Course Of Liver Disease Research Articles

Highly active antiretroviral therapy in HIV and hepatitis C coinfected individuals: friend or foe?

Highly active antiretroviral therapy dramatically reduces HIV-related morbidity and mortality. Liver disease has subsequently emerged as a major cause of death in HIV/hepatitis C virus-coinfected individuals. Whether HIV therapy also has a favourable impact on the course of liver disease needs to be explored and counterbalanced with toxicity issues related to the extended duration of antiretroviral therapy. Recent cohort studies have shown that highly active antiretroviral therapy is associated with a reduced rate of progression of hepatitis C virus liver disease, with some also showing a reduction in liver-related mortality. Increased mortality from liver disease has been linked with the extended duration of antiretroviral therapy. Highly antiretroviral therapy-associated liver steatosis has been described as an emerging cause of liver cirrhosis. New possibly HIV therapy-related adverse events such as hepatoportal sclerosis have been reported. Studies evaluating the impact of the early initiation of highly active antiretroviral therapy on liver disease in coinfected patients are urgently needed. The safety profile of currently available antiretroviral agents with regard to liver toxicity needs to be further elucidated in order to be able to recommend earlier HIV treatment in this particular patient population.

Response of Combination Therapy on Viral Load and Disease Severity in Chronic Hepatitis C

Influence of genotypes on viral kinetics and disease severity in chronic hepatitis C (CH-C) patients has been implicated, but requires further investigation. The 41 HCV patients were genotyped by restriction fragment length polymorphism and included for 48 weeks of combination therapy on the basis of clinical (alanine amino transferase > or =60 IU/l) and histological features (histological activity index > or =3). A significant number (30/41) of patients (6/9 of genotype 1, 23/30 of genotype 3 and 1/2 of mixed genotype) attain sustained virological response despite high viral load at baseline. More aggressive treatment was required in genotype 1 than in genotype 3 due to slow response rate. Significant (P < 0.05) difference in the viral load of sustained virological responder and non-responder (NR) was observed after 12 weeks of therapy. Severe course of liver disease was observed in 81.81% (9/11) of NR patients at baseline. Data indicate that genotype 1 was a slow responder compared to genotype 3 on combination therapy. Response to combination therapy was almost independent of baseline viral load. However, a positive correlation of viral load with disease severity was observed. The viral kinetics at 12 weeks is an important tool for determination of virological response.

Reduction in Hepatitis C–Related Liver Disease Associated With GB Virus C in Human Immunodeficiency Virus Coinfection

It has been reported that GB virus C infection (GBV-C) leads to improved morbidity and mortality in patients with human immunodeficiency virus (HIV) infection. However, GBV-C has no effect on the course of liver disease in hepatitis C virus (HCV) monoinfection. The aim of the study was to determine the influence of GBV-C infection on liver disease in patients with HCV/HIV coinfection. Data on 158 HCV/HIV patients were collected from January 1996 to October 2005. Two plasma specimens, collected at least 18 months apart, were tested for GBV-C RNA by reverse transcription-polymerase chain reaction with primers to the NS5B gene and confirmed using E2 gene primers and sequencing. Antibodies to GBV-C E2 protein were also determined. Liver-related morbidity and mortality were assessed from patient records. Fifty-seven of 158 (36%) patients had GBV-C RNA and 94 (59%) had evidence of exposure to GBV-C based on combined polymerase chain reaction and antibody results. Thirty-four (21%) patients had features of cirrhosis, with 20 having compensated and 14 having decompensated cirrhosis. Active GBV-C RNA was significantly associated with a reduction in cirrhosis, both compensated and decompensated in multivariate analysis (hazard ratio, 0.27; 95% confidence interval, 0.08-0.88; P = .03), as well as in analysis for cirrhosis-free survival vs duration of HCV infection (P = .006). No significant effect on liver-related or overall survival was observed. In these HCV/HIV-coinfected patients, GBV-C RNA was associated with a significant reduction in the severity of HCV-related liver disease.

