Virus-related Cirrhosis Research Articles

Reduced risk of hepatocellular carcinoma by achieving a subcirrhotic liver stiffness through antiviral agents in hepatitis B virus-related advanced fibrosis or cirrhosis.

A subcirrhotic range of liver stiffness (sc-LS), assessed by transient elastography, is associated with better outcomes in patients with chronic hepatitis B (CHB). We investigated whether the achievement of sc-LS by antiviral therapy (AVT) reduced the risk of developing hepatocellular carcinoma (HCC) in patients with CHB-related advanced fibrosis or cirrhosis. In total, 209 patients with CHB-related advanced fibrosis or cirrhosis, who received paired transient elastography examinations during AVT between 2007 and 2012, were enrolled. The cut-off LS value for ultrasonographic cirrhosis was defined as 11.6kPa. The median age of the study population was 51years, with males predominating (n=138, 66.0%). The median LS value at enrollment was 14.1kPa (interquartile range: 9.5-24.1kPa). After 2years of AVT, 140 (67.0%) patients achieved sc-LS. During the study period, 28 (13.4%) patients developed HCC after 2years of AVT. On multivariate analysis, the achievement of sc-LS after AVT was independently associated with a decreased risk of HCC development (hazard ratio [HR]=0.485, P=0.047), whereas older age (HR=1.071) and male gender (HR=3.704) were independently associated with an increased HCC risk (both P<0.05). Patients with a cirrhotic range of LS value after 2years of AVT were at a higher risk of HCC development than those with sc-LS (log-rank test, P=0.020). The achievement of sc-LS after AVT can reduce the risk of HCC development in patients with CHB, even when advanced fibrosis or cirrhosis is apparent on starting AVT.

Hepatitis C virus eradication by direct antiviral agents improves glucose tolerance and reduces post-load insulin resistance in nondiabetic patients with genotype 1.

Genotype 1 chronic hepatitis C is associated with an impairment of glucose homoeostasis, especially in the advanced stages of the disease. Glucose tolerance is an independent predictor of liver-related mortality in patients with cirrhosis because of chronic hepatitis C. However, no study has demonstrated so far weather hepatitis C virus clearance affects glucose tolerance. To this aim, we performed a prospective study assessing the effects of direct antiviral agents treatment in nondiabetic cirrhotic patients with genotypes 1a/1b and impaired glucose tolerance based on a 75-g oral glucose tolerance test. Impaired glucose tolerance was diagnosed by a 2-hour plasma glucose between 140 and 199mg/dL. Insulin resistance was estimated by the oral glucose insulin sensitivity index, an oral glucose tolerance test-derived measure. After meeting the inclusion criteria, the study population included 32 outpatients (26/6 genotypes 1b/1a; age 62±7.4years; 18 males) with compensated Child-A cirrhosis. All patients achieved a sustained virological response following direct antiviral agents treatment. After viral eradication, we did not observe change in fasting plasma glucose (103.5±7.1 vs 102.8±7.2mg/dL, P=.15) but 2-hour plasma glucose was reduced (165.2±22.7 vs 138.5±21.3mg/dL, P<.001). Hepatitis C virus eradication led also to a significant reduction in HbA1c (6.1±0.2% vs 5.7±0.3%, P<.001) and post-load insulin resistance as assessed by the oral glucose insulin sensitivity index (6.92±1.56 vs 9.52±1.39mg/kg/min, P<.001). These effects were observed despite no change in body mass index from baseline to follow-up (25.6±4.3 vs 25.8±4.4, P>.5). Our results indicate that hepatitis C virus eradication may early improve glucose tolerance in patients with hepatitis C virus-related cirrhosis.

Albumin-Bilirubin Score Predicts Short-Term Mortality in Patients with Hepatitis B Virus-Related Decompensated Cirrhosis.

