Insulin resistance

Insulin resistance [IR] is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhotic-NASH, and possibly HCC. The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of IRS 1 and 2, impairing expression of IRS 1 and 2 and blocking intracellular insulin signalling. The latter is mediated by increased levels of both TNF-alpha and suppressor of cytokine signalling 3 [SOC-3]. IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis, and even HCC. In addition, it has a role in impairing IFN signalling cascade [JAK-STAT-IFN genes], as insulin activates PI3K thus blocking STAT-1 translocation, avoiding the antiviral effect of interferon

HCV offensive mechanisms versus host's defensive strategies

At each stage of the life cycle of the virus, hepatitis C virus [HCV] interferes with the cellular antiviral mechanisms of the host. Therefore, HCV infection represents a fencing match between the virus and the host cell. The host's defense depends primarily on activation of the immune response, including activation of interferon [IFN] signalling, expression of cytokines [TNF-alpha, IL-12, IL-10, IFN-alpha] and stimulation of cellular immune response [CIR] and humoral immune response [HIR]. HCV offense relies on envelope mutation, evasion of the host immune response and interference with the endogenous cellular antiviral factors

Controlled trial with interferon alfa 2-b in chronic hepatitis C patients

Thirty-eight chronic hepatitis C [CHC] Egyptian patients with persistently elevated serum alanine aminotransferase [ALT] for 6 months were randomly allocated into 2 groups : Group I [19 patients] received 3 million units [MU] of interferon alpha - 2b [Intron-A] subcutaneously thrice weekly for 6 months. In group I, complete response [normalization of ALT by the end of treatment] was achieved in 8 patients [42.1%], partial response [decrease of ALT by at least 50% of the pretreatment values] in 7 patients [36.8%] and no response in 4 [21.1%]. Sustained response for 6 months after the end of therapy was attained in 4 of the 8 [50%] complete responders. Thus attaining an overall sustained response in 4 of the 19 patients [21.1%]. In group II, spontaneous normalization of ALT was established in 1 patient [5.3%]. Repeat liver biopsies in 16 patients of the interferon group, revealed moderate improvement in the degree of lobular inflammation, hepatocyte necrosis and portal inflammation. We conclude from this study that treatment of CRC with 3 MU of IFN-alfa 2b thrice weekly for 6 months is associated with a low response rate [21.1%]. To improve the results, escalation of the IFN dose and/or prolongation of the treatment period should be considered

Pancreatic cancer between ERCP and CT

Pancreatic tumors are often difficult to diagnose and need elaborate imaging techniques. Two such techniques, i.e. computerized tomography [CT] and endoscopic retrograde cholangiopancreatography [ERCP] were compared in cases suspected of having such tumors. Thirty-eight cases were studied and were diagnosed by both modalities in 58.3% of the cases. An ERCP examination alone revealed 25% of the cases, while CT could only diagnose 16.7%. Both modalities had their advantages and drawbacks and were thought to be complimentary

profile of the jaundiced cholangiocarcinoma patient

During April 1982 March 1987, 358 patients were referred to endoscopic retrograde cholangiopancreatography [ERCP] to diagnose the cause of their jaundice. Out of these cases, 21 were diagnosed as cholangiocarcinoma [5.9%]. In all the cholangiocarcinoma cases clinical and biochemical data pointed to the obstructive nature of jaundice. Ultrasonography showed moderate dilatation of the intrahepatic biliary tracts in 16 patients [76.2%], minimal dilatation in 3 [14.3%], and no dilatation in 2 patients [9.5%]. ERCP demonstrated affection of common-hepatic duct at the confluence in 14 patients [66.7%], distal common bile duct in 3 patients [11.3%], ERCP failed in one patient, who was diagnosed by percutaneous transhepatic cholangiography [PTC]. Biopsies were obtained by targeted liver biopsy in 3 patients and by surgical exploration in 15 patients. In those patients histological examination revealed nodular type in 14 [77.8%] papillary type in 2 [11.1%], and diffuse type in 2 [11.1%]. In the other 3 patients no histological diagnosis was obtained and the diagnosis was based on the clinical, ultrasonic, ERCP and laboratory findings