Serum immunoglobulins (IgG, IgA, IgM) in chronic hepatitis C. A comparison with non-cirrhotic alcoholic liver disease

BACKGROUND/AIMS: Serum immunoglobulin concentrations are commonly elevated in patients with liver cirrhosis. Immunoglobulin class increase may vary depending on the cause of liver disease. Hepatitis C virus is, together with alcohol, a leading cause of chronic liver disease. The present study aimed to evaluate serum IgG, IgA and IgM levels in chronic hepatitis C. Results were compared with those of patients with non-cirrhotic alcoholic liver disease and healthy controls. Special attention was given to cases with minimal liver disease, as an approach to evaluate if the causing agent, independently of liver damage, influences serum immunoglobulin levels. METHODOLOGY: A total of 274 patients with histologically-proven chronic hepatitis C, 121 alcoholics with non-cirrhotic liver disease (steatosis or alcoholic hepatitis), and 75 healthy controls were studied. Serum IgG, IgA, and IgM were assayed by nephelometry. RESULTS: Serum IgG was increased in patients with chronic hepatitis C with respect to both alcoholics (p < 0.001) and healthy controls (p < 0.001). IgG levels were similar in alcoholics and in controls. IgA was increased in patients with non-cirrhotic alcoholic liver disease with respect to both chronic hepatitis C patients (p < 0.001) and controls (p < 0.001). IgA values were similar in subjects with chronic hepatitis C and controls. Selective IgG or IgA alteration was present in cases with minimal liver disease (chronic hepatitis C with a Knodell index equal or lower than 3, and alcoholics with liver steatosis, respectively). CONCLUSIONS: Hepatitis C virus and alcohol are linked to a selective increase of serum IgG and IgA, respectively, even in cases with mild or minimal liver disease.     

Value of serum immunoglobulins in the diagnosis of liver disease

Serum immunoglobulins were determined in 145 consecutive patients with biopsy-proven steatosis, alcoholic hepatitis, alcoholic hepatitis with fibrosis, alcoholic hepatitis with cirrhosis, inactive cirrhosis, chronic active alcoholic hepatitis, chronic active hepatitis, primary biliary cirrhosis and nonspecific hepatitis. IgM was both a sensitive (90.5%) and specific (86.2%) marker for primary biliary cirrhosis, and mean IgM levels were higher in primary biliary cirrhosis than in other diagnostic categories (p less than 0.05). IgA levels were most commonly elevated in alcoholic liver disease (p less than 0.005). IgA detected 95% of alcoholic disease, but was poorly specific (41.1%). A trend of rising IgA with increasing severity of alcoholic injury was observed, but the differences were not significant. IgG was most commonly elevated in chronic active hepatitis and alcoholic hepatitis with cirrhosis, but the IgG values did not differ significantly from those found in other diagnostic categories. Our results substantiate assertions of a diagnostic sensitivity for elevated IgA in alcoholic liver disease and IgM in primary biliary cirrhosis. With the exception of IgM in primary biliary cirrhosis, however, serum immunoglobulins are not specific markers of liver histology.     

Clinical study of IgA antibody against hepatitis C virus core antigen in patients with type C chronic liver disease

Immunoglobulin A class antibody to hepatitis C virus core antigen (IgA anti-HCc) was measured in the serum of 128 patients with type C chronic liver disease. Fifty-eight patients (45.3%) were seropositive. IgA anti-HCc was detected in only one of 20 patients with chronic persistent hepatitis; however, 52.3% (46/88) of patients with chronic active hepatitis and 55% (11/20) of patients with liver cirrhosis were seropositive. Histological examination revealed that 22 (71.0%) of 31 patients with severe disease activity were seropositive compared to 35 (44.9%) of 78 patients with moderate (P<0.05) and one (5.3%) of 19 patients with mild (P<0.01) histological changes. IgA anti-HCc was measured sequentially in 65 patients who underwent interferon therapy. There was a significant difference between responders and other patients in the mean ratio of IgA anti-HCc titers one month after therapy. Three months after therapy, IgA anti-HCc was detectable in only two of 15 responders who were IgA anti-HCc seropositive at the start of therapy. In contrast, IgA anti-HCc reappeared three months after therapy despite a temporary decrease to undetectable levels in all nonresponders. We conclude that IgA anti-HCc is a useful marker to identify the presence of active type C liver disease and that the disappearance of IgA anti-HCc three months after interferon therapy predicts a good response in treated patients.     

IgA nephropathy featuring massive wire loop-like deposits in two patients with alcoholic cirrhosis

Background

Various renal manifestations are known to develop in patients with liver disease, including chronic hepatitis and cirrhosis.

Case presentation

We evaluated renal disease in two 47-year-old Japanese men with liver cirrhosis and chronic alcoholism for 34 years and 27 years, respectively. Renal biopsy demonstrated massive wire loop-like deposits in the subendothelial space of the glomerular basement membrane and in the mesangium. However, immunofluorescence was only positive for IgA and C3, and electron microscopy did not reveal any organized structures in the electron-dense deposits. IgA nephropathy was diagnosed, although the features were different from primary IgA nephropathy. Both patients had portosystemic shunts associated with liver cirrhosis. Their renal deposits and proteinuria resolved completely after 1 year of steroid therapy.

Conclusion

Alcohol abuse may have contributed to development of secondary IgA nephropathy in these two patients, probably via their portosystemic shunts.

