Hepatitis C Virus Related Cirrhosis Research Articles

Pretreatment Predictors Associated with Improvement in Hepatitis C Virus Related Decompensated Cirrhosis after Direct-Acting Antiviral Therapy

Background and Aim: The availability of hepatitis C virus (HCV) direct-acting antivirals (DAAs) has led to a paradigm change in the care of HCV related decompensated cirrhosis. Achieving a stained virologic response (SVR) is associated with considerable improvements in both Child-Turcotte- Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores in decompensated cirrhosis. We aimed to evaluate the pretreatment predictors associated with improvement in CTP B cirrhosis after DAAs and evaluate the efficacy and safety of DAAs in these patients.
 Patients and Methods: A prospective study conducted on 213 decompensated patients (CTP B, 134 received DAAs for 24 weeks and 79 for 12 weeks). Clinical and laboratory data obtained at baseline, during treatment, 12 weeks after end of treatment (EOT), 36 weeks after treatment start, and 24 weeks after SVR.
 Results: We had 48.4 % and 55.9 % had improved to CTP A at 36 weeks of treatment start and 24 weeks after SVR respectively. A high baseline BE3A score (which includes Body mass index (BMI), Encephalopathy, Ascites, Alanine aminotransferase (ALT) and Albumin) was the significant predictor of attaining CTP A at 36 weeks of treatment start, while high baseline ALT (> 60 IU/L) was the significant predictor of attaining CTP A at 24 weeks after SVR. SVR 12 achieved in 97.3% and DAAs were safe with mild tolerable adverse events.
 Conclusion: High baseline ALT and BE3A score were the significant predictors of hepatic improvement from CTP B to CTP A after DAAs. HCV DAAs were safe and effective with high SVR rates (97.3%) in decompensated cirrhosis.

Dynamics of liver stiffness predicts complications in patients with HCV related cirrhosis treated with direct-acting antivirals

BackgroundDirect acting antivirals(DAAs) are effective in reducing inflammatory ant fibrotic markers in patients with chronic hepatitis C virus(HCV) infection and to prevent liver-related complications. Two-dimensional shear wave elastography(2D-SWE) is an effective technique for the assessment of liver fibrosis. AimTo evaluate changes in liver stiffness(LS) in HCV cirrhotic patients undergoing DAA therapy and to identify non-invasive parameters that predict the occurrence of liver-related events. MethodsWe enrolled 229 patients who received DAAs between January 2015 and October 2018. Ultrasound parameters and laboratory data were assessed before treatment and 24(T1) and 48(T2) weeks after end of treatment. Patients were followed up every 6 months to evaluate the development of HCC and other liver related complications. Multiple Cox regression analysis was used to determine parameters associated with the development of complications. ResultsModel for End-stage Liver Disease(MELD) score(HR 1.16; CI 95% 1.01–1.33; p = 0.026) and a change in LS at T2(1-year Delta LS) < 20%(HR 2.98; CI 95% 1.01–8.1; p = 0.03) were independently associated with HCC risk. One-year Delta-LS <20% was independently associated with the development of ascites(HR 5.08; CI 95% 1.03 - 25.14; p = 0.04). ConclusionsDynamic changes of 2D-SWE-measured LS after DAA therapy may be a useful tool to identify patients who are at higher risk of liver related complications.

Global incidence and mortality of hepatitis B and hepatitis C acute infections, cirrhosis and hepatocellular carcinoma from 2010 to 2019.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) contribute to significant healthcare burden globally. We aim to provide an updated and comprehensive analysis of global trends in the incidence and mortality of HBV and HCV related acute infections, cirrhosis and hepatocellular carcinoma (HCC). Estimates of annual cause-specific disease incidence and mortality for HBV and HCV were analysed using the 2010-2019 Global Burden of Diseases, Injuries and Risk Factors Study database. Three distinct disease states were evaluated: acute infections, cirrhosis and HCC. Age-standardized disease incidence and mortality were presented per 100,000 population and stratified by age, sex, year and 21 world regions. From 2010 to 2019, overall incidence of acute HBV declined by 19.3% (95% CI 4.1-32.0, p<.05) and HBV cirrhosis declined by 15.0% (95% CI 9.8-20.7, p<.05). Incidence of HCV cirrhosis increased by 5.6% (95% CI 0.3-10.2, p<.05) and HCV HCC remained stable. Incidence of acute HCV declined until 2015, after which it began increasing. From 2010 to 2019, overall mortality for HBV cirrhosis and HCV cirrhosis declined, whereas mortality for acute infections and HCC remained stable. Major differences in HBV and HCV incidence and mortality trends were observed when stratified by world regions. In conclusion, while our analyses of global trends in HBV and HCV incidence and mortality demonstrate encouraging trends, disparities in disease epidemiology were observed across world regions. These observations will identify regions and populations where greater focus and resources are needed to continue progressing towards viral hepatitis elimination.