The albumin-bilirubin (ALBI) score is a new index for assessing the severity of liver dysfunction. Hepatitis B virus (HBV) related decompensated cirrhosis (HBV-DeCi) has a high short-term mortality rate. The purpose of this study was to elucidate the prognostic role of the ALBI score in patients with HBV-DeCi. This retrospective study included 81 patients who had been diagnosed with HBV-DeCi. All patients were followed up with for at least 2 months, and the relationships between prognosis and ALBI score were analysed. The ALBI score was positively correlated with the model for end-stage liver disease (MELD) score and Child-Turcotte-Pugh score. Moreover, non-surviving patients had a significantly higher ALBI score than surviving patients (-0.79 vs. -1.16, respectively; p = 0.001). Multivariate analysis suggested that the ALBI and MELD scores were independent predictors of 1-month mortality in HBV-DeCi patients (p < 0.05). The ALBI score is a simple biomarker to predict 1-month mortality in patients with HBV-DeCi and may assist physicians in determining treatment options.

Leukemic Pleural Effusion in Acute Promyelocytic Leukemia: A Case Report

In patients with acute myeloid leukemia (AML), pleural effusion may be attributed to various factors, including infection, hypoalbuminemia, and renal failure. However, leukemic infiltration of the pleural fluid is rarely reported and poorly understood. Extramedullary diseases have been reported with increasing frequency as the survival rates of patients with AML have increased. However, the reported prognostic effects of leukemic pleural effusion in patients with AML range from none to a worse prognosis. Here, we report a case of acute promyelocytic leukemia (APL) in a patient exhibiting leukemic pleural effusion with fluorescence in situ hybridization (FISH) results indicating the presence of the PML-RARA fusion gene. A 52-year-old man presented with pancytopenia, dyspnea, and fever. He had a medical history of hypertension, end-stage renal disease, and hepatitis B virus-related liver cirrhosis. A peripheral blood smear revealed the presence of multiple abnormally hypergranular promyelocytes. White blood cell differential counts were not performed due to severe pancytopenia. A bone marrow examination, immunophenotyping analysis, and cytogenetic and molecular studies revealed APL. The patient was treated with all-trans retinoic acid immediately after abnormal promyelocytes were observed in the peripheral blood smear, but induction chemotherapy was delayed because of his poor condition. His persistent dyspnea and abdominal discomfort led to a thoracentesis and the observation of abnormal promyelocytes that were positive for PML-RARA fusion gene by FISH. To our knowledge, this is the first report of leukemic pleural infiltration with PML-RARA fusion gene-positivity via FISH.

FABP1 Polymorphisms Contribute to Hepatocellular Carcinoma Susceptibility in Chinese Population with Liver Cirrhosis: A Case-Control Study.

Purpose: Single nucleotide variations in the liver fatty acid binding protein (L-FABP, FABP1) gene lead to changes in cellular signaling pathways and lipid metabolism. FABP1 polymorphisms were associated with some liver diseases, like steatotic hepatocellular carcinoma. However, the association between FABP1 rs1545224 and rs2241883 polymorphisms and hepatitis B virus-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC) has not been reported. We performed this study to explore their relationship.Methods: One thousand individuals (250 healthy controls, 250 chronic HBV (CHB), 250 LC, and 250 HCC patients) were recruited. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were applied to assess the difference in allele and genotype frequencies. Cochran-Armitage trend test was used to evaluate the cumulative effect. Significant difference would be defined when the P value was less than 0.05.Results: The distribution of rs1545224 GG, AG and AA genotypes in healthy controls or CHB carriers was not significant when compared to LC or HCC patients (P>0.05). LC patients carrying at least one A allele are more likely to develop HCC in contrast with those with G allele (P<0.05). After adjustment for confounders, meaningful results were only seen in the comparison between rs1545224 AG+AA genotype carriers and GG genotype carriers among the LC patients (P<0.05). Rs2241883 polymorphism did not influence the risk of developing LC or HCC in healthy and CHB individuals, nor did it influence the risk of HCC in LC patients (P>0.05).Conclusions: Taken together, FABP1 rs1545224 polymorphism might increase HCC risk in LC patients, indicating that FABP1 rs1545224 polymorphism may be related to the process of developing HCC in Chinese patients with LC.

