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1.  Prevalence of Diabetes and Incidence of Angiopathy in Patients with Chronic Viral Liver Disease 
Patients with chronic liver disease (CLD) often develops glucose intolerance. We explored the prevalence of diabetes mellitus in viral CLD, and analyzed factors profoundly affecting the diabetic angiopathies. 229 CLD patients (124 chronic hepatitis and 105 liver cirrhosis) entered the study. The diagnosis of diabetes was made with the criteria by World Health Organization. Laboratory investigation included serum asparate aminotransferase, alanine aminotransferase, albumin, fasting blood sugar, hemoglobin A1c (HbA1c), fasting immunoreactive insulin, and HOMA-R (FBS*IRI/405). The incidence of macro- and microangiopathy were also examined. Forty (17.5%) CLD patients were diagnosed diabetes, giving a significantly higher incidence than that of general cohort (5.3%) (p<0.001). Among them, 12 (30%) had the triopathy, significantly lower than that in a matched group of diabetic patients without CLD (65%) (p<0.001). Significantly increased levels of HbA1c and HOMA-R were observed in diabetic CLD with angiopathy compared with diabetic CLD without. Incidence of diabetes was increased in viral CLD patients. The rate of diabetic angiopathies in CLD, however, was relatively low, this could be explained by low coagulability in these patients. Poor control of hyperglycemia, partly due to insulin resistance, might explain the onset of angiopathy in diabetic CLD.
doi:10.3164/jcbn.40.116
PMCID: PMC2127229  PMID: 18188413
hepatogenous diabetes; chronic liver disease; diabetes mellitus; insulin resistance; glucose intolerance
2.  Prevalence and Factors Affecting Occurrence of Type 2 Diabetes Mellitus in Saudi Patients with Chronic Liver Disease 
Background/Aim
Type 2 diabetes mellitus (DM-2) is more common in patients with chronic liver disease (CLD) in general and chronic hepatitis C virus (HCV) infection in particular. We aimed to determine the prevalence and factors affecting the occurrence of DM-2 in Saudi patients with CLD.
Materials and Methods
Retrospective study at the King Fahd Central Hospital (KFCH), Gizan, Saudi Arabia. A total of 277 patients with either cirrhosis (CH) or hepatocellular carcinoma (HCC) were analyzed for patient demographics, severity of liver disease, HBsAg, and anti-HCV, associated diseases including DM-2, and presence of HCC. The prevalence of DM-2 was also estimated in 400 age- and sex-matched Saudi patients admitted for various nonliver diseases (control group). Chi-square test, univariate analysis, and multivariate regression.
Results
Prevalence of DM-2 in patients with CH was higher than in controls (19.2 vs. 9.2%; P = 0.001). Although those with HCC had a higher prevalence, the difference was not significant (10.9 vs. 9.2%; P = 0.5). Seventy-six percent of patients with HCC had associated CH. On multivariate analysis, age and hypertension were more common in diabetics. Although patients with HCV-related disease had a higher prevalence of DM-2 compared to HBV-related disease, the difference was not significant (26.3 vs. 15.7%; P > 0.05).
Conclusions
DM-2 occurred more frequently in CLD patients, particularly in cirrhotics. Age and hypertension predicted the occurrence of DM-2. Small sample size of patients with HCV-related CH probably precluded higher prevalence of DM-2 in them.
doi:10.4103/1319-3767.41729
PMCID: PMC2702913  PMID: 19568519
Cirrhosis; diabetes mellitus; hepatocellular carcinoma; Saudi Arabia
3.  Chronic Liver Disease Mortality Among Male Prison Inmates in Texas, 1989–2003 
OBJECTIVES
Alcohol abuse and chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the major etiologic factors for chronic liver disease/cirrhosis (CLD) in the United States. These CLD risk factors are highly prevalent in US adult incarcerated populations, but CLD-related mortality data from these populations are lacking. The primary objective of this study was to assess CLD-related mortality over time and across categories of race–ethnicity from 1989 through 2003 among male inmates in the Texas state prison system. The secondary objective was to examine patterns of recorded underlying, intervening, and contributing causes of death for CLD-related deaths.
METHODS
Prisoner decedent data were linked with Texas Vital Statistics multiple-cause-of-death data. Deaths were considered CLD-related if CLD or common sequelae were recorded as the underlying, intervening, or contributing causes of death. CLD-related crude annual death rates, 5-year average annual death rates, and average annual percentage changes were estimated.
RESULTS
Among male Texas prisoners from 1989 to 2003, CLD-related deaths accounted for 16% of deaths (688/4,316). CLD-related crude annual death rates were high and increased over the study period by an average of 4.5% annually, with similar rate increases across categories of race–ethnicity. CLD-related average annual death rates were higher among Hispanic prisoners than among black prisoners in each 5-year period, and were higher than those for white prisoners in the 1994–1998 and 1999–2003 periods. HBV or HCV was identified as a causal factor in more than a third (34%) of CLD-related deaths.
CONCLUSIONS
From 1989 to 2003, CLD-related death rates among male Texas prisoners were high and increased over time, particularly among Hispanics. Targeted prevention, screening, and treatment of CLD risk factors, especially HCV, and early detection and treatment of CLD should be considered as priorities of the US prison healthcare systems.
doi:10.1038/ajg.2009.106
PMCID: PMC2856927  PMID: 19491854
4.  High prevalence of undiagnosed diabetes and abnormal glucose tolerance in the Iranian urban population: Tehran Lipid and Glucose Study 
BMC Public Health  2008;8:176.