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Hyperammonemia and severe amino acid imbalances play central role in hepatic encephalopathy (HE). In the article is demonstrated that the main source of ammonia in cirrhotic subjects is activated breakdown of glutamine (GLN) in enterocytes and the kidneys and the main source of GLN is ammonia detoxification to GLN in the brain and skeletal muscle. Branched-chain amino acids (BCAA; valine, leucine, and isoleucine) decrease due to activated GLN synthesis in muscle. Aromatic amino acids (AAA; phenylalanine, tyrosine, and tryptophan) and methionine increase due to portosystemic shunts and reduced ability of diseased liver. The effects on aminoacidemia of the following variables that may affect the course of liver disease are discussed: nutritional status, starvation, protein intake, inflammation, acute hepatocellular damage, bleeding from varices, portosystemic shunts, hepatic cancer, and renal failure. It is concluded that (1) neither ammonia nor amino acid concentrations correlate closely with the severity of liver disease; (2) BCAA/AAA ratio could be used as a good index of liver impairment and for early detection of derangements in amino acid metabolism; (3) variables potentially leading to overt encephalopathy exert substantial but uneven effects; and (4) careful monitoring of ammonia and aminoacidemia may discover important break points in the course of liver disease and indicate appropriate therapeutic approach. Of special importance might be isoleucine deficiency in bleeding from varices, arginine deficiency in sepsis, and a marked rise of GLN and ammonia levels that may appear in all events leading to HE.

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Hyperammonemia and severe amino acid imbalances play central role in hepatic encephalopathy (HE). In the article is demonstrated that the main source of ammonia in cirrhotic subjects is activated breakdown of glutamine (GLN) in enterocytes and the kidneys and the main source of GLN is ammonia detoxification to GLN in the brain and skeletal muscle. Branched-chain amino acids (BCAA; valine, leucine, and isoleucine) decrease due to activated GLN synthesis in muscle. Aromatic amino acids (AAA; phenylalanine, tyrosine, and tryptophan) and methionine increase due to portosystemic shunts and reduced ability of diseased liver. The effects on aminoacidemia of the following variables that may affect the course of liver disease are discussed: nutritional status, starvation, protein intake, inflammation, acute hepatocellular damage, bleeding from varices, portosystemic shunts, hepatic cancer, and renal failure. It is concluded that (1) neither ammonia nor amino acid concentrations correlate closely with the severity of liver disease; (2) BCAA/AAA ratio could be used as a good index of liver impairment and for early detection of derangements in amino acid metabolism; (3) variables potentially leading to overt encephalopathy exert substantial but uneven effects; and (4) careful monitoring of ammonia and aminoacidemia may discover important break points in the course of liver disease and indicate appropriate therapeutic approach. Of special importance might be isoleucine deficiency in bleeding from varices, arginine deficiency in sepsis, and a marked rise of GLN and ammonia levels that may appear in all events leading to HE.

The benign course of liver disease in adults with cystic fibrosis and the effect of ursodeoxycholic acid

The life expectancy of patients with cystic fibrosis (CF) has been increasing and the associated liver disease has emerged as a significant medical issue. Our aim was to describe the clinical features, course and effect of ursodeoxycholic acid (UDCA) on liver disease in an adult CF population. From 1983 to 2005, 278 patients with CF were followed up at the Alfred Hospital, an adult tertiary referral centre. Twenty-seven patients (9.7%) satisfied the criteria for liver disease and their clinico-pathological features were assessed. The effect of UDCA on hepatobiliary symptoms and biochemical parameters was determined. The mean age at liver disease diagnosis was 23 years (range 8-47 years). Portal hypertension was present in 18 (67%) patients. During a median follow-up of 7 years (range 1.5-15), variceal haemorrhage occurred in two patients and ascites in three (one spontaneously). Nine (33%) patients died and five (19%) underwent lung transplantation. There was no encephalopathy, liver transplantation or liver-related deaths. UDCA was taken by 22 patients and was associated with a significant improvement in hepatobiliary symptoms [11/22 (50%) in the pre-UDCA period vs 1/22 (4%) in the post-UDCA period; P=0.0003] and a significant reduction in aspartate aminotransferase (P=0.005); alanine aminotransferase (P<0.001); gamma-glutamyltranspeptidase (P=0.021); and alkaline phosphatase (P<0.001). Liver disease in adults with CF is commonly complicated by portal hypertension, but morbidity and mortality associated with this in our small patient population were low. UDCA is associated with improvement in hepatobiliary symptoms and liver function tests.