Combination of Albumin-Bilirubin Grade and Platelet Count as a Predictor of Esophageal Varices’ Presence and Grading in Egyptian Patients with HCV Related Cirrhosis

Background: Screening guidelines recommend that all patients who are newly diagnosed with cirrhosis should be screened for esophageal varices (EV). This study aimed at predicting the presence of esophageal varices among Egyptian hepatitis C cirrhotic patients by a combination of albumin-bilirubin grade and platelet count score (ALBI-Platelet score). Methods: This study was performed on 150 cirrhotic patients. Eighty- seven patients with hepatitis C virus (HCV) related cirrhosis and esophageal varices formed Group (A), while Group (B) consisted of sixty-three patients with HCV related cirrhosis and no esophageal varices. Full metabolic profile, Complete blood count (CBC), ultrasonography, and endoscopy were done. Results: There was a significant difference between studied groups regarding serum bilirubin, serum albumin and platelet count. The cutoff point of platelets count as a predictor for esophageal varices among studied groups was &lt;154.5. The cutoff value for albumin-bilirubin (ALBI) score as a predictor for esophageal varices of any size was -1.67 with 52.9% sensitivity, 59.6% specificity, 47% negative predictive value (NPV) and 64% positive predictive value (PPV). The ALBI-Plt score &gt;3 had 42.5%, specificity 63.5%, negative predictive value 40% and positive predictive value 65%. The cutoff value for the ALBI score representing large-sized esophageal varices was -1.27. The ALBI-Plt score &gt;4 for large-sized varices had sensitivity 61.9%, specificity 55%, negative predictive value 59%, positive predictive value 50%. Conclusion: ALBI-Platelet score is a non-costly, readily available and reliable new non-invasive predictor of the presence of EV that could easily be used in screening for the presence of esophageal varices and risky large-sized esophageal varices in cases of hepatitis C Virus related hepatic cirrhosis, lessening the need for endoscopic screening.

Combination of Albumin-Bilirubin Grade and Platelet Count as a Predictor of Esophageal Varices’ Presence and Grading in Egyptian Patients with HCV Related Cirrhosis

Background: Screening guidelines recommend that all patients who are newly diagnosed with cirrhosis should be screened for esophageal varices (EV). This study aimed at predicting the presence of esophageal varices among Egyptian hepatitis C cirrhotic patients by a combination of albumin-bilirubin grade and platelet count score (ALBI-Platelet score). Methods: This study was performed on 150 cirrhotic patients. Eighty- seven patients with hepatitis C virus (HCV) related cirrhosis and esophageal varices formed Group (A), while Group (B) consisted of sixty-three patients with HCV related cirrhosis and no esophageal varices. Full metabolic profile, Complete blood count (CBC), ultrasonography, and endoscopy were done. Results: There was a significant difference between studied groups regarding serum bilirubin, serum albumin and platelet count. The cutoff point of platelets count as a predictor for esophageal varices among studied groups was &lt;154.5. The cutoff value for albumin-bilirubin (ALBI) score as a predictor for esophageal varices of any size was -1.67 with 52.9% sensitivity, 59.6% specificity, 47% negative predictive value (NPV) and 64% positive predictive value (PPV). The ALBI-Plt score &gt;3 had 42.5%, specificity 63.5%, negative predictive value 40% and positive predictive value 65%. The cutoff value for the ALBI score representing large-sized esophageal varices was -1.27. The ALBI-Plt score &gt;4 for large-sized varices had sensitivity 61.9%, specificity 55%, negative predictive value 59%, positive predictive value 50%. Conclusion: ALBI-Platelet score is a non-costly, readily available and reliable new non-invasive predictor of the presence of EV that could easily be used in screening for the presence of esophageal varices and risky large-sized esophageal varices in cases of hepatitis C Virus related hepatic cirrhosis, lessening the need for endoscopic screening.

