Hepatitis C-related Cirrhosis Research Articles

Survival benefits of adding simvastatin to standard therapy for secondary prevention of bleeding esophageal varices in patients with hepatitis C-related liver cirrhosis

BackgroundThe combination of endoscopic band ligation and beta-blockers is the standard of care treatment for secondary prevention of variceal bleeding; however, rebleeding still occurs with associated high mortality. Simvastatin (a lipid-lowering agent) was found to reduce portal hypertension and decrease hepatic fibrosis. This study aimed to assess the effect of adding simvastatin to the standard therapy to prevent variceal rebleeding and its impact on survival in patients with liver cirrhosis.ResultsThis single-center randomized controlled clinical trial included 80 patients with cirrhosis receiving the standard secondary prophylaxis for variceal bleeding composed of endoscopic variceal ligation and non-selective β-blockers (either propranolol or carvedilol). Two weeks after the first attack of hematemesis, patients were randomized into two groups: group I who received the standard therapy (40 patients) and group II who administered simvastatin (20 mg daily for 2 weeks and 40 mg daily after that). Patients were followed up for 1 year. The primary endpoints were rebleeding and overall survival. Thirty patients of group I completed the study while ten patients died during the follow-up period. The simvastatin group showed a significantly better overall 1-year survival (3 deaths during follow-up) compared to the control group (37/40, 92.5% vs. 30/40; 75%) (p-value 0.034); however, this was lacking in Child C patients. No similar difference was present in rebleeding rates between the two groups (5/40, 12.5% vs. 3/40, 7.5%) (p-value 0.456) in groups I and II, respectively.ConclusionsAdding simvastatin to the standard therapy in secondary prevention of variceal bleeding could be associated with survival benefits in patients with Child A and B cirrhosis, while was incapable of reducing rebleeding.

The expression of microRNA-331-3p and microRNA-23b3 in Egyptian patients with early-stage hepatocellular carcinoma in hepatitis C-related liver cirrhosis

BackgroundHepatocellular carcinoma and hepatitis C are strongly associated. The current work aimed to study the expression levels of microRNA-331-3p and microRNA-23b-3p as propable biomarkers for detecting liver cancer (HCC) at its early stages in patients with HCV-related liver cirrhosis. The current prospective study included two hundred participants, divided into three groups: group I, 100 patients with HCV-related liver cirrhosis; group II, 50 HCC patients at early stages; and group III, 50 apparentlyhealthy controls. All patients had routine laboratory workup and ultrasound hepatic assessment. Values of microRNA-331-3p and microRNA-23b-3p were measured by real-time quantitative PCR.ResultsLevels of miR-331-3p were significantly higher in HCC patients than in cirrhotic patients and controls (p < 0.001), while levels of miR-23b-3p were significantly lower in HCC patients compared to cirrhotics and controls (p < 0.001). ROC curve revealed that miR-23b-3p had 80% sensitivity and 74% specificity, miR-331-3p had 66% sensitivity and 61% specificity, and AFP had 64% sensitivity and 61% specificity of 61% in discrimination between HCC patients from controls.ConclusionSerum miR-23b-3p is a more effective predictor than miR-331-3p and AFP for the development of hepatocellular carcinoma in hepatitis C (HCV)-related cirrhotic patients.

Evaluation Transplantation of Bone-Derived Mesenchymal Stem Cell in the Patients with Hepatitis C-Related Liver Cirrhosis (Pi lot Study)