Does ascitic fluid lactoferrin has a role in the diagnosis and follow up of spontaneous bacterial peritonitis in hepatitis C virus cirrhotic patients

Background Polymorphonuclear leukocyte (PMNL) count in the ascitic fluid (AF) is the gold standard method for the diagnosis of spontaneous bacterial peritonitis (SBP). Its measurement is routinely performed by traditional manual counting which is operator dependent and false-negative results may occur due to lysis of the leukocyte during transport. Aims The aims of the study were to assess the accuracy of AF lactoferrin and the best cutoff value for the diagnosis of SBP and also to compare its level before and after treatment to be used as a marker for follow up. Patients and methods The present study included 150 Egyptian patients with hepatitis C virus-related liver cirrhosis and ascites. The cases were divided into 100 patients with SBP and 50 patients with no SBP based on an elevated AF PMNL count of greater than or equal to 250 cells/mm3, ascitic samples were examined for PMNL count, culture, chemistry, and lactoferrin concentration in non-SBP patients and in SBP patients before and after systemic antibiotic treatment. Results AF lactoferrin concentration is significantly higher in SBP patients than in non-SBP patients with a cutoff value of 75.55 ng/ml, significantly higher in culture positive than in culture-negative SBP patients and its concentration is decreased significantly in SBP patients after systemic antibiotic therapy. Conclusion Elevated AF lactoferrin levels in cirrhotic patients are reliable for the diagnosis and follow up of SBP after systemic antibiotic therapy. The level of AF lactoferrin level is higher in resistant cases of SBP than the cases that respond to systemic antibiotic treatment.

Liver transplantation for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome, and it is defined by the presence of steatosis in >5% of hepatocytes, according to histological analysis or detected by specific proton density fat fraction obtained magnetic resonance imaging. The term NAFLD covers two pathologically distinct conditions: non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), which can have similar clinical presentation, but with different prognosis. Both conditions can lastly lead to the development of cirrhosis. End stage liver-disease and hepatocellular carcinoma represent the two standard indications for liver transplantation (LT) in patients affected by NAFLD. Despite the evolution to end stage liver disease occur in 15-20% of NASH cases, the absolute number of LT performed for NAFLD is dramatically increased in the last decade. Between 2004 and 2013 new waitlist registrants for NAFLD as indication increased from 804 to 2174, becoming rapidly the second most common indication for liver transplantation in the USA. During the same period, indications to LT such as hepatitis C virus-related and alcohol-related cirrhosis increased only by 14% and 45% respectively. This review will focus on the management before and after LT for patients with NAFLD, with particular interest to comorbidities and outcomes.

Utility of post-liver transplantation MELD and delta MELD in predicting early and late mortality.

The performance of early post-liver transplantation (post-LT) model for end-stage liver disease (MELD) or even its dynamic changes over time (ΔMELD) in predicting the mortality after LT is still controversial. The aim of this study was to assess the ability of absolute and ΔMELD calculated at days 7 and 30 after LT to predict 1- and 5-year mortality. Data of 209 consecutive patients who underwent LT in two centers were reviewed. Patients who received LT for hepatocellular carcinoma were excluded, as well as those who did not survive for at least 1 month. MELD and [INCREMENT]MELD were calculated for each patient at 7 and 30 days after LT. One hundred fifty-six patients were included, mostly male [104 (66.7%)] with a mean age of 51.9±8.8 years. The main indications for transplantation were decompensated hepatitis C virus-related liver cirrhosis [138 (88.5%)] and hepatitis C and B virus co-infection [10 (6.4%)]. Grafts were obtained from 104 living donors and 52 deceased donors. Survival at 1 and 5 years was 89.7 and 85.9%, respectively, with a mean survival of 52.3±1.5 months. In univariate analysis, both absolute and ΔMELD at postoperative days 7 and 30 significantly predicted 1- and 5-year post-LT mortality. In multivariate analysis, MELD at postoperative day 30 was significantly associated with 1- (odds ratio: 1.24, 95% confidence interval: 1.14-1.35, P<0.0001) and 5-year mortality (odds ratio: 1.23, 95% confidence interval: 1.14-1.33, P<0.0001). The area under the curve for MELD at 30 days post-LT in the prediction of mortality was 0.823 (P=0.01) at 1 year and 0.812 (P<0.001) at 5 years. A cutoff of post-LT day 30 MELD less than 10 could predict mortality with a sensitivity and specificity of 90 and 68.1% at 1 year and 81.3 and 69.7% at 5 years, respectively. Failure of the MELD score to decline over the first postoperative month to less than 10 is a significant predictor of both early and late post-LT mortality.

