Association of pro-inflammatory cytokines, adipokines & oxidative stress with insulin resistance & non-alcoholic fatty liver disease.

Background & objectives: The cytokines, adipokines, and oxidative stress have been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD); however, such data remain scarce in India. The present study evaluated pro-inflammatory cytokines, adipokines, and markers of oxidative stress in patients with non-alcoholic fatty liver disease (NAFLD), and their association with degree of adiposity, insulin resistance and markers of disease severity. Methods: The present prospective cross-sectional pilot study included 79 subjects; 34 NAFLD, 22 chronic hepatitis B (CH-B) and 23 healthy controls (HC). The parameters studied were adiponectin, leptin, tumour necrosis factor α (TNFα), interleukin-1 and 6 (IL-1, IL-6), and systemic markers of oxidative stress. Results: The mean body mass index (kg/m2) in NAFLD patients, CHB, and HC were 26.4±3.7, 21.3±2.3, and 22.3±2.7, respectively. The median serum levels of all pro-inflammatory cytokines were significantly higher (P<0.001) in NAFLD compared to control groups. Compared to HC, levels of adiponectin and leptin were significantly (P<0.05, P<0.01) reduced in both NAFLD and CHB. IL-6 showed marked and selective increase only in NAFLD patients. The levels of IL-6 were significantly (P<0.02) higher in NAFLD patients with advanced histology grade and correlated with IR (r=0.42, P=0.02). In a sub-group, markers of oxidative stress were significantly higher, and that of antioxidant potential were significantly lower among NAFLD patients compared to control subjects. Interpretation & conclusions: Patients with NAFLD revealed significantly elevated levels of pro-inflammatory cytokines, increased oxidative stress, and a significant association of IL-6 with IR and advanced histopathology.

Pathogenesis of non alcoholic fatty liver disease: Present concepts.

Non alcoholic fatty liver disease has become a common cause for the chronic liver disease, a clinicopathological entity characterised by excessive triglyceride accumulation in hepatocytes. The spectrum of non alcoholic fatty liver disease varies from simple steatosis, a relatively benign condition, to steatohepatitis which may ultimately progress to cirrhosis and end stage liver disease. Its pathophysiology is complex, but visceral adipose tissue and insulin resistance are the key initiating and perpetuating factors. Adipose tissue is now considered as an endocrine organ, and crosstalk between adipocytes and hepatocytes, through adipokines plays an important role in governing the sensitivity of insulin on glucose and lipid metabolism. Once hepatic steatosis develops, various intracellular mechanisms, like oxidative stress and endoplasmic reticulum stress lead to progression to steatohepatitis and cirrhosis. The different natural history in various ethnic groups suggest that genetic and environmental factors may play a crucial role in the development of the ultimate phenotype.

Evaluation of hepatocellular carcinoma by contrast enhanced ultrasound : a novel technique.

Characterization of focal liver lesions remains a diagnostic challenge for the radiologists, more so when there is associated underlying chronic liver disease (CLD). Imaging plays a vital role and there has been a constant endeavor to improve the diagnostic accuracy of liver lesions. The introduction of mutiphasic CT and MRI has revolutionized the diagnostic ability of liver lesions. With the advent of ultrasound contrast agents (UCAs), it is possible to evaluate liver lesions using the non-invasive imaging technique of “contrast-enhanced ultrasonography” (CEUS).1-3 CEUS can overcome the limitations of grey scale and color doppler sonography4,5 and has been used for characterisation of focal liver lesions.2. It can depict arterialisation of hypervascular hepatocellular carcinoma (HCC)6,7 and can also help in assessment of the post-therapeutic response.8,9 We present two such cases of HCC evaluated by a recently available second generation ultrasound contrast agent, SonoVue (Bracco, UK).

Palliative treatment in advanced hepatocellular carcinoma: Has it made any difference.

Hepatocellular carcinoma (HCC) is a global health problem, the fifth most common cancer in the world.. HCC occurs in a histologically abnormal liver due to underlying chronic liver disease resulting as a sequele of the chronic viral infections, hepatitis B and C. Since these two viral infections are endemic in Asia and Africa, more than 80% of cases are encountered in these regions. In India, a large proportion of the population is “at risk” for developing chronic liver disease and, therefore, HCC. Due to the lack of screening programmes in the country, the majority of HCC patients are diagnosed at an advanced stage of the disease, and thus treatment remains a challenge. Palliative therapy forms the mainstay of treatment for this group of patients. The current era provides a plethora of options for the palliative management of HCC. This review concisely summarises the historical perspective and the current status of palliative treatment in advanced HCC.

Acral and palmo-plantar hyperpigmentation in a patient with disseminated hepatocellular carcinoma.

Capecitabine (5-fluorouracil prodrug) is being evaluated for the management of hepatocellular carcinoma, and is associated with a peculiar skin reaction called hand and foot syndrome (HFS). We describe one patient with HCC and drug-induced HFS.