Co-occurrence of opisthorchiasis and diabetes exacerbates morbidity of the hepatobiliary tract disease

Abstract

Complications arising from infection with the carcinogenic liver fluke Opisthorchis viverrini cause substantial morbidity and mortality in Thailand and adjacent lower Mekong countries. In parallel, the incidence rate of diabetes mellitus (DM) is increasing in this same region, and indeed worldwide. Many residents in opisthorchiasis-endemic regions also exhibit DM, but the hepatobiliary disease arising during the co-occurrence of these two conditions remains to be characterized. Here, the histopathological profile during co-occurrence of opisthorchiasis and DM was investigated in a rodent model of human opisthorchiasis in which diabetes was induced with streptozotocin. The effects of excretory/secretory products from the liver fluke, O. viverrini (OVES) on hepatocyte and cholangiocyte responses during hyperglycemic conditions also were monitored. Both the liver fluke-infected hamsters (OV group) and hamsters with DM lost weight compared to control hamsters. Weight loss was even more marked in the hamsters with both opisthorchiasis and DM (OD group). Hypertrophy of hepatocytes, altered biliary canaliculi, and biliary hyperplasia were more prominent in the OD group, compared with OV and DM groups. Profound oxidative DNA damage, evidenced by 8-oxo-2'-deoxyguanosine, proliferating cell nuclear antigen, and periductal fibrosis characterized the OD compared to OV and DM hamsters. Upregulation of expression of cytokines in response to infection and impairment of the pathway for insulin receptor substrate (IRS)/phosphatidylinositol-3-kinases (PI3K)/protein kinase B (AKT) signaling attended these changes. In vitro, OVES and glucose provoked time- and dose-dependent effects on the proliferation of both hepatocytes and cholangiocytes. In overview, the co-occurrence of opisthorchiasis and diabetes exacerbated pathophysiological damage to the hepatobiliary tract. We speculate that opisthorchiasis and diabetes together aggravate hepatobiliary pathogenesis through an IRS/PI3K/AKT-independent pathway.

Association of comorbidity between Opisthorchis viverrini infection and diabetes mellitus in the development of cholangiocarcinoma among a high-risk population, northeastern Thailand

“…viverrini infection group or the DM group alone. This is consistent with a previous study conducted in a hamster model [ 18 ]. Potential mechanisms to explain this increased CCA risk have been explored in some studies.…”

“…viverrini infection worsens diabetes-related damage to the liver and bile ducts in rodents, CCA patients’ tissues, and cultured human CCA cells [ 18 , 33 ]. As well, co-occurrence of opisthorchiasis and DM in hamsters and tissue cultures of human liver cells has been found to lead to more severe disease in the liver than is caused by either condition alone [ 18 ]. High glucose levels can stimulate the proliferation and metastatic ability of CCA cells derived from patients with chronic O .…”

“…The relationship between CCA and a combination of O . viverrini infection and DM has also been investigated in hamsters, revealing that infection with liver fluke during diabetes leads to more serious disease in the liver than is due to either condition alone [ 18 ]. However, there has been no previous investigation in humans of any relationship between CCA and a combination of O .…”

Opisthorchis viverrini Infection Augments the Severity of Nonalcoholic Fatty Liver Disease in High-Fat/High-Fructose Diet–Fed Hamsters

“…7 Moreover, infection causes hepatocyte enlargement and enhances severity of hepatobiliary disease in diabetic hamsters. 9 All of these reports suggest that, apart from the biliary system, Ov infection also may have negatively impacted hepatocyte biology along with a spectrum of other hepatobiliary diseases.…”

Metabolic syndromes, carbohydrate and lipid metabolism disorders in helminthic infections: review of the literature

“…при изучении сочетанного течения СД 1 и инвазии O. viverrini в ýксперименте наблюдали желтуху и гепатомегалию, повышение уровня трансаминаз, щелочной фосфатазы, повреждение гепатоцитов, их гипертрофию и пролиферацию. При сочетании СД 1 и описторхоза усугубляются фиброз печени и окислительное повреждение дезоксирибонуклеиновой кислоты, происходит повышенная ýкспрессия провоспалительных интерлейкинов 6, 12, 13 [40].…”