Hemispheric Outflow Reconstruction With Autologous Umbilical Vein in Living Donor Liver Transplantation

A 44-year-old man with hepatitis C virus-related cirrhosis underwent living donor liver transplantation (LDLT). The donor was his identical twin elder brother. On computed tomography, the markedly dilated umbilical vein was observed as a hepatofugal collateral. An extended left liver graft with the caudate lobe was harvested in a conventional manner. One orifice outflow reconstruction was performed by using an umbilical vein, which was extracted from the recipient. This vein-flap sheet was sutured to the outflow orifice of the liver graft in a two-thirds circle on the ventral side. One wide outflow orifice with a 90-mm vein umbilical-vein flap on the ventral wall of outflow was created. Excellent triphasic waveforms and velocities were demonstrated on postoperative Doppler ultrasonography. The post-transplant course was uneventful, with no need for immunosuppressants, and the patient was discharged without any complications on postoperative day 27. The volume of left liver increased from 406 cm3 to 1372 cm3 during the first 6 weeks after transplantation.

Unusual association of Merkel-cell carcinoma and hepatocellular carcinoma in alcohol and hepatitis C virus-related cirrhosis: Casual or causal relation?

Background: Merkel-cell carcinoma (MCC) is a rare and highly aggressive skin cancer. The estimated annual incidence rate of MCC is increasing, and the mortality rate is considerably higher worse than that of cutaneous melanoma. The risk of MCC is higher in immunosuppressed patients and in those with other malignancies.Case representation: The present report is the first description of MCC associated with hepatocellular carcinoma in an immunocompetent patient with alcohol and hepatitis C virus (HCV)-related liver cirrhosis.Conclusions: This case supports the hypothesis of HCV systemic oncogenicity, suggested by previous reports describing an association of this virus with lympho-proliferative disease, gastrointestinal, kidney, and breast malignancies, even though a causal relation or mechanism have not been clearly established. Further studies are needed to clarify whether the impairment of immune system associated with advanced cirrhosis may also play a role, by allowing opportunistic viruses to initiate oncogenic pathways. This paper finally highlights the importance of the screening for skin and systemic disorders in patients with chronic hepatitis C.

Clinical outcomes of direct-acting antiviral therapy in patients with compensated hepatitis C virus-related cirrhosis

Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.

Metabolic characterization of hepatitis B virus-related liver cirrhosis using NMR-based serum metabolomics

Liver cirrhosis (LC) is an advanced liver disease that can develop into hepatocellular carcinoma. Hepatitis B virus (HBV) infection is one of the main causes of LC. Therefore, there is an urgent need for developing a new method to monitor the progression of HBV-related LC (HBV-LC). In this study, we attempted to examine serum metabolic changes in healthy individuals as well as patients with HBV and HBV-LC. Furthermore, potential metabolite biomarkers were identified to evaluate patients progressed from health to HBV-LC. Metabolic profiles in the serum of healthy individuals as well as patients with HBV and HBV-LC were detected using an NMR-based metabolomic approach. Univariate and multivariate analyses were conducted to analyze serum metabolic changes during HBV-LC progression. Moreover, potential metabolite biomarkers were explored by receiver operating characteristic curve analysis. Serum metabolic changes were closely associated with the progression of HBV-LC, mainly involving energy metabolism, protein metabolism, lipid metabolism and microbial metabolism. Serum histidine was identified as a potential biomarker for HBV patients. Acetate, formate, pyruvate and glutamine in the serum were identified as a potential biomarker panel for patients progressed from HBV to HBV-LC. In addition, phenylalanine, unsaturated lipid, n-acetylglycoprotein and acetone in the serum could be considered as a potential common biomarkers panel for these patients. NMR-based serum metabolomic approach could be a promising tool to monitor the progression of liver disease. Different metabolites may reflect different stages of liver disease.

