论中医肝的实质与功能

中医把肝脏的物质代谢作用归之于脾,把神经调节作用赋予肝,即肝主疏泄,主要表现为肝调节脏腑和肝调节运动。肝调节脏腑分气、血、阴、阳、水、火六方面,分别是调畅气机、调节血液、调节先后天阴阳、调节水液代谢和调节君相之火。如果肝失调节,肝主疏泄异常,实者会出现肝气、肝火、肝阳、肝风等证,虚者表现为肝的气、血、阴、阳诸虚,可采用清·王泰林《西溪书屋夜话录》提出的治肝三十法治疗。

Scirrhous hepatocellular carcinoma displaying atypical findings on imaging studies

We describe a 15-mm scirrhous hepatocellular carcinoma （HCC） in a 60-year-old man with B-type cirrhosis. Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7. Contrast-enhanced US revealed heterogeneous, not diffuse, hypervascularity in the early phase and a defect in the Kupffer phase.Contrast-enhanced computed tomography （CT） revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase.Magnetic resonance imaging （MRI） revealed iso- to hypointensity at T1 and high intensity at T2-weighted sequences. Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase. Super-paramagnetic iron oxide-MRI revealed a hvoerintense nodule. CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect, respectively. Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC.Histologically, the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis. Immunohistochemically,the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin, and negative for cytokeratin 19. From the above findings, the nodule was diagnosed as scirrhous HCC. Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings, as shown in our case on the basis of chronic liver disease.

Patients without hepatocellular carcinoma progression after transarterial chemoembolization benefit from liver transplantation

AIM： To assess the outcome of patients, who underwent transarterial chemoembolization （TACE） for hepatocellular carcinoma （HCC） and subsequently liver transplantation （OLT） irrespective of tumor size when no tumor progression was observed. METHODS： Records, imaging studies and pathology of 84 patients with HCC were reviewed. Ten patients were not treated at all, 67 patients had TACE and 35 of them were listed for OLT. Tumor progression was monitored by ultrasound and AFP level every 6 wk. Fifteen patients showed signs of tumor progression without transplantation. The remaining 20 patients underwent OLT. Further records of 7 patients with HCC seen in histological examination after OLT were included. RESULTS： The patients after TACE without tumor progression underwent transplantation and had a median survival of 92.3 too. Patients, who did not qualify for liver transplantation or had signs of tumor progression had a median survival of 8.4 mo. The patients without treatment had a median survival of 3.8 mo. Independent of International Union Against Cancer （UICC） stages, the patients without tumor progression and subsequent OLT had longer median survival. No significant difference was seen in the OLT treated patients if they did not fulfill the Milan criteria. CONCLUSION： Selection of patients for OLT based on tumor progression results in good survival. The evaluation of HCC patients should not only be based on tumor size and number of foci but also on tumor progression and growth behavior under therapy.

Trans-arterial gene therapy for hepatocellular carcinoma in a rabbit model

AIM： To study the effect of adenovirus （Ad）-p53 gene therapy on hepatocellular carcinoma （HCC） in a rabbit model.METHODS： VX2 tumor was grown in the liver of 24rabbits. Animals were divided into four groups： group A receiving trans-arterial gene therapy （Ad-p53） only,group B receiving combined Ad-p53 therapy and transarterial embolization （lipiodol）, group C receiving transarterial chemoembolization （lipiodol ＋ mitomycin C）,control group （D） receiving sodium chloride. Tumor volume （V1） was measured by using MRI （d 13）.Interventional procedure was applied （d 14）.Tumor volume （V2） was assessed by MRT （d 21） and the mean ratio （V2/V1） was calculated. After the second MRI,specimens of the liver were abstained and examined immunohistochemically using mutant-type p53 antibody.The positive expression was scored.RESULTS： Compared with control group （（^-x） = 3.14± 0.64）, therapeutic groups all showed a significant decrease in the tumor growth ratio （P 〈 0.05）. A slight difference was found between group A （（^-x） =2.35 ±0.59） and group B （（^-x） = 1.75 ± 0.28） （P = 0.048）. Nostatistically significant difference was observed between group B and group C （（^-x） = 2.00 ± 0.44）. The positive expression rate of mutant-type p53 was the lowest in group B and significantly different between group A and group C （P 〈 0.05）.Compared to the control subjects, groups A and C both showed a decrease in the expression of mutant-type p53, but there was no significant difference between them.CONCLUSION： Trans-arterial Ad-p53 gene therapy can reduce tumor growth of HCC in rabbit model.

