The object of this study is to evaluate the possibility of chemical-induced liver disorder among workers exposed to various chemicals and to classify the the liver function abnormalities by causes and to analyse the risk factors for each liver disorders. A cross-sectional study including questionnaire survey, physical examination, laboratory tests and ultrasonography of liver was conducted on 1,126 workers, 459 workers in a coal chemical plant(company A) and 667 workers in an insulation material manufacturing factory(company B). An industrial hygienist reviewed the chemicals used in both companies and evaluated the work environments to classify the workers by chemical exposure semiquantitatively. The results are as follows: 1. Of 459 workers in company A, 83 workers(18.1%) are classified as nonexposed, group 163(35,5%) as short-term exposure group, 155(33.8%) as intermediately exposed group and 58(12.6%) as long-term exposed group bared on the mean daily exposure to hepatotoxic chemicals evaluated by an industrial hygienist. Of 667 workers in company B, 484(72.6%) workers were classified as nonexposed and 183(35.5%) as exposed group. 2. Workers with SGOT level higher than 40 IU/l were (10.0%) in company A and 77(11.5%) in company 3, and those with SGPT level higher than 35 IU/l were 118(25.7%) in company A and 198(29.7%) in company B. The differences were not significant between companies and between exposure groups(p>0.05). Workers with $\gamma-GT$ level higher than 62 IU/l were 29(6.3%) in company A and 77(11.5%) in company B (p<0.01). The difference between exposure groups was not significant(p>0.05) within companies. Workers with liver function abnormalities(defined as SGOT higher than 40 IU/l or SGPT higher than 35 IU/l) were 338(30.0%) among 1,126 workers. Of 338 workers with live. function abnormalities 139(12.3%) had fatty liver by ultrasonography, 79(7.0%) had alcoholic liver(defined as workers with liver function abnormalities with weekly alcohol consumption greater than 280 g for more than 5 years), 54(4.8%) had hepatitis B, 12(1.1%) had hepatitis C and the other 114(33.7%) was not otherwise classified. Prevalences of alcoholic liver and fatty liver were significantly lower in company A(prevalence ratio 0.24 for alcoholic liver, p<0.001, prevalence ratio 0.76 for fatty liver, p<0.05) but prevalences of liver disorders between exposure groups within companies were not significant(p>0.05). 3. Summary prevalence ratios(SPR) of live. function abnormalities, fatty live. and other liver disorders, adjusted by age and company were not significantly higher in exposed group in any chemicals(p>0.05) but in some chemicals, SPRs were significantly lower. 4. On simple analysis of risk factors for liver function abnormalities, prevalence odds ratio(POR) of those with age between 30 and 39 was 1.54(p<0.01) and those with age ever 40 was 1.51(p<0.01). POR of those with histories of liver disorders and general anesthesia was 1.77(p<0.001) and 4.02 for those with overweight and 6.23 for those with obesity, defined by body mass index(p<0.001). 5. On logistic regression analysis, risk factors of liver function abnormality were fatty liver(POR 2.92 for grade 1, 12.15 for grade 2), presence of hepatitis B surface antigen(POR 3.62) and obesity(POR 5.38 for overweight and 16.52 for obesity). Presence of hepatitis B surface antigen(POR 0.18) was the only preventive facto. of fatty live. Company(POR 0.30) and obesity(POR 2.49 for overweight, 4.52 for obesity) were related to the alcoholic live. Obesity(POR 2.94 for overweight) was the only significant risk factor of hepatitis B and there was no significant risk factor for liver function abnormality not otherwise classified. It is concluded that the evidence of liver disorder related with chemical exposure is not evident in these factories. It is also postulated that fatty liver and alcoholic liver is most common causes of liver function abnormalities among workers and effort for weight control and improvement of life style should be done.
Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor ${\alpha}$ (TNF${\alpha}$) plays a critical role in progression of alcoholic liver disease. In the present study, we investigated the effects of cilostazol, a selective inhibitor of type III phosphodiesterase on ethanol-mediated TNF${\alpha}$ production in vitro and $in$$vivo$, and the effect of cilostazol was compared with that of pentoxifylline, which is currently used in clinical trial. RAW264.7 murine macrophages were pretreated with ethanol in the presence or absence of cilostazol then, stimulated with lipopolysacchride (LPS). Cilostazol significantly suppressed the level of LPS-stimulated TNF${\alpha}$ mRNA and protein with a similar degree to that by pentoxifylline. Cilostazol increased the basal AMP- activated protein kinase (AMPK) activity as well as normalized the decreased AMPK by LPS. AICAR, an AMPK activator and db-cAMP also significantly decreased TNF${\alpha}$ production in RAW264.7 cells, but cilostazol did not affect the levels of intracellular cAMP and reactive oxygen species (ROS) production. The $in$$vivo$ effect of cilostazol was examined using ethanol binge drinking (6 g/kg) mice model. TNF${\alpha}$ mRNA and protein decreased in liver from ethanol gavaged mice compared to that from control mice. Pretreatment of mice with cilostazol or pentoxifylline further reduced the TNF${\alpha}$ production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNF${\alpha}$ production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNF${\alpha}$ production by cilostazol.
