Hepatic Encephalopathy-Related Hospitalizations in Cirrhosis: Transition of Care and Closing the Revolving Door.

Cirrhosis is associated with substantial morbidity and mortality. Development of complications of cirrhosis, including hepatic encephalopathy (HE), portends poorer outcomes. HE is associated with hospital readmission, impaired patient and caregiver quality of life, risk of falls, and mortality. Guidelines recommend lactulose as first-line therapy for HE and rifaximin in combination with lactulose for reducing the risk of HE recurrence. Improving post-discharge outcomes, including readmissions, is an important aspect in the management of patients with HE. Approaches focused on improving management and prevention of HE, including properly titrating lactulose dosing, overcoming medication-related nonadherence, and incorporating rifaximin as therapy to reduce the risk of recurrence, as well as incorporating supportive care initiatives, may ease the transition from hospital to home. Strategies to decrease readmission rates include using hospital navigators, who can offer patient/caregiver education, post-discharge planning, and medication review; and involving pharmacists in post-discharge planning. Similarly, telemedicine offers providers the opportunity to monitor patients with HE remotely and improves outcomes. Providers offering transitional care management may be reimbursed when establishing contact with patients within 2 days post-discharge and conducting an outpatient visit within 7 days or 14 days. Several approaches have been shown to improve outcomes broadly in patients post-discharge and may also be effective for improving outcomes specifically in patients hospitalized with cirrhosis and HE, thus closing the revolving door on rehospitalizations in this population.

Checkpoint Inhibition in the Treatment of Unresectable, Advanced Lymphoepithelioma-like Hepatocellular Carcinoma.

Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a very rare neoplasm, with distinct epidemiologic, morphologic and clinical characteristics. Molecular mechanistic insight into the pathogenesis of this carcinoma suggests a pivotal role for the host immune system in the proliferation and progression of this tumor. However, while detailed genomic profiling of these hepatic tumors have revealed an intra-tumoral inflammatory mutational signature that may predispose to immune checkpoint inhibitor efficacy, no published report has described their use in this tumor type. Unfortunately, with near 100 cases of LEL-HCC reported in the literature to date and the majority of cases confined to localized and resectable disease, current evidence-based practices in the unresectable setting are lacking, with unknown benefit of chemotherapy or immunotherapy. We report on the case of a 68 year-old man with unresectable, advanced LEL-HCC who had evidence of disease stability after starting on the immune checkpoint inhibitor nivolumab. His disease response persisted off therapy for over a year and was potentially augmented by radiotherapy at the site of local progression. For this extremely rare tumor subtype, this case highlights the potential efficacy and safety of immune checkpoint blockade in LEL-HCC and reinforces the need for more robust, large-scale analysis of patients with these rare tumors to better evaluate treatment strategies and outcomes.

Safety and efficacy of pharmacologic weight loss in patients with cirrhosis.

BACKGROUND: Obesity poses unique risks in patients with advanced liver fibrosis; however, given surgical risks of bariatric surgery in cirrhosis treatment recommendations are currently limited to lifestyle interventions. This study seeks to inform a potential treatment gap by describing the safety and efficacy of pharmacologic weight loss in patients with advanced liver disease. METHODS: A retrospective chart review of the electronic medical record was conducted for all patients in the Scripps Health system from 2005 to 2017 with established advanced liver fibrosis that were prescribed medications associated with weight loss. The primary outcome was safety as defined by the model for end-stage liver disease (MELD) score. Secondary outcomes included total body weight loss, reasons for medication discontinuation, medication adverse events, and hospitalization before and after medication initiation. RESULTS: Thirty-eight patients and 63 prescriptions were included in the final analysis. The most frequently prescribed medication associated with weight loss was metformin (63%, n = 24) followed by a GLP-1 agonist (39%, n = 15). There was no significant effect of weight-loss medication on MELD score (p > 0.18) or number of hospitalizations when adjusting for subject (p > 0.26). There was a significant adjusted mean weight loss of 2.2 kg (p < 0.02) following prescription of a medication associated with weight loss. The Federal Drug Administration-approved anti-obesity medications as a group resulted in a significant adjusted weight loss of 7.22 kg (p < 0.013). In a linear mixed-effects model accounting for subjects, weight loss was not independently associated with a change in MELD (t[51] = -1.972, p > 0.05). CONCLUSION: Pharmacologic weight loss in patients with advanced liver fibrosis appears feasible based on preliminary safety and efficacy outcomes in this study. Future prospective studies are warranted to evaluate a potential significant treatment gap in the management of obesity in this vulnerable population.