Introduction. Liver cirrhosis (LC) is the final stage in the progression of chronic diffuse diseases. As common, late stages of LC do not respond to conservative treatment methods, so liver transplantation is the most effective method at this stage. Widespread use of transplantation in clinical practice is due to serious obstacles: a shortage of donor organs, transplant rejection, complications during the operation and the postoperative period, as well as the high cost of such an intervention. We consider bone marrow stem cell transplantation as a potential treatment for liver cirrhosis and additional clinical trials for efficacy and safety.The aim of the study was to assess the efficacy and safety of intraparenchymal transplantation of autologous MSCs from the bone marrow for the treatment of patients with cirrhosis of the liver caused by the hepatitis C virus (HCV-LC).Materials and methods. A pilot open-label non-randomized prospective study with the inclusion of 6 patients with HCV-LP. Autologous MSCs were transplanted intraparenchymally into the liver tissue at the rate of 1x106/kg body weight — 1 ml at 5 points.Results. By 6 months after transplantation, there has been a decrease in the level of bilirubin (from 36,4 μmol/L to 27 μmol/L, p=0.03), MELD scores (from 11,5 to 8, p=0.035), and an increase in platelet levels by 3 months (from 83x109 / l to 124,6x109/l, p=0,031) and 6 months (up to 119,5x109/l, p=0,031). By 6 months after transplantation, there has been no statistically significant result in changing on points on the Child-Pugh scale (p=0,181), cytolysis indicators (maintaining elevated levels of ALT (p=0,062) and AST (p=0,844)), replicative activity of the virus (рreservation of HCV RNA in the blood) (p=0,219 ). Moreover, introduction of MSCs by 6 months after transplantation did not lead to resolution of liver cirrhosis and inflammatory infiltration according to light microscopy data, as well as to resolution of sinusoidal capillarization (p=0,586) and PCI transdifferentiation into myofibroblasts (p&gt;0,99) according to immunohistochemical studies. None of the procedures after the transplantation had an increase in body temperature, an increase in laboratory parameters, or changes in vital functions. One patient was admitted to hospital after 6 months. after MSC transplantation, deep vein thrombosis of the right leg was diagnosed.Conclusion. The positive effect of MSCs on the improvement of liver function was noted. There was no effect on the replicative activity of the virus. The continuing activity of the inflammatory process was observed. The used MSC transplantation technique is a safe procedure for patients with HCV-LC severity classes A and B and can be applied in clinical practice.

Vitamin D receptor gene polymorphisms and risk of hepatocellular carcinoma in hepatitis C-related liver cirrhosis

BackgroundHCV is a major risk factor for HCC; however, the exact mechanism of hepatocarcinogenesis is still not fully understood. Host genetic factors have been reported to play a significant role. Experimental studies support the tumor inhibitory effect of vitamin D on HCC cells. Several single nucleotide polymorphisms (SNPs) have been depicted in the vitamin D receptor (VDR) gene. We aimed to assess whether any of these polymorphisms could be significantly associated with increased risk of HCC.ResultsThis study was conducted on 76 patients with HCV-related liver cirrhosis (48 patients had HCC on top of cirrhosis, and the other 28 had liver cirrhosis only). All patients underwent full medical history assessment, clinical examination, laboratory investigations, abdominal ultrasonography, and genotyping of the VDR gene. HCC patients had a significantly higher frequency of ApaI CC genotype compared with those patients without HCC. There is no statistically significant difference between the studied groups at any TaqI genotypes, but the carriage of the ApaI CC genotype had a significant association with liver disease severity in both patients groups compared with ApaI CA/AA genotypes. The carriage of the ApaI CC genotype was an independent predictor for HCC in HCV-related liver cirrhosis.ConclusionsVDR ApaI polymorphism is significantly associated with the development of HCC; thus, ApaI CC genotype could be used as an important molecular marker to predict the risk of HCC in patients with HCV-related liver cirrhosis.

Outcome of hepatitis C-related liver transplantation in direct-acting antiviral era.

Hepatitis C virus (HCV) has become an easily treatable disease after the introduction of sofosbuvir-based direct-acting antiviral (DAA) regimens. This is a large single center experience of changing severity and outcome profile of HCV-related liver disease after availability of DAAs. A retrospective analysis of prospectively collected liver transplantation (LT) database of adults (age > 18years at the time of LT) was performed from June 2010 to July 2018. A total of 410 patients (including 26 co-infection with hepatitis B) underwent LT for hepatitis C-related decompensated cirrhosis and/or hepatocellular carcinoma (HCC) out of 1754 adult transplantation in the defined period. The study group comprised of 296 males and 114 females aged 52.1 ± 7.9years. HCV-related decompensated cirrhosis and/or HCC as indication of LT was present in 289/1016 (28.4%) during 2010-2014, which was reduced to 121/738 (16.3%) during2015-2018 (p = 0.000). The LT recipients for HCV-related cirrhosis had significantly lower Child's and model for end-stage liver disease (MELD) score during 2015-2018 as compared to that during2010-2014; Child's score was 7.9 ± 2.2 vs. 8.6 ± 2.1, p = 0.003; MELD scorewas 13.9 ± 5.3 vs. 17.1 ± 5.8, p = 0.000, respectively. There was a trend towards better survival in HCV patients during 2015-2018 as compared to that during 2010-2014. Significantly more patients had HCV RNA negative status before LT during 2015-2018 (38.8% vs. 13%, p = 0.000); moreover, the proportion of LT for decompensated cirrhosis (without HCC) decreased significantly in the latter period, 64.0% vs. 42.1% (p = 0.000). In the DAA era, HCV as an indication for LT has decreased and patients have less severe disease at transplantation. There is a trend towards better patient survival.

