Drug induced autoimmune hepatitis:An unfortunate case of herbal toxicity from Skullcap supplement:A case report

BACKGROUND The surge in traditional herbal dietary supplement(HDS)popularity has led to increased drug-induced liver injuries(DILI).Despite lacking evidence of efficacy and being prohibited from making medical claims,their acceptance has risen over sevenfold in the last two decades,with roughly 25%of United States(US)adults using these supplements monthly.An estimated 23000 emergency room visits annually in the US are linked to HDS side effects.NIH-funded research suggests HDS contribute to 7-20%of DILI cases,with similar trends in Europe—Spain reporting 2%and Iceland up to 16%.Patients with acute liver failure from HDS undergo liver transplantation more frequently than those from prescription medicines.Here we describe a case of drug-induced autoimmune hepatitis due to Skullcap supplements,this association appears to be the first documented instance in literature.CASE SUMMARY A middle-aged Caucasian woman,previously healthy,presented with sudden jaundice.Four months earlier,her liver enzymes were normal.She mentioned recent use of Skullcap mushroom supplements.Tests for chronic liver disease were negative.The first liver biopsy indicated severe resolving drug-induced liver injury.Despite treatment,she was readmitted due to worsening jaundice.Followup tests raised concerns about autoimmune hepatitis.A subsequent biopsy confirmed this diagnosis.The patient responded as expected to stopping the medication with improvement in liver enzymes.CONCLUSION This scenario highlights an uncommon instance of DILI caused by Skullcap supplements.It's crucial for hepatologists to recognize this connection due to the increasing prevalence of herbal supplements.

HIGH DOSE INTRA-ARTERIAL HEPATIC INFUSIONAL CHEMOTHERAPY WITH DRUG FILTRATION (HAI-F) FOR PRIMARY LIVER CANCER(A PRELIMINARY REPORT)

Fifteen patients with unresectable hepatocellular carcinoma were treated with unresectable hepatocellular carcinoma were treated with high dose MMC or ADR via hepatic artery with drug filtration in our hospital from April to December 1988. Among them, 11 cases (73%) had symptoms relief, 3 cases (20%) tumor minimal remission and AFP decreased in 4 cases (33%). One case dide of hep'atoma 8 months after HAI-F and another case was followed up only 2 months after treatment, the remaining 13 cases are alive for 5 to 10 months after HAI-F. The reasons of unsatisfactory results were analyzed and possible ways of improvement were suggested.

Study on synthesis and distribution in vivo of 5-Fu-cholic acid conjugate

A series of hepatic targeting drugs, 5-Fu-cholic acid conjugate T1-T5, were synthesized. 5-Fu and cholic acid was selected as starting material, after N-hydroxymethylation, condensation, hydrogenolysis to obtain carboxylated 5-Fu 5a-e. Carboxylated 5-Fu 5a-e were condensated with intermediate 3-hydroxyethyl cholic acid benzyl ester 6 to get 7a-e, 7a-e were deprotected to get T1- T5.

The 2016 Lasker-DeBakey Clinical Medical Research Award: Innovative hepatitis C virus(HCV) replicons leading to drug development for hepatitis C cure

The 2016 Lasker-DeBakey Clinical Medical Research Award was given to three scientists working on different stages of the translational sciences on bringing a high efficacious therapy against hepatitis C virus （HCV） infection to a reality. An effective treatment of HCV chronic infection was developed, by a team led by Michael Sofia, using a prodrug approach and the drug PSI-7977 or Sofosbuvir was approved in 2013 less than 28 years after the initial discovery of HCV.

Preliminary research on the co-infection of human immunodeficiency virus and hepatitis virus in intravenous drug users

