Non-alcoholic Steatohepatitis Pathogenesis, Diagnosis, and Treatment

There has been a rise in the prevalence of non-alcohol fatty liver disease (NAFLD) due to the popularity of western diets and sedentary lifestyles. One quarter of NAFLD patients is diagnosed with non-alcoholic steatohepatitis (NASH), with histological evidence not only of fat accumulation in hepatocytes but also of liver cell injury and death due to long-term inflammation. Severe NASH patients have increased risks of cirrhosis and liver cancer. In this review, we discuss the pathogenesis and current methods of diagnosis for NASH, and current status of drug development for this life-threatening liver disease.

A Study on the Serum γ-Glutamyltranspeptidase and Plasma Osteopontin in Alcoholic Liver Disease

Background Alcoholic liver disease (ALD) is a major source of alcohol-related morbidity and mortality. Heavy drinkers and alcoholics may progress from fatty liver to alcoholic hepatitis to cirrhosis. The enzyme γ-glutamyltranspeptidase (GGT) is a membrane-bound glycoprotein which catalyzes the transfer of the γ-glutamyl group from γ-glutamyl peptides to other peptides, amino acids, and water. Serum GGT activity mainly attributed to hepatobiliary system and thus is an important marker of ALD. Hence the present study is conducted to estimate and correlate the levels of GGT and osteopontin (OPN) in ALD. Aims and Objectives The objective of this study is to estimate and correlate the levels of GGT and OPN in ALD. Materials and Methods Sixty clinically diagnosed cases of ALD and sixty age- and gender-matched healthy controls were recruited for the study. Blood samples were collected from them and serum aspartate aminotransferase, serum alanine transaminases (ALTs), serum ALP levels, and plasma OPN levels were measured. Estimation of serum aspartate transaminases (AST), ALTs, and alkaline phosphatase (ALP) was assayed by standard photometric methods in autoanalyzer ERBA-XL (EM-200) using commercially available kits. OPN was estimated by using commercial kit based on enzyme-linked immunosorbent assay. Results The parameters of the liver function tests such as AST, ALT, and ALP were significantly increased in patients with ALD (p < 0.001) when compared with the healthy control subjects. In the present study, significantly increased levels of γ-glutamyl transferases and OPN were found in patients with ALD (p < 0.001) when compared with the control subjects. OPN showed significant positive correlations with AST (r = 0.76, p < 0.001), ALT (r = 0.64, p < 0.001), ALP (r = 0.68, p < 0.001), and GGT (r = 0.61, p < 0.001). Conclusion The present study focuses on the role of GGT and OPN that are sensitive indicators of liver cell injury and are most helpful in recognizing hepatocellular diseases such as ALD, hepatitis, and liver cirrhosis. Hence, the pattern of the GGT and OPN levels elevation can be helpful diagnostically.

Effect of Different Ratios of Yinchen and Gancao Decoction on ANIT-Treated Cholestatic Liver Injury in Mice and Its Potential Underlying Mechanism

Cholestasis is a pathological state that leads to serious liver disease; however, therapeutic options remain limited. Yinchen and Gancao are often used in combination at different ratios in traditional Chinese formulae for the treatment of jaundice and cholestasis. In the present study, we investigated the effect of decoctions containing different ratios of Yinchen and Gancao (YGD) on alpha-naphthyl isothiocyanate (ANIT)-treated intrahepatic cholestasis (IC) in mice, and further explored the underlying mechanism. Treatment with 0:4 and 1:4 YGD significantly reduced plasma total bile acid (TBA), total bilirubin (TBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities; decreased unconjugated and conjugated bile acid levels; and improved hepatocyte necrosis and inflammatory cells recruitment to hepatic sinusoids. Moreover, the expression levels of Toll-like receptor 4 (TLR4), interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), C-C ligand 2 (CCL2), and C-X-C ligand 2 (CXCL2) in the liver were significantly reduced. However, treatment with 4:1 and 4:0 YGD increased plasma TBA, TBIL, AST, ALT, and ALP activities and aggravated liver cell injury and inflammation. Moreover, the mRNA expression of the bile salt export pump (BSEP) in the liver was significantly increased in mice treated with 4:0 YGD. The present study demonstrates that YGD containing a high proportion of Gancao, which inhibits the TLR4/NF-κB pathway and reduces the inflammatory response, had protective effects against ANIT-treated IC in mice. However, YGD containing a high proportion of Yinchen aggravated the ANIT-treated IC in mice, which may be related to upregulation of BSEP and boosting bile acid regurgitation from damage cholangiocytes to liver in ANIT-treated IC mice.