Predictive Role for Serum Aldo-Keto Reductase Family1 Member B10 for Early Detection of Hepatocellular Carcinoma in Egyptian Patients

Background: Most patients with hepatocellular carcinoma (HCC) are diagnosed at late stages despite of improvement screening programs and lack of effective diagnostic methods for cases with preclinical HCC leads to a low rate of early detection. Aldo-keto reductase family 1 member B10 (AKR1B10) is associated with several types of cancer. However, to our knowledge, the diagnostic significance of AKR1B10 measurement in early stage of HCC has poorly understood.&#x0D; Aim&#x0D; To evaluate the diagnostic performance of serum AKR1B10 in hepatitis C virus (HCV)-related liver disorders and its unique role in diagnosing HCC.&#x0D; Methods&#x0D; Serum AKR1B10 was detected by sandwich ELISA in 30 patients with HCV-related HCC, 30 patients with HCV related liver cirrhosis, and 20 healthy controls. Both Serum AKR1B10 and α-fetoprotein (AFP) levels were analyzed, evaluated and compared.&#x0D; Results&#x0D; Serum AKR1B10 was significantly elevated in patients with HCC compared with. The sensitivity (86.7.0%) and specificity (70%) for HCC diagnosis with AKR1B10 were high at a cutoff value of 0.945 ng/ml, while alpha fetoprotein had sensitivity 67% and specificity 88% in early detection of HCC among studied groups at cutoff point higher than 17.9. ng/ml. Furthermore, concurrent measurement of Alpha fetoprotein and AKR1B10 had increased sensitivity to 97.6% and specificity 100% in early detection of HCC among studied groups at cutoff point higher than ≥150 ng/ml. Furthermore, concurrent measurement of serum AKR1B10 and AFP significantly increased sensitivity and negative predictive value for HCC diagnosis.&#x0D; Conclusions&#x0D; we concluded in the current study that AKR1B10 has a unique role as a biomarker for early-stage HCV-related HCC. Compared with AFP alone, a combination of serum AKR1B10 and AFP had an increased the diagnostic performance in patients with HCC.

Prevalence, clinical characteristics and related mortality of cirrhosis in a tertiary hospital setting in Sub Saharan Africa

Background: Published data on the prevalence and mortality associated to cirrhosis is rare in Cameroon. The aim of this study was to determine the prevalence, clinical and para clinical characteristics and associated mortality of cirrhosis at the Yaounde University Teaching Hospital (YUTH), Cameroon. Methods: Files of patient’s followed up or admitted for cirrhosis at the YUTH between June 1st 2016 and June 30th 2018 were reviewed. The diagnosis of cirrhosis was made based on clinical, biological, ultrasonographic and/or endoscopic signs of portal hypertension and chronic liver failure. In other to establish the cause of cirrhosis, markers of documented chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) was sought in the file of the patients and if not present, hepatitis C antibody and hepatitis B surface antigen testing were requested. In patients negative for HBV and HCV markers, alcohol intake was considered as a cause of cirrhosis in someone who have been consuming more than 30 g/day (for males) or more than 20 g/day (for females) of alcohol. Data analyses were performed using Epi info V 3.5.4. Results: During the period of study, 1748 patients were admitted in the internal medicine unit among which 117 had cirrhosis giving a prevalence of 6.7%. There were 67 males (57.3%) and 50 females (42.7%). The mean age of patients was 51 +/- 19.862 years. Patients with HCV related cirrhosis were older (mean age: 68years) than those with HBV induced cirrhosis (mean age: 38years). The most frequent signs were ascites 104 patients (88.9%), asthenia 92(78.6%), hepatomegaly 68(58.1%), jaundice 61(52.1%), abdominal distension 54(46.2%) and gastrointestinal bleeding 29(24.8%). Anaemia was present in 58 patients (49.6%), thrombocytopenia in 56 patients (47.9%), low prothrombine time in 64 patients (54.7%). Mean serum albumine was 27.59 g/l (6-70), mean total bilirubine 49.41mg/l (3-275mg/l), mean AFP 75693 mg/ml (0.8-1578022). Spontaneous bacterial peritonitis was found in 21 patients (17.9%) Performed in 30 patients (25.6%), upper digestive endoscopy showed oesophageal varices in 27 patients (90%), hypertensive gastropathy in 17 patients (56.7%) and an ulcer in 3 patients (10%). Found in 47 patients (40.2%), HBV infection was the most frequent cause of cirrhosis followed by chronic HCV infection in 43 cases (36.8%) and alcohol intake in 26 patients (22.2%). The most frequent Child-Pugh class was C in 32 patients (48.5%) followed by Child-Pugh B and A in 26 patients (39.4%) and 8 patients (12.1%) respectively. Mortality rate was estimated at 20.5% (24 patients) and death was attributed to hepatic encephalopathy in 19 patients, gastrointestinal bleeding in 3 patients and spontaneous bacterial peritonitis in 2 patients. Conclusion: Liver cirrhosis is frequent in our setting, mostly diagnosed on advanced stages with complications. The most common causes are viral hepatitis B and C. The mortality rate is high.

