Guide for diagnosis and treatment of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is ranked as the 5th common type of cancer worldwide and is considered as the 3rd common reason for cancer-related deaths. HCC often occurs on top of a cirrhotic liver. The prognosisis determined by several factors; tumour extension, alpha-fetoprotein(AFP) concentration, histologic subtype of the tumour, degree of liver dysfunction, and the patient's performance status. HCC prognosis is strongly correlated with diagnostic delay. To date, no ideal screening modality has been developed. Analysis of recent studies showed that AFP assessment lacks adequate sensitivity and specificity for effective surveillance and diagnosis. Many tumour markers have been tested in clinical trials without progressing to routine use in clinical practice. Thus, surveillance is still based on ultrasound(US) examination every 6 mo. Imaging studies for diagnosis of HCC can fall into one of two main categories: routine non-invasive studies such as US, computed tomography(CT), and magnetic resonance imaging, and more specialized invasive techniques including CT during hepatic arteriography and CT arterial portography in addition to the conventional hepatic angiography. This article provides an overview and spotlight on the different diagnostic modalities and treatment options of HCC.

Successful treatment of liver abscess secondary to foreign body penetration of the alimentary tract: A case report and literature review

Hepatic abscess caused by foreign body penetration of the alimentary tract is rare. We report a case of gastric antrum penetration due to a toothpick complicated by liver abscess formation. A 41-year-old man was admitted to our hospital with the chief complaint of upper abdominal pain for 2 mo. Esophagogastroduodenoscopy performed at a local clinic revealed a toothpick penetrating the gastric antrum. Computed tomography (CT) of the abdomen at our hospital revealed a gastric foreign body embedded in the posterior wall of gastric antrum with regional phlegmon over the lesser sac and adhesion to the pancreatic body without notable vascular injury, and a hepatic abscess seven cm in diameter over the left liver lobe. Endoscopic removal of the foreign body was successfully performed without complication. The liver abscess was treated with parenteral antibiotics without drainage. The patient’s recovery was uneventful. Abdominal ultrasonography demonstrated complete resolution of the hepatic abscess six months after discharge. Relevant literature from the PubMed database was reviewed and the clinical presentations, diagnostic modalities, treatment strategies and outcomes of 88 reported cases were analyzed. The results showed that only 6 patients received conservative treatment with parenteral antibiotics, while the majority underwent either image-guided abscess drainage or laparotomy. Patients receiving abscess drainage via laparotomy had a significantly shorter length of hospitalization compared with those undergoing image-guided drainage. There was no significant difference in age between those who survived and those who died, however, the latter presented to hospitals in a more critical condition than the former. The overall mortality rate was 7.95%.

Efficacy and Safety of Glecaprevir/Pibrentasvir in Combination Therapy in Chronic Hemodialysis Patients with Genotype 2 Hepatitis C Virus Infection

Background: Glecaprevir (nonstructural protein 3/4A protease inhibitor) and Pibrentasvir (nonstructural protein 5A inhibitor) (G/P), a coformulated once-daily, all oral, ribavirin (RBV)-free, direct-antiviral regimen, was evaluated for safety and efficacy in chronic hemodialysis patients with genotype 2 hepatitis C virus infection. Methods: In this prospective, observational, single-center study at Masuko Memorial Hospital, between November 2017 and December 2018, a total of 8 HD patients with an HCV infection genotype 2 received G/P combination therapy. Age was an average of 67.1 (61 - 75) years and there were four men and two women. It was FIB4 INDX an average of 2.67 (1.5 - 3.34) before the start of therapy. It was quantity of HCV RNA an average of 4.43 (2.1 - 6.5). HCV RNA levels were measured by real-time RCR-based method (COBAS AmpiPrep/COBAS TaqMan HCV Test. 4 cases 12 weeks were 2 cases eight weeks for dosing period. Patients were excluded if they had evidence of hepatocellular carcinoma. This study was approved by the ethics committee of our hospital, while we obtained written consent from the participants after providing a thorough explanation of the contents and methods of this study. Results: 6 patients were available for total dose internal use. As for the HCV RNA of the fourth week, (100%) HCV RNA became negative after administration start of therapy. Rapid virologic response (RVR) achieved all cases. 5 patients achieved 12-week sustained virologic response (SVR12) and were following up the 1 patient. The itching appeared in two cases (33%), but there was symptom improvement in nalfurafine hydrochloride use treatment, and treatment continuation was possible. Conclusion: It is thought that G/P can be given to the HD patients’ safety, but we will accumulate a case in future, and it is thought to be necessary to examine utility and safety.