Statin use and virus-related cirrhosis: A systemic review and meta-analysis

Liver cirrhosis and its complications are important factors contributing to mortality worldwide. Statin use is probably associated with lower risk of hepatic decompensation and mortality, but not with cirrhosis or fibrosis progression according to a recent systematic review. We aimed to evaluate the definite effects of statins on the risk of virus-related cirrhosis. We systematically searched four databases up to May 7, 2017, without language restriction. Studies were included if they evaluated and clearly defined exposure to statins, reported fibrosis progression, risk of cirrhosis in patients with chronic viral hepatitis or decompensation in cirrhotic patients, and reported relative risks (RRs) or odds ratios (ORs), or provided data for their estimation. Pooled RRs (or ORs) with 95% confidence intervals were calculated using the random-effects models irrespective of statistical heterogeneity assessed with the Cochran's Q statistic and I2 statistic. Ten observational studies involving 12,3445 patients (8 cohort studies, n=12,1823; 1 nested case-control, n=1350; and 1 abstract, n=272) were included. Statin use was associated with a statistically significant 51% reduction in the risk of virus-related cirrhosis (pooled RRs, 0.49; 95% CI, 0.30-0.80; P=0.004), with substantial heterogeneity (I2=98.3%; P<0.001). Statin use was also associated with a 51% reduction in the risk of decompensation (pooled RRs, 0.49; 95% CI, 0.41-0.59; P<0.001), which was statistically significant, with no heterogeneity (I2=33.8%; P=0.210). The meta-analysis showed that statin use was associated with a significantly reduced risk of virus-related cirrhosis and decompensation. However, these results should be interpreted with caution given the possibility of residual confounding. Large randomized controlled trials are warranted in future studies.

Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/β-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial

BackgroundThere is currently no anti-fibrotic drug therapy available to treat hepatitis C virus (HCV) cirrhosis. The aim of this study was to assess the safety, tolerability, and anti-fibrotic effect of PRI-724, a small-molecule modulator of Wnt signaling, in patients with HCV cirrhosis. MethodsIn this single-center, open-label, phase 1 trial, we sequentially enrolled patients with HCV cirrhosis who were classified as Child-Pugh (CP) class A or B. PRI-724 was administered as a continuous intravenous infusion of 10, 40, or 160mg/m2/day for six cycles of 1week on and 1week off. The primary endpoints were frequency and severity of adverse events. The secondary endpoint was efficacy of PRI-724 in treating cirrhosis based on CP score and liver biopsy. This study is registered with ClinicalTrials.gov (no. NCT02195440). FindingsBetween Sept 3, 2014 and May 2, 2016, 14 patients were enrolled: CP class A:B, 6:8; median age, 62 (range: 43 to 74) years; male:female, 10:4. Twelve of the 14 patients completed six cycles of treatment; one was withdrawn from the study due to possible study drug-related liver injury (grade 3) in the 160mg/m2/day dose cohort and one withdrew for personal reasons. Serious adverse events occurred in three patients [21% (3/14)], one of which was possibly related to PRI-724. The most common adverse events were nausea [29% (4/14)] and fatigue [21% (3/14)].After PRI-724 administration, the CP scores worsened by 1 point in two patients in the 10mg/m2/day cohort, improved in three patients at 1, 1, and 2 points in the 40mg/m2/day cohort, and improved in one patient by 3 points in the 160mg/m2/day cohort. The histology activity index scores of the liver tissue improved in two patients and exacerbated in two patients in the 10mg/m2/day cohort, and improved in one patient in the 40mg/m2/day cohort. InterpretationThis study showed that administration of 10 or 40mg/m2/day intravenous PRI-724 over 12weeks was well-tolerated by patients with HCV cirrhosis; however, liver injury as a possible related serious adverse event was observed in the 160mg/m2/day cohort. Funding SourceAMED.