Population impact of direct-acting antiviral treatment on new presentations of hepatitis C-related decompensated cirrhosis: a national record-linkage study

ObjectivePopulation-based studies demonstrating the clinical impact of interferon-free direct-acting antiviral (DAA) therapies are lacking. We examined the impact of the introduction of DAAs on HCV-related decompensated cirrhosis (DC) through analysis...

Interleukin-18 polymorphism as a diagnostic tumor marker for hepatocellular carcinoma in patients with hepatitis C-related cirrhosis

BackgroundEgypt has the highest hepatitis C virus prevalence worldwide where about 24% of the people are estimated to carry HCV and more than 50% of blood donors have anti-HCV in some towns. The burden of hepatocellular carcinoma has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. Thus, the aim of the present study was to analyze the interleukin-18 single nucleotide polymorphisms (SNPs) as a diagnostic tumor marker for hepatocellular carcinoma in patients with hepatitis C-related cirrhosis.ResultsThis study included 33 hepatocellular carcinoma (HCC) complicating HCV-related cirrhosis patients, 37 cirrhotic patients without HCC (cirrhosis group), and 20 healthy individuals who were included as a control for 9 months of follow-up. SNPs of the IL-18 gene were genotyped by polymerase chain reaction. There was a statistically significant difference in the GG genotype in the HCC group in comparison with the control group (P = 0.04). There was a statistically significant difference in the G allele in the cirrhosis and HCC groups in comparison with the control group (p1 < 0.001 and p2 = 0.03, respectively). Patients with GC genotype have a risk for developing HCC by 6.33-folds more than those with GG genotype while patients with GC genotype have a risk for developing cirrhosis by 5.43-folds more than those with GG genotype, and cirrhotic patients with CC and GC genotype had a risk for developing HCC by 1.17-folds more than those with GG genotype.ConclusionOur findings revealed that the analysis of IL-18 single nucleotide gene polymorphism could be a valuable marker for the prediction of progress towards cirrhosis in chronic HCV patients and also to subsequent development of HCC in HCV cirrhotic patients proved by the results of both GG genotype and its G allele; also, cirrhotic patients with CC and GC genotype have a risk for developing HCC by 1.17-folds more than those with GG genotype.

Advanced Glycation End Products as a Predictor of Diabetes Mellitus in Chronic Hepatitis C-Related Cirrhosis.

Background and Aims: Advanced glycation end products (AGEs) were found to be involved in the pathogenesis of various disorders. Chronic hepatitis C virus infection is the major cause of liver cirrhosis development and glucose metabolism alteration. We aimed to explore the association of AGEs with the development of diabetes mellitus (DM) in patients with cirrhosis in this study.Methods: Only 144 of the 165 non-diabetic patients with cirrhosis were consecutively included in this prospective cohort pilot study, in addition to 72 healthy control subjects. Clinical data and biochemical parameters including basal insulin secretion and insulin sensitivity indices together with AGEs were evaluated in all participants at baseline and every 1 year thereafter for 2 years. Multivariable Cox regression analysis was used to determine the parameters that could predict the development of DM within this period.Results: DM developed in 14 (10%) patients only. Univariate Cox regression analysis showed that AGEs (P = 0.004), Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) (P = 0.018), HOMA-β (P = 0.015), and age (P = 0.012) were associated with DM. After adjusting multiple confounders, the multivariable Cox regression model showed that AGEs, HOMA-IR, and age were the strongest variables associated with DM (all P < 0.05). Using the receiver operating characteristic curve, AGEs at a cutoff value of more than 82.4 ng/ml had 99.23% specificity, 100% sensitivity, and 0.992 area under the curve (AUC) (all P < 0.001) for DM prediction.Conclusion: Our study suggests that AGEs are related to increased incidence of DM, especially in patients with cirrhosis, which is very promising in lowering the risk of DM in these patients.