MicroRNA 122 as adiagnostic biomarker for hepatitis C- related hepatocellular carcinoma

Aim: To explore the potential usefulness of serum microRNA(miR-122) as non-invasive diagnostic marker for hepatitis C virus(HCV)-related hepatocellular carcinoma (HCC). Methods: Thestudy has been conducted on 100 participants and were divided into 4equal groups: Group I; Twenty five normal, healthy individuals. ageand gender-matched healthy volunteers (control group). Group II;Twenty five chronic HCV patients without cirrhosis. Group III;Twenty five HCV related cirrhosis without HCC. Group IV; Twentyfive HCV-related HCC (proved radiologically by abdominal ultrasonography(US) & Triphasic abdominal computed tomography (CT). Allparticipants underwent full clinical assessment and laboratoryinvestigations in addition to the evaluation of the level of serum miR-122 by RT-PCR. Results: microRNA-122 displayed significant foldincrease in expression level in chronic hepatitis group (9.85), and lesssignificant fold increase in cirrhosis group (3.73) and significantfold increase in expression level in HCC group (7.46). Comparingserum miR-122 expression level between different studied groupsdisplayed that, No significant fold change in miR-122 expressionwas found between different groups and that miRNA122 had nosignificant up-regulation in HCC patients in comparison to non-HCCpatients (Hepatitis and Cirrhosis); (P value = 0.682). Specificity &sensitivity was 94% & 16% respectively, with AUROC (0.529).Conclusion: miR-122 could not be used as a biomarker for earlydetection of HCC in HCV related cirrhosis.

L-Carnitine Supplementation During Hepatitis C Virus Treatment with Sofosbuvir/Daclatasvir Plus Ribavirin: Effect on Anemia: A Pilot Study

AbstractBackground: In the direct acting antiviral era, the role of ribavirin (RBV) in the treatment of hepatitis c virus (HCV) remains crucial, especially in patients with liver cirrhosis and treatment experienced patients. L-carnitine was reported to improve anemia in patients with HCV treated with interferon alone or with ribavirin.Aim of Study: To evaluate the effect of L-carnitine on improving ribavirin induced hemolytic anemia in patients with HCV treated with sofosbuvir/daclatasvir plus ribavirin (SOF/DCV/ RBV).Patients and Methods: Naive patients with HCV related liver cirrhosis and treatment experienced patients who received prior interferon therapy were randomized to receive either SOF/DCV/RBV plus L-carnitine (n=49) or SOF/DCV/RBV (n=49) for 12 weeks as a control group. Changes in hemoglobin concentration, reduction of ribavirin dose and its effect on sustained virological response (SVR) were evaluated.Results: After 4 and 12 weeks of treatment, the hemoglobin concentration was significantly higher in the L-carnitine group than in the control group (p<0.001). RBV dose was reduced in 10.2% of patients in the L-carnitine group versus 22.5% in the control group. The adherence of patients to their ribavirin dose was higher in patients treated with L-carnitine than patients in the control group (89.8% vs. 77.5%). SVR12 rate in the L-carnitine group was higher than that in the control group (93.9%% vs. 87.8%).Conclusion: L-carnitine is effective in improving hemo-lytic anemia induced by ribavirin in patients treated for hepatitis C virus and increase patient's adherence to treatment that guarantees the best opportunity to achieve an SVR.

Hepatitis C virus related cirrhosis decreased as indication to liver transplantation since the introduction of direct-acting antivirals: A single-center study.