The role of T helper 17 cells in the pathogenesis of hepatitis B virus-related liver cirrhosis (Review).

In chronic hepatitis B virus (HBV)-infected patients, T helper 17 (Th17) cells are significantly elevated. Th17 cells initiate immune-mediated pathogenesis and have a critical role in the process of HBV-related liver cirrhosis (HBV-LC). The mechanisms underlying this process are attributed to Th17-secreted cytokines, which include interleukin (IL)-17, IL-21 and IL-22; however, a systemic analysis regarding these mechanisms has yet to be conducted. Therefore, the present study aimed to investigate the role of Th17 cells in the pathogenesis of HBV-LC. All randomized clinical trials, case series, case reports and meta-analyses that contained the aforementioned keywords were included in the review process. In addition, unpublished information from the Food and Drug Administration was included. The findings indicated that Th17-secreted cytokines, including IL-17, IL-21 and IL-22, function by activating or silencing hepatic stellate cells, modulating proinflammatory and pro- or antifibrogenic effectors, regulating extracellular matrix formation, upregulating chemokine expression, and inducing hepatocellular damage or hepatoprotection during the HBV-LC process. In addition, Th17 cells and Th17-secreted cytokines may be considered a potential tool in the diagnosis or treatment of HBV-LC. The present review summarized the role of Th17 cells in the pathogenesis of HBV-LC in order to deepen the clinical understanding of the role of Th17 cells and also to support the development of effective therapies for patients with HBV-LC.

Metabolomics and eicosanoid analysis identified serum biomarkers for distinguishing hepatocellular carcinoma from hepatitis B virus-related cirrhosis.

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. It is a type of inflammation-related cancer that usually follows liver hepatitis that mostly caused by hepatitis B virus (HBV) in China. However, the metabolism disturbance of HCC and HBV-cirrhosis is not yet fully understood. In addition, there is little research on the relationships between inflammation mediators and HCC. In this study, we investigated serum metabolic abnormalities in HBV-cirrhosis and HCC patients through non-targeted metabolomics and targeted eicosanoid analysis. Metabolomic analysis identified 14 metabolites, i.e. malate, citrate, succinate, lysine, carnitine, proline, ornithine, serine, phenylalanine, tyrosine, arachidonic acid arabinose, galactose and uric acid are consistently altered in HBV-cirrhosis and HCC patients. Meanwhile, eicosanoid analysis uncovered several prostaglandins and leukotrienes are implicated in pathological processes in HBV-cirrhosis and HCC. Finally, these identified biomarkers possessed strong potential to distinguish and diagnose HCC from healthy controls and HBV-cirrhosis patients. This study provided a new perspective to understand the mechanism and discover probable biomarkers of HCC.

IL-18 polymorphisms contribute to hepatitis B virus-related cirrhosis and hepatocellular carcinoma susceptibility in Chinese population: a case-control study

IL-18 polymorphisms influence the transcriptional activity of the IL-18 gene and associated with various diseases. However, their relationships with hepatitis B virus-related liver diseases had not reached a consensus. So we conducted this case-control study with a view to clarifying the association. We included four groups: healthy controls, chronic hepatitis B virus (CHB) carriers, liver cirrhosis (LC) and hepatocellular carcinoma (HCC) groups with each group of 250 persons. Odd ratios (ORs) and 95% confidence intervals (95%CIs) with or without adjustment were calculated. Haplotype analysis was also performed. The results showed people carrying rs187238 CG genotype had a lower risk of LC (CG vs. CC: OR = 0.59, 95%CI = 0.38–0.91, P = 0.02), while GG genotype carriers had a higher risk of HCC (GG vs. CC+CG: OR = 4.73, 95%CI = 1.01–22.1, P = 0.03) than those with CC and CG genotypes in healthy group. Rs187238 GG genotype increased the risk from CHB to LC status (GG vs. CC: OR = 4.81, 95%CI = 1.03–22.6; GG vs. CC+CG: OR = 4.73, 95%CI = 1.01–22.1), meanwhile the trend also existed by controlling confounding factors (GG vs. CC: OR = 6.25, 95%CI = 1.09–35.8; GG vs. CC+CG: OR = 5.91, 95%CI = 1.04–33.7). Haplotype Crs187238Trs1946518 moderately decreased the risk of CHB carriers developing into HCC (OR = 0.69, 95%CI = 0.50–0.96, P = 0.03) after adjustment. In conclusion, IL-18 rs187238 GG genotype may increase the risk of HCC in healthy population and the risk of LC in CHB carriers.

