Impairment of bone mass development in children with chronic cholestatic liver disease

OBJECTIVE: To analyse aspects of mineral metabolism, bone mineral density (BMD), bone remodelling activity and serum IGF-1 levels in children with chronic cholestatic disease (CCLD). PATIENTS AND MEASUREMENTS: A total of 13 children with chronic cholestatic liver disease (CCLD; mean age 7.2 +/- 4.8 years) and 22 control subjects (mean age 7.6 +/- 4.5 years) were studied. Serum osteocalcin, bone alkaline phosphatase (BAP), 25-hydroxyvitamin D, PTH and IGF-1 levels and urinary deoxypyridinoline were determined. BMD was measured by dual-energy X-ray absorptiometry in the lumbar spine, total hip and whole body. Lumbar spine areal BMD was converted mathematically to apparent volumetric BMD (aBMD) and corrected for the bone age of the patient. RESULTS: Z-score of lumbar spine BMD was lower in CCLD patients than in controls and the difference was maintained when BMD was expressed as aBMD (control = 0.107 +/- 0.02 vs. CCLD = 0.092 +/- 0.02 g/cm(3), P < 0.05) and after conversion for bone age. All participants showed normal 25-hydroxyvitamin D levels, with no significant differences in serum levels of 25-hydroxyvitamin D and PTH between groups. IGF-1 levels were significantly lower in the CCLD group (control = 19.6 +/- 16.8 vs. CCLD = 6.4 +/- 7.6 nmol/l, P < 0.05) and a positive correlation was observed between whole body BMD and IGF-1 in this group. CONCLUSIONS: These results indicate that CCLD limits bone mass gain in children. A reduction in hepatic IGF-1 production might be responsible, at least in part, for the low bone mass of these patients.     

Regulatory failure of serum prohepcidin levels in patients with hepatitis C

BACKGROUND/AIMS: Elevated serum ferritin and hepatic iron concentrations are frequently observed in chronic hepatitis C (CHC), which may be related to hepcidin. Because the role of hepcidin in CHC patients remains unknown, we aimed in this study to generate some information about hepcidin in CHC. METHODS: To determine whether serum hepcidin correlates with markers of iron status in patients with viral hepatitis, we measured serum prohepcidin levels in patients with hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and in healthy controls. RESULTS: Serum prohepcidin and ferritin levels were negatively correlated (r=-0.182, P=0.037) in HCV patients and positively correlated in HBV patients and in healthy controls. The total iron scores in liver specimens from HCV patients were also negatively correlated (r=-0.403, P=0.013). Serum prohepcidin levels in patients with liver cirrhosis (LC) were significantly lower than in patients with chronic hepatitis (CH). In both CH and LC patients, serum prohepcidin levels were significantly lower in HCV patients than in HBV patients. CONCLUSION: Failure of homeostatic regulation of serum prohepcidin concentrations may be induced by HCV infection, resulting in elevation of serum ferritin levels, which leads to the progression of liver injury by iron overload in CHC patients.     

Influence of HCV infection on insulin-like growth factor 1 and proinflammatory cytokines: association with risk for growth hormone resistance development

Communications between the endocrine, immune systems and the liver have been postulated. The liver is the central organ in growth hormone/insulin-like growth factor (GH-IGF) axis. Infection with hepatitis C virus (HCV) can lead to liver problems. Although proinflammatory cytokines are an integral part of inflammation in chronic liver diseases, their involvement in mediating hepatic GH resistance during HCV infection remains to be elucidated. To address this issue, our study aimed at evaluating the influence of HCV infection on serum profile of IGF-1, TNF-alpha and IL-6 to assess their possible relation to hepatic dysfunction and GH resistance development. Twenty-five chronic HCV patients were studied together with 15 healthy control subjects. Serum concentration of IGF-1, TNF-alpha and IL-6 was determined by ELISA. HCV viral load was assessed by Real-time polymerase chain reaction using TaqMan probe technology. Basal serum GH levels were determined by a chemiluminescence assay and serum aminotransferases' activities were also measured. TNF-alpha and IL-6 demonstrated higher serum levels, while IGF-1 levels were significantly lower in HCV patients compared to healthy controls. A statistically significant positive correlation was observed between GH and IL-6 levels (P<0.05), a similar trend was found between GH levels, GH/IGF-1 ratio and AST/ALT ratio (P<0.01, P<0.01, respectively). A significant negative correlation was observed between HCV viral load and GH levels (P<0.05). The progressive increase in HCV viral load matches the decrease in circulating IGF-1 levels but without reaching statistical significance. We conclude that the GH insensitivity could be induced by HCV infection and mediated by proinflammatory cytokines through their possible role in blunting the hepatic response to GH. This crosstalk between proinflammatory cytokines and GH-IGF-1 axis could be responsible for triggering impaired glucose metabolism and diabetes later on in chronic HCV infection.     

