Luteolin is a flavonoid compound and exhibits antioxidant, antiinflammatory, antibacterial, antidiabetic and antiproliferative properties. Studies have shown that luteolin may inhibit cell proliferation, metastasis, and angiogenesis of numerous types of cancers, including breast cancer, through inducing cell cycle arrest and apoptosis and by modulating cell signaling. In this review, we have summarized the recent studies on inhibitory effects and underlying mechanisms of luteolin in breast cancer. These studies support that luteolin is a promising drug to treat breast cancer.

Recurrent acute bacterial cholangitis is a unique indication for liver transplantation in primary sclerosing cholangitis. We present the first report on utility of healthy donor fecal transplantation for management of recurrent acute bacterial cholangitis in a primary sclerosing cholangitis patient. We demonstrate the striking liver biochemistry, bile acid and bacterial community changes following intestinal microbiota transplantation associated with amelioration of recurrent cholangitis.

In parallel with the rising prevalence of metabolic syndrome globally, nonalcoholic fatty liver (NAFL) disease is the most common chronic liver disease in Western countries and nonalcoholic steatohepatitis (NASH) has become increasingly associated with hepatocellular carcinoma. Recent studies have identified NASH as the most rapidly growing indication for liver transplantation (LT). As a hepatic manifestation of the metabolic syndrome, NAFL disease can be histologically divided into NAFL and NASH. NAFL is considered a benign condition, with histological changes of hepatocyte steatosis but without evidence of hepatocellular injury or fibrosis. This is distinct from NASH, which is characterized by hepatocyte ballooning and inflammation, and which can progress to fibrosis and cirrhosis, hepatocellular carcinoma, and liver failure. As for any other end-stage liver disease, LT is a curative option for NASH after the onset of decompensated cirrhosis or hepatocellular carcinoma. Although some studies have suggested increased rates of sepsis and cardiovascular complications in the immediate postoperative period, the long-term posttransplant survival of NASH cases is similar to other indications for LT. Recurrence of NAFL following LT is common and can be challenging, although recurrence rates of NASH are lower. The persistence or progression of metabolic syndrome components after LT are likely responsible for NASH recurrence in transplanted liver. Therefore, while maintaining access to LT is important, concerted effort to address the modifiable risk factors and develop effective screening strategies to identify early stages of disease are paramount to effectively tackle this growing epidemic.

Background and Aims: The poor outcomes of hepatocellular carcinoma (HCC) patients may be due to not only malignant tumors but also limited liver function. Therefore, as stated in major guidelines, only patients with relatively normal liver function (Child-Pugh A) would be referred for curative hepatectomy. Even so, the postsurgery survival rate of patients is still extremely poor. Direct curative resection may benefit most patients. This study aimed to improve the prognosis predicting accuracy of the Child-Pugh scoring system.

Methods: This study included two cohorts: cohort A being composed of 613 HCC patients, with a 23-month median postsurgery follow-up time; and cohort B being composed of 554 tumor-free chronic liver disease patients. Kaplan–Meier test and Cox model were used for survival analysis. Independent-samples t test or one-way ANOVA was used to test the differences between different groups.

Results: Serum prealbumin levels were found inversely correlated with worsening of fibrotic scores (r = −0.482, p < 0.001). Lower levels of presurgery prealbumin was an independent factor of poor postsurgery prognosis in Child-Pugh A patients, with a hazard ratio of 0.731 (p = 0.001). By integrating prealbumin together with total bilirubin level, serum albumin concentration and prothrombin time, a modified liver disease prognosis scoring system was developed to define traditional Child-Pugh A HCC patients as Modified Child-Pugh MCP-1, MCP-2 and MCP-3, with median postsurgery overall survival times of 44.00, 28.00 and 11.00 months respectively.

Conclusions: Preoperative serum prealbumin is a valuable prognosis predicting biomarker for Child-Pugh A HCC patients who may be under consideration for curative resection. With serum prealbumin included as one of the parameters, the MCP scoring system might improve the postsurgery survival predicting accuracy for HCC patients.

Background and Aims: Spontaneous bacterial peritonitis (SBP) is a serious complication of liver cirrhosis and a prognostic model to predict it is needed. This study was designed to test the ability of different laboratory tests and the new scoring system by Wehmeyer and colleagues (consisting of age, C-reactive protein (CRP) and platelet count) to predict it.

Methods: Three-hundred patients admitted to the National Liver Institute, University of Menoufia, Egypt (2015–2016) with liver cirrhosis and ascites were included in our study. SBP was diagnosed if ascetic neutrophil count was ≥250/µL with no sign of secondary peritonitis.

