HCV Cirrhosis Research Articles

1. Impact of direct acting antiviral drugs in treatment naïve HCV cirrhosis on fibrosis and severity of liver disease: a real life experience from a tertiary care center of North India

Background and Aims: Treatment of chronic hepatitis C infection with direct-acting antiviral (DAA) drugs has been highly effective, but data regarding benefit in advanced liver disease is relatively scarce in Indian patients. The aim of this study was to determine the effects of DAA in patients with HCV related cirrhosis (compensated/decompensated) that achieved sustained virological response post therapy at 12 weeks (SVR12). Methods: 63 patients with HCV related cirrhosis treated with Sofosbuvir based regimen were evaluated. The primary end point was to evaluate the effect of treatment (SVR12) on the severity of liver disease with the secondary end point being to observe for any adverse events related to treatment. Results: Treatment naïve patients with HCV cirrhosis either due to genotype 1 or genotype 3 were divided into two groups: group A (compensated cirrhosis), group B (decompensated cirrhosis). SVR12 in group A was 91.66% (33/37) and in group, B was 73.17% (30/41). Baseline mean liver stiffness measurement (LSM) in group A was 16.81 ± 3.57 kPa which decreased to 11.19 ± 1.75 kPa at SVR12 (p-value < 0.0001). Baseline mean APRI and FIB-4 Score in group A were 1.228 ± 0.499 & 2.61 ± 1.06 and in group B were 2.156 ± 1.10 & 5.71 ± 2.06 respectively which decrease to 0.415 ± 0.115 & 1.25 ± 0.46 in group A, to 0.759 ± 0.275 & 2.60 ± 1.12 in group B following SVR12 (p value < .0001). Mean MELD-Na improved from baseline 9.93 ± 2.04, 20.70 ± 4.52 to 7.21 ± 0.92, 14.23 ± 4.51 respectively in group A and B at SVR12 (p-value < .0001). CTP Score improved by 1 in 27.27% (9/33) and ≥2 in 76.67% (23/30) of patients in group A and group B respectively. Conclusions: There was a significant improvement in severity of liver disease as depicted by the decrease in LSM and other noninvasive marker of fibrosis in patients who achieved SVR12 on DAA therapy. The authors have none to declare.

Hemoderivates Transfusion Differences Between Recipients of Liver Grafts from Donors After Uncontrolled Cardiac Death (uDCD) and Brain Death Donors (DBD)

Introduction The scarcity of grafts for liver transplantation (LT) from brain death donors (BDD), as well as the increasing mortality on waiting list have led us to look for other alternatives to achieve more liver grafts, being those from controlled and uncontrolled cardiac death (uDCD) the most attractive sources. However, intraoperative bleeding during LT has been higher when using uDCD donors, also related with higher morbi-mortality and lower patient and graft survival. Our aim is to compare the necessity of hemoderivates in uDCD and DBD groups. Materials and Methods Between January 2006 and December 2016 we performed 783 LT in adult recipients, excluding retransplants or patients undergoing OLT for acute liver failure. Liver grafts from uDCD donors (Group A) were used in 75 patients, and livers from BDD donors (Group B) were used in 708 patients. Results The mean age in group A was 59±8 years vs B 55±10 years in Group B (p=0.000). There were no significant differences in terms of sex, BMI and Child score. HCV cirrhosis was the indication for LT in 60% of cases in Group A vs 50.2% in group B (p=0.541). Hepatocellular carcinoma was present in 54.7% of patients in group A vs 38.9% in Group B (p=0.07). The mean of MELD score was 14.4±5 in Group A vs 14.5±6 in Group B (p=NS).The mean ICU stay was 6.8±7 days in Group A versus 6.3±9 days in group B (p=0.638). The mean transfusion of units of hemoderivates was as follows: 1) Packed red blood cells (PRBC): 12.3±13 units in Group A vs 8.6±10 Group B (p=0.008). 2) Fresh frozen plasma (FFP): 16.2±12 units in group A vs 10.7±8.8 in Group B (p=0.000). 3) Platelets: 2.29±2 units in group A vs 1.7±2 in group B (p=0.014). Using a logistic regression for multiple predictor variables, the only two factors with statistical significance related with MBT (>6 units of RBC) were uDCD condition (OR 2.3; CI 95%: 1.2-4.9; p=0.024), and higher Meld score (OR 2.75; CI 95%: 1.7-4.4; p=0.000) Survival at 1, 3 and 5 years was 81.3%, 70.2% and 68.6%, respectively, in group A vs 89%, 83.7% and 78.8%, respectively, in Group B (p= 0.070) Discussion. Conclusion The use of liver grafts from uDCD donors is associated with increased necessity of transfusion of hemoderivates in comparison with the use of BDD donors.