Serum adiponectin in chronic hepatitis C and B

Adiponectin possesses anti-inflammatory, insulin-sensitizing and anti-atherosclerotic properties. The aim of this study was to assess the levels of serum adiponectin in patients with chronic viral hepatitis C and B and correlate them with parameters exploring insulin resistance and indices of chronic liver disease. Seventy-two patients with chronic hepatitis C virus (HCV) infection and 73 patients with chronic hepatitis B virus (HBV) infection, matched for age and sex, were studied. All individuals were examined for serum concentrations of adiponectin, insulin, C-peptide and homeostasis model assessment for insulin resistance (HOMA-IR). Viral parameters and liver histology were also evaluated. Serum adiponectin levels were significantly higher in HCV compared with HBV-infected patients. Correlation analysis in the whole group demonstrated that serum adiponectin was positively correlated with aspartate aminotransferase, alkaline phosphatase, globulins, high-density lipoprotein cholesterol and staging score, while it was negatively correlated with body mass index, insulin, C-peptide and HOMA-IR. Logistic regression analysis identified type of infection (HCV vs HBV), alcohol consumption more than 25 g daily, serum total globulin and low C-peptide as significant predictive variables associated with high adiponectin levels. Higher levels of serum adiponectin in HCV compared with HBV patients could have a role in the slower disease progression of chronic HCV infection. In addition, alcohol intake more than 25 g daily seems to be a significant predictor for hyperadiponectinaemia in patients with chronic viral hepatitis C or B. Finally, in this study, a clear positive association between adiponectin and hepatic necroinflammation or staging score was not found.     

Correlation of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function in Chinese patients with chronic hepatitis C virus infection

AIM: To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis C virus (HCV) infection and their potential clinical implications. METHODS: Forty-two chronic HCV-infected patients without anti-viral treatment were enrolled in this study, 30 patients had chronic hepatitis C, 10 had cirrhosis, and 2 had hepatocellular carcinoma (HCC). Thirty age- and sex-matched healthy individuals served as controls. Serum leptin levels were determined by ELISA. The biochemical liver function and serum lipids were determined at the same time. The height and body weight of patients and controls were measured, and body mass index (BMI) and body fat were calculated simultaneously. The correlations of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function were assessed statistically. RESULTS: The mean of serum leptin levels in patients with chronic hepatitis C, HCV-associated cirrhosis, HCV-associated HCC and control groups was (6.13±3.94), (5.25±4.21), (4.17±0.28), and (3.59±3.44) ng/mL, respectively. The serum leptin level in patients with chronic hepatitis C was significantly higher than that in controls. The serum leptin levels between cirrhotic patients and controls and between male and female cirrhotic patients had no significant difference. Serum leptin levels were positively-correlated with body fat, BMI, and apolipoprotein B (Apo B) in patients with chronic HCV infection. The serum alanine aminotransferase (ALT) levels were closely-correlated with BMI in patients with chronic hepatitis C. CONCLUSION: HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.     

Circulating soluble-CD30 (sCD30) in patients with HCV-related chronic hepatitis and in patients with alcoholic liver disease

BACKGROUND/AIMS: Serum sCD30 (soluble CD30) is a marker of cells producing Th2-type (T-helper-2-type) cytokines. High levels of sCD30 have been found in the active phase of HBV infection. The Th2-type cytokine profile has been documented in alcoholic liver diseases, which have particularly high IgE and IgA serum levels. The aims were: 1) to evaluate sCD30 levels in patients with (a) alcoholic liver diseases and (b) HCV-related chronic hepatitis before and after interferon treatment; 2) to correlate sCD30 concentrations with IgE and IgA serum levels. METHODOLOGY: Serum samples from 34 HCV-related chronic hepatitis patients, before and after interferon treatment, and 17 alcoholic liver disease patients were tested for sCD30 using the ELISA method (Dako, CD30-Ki-1 Antigen, Denmark). RESULTS: Significantly higher levels of sCD30 were found in alcoholic liver disease than in HCV-related chronic hepatitis patients (73.3 +/- 120 vs. 27.5 +/- 44 U/mL, P < 0.05). Alcoholic liver disease patients also exhibited significantly higher levels of IgA than HCV-related chronic hepatitis patients (P < 0.0001). No correlation was found between sCD30 and serum IgA or IgE or response to interferon. CONCLUSIONS: Th2 cells are strongly expanded in alcoholic liver diseases, though the particular immunoglobulin profile observed in this condition has yet to be explained. Th2 function also plays a crucial part in chronic HCV infection, but seems unrelated to interferon response.     