Severe acute alcoholic liver disease (SAAH) unresponsive to medical therapy shows one-year-mortality rates of up to 90%. Most transplant centers request six months of alcohol abstinence prior to transplantation, the so-called "6-month rule." This regulation is not based on strong evidence, repeatedly making it a topic of controversial debates. The majority of patients with SAAH will die before fulfilling the 6-month rule. Therefore, liver transplantation (LT) protocols are becoming more flexible towards the rigid abstinence regulation, especially concerning SAAH patients. We conducted a literature review regarding LT in SAAH and its outcomes, including post-transplant mortality and recidivism. We studied available data on PubMed from 2011 and onwards whilst including articles dealing with genetic components, medical therapy and historic snapshots of alcoholism. Emerging studies recommend LT in SAAH not responding to medical therapies even without realizing the required abstinence period, since the majority of these patients would die within 6 months. SAAH without response to medical therapy has one-year-mortality rates of up to 90%. The 6-month rule is not based on strong evidence and is repeatedly a topic of controversial debates. There is genetic linkage to alcoholism and medical therapy is not as effective as estimated, yet. The 6-months-regulation has not shown to evidently decrease the risk of recidivism post-LT, which is a lifesaving treatment in SAAH patients. Insisting on rigid sobriety rules results in excluding patients with a low risk of recidivism from being transplanted. Moreover, the genetic linkage of alcoholism must be recognized.
Ferroptosis is a type of regulated cell death recently discovered, characterized by the accumulation of iron-dependent lipid peroxides in the cell membrane, and it involves a complex network of signaling pathways, including iron metabolism, lipid peroxidation, and redox regulation. The dysregulation of these pathways can lead to the induction of ferroptosis and the development of liver diseases, such as alcoholic liver disease, non-alcoholic fatty liver disease, viral hepatitis, and liver cancer. Studies have demonstrated that targeting key molecules involved in iron metabolism, lipid peroxidation, and redox regulation can reduce liver injury and improve liver function in different liver diseases by inhibiting ferroptosis. Thus, modulation of ferroptosis presents a promising therapeutic target for treating liver diseases. However, further research is required to gain a more comprehensive understanding of the mechanisms underlying the role of ferroptosis in liver diseases and to develop more effective and targeted treatments.
Alcoholic and nonalcoholic steaohepatitis is a leading form of chronic liver disease with few biomakers ad treatment options currently available. a progressive disease of NAFLD may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Recently, we extracted HIMH0021, which is an active flavonoid component in the Acer tegmentosum extract, has been shown to protect against liver damage caused by hepatic dysfunction. Therefore, in this study, we aimed to investigate whether HIMH0021 could regulate steatohepatitis and liver fibrosis during alcoholic or nonalcoholic metabolic process. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1a. These findings suggested that HIMH0021 could be used to target a TNFα-related pathway for treating patients with alcoholic hepatitis.
Objective: The objective of our present study was to assess the efficacy of carcinoembryonic antigen (CEA) for differentiating and diagnosis of pancreatic and liver diseases in Pokhara valley. Materials and methods: A hospital based retrospective study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st January, 2011 and 31st October, 2011. Estimation of CEA was performed by ELISA reader for all cases. Approval for the study was obtained from the institutional research ethical committee. Results: Of the 771 subjects, 208 (27%), 60(7.8%), 240(31.1%), 54(7.0%), 75(9.7%), 59(7.7%), 75(9.7%) cases were of active chronic hepatitis, cryptogenic cirrhosis, alcoholic cirrhosis, primary biliary cirrhosis, hepatoma, acute or chronic pancreatitis, carcinoma of pancreas respectively. The majority of cases (104) of active chronic hepatitis had CEA levels <5ng/ml(50%). CEA levels were found to be increased in cases of alcoholic cirrhosis with maximum number of cases (106) in range of 10 to 20 ng/ml (44%). There were no cases having more than 20ng/ml of CEA in primary biliary cirrhosis and acute or chronic pancreatitis. In cases of pancreatic cancer, maximum number of cases (35) were having CEA >20ng/ml(47%). Conclusion: High levels of CEA are associated with advanced stage of disease. CEA can thus provide an important improvement in the diagnosis by differentiating pancreatic cancer especially from chronic pancreatitis when there is a high suspicion of malignancy. Increased CEA levels may also signify progression from benign to malignant transformation in the liver.