Burden of Liver Cirrhosis in Portugal between 2010 and 2017

Introduction: Liver cirrhosis is a prevalent disease in Portugal. Recent changes in alcohol consumption, as well as the wide use of direct-acting antivirals for hepatitis C since 2015, may be contributing to changes in the national burden of liver cirrhosis in the last few years. Objectives: We aim to characterize the burden of cirrhosis in Portugal between 2010 and 2017. Patients and Methods: We analyzed all hospital admission episodes due to cirrhosis in Portugal Mainland between 2010 and 2017, registered in the national Diagnosis-Related Group database, according to etiology of cirrhosis. We also analyzed data on mortality and potential years of life lost from liver cirrhosis and chronic liver disease, retrieved from Statistics Portugal (National Institute for Statistics). Results: Between 2010 and 2017, a total of 51,438 admissions for liver cirrhosis occurred in Portugal. The annual number of admissions decreased (p = 0.044) during the analyzed period. The most frequent cause of cirrhosis was alcoholic liver disease, present in 78.9% of all admissions (n = 40,595), followed by chronic hepatitis C virus infection, present in 11.3% (n = 5,823). A male predominance was identified in the admissions for every analyzed cause of cirrhosis. Annual admissions for alcoholic cirrhosis remained stable (p = 0.075) during the 8-year period. The same stable tendency was observed in the number of admissions for cirrhosis caused by hepatitis C virus (p = 0.861) and alcohol plus hepatitis C virus infection (p = 0.082), although these admissions for hepatitis C-related cirrhosis increased until 2014–2015 and steadily decreased thereafter. Annual deaths due to liver cirrhosis and chronic liver disease decreased from 1,357 in 2010 to 1,038 in 2017 (p = 0.002). The number of potential years of life lost decreased as well in the period (p = 0.001). Conclusion: The burden of cirrhosis, evaluated by hospital admissions, mortality, and potential years of life lost, decreased in Portugal between 2010 and 2017.

S2469 A Rare Case of Hepatocellular Carcinoma With Isolated Recurrence to the Stomach

INTRODUCTION: Hepatocellular carcinoma (HCC) is the sixth-most common cancer worldwide and fourth leading cause of cancer-related mortality according to the WHO. It primarily metastasizes to the lungs, lymph nodes, and bones. Metastases of HCC to the gastrointestinal (GI) tract and specifically to the stomach are very infrequent. In this report, we present a unique case of HCC metastatic to the stomach. CASE DESCRIPTION/METHODS: A 61-year-old African-American (AA) female with hepatitis C-related cirrhosis complicated by HCC, originally diagnosed in 2015 and managed by partial hepatic resection. In April 2020, she underwent routine HCC surveillance imaging. MRI abdomen and pelvis (Figure 1) demonstrated no new liver lesions but was significant for an isolated 3.4 × 2.7 cm mass that was identified at the greater curvature of the stomach. She underwent upper endoscopy with endoscopic ultrasound revealing a 3.1 × 2.9 cm hypoechoic mass (Figure 2). Fine needle aspiration biopsy was performed, and pathology demonstrated an epithelioid mass compatible with HCC. Immunohistochemistry staining was positive for Cam5.2, glypican-3, and hepatocyte (partial) positive, confirming metastatic HCC. CT chest was negative for intrathoracic metastasis. The patient underwent partial gastrectomy in May 2020 given the isolated metastatic gastric lesion. Surgical pathology confirmed the diagnosis of moderately-differentiated metastatic HCC. DISCUSSION: We report a very rare case of metastatic HCC in an asymptomatic AA female, diagnosed on routine surveillance imaging for HCC. To our knowledge, this is the first reported case of HCC metastatic to the stomach in an African-American. Cases of HCC metastatic to the GI tract are exceedingly rare. The majority of cases of HCC with metastatic lesions in the stomach occur by direct extension rather than by hematologic dissemination. In documented cases, patients have presented most frequently with either iron deficiency anemia or abdominal pain. Almost all the reported cases have occurred in non-white individuals, and most have occurred in patients of East Asian ethnicities.Figure 1.: Greater curvature gastric mass.Figure 2.: EUS image of gastric mass.