Reversal of hypercoagulability in patients with HCV-related cirrhosis after treatment with direct-acting antivirals.

The long-term impact of sustained virological response (SVR) after direct-acting antivirals (DAAs) on the hypercoagulability associated with HCV cirrhosis is unknown. We longitudinally evaluated the effect of DAAs treatment on cirrhotic coagulopathy. Pro- and anticoagulant factor levels and thrombin generation were assessed in patients with HCV-related cirrhosis at baseline, end of therapy (EOT), at 12, 24 and 48weeks (W) after EOT. Fifty-eight patients were enrolled (86% Child's A). SVR was 100%. Median factor VIII activity significantly decreased at EOT, 12weeks and 24weeks compared with baseline, whereas protein C significantly increased at 24weeks and 48weeks. Cirrhotic patients showed a slight but sustained increase in endogenous thrombin potential (ETP) with a statistically significant difference at EOT, 12weeks, 24weeks and 48weeks compared with baseline. Conversely, thrombomodulin-modified ETP was elevated before treatment and decreased over time to normal levels at 24weeks and 48weeks. The ETP ratio decreased slowly at EOT and 12weeks, and was significantly decreased at 24weeks and 48weeks compared with baseline (P<.001 for both comparisons), being not statistically different from ETP ratio measured in healthy controls. Child's B patients showed a significantly higher ETP ratio compared to Child's A at baseline and did not show any significant improvement in ETP ratio through 12weeks. Two Child's B patients developed PVT with an incidence rate of 1.1% p-yrs (95%CI, 0.18 to 3.58). DAAs therapy in HCV-related cirrhotic patients is associated with significant changes in thrombin generation suggesting a reversal of hypercoagulability particularly in Child's A patients.

Sofosbuvir-Based Therapy in the Pre-Liver Transplant Setting: The Canadian National Experience

Introduction and aim. Sofosbuvir (SOF)-based regimen has been shown to have high efficacy even in patients with decompensated cirrhosis. Treated patients may experience various degrees of hepatic recovery ranging from stabilization of liver function, to removal from liver transplant wait lists. The frequency of these occurrences in larger transplant eligible patient populations is unknown. The aim of this study was to assess the efficacy of SOF-based therapy in HCV infected transplant eligible patients and to evaluate short term changes in liver function and the effect on their liver transplant status.Material and methods. A retrospective multicenter Canadian study of liver transplant candidates with advanced HCV cirrhosis treated with SOF-based therapy. Outcomes included sustained virologic response (SVR), and liver transplant status.Results. 105 liver transplant candidates with advanced liver disease due to HCV were evaluated. The overall SVR was 83.8%. Hepatocellular carcinoma was diagnosed in 39 (37.1%) prior to transplant evaluation. In short term follow-up, 14 (13.3%) remained active on the list at the time of SVR12, 22 (20.9%) patients underwent liver transplantation, 7 (6.6%) patients were deactivated due to clinical improvement, 3 patients were delisted, and 10 deaths were reported.Conclusions. SOF-based therapy for patients progressing to liver transplantation leads to high SVR rates, short term stability in liver function, and deactivation from the transplant list.

