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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.
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 
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.
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).
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.
PMCID: PMC2702913  PMID: 19568519
Cirrhosis; diabetes mellitus; hepatocellular carcinoma; Saudi Arabia
3.  Heme Oxygenase-1 mRNA Expression in Egyptian Patients With Chronic Liver Disease 
Hepatitis Monthly  2012;12(4):278-285.
Chronic liver disease (CLD) is a global medical problem. This disease is associated with increased hepatic oxidative stress. One of the antioxidant enzymes that protect cells against this stress is heme oxygenase-1 (HO-1).
This study aimed to investigate the mRNA expression of HO-1 in Egyptian patients with CLD and its relation to oxidative stress biomarkers.
Patients and Methods
Levels of serum ferritin, carboxyhemoglobin, malondialdehyde (MDA), and erythrocyte-reduced glutathione (GSH) were measured, and HO-1 mRNA expression was detected in 45 CLD patients (15 with nonalcoholic steatohepatitis [NASH], 15 with chronic hepatitis C, and 15 with liver cirrhosis) and 15 healthy controls.
HO-1 mRNA expression was increased in patients with NASH, chronic hepatitis C, and liver cirrhosis compared to controls. The expression in cirrhotic patients was significantly higher than that in patients with NASH and chronic hepatitis C. Compared to controls, patients with NASH, chronic hepatitis C, and liver cirrhosis had higher levels of ferritin, carboxyhemoglobin, and MDA and lower levels of GSH. HO-1 mRNA expression was positively correlated with levels of carboxyhemoglobin, serum ferritin, and serum MDA and negatively correlated with levels of erythrocyte GSH in CLD patients.
HO-1 mRNA expression was significantly increased in CLD patients, and the increase reflected the severity of the disease. The significant relationship between the increased HO-1 expression and oxidative stress biomarkers in patients with CLD suggests that HO-1 may play an important role in protecting the liver from oxidative stress-dependent damage. Therefore, induction of HO-1 could be a novel therapeutic option for CLD.
PMCID: PMC3360938  PMID: 22690236
Gene Expression; Heme Oxygenase-1; Hepatitis C Virus; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Oxidative Stress
4.  Platelet IgG antibodies are significantly increased in chronic liver disease 
The aim of this study was to investigate the presence of IgG antiplatelet (anti-P) IgG antibodies in patients with chronic liver disease (CLD) of diverse but well defined etiology.
One-hundred fifty-six consecutive patients with CLD (65 with chronic hepatitis B, 57 with chronic hepatitis C, 23 with alcoholic liver disease and 11 with primary biliary cirrhosis), and 240 healthy blood donors were investigated for the presence of anti-P antibodies.
Anti-P antibodies were present in 36.5% (57/156) of patients with CLD, and 2.9% (7/240) of controls (P=0.0001). In detail, anti-P antibodies were detected in 35.4% (23/65) of patients with chronic hepatitis B, 26.3% (15/57) of patients with chronic hepatitis C, 47.8% (11/23) of patients with alcoholic liver disease and 72.7% (8/11) of those with primary biliary cirrhosis. The study also demonstrated the significantly higher prevalence of anti-P antibodies in patients with cirrhosis (53.0%) than in non cirrhotic patients (26.4%, P=0.0018). The association of anti-P antibodies with thrombocytopenia was inconsistent.
This study showed a high prevalence of anti-P IgG antibodies in patients with CLD compared to healthy controls.
PMCID: PMC3959471  PMID: 24714308
antiplatelet antibodies; chronic liver disease; thrombocytopenia; chronic hepatitis; cirrhosis
5.  Type and etiology of liver cirrhosis are not related to the presence of hepatic encephalopathy or health-related quality of life: a cross-sectional study 
BMC Gastroenterology  2008;8:46.
Hepatic encephalopathy has a negative impact on health-related quality of life (QoL) in liver cirrhosis. There are scarce and conflicting data on whether type or etiology of liver cirrhosis could be related to hepatic encephalopathy in patients with cirrhosis. We aimed to determine the impact of cirrhosis etiology on hepatic encephalopathy and whether hepatic encephalopathy affects health-related QoL among patients with cirrhosis of different etiologies.
A total of 156 cirrhotic patients were prospectively evaluated for the presence of hepatic encephalopathy according to the West-Haven criteria as well as by means of two psychometric tests. Patients with cryptogenic cirrhosis or cirrhosis due to mixed hepatocellular/cholestatic etiologies were excluded. Fasting plasma glucose levels were also measured. QoL was evaluated by means of a validated questionnaire (SF-36).
Diabetes mellitus was more common in patients with hepatocellular cirrhosis compared to those with cholestatic cirrhosis but the two groups did not differ in cirrhosis severity or the prevalence of hepatic encephalopathy (p > 0.05). The groups of patients with cirrhosis due to alcohol, hepatitis C, or cholestatic liver disease did not differ in severity of liver cirrhosis or the prevalence of hepatic encephalopathy (p > 0.05). Patients with cirrhosis of different etiologies did not differ in any SF-36 domain (p > 0.05). In multivariate analysis, performance at neuropsychological testing was independently related only to age, diabetes mellitus, and the Child-Pugh score whereas the SF-36 physical component summary only to the Child-Pugh score and hepatic encephalopathy.
Cirrhosis etiology does not seem to be related to hepatic encephalopathy or health-related QoL. Cognitive impairment is associated mainly with age, liver disease severity and diabetes mellitus.
