钟森教授谈药物性肝损伤的辨证论治

钟森教授是成都中医药大学博士研究生导师，中国中西医结合学会传染病专业委员会和肝病专业委员会委员，四川省中西医结合学会肝病专业委员会副主任委员。钟教授对肝病和结核病研究多年，擅长运用中医学理论解决现代临床新问题。笔者有幸跟随导师学习，现将其治疗“药疸”（即药物性肝损伤）所致黄疸的临证经验总结如下。

Resolution of tuberculous biliary stricture after medical therapy

Tuberculosis （TB） is a very rare cause of biliary stricture that is difficult to diagnose and usually requires surgical intervention in order to rule out underlying malignant etiology. We report a 56-year-old man presented with jaundice, weight loss and poor appetite. Initial work up showed the dilated biliary system secondary to distal common bile duct stricture. Investigations to define the etiology of this stricture showed inconclusive brush cytology with absent abdominal masses and lymph nodes but enlarged mediastinal lymph nodes. Biopsy from these lymph nodes showed a non-caseating epitheliod granuloma with negative acid fast bacilli （AFB） stain. The patient had a dramatic response to empirical antituberculosis therapy. Six weeks later, culture from lymph nodes was positive for Mycobacteriurn tuberculosis. Three months later, follow-up cholangiogram showed complete resolution of the stricture with normalization of liver enzymes 6 mo after starting anti-tuberculosis therapy. Treatment was continued for 12 mo and the patient had a normal life with normal liver enzymes and regression of the mediastinal lymph nodes at the time when he was reported in this paper. Although 16 cases of tuberculous biliary stricture are available in the English literature, up to our knowledge, this is the second published report of tuberculous biliary stricture, which resolved completely after medical therapy alone and the second reported case from the Middle East. This report emphasizes the importance of keeping TB as a possibility of biliary stricture in this part of the world.

N-acetyl cysteine therapy in acute viral hepatitis

AIM: To investigate the effect of N-acetyl cysteine (NAC)on acute viral hepatitis (AVH).METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control group. All patients were hospitalized and diagnosed as AVH. Blood total and direct bilirubin, ALT, AST,alkaline phosphatese, albumin and globulin levels of each patient were measured twice weekly until total bilirubin level dropped under 2 mg/dl, ALT level under 100 U/L, follow up was continued and then the patients were discharged.RESULTS: A total of 41(13 female and 28 male) AVH patients were included in our study. The period for normalization of ALT and total bilirubin in the study group was 19.7±6.9 days and 13.7±8.5 days respectively. In the control group it was 20.4±6.5 days and 16.9±7.8 days respectively (P＞0.05).CONCLUSION: NAC administration effected neither the time necessary for normalization of ALT and total bilirubin values nor duration of hospitalization, so we could not suggest NAC for the treatment of icteric AVH cases. However, our results have shown that this drug is not harmful to patients with AVH.

The effect of traditional Chinesemedicine washing combined withmassage for neonataljaundice： a meta-analysis

Objective： To systematically assess the effect of traditional Chinese medicine washing （TCM washing） combined withmassage for the treatment of neonatal jaundice.Methods and analysis： Databases, including PubMed, the Cochrane Library, Embase, Web of Science, the ChineseBiomedical Literature Database （CBM）, CNKI, and Wanfang Data were electronically searched for randomizedcontrolled trials （from inception to July 2017）. The methodological qualities of included trials were evaluated by theCochrane risk of bias assessment tool. The meta-analysis was performed by using RevMan 5.3 software.Results： Overall, thirteen trials with a total of 1998 participants were included. The results of meta-analysis indicatedthat TCM washing combined with massage group was significantly superior to the control group in the first meconiumtime （MD, -16.67; 95% CI, -24.59 to -8.74; P〈0.001）, time for transformation of meconium （MD, -15.44; 95% CI,-23.59 to -7.28; P〈0.001）, transcutaneous bilirubin index changes [after treating three days （MD, -1.99; 95% CI, -2.57 to-1.40; P〈0.001）, after treating four days （MD, -1.86; 95% CI, -2.77 to -0.95; P〈0.001）, after treating five days （MD,-2.44; 95% CI, -3.47 to -1.42; P〈0.001）, after treating six days （MD, -2.23; 95% CI, -3.30 to -1.16; P〈0.001）, and thechanges of serum bilirubin levels [after treating five days （MD, -3.17; 95% CI, -5.83 to -0.50; P=0.02）, after treating sixdays （MD, -1.63; 95% CI, -3.10 to -0.16; P=0.03）, after treating fifteen days （MD,-1.20; 95% CI, -1.99 to -0.41; P=0.003）.Conclusions： TCM washing combined with massage may be an effective therapy for the treatment of neonatal jaundice.It can accelerate the excretion of meconium, shorten the time for transformation of meconium, and decreasetranscutaneous bilirubin index and the level of serum bilirubin. But it should be careful to interpreting these findings.Well-designed RCTs are needed to further clarify the conclusion.