Abundance of Phase 1 and 2 Drug-Metabolizing Enzymes in Alcoholic and Hepatitis C Cirrhotic Livers: A Quantitative Targeted Proteomics Study.

To predict the impact of liver cirrhosis on hepatic drug clearance using physiologically based pharmacokinetic (PBPK) modeling, we compared the protein abundance of various phase 1 and phase 2 drug-metabolizing enzymes (DMEs) in S9 fractions of alcoholic (n = 27) or hepatitis C (HCV, n = 30) cirrhotic versus noncirrhotic (control) livers (n = 25). The S9 total protein content was significantly lower in alcoholic or HCV cirrhotic versus control livers (i.e., 38.3 ± 8.3, 32.3 ± 12.8, vs. 51.1 ± 20.7 mg/g liver, respectively). In general, alcoholic cirrhosis was associated with a larger decrease in the DME abundance than HCV cirrhosis; however, only the abundance of UGT1A4, alcohol dehydrogenase (ADH)1A, and ADH1B was significantly lower in alcoholic versus HCV cirrhotic livers. When normalized to per gram of tissue, the abundance of nine DMEs (UGT1A6, UGT1A4, CYP3A4, UGT2B7, CYP1A2, ADH1A, ADH1B, aldehyde oxidase (AOX)1, and carboxylesterase (CES)1) in alcoholic cirrhosis and five DMEs (UGT1A6, UGT1A4, CYP3A4, UGT2B7, and CYP1A2) in HCV cirrhosis was <25% of that in control livers. The abundance of most DMEs in cirrhotic livers was 25% to 50% of control livers. CES2 abundance was not affected by cirrhosis. Integration of UGT2B7 abundance in cirrhotic livers into the liver cirrhosis (Child Pugh C) model of Simcyp improved the prediction of zidovudine and morphine PK in subjects with Child Pugh C liver cirrhosis. These data demonstrate that protein abundance data, combined with PBPK modeling and simulation, can be a powerful tool to predict drug disposition in special populations.

Considerations When Treating Hepatitis C in a Cirrhotic Transplant Candidate.

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. 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.

Cytomegalovirus reactivation in liver transplant recipients due to hepatitis C cirrhosis is associated with higher cardiovascular risk - an observational, retrospective study.

The association between cytomegalovirus (CMV) reactivation and cardiovascular risk has been reported in solid organ transplant populations; however, it has yet to be assessed in liver transplantation (LT). We aim to evaluate whether CMV reactivation is associated with cardiovascular events (CVE) in HCV-LT patients. LT patients (2010 and 2014) due to HCV cirrhosis were included. Clinically significant CMV (CS-CMV) was defined as viral load (VL) >5000copies/ml, need of therapy or CMV disease. Baseline variables and endpoint measures (CVE, survival, severe recurrent hepatitis C, de novo tumors, and diabetes) were collected. One hundred and forty patients were included. At LT, a history of AHT was present in 23%, diabetes 22%, tobacco use 45%, obesity 20%, and renal impairment (eGFR<60ml/min) in 26.5%. CS-CMV reactivation occurred in 25% of patients. Twenty-six patients (18.5%) developed a CVE. Cox regression analysis revealed two factors significantly associated with CVE: Pre-LT DM [HR=4.6 95% CI (1.6, 13), P=0.004] and CS-CMV [HR=4.7 95% CI (1.8, 12.5), P=0.002]. CS-CMV was not independently associated with the remaining endpoints except for survival (P=0.03). In our series, CS-CMV reactivation was associated with a greater risk of developing CVE, thus confirming data from other solid organ transplant populations and emphasizing the need for adequate CMV control.

The impact of treatment of hepatitis C with DAAs on the occurrence of HCC.