PMCID: PMC2575200  PMID: 18922174
6.  Chronic Liver Disease Mortality Among Male Prison Inmates in Texas, 1989–2003 
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.
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.
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.
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.
PMCID: PMC2856927  PMID: 19491854
7.  Association of HCV with diabetes mellitus: an Egyptian case-control study 
Virology Journal  2011;8:367.
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.
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.
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.
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.
PMCID: PMC3199807  PMID: 21791087
8.  Health-Related Quality of Life in Chinese Patients with Chronic Liver Disease 
Aim. To investigate the factors contributing to health-related quality of life (HRQOL) in Chinese patients with chronic liver disease (CLD). Methods. HRQOL was measured with SF-36v2 Chinese version. Demographic and clinical data were collected, and patients with liver cirrhosis were divided into Child's Class A, B, and C according to Child-Turcotte-Pugh scoring system. Results. A total of 392 Chinese patients with CLD and 91 healthy controls were enrolled. HRQOL in patients with CLD was lower than that in healthy controls. Score of PCS in healthy controls was 54.6 ± 5.5 and in CLD was 47.8 ± 8.8 (P = 0.000). Score of MCS in healthy controls was 56.4 ± 8.1 and in CLD was 51.7 ± 7.4 (P = 0.000). Increasing severity of CLD from no cirrhosis to advanced cirrhosis was associated with a decrease on all domains of the SF-36 (P < 0.05). Stepwise linear regression analysis showed that severity of disease, age, present ascites, present varices, and prothrombin time had significant effect on physical health area. Severity of disease, female, present varices, total bilirubin, prothrombin time, and hemoglobin had significant effect on mental health area. Conclusions. Patients with CLD had impaired HRQOL. Increasing severity of CLD was associated with a decrease on HRQOL. Old age, female gender, advanced stage of CLD, present ascites, hyperbilirubinemia, and prolonging prothrombin time were important factors reducing HRQOL.
PMCID: PMC3371692  PMID: 22701477
9.  Disturbances of parathyroid hormone–vitamin D axis in non-cholestatic chronic liver disease: a cross-sectional study 
Hepatology International  2010;4(3):634-640.
Liver has an important role in metabolism of vitamin D. This study aimed to evaluate the patterns of vitamin D–parathyroid hormone (PTH) disturbance and correlate it in patients with non-cholestatic chronic liver disease (CLD).
A total of 40 healthy controls and 90 consecutive patients with evidence of non-cholestatic CLD due to hepatitis C (n = 28), hepatitis B (n = 26), autoimmune hepatitis (n = 19), and cryptogenic causes (n = 17) were enrolled. Cirrhosis was evident in 51 patients. Serum concentrations of 25-hydroxy vitamin D, PTH, calcium, phosphate, and liver enzymes were measured. Child–Pugh classification was determined in cirrhotic patients.
Vitamin D deficiency (<50 nmol/l) was found in 46 (51.1%) patients and vitamin D insufficiency (50–80 nmol/l) in 15 (16.7%) patients. Secondary hyperparathyroidism (serum PTH > 6.8 pmol/l) was present in 6 (6.7%) patients. The prevalence of vitamin D deficiency was significantly higher in cirrhotic versus noncirrhotic patients (76.5 vs. 17.9%; P < 0.001), whereas there was no significant difference in serum calcium, phosphate, and PTH levels. Child–Pugh class B and C patients had significantly lower vitamin D level compared with class A patients (P < 0.001), whereas there was no significant difference in serum calcium, phosphate, and PTH levels. No significant correlation was seen between vitamin D and PTH, calcium or phosphate levels. Lower serum level of vitamin D was associated with coagulopathy, hyperbilirubinemia, hypoalbuminemia, anemia, and thrombocytopenia.
Vitamin D inadequacy and the severity of liver dysfunction move in parallel in patients with non-cholestatic CLD. Vitamin D assessment and replacement should be considered in the management of patients with non-cholestatic CLD.
PMCID: PMC2940008  PMID: 21063488
Vitamin D; Liver; Cirrhosis; Parathyroid hormone; Child–Pugh score; MELD
10.  Assessment of Factors Associated with Pre-diabetes in HCV Infection Including Direct and Dynamic Measurements of Insulin Action 
Journal of Viral Hepatitis  2011;19(7):480-487.
Background and Aims
Although hepatitis C (HCV) is associated with diabetes, few studies have examined pre-diabetes in this population. We aimed to evaluate factors associated with pre-diabetes in HCV-infected patients, including direct measurement of insulin action.
Ninety-seven non-cirrhotic, non-diabetic, HCV-infected patients underwent clinical evaluation and oral glucose tolerance testing (OGTT). Insulin sensitivity was measured directly by steady-state plasma glucose (SSPG) concentration during insulin suppression test. Early phase and total insulin secretion were determined using OGTT.