AIMTo evaluate waiting list (WL) registration and liver transplantation (LT) rates in patients with hepatitis C virus (HCV)-related cirrhosis since the introduction of direct-acting antivirals (DAAs).METHODSAll adult patients with cirrhosis listed for LT at Padua University Hospital between 2006-2017 were retrospectively collected using a prospectively-updated database; patients with HCV-related cirrhosis were divided by indication for LT [dec-HCV vs HCV/ hepatocellular carcinoma (HCC)] and into two interval times (2006-2013 and 2014-2017) according to the introduction of DAAs. For each patient, indications to LT, severity of liver dysfunction and the outcome in the WL were assessed and compared between the two different time periods. For patients receiving DAA-based regimens, the achievement of viral eradication and the outcome were also evaluated.RESULTSOne thousand one hundred and ninty-four [male (M)/female (F): 925/269] patients were included. Considering the whole cohort, HCV-related cirrhosis was the main etiology at the time of WL registration (490/1194 patients, 41%). HCV-related cirrhosis significantly decreased as indication to WL registration after DAA introduction (from 43.3% in 2006-2013 to 37.2% in 2014-2017, P = 0.05), especially amongst dec-HCV (from 24.2% in 2006-2013 to 15.9% in 2014-2017, P = 0.007). Even HCV remained the most common indication to LT over time (289/666, 43.4%), there was a trend towards a decrease after DAAs introduction (from 46.3% in 2006-2013 to 39% in 2014-2017, P = 0.06). HCV patients (M/F: 43/11, mean age: 57.7 ± 8 years) who achieved viral eradication in the WL had better transplant-free survival (log-rank test P = 0.02) and delisting rate (P = 0.002) than untreated HCV patients.CONCLUSIONIntroduction of DAAs significantly reduced WL registrations for HCV related cirrhosis, especially in the setting of decompensated cirrhosis.

Impact of IL-27p28 (rs153109) and TNF-α (rs1800629) Genetic Polymorphisms on the Progression of HCV Infection in Egyptian Patients

ABSTRACTBackground: Hepatitis C virus (HCV) is a universal health problem. HCV infection may proceed to liver fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). The latest is the third leading global cause of cancer-related mortality. Cytokines including IL-27 and TNF-α play a major role as a link between innate and adaptive immunity which in turn deduct the outcome of HCV infection.Aim: The present study examined the role of both (-964 A/G) single-nucleotide polymorphism (SNP) of IL-27p28 rs153109 and (-308 G/A) SNP of TNF-α rs1800629 on the progression of HCV infection in genotype 4a infected patients.Patients and Methods: The patients enrolled in the study were divided into three main groups group I: 38 fibrotic patients, group II: 51 cirrhotic patients, and finally group III: 29 HCC patients. Sixteen healthy volunteers were used as controls. IL-27p28 rs153109 and TNF-α rs1800629 genotyping were performed using polymerase chain reaction-restriction fragment length polymorphism assay.Results: There was no statistically significant difference between the studied groups regarding the IL-27p28 genotypes. However, TNF-α (-308) studied polymorphism showed a significant difference between the HCC and fibrosis group (p = 0.00), and also between the cirrhosis and fibrosis group (p = 0.031) revealing that AA genotype is the genotype of risk. Furthermore, the association found between allele frequencies of two studied SNPs and the four studied groups were non-significant.Conclusion: TNF-α rs1800629 polymorphism is a potential genetic-susceptibility factor for HCV related cirrhosis and HCC progression.

Analysis of Hepatitis C Virus NS5A Region in Patients with Cirrhosis Using an Ultra-Deep Pyrosequencing Method.

HCV (Hepatitis C Virus) is genetically more diverse than HBV and HIV (Human Immunodeficiency Virus) and exists as quasispecies within infected individuals. This is due to the lack of efficient proofreading of the viral RNA-dependent RNA polymerase. Consequently, quasispecies emerge depending on the mutation rate of the viral polymerase, which may display a high level of genetic variability in a population. In infected individuals, HCV replicates and circulates as quasispecies composed of a complex mixture of different but closely related genomes that undergoes continuous change due to competitive selection and cooperation between arising mutants. The aim of this study is to investigate mutations in the NS5A region as a whole, including ISDR, PKRBD, IRRDR, and V3 of HCV genotype 1b cirrhosis patients being naive and nonresponders, treated with IFN (interferon) + ribavirin (RBN) by using an ultra-deep pyrosequencing method (UDPS). During the study, five patients (four females, and one male, mean age 59.8 ± 11 years) with HCV related cirrhosis were analyzed. Three patients received IFN + RBN for six months, but two patients did not receive any therapy. HCV-RNA concentrations in patients' sera were determined using a COBAS AMPLICOR HCV MONITOR Test, Version 2.0. Genotyping was performed by using a commercial reverse hybridization method, Line Probe Assay. The quasispecies for the NS5A region were investigated using UDPS. All five patients were HCV genotype 1b (Mean Child-Pugh score 7.2 ± 1.9, 2 pts Child A, 2 pts Child B, and one pt Child C) but only one patient had hepatocellular carcinoma (HCC). A total of 19 different mutations were detected in each of the five patients (ranging from 3 to 6 mutations per patient). In all five patients, several mutations in the ISDR and PKR-BD regions were detected. On the other hand, mutations in the V3 and IRRDR regions were only detected in one patient. UDPS is a new sequencing technology and a very sensitive method in detection of quasispecies with low frequency NS5A region mutations. These mutations may affect the antiviral response and development of HCC. However, further studies in larger number of patients should be conducted to clarify this hypothesis.