Undifferentiated embryonal sarcoma of liver in a 9-year-old: case report

<p>The embryonal sarcoma of the liver is an extremely malignant, aggressive and infrequent condition of the liver, predominantly affecting children in the age groups of four to ten. The disease manifests with fever, abdominal pain or mass, nausea and laboratory findings suggestive of liver cell injury. The diagnosis can be made using tumor markers, imaging, immunohistochemistry and histopathology. The multimodal management protocol focuses the use of surgical resection, chemotherapy and radiation to significantly improved survival rates and quality of life in these patients.</p>

An HBV-encoded miRNA activates innate immunity to restrict HBV replication

We previously identified that hepatitis B virus (HBV) encodes a microRNA (HBV-miR-3) that restrains HBV replication by targeting the HBV transcript. However, whether HBV-miR-3 affects host innate immunity to modulate HBV replication remains unclear. Here, we examined the vital functions of HBV-miR-3 in the innate immune response after HBV infection. We found that HBV-miR-3 expression gradually increased in a dose- and time-dependent manner in HBV-infected HepG2-NTCP cells. HBV-miR-3 activated the JAK/STAT signaling pathway by downregulating SOCS5 in hepatocytes, thereby enhancing the IFN-induced anti-HBV effect. In addition, HBV-miR-3 in exosomes facilitated the M1 polarization of macrophages. Furthermore, exosomes containing HBV-miR-3 enhanced the secretion of IL-6 via inhibiting the SOCS5-mediated ubiquitination of EGFR. In short, these results demonstrate that HBV-miR-3 activates the innate immune response to restrain HBV replication by multiple pathways, which may suppress HBV-induced acute liver cell injury and affect the progression of persistent HBV infection.

Evaluation of Protective Activity of Curcumin in Reducing Methotrexate Induced Liver Cells Injury: An Experimental Study on Iraqi White Domestic Rabbits

Background: Hepatotoxicity is a common problem in medical practice, most of the commonly used drugs are potentially hepatotoxic. Although Methotrexate is a hepa- toxic drug, it is widely used in the treatment of many cancerous and non-cancerous conditions because of its cytotoxic and immunosuppressant activity. Curcumin con- tains a variety of natural substances with antioxidant properties, it is widely used in folk medicine.Antioxidant activity of Curcumin can reduce liver cell injury induced by Methotrexate administration. Objective: The research aims to study the methotrexate hepatoxicity on rabbits, and the hepatoprotective activity of Curcumin. Materials and Methods: Thirty white domestic rabbits were bought from animal market and grouped randomly into three groups; control group received intraperitoneal normal saline, methotrexate group received 6.5 mg/Kgm body weight intraperitoneal methotrexate, and curcumin group received oral Curcumin in addition to intraperitoneal methotrexate. Results: The study showed abnormal liver function tests, INR, liver tissues oxida- tive markers, and liver cell injury on histopathology in Methotrexate group, and normal findings in Curcumin groups. Conclusion: It is concluded that the Methotrexate is a hepatotoxic drug. The results also shoe that the concomitant administration of Curcumin reduced hepatotoxicity. Recommendation: It is recommended to use of Curcumin in clinical practice as a food supplement to patient receiving methotrexate to reduce hepatotoxicity.