Background
To estimate the prevalence of diagnosed and undiagnosed diabetes mellitus, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT in a large urban Iranian population aged ≥ 20 years.
Methods
The study population included 9,489 participants of the Tehran Lipid and Glucose Study with full relevant clinical data. Age-standardized prevalence of diabetes and glucose intolerance categories were reported according to the 2003 American Diabetes Association definitions. Age-adjusted logistic regression models were used to estimate the numbers needed to screen (NNTS) to find one person with undiagnosed diabetes.
Results
The prevalence of diagnosed and undiagnosed diabetes, isolated IFG, isolated IGT, and combined IFG/IGT were 8.1%, 5.1%, 8.7%, 5.4% and 4.0% in men and 10%, 4.7%, 6.3%, 7.6%, and 4.5% in women respectively. Participants with undiagnosed diabetes had higher age, body mass index (BMI), waist circumference, systolic and diastolic blood pressures, triglycerides (all p values <0.001) and lower HDL-cholesterol (only in women, p < 0.01) compared to normoglycemic subjects. Undiagnosed diabetes was associated with family history of diabetes, increased BMI (≥ 25 kg/m2), abdominal obesity, hypertriglyceridemia, hypertension and low HDL-cholesterol levels. Among men, a combination of increased BMI, hypertension, and family history of diabetes led to a NNTS of 1.6 (95% CI: 1.57–1.71) and among women a combination of family history of diabetes and abdominal obesity, yielded a NNTS of 2.2 (95% CI: 2.1–2.4).
Conclusion
In conclusion, about one third of Tehranian adults had disturbed glucose tolerance or diabetes. One- third of total cases with diabetes were undiagnosed. Screening individuals with BMI ≥ 25 kg/m2 (men), hypertension (men), abdominal obesity (women) and family history of diabetes may be more efficient.
doi:10.1186/1471-2458-8-176
PMCID: PMC2413226  PMID: 18501007
5.  Post-load hyperglycemia as an important predictor of long-term adverse cardiac events after acute myocardial infarction: a scientific study 
Background
Diabetes mellitus (DM) and impaired glucose tolerance (IGT) are risk factors for acute myocardial infarction (AMI). However, it is unknown whether hyperglycemic state is associated with increased major adverse cardiovascular events (MACE) after AMI. In this study, we evaluated the relationship between glucometabolic status and MACE in patients after AMI, and determined the critical level of 2 h post-load plasma glucose that may be used to predict MACE.
Methods
AMI patients (n = 422) were divided into 4 groups as follows: normal glucose tolerance (NGT) group, IGT group, newly diagnosed DM (NDM) group, and previously known DM (PDM) group. MACE of the 4 groups were compared for 2 years from AMI onset.
Results
The NDM group had a significantly higher event rate than the IGT and NGT groups and had a similar event rate curve to PDM group. The logistic models analyses revealed that 2 h post-load plasma glucose values of ≥160 mg/dL was the only independent predictor of long-term MACE after AMI (p = 0.028, OR: 1.85, 95% CI: 1.07-3.21). The 2-year cardiac event rate of patients with a 2 h post-load hyperglycemia of ≥160 mg/dL was significantly higher than that of patients with 2 h post-load glucose of <160 mg/dL (32.2% vs. 19.8%, p < 0.05) and was similar to that of PDM group (37.4%, p = 0.513).
Conclusions
NDM increases the risk of MACE after AMI as does PDM. Particularly, post-AMI patients with a 2 h post-load hyperglycemia ≥160 mg/dL may need adjunctive therapy after AMI.
doi:10.1186/1475-2840-9-75
PMCID: PMC2996353  PMID: 21070650
6.  Pathogenesis of Impaired Glucose Tolerance and Type II Diabetes Mellitus—Current Status 
Western Journal of Medicine  1985;142(2):219-229.
The insulin response to glucose taken orally is increased in patients with impaired glucose tolerance (IGT) but decreased in those with type II diabetes mellitus. The insulin response to meals, however, is normal in patients with type II diabetes, although the glucose concentrations are obviously elevated. The acute insulin response to intravenously administered glucose is absent in cases of both IGT and type II diabetes when the fasting plasma glucose level exceeds 115 mg per dl. On the other hand, the response to other intravenously given secretagogues is either normal or nearly so. The absent acute insulin response to intravenously administered glucose can be restored by α-adrenergic blockade, prostaglandin synthesis inhibition, dopaminergic blockade and euglycemia.
Insulin antagonism characterizes patients with both IGT and type II diabetes. Those with IGT and mild diabetes mellitus (untreated fasting plasma glucose concentrations < 180 mg per dI) have a receptor defect probably due to down regulation. Diabetic patients with more severe type II diabetes show a postreceptor defect. The relation (if any) between receptor and postreceptor defects is unclear.
PMCID: PMC1305982  PMID: 3892914
7.  Can Admission and Fasting Glucose Reliably Identify Undiagnosed Diabetes in Patients With Acute Coronary Syndrome?  
Diabetes Care  2008;31(10):1955-1959.
OBJECTIVE—Our objectives were to determine the prevalence of previously undiagnosed abnormal glucose tolerance, i.e., diabetes and impaired glucose tolerance (IGT) in patients with acute coronary syndrome and to assess the utility of admission and fasting glucose in identifying diabetes in these patients.
RESEARCH DESIGN AND METHODS—Glycemic status was characterized on the basis of admission plasma glucose (APG), fasting plasma glucose (FPG), and an oral glucose tolerance test (OGTT) in 140 patients admitted to the hospital with acute coronary syndrome, who were not known to have diabetes (mean ± SD age 67.3 ± 13.4 years; 79% men). OGTTs were performed on days 5–7 after admission.