An assessment of serum leptin levels in patients with chronic viral hepatitis: a prospective study

BackgroundThe role of leptin in the course of liver disease due to chronic viral hepatitis (CVH) remains controversial. Our aims were to investigate the relationship between serum leptin concentrations and the severity of liver disease in a cohort of subjects with HBeAg negative chronic hepatitis B (CHB) and C (CHC) and to analyze the effect of body composition, the leptin system and insulin resistance together with viral factors on virologic response to antiviral treatment.MethodsWe studied 50 (36 men) consecutive patients suffering from biopsy-proven CVH due to HBV (n = 25) or HCV (n = 25) infection. Thirty-two (17 men) healthy volunteers served as controls. Levels of serum leptin and insulin were determined by immunoassays at baseline and at the end of the treatment.ResultsA significant association between serum leptin levels and the stage of hepatic fibrosis was noted; patients with cirrhosis presented higher serum leptin levels compared to those with lower fibrosis stage [CHB patients (17436 pg/ml vs 6028.5 pg/ml, p = 0.03), CHC patients (18014 pg/ml vs 4385 pg/ml, p = 0.05]. An inverse correlation between lower leptin levels and response to lamivudine monotherapy was noted in patients with CHB; those with a virologic response presented lower serum leptin levels (5334 vs 13111.5 pg/ml; p-value = 0.003) than non-responders. In genotype 1 CHC patients, insulin resistance played a significant role in the response to antiviral therapy.ConclusionOur data clearly suggest that cirrhosis due to CHB or CHC is associated with higher leptin levels. Increased serum leptin levels represent a negative prognostic factor for response to lamivudine monotherapy in patients with CHB. In CHC patients insulin resistance strongly influences the response to antiviral treatment in patients infected with genotype 1.

Virological Outcome of Chronic Hepatitis B Virus Infection in HIV-Coinfected Patients Receiving Anti-HBV Active Antiretroviral Therapy

The immune suppression caused by HIV infection accelerates the course of liver disease caused by chronic hepatitis B virus (HBV) infection. We assessed the outcome of HIV/HBV-coinfected patients exposed to highly active antiretroviral therapy (HAART) including anti-HBV active drugs. Baseline and follow-up plasma HBVDNA and HIV-RNA levels, HBV serological markers, and CD4 counts were longitudinally evaluated in all HBsAg(+) individuals with HIV infection on regular follow-up at an urban HIV reference clinic. Out of 79 HBsAg(+) chronic carriers identified, 39 (50%) were HBeAg(+). Lamivudine (3TC) alone had been received by 37% of patients, while 3TC plus tenofovir (concomitantly or consecutively) had been taken by 58% of them. The median follow-up was of 52 months. Loss of HBeAg or HBsAg occurred in 28% (10/36) and 13% (10/75) of patients, respectively. In multivariate analysis, only undetectable plasma HIV-RNA levels [OR 4.58 (95% CI 1.25-16.78); p = 0.02] and greater CD4 gains on HAART [OR 1.003 (95% CI 1.000-1.006); p = 0.03] were associated with undetectable serum HBV-DNA at the end of follow-up. Anti-HBV active HAART makes it possible to achieve HBsAg clearance, anti-HBe seroconversion, and suppression of HBV replication in a substantial proportion of HBV/HIV-coinfected patients, particularly in those with complete HIV suppression and greater immune recovery. Thus, HBV/HIV-coinfected patients might benefit from an earlier introduction of HAART.

What Is the Role of GB Virus C Infection in Hepatitis C Virus/HIV Coinfection?