Effect of verapamil on nitric oxide synthase in a portal veinligated rat model: Role of prostaglandin

AIM： To investigate the effects of verapamil on nitric oxide （NO） synthesis in a portal vein-ligated rat model. METHODS： Systemic and splanchnic hemodynamics were measured by radiolabeled microspheres in portal hypertensive rats after acute administration of verapamil （2 mg/kg） on chronic treatment with N^W-nitro-L-arginine （NNA）（80 mg/kg） and/or indomethacin （2 mg/kg） . RESULTS： Verapamil （2 mg/kg） caused a marked fall in both arterial pressure and cardiac output accompanied by an insignificant change in the portal pressure and no change in portal venous inflow. This result suggested that verapamil did not cause a reduction in portal vascular resistance of portal hypertensive rats, which was similar between N^w- nitro-Loarginine-treated and indomethacin-treated groups. CONCLUSION： In portal hypertensive rats pretreated with NNA and/or indomethacin, acute verapamil administration can not reduce the portal pressure, suggesting that NO and prostaglandin play an important role in the pathogenesis of splanchnic arterial vasodilation in portal hypertension.

Megacolon in adulthood after surgical treatment of Hirschsprung's disease in early childhood

Hirschsprung＇s disease （HD） is a disorder associated with congenital malformation of the enteric nervous system with segmental aganglionosis. Prevailing therapy includes a resection of the affected part of the bowel, However, patients often do not obtain complete functional improvement after surgical treatment. We present the case of a 25-year-old woman who had surgical treatment of lid in early childhood. After that procedure she had clinical features of constipation for years in the end, passing of stool once a week, requiring laxatives and enemas. We diagnosed an incomplete resection of the aganglionic bowel via rectal biopsy and resected the remaining aganglionic segment. Two months after surgery the patient＇s bowel function improved to a frequency of 1-4 stools per day. We conclude that regular follow-up is required to identify lid patients with persistent alterations of bowel function after surgery. In patients presenting with constipation, recognition of a remaining aganglionic segment or other alterations of the enteric nervous system should be aimed at in an early stage. 2005 The WJG Press and Elsevier Inc. All rights reserved

Anaemia in Waldmann's disease: A rare presentation of a rare disease

A 32-year-old female presented with 5-year history of iron deficiency anemia, marked pallor and edema of both lower limbs. Laboratory investigations including complete blood count, blood film, iron studies, lipid profile, ascitic fluid analysis, test of stool for occult blood and alpha 1 anti-trypsin. Upper, lower gastrointestinal(GIT) endoscopies, and enteroscopy were performed. Imaging techniques as abdominal ultrasonography and computed tomography were done. Echocardiography, lymph node biopsy and bone marrow examination were normal. The case was diagnosed as Waldmann's disease with protein losing enteropathy and recurrent GIT bleeding. Management started with low fat diet with medium chain triglyceride, octreotide 200 μg twice a day, tranexamic acid and blood transfusion. Then, exploratory laparotomy with pathological examination of resected segment was done when recurrent GIT bleeding occurred and to excluded malignant transformation.

NS-398 induces caspase-dependent, mitochondria-mediated intrinsic apoptosis of hepatoma cells

The present study was conducted to investigate whether mitochondrial pathway of apoptosis is involved in cyclooxygenase-2 (COX-2) inhibitor-induced growth inhibition of hepatoma cells. The growth rate and pattern of NS-398 (selective COX-2 inhibitor)-treated Hep3B hepatoma cells were analyzed by microscopic examination, DNA fragmentation gel analysis and flow cytometry followed by the cleavage of down-stream caspase 3 and the release of cytosolic fraction of cytochrome c assessed by Western blot analysis. NS-398 induced the growth inhibition of hepatoma cells depending on the concentration of this COX-2 inhibitor and time sequence. Ladder patterned-DNA fragmentation and cytometric redistribution to sub-G1 phase in cell cycle were revealed in NS-398-induced growth inhibition of hepatoma cells. Cytochrome c was translocated from mitochondria to cytosol in time-dependent manner following NS-398 treatment to hepatoma cells. COX-2 inhibitor induces the growth inhibition of hepatoma cells via caspase-dependent, mitochondria-mediated intrinsic apoptosis pathway. These results strongly suggest the possibility of therapeutic implication of COX-2 inhibitor in HCC.

胆固醇结石病人肝脏脂质代谢异常的分子生物学研究

目的:研究导致胆石病人胆汁胆固醇过饱和的肝脏胆固醇和胆汁酸代谢途径中的分子生物学改变。方法:收集22例胆石病人和13例无胆石病的对照病人肝脏活检组织、胆囊胆汁和血浆。采用实时定量PCR检测肝脏基因表达,采用Western印迹法测定蛋白含量。结果:胆石病人较对照组ABCG5/ABCG8和LXRα基因的mRNA表达水平分别增加51%、59%和102%。肝脏SRBI的mRNA和蛋白含量均增加。结论:胆石病人ABCG5/ABCG8基因表达上调,可能与LXRα表达增加促进相关,这些异常是导致胆汁胆固醇过饱和的原因。此外,胆汁中过多的胆固醇可能来源于经肝脏高密度脂蛋白受体SRBI的摄取,而不是由于肝脏合成和酯化的异常。

Pyogenic liver abscess associated with large colonic tubulovillous adenoma

Pyogenic liver abscesses usually occur in association with a variety of diseases. Rarely, liver abscess has been reported as the presenting manifestation of colonic tubulovillous adenoma. We report two cases of pyogenic liver abscess without hepatobiliary disease or other obvious etiologies except that one had a history of diabetes mellitus （DM）. The pathogen in the patient with DM was Klebsiella pneumonia （KP）. In both of the patients, Ueus developed about two to three weeks after the diagnosis of liver abscess. Colonoscopy revealed large polypoid tumors with pathological findings of tubulovillous adenoma in both cases. Two lessons were learned from these two cases： （1） an underlying cause should be aggressively investigated in patients with cryptogenic liver abscess; （2） DM could be one of the etiologies but not necessarily the only cause of KP liver abscess.

