, 12 or 24-wk of OBV/PTV/r + DSV +/- RBV is highly effective and tolerable and results in better mental and physical health following treatment.

Sofosbuvir-velpatasvir-voxilaprevir with or without ribavirin in direct-acting antiviral-experienced patients with genotype 1 hepatitis C virus.

The optimal retreatment strategy for hepatitis C virus (HCV) genotype 1-infected patients who fail direct-acting antiviral (DAA)-based regimens remains unknown. In this phase 2, open-label study conducted at a single center in the United States, patients with HCV genotype 1 infection who previously failed to achieve sustained virological response (SVR) on a DAA-based regimen were randomized to receive treatment with a fixed-dose combination tablet of sofosbuvir-velpatasvir-voxilaprevir with or without ribavirin (RBV) for 12 weeks. Patients were stratified by their cirrhosis and past nonstructural protein (NS) 5A inhibitor exposure. The primary efficacy endpoint was the proportion of patients with SVR at 12 weeks after treatment (SVR12). SVR12 was achieved by 24 of 24 patients (100%; 95% confidence interval [CI], 86-100) receiving sofosbuvir-velpatasvir-voxilaprevir alone and 24 of 25 (96%; 95% CI, 80-100) receiving the same treatment with RBV. None of the patients discontinued sofosbuvir-velpatasvir-voxilaprevir therapy because of an adverse event (AE). The most commonly reported AEs with sofosbuvir-velpatasvir-voxilaprevir alone were diarrhea and bronchitis; and with sofosbuvir-velpatasvir-voxilaprevir plus RBV were fatigue, anemia, gastroenteritis, and nausea. CONCLUSION: A fixed-dose combination of sofosbuvir-velpatasvir-voxilaprevir was well tolerated and effective at achieving virological response in patients with HCV genotype 1 infection and past DAA treatment experience. (Hepatology 2017;65:1803-1809).

Short-duration treatment with elbasvir/grazoprevir and sofosbuvir for hepatitis C: A randomized trial.

Direct-acting antiviral agents (DAAs) represent the standard of care for patients with hepatitis C virus (HCV) infection. Combining DAAs with different mechanisms may allow for shorter treatment durations that are effective across multiple genotypes. The aim of the C-SWIFT study was to identify the minimum effective treatment duration across multiple genotypes. C-SWIFT was an open-label, single-center trial in treatment-naïve patients with chronic HCV genotype (GT)1 or 3 infection. All patients received elbasvir (EBR) 50 mg/grazoprevir (GZR) 100 mg with sofosbuvir (SOF) 400 mg for 4-12 weeks. Patients with GT1 infection who failed therapy were eligible for retreatment with EBR/GZR+SOF and ribavirin for 12 weeks. The primary efficacy endpoint was sustained virological response [SVR]12 (SVR of HCV RNA <15 IU/mL 12 weeks after the end of therapy). Rates of SVR12 were 32% (10 of 31) and 87% (26 of 30) in patients without cirrhosis with GT1 infection treated for 4 and 6 weeks and 80% (16 of 20) and 81% (17 of 21) in GT1-infected patients with cirrhosis treated for 6 and 8 weeks. Among GT3-infected patients without cirrhosis, SVR12 was 93% (14 of 15) and 100% (14 of 14) after 8 and 12 weeks. SVR12 in GT3-infected patients with cirrhosis was 83% (10 of 12) after 12 weeks of treatment. Twenty-three GT1-infected patients who relapsed following initial treatment completed retreatment; all achieved SVR12. In the initial treatment phase, there was one serious adverse event of pneumonia, which led to treatment discontinuation, and during retreatment, 1 patient discontinued ribavirin because of pruritus. CONCLUSION: Data from this study support the use of 8-week treatment regimens that maintain high efficacy, even for patients with HCV GT3 infection. Retreatment of patients who failed short-duration therapy was achieved through extended treatment duration and addition of ribavirin. (Hepatology 2017;65:439-450).

Lorcaserin Use in the Management of Morbid Obesity in a Pre-Liver Transplant Patient.