Rates of pre-diabetes were: 21% impaired fasting glucose (IFG), 7% impaired glucose tolerance (IGT), and 9% combined IFG/IGT. 12% of Caucasians, 50% of African-Americans, and 70% of Latinos had pre-diabetes (p=0.002). Patient characteristics among the glucose metabolism categories were similar except those with combined IFG/IGT who had a higher BMI versus normal glucose tolerance (NGT) (30 vs. 26 kg/m2, p=0.007) and lower LDL versus NGT and IGT (74, 104, and 112 mg/dL, respectively, p≤0.01). On multivariable analysis, non-Caucasian race (OR 23.1, p=0.003), BMI (OR 3.4, p=0.02), and greater liver inflammation (OR 7.9, p=0.03) predicted IFG, whereas non-Caucasian race (OR 14.8, p=0.01) and SSPG (OR 1.1/per 10 units, p=0.01) predicted IGT. Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in pre-diabetes compared to NGT (p=0.01 and p=0.02, respectively).
Pre-diabetes is highly prevalent among HCV-infected patients, and in some instances coincides with host responses to the virus. In most cases, however, factors that are associated with pre-diabetes in HCV-infected patients are similar to those observed in the non-HCV population.
PMCID: PMC3375865  PMID: 22676360
Chronic Hepatitis C Virus Infection; Insulin Resistance; Insulin Secretion; Impaired Glucose Tolerance; Liver Inflammation; Impaired Fasting Glucose
11.  Interleukin-8 Is Activated in Patients with Chronic Liver Diseases and Associated with Hepatic Macrophage Accumulation in Human Liver Fibrosis 
PLoS ONE  2011;6(6):e21381.
Interleukin-8 (IL-8, CXCL8) is a potent chemoattractant for neutrophils and contributes to acute liver inflammation. Much less is known about IL-8 in chronic liver diseases (CLD), but elevated levels were reported from alcoholic and hepatitis C-related CLD. We investigated the regulation of IL-8, its receptors CXCR1 and CXCR2 and possible IL-8 responding cells in CLD patients.
Serum IL-8 levels were measured in CLD patients (n = 200) and healthy controls (n = 141). Intrahepatic IL-8, CXCR1 and CXCR2 gene expression was quantified from liver samples (n = 41), alongside immunohistochemical neutrophil (MPO) and macrophage (CD68) stainings. CXCR1 and CXCR2 expression was analyzed on purified monocytes from patients (n = 111) and controls (n = 31). In vitro analyses explored IL-8 secretion by different leukocyte subsets.
Principal Findings
IL-8 serum levels were significantly increased in CLD patients, especially in end-stage cirrhosis. Interestingly, patients with cholestatic diseases exhibited highest IL-8 serum concentrations. IL-8 correlated with liver function, inflammatory cytokines and non-invasive fibrosis markers. Intrahepatically, IL-8 and CXCR1 expression were strongly up-regulated. However, intrahepatic IL-8 could only be associated to neutrophil infiltration in patients with primary biliary cirrhosis (PBC). In non-cholestatic cirrhosis, increased IL-8 and CXCR1 levels were associated with hepatic macrophage accumulation. In line, CXCR1, but not CXCR2 or CXCR3, expression was increased on circulating monocytes from cirrhotic patients. Moreover, monocyte-derived macrophages from CLD patients, especially the non-classical CD16+ subtype, displayed enhanced IL-8 secretion in vitro.
IL-8 is strongly activated in CLD, thus likely contributing to hepatic inflammation. Our study suggests a novel role of IL-8 for recruitment and activation of hepatic macrophages via CXCR1 in human liver cirrhosis.
PMCID: PMC3120868  PMID: 21731723
12.  Portalsystemic hemodynamic changes in chronic severe hepatitis B: An ultrasonographic study 
AIM: To evaluate portalsystemic hemodynamic changes in chronic severe hepatitis B.
METHODS: Hemodynamic parameters included portal vein diameter (PVD), portal vein peak velocity (PVPV), portal vein volume (PVV), spleen length (SPL), spleen vein diameter (SPVD), spleen vein volume (SPVV) and umbilical vein recanalization. They were measured by Color Doppler ultrasonography in 36 patients with chronic severe hepatitis B, compared with 51 normal controls, 61 patients with chronic hepatitis B, 46 patients with compensable cirrhosis, and 36 patients with decompensable cirrhosis.
RESULTS: In the group of chronic severe hepatitis B, PVD (12.38 ± 1.23 mm) was significantly different from the normal control, compensable cirrhosis and decompensable cirrhosis groups (P = 0.000-0.026), but not significantly different from the chronic hepatitis group. PVPV (16.15 ± 3.82 cm/s) dropped more significantly in the chronic severe hepatitis B group than the normal control, chronic hepatitis B and compensable cirrhosis groups (P = 0.000-0.011). PVV (667.53 ± 192.83 mL/min) dropped significantly as compared with the four comparison groups (P = 0.000-0.004). SPL (120.42 ± 18.36 mm) and SPVD (7.52 ± 1.52 mm) were longer in the normal control and chronic hepatitis B groups (P = 0.000-0.009), yet they were significantly shorter than those in the decompensable cirrhosis group (P = 0.000). SPVV (242.51 ± 137.70 mL/min) was also lower than the decompensable cirrhosis group (P = 0.000). The umbilical vein recanalization rate (75%) was higher than the chronic hepatitis B and compensable cirrhosis groups. In the course of progression from chronic hepatitis to decompensable cirrhosis, PVD, SPL and SPVD gradually increased and showed significant differences between every two groups (P = 0.000-0.002).
CONCLUSION: Patients with chronic severe hepatitis B have a tendency to develop acute portal hypertension, resulting in significantly reduced portal vein perfusion. Observation of the portalsystemic hemodynamic changes may be contributed to the disease progression of chronic liver disease.