Multicenter, Double-Blind, Randomized Trial of Emricasan in Hepatitis C-Treated Liver Transplant Recipients With Residual Fibrosis or Cirrhosis.

Despite achieving sustained virologic response (SVR) to hepatitis C virus (HCV) therapy, there remains a post liver transplantation population with advanced fibrosis/cirrhosis. Emricasan is an orally active, pan-caspase inhibitor that suppresses apoptosis and inflammation, potentially decreasing hepatic inflammation and fibrosis. We aimed to determine the safety and efficacy of emricasan (IDN-6556-07) in a double-blind, randomized, placebo-controlled, multicenter study in reducing or preventing the progression of hepatic fibrosis in HCV liver transplant recipients with residual fibrosis or cirrhosis after achieving SVR. A total of 64 participants were randomly assigned to receive 25 mg twice daily of emricasan or placebo in a 2:1 ratio for 24 months. 41 participants were randomly assigned to emricasan and 23 to placebo; 32 participants in the emricasan group (78.0%) and 19 who took a placebo (82.6%) completed the study. There was no difference in the primary endpoint (Ishak fibrosis stages F2-F5, improvement in fibrosis or stability; Ishak fibrosis stage F6, improvement) between the emricasan (77.1%) and placebo groups (74.1%); P = NS. There was no difference between the emricasan (54.5%) and placebo (60.7%) arms in the rate of fibrosis improvement alone. However, those in the prespecified F3 to F5 subgroup had higher rates of stability or improvement in fibrosis in the emricasan group (95.2%) compared with placebo (54.6%) (P = 0.01). The tolerability and safety profiles were similar in both groups. In conclusion, overall stability in the Ishak fibrosis stage was similar between emricasan and placebo groups at 24 months. However, there was improvement and/or stability in fibrosis stage in the prespecified F3 to F5 subgroup with emricasan versus placebo, suggesting that patients with moderate fibrosis may benefit with emricasan.

Outcomes of Liver Transplantation Among Older Recipients With Nonalcoholic Steatohepatitis in a Large Multicenter US Cohort: the Re-Evaluating Age Limits in Transplantation Consortium.

The liver transplantation (LT) population is aging, with the need for transplant being driven by the growing prevalence of nonalcoholic steatohepatitis (NASH). Older LT recipients with NASH may be at an increased risk for adverse outcomes after LT. Our objective is to characterize outcomes in these recipients in a large multicenter cohort. All primary LT recipients ≥65 years from 2010 to 2016 at 13 centers in the Re-Evaluating Age Limits in Transplantation (REALT) consortium were included. Of 1023 LT recipients, 226 (22.1%) were over 70 years old, and 207 (20.2%) had NASH. Compared with other LT recipients, NASH recipients were older (68.0 versus 67.3 years), more likely to be female (47.3% versus 32.8%), White (78.3% versus 68.0%), Hispanic (12.1% versus 9.2%), and had higher Model for End-Stage Liver Disease-sodium (21 versus 18) at LT (P < 0.05 for all). Specific cardiac risk factors including diabetes with or without chronic complications (69.6%), hypertension (66.3%), hyperlipidemia (46.3%), coronary artery disease (36.7%), and moderate-to-severe renal disease (44.4%) were highly prevalent among NASH LT recipients. Graft survival among NASH patients was 90.3% at 1 year and 82.4% at 3 years compared with 88.9% at 1 year and 80.4% at 3 years for non-NASH patients (log-rank P = 0.58 and P = 0.59, respectively). Within 1 year after LT, the incidence of graft rejection (17.4%), biliary strictures (20.9%), and solid organ cancers (4.9%) were comparable. Rates of cardiovascular (CV) complications, renal failure, and infection were also similar in both groups. We observed similar posttransplant morbidity and mortality outcomes for NASH and non-NASH LT recipients. Certain CV risk factors were more prevalent in this population, although posttransplant outcomes within 1 year including CV events and renal failure were similar to non-NASH LT recipients.

Spotlight on Impactful Research: Utilization of Aspirin and Statin in Management of Coronary Artery Disease in Patients With Cirrhosis Undergoing Liver Transplant Evaluation.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-reading-frankul a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-interview-frenette an interview with the author Answer questions and earn https://www.wileyhealthlearning.com/Activity/7036138/disclaimerspopup.aspx.

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.