Serum Golgi protein-73 in combination with \u03b1-fetoprotein for diagnosing hepatocellular carcinoma in Egyptian patients

Background and aimHepatocellular carcinoma (HCC) is the third cause of cancer-related mortality. α-fetoprotein (AFP) is not a highly sensitive marker for predicting HCC despite its high specificity. Serum Golgi protein-73 (sGP73) seems to be promising new marker. This study aimed at evaluating the role of sGP73 alone and in combination with AFP for diagnosing HCC.Patients and methodsThis study was conducted on 90 Egyptian patients who were equally divided into two groups. Group 1 included 45 patients with hepatitis C virus-related liver cirrhosis without clinical or radiological evidence of HCC, and group 2 included 45 patients diagnosed as having HCC by triphasic abdominal computed tomography. Serum AFP and GP73 were measured using enzyme-linked immunosorbent assay.ResultsA cutoff value greater than or equal to 40ng/ml for AFP had a sensitivity of 51.1%, specificity of 97.8%, and area under the curve (AUC) of 0.802. sGP73 with a cutoff value greater than or equal to 1.4 ng/ml yielded a sensitivity of 75.6%, specificity of 97.8%, diagnostic accuracy of 86.7%, and AUC of 0.908. The combined use of AFP and sGp73 led to an increase in sensitivity to 84.4%, specificity to 95.6%, diagnostic accuracy to 90%, and AUC to 0.947.ConclusionThe combined use of AFP and sGp73 could increase the sensitivity and specificity for HCC diagnosis.

Statins decrease the risk of decompensation in hepatitis B virus- and hepatitis C virus-related cirrhosis: A population-based study.

Statin use decreases the decompensation rate in both HBV- and HCV-related cirrhosis. Of borderline significance is a decreased decompensation rate in alcohol-related cirrhosis. (Hepatology 2017;66:896-907).

C-reactive protein-to-albumin ratio is a predictor of hepatitis B virus related decompensated cirrhosis: time-dependent receiver operating characteristics and decision curve analysis.

Hepatitis B virus (HBV) infection remains a major health problem and HBV-related-decompensated cirrhosis (HBV-DC) usually leads to a poor prognosis. Our aim was to determine the utility of inflammatory biomarkers in predicting mortality of HBV-DC. A total of 329 HBV-DC patients were enrolled. Survival estimates for the entire study population were generated using the Kaplan-Meier method. The prognostic values for model for end-stage liver disease (MELD) score, Child-Pugh score, and inflammatory biomarkers neutrophil/lymphocyte ratio, C-reactive protein-to-albumin ratio (CAR), and lymphocyte-to-monocyte ratio (LMR) for HBV-DC were compared using time-dependent receiver operating characteristic curves and time-dependent decision curves. The survival time was 23.1±15.8 months. Multivariate analysis identified age, CAR, LMR, and platelet count as prognostic independent risk factors. Kaplan-Meier analysis indicated that CAR of at least 1.0 (hazard ratio, 7.19; 95% confidence interval, 4.69-11.03), and LMR less than 1.9 (hazard ratio, 2.40; 95% confidence interval, 1.69-3.41) were independently associated with mortality of HBV-DC. The time-dependent receiver operating characteristic indicated that CAR showed the best performance in predicting mortality of HBV-DC compared with LMR, MELD score, and Child-Pugh score. The results were also confirmed by time-dependent decision curves. CAR and LMR were associated with the prognosis of HBV-DC. CAR was superior to LMR, MELD score, and Child-Pugh score in HBV-DC mortality prediction.