Hepatitis C virus infection is a major cause of chronic hepatitis resulting in cirrhosis and hepatocellular carcinoma (HCC). The recent introduction of direct acting antivirals (DAA), results in sustained virological response (SVR) rates of >90% in treated patients whatever the stage of liver fibrosis with an excellent safety profile. This major advancement has allowed treatment of a larger number of patients, some with more advanced liver dysfunction and a higher risk of HCC. An SVR is associated with a reduced risk of hepatic decompensation, the need for liver transplantation and both liver-related and overall mortality. This high rate of SVR has raised hopes that there would be a significant reduction in the incidence of HCC. However, the impact of DAA-based regimens on the occurrence of HCC in patients with cirrhosis, and in particular the recurrence of HCC following successful curative treatment is controversial. Published studies suggest that DAA does not increase the risk of de novo HCC following SVR. A more controversial topic is the effect of a DAA-based SVR on the recurrence of HCC following curative treatment of early HCC. Well-designed studies with robust comparisons are needed to determine the effect of DAA on the recurrence of HCC. At present, patients with HCV cirrhosis who have undergone resection or ablation for HCC should not be dissuaded from receiving DAA therapy to prevent the progression of liver disease. Monitoring for HCC with liver imaging and AFP should be performed twice a year indefinitely post-SVR in patients with HCV cirrhosis.

Impact of Direct Acting Antiviral Drugs in Treatment Naïve HCV Cirrhosis on Fibrosis and Severity of Liver Disease: A Real Life Experience from a Tertiary Care Center of North India

Treatment of chronic hepatitis C infection with direct-acting antiviral (DAA) drugs has been highly effective, but data regarding benefit in advanced liver disease is relatively scarce in Indian patients. The aim of this study was to determine the effects of DAA in patients with HCV related cirrhosis (compensated/decompensated) who achieved sustained virological response post-therapy at 12 weeks (SVR12). Sixty-three patients with HCV related cirrhosis treated with sofosbuvir based regimen were evaluated. Data regarding baseline demographics, the severity of liver disease and treatment regimen were collected. The primary end point was to evaluate the effect of treatment (SVR12) on the severity of liver disease with the secondary end point being to observe for any adverse events related to treatment. Treatment naïve patients with HCV cirrhosis either due to genotype 1 or genotype 3 were divided into two groups: group A (compensated cirrhosis), group B (decompensated cirrhosis). SVR12 in group A was 91.66% (33/37) and in group, B was 73.17% (30/41). Baseline mean liver stiffness measurement (LSM) in group A was 16.81±3.57kPa which decreased to 11.19±1.75kPa at SVR12 (P-value <0.0001). Baseline mean APRI and FIB-4 score in group A were 1.228±0.499 and 2.61±1.06 and in group B were 2.156±1.10 and 5.71±2.06 respectively which decrease to 0.415±0.115 and 1.25±0.46 in group A, to 0.759±0.275 and 2.60±1.12 in group B following SVR12 (P value <0.0001). Mean MELD-Na improved from baseline 9.93±2.04, 20.70±4.52 to 7.21±0.92, 14.23±4.51 respectively in group A and B at SVR12 (P-value <0.0001). Child-Turcotte-Pugh score improved by 1 in 27.27% (9/33) and ≥2 in 76.67% (23/30) of patients in group A and group B respectively. There was a significant improvement in severity of liver disease as depicted by the decrease in LSM and other noninvasive marker of fibrosis in patients who achieved SVR12 on DAA therapy.