Much has been published over the past 10 years regarding the influence of GB virus C (GBV-C) on HIV infection. Several studies have reported that coinfection with HIV and GBV-C leads to a more favorable outcome in patients with a delay in the development of AIDS compared with the outcome in patients infected with HIV alone. This has led some groups to look for the putative mechanism of this beneficial effect and alterations in the cellular immune response have been implicated. However there is still considerable controversy regarding this interaction because not all studies have shown a beneficial effect of GBV-C infection on the progression of HIV disease. By contrast there is no debate that GBV-C plays little role if any in hepatitis C virus (HCV) infection with no effect on the progression of HCV-related liver disease or on the effectiveness of interferon (IFN)--based therapy. Similarly there is no dispute that the course of liver disease is accelerated in patients with HCV/HIV coinfection. Indeed HCV related liver disease has been a significant cause of morbidity and mortality in HIV infected patients during the era of highly active antiretroviral therapy (HAART). This has stimulated increased interest in HCV therapy in HCV/HIV-coinfected subjects particularly given that HCV clearance rates of >40% are possible with combination pegylated (PEG)--IFN and ribavirin therapy. (excerpt)

Hepatic intra-arterial chemotherapy in patients with metastatic breast cancer

10581 Background: Hepatic intra-arterial chemotherapy has been reported to produce higher response rate than systemic in patients (pts) with metastatic colorectal cancer. In breast cancer the liver is involved in up to 60% of cases and often conditions the prognosis. Nevertheless, only rare hepatic arterial infusion studies were published. Therefore, based on our previous experience in hepatic metastatic colorectal malignancies, we evaluated efficacy and toxicity of hepatic intra-arterial chemotherapy in pts with metastatic breast cancer. Methods: A three-day continuous arterial infusion (CAI) of fluorouracil 1000 mg/m2 q 24 hrs, with cisplatin 10 mg/m2 twice daily, and mitomycin-c 1 mg/m2 twice daily, was performed through a percutaneous radiological temporary trans-subclavicular catheter. Pts with responsive disease received up to four cycles every six weeks. Pts still responding could carry on with cisplatin and fluorouracil, without mitomycin-c. Pts were hospitalized and the catheter was removed upon end of infusion. Results: From 9.2000 to 6.2005, 25 pts with progressive liver metastases from breast cancer were treated. Nine had more than 50% of liver involvement. Fifteen had also extra-hepatic metastases. All had received antracyclines and 22/25 taxanes. Pts had a median of five previous chemotherapy lines. Median time from diagnosis of liver metastases to first CAI was 33 months (range: 7–110). Sixty-four total courses were administered, with a median of 2 (range: 1–7) per pts. Epigastric pain was the main clinical toxicity (54%) and iatrogenic gastro-duodenal ulcer, the main complication (28%). No relevant catheter-related complications occurred. Fifteen partial responses (60%) and eight stable diseases (32%) were observed. Response duration was 5.4 months (range: 2 - 27), time to progression 5.1 months (range: 2.5–29+), and median overall survival 13 months (range: 3.5+–32+). Conclusions: Hepatic arterial infusion of chemotherapy in heavily pre-treated pts with metastatic breast cancer is feasible and effective. A specific evaluation of quality of life should be performed to verify a real clinical benefit. An earlier timing during course of liver disease, and a shift to radiological implanted arterial port (allowing out-patient treatment), will be investigated. No significant financial relationships to disclose.

Involvement of the Transforming Growth Factor &amp;#946; in the Pathogenesis of Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is characterized by vessel alterations such as dilatation of postcapillary venules and arterio-venous communications, which account for the major clinical manifestations of the disease. Two types of HHT have been characterized HHT-1 and HHT-2, respectively, depending the former on endoglin mutations and the latter on activin receptor-like kinase 1 (ALK-1) mutations. Both endoglin and ALK-1 bind to the transforming growth factor (TGF) superfamily which, physiologically, regulates the activities of endothelial cells and also those related to the extracellular matrix. In this review, the salient features of TGF-beta will be outlined with special reference to its activity on the immune system and on tumorigenesis. Furthermore, the involvement of TGF-beta in the pathogenesis of some gastrointestinal diseases will be discussed and, in particular, in the course of liver disease, Helicobacter pylori infection and inflammatory bowel disease. In the light of these data and of animal model of HHT, the potential risk of developing other diseases in HHT patients will be discussed.