Nutrition status and small intestinal bacterial overgrowth in patients with virus-related cirrhosis.

Malnutrition and small intestinal bacterial overgrowth (SIBO) is frequently present in patients with liver cirrhosis (LC). However, the direct relationship between SIBO and nutrition status in the LC patients has not been elucidated. The aim of this study was to investigate whether there was an association between nutrition status, evaluated by the subjective global assessment (SGA) and SIBO in patients with Hepatitis B virus (HBV) or hepatitis C virus (HCV) related cirrhosis. A total of 120 patients with HBV or HCV-related cirrhosis and 30 healthy controls were included. Nutritional status was determined according to SGA and anthropometry. All patients and healthy controls underwent a glucose hydrogen breath test for SIBO. The prevalence of malnutrition for the patients with HBV or HCV related cirrhosis ranged 19.4%-60% in China. The highest prevalence of malnutrition was detected by SGA, the lowest by triceps skinfold thickness. The frequency of SIBO was significantly higher in the malnourished (SGA-B/C) than in the well-nourished (SGA-A) patients with HBV or HCV related cirrhosis [41/72 (56.9%) vs 12/48 (25.0%) (p=0.001)]. Univariate analysis showed that SIBO, ascites, and Child-Turcotte-Pugh (CTP) class were associated with malnutrition. Multivariate analysis demonstrated that SIBO [odds ratio (OR) 8.10; p=0.002] and ascites (OR 4.56; p=0.022) were independently associated with the occurrence of malnutrition (SGA-B/C) in the same subjects. SIBO is independently related to the occurrence of malnutrition (SGA-B/C) in patients with HBV or HCV cirrhosis. We deduce that SIBO may play an important role in nutrition status in patients with HBV or HCV cirrhosis.

Abstract 3247: SAMe versus placebo for the reduction of serum AFP in patients with hepatitis C cirrhosis and moderately elevated AFP: A randomized, placebo-controlled, double-blind phase II trial

Abstract Background: Hepatocellular carcinoma (HCC) is a common complication of hepatitis C virus related cirrhosis (HCV-C). Alpha-fetoprotein (AFP) has been proposed as a biomarker of HCC risk. S-adenosylmethionine (SAMe) is a food supplement that has an excellent safety profile. The use of SAMe as a chemopreventive is based on abnormalities in methionine cycle (with decreased SAMe levels) in patients with cirrhosis, increased risk of HCC in experimental animals deprived of SAMe, and the prevention of liver cancer by SAMe administration in animal models of chemically-induced HCC. Methods: This was a prospective, randomized, placebo-controlled, double-blind phase IIb trial to determine if SAMe (up to 2.4 grams/day) for 24 weeks reduced serum AFP levels in patients with HCV-C. Inclusion criteria: lab evidence of HCV-C (platelet count &amp;lt;150,000/mm3), AFP 15-100 ng/mL (normal less than 9 ng/mL). Exclusion criteria: non-HCV liver diseases, decompensated HCV-C (MELD&amp;gt;15), or history of, or mass suspicious for HCC. Primary outcome was decline in AFP between week 0 and 24. Secondary outcomes: change in other HCC-related markers (des-gamma carboxyprothrombin, AFP-L3), blood tests for HCV RNA, SAMe metabolites, serum markers of oxidative stress, and quality of life. Results: A total of 110 patients were enrolled and 87 completed study. After the 24-week treatment, AFP declined among patients receiving SAMe (-1.9 ng/mL) and increased among patients receiving placebo (+5.9 ng/mL; p=0.16). Neither des-gamma carboxyprothrombin (DCP) nor AFP-L3 changed significantly with SAMe treatment. There were no significant differences in serum HCV RNA between groups. Blood levels of SAMe and S-adenosylhomocysteine (SAH) increased 3-5 fold among patients receiving SAMe and were unchanged in placebo group (p&amp;lt;0.01). Serum glutathione and methionine did not change significantly. Several components of quality of life improved among patients receiving SAMe. There were 5 serious adverse events in the placebo group and 7 in the SAMe group; none were attributable to SAMe. Conclusions: SAMe administration for 24 weeks in patients with HCV-C and elevated AFP did not decrease AFP significantly nor alter liver function. SAMe significantly increased serum SAMe and SAH levels, but did not alter serum glutathione level or serum markers of oxidative stress. Citation Format: Timothy Morgan, Frank L. Meyskens, John Hoefs, Ke-Qin Hu, Tarek Hassanein, Thomas D. Boyer, Neville R. Pimstone, Kathy Osann, Rachel Gonzalez, L M. Rodriguez. SAMe versus placebo for the reduction of serum AFP in patients with hepatitis C cirrhosis and moderately elevated AFP: A randomized, placebo-controlled, double-blind phase II trial. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3247. doi:10.1158/1538-7445.AM2014-3247