A case of hepatitis C-related liver cirrhosis treated with lusutrombopag before coil embolization for splenic artery aneurysm

A case of hepatitis C-related liver cirrhosis treated with lusutrombopag before coil embolization for splenic artery aneurysm

Hepatitis C-related cirrhosis will be a marginal cause of hospital admissions by 2025

Complications of cirrhosis are the main cause of hospital admissions in liver units. In areas where HCV is prevalent, most of these admissions are attributable to HCV-related cirrhosis (HCV-cirrhosis). This study assessed the impact of direct-acting antivirals (DAA) in the profile of patients with liver disease admitted to a referral liver unit from a university hospital. We registered hospital admissions resulting from cirrhosis to the Liver Unit of the Hospital Clinic of Barcelona, from 2011 to 2014 (pre-DAA period) and from 2015 to 2019 (post-DAA period). From a total of 14,865 hospital admissions, 10,053 resulted from cirrhosis (corresponding to 6,272 patients). The number and proportion of hospital admissions because of HCV-cirrhosis remained stable during the period 2011-2014 (525 per year, 48.8% of the total), but decreased progressively after 2015 (p <0.001), reaching <300 (27.1%) admissions in 2019. Similarly, HCV-cirrhosis accounted for 3,885 inpatient days per year (44.9%) during the pre-DAA period and decreased steadily after 2015 (p >0.001), reaching only 1,909 inpatient days (22%) in 2019. The figures for intensive care unit admissions followed a similar pattern. By means of a slope analysis (binomial regression model), we predicted that HCV-cirrhosis hospital admissions will be residual by 2025 (2.3%, 95% CI 0-10.9%). By contrast, we observed a significant increase in hospital admissions because of metabolic-associated fatty liver disease (5-fold) and autoimmune hepatitis (4-fold) during the study period. In summary, our data showed a profound reduction in HCV-cirrhosis hospitalisation burden since 2015, coincident with the wide use of DAAs in Spain. Our predictions suggest that, by 2025, HCV-cirrhosis will be a marginal cause of hospital admissions for patients with liver disease. Over the past few years, the wide use of antiviral drugs that cure HCV has had a significant effect on patients being admitted to hospital. Most patients with HCV and cirrhosis are treated (and often cured) in the community and, thus, the number of hospital admissions because of severe forms of HCV has decreased drastically. HCV is no longer the first cause of admission into liver units and, in only a few years from now, it is likely to be only a residual cause of hospitalisation.

Albumin and Magnetic Resonance Imaging-Liver Volume to Identify Hepatitis C-related Cirrhosis and Esophageal Varices

Background: Liver cirrhosis is the 3rd leading cause of death globally, with increasing mortality rate worldwide portal hypertension is a frequent consequence in the progress of liver cirrhosis and plays a crucial role in the progression of the disease. One of the most serious complications of portal hypertension is the development of esophageal varices. Objective: To evaluate the changes in the liver lobes volume with that of albumin as non-invasive predictors of liver cirrhosis and esophageal varices. Patients and methods: One hundred cases are chosen and classified into four groups as 20 healthy as controls, 20 cases HCV without cirrhosis, 40 cases with cirrhosis but without varices, and 20 cirrhotic cases with varices. All participants undergo magnetic resonance imaging for liver lobes volume, biochemical analysis of serum albumin. All cirrhotic patients are exposed to upper gastro-intestinal endoscopy to differentiate cirrhotic with or without varices. Statistical analysis was done to determine the combination of liver lobes volume change together with albumin changes to predict the severity of cirrhosis and for esophageal varices. Results: RV, LMV, LLV, and albumin are significantly lower in cases of cirrhosis and LMV/albumin LLV/ALB, CV/Albumin shows a more significant difference in cirrhotics with varices. Conclusion: From the results of our study we conclude that MRI liver lobes volume and albumin are good predictors noninvasive markers of liver cirrhosis.