Experimental Study of the Effect of the Bax Gene on Human Hepatocellular Carcinoma and Therapy via Hepatic Artery Delivery

OBJECTIVE To investigate apoptosis induced by Bax in hepatocellular carcinoma cells and to examine the results of 2 different routes for in vivo gene delivery. METHODS The anti-hepatocellular carcinoma activity of the Bax gene transferred to the human hepatocellular carcinoma QGY7703 cell line was examined. In addition the Bax gene was transferred in vivo in mice via the caudal vein or hepatic artery to investigate the differences in target organ and non-target organ transfection. RESULTS 1）The Bax gene mediated by a binary adenoviral vector system induced apoptosis in the human hepatic carcinoma QFY7703 cell line. The cell apoptotic rate in the experimental group （Bax） was 50.2±6.9% but only 32.1 ± 9.7% in the Ad/CMV-p53 group, showing that the Bax-apoptotic rate was significantly higher than the control group. 2） LacZ expression was higher in the target organ （liver） when given through the hepatic artery than through the tail vein. In contrast, LacZ expression in the nontarget organs was higher if given through the tail vein compared to the hepatic artery. CONCLUSION Superselective hepatic artery delivery with Bax gene therapy is safe, specific, effective and has low toxicity. This study provided the basis for Bax-gene therapy via the hepatic artery in vivo.

Interventional and synthetic therapy of advanced hepatocellular carcinoma

OBJECTIVE: To evaluate the clinical efficacy of interventional therapy in the treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-three patients with HCC were synthetically treated by systematic measures. Among them, percutaneous port-catheter system (PCS) implantation via the femoral artery was performed in 21 cases. Patients with haemorrhage were treated with prothrombin complex concentrate and fibroraas, and patients with hepatic encephalopathy by branched-chain amino acids and arginine. RESULTS: All indwelling catheters of PCS were patent and no catheter tip dislocations were observed. Of 33 patients with advanced HCC, the mean survival rate was 20.1 months and 12 (36%) patients survived more than 2 years. CONCLUSION: Patients with advanced HCC were treated by synthetic measures. Survival was prolonged, quality of life was improved significantly, and the effectiveness of interventional therapy was further improved.

Utility of Doppler ultrasonography for predicting improvement of platelet count after transjugular intrahepatic portosystemic shunt

Objective.Portal pressure gradient(PPG)after transjugular intrahepatic portosystemic shunt(TIPS)<12mmHg has been reported as the only factor predictive of increase in platelet count.As flow velocities measured on Doppler ultrasound are related to pressure gradient based on the Bernoulli equation,we used this parameter to predict increased platelet count after TIPS placement.Methods.A total of 161 consecutive patients who underwent TIPS placement entered this retrospective study.The platelet count was measured before,one week after and one month after TIPS placement.Clinically significant thrombocytopenia was defined as platelet count≤100000.Pre-and post-TIPS PPGs were measured.The velocity of blood flow in the proximal,mid and distal TIPS stent was measured using Doppler ultrasound,and the difference in the highest and lowest measured velocity was entitled flow velocity gradient(FVG),which was considered normal when≤100 cm/s.Results.In 121 patients with pre-TIPS thrombocytopenia,the mean platelet count one week and one month after TIPS placement increased 25.7×10^(3) and 35.0 × 10^(3) in 90 patients with PPG≤12mmHg(P=0.028 and P=0.015),while there was no significant change in platelet count in patients with a PPG>12mmHg(P=0.098 and P=0.075).Platelets increased significantly when FVG≤100 cm/s(n=95)vs FVG>100 cm/s(n=26)one week(37.0×10^(3) vs 11.0×10^(3);P=0.005 vs 0.07)and one month after TIPS placement(17.0×10^(3) vs 5.2×10^(3);P=0.01 vs 0.21).Conclusion.FVG>100 cm/s is not associated with increase in post-TIPS platelet count.On the other hand,findings suggestive of proper TIPS function(FVG≤100 cm/s and PPG≤12mmHg)predict a significant increase in post-TIPS platelet count.