Management of obesity and decompensated cirrhosis in those requiring liver transplantation (LT) is a challenging dilemma. Because of concerns for perioperative complications, many centers avoid transplant in those with a body mass index (BMI) greater than 40 kg/m(2) . Bariatric surgery is associated with increased risk attributable to complications of portal hypertension, including variceal rupture. Therefore, weight loss and LT options are limited. Several new classes of weight loss drugs are commercially available, including the anoretic, lorcaserin. This case illustrates the successful use of lorcaserin in a morbidly obese individual with decompensated cirrhosis evaluated for LT listing. (Hepatology 2016;64:301-302).

Dual therapy of grazoprevir and elbasvir for the treatment of hepatitis C infection.

The impact of chronic hepatitis C (HCV) worldwide is expected to increase as the population infected with HCV ages and more undiagnosed individuals are identified and linked to care through nation-wide initiatives. The development of interferon-free regimens involving the use of direct-acting antiviral agents, which disrupt key steps in viral replication, has revolutionized the treatment of chronic HCV infection. However, there remains a great medical need for HCV therapy that is of shorter duration, all-oral, with a high barrier to resistance, and highly effective for all patient populations including those with end-stage renal disease (ESRD) and cirrhosis. Grazoprevir, an HCV NS3/4A protease inhibitor and elbasvir, an NS5A inhibitor, have broad in vitro activity against most HCV genotypes and retain in vitro activity against many clinically relevant resistance-associated variants. The once daily regimen is well-tolerated and highly efficacious across wide-ranging patient populations including those with ESRD on hemodialysis.

Nonalcoholic fatty liver disease and the metabolic syndrome: clinical implications and treatment.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is expected to rise along with the global obesity epidemic. As NAFLD is the most common cause of chronic liver disease in the United States, it has become a major health concern. It affects all ethnicities, with the highest prevalence among the Hispanic population. Individuals with nonalcoholic steatohepatitis (NASH), the more serious form of NAFLD, are at increased risk of developing cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Since NAFLD is intricately associated with the metabolic syndrome and insulin resistance, increased risk of cardiovascular disease and mortality become a real concern. It has recently been shown that current nutrition trends, such as increased consumption of high-fructose corn syrup and certain types of fats, may have an important role in the increased NAFLD prevalence. As there are no ideal treatment options available for NAFLD, a multifaceted treatment approach should be tailored to each individual patient.

Long-term follow-up of liver transplantation for Budd-Chiari syndrome with antithrombotic therapy based on the etiology.

BACKGROUND: Because myeloproliferative disorders (MPDs) are a frequent cause of Budd-Chiari syndrome (BCS), treatment directed toward altering platelet production and function may be more rational and effective than anticoagulation after liver transplantation. METHODS: We reviewed data on 25 patients who received liver transplantation for BCS at our institution from 1987 to 2007. Posttransplant antithrombotic treatment was based on the cause of BCS: 17 patients with MPDs received hydroxyurea/aspirin; 5 received warfarin; and 3 (2 whose hypercoagulable disorder was corrected and 1 with sarcoidosis) received no therapy. RESULTS: Both graft survival (88% at 5 years) and patient survival (92% at 5 years) were superior in the BCS group compared with the 2609 patients who received liver transplants for other indications. Vascular complications included three instances of hepatic artery stenosis (NS compared with non-BCS liver recipients), one of portal vein thrombosis (nonsignificant [NS]), and one of portal vein stenosis (NS). All 25 patients underwent multiple liver biopsies with no bleeding complications. CONCLUSIONS: Using hydroxyurea and aspirin to treat patients with BCS caused by an MPD seems to be safe and effective and avoids the risks of anticoagulation with warfarin.

Patients with NASH and cryptogenic cirrhosis are less likely than those with hepatitis C to receive liver transplants.