RESULTS—The prevalences of diabetes and IGT were 27 and 39%, respectively, according to OGTT criteria. Receiver operating characteristic curves showed that the area under the curve for diagnosing diabetes was 0.83 (P < 0.001) for FPG, 0.79 (P < 0.001) for APG, and 0.84 (P < 0.001) for FPG and APG applied in combination. A FPG cutoff ≥5.6 mmol/l (100 mg/dl) and/or APG ≥7.8 mmol/l (140 mg/dl) yielded a sensitivity of 89.5% and a positive predictive value of 43.6% for detecting diabetes.
CONCLUSIONS—A high prevalence of abnormal glucose tolerance was seen in patients with acute coronary syndrome. The combination of FPG ≥5.6 mmol/l (100 mg/dl) and/or APG ≥7.8 mmol/l (140 mg/dl) was highly sensitive for identifying diabetes. Although weakly specific, this simple algorithm could offer a practical initial screening tool at the acute setting in the high-risk population with acute coronary syndrome.
doi:10.2337/dc08-0197
PMCID: PMC2551634  PMID: 18591399
8.  Prevalence of IgG anti-HAV in patients with chronic hepatitis B and in the general healthy population in Korea 
The Korean Journal of Hepatology  2010;16(4):362-368.
Background/Aims
Few studies have investigated hepatitis A virus (HAV) seroepidemiology in Koreans with chronic liver disease (CLD). This study compared the prevalence of IgG anti-HAV between the general healthy population and patients with hepatitis B virus-related CLD (HBV-CLD), with the aim of identifying predictors of HAV prior exposure.
Methods
In total, 1,319 patients were recruited between June 2008 and April 2010. All patients were tested for IgG anti-HAV, hepatitis B surface antigen (HBsAg), and antibodies to hepatitis C virus. The patients were divided into the general healthy population group and the HBV-CLD group based on the presence of HBsAg. The seroprevalence of IgG anti-HAV was compared between these two groups.
Results
The age-standardized seroprevalence rates of IgG anti-HAV in the general healthy population and patients with HBV-CLD were 52.5% and 49.1%, respectively. The age-stratified IgG anti-HAV seroprevalence rates for ages ≤19, 20-29, 30-39, 40-49, 50-59, and ≥60 years were 14.3%, 11.2%, 45.5%, 90.5%, 97.6% and 98.3%, respectively, in the general healthy population, and 0%, 9.8%, 46.3%, 91.1%, 97.7%, and 100% in the HBV-CLD group. In multivariate analysis, age (<30 vs. 30-59 years: OR=19.339, 95% CI=12.504-29.911, P<0.001; <30 vs. ≥60 years: OR=1060.5, 95% CI=142.233-7907.964, P<0.001) and advanced status of HBV-CLD (OR=19.180, 95% CI=4.550-80.856, P<0.001) were independent predictors of HAV prior exposure.
Conclusions
The seroprevalence of IgG anti-HAV did not differ significantly between the general-healthy-population and HBV-CLD groups. An HAV vaccination strategy might be warranted in people younger than 35 years, especially in patients with HBV-CLD.
doi:10.3350/kjhep.2010.16.4.362
PMCID: PMC3304616  PMID: 21415579
Hepatitis A; Seroprevalence; Chronic hepatitis B; Korea
9.  Prevalence of type 2 diabetes in Algerian patients with hepatitis C virus infection 
AIM: To investigate the prevalence of, and risk factors for, diabetes mellitus (DM) in Algerian patients with chronic hepatitis C virus (HCV) infection and in a control group.
METHODS: A cross-sectional study was undertaken. A total of 416 consecutive patients with viral chronic hepatitis attending the Internal Medicine Department of the University Hospital Center Touhami Benflis in Batna [290 HCV-infected and 126 hepatitis B virus (HBV)-infected patients] were prospectively recruited.
RESULTS: The prevalence of DM was higher in HCV-infected patients in comparison with HBV-infected patients (39.1% vs 5%, P < 0.0001). Among patients without cirrhosis, diabetes was more prevalent in HCV-infected patients than in HBV-infected patients (33.5% vs 4.3%, P < 0.0001). Among patients with cirrhosis, diabetes was more prevalent in HCV-infected patients, but the difference was not significant (67.4% vs 20%, P = 0.058). The logistic regression analysis showed that HCV infection [odds ratio (OR) 4.73, 95% CI: 1.7-13.2], metabolic syndrome (OR 12.35, 95% CI: 6.18-24.67), family history of diabetes (OR 3.2, 95% CI: 1.67-6.13) and increased hepatic enzymes (OR 2.22, 95% CI: 1.1-4.5) were independently related to DM in these patients.
CONCLUSION: The high prevalence of diabetes in HCV-infected patients, and its occurrence at early stages of hepatic disease, suggest that screening for glucose abnormalities should be indicated in these patients.
doi:10.3748/wjg.v16.i27.3427
PMCID: PMC2904891  PMID: 20632447
Prevalence; Hepatitis C virus; Hepatitis B virus; Diabetes mellitus; Algeria
10.  Clinical Significance of Isolated Anti-HBc Positivity in Cases of Chronic Liver Disease in New Delhi, India 
Background:
The presence of anti-HBc IgG in the absence of HBsAg is usually indicative of a past self-limiting HBV infection. But it is frequently associated with co-infection with HCV which can worsen the existing status of chronic liver disease (CLD).
Objectives:
The present study was planned to evaluate the significance of isolated HBc IgG positivity in patients of CLD and look for the presence of HCV co-infection in such patients.