MicroRNAs in biliary diseases

Cholangiopathies are a group of diseases primarily or secondarily affecting bile duct cells, and result in cholangiocyte proliferation, regression, and/or transformation. Their etiopathogenesis may be associated with a broad variety of causes of different nature, which includes genetic, neoplastic, immune-associated, infectious, vascular, and drug-induced alterations, or being idiopathic. miRNAs, small non-coding endogenous RNAs that post-transcriptionally regulate gene expres sion, have been associated with pathophysiological processes in different organs and cell types, and are postulated as potential targets for diagnosis and therapy. In the current manuscript, knowledge regarding the role of miRNAs in the development and/or progression of cholangiopathies has been reviewed and the most relevant findings in this promising field of hepatology have been highlighted.

Somatic second-hit mutations leads to polycystic liver diseases

Polycystic liver diseases(PCLDs) are a heterogeneous group of genetic disorders characterized by the development of multiple fluid-filled cysts in the liver,which derive from cholangiocytes,the epithelial cells lining the bile ducts.When these cysts grow,symptoms such as abdominal distension,nausea,and abdominal pain may occur.PCLDs may exist isolated(i.e.,autosomal dominant polycystic liver disease,ADPLD) or in combination with renal cystogenesis(i.e.,autosomal dominant polycystic kidney disease and autosomal recessive polycystic liver disease).The exact prevalence of PCLDs is unknown,but is estimated to occur in approximately 1:1000 persons.Although the pathogenesis of each form of PCLD appears to be different,increasing evidences indicate that hepatic cystogenesis is a phenomenon that may involve somatic loss of heterozygosity(LOH) in those pathological conditions inherited in a dominant form.A recent report,using highly sophisticated methodology,demonstrated that ADPLD patients with a germline mutation in the protein kinase C substrate 80K-H(PRKCSH) gene mostly develop hepatic cystogenesis through a second somatic mutation.While hepatocystin,the PRKCSH-encoding protein,was absent in the hepatic cysts with LOH,it was still expressed in the heterozygous cysts.On the other hand,no additional trans-heterozygous mutations on the SEC63 homolog(S.cerevisiae /SEC63) gene(also involved in the development of PCLDs) were observed.These data indicate that PCLD is recessive at the cellular level,and point out the important role of hepatocystin loss in cystogenesis.In this commentary,we discuss the knowledge regarding the role of somatic second-hit mutations in the development of PCLDs,and the most relevant findings have been highlighted.

β-arrestin-2 predicts the clinical response to β-blockers in cirrhotic portal hypertension patients: A prospective study

BACKGROUND Portal hypertension,a common complication associated with liver cirrhosis,can result in variceal bleeding,which greatly impacts patient survival.Recently,β-arrestin-2 has been shown to predict the acute hemodynamic response to nonselectiveβ-blocker therapy for cirrhotic portal hypertension.However,more data is needed on the long-term effects of and changes inβ-arrestin-2 following nonselectiveβ-blocker therapy.AIM To investigate the expression and role ofβ-Arrestin-2 in predicting the long-term response to nonselectiveβ-blockers in cirrhotic portal hypertensive patients.METHODS We prospectively enrolled 91 treatment-naïve patients with cirrhotic portal hypertension.Baseline clinical and laboratory data were obtained.Gastroscopy was performed for grading and treating varices and obtaining gastric antral biopsies.We measured the serum and antral expression ofβ-arrestin-2 and obtained Doppler measurement of the portal vein congestion index.Treatment with nonselectiveβ-blockers was then started.The patients were followed up for 18 mo,after which they have undergone a repeat antral biopsy and re-evaluation of the portal vein congestion index.RESULTS A higher serum level and antral expression ofβ-arrestin-2 was associated with longer bleedingfree intervals,greater reduction in the portal vein congestion index,and improved grade of varices.Among patients with a lowβ-arrestin-2 expression,17.6%were nonselectiveβ-blocker responders,whereas,among those with high expression,95.1%were responders(P<0.001).A serumβ-arrestin-2 value≥2.23 ng/mL was associated with a lower likelihood of variceal bleeding(90%sensitivity and 71%specificity).β-arrestin-2 expression significantly decreased after nonselectiveβ-blocker therapy.CONCLUSIONβ-arrestin-2 expression in cirrhotic portal hypertension predicts the clinical response to long-term nonselectiveβ-blocker treatment.Serumβ-arrestin-2 is a potential noninvasive biomarker for selecting the candidate patients for nonselectiveβ-blockers.