Bilirubin Lowering Potential of Aqueous Carica Papaya Extract in Induced Jaundice in Rats

Background： The mature unripe fruit of aqueous Carica papaya （ACP） is used in Nigerian traditional medicine for the treatment of jaundice. Work done on aqueous extract of the unripe C. papaya in an acute oral toxicity study in rats showed the LD50 to be 2,520 mg/kg in rats. Current study evaluated the bilirubin-lowering potential of ACP extract in phenylhydrazine （40 mg/kg） induced jaundice in adult rats. Method： Jaundice was assessed by measuring the levels of TB （total bilirubin） and DB （direct bilirubin） in phenylhydrazine-treated animals with or without drug treatment, with CUR （curative）, PRO （prophylactic study）, and in animals with RLC （reduced liver capacity）. Results： Result demonstrated that TB level of 24.0 μmols/L, 22.0 μmols/L and 45.0 μmols/L in the jaundiced group of the CUR, PRO and RLC respectively was significantly lowered （p 〈 0.05） to 10.0, 13.0, and 17.0 respectively by 400 mg/kg of the extract. Total bilirubin level of 24.0 btmols/L, 22.0 lamols/L and 45.0 μmols/L in the jaundiced group of the CUR, PRO and RLC respectively was significantly lowered （p 〈 0.05） to 7.0, 10.0, and 17.0 respectively by 800 mg/kg extract. Conclusion： The study concluded that ACP fruit extract has ability to lower elevated bilirubin level and confer hepatoprotective effect as seen from the liver function test indices thus justifying its ethnomedicinal use.

Daily administration times of Canhuang tablet based on a pharmacodynamic/pharmacokinetic model in jaundiced rats

OBJECTIVE: To study the daily administration times of Canhuang tablet(CHT) for treating jaundice in rats based on a pharmacodynamic/ pharmacokinetic model.METHODS: Rats were modeled by 4% 1-Naphthylisothiocyanate(75 mg/kg, p.o.). After 48 h, CHT was given(p.o.) at 0.75 g/kg once a day, 0.375 g/kg twice a day, and 0.25 g/kg three times a day. Blood was collected from the orbital sinus at different intervals. Levels of liver enzymes and bilirubin were detected using these blood samples. Bile was collected and determined after the first administration of CHT. High-performance liquid chromatography was used to determine the concentration of berberine in bile simultaneously. Time-effect and time-dose curves were then obtained.RESULTS: Compared with rats taking CHT twiceand three times a day, the total amount of bile within 10 h of rats taking CHT once a day were 1.32-and 1.47-fold higher, respectively. There was good consistency between the pharmacokinetics of berberine and the pharmacodynamics of the effect on liver enzymes and bilirubin in vivo. The pharmacokinetic analyses showed that rats administered CHT once daily maintained a higher concentration of berberine in bile for a longer period than rats administered CHT two- and three-times daily.CONCLUSION: In jaundiced rats, taking CHT once a day is better than taking CHT twice or three times a day. These data may provide a reference for the clinical application of CHT.