Serum lipid profile of patients with genotype 1b hepatitis C viral infection in Japan

Hepatitis C virus (HCV) infection is associated with the development of steatosis in the liver. Recently, infection with genotype 3a HCV has been reported to have a closer association with hepatic steatosis than that with genotype 1 or 2 HCV. Moreover, infection with genotype 3a HCV but not with genotype 1 has been shown to be associated with serum hypocholesterolemia or hypobetalipoproteinemia in European countries. We conducted a case control study to characterize the serum lipid profile in patients infected with genotype 1b HCV, which is the most prevalent HCV genotype in Japan. These patients had significantly lower serum cholesterol levels than those infected with HBV or genotype 2a HCV who had similar liver disease progression and body mass index. Further analysis of serum apolipoproteins revealed that not only apolipoprotein B but also apolipoprotein CII and apolipoprotein CIII levels were significantly reduced, while apolipoprotein AI, AII and E levels were similar in patients infected with genotype 1b HCV and those with HBV or genotype 2a HCV. These results indicate that, in Japan, infection with genotype 1b HCV is a cause of lipid metabolism disturbances, which may be associated with the pathogenesis of hepatitis C liver disease.     

Occult hepatitis B virus infection in patients with chronic liver disease due to hepatitis C virus and hepatocellular carcinoma in Brazil

BACKGROUND: The prevalence and consequences of occult HBV infection in patients with chronic liver disease by HCV remain unknown. AIMS: To evaluate the prevalence of occult HBV infection in a population of HCV-infected patients with hepatocellular carcinoma. METHODS: The serum samples were tested for HBV DNA by nested PCR and liver tissue analysis was carried out using the immunohistochemical technique of 66 HBsAg-negative patients: 26 patients with chronic hepatitis by HCV (group 1), 20 with hepatocellular carcinoma related to chronic infection by HCV (group 2) and 20 with negative viral markers for hepatitis B and C (control group). RESULTS: Occult HBV infection was diagnosed in the liver tissue of 9/46 (19.5%) HCV-infected patients. Prevalence of occult B infection was evaluated in the HCV-infected patients with and without hepatocellular carcinoma, and there were seven (77.7%) of whom from group 2, conferring a 35% prevalence of this group. No serum sample was positive for HBV DNA in the three groups. CONCLUSION: Occult infection B is frequently detected in liver tissue of HCV-infected patients, especially in cases of hepatocellular carcinoma. However large studies are needed to confirm that co-infection could determine a worse progress of chronic liver disease in this population.     

Human parvovirus B19 infection in patients with chronic hepatitis B or hepatitis C infection

BACKGROUND AND AIM: Parvovirus B19 has been reported to be detected in the sera of patients with acute or chronic hepatitis. The prevalence and clinical significance of B19 DNA in serum samples from patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were investigated. METHODS: Serum samples from 54 patients with HBV infection, 51 with HCV infection and 53 normal controls were examined for anti-B19 antibodies and B19 DNA by enzyme-linked immunosorbent assay (ELISA), the nested polymerase chain reaction (PCR), Southern blotting and direct nucleotide sequencing, respectively. RESULTS: Anti-B19 IgM and IgG antibodies were detected in 19 (35.2%) and 46 (85.2%) of 54 serum samples from patients with HBV infection, and eight (15.7%) and 36 (70.6%) of 51 serum samples from patients with HCV infection. B19 DNA was detected in serum samples of 20 (37%) of 54 patients with HBV infection and 12 (23.5%) of 51 patients with HCV infection, but not in 53 serum samples from normal controls. The occurrence of liver dysfunction was not affected by B19 infection in patients with HBV and HCV infection (P > 0.05). All of the 20 serum samples with B19 DNA from patients with chronic HBV infection and all of the 12 serum samples with B19 DNA from patients with chronic HCV infection exhibited TW-3 subtype and TW-9 subtype, respectively. The variant subtypes of B19 were found to be distinctive in patients with HBV or HCV infection. CONCLUSIONS: These data revealed that human parvovirus B19 infection was frequently found in patients with chronic HBV or HCV infection. The variant genotypes were present in patients with different chronic hepatitis. The coinfection of B19 with HBV or HCV did not increase the frequency of liver dysfunction in patients with chronic hepatitis. Long-term longitudinal studies are required to determine the natural course of parvovirus B19 infection and whether its coinfection affects the natural history of chronic hepatitis B or hepatitis C.     