Current indications of liver biopsy

2) regarding the technique for liver biopsy col-lection, the use of this procedure has become widespread,which has allowed a better understanding of the patholo-gy and course of liver diseases, and the basing of our di-agnoses on objective, pathologic grounds. Presently, liverbiopsy is considered a procedure indicated: a) to establishthe origin of abnormal liver tests; b) to assess activity ex-tent and stage in chronic hepatitis; c) to evaluate alcohol-related liver disease; d) to study fever of unknown origin;e) in the diagnosis of multisystemic infiltrating and gran-ulomatous diseases; f) to evaluate cholestatic conditions;g) in the diagnosis of neoplasm; h) in the assessment ofdrug-induced liver lesions; i) in the diagnosis of heredi-tary metabolic disease; j) in the assessment of response totherapy; k) in the evaluation of the liver following a livertransplantation; and l) to evaluate obscure jaundice, acutehepatitis, and hepatomegaly (3)

Impact of the hepatitis B virus genotype and genotype mixtures on the course of liver disease in Vietnam†

Eight genotypes (A-H) of hepatitis B virus (HBV) have been identified. However, the impact of different genotypes on the clinical course of hepatitis B infection remains controversial. We investigated the frequency and clinical outcome of HBV genotypes and genotype mixtures in HBV-infected patients from Vietnam, Europe, and Africa. In addition, we analyzed the effects of genotype mixtures on alterations in in vitro viral replication. In Asian patients, seven genotypes (A-G) were detected, with A, C, and D predominating. In European and African patients, only genotypes A, C, D, and G were identified. Genotype mixtures were more frequently encountered in African than in Asian (P = .01) and European patients (P = .06). In Asian patients, the predominant genotype mixtures included A/C and C/D, compared to C/D in European and A/D in African patients. Genotype A was more frequent in asymptomatic compared with symptomatic patients (P < .0001). Genotype C was more frequent in patients with hepatocellular carcinoma (HCC; P = .02). Genotype mixtures were more frequently encountered in patients with chronic hepatitis in comparison to patients with acute hepatitis B (P = .015), liver cirrhosis (P = .013), and HCC (P = .002). Viral loads in patients infected with genotype mixtures were significantly higher in comparison to patients with a single genotype (P = .019). Genotype mixtures were also associated with increased in vitro HBV replication. In conclusion, infection with mixtures of HBV genotypes is frequent in Asia, Africa, and Europe. Differences in the replication-phenotype of single genotypes compared to genotype-mixtures suggest that co-infection with different HBV-genotypes is associated with altered pathogenesis and clinical outcome.

Increased liver enzymes and hormonal therapies in girls and adolescents with Turner syndrome

Elevated liver enzymes can be seen relatively frequently in patients with Turner syndrome (TS), while the pathogenesis of this remains unclear. Our epidemiological and prospective study aimed to investigate: a) the natural 2-yr course of liver disease in a selected cohort of young patients with TS, who had been preliminarily recruited on the basis of persistently elevated liver enzymes; b) the role of prolonged hormonal therapies in the etiology of liver dysfunction. From an overall population of 214 TS patients younger than 20 yr, only 19 (8.9%) were recruited, according to the following inclusion criteria: increased serum concentrations of one or more liver enzymes, exceeding the uppermost limit of the respective normal ranges, and persistence of these liver alterations for 6 months after the preliminary assessment. On the basis of the results of this prospective study, we can conclude that: a) the prevalence of liver abnormalities in girls and adolescents with TS is much lower and more strictly related to hormonal therapies than in TS adults; b) both autoimmunity and obesity are not frequently involved in the etiology of TS liver dysfunction; c) liver damage is either mild or moderate and its severity is not conditioned by karyotype; d) its course may be self-limiting; e) its natural history may be characterized in some cases by a slight deterioration of intrahepatic cholestasis, with no negative repercussions on liver synthetic function.