A Practical Guideline for Hepatocellular Carcinoma Screening in Patients at Risk.

Hepatocellular carcinoma (HCC) arises in the context of cirrhosis and chronic hepatitis B virus (HBV) infections, and the diagnosis is often made at advanced stages. Because early-stage diagnosis improves survival, guidelines recommend screening patients at risk for HCC, such as patients with cirrhosis. However, adherence to screening programs is suboptimal. In this review, we discuss the value of HCC screening and provide practical guidance on patient selection and screening methods. International guidelines concordantly recommend HCC screening in patients with cirrhosis, including patients with HBV infections, hepatitis C virus infections with or without sustained virologic response, and nonalcoholic fatty liver disease. There is no consensus on screening patients without cirrhosis, although patients with advanced fibrosis, HBV infections, or nonalcoholic fatty liver disease without cirrhosis have an increased risk for development of HCC. Screening for HCC improves early tumor detection, receipt of curative treatment, and overall survival in at-risk patients. However, potential harms of HCC screening have not been well quantified. Semiannual abdominal ultrasonography is the screening modality of choice. Using ultrasonography in combination with biomarkers, such as α-fetoprotein, may increase accuracy for early HCC detection. The use of magnetic resonance imaging and computed tomography is limited by cost-effectiveness and practical considerations. Increased awareness of HCC screening will allow for earlier diagnosis and potentially curative treatment. We propose a comprehensive screening algorithm for patients at risk for development of HCC, recommending lifelong, semiannual ultrasonography combined with α-fetoprotein testing in patients with cirrhosis and selected patients without cirrhosis.

A Practical Review of Cytomegalovirus in Gastroenterology and Hepatology.

Human cytomegalovirus (CMV) is a ubiquitous Herpesviridae virus with a wide spectrum of pathology in humans. Host immunity is a major determinant of the clinical manifestation of CMV and can vary widely in the gastroenterology and hepatology practice setting. Immunocompetent patients generally develop a benign, self-limited mononucleosis-like syndrome whereas gastrointestinal tissue-invasive disease is more frequently seen in immunocompromised and inflammatory bowel disease patients. Additionally, liver allograft dysfunction is a significant consequence of CMV infection in liver transplant patients. While polymerase chain reaction and immunohistochemistry techniques allow for the reliable and accurate detection of CMV in the human host, the diagnostic value of different serologic, endoscopic, and histologic tests depends on a variety of factors. Similarly, latent CMV, CMV infection, and CMV disease carry different significance depending on the patient population, and the decision to initiate antiviral therapy can be complex and patient-specific. This review will focus on the pathophysiology, diagnosis, and management of CMV in patient populations relevant to the practice of gastroenterology and hepatology-liver transplant recipients, inflammatory bowel disease patients, and otherwise immunocompetent patients.

Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel.

BACKGROUND AND AIMS: This article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment. METHODS: In May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice. RESULTS: These recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms. CONCLUSIONS: Pruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.

Increasing Awareness on Racial Disparities in Liver Transplantation for Hepatocellular Carcinoma in the United States.

Hepatocellular carcinoma (HCC) is one of the main indications for liver transplantation in the United States. Studies have shown racial disparities in rates of liver transplant for HCC. The underlying etiologies of these disparities are important to understand in order to overcome barriers to liver transplant in disadvantaged racial and ethnic groups.

Emricasan Improves Liver Function in Patients With Cirrhosis and High Model for End-Stage Liver Disease Scores Compared With Placebo.