Study of glycated albumin to glycated hemoglobin ratio as a predictor of esophageal varices bleeding risk

Objectives To evaluate glycated albumin (GA) to glycated hemoglobin (HbA1c) ratio as a predictor of variceal bleeding in patients with liver cirrhosis. Background Variceal hemorrhage is a severe complication of liver cirrhosis and can be a direct cause of bleeding-related death. Therefore, upper endoscopy is considered necessary for all cirrhotic patients to evaluate the risk of variceal bleeding. Patients and methods A prospective clinical study was conducted on 100 patients with chronic hepatitis C-related cirrhosis who attended the Gastrointestinal Endoscopy Unit of the Department of Internal Medicine, Menoufia University hospitals, during the period between January 2017 and March 2018. Liver cirrhosis was diagnosed depending upon clinical examination in addition to laboratory and imaging studies. Various indicators for hepatic functions, HbA1c, and GA were measured. GA/HbA1c ratio was measured, and its relationship with the presence and bleeding risk of esophageal varices was analyzed. Results The GA/HbA1c ratio in hepatitis C virus (HCV)-positive cirrhotic patients increases with the severity of the esophageal varices. GA/HbA1c ratio may help in discrimination of low-risk from high-risk varices because GA/HbA1c ratio was the most significantly different among all of the other parameters tested; however, this is still doubtful. Conclusion Thrombocytopenia and prolonged prothrombin time parameters are associated with an increased risk of variceal bleeding. GA/HbA1c ratio in HCV-positive cirrhotic patients increases with the severity of the esophageal varices. GA/HbA1c ratio may help in discrimination of low-risk from high-risk varices. It is of interest and is not redundant to use the GA/HbA1c ratio to predict esophageal variceal bleeding risk in chronic HCV disease.

Albumin and Magnetic Resonance Imaging-Liver Volume to Identify Hepatitis C-related Cirrhosis and Esophageal Varices

Background: Liver cirrhosis is the 3rd leading cause of death globally, with increasing mortality rate worldwide portal hypertension is a frequent consequence in the progress of liver cirrhosis and plays a crucial role in the progression of the disease. One of the most serious complications of portal hypertension is the development of esophageal varices. Objective: To evaluate the changes in the liver lobes volume with that of albumin as non-invasive predictors of liver cirrhosis and esophageal varices. Patients and methods: One hundred cases are chosen and classified into four groups as 20 healthy as controls, 20 cases HCV without cirrhosis, 40 cases with cirrhosis but without varices, and 20 cirrhotic cases with varices. All participants undergo magnetic resonance imaging for liver lobes volume, biochemical analysis of serum albumin. All cirrhotic patients are exposed to upper gastro-intestinal endoscopy to differentiate cirrhotic with or without varices. Statistical analysis was done to determine the combination of liver lobes volume change together with albumin changes to predict the severity of cirrhosis and for esophageal varices. Results: RV, LMV, LLV, and albumin are significantly lower in cases of cirrhosis and LMV/albumin LLV/ALB, CV/Albumin shows a more significant difference in cirrhotics with varices. Conclusion: From the results of our study we conclude that MRI liver lobes volume and albumin are good predictors noninvasive markers of liver cirrhosis.

The Differential Influence of Cold Ischemia Time on Outcome After Liver Transplantation for Different Indications-Who Is at Risk? A Collaborative Transplant Study Report.

Introduction: Despite increasing awareness of the negative impact of cold ischemia time (CIT) in liver transplantation, its precise influence in different subgroups of liver transplant recipients has not been analyzed in detail. This study aimed to identify liver transplant recipients with an unfavorable outcome due to prolonged cold ischemia.Methods: 40,288 adult liver transplantations, performed between 1998 and 2017 and reported to the Collaborative Transplant Study were analyzed.Results: Prolonged CIT significantly reduced graft and patient survival only during the first post-transplant year. On average, each hour added to the cold ischemia was associated with a 3.4% increase in the risk of graft loss (hazard ratio (HR) 1.034, P < 0.001). The impact of CIT was strongest in patients with hepatitis C-related (HCV) cirrhosis with a 24% higher risk of graft loss already at 8–9 h (HR 1.24, 95% CI 1.05–1.47, P = 0.011) and 64% higher risk at ≥14 h (HR 1.64, 95% CI 1.30–2.09, P < 0.001). In contrast, patients with hepatocellular cancer (HCC) and alcoholic cirrhosis tolerated longer ischemia times up to <10 and <12 h, respectively, without significant impact on graft survival (P = 0.47 and 0.42). In HCC patients with model of end-stage liver disease scores (MELD) <20, graft survival was not significantly impaired in the cases of CIT up to 13 h.Conclusion: The negative influence of CIT on liver transplant outcome depends on the underlying disease, patients with HCV-related cirrhosis being at the highest risk of graft loss due to prolonged cold ischemia. Grafts with longer cold preservation times should preferentially be allocated to recipients with alcoholic cirrhosis and HCC patients with MELD <20, in whom the effect of cold ischemia is less pronounced.