PMCID: PMC2684011  PMID: 18205274
Color doppler ultrasonography; Portalsystemic hemodynamics; Chronic severe hepatitis B
13.  Deep vein thrombosis in patients with advanced liver cirrhosis: a rare condition? 
Hepatology International  2010;4(1):433-438.
Patients with liver cirrhosis are generally considered to be “auto-anticoagulated” because of coagulopathy and thrombocytopenia. However, deep vein thrombosis (DVT) has been reported in patients with liver cirrhosis. The objectives of this study were to know the prevalence of DVT among cirrhotic patients and to compare clinical pictures between cirrhotic patients with and without DVT.
A case–control study was performed on the basis of medical record data of patients with liver cirrhosis admitted between August 2004 and July 2007 in Medistra hospital in Jakarta. Diagnosis of DVT was established by duplex Doppler ultrasonography of the lower extremities. Patients with splanchnic thrombosis were excluded from this study. Diagnosis of liver cirrhosis was based on history and clinical manifestation, consistent with liver cirrhosis and confirmed by ultrasonography or computed tomography.
A total of 256 patients with liver cirrhosis were included in this study; 164 (64.1%) among them were men. Patients’ mean age was 60.5 ± 12.5 years, ranging from 16 to 88 years. Viral hepatitis accounted for 74.6% of patients with liver cirrhosis. DVT was found in 12 (4.7%) patients. There was no significant laboratory difference between cirrhotic patients with and without DVT (serum albumin, platelet count, aminotransferases, γ-glutamyl transpeptidase, alkaline phosphatase, total bilirubin levels, and prothrombin time). Diabetes mellitus was significantly higher in the DVT group than that in the control group (66.6 vs. 34.0%, P = 0.025). Multivariate analysis confirmed diabetes mellitus as an independent risk factor for the occurrence of DVT (odds ratio = 4.26; 95% confidence interval = 1.206–15.034; P = 0.024).
The prevalence of DVT in patients with liver cirrhosis was 4.7%, and Deep vein thrombosis is not a rare condition in cirrhotic patients with coagulopathy and warrants further studies on the mechanisms and prevention.
PMCID: PMC2836440  PMID: 20305762
DVT; Liver cirrhosis; Autoanticoagulated; Coagulopathy
14.  The impact of hepatitis viruses on chronic lymphoproliferative disorders; preliminary results  
Journal of Medicine and Life  2010;3(3):320-329.
The aim of this study is to analyze a group of patients with chronic lymphoproliferative disorders associated with B, C, D hepatitis viral infection. This group of chronic lymphoproliferative disordered patients with associated hepatitis viral infection has been diagnosed and monitored in the Hematology Department of the University Emergency Hospital of Bucharest, between December 2007 and January 2009. Our study is meant to observe the influence of the viral infection on clinical and biological evolution of the enrolled patients.
The diagnosis of the chronic lymphoproliferative disorder was based on the bone marrow / lymph node biopsy and flow–cytometry analysis. The positive diagnosis for hepatitis viral infection was established by ELISA serological tests and viremia was performed by TaqMan method at INBI ‘Matei Bals’ Bucharest.
The analyzed group is made up of 41 patients, 25/41 (60,97%) females and 16/41 (39,02%) males, with ages: 20–50 years old – 6/41 (14,63%), 51–70 years old – 23/41 (56,09%) and over 71 years old – 12/41 (29,26%) patients. The histological types of CLD: B–cell non–Hodgkin's lymphoma – in 28/41 (68,29%) patients, T–cell non–Hodgkin's lymphoma – 2/41 (4,87%) patients, Hodgkin's lymphoma – 2/41 (4,87%), chronic lymphocytic leukemia – 7/41 (17,07%), Waldenström disease – 2/41 (4,87%) patients. Regarding the type of CLD, 19/41 (46,34%) of the patients have an aggressive type of CLD and 22/41 (53,65%) a non–aggressive type of CLD. The hepatitis viral infection distribution in our patients: 14/41 (34,14%) have HBV infection, 24/41 (58,53%) have HCV infection, double/triple association of viral infection was found in 3/41 (7,31%) patients. Within HBV infection subgroup 9/14 (64,28%) patients have an aggressive type of CLD and 5/14 (35,71%) patients have a non–aggressive type, whereas within the group with HCV infection we found a different distribution: 9/24 (37,5%) patients with aggressive type and 15/24 (62,5%) with non–aggressive type of CLD. The clinical parameters monitored were: B signs were present in 19/41 (43,34%) patients, the superficial or profound adenopathies –were found in 29/41 (70,73%) patients, hepatomegaly – in 38/41 (92,68%) patients, splenomegaly – in 21/41 (51,21%) patients, extra–nodal involvements in 10/41 (24,39%) patients and most frequent in the non–aggressive type of CLD – 6/10 (60%) patients. The hematological and biochemical parameters were: the presence of anemia and thrombocytopenia – found in a small number of patients; lymphocytosis – positive in 33/41 (80,48%) patients, most with HCV infection and non–aggressive type of disease, the presence of autoimmune hemolytic anemia – in 4/41 (9,75%) patients, cryoglobulins – 8/41 (19,51%) patients, all with HCV infection; also the liver function was monitored. Antiviral therapy was administered to 12/41 (29,26%) patients – Lamivudine to 8/41 (19,51%) patients and Ribavirine/Interferon to 4/41 (9,75%) patients. Chemotherapy was given in 32/41 (78%) patients. Monoclonal antibodies anti CD20 (Rituximab) therapy was associated in 6/41 (14,63%) patients.