Comparable ten-year outcome in hemodialysis patients with hepatitis C virus and hepatitis B virus coinfection and single hepatitis B virus infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection in comparison with single HBV infection causes more severe liver disease in nonuremic population. The long-term impact of HBV/HCV coinfection on severity of liver diseases and patient survival in hemodialysis patients is unclear. Forty-eight HBV-positive patients and 19 HBV/HCV-positive patients were followed up from February 1996 to September 2006. During 10-year follow-up, there was no difference in acute hepatitis episodes, abnormal serum alanine aminotransferase period, occurrence of cirrhosis and hepatocellular carcinoma, and patient survival between the two groups. The serum HBV DNA levels in HBV/HCV-positive patients were significantly lower than those in HBV-positive patients during the first 27-month follow-up. In conclusion, HCV infection suppresses the serum HBV DNA level in hemodialysis patients. Nevertheless, HBV/HCV coinfection in comparison with single HBV infection does not cause more severe liver diseases or reduce patient survival in hemodialysis patients during 10-year follow-up.     

Bone alterations in hepatitis C virus infected patients

Background and aimsMost studies have shown that patients with chronic hepatitis C virus (HCV) infection are affected by osteoporosis. However, liver function impairment and deranged nutrition may both play a role in the bone alterations observed. In some works no osteoporosis was found, and some cases of osteosclerosis have been reported. The aim of the study is to assess bone alterations in treatment-naïve, well-nourished HCV patients, in order to discern whether or not HCV infection causes osteoporosis.MethodsWhole-body bone densitometry and assessment of T-score at lumbar spine and hip were performed to 40 patients and 40 age‐ and sex-matched controls, with a Lunar Prodigy Advance (General Electric, Piscataway, NJ, USA). All the patients underwent liver biopsy. Nutritional evaluation was performed by subjective nutritional assessment, body mass index (BMI), and densitometric assessment of total lean mass and total fat mass. Serum osteocalcin, osteoprotegerin, RANKL, PTH, crosslaps, vitamin D3, testosterone, IGF-1, and estradiol were determined.ResultsPatients did not show differences in total bone mineral density (BMD) or T-score with controls. On the contrary, about a third of them showed positive T scores. Patients showed lower IGF-1, vitamin D3 and testosterone, but higher telopeptide levels, and a trend to higher osteoprotegerin levels. Multivariate analyses disclosed that age, sex, and total lean mass were the only parameters independently related with BMD.ConclusionsTherefore, chronic HCV infection in well nourished patients with preserved liver function does not cause osteoporosis.     

Pathogenesis of osteoporosis in liver cirrhosis

BACKGROUND/AIMS: Osteoporosis has been recognized in patients with liver cirrhosis, although the prevalence and the exact mechanisms vary considerably in the literature. We have studied the prevalence of bone disease in cirrhotic patients, the pathogenesis and the relation to the etiology and the severity of liver failure. METHODOLOGY: The study included 83 hospitalized patients with various types of cirrhosis, where 25 healthy individuals served as controls. Patients were classified according to Child-Pugh's stages as follows: Child A: 49, Child B: 20, Child C: 14. Serum levels of iPTH, 250HD, LH, FSH, SHBG, testosterone, estradiol, IGF-I, osteocalcin and urine levels of cross-linked N-telopeptides of collagen type 1 (NTX) were measured in all patients. Bone mineral density (BMD) was measured by DEXA at the spine of both patients and controls. RESULTS: The prevalence of osteoporosis was higher in patients (26/83) 31.3% than in controls (4/25) 16%. Osteopenia was positively related with the elevated levels of crosslinked N-telopeptides (p=0.048). There were no differences in BMD between the types of cirrhosis. BMD was found to be significantly lower in Child B and C male patients than in Child A (p=0.043). Patients' groups B, and C had lower testosterone levels with a trend to contribute to the low BMD (p=0.15). 250HD and IGF-1 were significantly lower in decompensated cirrhosis (p<0.002), but did not correlate with BMD. CONCLUSIONS: Cirrhosis is a major cause of osteoporosis and the degree of osteopenia is related to the severity and not the etiology of the liver disease. The biochemical markers of bone remodeling suggest a high-turnover osteoporosis in cirrhosis.     