BACKGROUND & AIMS: Caspase-mediated apoptosis and inflammation contribute to progression of liver disease. Emricasan is a pan-caspase inhibitor that reduced serum markers of apoptosis and liver inflammation in patients with hepatitis C and non-alcoholic steatohepatitis (NASH). METHODS: We performed a multicenter study of 86 patients with cirrhosis (Child-Pugh class A or B; mean score, 6.9; 38% with alcohol-associated cirrhosis, 29% with HCV-associated cirrhosis, and 23% with NASH) and model for end-stage liver disease (MELD) scores of 11-18 (mean, 12.8). Patients were randomly assigned to groups given placebo (N = 42) or Emricasan (25 mg, N = 44), twice daily for 3 months; subjects then received open-label Emricasan (25 mg) twice-daily for 3 months. The primary endpoint was the change from baseline in serum levels of cleaved keratin 18 (CK-18) at month 3. RESULTS: Seventy-four patients completed the 3-month study period (40 given Emricasan and 34 given placebo); 69 patients received open-label Emricasan for 3 months afterward. At the 3-month timepoint, Emricasan significantly reduced mean MELD (P = .003) and Child-Pugh (P = .003) scores in subjects with high MELD scores (15 or more), compared with placebo, with significant reductions in INR (95% CI, -0.2882 to -0.0866) and total bilirubin (95% CI, -1.5069 to -0.0823) vs placebo. There were no significant differences between Emricasan and placebo groups in mean MELD (P = .466) or Child-Pugh (P = .124) scores overall at 3 months compared to placebo. Of patients with high MELD scores, 6/9 given Emricasan (67%) had a reduction of 2 points or more at month 3, compared with 2/10 given placebo (20%). Serum levels of full-length CK-18 (P = .02) and caspase 3/7 (P < .001), but not cleaved CK-18 (P = .092), decreased significantly at 3 months in the Emricasan vs placebo group. Emricasan was well tolerated, and adverse events were balanced between groups. Emricasan's effects were generally maintained or increased after 6 months of treatment. CONCLUSIONS: In a randomized trial of patients with cirrhosis, we found 3 months treatment with Emricasan to improve liver function, compared with placebo, reducing MELD and Child-Pugh scores, INR, and total bilirubin in patients with MELD scores ≥15. ClinicalTrials.gov no: NCT02230670.

Trapped vessel of abdominal pain with hepatomegaly: A case report.

Abdominal pain with elevated transaminases from inferior vena cava (IVC) obstruction is a relatively common reason for referral and further workup by a hepatologist. The differential for the cause of IVC obstruction is extensive, and the most common etiologies include clotting disorders or recent trauma. In some situations the common etiologies have been ruled out, and the underlying process for the patient's symptoms is still not explained. We present one unique case of abdominal pain and hepatomegaly secondary to IVC constriction from extrinsic compression of the diaphragm. Based on this patient's presentation, we urge that physicians be cognizant of the IVC diameter and consider extrinsic compression as a contributor to the patient's symptoms. If IVC compression from the diaphragm is confirmed, early referral to vascular surgery is strongly advised for further surgical intervention.

Morphometry Confirms Fibrosis Regression From Sustained Virologic Response to Direct-Acting Antivirals for Hepatitis C.

Sustained virologic response (SVR) after direct-acting antiviral (DAA) therapy for chronic hepatitis C results in significant decreases in liver stiffness measured by transient elastography (TE). The aim of this study was to clarify if TE can guide post-SVR management in patients with advanced fibrosis or cirrhosis prior to treatment as current guidelines are unclear on the role of TE after SVR. In total, 84 patients with hepatitis C virus and advanced fibrosis or cirrhosis and from a single center underwent DAA treatment and achieved SVR. Overall, 62% had improved liver stiffness that was consistent with regression of at least one stage of fibrosis. In the cirrhosis group, 48% showed fibrosis regression by at least two stages by TE (<9.5 kPa). In the F3 fibrosis group, 39% regressed by at least two stages (<7 kPa). The median time from SVR to regression by TE was 1 year. Fifteen patients with liver biopsies prior to SVR underwent a biopsy after SVR; 13 of these patients had improved liver stiffness (to <9.5 kPa). The post-SVR liver biopsies of only 4 patients showed F1-F2 while 11 patients showed F3-F4; however, morphometry of the first 11 biopsied patients revealed that 10 patients had an average 46% decrease in collagen content. Conclusion: This is the first DAA study that also has paired liver biopsies showing fibrosis regression. After SVR is achieved, improvements in liver stiffness measured by TE are seen in a majority of patients with advanced fibrosis/cirrhosis within 2 years. TE improvements are overstated when compared to histologic staging but confirmed with morphometric analysis. It is unclear whether TE following SVR can reliably predict when patients no longer require advanced fibrosis/cirrhosis monitoring after SVR.

Excellent Outcomes of Liver Transplantation Following Down-Staging of Hepatocellular Carcinoma to Within Milan Criteria: A Multicenter Study.