Methods:
Clinical profiles and biochemical tests were done for all the 77 CLD cases included in the study. Blood samples were taken from these patients and tested by the commercially available EIA for the presence of HBsAg, anti-HBc IgG, anti-HBs and anti-HCV. HBV DNA was detected by amplifying the surface region in all the cases.
Results:
Isolated anti-HBc IgG positivity defined as the presence of anti-HBc IgG in absence of any other serological markers of HBV infection was detected in 28 patients. Out of 64 patients positive for anti-HBc IgG 36 had the markers of HBV, either HBsAg, HBV DNA or anti-HBs alone or in combination. There was a significant association between isolated anti-HBc IgG positivity and HCV co-infection.
Conclusion:
Anti-HBc IgG should be tested in all patients with CLD as it is frequently the only marker of HBV infection in such patients and they should be monitored closely as such patients can develop CLD. Presence of co-infection with HCV should be actively searched for in such patients.
doi:10.4103/0974-777X.52978
PMCID: PMC2840942  PMID: 20300383
Isolated anti-HBc IgG; HCV co-infection; Liver disease
11.  Should the first degree relatives of type 2 diabetic patients with isolated impaired fasting glucose be considered for a diabetes primary prevention program? 
BACKGROUND:
The aim of this study is to investigate the need for diabetes primary prevention program in isolated impaired fasting glucose (i-IFG) of the first degree relatives of type 2 diabetics.
METHODS:
In a cross sectional study, 793 individuals with prediabetes [543 with i-IFG and 250 with isolated impaired glucose tolerance (i-IGT)] who were the first degree relatives of type 2 diabetic patients, were enrolled. Isolated IFG was considered as fasting plasma glucose between 100-125 mg/dl and 2 hour plasma glucose < 140 mg/dl and isolated IGT as FPG < 100 mg/dl and 2 hour plasma glucose between 140-199 mg/dl during an overnight fasting 75 g oral glucose tolerance test. Mean of the age, weight, waist circumference, body mass index, systolic and diastolic blood pressure, plasma glucose, HbA1C, and lipid profile were compared between two groups (i-IFG and i-IGT). The prevalence of cardiometabolic risk factors (BMI ≥ 25 kg/m2, hypertension, cholesterol ≥ 200 mg/dl, LDL-C ≥ 100 mg/dl, HDL-C ≤ 40 mg/dl, and triglyceride ≥ 150 mg/dl) adjusted by age, sex and BMI were compared.
RESULTS:
The prevalence of cardiometabolic risk factors is higher in i-IFG group than i-IGT. The mean level of LDL-C is significantly higher in i-IFG than i-IGT group.
CONCLUSIONS:
First degree relatives of T2DM with isolated impaired fasting glucose should probably be included in the primary preventive program for diabetes. However, longitudinal cohort study is required to show high progression of i-IFG to T2DM.
PMCID: PMC3082819  PMID: 21526094
Prediabetic States; Diabetes Mellitus; Type II; Oral Glucose Tolerance Test; Primary Prevention; Dyslipidemia; Risk Factor; Iran
12.  Plasma gelsolin protein: a candidate biomarker for hepatitis B-associated liver cirrhosis identified by proteomic approach 
Blood Transfusion  2010;8(Suppl 3):s105-s112.
Background.
Despite the significant improvement in internal medicine and supportive therapy in recent years, liver fibrosis/cirrhosis remains a serious health issue in hepatitis B virus (HBV) infected patients. Invasive liver biopsy is presently the best means of diagnosing cirrhosis, but it carries a significant risk and has well recognised limitations such as sampling error, hence the importance in developing early diagnosis biomarkers. With this aim, we performed a pilot proteomic study to assess this as a strategy for plasma marker detection in patients suffering from HBV-associated liver cirrhosis.
Methods.
Plasma from eight chronic HBV-infection patients and from eight HBV-related cirrhotic patients were selected and proteome profiles were created by two-dimensional electrophoresis. The strategy included the use of ProteoMiner enrichment kit for the reduction of highly abundance proteins (e.g. albumin and IgG) prior to proteomic analyses with the goal to improve detection of novel candidate markers.
Results.
One reproducible spot was found to be completely repressed in plasma samples from cirrhotic patients and mass spectrometry analysis identified this a specific variant of the gelsolin actin-depolymerizing factor. Though further investigations are needed, especially in term of clinical validation, to our knowledge this is the first time that gelsolin is proposed as potential biomarker in HBV-related liver pathologies.
Conclusions.
Our findings confirm the potential utility of gelsolin either as a prognostic marker or a replacement therapeutic agent to alleviate liver injury.
doi:10.2450/2010.017S
PMCID: PMC2897206  PMID: 20606740
hepatitis B virus (HBV); inactive chronic HBV-infection; HBV-associated liver cirrhosis; human plasma; biomarker discovery
13.  Prevention of type 2 diabetes in adults with impaired glucose tolerance: the European Diabetes Prevention RCT in Newcastle upon Tyne, UK 
BMC Public Health  2009;9:342.
Background
Diabetes prevalence is increasing. The Finnish Diabetes Prevention Study (DPS) showed a 58% reduction in Type 2 Diabetes (T2D) incidence in adults with impaired glucose tolerance (IGT). The European Diabetes Prevention Study (EDIPS) extends the DPS to different European populations, using the same study design. In the Newcastle arm of this study (EDIPS-Newcastle), we tested the hypothesis that T2D can be prevented by lifestyle intervention and explored secondary outcomes in relation to diabetes incidence.