Low‐level hepatitis C viremia and humoral immune response to NS4 in chronic hepatitis B virus‐hepatitis C virus coinfection

Background: There is a limited amount of published data on the interference of hepatitis B virus (HBV) on hepatitis C virus (HCV). The aim of this study was to investigate the effect of concurrent HBV infection on serum titers of HCV RNA and HCV antibody profiles in chronic HCV infection. Methods: The clinical and virological profiles (serum titers of HCV RNA, HCV genotypes and antibody profiles) of 25 patients with chronic HBV‐HCV coinfection were compared with those of 25 age‐ and sex‐matched patients with HCV infection alone. Results: Among the 25 patients with HBV‐HCV coinfection, only 3 were found hepatitis Be antigen (HBeAg) and HBV DNA positive by hybridization assays, and the other 11 were found HBV DNA positive by polymerase chain reaction. Genotype 1b was dominant in both HBV‐HCV coinfection and HCV infection alone (64% versus 84%, P?>?0.1). Patients with HBV‐HCV coinfection had significantly lower alanine aminotransferase (ALAT) levels and inflammatory scores but higher fibrosis scores than those with HCV infection alone. Serum titers of HCV RNA were significantly lower in HBV‐HCV coinfection than in HCV infection alone. The frequency and relative intensity of antibody response to core, E2/NS1, NS3, and NS5 showed no significant difference between the two groups, but antibody response to NS4 was diminished significantly in HBV‐HCV coinfection. Conclusions: In HBV‐HCV coinfection, serum levels of HBV DNA are usually low or undetectable. Concurrent HBV infection, however, could interfere with HCV replication and suppress antibody response to NS4. The biological significance of selective inhibition of humoral immune response to NS4 in HBV‐HCV coinfection should be further studied.     

Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B

AIM： To study the relationship between hepatitis B virus （HBV） DNA levels and liver histology in patients with chronic hepatitis B （CHB） and to determine the prevalence and characteristics of hepatitis B e antigen （HBeAg） negative patients.
METHODS： A total of 213 patients with CHB were studied, and serum HBV DNA levels were measured by the COBAS Amplicor HBV Monitor test. All patients were divided into two groups according to the HBeAg status.The correlation between serum HBV DNA levels and liver damage （liver histology and biochemistry） was explored.
RESULTS： Of the 213 patients with serum HBV DNA levels higher than 10^5 copies/mL, 178 （83.6%） were HBeAg positive, 35 （16.4%） were HBeAg negative. The serum HBV DNA levels were not correlated to the age,history of CHB, histological grade and stage of liver disease in either HBeAg negative or HBeAg positive patients. There was no correlation between serum levels of HBV DNA and alanine aminotransferanse （ALT）,aspartate aminotrans-ferase （AST） in HBeAg positive patients. In HBeAg negative patients, there was no correlation between serum levels of HBV DNA and AST,while serum DNA levels correlated with ALT （r = 0.351, P = 0.042）. The grade （G） of liver disease correlated with ALT and AST （P 〈 0.05, r = 0.205, 0.327 respectively）in HBeAg positive patients. In HBeAg negative patients,correlations were shown between ALT, AST and the G （P 〈 0.01, and r = 0.862, 0.802 respectively）. HBeAg negative patients were older （35 ± 9 years vs 30 ±9 years, P 〈 0.05 ） and had a longer history of HBV infection （8 ± 4 years vs 6 ± 4 years, P 〈 0.05） and a lower HBV DNA level than HBeAg positive patients （8.4± 1.7 Log HBV DNA vs 9.8 ± 1.3 Log HBV DNA, P 〈0.001）. There were no significant differences in sex ratio,ALT and AST levels and liver histology between the two groups.
CONCLUSION： Serum HBV DNA level is not correlated to histological grade or stage of liver disease in CHB patients with HBV DNA mor     

Lack of association between occult hepatitis B virus DNA viral load and aminotransferase levels in patients with hepatitis C virus-related chronic liver disease

