Heavy smoking and liver

Smoking causes a variety of adverse effects on organs that have no direct contact with the smoke itself such as the liver. It induces three major adverse effects on the liver: direct or indirect toxic effects, immunological effects and oncogenic effects. Smoking yields chemical substances with cytotoxic potential which increase necroinflammation and fibrosis. In addition, smoking increases the production of pro-inflammatory cytokines (IL-1, IL-6 and TNF-α) that would be involved in liver cell injury. It contributes to the development of secondary polycythemia and in turn to increased red cell mass and turnover which might be a contributing factor to secondary iron overload disease promoting oxidative stress of hepatocytes. Increased red cell mass and turnover are associated with increased purine catabolism which promotes excessive production of uric acid. Smoking affects both cell-mediated and humoral immune responses by blocking lymphocyte proliferation and inducing apoptosis of lymphocytes. Smoking also increases serum and hepatic iron which induce oxidative stress and lipid peroxidation that lead to activation of stellate cells and development of fibrosis. Smoking yields chemicals with oncogenic potential that increase the risk of hepatocellular carcinoma (HCC) in patients with viral hepatitis and are independent of viral infection as well. Tobacco smoking has been associated with supression of p53 (tumour suppressor gene). In addition, smoking causes suppression of T-cell responses and is associated with decreased surveillance for tumour cells. Moreover, it has been reported that heavy smoking affects the sustained virological response to interferon (IFN) therapy in hepatitis C patients which can be improved by repeated phlebotomy. Smoker’s syndrome is a clinico-pathological condition where patients complain of episodes of facial flushing, warmth of the palms and soles of feet, throbbing headache, fullness in the head, dizziness, lethargy, prickling sensation, pruritus and arthralgia.

Hepatocellular carcinoma in Egypt: A single center study over a decade

AIM: To identify the trend, possible risk factors and any pattern change of hepatocellular carcinoma (HCC) in Egyptover a decade.METHODS: All HCC patients attending Cairo Liver Center between January 1993 and December 2002, were enrolledin the study. Diagnosis of HCC was based on histopath ological examination and/or detection of hepatic focal lesions by two imaging techniques plus α-fetoprotein level above 200 ng/mL. The duration of the study was divided into two periods of 5 years each; period Ⅰ (1993-1997) and period Ⅱ (1998-2002). Trend, demographic features of patients (age, gender, and residence), risk factors (HBsAg,HCV-Ab, schistosomiasis and others) and pattern of the focal lesions were compared between the two periods.Logistic regression model was fitted to calculate the adjusted odds ratios for the potential risk factors. The population attributable risk percentage was calculated to estimate the proportion of HCC attributed to hepatitis B and C viral infections.RESULTS: Over a decade, 1 328 HCC patients out of 22 450 chronic liver disease (CLD) patients were diagnosed with an overall proportion of 5.9%. The annual proportion of HCC showed a significant rising trend from 4.0% in 1993 to 7.2% in 2002 (P = 0.000). A significant increase in male proportion from 82.5% to 87.6% (P = 0.009); M/F from 5:1 to 7:1 and a slight increase of the predominant age group (40-59 years) from 62.6% to 66.8% (P = 0.387)in periods Ⅰ and Ⅱ respectively, reflecting a shift to younger age group. In the bivariate analysis, HCC was significantly higher in rural residents, patients with history of schistosomiasis and/or blood transfusion. Yet, after adjustment, these variables did not have a significant risk for development of HCC. There was a significant decline of HBsAg from 38.6% to 20.5% (P = 0.000), and a slight increase of HCV-Ab from 85.6% to 87.9% in periods Ⅰ and Ⅱ respectively. HBV conferred a higher risk to develop HCC more than HCV in period Ⅰ (OR 1.9 vs 1.6) and period Ⅱ (OR 2.7 vs 2.0), but the relative contribution of HBV for development of HCC declined in period Ⅱ compared to period Ⅰ (PAR% 4.2%, 21.32%). At presentation,diagnostic α-fetoprotein level (≥200 ng/mL) was demonstrated in 15.6% vs28.9% and small HCC (≤3 cm)represented 14.9% vs 22.7% (P = 0.0002) in periods Ⅰ and Ⅱ respectively.CONCLUSION: Over a decade, there was nearly a twofold increase of the proportion of HCC among CLD patients in Egypt with a significant decline of HBV and slight increase of HCV as risk factors. α-Fetoprotein played a limited role in diagnosis of HCC, compared to imaging techniques.Increased detection of small lesions at presentation reflects increased awareness of the condition.