Undefined/non-malignant hepatic nodules are associated with early occurrence of HCC in DAA-treated patients with HCV-related cirrhosis

An unexpected early increase in incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported (and refuted) in patients with HCV-related cirrhosis following direct-acting antiviral (DAA) treatment. To address this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients, with or without a history of HCC, undergoing DAA therapy. A total of 1,161 HCC-free cirrhotics (group 1) and 124 cirrhotics who had received a curative treatment for an HCC (group 2) were enrolled. Clinical features, including presence of undefined/non-malignant liver nodules (UNMNs), were analyzed with respect to HCC incidence and recurrence. During a median study time of 17 months in group 1 and 16 months in group 2, de novo HCC developed in 48 patients (yearly incidence 3.1/100 patient-years, 75% BCLC 0-A) and recurred in 40 (mean yearly incidence 29.9/100 patient-years, 83% BCLC 0-A). A peak of HCC instant incidence was observed at 4.2 months in group 1 patients with UNMNs, and at 7.7 months in group 2. By multivariable Cox regression models, UNMNs (hazard ratio [HR] 3.11; 95% CI 1.47-6.57: p= 0.003), ascites detected any time before enrolment (HR 3.04; 95% CI 1.23-7.51; p= 0.02), and alpha-fetoprotein log-value (HR 1.90; 95% CI 1.05-3.44; p= 0.03) were the variables independently associated with the incidence of de novo HCC, while history of alcohol abuse (HR 2.10; 95% CI 1.08-4.09; p= 0.03) and history of recurrence of HCC (HR 2.87; 95% CI 1.35-6.09; p= 0.006) were associated with HCC recurrence. An early high incidence of both de novo HCC, in patients with UNMNs, and recurrent HCC was observed in DAA-treated patients; this was not accompanied by increased tumor aggressiveness. This prospective study focuses on the risk of developing de novo or recurrent hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment in patients with hepatitis C-related cirrhosis. We found that DAA treatment was associated with an early high HCC incidence in patients with undefined or non-malignant nodules, as well as in those with a history of complete response to HCC treatment. Whether this is related to the presence of clinically undetectable nests of cancer cells or to precancerous lesions that may progress to overt HCC upon DAA treatment remains unanswered. No evidence of increased clinical aggressiveness was reported in de novo or recurrent HCC.

Laparoscopic left hepatectomy for HCC in a cirrhotic patient with right-to-left lobe volume shift

Presenter: Jaime Kruger MD | Hospital das Clinicas - University of Sao Paulo Background: Cirrhotic patients derive great benefit of laparoscopic liver resection, mostly related to reduced blood loss and fewer liver-related complications such as hepatic insufficiency, biliary fistula and ascites. Despite being the preferred method for cirrhotic patients, laparoscopic operations might prove difficult when facing a chronically diseased liver, which is in higher risk of blood loss, difficult transection associated with a fibrotic parenchyma and a distorted anatomy secondary to fibrotic and blood flow modifications induced by chronic inflammatory changes. Methods: Surgical technique video describing a laparoscopic left hepatectomy. A 71 years-old patient with hepatitis-C related cirrhosis was diagnosed with a 5 cm hepatocellular carcinoma on the left lobe. There were no signs of portal hypertension, liver function was Chil-Pugh class A/MELD 8. Chronic liver disease resulted in anatomic changes with predominant left-lobe corresponding to 60% of total liver volume. A totally laparoscopic left hepatectomy was performed utilizing 5 ports and a 10 mm 30 degree scope. Transection was carried out with a ultrasonic scalpel after classic hilar approach, dissecting individually arterial and portal venous elements. The left biliary duct was transected intraparenchymally with vascular stapler. Results: Operative time was 180 minutes and estimated blood loss was 100 milliliters. During postoperative recovery the patient developed transient renal disfunction managed conservatively and was discharged on the 7th POD. Pathology report confirmed a 51 mm HCCwith microvascular invasion and free margins (20 mm). Patient is disease-free 12 months after surgery. Conclusion: Chronic changes on the morphology of cirrhotic livers may increase difficulty of laparoscopic liver operations. Even in cases of altered anatomy minimally invasive resections should be pursued as those operations benefit cirrhotic patients and can be safely performed in specialized HPB centers with expertise in laparoscopic liver surgery.