BACKGROUND AND AIM: Occult hepatitis B virus (HBV) infection in hepatitis C virus (HCV)-infected patients might enhance the severity of chronic liver disease (CLD). To elucidate the correlation between occult HBV infection and the clinical course of HCV-related CLD, we evaluated whether the fluctuation of occult HBV-DNA directly affects the serum alanine aminotransferase (ALT) level. METHODS: Forty-one patients with HCV-related CLD who received regular outpatient treatment and 42 age-, sex-, and antibody to hepatitis B core antigen positivity-matched healthy volunteers were enrolled. Serum HBV-DNA was quantitatively detected using real-time detection polymerase chain reaction (RTD-PCR). Serial serum samples in three patients were measured for HBV-DNA, ALT and HCV core antigen. RESULTS: Hepatitis B virus DNA was amplified in eight of the HCV-related CLD patients (19.5%), which was significantly higher than that of healthy volunteers (2.4%). No significant difference between the genotype 1 HCV-related CLD group and the genotype 2 group was found. Based on the analyses using serial serum samples, the elevation of HBV-DNA did not occur before the ALT flares, but occurred at the same time or after the ALT flares. CONCLUSIONS: The prevalence of occult HBV infection of HCV-related CLD is significantly higher than that of control. Occult HBV infection has no influence on ALT flares among patients with HCV-related CLD.     

Clinical implication of VEGF serum levels in cirrhotic patients with or without portal hypertension

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Low-level hepatitis C viremia and humoral immune response to NS4 in chronic hepatitis B virus-hepatitis C virus coinfection

BACKGROUND: There is a limited amount of published data on the interference of hepatitis B virus (HBV) on hepatitis C virus (HCV). The aim of this study was to investigate the effect of concurrent HBV infection on serum titers of HCV RNA and HCV antibody profiles in chronic HCV infection. METHODS: The clinical and virological profiles (serum titers of HCV RNA, HCV genotypes and antibody profiles) of 25 patients with chronic HBV-HCV coinfection were compared with those of 25 age- and sex-matched patients with HCV infection alone. RESULTS: Among the 25 patients with HBV-HCV coinfection, only 3 were found hepatitis Be antigen (HBeAg) and HBV DNA positive by hybridization assays, and the other 11 were found HBV DNA positive by polymerase chain reaction. Genotype 1b was dominant in both HBV-HCV coinfection and HCV infection alone (64% versus 84%, P > 0.1). Patients with HBV-HCV coinfection had significantly lower alanine aminotransferase (ALAT) levels and inflammatory scores but higher fibrosis scores than those with HCV infection alone. Serum titers of HCV RNA were significantly lower in HBV-HCV coinfection than in HCV infection alone. The frequency and relative intensity of antibody response to core, E2/NS1, NS3, and NS5 showed no significant difference between the two groups, but antibody response to NS4 was diminished significantly in HBV-HCV coinfection. CONCLUSIONS: In HBV-HCV coinfection, serum levels of HBV DNA are usually low or undetectable. Concurrent HBV infection, however, could interfere with HCV replication and suppress antibody response to NS4. The biological significance of selective inhibition of humoral immune response to NS4 in HBV-HCV coinfection should be further studied.     

Ghrelin in chronic liver disease

BACKGROUND/AIMS: Ghrelin is a novel endogenous ligand for the growth hormone (GH) secretagogue receptor involved in energy metabolism, glucose homeostasis and food intake. We investigated the role of ghrelin and insulin-like growth factor-1 (IGF-1), the mediator of the GH axis, in patients with chronic liver diseases (CLD). METHODS: Ghrelin and IGF-1 serum levels were determined in 105 CLD patients and 97 healthy controls and correlated with clinical and biochemical parameters. RESULTS: Ghrelin was significantly elevated and IGF-1 reduced in CLD patients compared with healthy controls. IGF-1 serum levels inversely correlated with Child's classification. Ghrelin levels were significantly elevated in Child C cirrhosis patients independent of the aetiology of liver disease. Ghrelin levels did not correlate with liver function. In contrast, there was a correlation of ghrelin with clinical (gastrointestinal bleeding, ascites, encephalopathy) and biochemical (anaemia, inflammatory markers, hypoglycaemia, renal dysfunction) parameters. In a subgroup of patients with CLD and hepatocellular carcinoma (HCC), we observed a strong inverse correlation between alpha-fetoprotein (AFP) and ghrelin levels. CONCLUSIONS: Unlike IGF-1, ghrelin is not correlated with liver function, but increases in Child C cirrhosis and with complications of CLD. The inverse correlation with AFP in HCC patients requires further studies on the potential impact of ghrelin on the pathogenesis of anorexia-cachexia syndrome.