Methods
We recruited 102 participants (42 men and 60 women, mean age 57 years, mean BMI 34 kgm-2) with IGT to EDIPS-Newcastle and randomised to Intervention and usual care Control groups. The intervention included individual motivational interviewing aimed at: weight reduction, increase in physical activity, fibre and carbohydrate intake and reduction of fat intake (secondary outcomes). The primary outcome was diagnosis of T2D.
Results
Mean duration of follow-up was 3.1 years. T2D was diagnosed in 16 participants (I = 5, C = 11). Absolute incidence of T2D was 32.7 per 1000 person-years in the Intervention-group and 67.1 per 1000 person-years in the Control-group. The overall incidence of diabetes was reduced by 55% in the Intervention-group, compared with the Control-group: RR 0.45 (95%CI 0.2 to 1.2).
Explanatory survival analysis of secondary outcomes showed that those who sustained beneficial changes for two or more years reduced their risk of developing T2D.
Conclusion
Our results are consistent with other diabetes prevention trials. This study was designed as part of a larger study and although the sample size limits statistical significance, the results contribute to the evidence that T2D can be prevented by lifestyle changes in adults with IGT. In explanatory analysis small sustained beneficial changes in weight, physical activity or dietary factors were associated with reduction in T2D incidence.
Trial Registration
International Standard Randomised Controlled Trial Number registry (ISRCTN)
Registry number: ISRCTN 15670600
doi:10.1186/1471-2458-9-342
PMCID: PMC2760530  PMID: 19758428
14.  Glucose tolerance, insulin resistance and insulin secretion in young south Indian adults; relationships to parental size, neonatal size and childhood body mass index 
Objective
To study the relationship of newborn size and post-natal growth to glucose intolerance in south Indian adults.
Research design and Methods
2,218 men and women (mean age 28 years) were studied from a population-based birth cohort born in a large town and adjacent rural villages. The prevalence of adult diabetes mellitus [DM] and impaired glucose tolerance [IGT], and insulin resistance and insulin secretion (calculated) were examined in relation to BMI and height at birth, and in infancy, childhood and adolescence and changes in BMI and height between these stages.
Results
Sixty-two (2.8%) subjects had type 2 diabetes (DM) and 362 (16.3%) had impaired glucose tolerance (IGT). IGT and DM combined (IGT/DM) and insulin resistance were associated with low childhood body mass index (BMI) (p<0.001 for both) and above-average BMI gain between childhood or adolescence and adult life (p<0.001 for both). There were no direct associations between birthweight or infant size and IGT/DM; however, after adjusting for adult BMI, lower birthweight was associated with an increased risk.
Conclusions
The occurrence of IGT and Type 2 DM is associated with thinness at birth and in childhood followed by accelerated BMI gain through adolescence.
doi:10.1016/j.diabres.2009.11.015
PMCID: PMC3428893  PMID: 20115937
Type 2 diabetes mellitus; impaired glucose tolerance; insulin resistance; childhood body mass index; young adulthood
15.  The occurrence of hepatitis B and C viruses in Pakistani patients with chronic liver disease and hepatocellular carcinoma. 
Epidemiology and Infection  1996;117(2):327-332.
To study the occurrence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients with chronic liver disease (CLD) and hepatocellular carcinoma (HCC) in Pakistan, blood samples from 105 sequential patients with biopsy-proven CLD (n = 82) and HCC (n = 23) were tested for HBV and HCV markers. Of the 105, 87 (83%) had evidence of hepatitis B exposure, 58 (55%) were positive for hepatitis B surface antigen (HBsAg), 23 (22%) had hepatitis C antibodies and 25 (24%) had detectable HCV RNA. Significantly more patients with HCC had evidence of HBV exposure in the absence of HCV markers (49/82 vs. 20/23, odds ratio 4.49, 95% CI 1.17-25.16). The proportion of patients positive for HBsAg with no HCV markers was also significantly higher in the HCC group (34/82 vs. 18/23, odds ratio 5.08, 95% CI 1.59-18.96). There were more patients with only HCV markers in the CLD group than the HCC group but the difference was not statistically significant (19/82 vs. 1/23, odds ratio 6.63, 95% CI 0.93-288.01). A modified non-isotopic restriction fragment length polymorphism study on PCR products was used to investigate the epidemiology of HCV genotypes in Pakistan. Due to depletion of the initial samples, a second series of specimens collected one year afterwards was used. Fifteen out of 40 samples had amplifiable product and all were identified as type 3. A commercial serological typing method on the same samples also confirmed that type 3 was the predominant HCV genotype in Pakistan.
PMCID: PMC2271701  PMID: 8870630
16.  Diabetes, Insulin Resistance and Atherosclerosis Surrogates in Patients With Coronary Atherosclerosis 
Korean Circulation Journal  2010;40(2):62-67.
Background and Objectives
Undiagnosed diabetes mellitus (DM) or impaired glucose tolerance (IGT) is not uncommon in patients with coronary atherosclerosis and is known to be associated with abnormal scores for atherosclerosis surrogates. We sought to determine the prevalence of undiagnosed DM or IGT, and the association between insulin resistance (IR) and atherosclerosis surrogates in patients with coronary atherosclerosis.
Subjects and Methods
The study population consisted of 187 consecutive patients with angiographically proven coronary atherosclerosis (mean: 61 years old, 94 males). We measured carotid intima-media thickness (IMT) and flow mediated brachial artery dilatation (FMD). We also did oral glucose tolerance tests (OGTT), quantitative insulin-sensitivity check indexes (QUICKI) and homeostasis model assessment-IR (HOMA-IR).