BACKGROUND & AIMS: Single-center studies have reported excellent outcomes of patients who underwent liver transplantation for hepatocellular carcinoma (HCC) after successful down-staging (reduction of tumor burden with local-regional therapy), but multi-center studies are lacking. We performed a multi-center study, applying a uniform down-staging protocol, to assess outcomes of liver transplantation and performed an intention to treat analysis. We analyzed factors associated with treatment failure, defined as dropout from the liver transplant waitlist due to tumor progression, liver-related death without transplant, or recurrence of HCC after transplant. METHODS: We performed a retrospective multi-center study of 187 consecutive adults with HCC enrolled in the down-staging protocol at 3 liver transplant centers in California (Region 5), from 2002 through 2012. All patients underwent abdominal imaging 1 month after each local-regional treatment, and at a minimum of once every 3 months. The primary outcome was probability of treatment failure. RESULTS: Liver transplantation was performed after successful down staging in 109 patients (58%). Tumor explant from only 1 patient had poorly differentiated grade and 7 (6.4%) had vascular invasion. Based on Kaplan-Meier analysis of data collected a median 4.3 years after liver transplantation, 95% of patients would survive 1 year and 80% of patients would survive 5 years; probabilities of recurrence-free survival were 95% and 87%, respectively. There were no center-specific differences in survival in the intention to treat analysis (P = .62), in survival after liver transplantation (P = .95), or in recurrence of HCC (P = .99). Patients were removed from the liver transplantation waitlist due to tumor progression in (n = 59; 32%) or liver-related death without liver transplantation (n = 9; 5%). Factors associated with treatment failure, based on multivariable analysis, were pre-treatment levels of alpha-fetoprotein (AFP) >1000 ng/mL (hazard ratio, 3.3; P < .001) and Child Pugh class B or C (hazard ratio, 1.6; P < .001). The probability of treatment failure at 2 years from the first down-staging procedure was 100% for patients with levels of AFP >1000 and Child Pugh class B or C vs 29.4% for patients with neither risk factor (P < .001). CONCLUSIONS: In a retrospective, multi-center study on HCC down staging under a uniform protocol, we found patients to have excellent outcomes following liver transplantation, with no center-specific effects. Our findings support application of the down-staging protocol on a broader scale. Patients with Child Pugh class B or C and AFP >1000 are unlikely to benefit from down staging.

A rare localised nasal CD30+ primary cutaneous T-cell lymphoma following liver transplantation.

Cutaneous T-cell post-transplant lymphoproliferative disorder (PTLD) is a rare clinical presentation that can potentially turn aggressive in solid-organ transplant recipients if not detected and intervened on early. We encountered a rare case of rapidly worsening primary cutaneous CD30-positive, Epstein-Barr virus-negative anaplastic large cell lymphoma (ALCL) of T-cell origin, manifesting as an isolated nasal tip lesion in a 71-year-old man 4 years after orthotopic liver transplantation. Excisional biopsy with partial rhinectomy showed subepithelial diffuse infiltration of medium-to-large lymphoid cells having round-to-irregular nuclei, partially condensed chromatin and prominent nucleoli. Immunophenotypic studies revealed CD30-positive primary cutaneous ALCL. Positron emission tomography/CT imaging revealed a locally active disease, and radiation therapy was initiated with complete response. A high index of suspicion for PTLD when evaluating skin lesions in a post-transplant patient is paramount for its early recognition, prompt diagnosis and timely intervention while the window for curative therapy remains possible.

Occurrence and Recurrence of Hepatocellular Carcinoma After Successful Direct-Acting Antiviral Therapy for Patients With Chronic Hepatitis C Virus Infection.

Chronic hepatitis C virus (HCV) infection has generally been associated with a slightly increased risk of developing hepatocellular carcinoma (HCC). For the past several decades, most patients with chronic HCV cirrhosis have been treated with pegylated interferon and ribavirin therapies, which were known to achieve sustained virologic response (SVR) but also carried their own side effects and toxicities. The recent implementation of direct-acting antiviral (DAA) treatments revealed an increased efficacy in difficult-to-treat populations and higher adherence rates given the all-oral nature of the regimens. However, while these regimens are excellent in terms of improving the side-effect profile and achieving SVR at a higher rate and in a shorter time frame than interferon and ribavirin, some researchers are now discovering an increased rate of de novo and recurrent HCC in patients with HCV cirrhosis compared to interferon treatment protocols. Although other studies were not able to reproduce similar findings, the question as to the role of DAA therapy in HCC occurrence after achieving SVR in patients with HCV cirrhosis continues to persist. Possible theories as to the mechanisms behind tumor relapse after DAA therapy include alterations of immunosurveillance and gene expression, a protective and antineoplastic effect from inflammation secondary to chronic HCV infection that is then abolished with DAA therapy, and delay in radiographic identification of previously undetectable tumors. This article reviews the current literature regarding concern for the possible increase of HCC after DAA therapy.