Simultaneous CMV Colitis and Kayexalate-Induced Ulcer Presenting as Hematochezia

We present a rare case of hematochezia caused by 2 concurrent ulcers caused by different etiologies: CMV and Kayexalate (sodium polystyrene). A 66 year old man with history of deafness and HCV cirrhosis with prolonged hospitalization from a motor-vehicle accident had multiple episodes of hematochezia with a resultant decrease in hemoglobin from 8.2mg/dL to 5.3mg/dL. Colonoscopy was performed, which showed two relatively isolated ulcers located in the transverse colon and in the rectum. The remainder of the colonic mucosa, however, was normal. Both ulcers were biopsied for pathology. Surprisingly, the rectal ulcer demonstrated findings of crystal-like structures suggestive of Kayexalate crystals, while the transverse ulcer stained positive for CMV on viral immunohistochemistry stains. Upon review of the patient's chart, he received 2 separate doses of Kayexalate 5 days prior and immediately prior to endoscopy for transient hyperkalemia due to acute renal failure. He did not have diarrhea or increased number of bowel movements prior to colonoscopy. There was no obvious evidence of immunodeficiency or compromise. He was started on gancyclovir for his CMV colitis and Kayxelate was no longer used during his hospitalization. The patient subsequently did well with no further hematochezia. There are a number of cases that describe ulcers caused by Kayexalate, however, simultaneous infection with CMV has not been reported. Rare causes of hematochezia can be missed if the entire colon is not examined. Obtaining a biopsy of each ulcer should be considered because management can change depending on pathology results. Careful review of medications and associated medical conditions can help broaden the suspected differential diagnosis during cases.Figure: Transverse colon ulcer.Figure: Kayexalate crystal from rectal ulcer biopsy.

CD34 Expression as a marker of progression of chronic hepatitis C

Background In Egypt, the rate of death/transplantation, decompensation and HCC in patients with compensated HCV cirrhosis is 4.58%, 6.37% and 3.36%, respectively. It is estimated that Egyptian patients with HCV cirrhosis had an annual incidence of HCC with 5.3%. CD34 is a 110-kDa transmembrane glycoprotein present on leukemic cells, endothelial cells and stem cells). CD34 is preferentially expressed on the surface of regenerating or migrating endothelial cells and is a marker of proliferating endothelial cells in the growing sprouts during angiogenesis. Aim of the work: The aim of the present study was to analyses the correlation between CD34 and the clinical severityof CHC. Methods: A total of 70 adult patients with chronic hepatitis C infection in various stages with no evidence of cirrhosis, were recruited for the study. We studied the expression of CD34 in liver specimens from chronic HCV infected patients using a computer-based analysis of immunohistochemical staining and confirmed it by Western Blot. Results: CD34 significantly related with AST and ALT levels. Also, it is significantly related with alpha-fetoprotein and prothrombin concentration. Also, There was a significant relation between CD34 and fibrosis stage. Conclusion: A direct correlation existed between endothelial cell markers CD34 expression and the progression of fibrosis in chronic hepatitis C. The immunohistochemical methods of this molecule can be important clue in future prognostic strategies.

Non-neoplastic portal vein thrombosis in HCV cirrhosis: the weight of inflammation on a fragile hemostatic balance

The historical paradigm of spontaneous bleeding tendency of cirrhosis as consequence of an intrinsic coagulopathy has faded in the last years (1). This theory has been first challenged by milestones studies of Tripodi et al . demonstrating normal thrombin generation by plasma from cirrhotic patients and, consequently, the need of more comprehensive coagulation tests to evaluate hemostatic changes in advanced chronic liver disease (2). This is coherent with the clinical observation of thrombotic events occurring among cirrhotic patients, despite altered prothrombin- and partial thromboplastin-time, which are inadequate to evaluate the profound changes in balance between pro- and anti-coagulant factors alongside the disruption of liver function (3,4). Moreover, plasma from patients with cirrhosis shows a pro-coagulant imbalance alongside disease severity, as expressed by the resistance to the action of thrombomodulin, a strong anti-coagulant factor (5).

Safety and Efficacy of Ledipasvir/Sofosbuvir on Hepatitis C Eradication in HCV/ HIV Co-infected Patients