Laparoscopic Right Hepatectomy In A Cirrhotic Patient: Anterior Approach And Extrafascial Pedicle Control

Presenter: Jaime Kruger MD | Hospital das Clinicas - University of Sao Paulo Background: Laparoscopic liver resections have gained progressive acceptance among liver surgeons. The second international consensus on minimally invasive liver operations indicated that major liver resections are increasingly being performed. Due to the complexity of such operations, most of them are performed in specialized tertiary academic centers. Along with the complexity of major resections, patient's characteristics such as liver cirrhosis may increase procedure difficulty and demand different approaches in order to successfully perform the operation. Methods: Video describing surgical technique for laparoscopic right hepatectomy. A 53 years-old male patient with hepatitis-C related cirrhosis was diagnosed with a right lobe hepatocellular carcinoma. The patient had normal liver function and no signs of portal hypertension. A totally laparoscopic right hepatectomy was performed, five ports were placed, a 10 mm 30 degree scope was used and pneumoperitoneal was set to 12 mmHg. Due to an enlarged an stiff liver an anterior approach was applied to avoid difficult mobilization and reduce hemodynamic stress. Pedicle was managed with an extrafascial extra hepatic approach and parenchymal transection was carried out with ultrasonic scalpel. Results: Operative time was 360 minutes, estimated blood loss was 500 mL, no blood transfusion was required. Patient was discharged from ICU on 1st POD and from hospital on the 7th POD. The patient developed transient liver insufficiency (5th POD total bilirubin 2.05 mg/dL) and was discharged with improving clinical and biochemical tests. Pathology report confirmed a moderately differentiated HCC, 80 mm in the largest diameter associated with satellite nodules and microvascular invasion. The patient recurred 12 months after resection and was managed with TACE, being alive 30 months after operation. Conclusion: Cirrhotic patients benefit from laparoscopic liver resection, which Results in lesser blood loss and fewer liver-related complications. Anterior approach allows less liver mobilization with theoretical benefits of less hemodynamic stress and fewer microscopic tumor spillage into venous circulation. Extrafascial pedicle control is an interesting technical option for tumors located far from the pedicle as it Results in complete control of the portal triad without prolonged hilar dissection.

Study of Dickkopf-1 (DKK-1) in patients with chronic viral hepatitis C-related liver cirrhosis with and without hepatocellular carcinoma

Aim of the studyDickkopf-1 (DKK-1) is a secreted protein which acts as an inhibitor of Wnt/β-catenin signaling. DKK-1 was found to be a helpful biomarker for many cancers including hepatocellular carcinoma (HCC). HCC is multifactorial in origin and its main etiology in Egypt is attributed to chronic hepatitis C virus (HCV) infection. Objectives: To assess the serum level and diagnostic performance of DKK-1 and α-fetoprotein (AFP) in Egyptian patients with chronic HCV-related liver cirrhosis with and without HCC.Material and methods80 subjects were divided into: a control group (group I, 20 healthy volunteers) and two patient groups: group II (HCV with liver cirrhosis, 30 patients), and group III, (HCV-related liver cirrhosis with HCC, 30 patients). Thorough physical examination, triphasic computed tomography, calculation of Child-Pugh score, laboratory investigations (complete blood picture, liver profile, hepatitis B surface antigen, anti-HCV antibodies, AFP (chemiluminometry) and DKK-1 (ELISA) were performed.ResultsThere was a significant decrease in DKK-1 level in HCV patients with liver cirrhosis (group II) and HCV patients with HCC (group III) compared to the control group (group I) (p < 0.001). However, there was a significant increase in DKK-1 level in HCV patients with HCC (group III) compared to HCV patients with liver cirrhosis (group II) (p < 0.033). The ROC curve showed that DKK-1 has less sensitivity but higher specificity in HCV patients with HCC (group III) compared with HCV patients with liver cirrhosis (group II).ConclusionsThe combination of DKK-1 and AFP could further improve the diagnostic accuracy of HCV-related cirrhosis with or without HCC.