Change in composition of inflammatory infiltrate in the course of hepatitis C reinfection and concomitant acute rejection after orthotopic liver transplantation

Hepatitis C virus (HCV) reinfection occurs in almost all patients after orthotopic liver transplantation (OLT) for HCV related liver cirrhosis and presents serious therapeutic challenge for a transplant team. The reinfection is concomitant with other posttransplant complications that influence presentation of the disease. Microscopic histological examination of a liver biopsy specimen remains the standard diagnostic procedure. The aim of the study was to analyze the composition of inflammatory infiltrate in HCV reinfection and determine whether its features may help in the differentiation between HCV reinfection and acute rejection (AR). Seventy seven post-OLT liver biopsy specimens from patients after OLT for HCV related cirrhosis were examined. Characteristics of inflammatory infiltrate and changes in its composition related to a time interval between OLT and biopsy and concomitant AR were analyzed. Significant differences in the composition of inflammatory infiltrate between the analyzed time intervals between OLT and biopsy were found. In the group of patients with HCV reinfection and concomitant AR the infiltrate was significantly more extensive than in the patients with HCV reinfection alone with predominantly CD8+ and CD5+ lymphocytes responsible for this finding. Significant changes in inflammatory infiltrate contents were found depending on the time period between OLT and graft biopsies.

Outcomes after liver transplantation for combined alcohol and hepatitis C virus infection.

Alcohol abuse and chronic hepatitis C virus (HCV) infection are two major causes of chronic liver disease in the United States. About 10%-15% of liver transplants performed in the United States are for patients with cirrhosis due to combined alcohol and HCV infection. Data on outcomes on graft and patient survival, HCV recurrence, and relapse of alcohol use comparing transplants in hepatitis C positive drinkers compared to alcohol abuse or hepatitis C alone are conflicting in the literature. Some studies report a slightly better overall outcome in patients who were transplanted for alcoholic cirrhosis vs those transplanted for HCV alone or for combined HCV and alcohol related cirrhosis. However, some other studies do not support these observations. However, most studies are limited to a retrospective design or small sample size. Larger prospective multicenter studies are needed to better define the outcomes in hepatitis C drinkers.

Treatment of patients with HCV related cirrhosis: many rewards with very few risks.

Antiviral treatment of chronic hepatitis C virus (HCV) is aimed at the persistent eradication of the virus, the so-called sustained virological response (SVR), with the aim ultimately being to prevent the development of liver-related complications and improve patients' survival. Patients with HCV-related compensated cirrhosis are the group most likely to benefit from viral clearance, as several retrospective studies have shown liver complications rates to be positively modified by the achievement of a SVR. Whether these benefits rely on viral clearance or on the histological improvements seen following successful interferon (IFn)-based therapies has recently been a matter for debate, as studies have shown cirrhosis to regress in some patients with a SVR. Whatever the mechanisms, cirrhosis has the uncanny ability to be both a dominant indication for therapy, as well as one of the strongest baseline factors associated with reduced efficacy of any IFn-based regimen. This has led to the development of alternative treatment strategies, such as low dose pegylated IFn (PegIFn) monotherapy, that unfortunately has proven to be of limited efficacy. For this reason regimens able to clear the virus without relying on the broad antiviral effect of IFN are eagerly awaited.