Introduction: There are few published data on the experience of FDA-approved oral combination of ledipasvir/sofosbuvir in HIV/HCV co-infected patients. The aim of this study is to evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with HCV and HIV co-infection in an urban HIV clinic center in Orlando.Figure: Demographic Characteristics of the Patients at Baseline.Figure: Antiviral regimen.Methods: A retrospective study was performed in patients co-infected with HIV-1 and HCV who were treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 weeks from 2014 to 2016. All patients included were receiving antiretroviral therapy (ART) with HIV RNA values of 100 copies/mL or fewer regardless of baseline HCV RNA level. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.Figure: Response during and after Therapy.Results: Of the 40 patients enrolled, 55% were black, 22.5 % had been previously treated for HCV, and 25 % had cirrhosis. The patients were on a wide range of ART. Overall, 39 patients (97.5 %) had a sustained virologic response at 12 weeks after the end of therapy, including rates of 97.1% in patients with HCV genotype 1a and 100% in those with HCV genotype 1b.One patient with HCV genotype 3a was included and achieved SVR12 successfully. Rates of SVR12 were similar regardless of previous treatment or the presence of compensated cirrhosis. Only 1 patient experienced relapse at week 12 following treatment and deep sequencing didn't reveal any resistance associated mutation in the NS5A or NS5B region. Interestingly, 7(17.5%) patients who were adherent to ART experienced HIV viral breakthrough which resolved after continuing the same ART regimen. Two (5%) patients experienced HIV-1 virologic rebound due to noncompliance with HIV therapy, which resolved after resuming the same ART regimen. No severe adverse events were observed and no patient discontinued treatment because of adverse events. The most common adverse events included headache (12.5 %), fatigue (10%), and diarrhea (2.5%). Conclusion: This retrospective study demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV, regardless of HCV baseline levels, HCV treatment history or cirrhosis condition. The oral combination of ledipasvir/sofosbuvir represents a safe and well-tolerated HCV treatment option that does not require modification for many of the common HIV ART. HIV virologic rebound during the treatment emphasized the importance of closely monitoring HIV RNA level while treating HCV.

Early Abdominal Surgery After Elective Transjugular Intrahepatic Portosystemic Shunt (TIPS) May Increase Morbidity and Mortality Post-Operatively: Case Series of 2 Patients

Background: Abdominal surgery in cirrhotic patients has high morbidity and mortality due to portal hypertension. Preoperative portal decompression by TIPS placement is a logical approach to reduce perioperative complications. However this is controversial. We report outcome of 2 cases of elective TIPS prior to abdominal surgery. Case 1: 60 y/o male with history of decompensated ETOH cirrhosis, Child Pugh C, MELD 16 had elective TIPS prior to surgery for ascending colon adenocarcinoma. Post TIPS hepatic venous pressure gradient (HVPG) decreased from 16 to 6 mmhg. 7 days later patient underwent right hemicolectomy and ileocolonic anastomosis. Intraoperative blood loss was 600 ml. 4 days after surgery patient developed altered mental status (AMS) and sepsis. Work up revealed intra-abdominal abscess from anastomotic leak requiring repeat ex-lap. Subsequent hospital course complicated by septic shock, renal failure, prolonged intubation due to hepatic encephalopathy (HE). Patient went to hospice care and passed away 28 days after initial surgery. Case 2: 70 y/o female with history of decompensated HCV cirrhosis, Child Pugh B, MELD 11 had elective TIPS prior to surgery for cecum adenocarcinoma. Post TIPS HVPG decreased from 14 to 4 mmhg. 3 days later patient underwent right hemicolectomy. Intraoperative blood loss was 50 cc. Postoperative course complicated by HE from use of pain medications. AMS lead to development of aspiration pneumonia. Despite medical optimization with lactulose, Rifaximin and avoiding narcotic she remained encephalopathic. 17 days after surgery TIPS was revised to increase HVPG from 2 to 7 mmhg. HE improved and patient was discharged after 34 days of hospitalization. Discussion: Decompression of portal pressure by TIPS prior to abdominal surgery is expected to improve postoperative outcome. Only retrospective controlled study by Vinet et al1 suggests that elective TIPS within 72±21 days of abdominal surgery has similar outcome compared to those without TIPS. Our patients had increase mortality; morbidity and prolonged hospital stay from early abdominal surgery within 1 week of TIPS placement. We emphasize need for the prospective control study to help determine timing of elective TIPS and assess its effect on outcome of abdominal surgery.

Imaging features of microvascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy in HCV-related cirrhosis.