Curse of schistosomiasis on Egyptian liver

Schistosomiasis is a chronic parasitic disease caused by atrematode blood fluke of the genus schistosoma that belongsto the schistosomatidae family. The ancient Egyptianscontracted the disease more than 4 000 years ago. It wasrecognized through haematuria, the main sign of urinarybilharziasis was recorded in the Kahun papyrus 1900 B.C.' a-a-a-' disease.

Hepatitis C virus induced insulin resistance impairs response to anti viral therapy

Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (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 insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 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, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon.

Hepatic steatosis:A benign disease or a silent killer

Steatosis is a common feature of many liver diseases,namely non-alcoholic steatohepatitis(NASH) and hepatitis C virus(HCV) infection,but the pathogenic mechanisms differ.Insulin resistance(IR),a key feature of metabolic syndrome,is crucial for NASH development,associated with many underlying genetically determined or acquired mitochondrial and metabolic defects and culminates to inflammation and progression to fibrosis.This may have potential implications for new drug therapy.In HCV-related disease,steatosis impacts both fibrosis progression and response to treatment.Steatosis in HCV-related disease relates to both viral factors(HCV genotype 3),and host factors(alcohol consumption,overweight,hyperlipidemia,diabetes).Among others,IR is a recognized factor.Hepatic steatosis is reported to be associated with disturbance in the signaling cascade of interferon and downregulation of its receptors.Thus,hepatic steatosis should not be considered a benign feature,but rather a silent killer.

Hepatitis C comorbidities affecting the course and response to therapy

Several studies have demonstrated that the outcome of chronic hepatitis C (CHC) infection is profoundly influenced by a variety of comorbidities. Many of these comorbidities have a significant influence on the response to antiviral therapy. These comorbidities negatively affect the course and outcome of liver disease, often reducing the chance of achieving a sustained virological response with PEGylated interferon and ribavirin treatments. Comorbidities affecting response to antiviral therapy reduce compliance and adherence to inadequate doses of therapy. The most important comorbidities affecting the course of CHC include hepatitis B virus coinfection, metabolic syndrome, and intestinal bacterial overgrowth. Comorbidities affecting the course and response to therapy include schistosomiasis, iron overload, alcohol abuse, and excessive smoking. Comorbidities affecting response to antiviral therapy include depression, anemia, cardiovascular disease, and renal failure.

Impact of cigarette smoking on response to interferon therapy in chronic hepatitis C Egyptian patients

AIM: Smoking may affect adversely the response rate to interferon-α. Our objective was to verify this issue among chronic hepatitis C patients. METHODS: Over the year 1998, 138 chronic hepatitis C male Egyptian patients presenting to Cairo Liver Center, were divided on the basis of smoking habit into: group I which comprised 38 smoker patients (>30 cigarettes/d) and group II which included 84 non-smoker patients. Irregular and mild smokers (16 patients) were excluded. Non eligible patients for interferon-~ therapy were excluded from the study and comprised 3/38 (normal ALT) in group I and 22/84 in group II (normal ALT, advanced cirrhosis and thrombocytopenia). Group I was randomly allocated into 2 sub-groups: group Ia comprised 18 patients who were subjected to therapeutic phlebotomy while sub-group Ib consisted of 17 patients who had no phlebotomy. In sub-group Ia, 3 patients with normal ALT after repeated phlebotomies were excluded from the study. Interferon-α2b 3 MU/TIW was given for 6 mo to 15 patients in group Ia, 17 patients in group Ib and 62 patients in group II. Biochemical, virological end-of- treatment and sustained responses were evaluated.RESULTS: At the end of interferon-α treatment, ALT was normalized in 3/15 patients (20%) in group Ia and 2/17 patients (11.8%) in group Ib compared to17/62 patients (27.4%) in group II (P=0.1). Whereas 2/15 patients (13.3%) in group Ia. and 2/17 patients (11.8%) in group Ib lost viraemia compared to 13/62 patients (26%) in group II(P=0.3). Six months later, ALT was persistently normal in 2/15 patients (13.3%) in group la and 1/17 patients (5.9%) in group Ib compared to 9/62 patients (14.5%) in group Ⅱ (P= 0.47). Viraemia was eliminated in 1/15 patients (6.7%) in group Ia and 1/17 patients (5.9%) in group Ib compared to 7/62 patients (11.3%) in group Ⅱ, but the results did not mount to statistical significance (P = 0.4). CONCLUSION: Smokers suffering from chronic hepatitis C tend to have a lower response rate to interferon-α compared to non-smokers. Therapeutic phlebotomy improves the response rate to interferon-α therapy among this group.