BACKGROUND & AIMS: Many patients with cryptogenic cirrhosis (CC) have other conditions associated with nonalcoholic steatohepatitis (NASH) that put them at risk for complications that preclude orthotopic liver transplantation (OLT). METHODS: We followed all patients with NASH and CC who were evaluated for OLT (n = 218) at Baylor Simmons Transplant Institute between March 2002 and May 2008. Data were compared with those from patients evaluated for OLT because of hepatitis C virus (HCV)-associated cirrhosis (n = 646). RESULTS: Patients with NASH and CC were older, more likely to be female, had a higher body mass index, and a greater prevalence of diabetes and hypertension, compared with patients with HCV-associated cirrhosis, but the 2 groups had similar model for end-stage liver disease (MELD) scores. NASH and CC in patients with MELD scores ≤15 were less likely to progress; these patients were less likely to receive OLT and more likely to die or be taken off the wait list because they were too sick, compared with patients with HCV-associated cirrhosis. The median progression rate among patients with NASH and CC was 1.3 MELD points per year versus 3.2 MELD points per year for the HCV group (P = .003). Among patients with MELD scores >15, there were no differences among groups in percentage that received transplants or rate of MELD score progression. Hepatocellular carcinoma occurred in 2.7% of patients with NASH and CC per year, compared with 4.7% per year among those with HCV-associated cirrhosis. CONCLUSIONS: Patients with NASH and CC and low MELD scores have slower disease progression than patients with HCV-associated cirrhosis and are less likely to receive OLT.

Development of a disease-specific questionnaire to measure health-related quality of life in liver transplant recipients.

Currently, no disease-targeted instrument is available for measuring health-related quality of life (HRQOL) in liver transplant recipients. We developed and tested a post-liver transplant quality of life (pLTQ) instrument. Item selection for the pLTQ instrument was based on responses from liver transplant recipients, 12 liver experts, and a literature search. Impact scores were generated, and a factor analysis was conducted to organize the items into domains. Questions were constructed for each item, and redundant questions were removed. The pLTQ instrument was initially administered to 196 liver transplant patients and then was again administered to 77 patients 6 to 9 months later with a generic HRQOL survey [Medical Outcomes Study Short Form 36 (SF-36)]. Analysis of variance was used to compare the scores of patients at different times since transplantation and with various indications for transplantation. After redundancies were eliminated, the pLTQ instrument included 32 items in 8 domains: Emotional Function, Worry, Medications, Physical Function, Healthcare, Graft Rejection Concern, Financial, and Pain. We found stable pLTQ instrument and SF-36 instrument scores over time. Data 6 to 9 months after the initial assessment indicated stable quality of life outcomes. The pLTQ instrument is applicable to a variety of liver transplant recipients. The questionnaire was tested with a cross-sectional and longitudinal approach.

De-novo cholangiocarcinoma in native common bile duct remnant following OLT for primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic, progressive, inflammatory and obstructive disease of the intra- and extra-hepatic bile ducts of unknown etiology. Currently, orthotopic liver transplantation (OLT) is the only definitive treatment for PSC-related end-stage liver disease. However, PSC has been known to recur in the grafted liver. Roux-en-Y hepaticojejunostomy is more commonly performed than choledochocholedochostomy for PSC, although choledochocholedochostomy has been found to be safe and efficacious for PSC if the distal common bile duct is uninvolved at the time of OLT. Our case is unique in that it describes a patient who developed de-novo cholangiocarcinoma in the remnant portion of the native common bile duct six years after OLT with choledochocholedochostomy for PSC-associated end-stage liver disease without having PSC recurrence. In conclusion, our case report indicates that choledochocholedochostomy may not be desirable in PSC due to an increased risk of developing cholangiocarcinoma in the native common bile duct. This risk exists as well with a Roux-en-Y hepaticojejunostomy in the remaining intra-duodenal and intra-pancreatic biliary epithelium, although in theory to a lesser extent. Therefore, the risk of developing cholangiocarcinoma in the recipient common bile duct can only be completely eliminated by performing a Whipple procedure at the time of OLT.

Hepatocellular carcinoma in a hepatitis C patient with sustained viral response and no fibrosis.