Cirrhosis in Children With Celiac Disease

Liver involvement represents an extra-intestinal feature of celiac disease (CD) and shows a clinical spectrum varying from nonspecific reactive hepatitis to cirrhosis. Here we report the association of cirrhosis with CD in 5 children. The mean age of the patients was 9.4 +/- 2.8 years. Viral, metabolic, and autoimmune etiology of liver disease was ruled out. Intestinal and liver biopsies were performed to confirm the histologic diagnosis in all subjects. Three of the patients had chronic diarrhea and hepatosplenomegaly in whom diagnoses of CD and cirrhosis were established at presentation simultaneously. In the other 2 patients, CD was diagnosed following an initial diagnosis of cirrhosis. At diagnosis, alanine aminotransferase (range, 64-271 IU/L) and aspartate aminotransferase (range, 90-225 IU/L) values were elevated. After 1 to 5 years of a gluten-free diet (GFD), normalization of serum aminotransferase levels and clinical improvement were observed in 3 patients with strict GFD. The other 2 patients without improvement of the liver disease had poor dietary compliance. CD may be associated with severe hepatic damage in children and strict GFD may have beneficial effect on the course of liver disease. Serologic screening of CD should be included in differential diagnosis of chronic liver disease of unknown origin.

HBV Genotype F: Natural History and Treatment

The analysis of the HBV genome revealed the existence of 10 genotypes, named A-J. Evidence of the influence of the different genotypes in the natural history and treatment response to nucleoside/nucleotide analogues or interferon-based regimens is scant. HBV genotype F is one of the most prevalent circulating genotypes in South America and the Arctic Circle. Since most of the available information on HBV is from Asia, the US and Europe, it reflects their predominant genotypes: A, B, C and D. To date, the evidence is not fully confirmed, but it appears that genotype F chronic hepatitis B is associated with a more aggressive course of liver disease, reflected by higher histological indexes, a higher risk of development of hepatocellular carcinoma and a higher rate of liver-related mortality. In terms of treatment response, the available data is, unfortunately, even more limited; however, what data is available suggests acceptable and similar response rates to pegylated interferon-α2a in genotype F compared to genotype A. Response rates to nucleoside/nucleotide analogues is not influenced by genotype. The review of this limited data sheds light on the necessity to conduct further studies in South America and the Arctic Circle in order to better understand the different aspects of HBV genotype F, especially in relation to treatment response.

Diagnostische Verfahren bei der Hepatitis C und ihre Zuverlässigkeit. Reliability of diagnostic procedures for hepatitis C

Abstract The diagnosis of HCV infection is often hampered by false positive reactivities in antibody screening assays. Therefore, confirmatory assays are necessary. Since most unspecific reactivities are only slightly above the cut-off value, the intensity of the reactivity should always be considered. Particularly in groups with low HCV risk such as blood donors, positive reactivities obtained by one test system can often be ruled out by re-testing with another format (e.g. an enzyme immunoassay instead of a microparticle enzyme immunoassay). Most confirmatory assays are based on a recombinant immunoblot assay (RIBA); these tests should always be done in patients diagnosed as HCV positive for the first time. Additionally, in many cases, tests for HCV RNA are necessary. Based on these results, an evaluation of the risk of transmission to household contacts is possible and in patients receiving antiviral treatment, the success can be monitored. A negative PCR result in patients showing high positive antibody reactivities does not necessarily represent loss of the virus since even in chronic carriers, viral replication can be intermittently very low. Immuno-compromised patients often show prolonged seroconversion so that antibody screening assays remain negative for a long time while the patients have high level viraemia. Therefore, we recommend regular RT-PCR in populations at risk such as patients on chronic dialysis. To evaluate patients for antiviral treatment, the determination of the genotype is necessary. The HCV genotype also has an influence on the course of liver disease in chronic carriers. Possible transmission of HCV, e.g. by blood products, can be elucidated by sequence analysis of the high variance region (HVR) of the virus.