Portal vein thrombosis in patients with cirrhosis

Portal vein thrombosis(PVT)is frequent in patients with liver cirrhosis and possible severe complications such as mesenteric ischemia are rare,but can be life-threatening.However,different aspects of clinical relevance,diagnosis and management of PVT are still areas of uncertainty and investigation in international guidelines.In this article,we elaborate on PVT classification,geographical differences in clinical presentation and standards of diagnosis,and briefly on the current pathophysiological understanding and risk factors.This review considers and highlights the pitfalls of the various treatment approaches and prophylactic treatments.Finally,we review the controversial issue of clinical impact of PVT on prognosis,especially considering liver transplantation and future perspectives.

Renal-function change after transjugular intra-hepatic portosystemic shunt placement and its relationship with survival:a single-center experience

Background:The effect of transjugular intra-hepatic portosystemic shunt(TIPS)placement on renal function and the correlation of post-TIPS Cr with mortality remain unclear.This study aimed to assess the effect of TIPS placement on renal function and to examine the relationship between post-TIPS Cr and mortality risk.Methods:A total of 593 patients who underwent de novo TIPS placement between 2004 and 2017 at a single institution were included in the study.The pre-TIPS Cr level(T0;within 7 days before TIPS placement)and post-TIPS Cr levels,at 1–2 days(T1),5–12 days(T2),and 15–40 days(T3),were collected.Predictors of Cr change after TIPS placement and the 1-year mortality rate were analysed using multivariable linear-regression and Cox proportional-hazards models,respectively.Results:Overall,21.4%of patients(n=127)had elevated baseline Cr(≤1.5 mg/dL;mean,2.5161.49 mg/dL)and 78.6%(n=466)had normal baseline Cr(<1.5 mg/dL;mean,0.9260.26 mg/dL).Patients with elevated pre-TIPS Cr demonstrated a decrease in post-TIPS Cr(difference,-0.60 mg/dL),whereas patients with normal baseline Cr exhibited no change(difference,<0.01 mg/dL).The 30-day,90-day,and 1-year mortality rates were 13%,20%,and 32%,respectively.Variceal bleeding as a TIPS-placement indication(hazard ratio=1.731;P=0.036),higher T0 Cr(hazard ratio=1.834;P=0.012),and higher T3 Cr(hazard ratio=3.524;P<0.001)were associated with higher 1-year mortality risk.Conclusion:TIPS placement improved renal function in patients with baseline renal dysfunction and the post-TIPS Cr level was a strong predictor of 1-year mortality risk.

Variceal bleeding in cirrhotic patients

Variceal bleeding is one of the major causes of death in cirrhotic patients.The management during the acute phase and the secondary prophylaxis is well defined.Recent recommendations(2015 Baveno VI expert consensus)are available and should be followed for an optimal management,which must be performed as an emergency in a liver or general intensive-care unit.It is based on the early administration of a vasoactive drug(before endoscopy),an antibiotic prophylaxis and a restrictive transfusion strategy(hemoglobin target of 7 g/dL).The endoscopic treatment is based on band ligations.Sclerotherapy should be abandoned.In the most severe patients(Child Pugh C or B with active bleeding during initial endoscopy),transjugular intrahepatic portosystemic shunt(TIPS)should be performed within 72 hours after admission to minimize the risk of rebleeding.Secondary prophylaxis is based on the association of non-selective beta-blockers(NSBBs)and repeated band ligations.TIPS should be considered when bleeding reoccurs in spite of a well-conducted secondary prophylaxis or when NSBBs are poorly tolerated.It should also be considered when bleeding is refractory.Liver transplantation should be discussed when bleeding is not controlled after TIPS insertion and in all cases when liver function is deteriorated.