Objectives: The purpose of this study was to retrospectively assess the effectiveness of Chunggan plus extract (CGX) in improving liver function in a Korean medical clinic. Methods: We collected the data of inpatients who received CGX to improve abnormal liver function test (LFT) results from March 2016 to February 2020. We analyzed the changes in LFT and adverse events based on subjective symptom changes and creatinine results. Results: The data of eight patients, three male and five female, were selected by inclusion criteria (patients who did LFT before and after the prescription of CGX and who prescribed CGX more than 6 days) and exclusion criteria (patients who administered other herbal medicine for improving liver function except CGX and who are diagnosed with terminal stage of hepatobiliary cancer). As a cause of abnormal LFT, one case was diagnosed with alcoholic liver disease, two cases with non-alcoholic fatty hepatitis, and one case with cholecystitis. Three of the other four were suspected to have drug-induced hepatitis, and one case was determined to have an unknown cause. Most patients showed a decrease in LFT results (Aspartate transaminase 87.5%, Alanine transaminase 87.5%, and Alkaline Phosphatase 100%) without any critical adverse events. Conclusions: CGX may be an efficient and convenient herbal medicine for improving liver function regardless of the chief impression. Further study should be conducted to evaluate the effectiveness of CGX.
Objectives: The purpose of this study was to examine the efficacy of Gamichunggan-san(Jiaweiqinggan-san) on 25 patients who have suffered from alcoholic liver disease. Methods: Gamichunggan-san(Jiaweiqinggan-san) was administered to patients for over 1 months continuously. We checked improvement of clinical symptoms, changes of chemistry hematological test and especially lymphocyte count. Results: The results obtained are summarized as follows. Gamichunggan-san(Jiaweiqinggan-san) has significant effect on the improvement of clinical symptoms. And the improvement ratio of AST, ALT, ${\gamma}$-GTP was 77.8%, 61.5%, 76.2%. In patients with alcohoiic hepatitis, WBC was increased effectively within normal range and those with liver cirrhosis, All of the patients with the inverted ratio of lymphocyte was improved. Conclusions: From the above results, it is suggested that Gamichunggan-san(Jiaweiqinggan-san) have significant effects on recovery of liver malfunction and immune modulation, and also could be recommended as a prescription for alcoholic liver disease.
Objectives: This study aimed to investigate the trend in the research on alcoholic liver disease (ALD) using Korean traditional medicine. Methods: This review was conducted using six electronic databases (NDSL, KMBASE, Koreantk, KISS, KISTI, and KoreaMed) with no restrictions in year. The search terms were "alcoholic liver disease", "alcoholic fatty liver", "alcoholic hepatitis", "alcoholic cirrhosis", "herbal medicine", "acupuncture" and "traditional medicine". The searched studies were analyzed according to the type of research. Results: After screening, 37 studies were selected among 552. The types of studies were as follows: 8 in vivo studies, 17 case reports, 7 case series, 1 assessment scale study, 1 randomized controlled trial, and 3 research reviews. The in vivo studies reported the efficacy and its mechanism in the animal phase of single or complex herbal medicine. In the clinical research, interventions such as herbal medicine and acupuncture were most commonly used for ALD treatment. Conclusions: We analyzed the trends in ALD treatment using Korean traditional medicine through this review. The results showed that Korean traditional medicine could be an effective method for ALD treatment. Conducting related in-depth studies, such as well-designed randomized controlled trial based on the results of experimental research, is necessary.
Objective: To investigate the possibility of hepatotoxicity by supplemental foods or folk herbs such as Salvia Plebeia R. Br. Methods: A hospitalized male patient with alcoholic liver disease and electrolyte imbalance had recovered, and then followed by rapid hepatic serum enzymes after taking S. Plebeia. This study monitored the clinical outcome and biochemical parameters. Result: A 58-year male had drunk frequently, which led to alcoholic steatohepatitis and hospitalization. Two weeks after his discharge from hospital, he felt nausea, dizziness, and mild difficulties in speech and walking, resulting in re-hospitalization at the Korean Medical Hospital. The symptoms disappeared on correction of the electrolyte imbalance suspected to have been caused by severe sweating while working in the outdoors, and the patient was discharged. During treatment and monitoring of his health as an outpatient, the serum hepatic enzyme rapidly elevated approximately 10-fold in hepatic enzymes; the enzyme levels fluctuated according to whether or not he was taking the boiled water of S. Plebeia. The RUCAM score was 12, which met the criteria for toxic hepatitis by S. Plebeia. His general condition and abnormal hepatic enzymes recovered with cessation of S. Plebeia and administration of Chungganplus syrup (CGX). Conclusion: This study reports the hepatotoxic risk of Salvia Plebeia, which is commonly used as a folk remedy in Korea.
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