To evaluate imaging features of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) developed after direct-acting antiviral (DAA) therapy in HCV-related cirrhosis. Retrospective cohort study on 344 consecutive patients with HCV-related cirrhosis treated with DAA and followed for 48-74 weeks. Using established imaging criteria for MVI, HCC features were analysed and compared with those in nodules not occurring after DAA. After DAA, HCC developed in 29 patients (single nodule, 18 and multinodular, 11). Median interval between therapy end and HCC diagnosis was 82 days (0-318). Forty-one HCC nodules were detected (14 de novo, 27 recurrent): maximum diameter was 10-20 mm in 27, 20-50 mm in 13, and > 50 mm in 1. Imaging features of MVI were present in 29/41 nodules (70.7%, CI: 54-84), even in 17/29 nodules with 10-20 mm diameter (58.6%, CI: 39-76). MVI was present in only 17/51 HCC nodules that occurred before DAA treatment (33.3%, CI: 22-47) (p= 0.0007). MVI did not correlate with history of previous HCC. HCC occurs rapidly after DAA therapy, and aggressive features of MVI characterise most neoplastic nodules. Close imaging evaluations are needed after DAA in cirrhotic patients. • In HCV cirrhosis, hepatocellular carcinoma develops soon after direct-acting antiviral therapy. • HCC presents imaging features of microvascular invasion, predictive of more aggressive progression. • Cirrhotic patients need aggressive and close monitoring after direct-acting antiviral therapy.

Chronic Hepatitis C-Related Cirrhosis Hospitalization Cost Analysis in Bulgaria.

HCV infection is a leading cause of chronic liver disease with long-term complications-extensive fibrosis, cirrhosis, and hepatocellular carcinoma. The objective of this study is to perform cost analysis of therapy of patients with chronic HCV-related cirrhosis hospitalized in the University Hospital "Queen Joanna-ISUL" for 3-year period (2012-2014). It is a prospective, real life observational study of 297 patients with chronic HCV infection and cirrhosis monitored in the University Hospital "Queen Joanna-ISUL" for 3-year period. Data on demographic, clinical characteristics, and health-care resources utilization (hospitalizations, highly specialized interventions, and pharmacotherapy) were collected. Micro-costing approach was applied to evaluate the total direct medical costs. The points of view are that of the National Health Insurance Fund (NHIF), hospital and the patients. Collected cost data are from the NHIF and hospitals tariffs, patients, and from the positive dug list for medicines prices. Descriptive statistics, chi-squared test, Kruskal-Wallis, and Friedman tests were used for statistical processing. 76% of patients were male. 93% were diagnosed in grade Child-Pugh A and B. 97% reported complications, and almost all developed esophageal varices. During the 3 years observational period, patients did not change the critical clinical values for Child-Pugh status and therefore the group was considered as homogenous. 847 hospitalizations were recorded for 3 years period with average length of stay 17 days. The mortality rate of 6.90% was extremely high. The total direct medical costs for the observed cohort of patients for 3-year period accounted for 1,290,533 BGN (€659,839) with an average cost per patient 4,577 BGN (€2,340). Statistically significant correlation was observed between the total cost per patient from the different payers' perspective and the Child-Pugh cirrhosis score. HCV-related cirrhosis is resource demanding and sets high direct medical costs as it is related with increased hospitalizations and complications acquiring additional treatment.

Non-neoplastic Portal Vein Thrombosis in HCV Cirrhosis Patients: is it an Immuno-Inflammatory Disorder?