Objective To confirm the close relationship of high co-infection rate between HIV and hepatitis virus in intravenous drug users (IVDUs).Methods Anti-HIV, HBV and HCV were detected by ELISA in the serum from 35 scattered and 15 massed IVDUs. PCR and RT-PCR were performed to confirm the infection of HIV, HBV, HCV, HGV and TTV among the 15 massed intravenous drug abusers.Results Among the 50 IVDUs, the positive rates of anti-HCV, HBsAg, anti-HBe and anti-HBc were 92% (46/50), 12% (6/50), 10% (5/50) and 66% (33/50), respectively. In the samples of HBsAg positive, their HBeAg was also positive. Although the positive rate of serum markers was different in the massed IVDUs compared to the scattered IVDUs, no significant difference was shown. In the cases of massed IVDUs, the positive rates of HIV DNA, HBV-DNA, HCV-RNA, HGV-RNA, and TTV-DNA were 100% (15/15), 26. 6% (4/15), 53. 3% (8/15), 33. 3% (5/15) and 26. 6% (4/15), respectively. Among the 15 massed intravenous drug users, one was infected with HIV, HBV, HCV, HGV and TTV; two were infected with HIV, HBV, HCV and HGV; three were infected only with HIV; and the remaining had other forms of co-infection.Conclusion The co-infection rate of HIV, HBV, HCV, HGV and TTV in intravenous drug users is very high.

S-1 induced hepatic steatosis in patients with pancreatic cancer:Retrospective analysis

To determine whether S-1 induces hepatic steatosis in patients being treated for pancreatic cancer. METHODSThis retrospective study evaluated 22 patients who received oral S-1 as a first-line treatment for pancreatic cancer between January 2008 and July 2015 at the Ishikawa Prefectural Central Hospital. Patients underwent abdominal computed tomography (CT) scans before chemotherapy and within 3 mo from the start of treatment. CT numbers of the liver and spleen were measured before and after S-1 administration. Steatosis was diagnosed when the ratio of the CT number of the liver to that of the spleen (liver/spleen ratio) was < 0.9. RESULTSMedian patient age was 68 years (range, 48-85 years), and median body mass index was 21 kg/m2 (range, 18-27 kg/m2). Of the 22 patients, six (27%) regularly consumed alcohol, and five (23%) had liver metastases. The mean ratio of CT number of the liver to the spleen was significantly higher before administration of S-1 (1.27 vs 1.09, P = 0.012) compared with after. Of the 22 patients, five (23%) had hepatic steatosis and 17 (77%) did not. The pretreatment demographic and clinical characteristics of these two groups showed no significant differences. The relationship between liver/spleen ratio and alanine transaminase activity in these patients. A statistically significant inverse correlation was observed (r = -0.417, P < 0.027). CONCLUSIONOf the 22 patients with pancreatic cancer, five (23%) experienced S-1 induced hepatic steatosis. Care should be taken during S-1 treatment of patients with pancreatic cancer.

M2-type macrophage membrane-mediated delivery of Carvedilol nanocomplex for acute liver failure treatment and remodeling inflammatory microenvironment

Interactions of hepatic macrophages with local inflammatory microenvironment is the key factor promoting the development of acute liver failure(ALF).Hence,reprogramming pro-inflammatory M1 into anti-inflammatory M2 phenotype may offer a promising strategy for treating ALF by targeting inflammation.Our group found Carvedilol possessed potential anti-inflammatory property previously,which had been scarcely reported in ALF.We present a synergy strategy to induce macrophages into the phenotype M2-type anti-inflammatory macrophages with interleukin-4(IL-4)and IL-10 at first.Then Carvedilol is loaded on the macrophage membrane-camouflaged biomimetic nano-platform(termed as M2M@CNP)to evade reticuloendothelial system(RES)and afford Carvedilol delivery to the inflammatory environment with overproduced reactive oxygen species(ROS),further prolonging its circulation and accumulation.Sustainably released Carvedilol produced anti-inflammatory,antioxidant and anti-apoptosis effects,combining local M2-type cell membranes(M2-CM)inhibited pro-inflammatory cytokines and ROS levels,which in turn promoted and amplified M1 to M2 phenotype polarization efficiency.This study offers new insights into the rational design of biomimetic nanosystems for safe and effective ALF therapy to accelerate the clinical translation.

Investigating Genotype 1a HCV Drug Resistance in NS5A Region via Bayesian Inference

Hepatitis C virus（HCV） treatment is on the cutting edge of medicine. Due to the high rate of mutations and low fidelity of HCV replication, resistant strains quickly become dominant in a viral population under the selection pressure of a drug. In this paper, we examined the drug resistance mechanism in the NS5 A region of genotype1 a HCV virus by comparing the sequence data from interferon-ribavirin treated and untreated patients. To find the drug resistance difference, we used innovative Bayesian probability models to detect mutation combinations and inferred detailed interaction structures of these mutations. We aim to provide reference to drug design and mutation mechanism understanding through our work.