Hepatitis C poses a substantial global health burden. Three to five percent of individuals with liver cirrhosis secondary to hepatitis C will develop hepatocellular carcinoma. The development of hepatocellular carcinoma is closely associated with cirrhosis in hepatitis C infection, whereas in hepatitis B virus infection, hepatocellular carcinoma may occur in the absence of cirrhosis. Although uncommon, hepatocellular carcinoma has been reported in hepatitis C patients without cirrhosis and, in very rare cases, in the absence of active viral replication. We report the case of a 51-year-old patient with hepatitis C who developed hepatocellular carcinoma in the absence of fibrosis and after having achieved sustained virological response with combination peginterferon and ribavirin therapy seven years prior. The patient successfully underwent surgical resection, and histopathological examination of the resected tissue demonstrated a poorly-differentiated hepatocellular carcinoma in an otherwise unremarkable liver. The patient continues to do well and has no evidence of tumor recurrence 18 months post-operatively. This case raises question regarding the carcinogenesis of hepatocellular carcinoma as a sequela of chronic hepatitis C in noncirrhotic liver and moreover after achieving sustained virological response.

Rapid virological response to peginterferon alfa and ribavirin treatment of chronic hepatitis C predicts sustained virological response and relapse in genotype 1 patients.

The treatment of chronic hepatitis C is a rapidly changing arena with new medications, new guidelines, and an evolving understanding of the virus, host factors and natural history. With the explosion of new information, the educational infrastructure to update clinicians has been outpaced; many feel uncertain if the tools they are using to care for patients are meeting the standard of practice. This review focuses on the most common genotype of the hepatitis C virus and the rules of engagement when treating with pegylated interferon and ribavirin. Viral assessment guideposts are evaluated and put into context for a clinical audience. The expected arrival of newer antiviral therapies is still years away, and maximizing the current treatment regimens is of utmost importance to eradicate virus when feasible, while minimizing toxicity.

Intraductal oncocytic papillary neoplasm of the liver: case and review of a rare variant.

Intrahepatic cholangiocarcinoma (ICCA) comprises 10% of all cholangiocarcinoma (CCA). It can be divided into three macroscopic subtypes, the least common of which is characterized by intraductal growth and believed to be more amenable to good outcomes with surgical resection compared to other ICCA. Recently, the rare finding of oncocytic differentiation has been described in this subtype and termed <> (IOPN), but it remains unclear if the presence of oncocytes confers a different tumor behavior. We present the eighth reported case of IOPN, which to our knowledge, is the first such case that, due to its location and vascular compromise, required orthotopic liver transplantation (OLT). This case adds to the little that is known about the behavior of IOPN and supports the observation that resection, or OLT when resection is not possible, is a valid treatment option.

The MELD score in advanced liver disease: association with clinical portal hypertension and mortality.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) score is a measure of chronic liver disease severity. Patients awaiting transplantation are assessed using this score. However, it has recently been suggested that changes in MELD score may be as important as the absolute MELD score in predicting short-term survival. However, clinical factors that affect the MELD score are unknown. We sought to identify predictors of mortality for potential transplant patients and examine factors that might predict changes in MELD score. MATERIALS AND METHODS: Between January 1, 2002, and July 30, 2004, we retrospectively examined risk factors of 429 adult patients awaiting liver transplantation at the University of California at Los Angeles (UCLA). Analysis of the data was performed using demographics, manifestations of portal hypertension, time between last MELD recorded and event, and laboratory values. Significant factors in univariate analysis were further studied using Cox proportional hazards regression multivariate analysis. RESULTS: At mean follow-up of 2.15 years (+/-1.49 years), 71 patients (16.5%) had MELD scores that increased 5-10 points, 22 had changes of 10-15 points, and 14 had changes of 15-20 points. Manifestations of portal hypertension, laboratory values, and etiology of liver disease did not predict changes in MELD score. However, development of hepatic encephalopathy (HR, 3.95; P=.002; 95% CI, 1.70 to 9.42) and MELD score (HR, 1.04; P=.001; 95% CI, 1.004 to 1.08) were associated with variceal bleeding. Also, MELD score (HR, 1.07; P<.001; 95% CI, 1.05 to 1.09), refractory ascites (HR, 2.15; P=.002; 95% CI, 1.31 to 3.53), and alcoholic cirrhosis (HR, 0.40; P=.04; 95% CI, 0.18 to 0.94) were independent predictors of mortality. CONCLUSIONS: Encephalopathy and MELD score were associated with variceal bleeding. Patients with an elevated MELD score, refractory ascites, and alcoholic cirrhosis had increased mortality while on the liver transplant list. No factors predicting changes in the MELD score were identified.