Background and aimsPortal vein thrombosis (PVT) is a critical complication in cirrhotic patients. We explored the role of the activated factor VII-antithrombin (FVIIa-AT) complex and enhanced monocytic tissue factor (TF) expression in the development and prediction of non-neoplastic PVT in cirrhotic patients. Material and methodsA total of 30 HCV-cirrhosis patients were included in our study. They were compared to 35 cirrhotic patients without PVT, 15 non-cirrhotic patients with PVT, and 15 healthy controls. The plasma level of the FVIIa-AT complexes was analyzed by ELISA. MIF CD142, CD86, and HLA-DR on monocytes (CD14) were determined by flow cytometry. ResultsCompared with cirrhotic patients without PVT, cirrhotic patients with PVT had comparable plasma values of FVIIa, AT, and the FVIIa-AT complex. However, they had significantly lower values compared to non-cirrhotic patients with PVT and healthy controls. Cirrhotic patients with PVT had increased monocytic TF expression (MIF CD142) compared to non-PVT cirrhotic patients and healthy controls [86.5 (93.5) vs. 18 (32.0) and 11.0 (6.0), respectively; p < 0.001 for each]. However, cirrhosis PVT could not be distinguished from non-cirrhosis PVT. The area under the ROC curve of MIF CD142 was 0.759 (0.641-0.876; p = 0.000) at an optimal cut-off value of 45, which yielded a sensitivity of 60% and a specificity of 77.1%, as well as a PPV and NPV of 69.2% for each. ConclusionEnhanced expression of monocytic TF may have a role in the development and prediction of non-neoplastic PVT in HCV-cirrhosis patients. Large multicenter studies are necessary to validate our results.

Dynamics of Liver Stiffness Values by means of Transient Elastography in Patients with HCV Liver Cirrhosis undergoing Interferon Free Treatment

Liver stiffness (LS) measurement by Transient Elastography (TE) has been widely accepted as a tool for fibrosis assessment. The aim of this study was to assess LS dynamics in a group of patients with HCV liver cirrhosis after interferon free treatment (IFT). This two-center clinical trial included 225 patients with compensated HCV cirrhosis (all genotype 1b), who received IFT for 12 weeks. All patients were evaluated by means of TE at the beginning and at the end of treatment (EOT), and a subgroup (170 patients) also 12 weeks after EOT; all of them had sustained viral response (SVR). Reliable LS measurements (LSM) were defined as a median value of 10 valid LSM, with IQR <30% and SR >/=60%. Both M and XL probes were used. For diagnosing cirrhosis we used a cut-off value of 12kPa as proposed by the Tsochatzis meta-analysis. We considered a decrease or increase of more than 10% in LSM as being significant. Out of 225 subjects, reliable measurements were obtained in 93.7%, so that the final analysis included 211 patients. The mean LS values decreased significantly after IFT: 26.4+/-11.7 vs. 23.5+/-13.3 kPa (p=0.01). Most patients, 59.2% (125/211) presented more than 10% decrease in LS values, 24.1% (51/211) had stable LS values, while in 16.4% (35/211) cases, the LS values increased. In the subgroup of 170 patients with LSM also performed 12 weeks after EOT (SVR), the mean LS values were significantly lower as compared to baseline: 21.3+/-11 kPa vs. 27.4+/-11.9 kPa (p<0.0001) and also as compared to EOT: 21.3+/-11 kPa vs. 23.7+/-13.3 kPa (p<0.0001). In our patients with HCV liver cirrhosis, the mean LS values evaluated by TE significantly decreased after antiviral treatment at EOT and also 12 weeks after EOT as compared to baseline. Overall, about 60% of patients had LS values at EOT lower than at baseline, while 12 weeks after EOT about 75% of patients had LS values lower than at baseline.

Su1490 - Real Life Experience with Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir and Ribavirin Regimen in Patients with Compensated HCV Cirrhosis

Su1490 - Real Life Experience with Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir and Ribavirin Regimen in Patients with Compensated HCV Cirrhosis

Non-invasive tools to ruling out large varices: RESIST-HCV vs Baveno VI criteria in a large cohort of patients with HCV cirrhosis

Background: Patients with cirrhosis should undergo to endoscopic variceal screening to identify large esophageal varices (LEV-F2/F3) requiring primary prophylaxis. Recently, Baveno VI consensus suggested criteria to avoid esophagogastroduodenoscopy (EGD) in patients with liver stiffness by Transient elastography (TE) 150,000/mm3.