Results: The patient population had age range of 29–81 years old, was 60% men and showed a majority (91.7%) with primary cause of liver disease being hepatitis C. By univariate analysis, associations with age, total bilirubin, aspartate aminotransferase level, creatinine level, international normalized ratio, model for end-stage liver disease score, total leucocytic count, platelet count and CRP level were significant. By multivariate analysis, independent predictors were age, platelet count and CRP level (p = 0.004, 0.013 and <0.001, respectively). CRP at a cut-off point ≥13.5 mg/L could predict SBP (sensitivity of 86.4% and specificity of 66.0%). Wehmeyer’s SBP scoring system was predictive (p < 0.001); only 4% of patients with 0 score developed SBP (CRP cut-off of 30 mg/L), while 92.8% with score of 3 or 4 developed SBP. By using our modified Wehmeyer score with CRP cut-off value of 13.5 mg/L, no patient with 0 score developed SBP.

Conclusions: Age, CRP level and platelet count are independent predictors for SBP and a scoring system including them could easily predict the condition. SBP diagnosis could be excluded in patients with 0 score, using CRP cut-off value of 13.5 mg/L.

Background and Aims: To report long-term results in treatment of intermediate hepatocellular carcinoma (HCC) in cirrhotics using new high-powered microwaves (MWS) ablation alone.

Methods: This multicenter study included 215 cirrhotics (age range: 67–84 years; 137 males; 149 Child A, 66 Child B) who underwent percutaneous ultrasound-guided high-powered MWS ablation instead of transarterial chemoembolization. Among the patient population, 109 had a single nodule (Ø 5.3–8 cm) [group A], 70 had 2 nodules (Ø 3–6 cm) [group B] and 36 had 3–5 nodules (Ø 1.5–6.8 cm) [group C]. MWS ablation efficacy was evaluated using enhanced-computed tomography and/or magnetic resonance imaging. Primary end-point was 5-year cumulative overall survival (OS).

Results: On enhanced-computed tomography and/or magnetic resonance imaging, complete ablation rates were 100% for 1.5–3.5 cm nodules. In nodules >3.5–5 cm, it was 89% for the first ablation and 100% for the second. For lesions >5–8 cm, ablation was up to 92%. Overall, 1-, 3- and 5-year survival rates were 89, 60, and 21%, respectively. The cumulative OS rate of group A was 89%, 66% and 34% at 1, 3 and 5 years. The cumulative OS rate of group B was 88%, 60% and 11% at 1, 3 and 5 years. The cumulative OS rate of group C was 86%, 55% and 0%. The 5-year survival rate was significantly different among the groups (p <0.001). One patient died from rupture of HCC. Upon multivariate analysis, preablation total bilirubin >1.5 mg/dL was an independent factor for predicting lower survival.

Conclusions: Percutaneous MWS ablation of intermediate HCC is safe and effective in inducing large volume of necrosis in intermediate HCC nodules, providing long-term survival rates similar to transarterial chemoembolization. Preablation total bilirubin >1.5 mg/dL as expression of liver function reserve is the main factor predicting a worse outcome.

Background and Aims: Hepatitis C Virus (HCV) is uniformly recurrent after liver transplant (LT) and recurrence is associated with an increased risk of mortality. Immunosuppressive medications increase the risk of chronic kidney disease, and the presence of chronic kidney disease presents a challenge for HCV treatment in LT recipients. The aim of this study was to assess changes in glomerular filtration rates (GFRs) of LT recipients receiving HCV treatment.

Methods: This is a retrospective study of LT patients who received HCV treatment between 2015 and 2016 (n = 60). The outcomes of interest were differences in serum creatinine levels and in GFR, measured at treatment initiation and at 24 weeks after treatment. The average age of the patients was 59 years-old, and 17% were cirrhotic and 67% were treatment-experienced. All patients received sofosbuvir/ledipasvir without ribavirin.

Results: All patients achieved sustained virologic response at 12 weeks after treatment (SVR12). At baseline, 55% of patients had GFR <60 mL/min per 1.73 m2. Among those patients, GFR did not change in 18%, 33% had improved GFR, and 48% had worsened GFR. Up to 45% of the patients had a GFR >60 mL/min per 1.73 m2. Among those patients, GFR did not change in 81%, and 19% had worsened GFR. In the entire cohort, 65% of patients had improved or stable GFR and 35% had worsened GFR. The average change in serum creatinine between baseline and 24 weeks was 0.10 (p = 0.18).

Conclusions: This study showed improved or unchanged GFR in 65% and worsened GFR in 35% of LT recipients who achieved SVR12. Worsening of GFR was more frequently encountered in those with impaired renal function at baseline. Caution should be used when treating HCV in LT recipients, especially those with baseline status of renal impairment.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is a complex clinical entity that has an estimated worldwide prevalence of 1–15%. Most clinical studies have shown that progression of disease is faster in HBV-HCV coinfected patients compared to those with monoinfection. Hepatocellular carcinoma development appears to have higher rate in coinfections. Viral replication in coinfected cells is characterized by a dominance of HCV over HBV replication. There are no established guidelines for treatment of HBV-HCV coinfection. Studies on interferon-based therapies and direct-acting antivirals have shown varying levels of efficacy. Clinical reports have indicated that treatment of HCV without suppression of HBV increases the risk for HBV reactivation. In this review, we appraise studies on both direct-acting antivirals and interferon-based therapies to evaluate the efficacy and rates of reactivation with each regimen. Screening for and prevention of coinfection are important to prevent serious HBV reactivations.