Liver Biopsy in Liver Transplant Recipients

Liver biopsy has been used in the assessment of the nature and course of liver diseases and to monitor treatments. In nontransplanted patients, liver biopsies have been well described. Less has been written on the biopsies of transplanted livers. In the liver transplant population, liver biopsy remains the "gold standard" for the diagnosis of rejection. The transplanted liver has additional considerations that can make biopsy less routine and more challenging.

Thrombopoietin (TPO) Levels in Hepatic Patients with Thrombocytopenia

Thrombocytopenia is a common problem complicating the course of liver disease. One of the postulated mechanisms in chronic liver disease is impaired production of the hormone, thrombopoietin (TPO). The aim of present study was to evaluate the role of TPO on the occurrence of thrombocytopenia. Serum TPO levels was determined by ELISA in 40 patients with liver disease (11 seropositive with hepatitis C; 10 with mixed liver cirrhosis; 19 with bilharzial hepatic fibrosis), plus 14 normal healthy subjects as a control group. The sTPO levels were unevenly distributed among the liver disease subgroups being the highest in the group with HCV (median 1232.0, range 154.7-2042.0 pg/ml) followed by the mixed cirrhosis group (556.5; 342.0-1497.0 pg/ml) and lowest among the bilharzial hepatic fibrosis group (130.0; 22.0-204.0 pg/ml) ( P <0.01). While sTPO levels in HCV and cirrhotic group were significantly higher when compared to the control group (97.0; 19.0-377.0 pg/ml), those in the Bilharzial hepatic fibrosis group were not significantly elevated ( P > 0.05). There is significant negative correlation between sTPO levels and spleen size ( R =−0.3, P =0.043); but there was no correlation with platelet count ( R =0.09, P >0.05). In addition, sTPO levels were significantly higher in patients with platelet counts ≥60×10 9 /l as compared to those with platelet counts <60×10 9 /l ( P =0.04). Using the receiver operating curve (ROC) at sTPO cut off value ≥ vs. < 368 ng/ml, most of HCV and cirrhotic patients had higher sTPO levels (81.8 and 80.0%, respectively), while all Bilharzial hepatic fibrosis group (100%) had lower sTPO levels. In conclusion, sTPO levels had no role in the occurrence of thrombocytopenia in liver disease patients and other factors appear to be more important. It also appears that the mechanism controlling sTPO levels might be different in cirrhotic patients compared to Bilharzial hepatic fibrosis patients.

Predominance of type 1 (Th1) cytokine production in the liver of patients with HCV-associated mixed cryoglobulinemia vasculitis

Patients with hepatitis C virus (HCV) mixed cryoglobulinemia (MC) vasculitis have a higher mortality rate and more frequent incidence of cirrhosis than their cryoglobulin-negative counterparts. To compare the cytokine profile of liver-infiltrating T cells in HCV-infected patients with or without MC vasculitis. Hepatic biopsy specimens were obtained from HCV infected patients with and without MC vasculitis. Using intracellular staining and flow cytometry, we assessed the ability of freshly isolated liver T cells from these biopsies to produce IFN-gamma, TNF-alpha, IL-2, IL-4, and IL-10 in response to stimulation with PMA and ionomycin. HCV-MC vasculitis patients compared to HCV-MC negative controls have an enhanced hepatic T cells production of Th1-type cytokines [i.e. TNF-alpha(30.3 +/- 13% vs. 15.5 +/- 5%, P = 0.01), IL-2 (20.2 +/- 9% vs. 10 +/- 4%, P = 0.01) and IFN-gamma (22.2 +/- 11% vs. 9.4 +/- 4%, P = 0.008)], whereas IL-10, a representative Th2-type cytokine, was significantly lower (7.2 +/- 4% vs. 17 +/- 7%, P = 0.01). T cell from the liver of HCV-MC vasculitis patients display a significantly augmented liver Th1 profile compared to MC-negative controls. This enhanced production of type-1 cytokines may account for a more severe course of liver disease.