Results
Abnormal OGTT was found in 164 patients (87.7%), even though there were only 63 known cases of DM (33.7%). There were 58 patients (31%) with newly diagnosed IGT and 43 patients (23%) with newly diagnosed DM. There were 71 patients (38%) who had IR (defined as measured HOMA-R ≥3.0). HOMA-IR showed a positive correlation with body mass index (BMI) (r=0.275, p<0.001) and triglycerides (r=0.2, p=0.01), whereas QUICKI had a negative correlation with BMI (r=-0.26, p<0.001), total cholesterol (r=-0.15, p=0.04), triglycerides (r=-0.21, p=0.004) and low-density lipoprotein-cholesterol (LDL-C) (r=-0.17, p=0.02). HOMA-IR and QUICKI were not significantly correlated with IMT or FMD.
Conclusion
This study suggests that there is a high incidence of undiagnosed DM and IGT, but atherosclerosis surrogates are not associated with IR in patients with coronary atherosclerosis.
doi:10.4070/kcj.2010.40.2.62
PMCID: PMC2827804  PMID: 20182590
Coronary atherosclerosis; Diabetes; Insulin resistance
17.  Distribution of hepatitis B viral genotypes and mutations in the core promoter and precore regions in acute forms of liver disease in patients from Chiba, Japan 
Gut  2003;52(11):1630-1637.
Background: Although it has been reported that different hepatitis B virus (HBV) genotypes induce different clinical characteristics in patients with chronic liver diseases (CLD), there have been few reports that have detailed the distribution of HBV genotypes in acute forms of liver disease.
Methods: HBV genotypes were determined in 61 patients who had acute forms of liver disease (45 had acute self limited hepatitis (AH) and 16 had fulminant hepatitis (FH)) and in 531 patients with CLD, including 19 patients with severe acute exacerbation of CLD. We also analysed the enhancer II, core promoter, and precore region sequences for the presence of mutations.
Results: Expression of genotype B in patients with acute forms of liver disease was significantly greater than in those with CLD (39.3% v 11.7%, respectively; p<0.001). Furthermore, expression of genotype B was significantly greater in patients with FH than in those with AH (62.5% v 31.1%, respectively; p=0.027). The precore mutation A1896 and the core promoter mutation at nt 1753 and 1754 were found more frequently in FH than in AH, and genotype B was predominant in FH regardless of the presence of these mutations.
Conclusions: HBV genotype B was found more frequently in patients with acute forms of liver disease than in patients with CLD, and more frequently in patients with FH than in those with AH. These results suggest that this HBV genotype may induce more severe liver damage than other viral genotypes, at least in patients from Chiba, Japan.
PMCID: PMC1773865  PMID: 14570734
acute self limited hepatitis; fulminant hepatitis; hepatitis B virus; genotype
18.  Association of HCV with diabetes mellitus: an Egyptian case-control study 
Virology Journal  2011;8:367.
Background
The highest Hepatitis C Virus (HCV) prevalence in the world occurs in Egypt. Several studies from different parts of the world have found that 13% to 33% of patients with chronic HCV have associated diabetes, mostly type II Diabetes Mellitus (DM). In Egypt the prevalence of DM is 25.4% among HCV patients. Therefore, it is important to identify the magnitude of the problem of diabetes in order to optimize the treatment of chronic hepatitis C.
Methods
The objective of this case-control study was to evaluate the prevalence of DM and other extrahepatic (EH) manifestations among patients with different HCV morbidity stages including asymptomatic, chronic hepatic and cirrhotic patients. In this study, 289 HCV patients older than 18 were selected as cases. Also, 289 healthy controls were included. Laboratory investigations including Liver Function tests (LFT) and blood glucose level were done. Also serological assays including cryoglobulin profile, rheumatoid factor, antinuclear antibody, HCV-PCR were performed.
Results
Out of 289 HCV cases, 40 (13.84%) were diabetic. Out of 289 healthy controls, 12 (4.15%) were diabetic. It was found that the diabetic HCV group mean age was [48.1 (± 9.2)]. Males and urbanians represented 72.5% and 85% respectively. Lower level of education was manifested in 52.5% and 87.5% were married. In the nondiabetic HCV group mean age was [40.7 (± 10.4)]. Males and urbanians represented 71.5% and 655% respectively. secondary and higher level of education was attained in 55.4% and 76.7% were married. Comparing between the diabetic HCV group and the non diabetic HCV group, age, residence and alcohol drinking were the only significant factors affecting the incidence of diabetes between the two groups. There was no significant difference regarding sonar findings although cirrhosis was more prevalent among diabetic HCV cases and the fibrosis score was higher in diabetic HCV patients than among the non diabetic HCV cases.
Conclusion
The diabetic patients in the HCV group were older, more likely to have a history of alcohol drinking than the non diabetic HCV cases. Age and alcohol drinking are factors that could potentially contribute to the development of type 2 diabetes. Logistic regression analyses showed that age and residence in urban regions were the predictive variables that could be associated with the presence of diabetes. Alcohol consumption was not a significant predictive factor.
doi:10.1186/1743-422X-8-367
PMCID: PMC3199807  PMID: 21791087
19.  Clinical significance of connective tissue growth factor in hepatitis B virus-induced hepatic fibrosis 
AIM: To determine the utility of connective tissue growth factor (CCN2/CTGF) for assessing hepatic fibrosis in hepatitis B virus (HBV)-induced chronic liver diseases (CLD-B).