Seroprevalence of anti-HAV among patients with chronic viral liver disease

To investigate the current seroprevalence of hepatitis A virus (HAV) antibodies in patients with chronic viral liver disease in Korea. We also tried to identify the factors affecting the prevalence of HAV antibodies. We performed an analysis of the clinical records of 986 patients (mean age: 49 ± 9 years, 714 males/272 females) with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection who had undergone HAV antibody testing between January 2008 and December 2009. The overall prevalence of IgG anti-HAV was 86.61% (854/986) in patients with chronic liver disease and was 88.13% (869/986) in age- and gender-matched patients from the Center for Health Promotion. The anti-HAV prevalence was 80.04% (405/506) in patients with chronic hepatitis B, 86.96% (20/23) in patients with chronic hepatitis C, 93.78% (422/450) in patients with HBV related liver cirrhosis, and 100% (7/7) in patients with HCV related liver cirrhosis. The anti-HAV prevalence according to the decade of age was as follows: 20s (6.67%), 30s (50.86%), 40s (92.29%), 50s (97.77%), and 60s (100%). The anti-HAV prevalence was significantly higher in patients older than 40 years compared with that in patients younger than 40 years of age. Multivariable analysis showed that age ≥ 40 years, female gender and metropolitan cities as the place of residence were independent risk factors for IgG anti-HAV seropositivity. Most Korean patients with chronic liver disease and who are above 40 years of age have already been exposed to hepatitis A virus.

Survival rates of early-stage HCV-related liver cirrhosis patients without hepatocellular carcinoma are decreased by alcohol

Although alcohol abuse is the most common cause of liver cirrhosis in the United States, the enhancing effects of alcohol on the long-term prognosis of hepatitis C virus (HCV) related liver cirrhosis has not been clarified. To investigate how alcohol abuse influences the prognosis of hepatitis virus related liver cirrhosis, we studied 716 Japanese patients. Cumulative survival and hepatocellular carcinoma (HCC) development rates were analyzed in alcohol abusive, cirrhotic patients with or without hepatitis virus infection. Patients who abused alcohol were younger (p<0.0001) than HCV infected, non-abusive patients. The overall survival rate among patients with alcoholic cirrhosis (Al group), HCV related cirrhosis (HCV group), and HCV infected + alcoholic cirrhosis (HCV + Al group), showed no significant differences, although the 10-year cumulative survival rate of Al group was the highest of the three groups. The HCC development rate of Al group was the lowest. In addition, alcohol abuse decreased the survival rates of HCV group in the early stage with no HCC (p = 0.0028). In conclusion, alcohol abuse might affect the progression of liver damage in HCV infected patients with liver cirrhosis in the early stage, although the influence of alcohol abuse on the long term prognosis seems to be rather small.

Liver stiffness measurement as a predictive tool of clinically significant portal hypertension in patients with compensated hepatitis C virus or alcohol‐related cirrhosis

Hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence and the severity of portal hypertension (PHT). Liver stiffness measurement (LSM) is a non-invasive method for liver fibrosis assessment. To assess the relationship between LSM and HVPG in patients with compensated cirrhosis related to hepatitis C virus (HCV) or alcohol and to define the performance and the best cut-off of LSM for the diagnosis of PHT in these patients. Between January 2004 and September 2006, we studied all the consecutive patients with compensated HCV or alcohol-related-cirrhosis referred for transjugular liver biopsy with HVPG measurement and LSM performed the same day. Ninety-two patients were eligible, 44 had HCV related-cirrhosis and 48 alcoholic cirrhosis. LSM was positively correlated to HVPG in both groups. The area under the receiver operating characteristic curve for the diagnosis of significant PHT was 0.76 +/- 0.07 in HCV patients (best cut-off at 20.5 kPa) and 0.94 +/- 0.03 (best cut-off at 34.9 kPa) in alcoholic patients. Liver stiffness measurement and HVPG were significantly correlated in patients with compensated cirrhosis because of HCV infection or alcohol. LSM could predict significant PHT in both these groups of patients with a higher cut-off and a better performance in alcoholic patients.