Conclusions. A high incidence in female sex of over 50 years old was noticed. A strong association between B–cell chronic lymphoproliferative disorders and hepatitis viral infection B, C, D was revealed, the most frequent being the C hepatitis virus, associated with the non–aggressive type of CLD, extra–nodal involvement, splenomegaly, lymphocytosis, cryoglobulins, cytolysis and colestasis. The clinical and biological disease history will be monitored during chemotherapy and antiviral treatment.
PMCID: PMC3019001  PMID: 20945824
15.  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 Egypt over a decade.
METHODS: All HCC patients attending Cairo Liver Center between January 1993 and December 2002, were enrolled in the study. Diagnosis of HCC was based on histopathological 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 schistoso-miasis 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% vs 28.9% 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.
PMCID: PMC4320394  PMID: 16127751
Hepatocellular carcinoma; HCC prevalence; HCC risk factors; Pattern of HCC; HCV and HCC; HBV and HCC
16.  Influence of chronic HBV infection on superimposed acute hepatitis E 
AIM: To investigate the influence of chronic hepatitis B virus (HBV) infection [based on the status of hepatitis B e antigen (HBeAg), HBV DNA, and cirrhosis] on superimposed acute hepatitis E.
METHODS: A total of 294 patients were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital, Sun Yat-sen University, from January 2003 to January 2012. The patients were classified into two groups: an HBV + hepatitis E virus (HEV) group (a group with chronic HBV infection that was superinfected with acute hepatitis E, n = 118) and an HEV group (a group with acute hepatitis E, n = 176). We retrospectively analyzed and compared the clinical features of the two groups. Statistical analyses were performed using the χ2 test or Fisher’s exact test for categorical variables and the Student’s t test for continuous variables. A P value < 0.05 was considered statistically significant.
RESULTS: The peak values of prothrombin time, serum total bilirubin, and Model for End-Stage Liver Disease scores were significantly higher in the HBV + HEV group. More patients in the HBV + HEV group had complications (39.8% vs 16.5%, P = 0.000) and developed liver failure (35.6% vs 8.5%, P = 0.000). Additionally, the mortality of the HBV + HEV group was significantly higher (20.3% vs 7.4%, P = 0.002). Further analysis of the HBV + HEV group showed that there were no significant differences in complication occurrence, liver failure incidence, or mortality between patients with different HBeAg and HBV DNA statuses. However, in patients with underlying cirrhosis, complication occurrence and liver failure incidence significantly increased. In total, 12.7% of the patients in the HBV + HEV group received anti-HBV treatment, but this therapy failed to reduce mortality in patients who developed liver failure.
CONCLUSION: The presence of underlying cirrhosis in chronic HBV infection results in more severe clinical outcomes with superimposed acute hepatitis E. Anti-HBV treatment cannot improve the prognosis of liver failure caused by HBV-HEV superinfection.
PMCID: PMC3793145  PMID: 24124337
Chronic hepatitis B virus infection; Acute hepatitis E; Superinfection; Clinical profile; Anti-hepatitis B virus treatment
17.  Adiponectin and Its Receptors in Chronic Hepatitis B Patients With Steatosis in China 
Hepatitis Monthly  2013;13(4):e6065.
HBV infection is a serious public health problem worldwide, which can contribute to the incidence of chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma (HCC).
In the present report, we assessed the association between adiponectin, its receptors and hepatic steatosis, fibrosis, and inflammation with hepatitis B virus.
Patients and Methods
Liver biopsies from 89 patients with untreated chronic hepatitis B (34 steatosis vs. 55 without steatosis) were analyzed; liver biopsies from 50 healthy adults were used as control. The liver biopsies were subjected to routine histological examination, and stained immunohistochemically for adiponectin and adiponectin receptor2 (adipoR2).
The two groups were found to be comparable with respect to demographic, biochemical, metabolic, histological, and viral characteristics. BMI, γ-GT, FPG, insulin, and insulin sensitivity estimated by the HOMA index were significantly higher in patients with steatosis. The viral load of HBV and HBeAg positivity was higher in patients with steatosis than those without steatosis. High serum adiponectin levels were significantly correlated with abnormal serum ALT level (vs. normal ALT, P = 0.000), and HBV genotype C (vs. genotype B, P = 0.018). In patients with chronic HBV, the insulin sensitizing adipokine adiponectin, and its receptor AdipoR2were associated with steatosis. While adiponectin may becorrelated with inflammation, adiponectin, and its receptors were not associated with viral factors.
Our results suggest that the role of adiponectin might be impaired in chronic hepatitis B with steatosis. Reduced hepatic expression of adiponectin and adipoR2 might be of pathophysiological relevance in CHB patients with steatosis. These findings indicated that reduced liver adiponectin expression may play an important role in the pathogenesis, and progression of CHB patients with steatosis. However, hepatic expression of adiponectin, and adipoR2 was not associated with various measures of HBV infection.
PMCID: PMC3725260  PMID: 23914225
Hepatitis B, Chronic; Adiponectin; Receptors, Adiponectin; liver
18.  Staging of portal hypertension and portosystemic shunts using dynamic nuclear medicine investigations 
AIM: To explore portal hypertension and portosystemic shunts and to stage chronic liver disease (CLD) based on the pathophysiology of portal hemodynamics.