Repair of sustained liver injury results in fibrosis (i.e. the accumulation of extracellular matrix proteins), and ultimately the complete distortion of parenchymal architecture of the liver, which we call cirrhosis. Detecting and staging of fibrosis is thus a mainstay in the management of chronic liver diseases, since many clinically relevant decisions, such as starting treatment and/or monitoring for complications including hepatocellular carcinoma, may depend on it. The gold standard for fibrosis staging is liver biopsy, the role of which, however, is questioned nowadays because of cost, hazards and poor acceptance by patients. On the other hand, imaging techniques and/or measurement of direct and indirect serum markers have not proved to be completely satisfactory under all circumstances as alternatives to liver biopsy. Making progress in this field is now more crucial than ever, since treatments for established fibrosis appear on the horizon. Fine dissection of the pathways involved in the pathophysiology of liver diseases has put forward several novel candidate biomarkers of liver fibrosis, such as growth arrest-specific6, Mac-2-binding protein, osteopontin, placental growth factor, growth/differentiation factor 15 and hepatocyte growth factor. All molecules have been suggested to have potential to complement or substitute methods currently used to stage liver diseases. Here, we review the pros and cons for their use in this setting.

Background and Aims: To evaluate the prevalence and significance of elevated cancer antigen-125 (CA-125) levels in patients with cirrhosis being treated in a tertiary care liver center and its correlation with objective markers of disease severity.

Methods: We retrospectively reviewed medical records of 172 adult patients with cirrhosis (due to any etiology) after obtaining CA-125 serum analysis. Demographics, etiology of cirrhosis, model of end-stage liver disease (MELD) score, Child’s Turcotte-Pugh classification, albumin bilirubin (ALBI) score, degree of ascites, presence of esophageal varices, serum CA-125 level and various other parameters were collected. Statistical analysis was performed using SPSS software and descriptive statistics.

Results: Elevated CA-125 levels were noted in 147 patients (85%) of the study population. Higher MELD score was associated with higher CA-125 levels (p = 0.001). Statistically significant correlation was observed between elevated CA-125 levels and degree of ascites (p < 0.001), ALBI score (p < 0.001) and Child’s Turcotte-Pugh class (p < 0.001). No correlation was observed with presence or absence of esophageal varices. Near-normal CA-125 levels were noted in patients with cirrhosis but undetectable ascites on ultrasound imaging. No differences were observed in mean values between male and female patients (p = 0.207). Regression analysis confirmed that CA-125 levels had a better correlation with degree of ascites than MELD score or ALBI score.

Conclusions: Elevated CA-125 levels were noted in 85% of patients with cirrhosis at our center. Our study establishes that the more advanced the degree of decompensation based on MELD score, Child’s Turcotte-Pugh classification and ALBI score, the higher the elevation in CA-125. Absence of ascites was associated with normal CA-125 level, with a direct correlation between high levels and worsening ascites, but there was no statistically significant correlation with esophageal varices, indicating that elevated CA-125 levels could be related to mechanical stretch of the peritoneum rather than portal hypertension itself. Further multi-centered studies are required to confirm and validate these findings.

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. It also causes acute liver failure and acute-on-chronic liver failure in many patients, such as those suffering from other infections/liver injuries or organ transplant/chemotherapy recipients. Despite widespread sporadic and epidemic incidents, there is no specific treatment against HEV, justifying an urgent need for developing a potent antiviral against it. This review summarizes the known antiviral candidates and provides an overview of the potential targets for the development of specific antivirals against HEV.

The composite tumors of the liver are very rare, including the coexistence of HCC (hepatocellular carcinoma) with NEC (neuroendocrine carcinoma). The rare occurrence of these tumors necessitates more reported cases in order to fully understand their clinical characteristics, behaviors and treatments. Herein is described an incidental collision tumor of HCC-NEC, along with a review of the literature focusing on their clinicopathological findings and prognosis. The tumor presented here was found incidentally in the hepatectomy specimen of a 56-year-old man who had undergone liver transplantation for rapidly progressive liver failure because of alcoholic hepatitis and cirrhosis. Imaging and laboratory examinations did not demonstrate tumor-related findings. During macroscopic examination, two sharply defined and distinctive areas (1.7 cm and 0.6 cm dimension respectively) were detected among the cirrhotic nodules. The characteristic histopathological features and immunohistochemical findings allowed a diagnosis of HCC-NEC to be made. There was no evidence of recurrence and metastasis after 10 months following surgery. The present case and review revealed that these tumors are frequently found in older ages and males. Although serum markers are valuable in the discrimination of malignant tumors, their absence cannot completely rule out composite HCC-NEC. Diagnosis requires a comprehensive histopathological evaluation together with immunohistochemistry. The NEC component might influence the treatment strategy and eventually the outcome of the patient. In conclusion, the rare occurrence of HCC-NEC and the lack of diagnostic clinical signs and symptoms do not exclude their consideration in the differential diagnosis of liver tumors, especially in patients with the chronic liver disease.