METHODS: Enzyme-linked immunosorbent assay was used to measure CCN2 in sera from 107 patients with chronic hepatitis B (CHB) and 39 patients with HBV-induced active liver cirrhosis and 30 healthy individuals. Liver samples from 31 patients with CHB, 8 patients with HBV-induced liver cirrhosis and 8 HBV carriers with normal liver histology were examined for transforming growth factor β-1 (TGF-β1) or CCN2 mRNA levels by in situ hybridization, and computer image analysis was performed to measure integrated optimal density (IOD) of CCN2 mRNA-positive cells in liver tissues. Histological inflammation grading and fibrosis staging were evaluated by H and E staining and Van Gieson’s method.
RESULTS: Serum CCN2 concentrations were, respectively, 4.0- or 4.9-fold higher in patients with CHB or active liver cirrhosis as compared to healthy individuals (P < 0.01). There was good consistency between the levels of CCN2 in sera and CCN2 mRNA expression in liver tissues (r = 0.87, P < 0.01). The levels of CCN2 in sera were increased with the enhancement of histological fibrosis staging in patients with CLD-B (r = 0.85, P < 0.01). Serum CCN2 was a reliable marker for the assessment of liver fibrosis, with areas under the receiver operating characteristic (ROC) curves (AUC) of 0.94 or 0.85 for, respectively, distinguishing normal liver controls from patients with F1 stage liver fibrosis or discriminating between mild and significant fibrosis.
CONCLUSION: Detection of serum CCN2 in patients with CLD-B may have clinical significance for assessment of severity of hepatic fibrosis.
doi:10.3748/wjg.v18.i18.2280
PMCID: PMC3351780  PMID: 22611323
Connective tissue growth factor; Liver fibrosis; Chronic hepatitis B; Chronic liver disease; Chronic hepatitis C
20.  Evaluation of Zinc Plasma Level in Iranian Cirrhotic Patients due to Hepatitis B and Hepatitis C 
Hepatitis Monthly  2010;10(1):62-64.
Background and Aims
Zinc (Zn) has various significant roles in physiological functions of the liver. Furthermore, it has been reported that the administration of zinc has an important role in pharmacotherapy of viral hepatitis. Cirrhotic patients with decrease in plasma zinc level have been covered in previous studies. It is seemingly necessary to assess the zinc level, in Iranian cirrhotic patients, as a distinct population, Because of the large phytate amounts in Iranians diet. Regarding to etiology, disease progress, and treatment, there are some differences in the 2 most common causes of cirrhosis in the Iranian population (hepatitis B and hepatitis C) and it is possible that the zinc level may be different between the two. This study was done to shadow some lights on the subject.
Methods
Between April 2008 and November 2008, plasma zinc level was determined, by atomic absorption method, in 60 cirrhotic inpatients treated due to hepatitis B or hepatitis C in Talighani hospital (a referral center for gastrontestinal and liver diseases in Tehran, Iran).
Results
Mean ± standard deviation (SD) plasma zinc levels determined 0.34±0.22 mg/L and 0.37±0.22 mg/L in hepatitis B and hepatitis C patients respectively. Analysis of t-test showed there is no significant difference between 2 groups regarding to plasma zinc level (P = 0.745).
Conclusions
It is concluded that zinc level of studied cirrhotic patients is less than half of the normal range. Moreover, there is no difference in plasma zinc level between cirrhotic patients due to hepatitis B or hepatitis C. Regarding to this result, supplementation with complementary zinc, may be recommended in both groups in order to optimize the nutritional support and probably better the treatment response.
PMCID: PMC3270348  PMID: 22308129
Zinc; Cirrhosis; Hepatitis B; Hepatitis C; Iran
21.  Chronic liver disease in Aboriginal North Americans 
A structured literature review was performed to detail the frequency and etiology of chronic liver disease (CLD) in Aboriginal North Americans. CLD affects Aboriginal North Americans disproportionately and is now one of the most common causes of death. Alcoholic liver disease is the leading etiology of CLD, but viral hepatitis, particularly hepatitis C, is an important and growing cause of CLD. High rates of autoimmune hepatitis and primary biliary cirrhosis (PBC) are reported in regions of coastal British Columbia and southeastern Alaska. Non-alcoholic liver disease is a common, but understudied, cause of CLD. Future research should monitor the incidence and etiology of CLD and should be geographically inclusive. In addition, more research is needed on the treatment of hepatitis C virus (HCV) infection and non-alcoholic fatty liver disease (NAFLD) in this population.
doi:10.3748/wjg.14.4607
PMCID: PMC2738784  PMID: 18698674
Hepatitis C virus; Hepatitis B virus; American Indian; Alaska Native; Chronic liver disease
22.  A review of nateglinide in the management of patients with type 2 diabetes 
Impaired insulin secretion occurs early in the pathogenesis of type 2 diabetes mellitus (T2DM) and is chronic and progressive, resulting initially in impaired glucose tolerance (IGT) and eventually in T2DM. As most patients with T2DM have both insulin resistance and insulin deficiency, therapy for T2DM should aim to control not only fasting, but also postprandial plasma glucose levels. While oral glucose-lowering treatment with metformin and thiazolidinediones corrects fasting plasma glucose, these agents do not address the problem of mealtime glucose spikes that have been shown to trigger atherogenic processes. Nateglinide is a derivative of the amino acid D-phenylalanine, which acts directly on the pancreatic β-cells to stimulate insulin secretion. Nateglinide monotherapy controls significantly mealtime hyperglycemia and results in improved overall glycemic control in patients with T2DM by reducing glycosylated hemoglobin (HbA1c) levels. The combination of nateglinide with insulin-sensitising agents, such as metformin and thiazolidinediones, targets both insulin deficiency and insulin resistance and results in reductions in HbA1c that could not be achieved by monotherapy with other antidiabetic agents. In prediabetic subjects with IGT, nateglinide restores early insulin secretion and reduces postprandial hyperglycemia. Nateglinide has an excellent safety and tolerability profile and provides a lifetime flexibility that other antidiabetic agents could not accomplish. The aim of this review is to identify nateglinide as an effective “gate-keeper” in T2DM, since it restores early-phase insulin secretion and prevents mealtime glucose spikes throughout the day and to evaluate the results of ongoing research into its potential role in delaying the progression to overt diabetes and reducing its complications and mortality.