METHODS: Per-rectal portal scintigraphy (PRPS) was performed on 312 patients with CLD and liver angioscintigraphy (LAS) on 231 of them. The control group included 25 healthy subjects. We developed a new model of PRPS interpretation by introducing two new parameters, the liver transit time (LTT) and the circulation time between right heart and liver (RHLT). LTT for each lobe was used to evaluate the early portal hypertension. RHLT is useful in cirrhosis to detect liver areas missing portal inflow. We calculated the classical per-rectal portal shunt index (PRSI) at PRPS and the hepatic perfusion index (HPI) at LAS.
RESULTS: The normal LTT value was 24 ± 1 s. Abnormal LTT had PPV = 100% for CLD. Twenty-seven non-cirrhotic patients had LTT increased up to 35 s (median 27 s). RHLT (42 ± 1 s) was not related to liver disease. Cirrhosis could be excluded in all patients with PRSI < 5% (P < 0.01). PRSI > 30% had PPV = 100% for cirrhosis. Based on PRPS and LAS we propose the classification of CLD in 5 hemodynamic stages. Stage 0 is normal (LTT = 24 s, PRSI < 5%). In stage 1, LTT is increased, while PRSI remains normal. In stage 2, LTT is decreased between 16 s and 23 s, whereas PRSI is increased between 5% and 10%. In stage 3, PRSI is increased to 10%-30%, and LTT becomes undetectable by PRPS due to the portosystemic shunts. Stage 4 includes the patients with PRSI > 30%. RHLT and HPI were used to subtype stage 4. In our study stage 0 had NPV = 100% for CLD, stage 1 had PPV = 100% for non-cirrhotic CLD, stages 2 and 3 represented the transition from chronic hepatitis to cirrhosis, stage 4 had PPV = 100% for cirrhosis.
CONCLUSION: LTT allows the detection of early portal hypertension and of opening of transhepatic shunts. PRSI is useful in CLD with extrahepatic portosystemic shunts. Our hemodynamic model stages the evolution of portal hypertension and portosystemic shunts. It may be of use in the selection of patients for interferon therapy.
PMCID: PMC2721440  PMID: 18609707
Chronic liver disease; Portal hypertension; Portosystemic shunts; Per-rectal portal scintigraphy; Angioscintigraphy
19.  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.
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.
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.
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).
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.
PMCID: PMC2413226  PMID: 18501007
20.  Early Detection, Curative Treatment, and Survival Rates for Hepatocellular Carcinoma Surveillance in Patients with Cirrhosis: A Meta-analysis 
PLoS Medicine  2014;11(4):e1001624.
Amit Singal and colleagues conducted a systematic review of the evidence that surveillance for hepatocellular carcinoma in patients with cirrhosis improves early detection, receipt of curative treatment, and overall survival.
Please see later in the article for the Editors' Summary
Surveillance for hepatocellular carcinoma (HCC) has level I evidence among patients with hepatitis B but only level II evidence in patients with cirrhosis. This lack of randomized data has spurred questions regarding the utility of HCC surveillance in this patient population; however, lack of randomized data does not equate to a lack of data supporting the efficacy of surveillance. The aim of our study was to determine the effect of HCC surveillance on early stage tumor detection, receipt of curative therapy, and overall survival in patients with cirrhosis.
Methods and Findings
We performed a systematic literature review using Medline from January 1990 through January 2014 and a search of national meeting abstracts from 2009–2012. Two investigators identified studies that reported rates of early stage tumor detection, curative treatment receipt, or survival, stratified by HCC surveillance status, among patients with cirrhosis. Both investigators independently extracted data on patient populations, study methods, and results using standardized forms. Pooled odds ratios, according to HCC surveillance status, were calculated for each outcome using the DerSimonian and Laird method for a random effects model.
We identified 47 studies with 15,158 patients, of whom 6,284 (41.4%) had HCC detected by surveillance. HCC surveillance was associated with improved early stage detection (odds ratio [OR] 2.08, 95% CI 1.80–2.37) and curative treatment rates (OR 2.24, 95% CI 1.99–2.52). HCC surveillance was associated with significantly prolonged survival (OR 1.90, 95% CI 1.67–2.17), which remained significant in the subset of studies adjusting for lead-time bias. Limitations of current data included many studies having insufficient duration of follow-up to assess survival and the majority not adjusting for liver function or lead-time bias.
HCC surveillance is associated with significant improvements in early tumor detection, receipt of curative therapy, and overall survival in patients with cirrhosis.
Please see later in the article for the Editors' Summary
Editors' Summary
Hepatocellular cancer (HCC) is the commonest form of primary liver cancer—a type of cancer that starts when a cell in the liver acquires genetic changes that allow it to grow uncontrollably. Primary liver cancer is the third leading cause of cancer-related death worldwide, killing more than 600,000 people every year. The symptoms of HCC are vague and rarely appear until the cancer has spread throughout the liver. They include unexplained weight loss, feeling sick, tiredness, and jaundice (yellowing of the skin and eyes). If liver cancer is diagnosed in its early stages, it can be treated by surgically removing part of the liver, by liver transplantation, or by a procedure called radiofrequency ablation in which an electric current is used to destroy the cancer cells. However, most people are diagnosed with HCC when the cancer is advanced and cannot be treated. These individuals are given palliative treatment to relieve pain and discomfort. Although most patients who are diagnosed with HCC at an early stage survive more than 5 years, patients with more advanced HCC have an average survival less than one year. The exact cause of HCC is unknown, but it is thought to be related to cirrhosis (scarring) of the liver. This condition is the end result of long-term (chronic) liver damage caused by, for example, alcohol abuse or infection with hepatitis B virus (HBV).