PMCID: PMC2350129  PMID: 18200800
nateglinide; type 2 diabetes mellitus; postprandial glycemia; impaired glucose tolerance; prevention of type 2 diabetes
23.  Anti-hepatitis A seroprevalence among chronic viral hepatitis patients in Kelantan, Malaysia 
AIM: To determine the seroprevalence of anti-hepatitis A virus (HAV) antibodies in patients with chronic liver disease (CLD) and to justify the need for hepatitis A vaccination.
METHODS: Patients (n = 119) were enrolled between July and September 2009. The diagnosis of CLD was based on the presence of viral markers for more than 6 mo. The diagnosis of liver cirrhosis was based on clinical, biochemical and radiological profiles. Patient serum was tested for anti-HAV IgG.
RESULTS: The overall anti-HAV seroprevalence was 88.2%. The aetiology of CLD was hepatitis B in 96 patients (80.7%) and hepatitis C in 23 patients (19.3%). Mean age was 44.4 ± 14 years. Patients were grouped according to age as follows: 24 (20.2%) patients in the 21-30 years age group, 22 (18.5%) in the 31-40 years age group, 31 (26.1%) in the 41-50 years age group, 23 (19.3%) in the 51-60 years age group and 19 (16.0%) patients aged greater than 60 years, with reported seroprevalences of 66.7%, 95.5%, 93.5%, 91.3% and 94.7%, respectively. There was a marked increase of seroprevalence in subjects older than 30 years (P = 0.001).
CONCLUSION: Our study demonstrated that patients aged greater than 30 years of age were likely to have natural immunity to hepatitis A. Therefore, hepatitis A vaccination may not be routinely required in this age group.
doi:10.3748/wjg.v17.i36.4130
PMCID: PMC3203366  PMID: 22039329
Hepatitis A seroprevalence; Chronic viral hepatitis; Malaysia; Hepatitis A vaccination
24.  Past exposure to hepatitis B virus as a risk factor for hepatocellular carcinoma in patients with chronic liver disease. 
British Journal of Cancer  1998;77(11):2028-2031.
The aim of the study was to determine whether past exposure to hepatitis B virus (HBV) influences the risk of the development of hepatocellular carcinoma (HCC) in Japanese patients with chronic liver disease (CLD). We conducted a hospital-based case-control study of 141 HCC patients with CLD and 151 controls with CLD but without HCC. Past exposure to HBV was assessed by antibody to hepatitis B core antigen (anti-HBc) positivity. Ninety-two patients (65%) with HCC were anti-HBc positive compared with 65 patients (43%) with CLD alone (P < 0.01). A multivariate analysis using logistic regression modelling revealed that anti-HBc positivity significantly increased the risk of the development of HCC [odds ratio (OR) 2.0, P = 0.01]. In the anti-HBc-positive patients, a significantly increased risk of HCC was seen among the patients positive for anti-HBc alone (OR, 2.6; P < 0.01). However, a significant OR was not obtained among the patients with a transient HBV infection implied by positivity for both antibody to hepatitis B surface antigen and anti-HBc (OR, 1.5; P = 0.48). These results indicate that past exposure to HBV is a risk factor for HCC in Japanese CLD patients, especially when they have no serological evidence of immunity to HBV.
PMCID: PMC2150336  PMID: 9667687
25.  Urinary N-acetyl-β-d-Glucosaminidase Levels are Positively Correlated With 2-Hr Plasma Glucose Levels During Oral Glucose Tolerance Testing in Prediabetes 
Background
Urinary N-acetyl-β-D-glucosaminidase (NAG) excretion is increased in patients with impaired glucose tolerance (IGT). This study investigated when during the oral glucose tolerance test (OGTT) the plasma glucose, urine glucose, and insulin levels correlate most strongly with urinary N-acetyl-β-d-glucosaminidase (NAG) levels in prediabetic subjects.
Methods
The OGTT was administered to 80 subjects who had not yet received a diagnosis of diabetes mellitus (DM) and in whom HbA1c levels were ≤6.8% and fasting plasma glucose levels were <7.0 mmol/l. Forty-two subjects had normal glucose tolerance (NGT), 31 had impaired glucose tolerance (IGT), and 7 had DM according to World Health Organization criteria. Serum levels of cystatin C, the estimated glomerular filtration rate, the urinary albumin-to-creatinine (Cr) ratio, urinary and serum β2-microglobulin, and urinary NAG were measured as markers of renal function.
Results
NAG levels were significantly higher in subjects with DM and in subjects with IGT than in subjects with NGT. No significant associations were observed between glycemic status and other markers of renal function. Multiple linear regression analysis showed that the NAG level was positively correlated with plasma glucose levels at 120 min of the OGTT and was associated with the glycemic status of prediabetic patients.
Conclusion
These results suggest that postprandial hyperglycemia is an independent factor that causes renal tubular damage in prediabetes patients.
doi:10.1002/jcla.21549
PMCID: PMC3558795  PMID: 23143631
cystatin C; N-acetyl-β-d-glucosaminidase; tubular dysfunction; impaired glucose tolerance; diabetic nephropathy

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