Why Was This Study Done?
Because HCC tends to be untreatable when it is diagnosed at a late stage, if the tumor can be found early by regularly measuring blood levels of alpha fetoprotein (a liver cancer biomarker) and using ultrasound, outcomes for patients at high risk of developing HCC might be improved. Indeed, American and European guidelines recommend HCC surveillance with ultrasound every 6 months in patients with HBV infection and/or cirrhosis. However, although randomized controlled trial results support HCC surveillance among patients infected with HBV, no randomized trials have investigated its use among patients with cirrhosis. Here, the researchers use predefined criteria to identify all the published cohort and case-control studies (two types of non-randomized studies) that have examined the impact of HCC surveillance on outcomes in patients with cirrhosis. They then pool the data from these studies using a statistical approach called meta-analysis to estimate whether HCC surveillance is associated with improvements in early tumor detection, curative treatment receipt, and survival rates among patients with cirrhosis.
What Did the Researchers Do and Find?
The researchers identified 47 studies that examined the association of HCC surveillance with outcomes in 15,158 patients with cirrhosis who developed HCC. In 41.4% of these patients, HCC was detected by surveillance. Among patients who had undergone HCC surveillance, the pooled rate of early detection was 70.9%, whereas among patients who had not undergone surveillance but who were diagnosed incidentally or who presented with symptoms, the pooled rate of early detection was 29.9%. The researchers calculated that the pooled odds (chances) of early detection among patients undergoing surveillance compared to early detection among patients not undergoing surveillance was 2.08 (an odds ratio [OR] of 2.08). The pooled rate of curative treatment receipt among patients undergoing surveillance was 51.3% compared to only 23.8% among patients not undergoing surveillance (OR 2.24). Finally, among those patients for whom the relevant data were available, 50.8% of patients who had undergone HCC surveillance but only 28.2% of those who had not undergone surveillance survived for at least 3 years after diagnosis (OR 1.90).
What Do These Findings Mean?
These findings show that HCC surveillance is associated with significant improvements (improvements that are unlikely to have happened by chance) in early tumor detection, receipt of curative treatment, and overall survival among patients with cirrhosis. Importantly, the association with improved overall survival remained significant after adjusting for the possibility that patients who underwent surveillance died at the same time as they would have done without surveillance but appeared to survive longer because they were diagnosed earlier (this is called adjustment for lead-time bias). These results must be interpreted cautiously, however, because many of the studies included in the meta-analysis had insufficient follow-up to assess survival adequately, not all the studies adjusted for lead-time bias, and none of the studies assessed potential downstream harms of HCC surveillance such as complications of liver biopsies. Nevertheless, overall, these findings provide sufficient evidence to support guidelines that recommend regular HCC surveillance for patients with cirrhosis.
Additional Information
Please access these websites via the online version of this summary at
The US National Cancer Institute provides information about all aspects of cancer, including detailed information for patients and professionals about primary liver cancer and about screening for primary liver cancer (in English and Spanish)
The American Cancer Society also provides information about liver cancer (available in several languages)
The UK National Health Service Choices website provides information about primary liver cancer and about cirrhosis (including patient stories)
Cancer Research UK (a not-for-profit organization) also provides detailed information about primary liver cancer
MedlinePlus provides links to further resources about liver cancer and cirrhosis (in English and Spanish)
Information is available at the American Liver Foundation
American Association for the Study of Liver Diseases provides practice guidelines
PMCID: PMC3972088  PMID: 24691105
21.  Value of duplex doppler ultrasonography in non-invasive assessment of children with chronic liver disease 
AIM: To investigate the value of duplex Doppler ultrasonography (US) in the assessment of the hemodynamics of the portal and hepatic veins in a cohort of children with chronic liver disease (CLD) and to detect any relationship between the US changes, etiology and severity (or stage) of CLD.
METHODS: We prospectively enrolled 25 children with biopsy-proven CLD. Thirteen had cirrhosis (aged 8.9 ± 2.0 years) and 12 had chronic hepatitis (aged 9.3 ± 2.3 years). Gray scale and color-coded duplex Doppler US were performed for all, as well as 30 healthy age and sex-matched controls. Findings were correlated with clinical, laboratory and histopathological characteristics.
RESULTS: Prominent caudate lobe was detected in 100% of cirrhotics, but none of the chronic hepatitis or controls. Thickened lesser omentum and loss of the triphasic waveform of the hepatic vein were present in 69.2% and 53.8% of cirrhotics vs 33.3% and 8.3% of chronic hepatitis respectively. Portal vein flow velocity was significantly lower (P < 0.0001) and the congestion index was significantly higher (P < 0.005) in both patient groups compared to controls. Child-Pugh’s staging showed a positive correlation with both abnormal hepatic vein waveform and direction of portal blood flow; and a negative correlation with both hepatic and portal vein flow velocities. No correlation with the etiology of CLD could be detected.
CONCLUSION: Duplex Doppler added to grayscale US can detect significant morphologic and portal hemodynamic changes that correlate with the severity (stage) of CLD, but not with etiology.
PMCID: PMC3012578  PMID: 21182231
Chronic hepatitis; Chronic liver disease; Cirrhosis; Doppler; Grayscale; Pediatrics; Ultrasound
22.  Safety and Efficacy of Hepatitis B Vaccination in Cirrhosis of Liver 
Advances in Virology  2013;2013:196704.
Introduction. Patients with chronic liver disease (CLD) are more likely to have severe morbidity and fatality rate due to superimposed acute or chronic hepatitis B (HBV) infection. The literature has shown that hepatitis B vaccines are safe and effective in patients with CLD, but the data in cirrhosis liver is lacking. We assessed the safety and immunogenicity of HBV vaccine in patients with cirrhosis liver. Methods. CTP classes A and B CLD patients negative for hepatitis B surface antigen and antibody to hepatitis B core antigen were included. All patients received three doses of hepatitis B vaccine 20 mcg intramuscularly at 0, 30, and 60 days. Anti-HBs antibody was measured after 120 days. Results. 52 patients with mean age 47.48 ± 9.37 years were studied. Response rates in CTP classes A and B were 88% and 33.3%. We observed that the alcoholic chronic liver disease had less antibody response (44%) than other causes of chronic liver disease such as cryptogenic 69% and HCV 75%. Conclusions. Patients with cirrhosis liver will have low antibody hepatitis B titers compared to general population. As the age and liver disease progress, the response rate for hepatitis B vaccination will still remain to be weaker.
PMCID: PMC3690205  PMID: 23840211
23.  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.
PMCID: PMC3351780  PMID: 22611323
Connective tissue growth factor; Liver fibrosis; Chronic hepatitis B; Chronic liver disease; Chronic hepatitis C
24.  Prevalence of Type 2 Diabetes Mellitus in Hepatitis C Virus Infected Population: A Southeast Asian Study 
Journal of Diabetes Research  2013;2013:539361.
Purpose. The study was aimed to investigate the frequency of diabetes mellitus type 2 in patients infected with chronic hepatitis C virus and its association with cirrhosis. Patients and Methods. This prospective case series was conducted at Section of Gastroenterology and Hepatology, Isra University Hospital, Hyderabad, over a period of 4 months from June 2009 to October 2009. Hepatitis C virus seropositive patients who were older than 18 years, diabetic or nondiabetic, were included. Basic demographic data collected by questionnaire and laboratory investigations including fasting blood glucose levels, serum cholesterol, and liver function tests were done. A logistic regression model was used to explore the association between diabetic and nondiabetic HCV seropositives and type 2 diabetes mellitus with cirrhosis. Results. A total of 361 patients with hepatitis C were analyzed; the prevalence of type 2 diabetes mellitus in HCV patients was 31.5%. Out of the total number of the participants, 58.4% (n = 211) were cirrhotics, while 41.6% (n = 150) were noncirrhotic HCV seropositives. In multivariate analysis, cirrhotic patients appeared significantly more likely (P = 0.01) to be diabetic as compared with noncirrhotic patients (OR = 2.005, 95% CI: 1.15, 3.43). Conclusion. Advancing age, increased weight, and HCV genotype 3 are independent predictors of type 2 diabetes in HCV seropositive patients, and there is a statistically significant association of cirrhosis observed with type 2 diabetes mellitus.
PMCID: PMC3747388  PMID: 23984431
25.  The association of complex liver disorders with HBV genotypes prevalent in Pakistan 
Virology Journal  2007;4:128.
Genotyping of HBV is generally used for determining the epidemiological relationship between various virus strains and origin of infection mostly in research studies. The utility of genotyping for clinical applications is only beginning to gain importance. Whether HBV genotyping will constitute part of the clinical evaluation of Hepatitis B patients depends largely on the availability of the relevance of the evidence based information. Since Pakistan has a HBV genotype distribution which has been considered less virulent as investigated by earlier studies from south East Asian countries, a study on correlation between HBV genotypes and risk of progression to further complex hepatic infection was much needed
A total of 295 patients with HBsAg positive were selected from the Pakistan Medical Research Council's (PMRC) out patient clinics. Two hundred and twenty six (77%) were males, sixty nine (23%) were females (M to F ratio 3.3:1).
Out of 295 patients, 156 (53.2%) had Acute(CAH), 71 (24.2%) were HBV Carriers, 54 (18.4%) had Chronic liver disease (CLD) Hepatitis. 14 (4.7%) were Cirrhosis and HCC patients. Genotype D was the most prevalent genotype in all categories of HBV patients, Acute (108), Chronic (39), and Carrier (53).
Cirrhosis/HCC (7) were HBV/D positive. Genotype A was the second most prevalent with 28 (13%) in acute cases, 12 (22.2%) in chronics, 14 (19.7%) in carriers and 5 (41.7) in Cirrhosis/HCC patients. Mixed genotype (A/D) was found in 20 (12.8%) of Acute patients, 3 (5.6%) of Chronic and 4 (5.6%) of carriers, none in case of severe liver conditions.
Mixed HBV genotypes A, D and A/D combination were present in all categories of patients except that no A/D combination was detected in severe conditions. Genotype D was the dominant genotype. However, genotype A was found to be more strongly associated with severe liver disease. Mixed genotype (A/D) did not significantly appear to influence the clinical outcome.
PMCID: PMC2212638  PMID: 18042293

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