     

Malignant fibrous histiocytoma complicating nephrogenic systemic fibrosis post liver transplantation

A 46-year-old man with cirrhosis secondary to hepatitis C virus infection and alcohol underwent orthotopic liver transplantation, which required urgent re-grafting because of biliary sepsis from necrosis of the left liver lobe. Recovery was complicated by renal failure and nephrogenic systemic fibrosis (probably related to intravenous gadolinium exposure). He subsequently developed a malignant fibrous histiocytoma. We present this case highlighting the occurrence of two rare conditions in the same patient following liver transplantation. We believe this is the first case of its kind to be reported.     

Association of HLA Class-II Genes and Anti-Neutrophil Cytoplasmic Antibodies in Chinese Patients with Inflammatory Bowel Disease

Background: In a preliminary study we showed that antibodies to the endoplasmic reticulum protein calreticulin (CR) occur in primary biliary cirrhosis (PBC) and autoimmune hepatitis type 1 (AIH). Since anti-CR antibodies have also been found in patients with infectious diseases, we investigated their prevalence and immunoglobulin classes in patients with various hepatic and intestinal diseases, hoping to get some information on a possible relationship between an infectious trigger and the induction of a certain class of anti-CR antibodies. Methods: Sera were tested for anti-CR antibodies of the IgA, IgG, and IgM class by Western blotting, using CR isolated from human liver: in autoimmune liver diseases (primary biliary cirrhosis (PBC) (n = 86) and autoimmune hepatitis (AIH) type 1 (n = 57)), alcoholic liver cirrhosis (ALC) (n = 32), viral liver infections (acute hepatitis A (n = 8), acute hepatitis B (n = 20), and chronic hepatitis C (n = 28)), and intestinal diseases (Crohn disease (CD) (n = 30), acute yersiniosis (n = 26)). Sera from 100 healthy individuals served as negative controls. Results: The most prominent finding was the high prevalence of anti-CR antibodies of the IgA class and the similarity in the anti-CR antibody class pattern in PBC (IgA, 62%; IgG, 43%; IgM, 55%) and yersiniosis (IgA, 62%; IgG, 39%; IgM, 42%). Class IgA anti-CR antibodies also occurred frequently in ALC (IgA, 44%; IgG, 41%; IgM, 19%). In contrast, in AIH anti-CR antibodies were predominantly of class IgG (IgA, 28%; IgG, 60%; IgM, 33%). In hepatitis A anti-CR antibodies were absent. In the other diseases they had a low prevalence and were mostly of class IgG (acute hepatitis B: IgA, 0%; IgG, 15%; IgM, 0%; chronic hepatitis C: IgA, 7%; IgG, 21%; IgM, 0%; CD: IgA, 13%; IgG, 20%; IgM, 13%). Of the healthy individuals 7% had anti-CR antibodies exclusively of class IgG. Conclusions: The high prevalence of anti-CR antibodies of class IgA in patients with PBC and yersiniosis as well as in alcoholic liver disease reflects a reactivity of the gut-associated immune system and could imply that a still undefined gut-derived bacterial (?) agent may trigger PBC.     

Ascites and spontaneous bacterial peritonitis in patients with liver cirrhosis

Liver cirrhosis is a frequent phenomenon in chronic liver diseases such as hepatitis B, hepatitis C, alcohol-related liver damage, autoimmune hepatitis and hemochromatosis. Ascites is the most frequent complication of cirrhosis. We discuss pathogenesis, diagnosis and state-of-the-art clinical management of ascites with emphasis on recent promising developments, such as covered transjugular intrahepatic portosystemic shunt (TIPS). Spontaneous bacterial peritonitis occurs in up to 10% of patients with ascites because of bacterial overgrowth with translocation through the increased permeable small intestinal wall and impaired defence mechanisms. The addition of albumin to standard antibiotic therapy may decrease mortality of spontaneous bacterial peritonitis by decreasing the incidence of renal insufficiency. Patients with coexistent marked hyperbilirubinaemia or pre-existent renal impairment could benefit from adjuvant albumin. Probiotics (bacterial food supplements) have been claimed to improve the state of underlying liver disease and may be useful in the primary and secondary prevention of spontaneous bacterial peritonitis.     

Hepatocellular carcinoma in a noncirrhotic patient with HIV: a case report and review of the literature

A 59-year-old man with human immunodeficiency virus (HIV) was referred for persistently elevated liver enzyme activities. His HIV was well controlled on antiretroviral therapy and his viral load was undetectable. He had no history of chronic liver disease and had minimal alcohol intake. He was asymptomatic and his physical exam was unremarkable without any stigmata of liver disease. Beyond the elevations in alkaline phosphatase and gamma-glutamyl transferase, the rest of his laboratory work, including viral hepatitis serologies and serum α-fetoprotein, was within normal limits. A computed tomography (CT) scan revealed a mildly nodular liver but hepatic mass or ascites was not seen. He was subsequently followed every 3 to 6 months without any change in his clinical symptoms, laboratory values, or imaging tests. Two years after the original visit, the patient presented with acute onset of abdominal pain, an AFP of 15.8 ng/mL, and a 9-cm hepatic mass on imaging. Given his preserved liver function, he underwent right hepatic lobectomy. Histologic examination of the resected tissue was consistent with hepatocellular carcinoma (HCC). The uninvolved liver was noncirrhotic and unremarkable except for mild portal inflammation. As the vast majority of HIV patients who develop HCC have established chronic liver diseases such as hepatitis B and/or C along with cirrhosis, this case of HCC in an HIV patient without cirrhosis or viral hepatitis is rare. Although current screening guidelines recommend imaging only for patients with HIV and hepatitis B/C cirrhosis, closer monitoring may be important in HIV patients with even subtle liver dysfunction.     

IgA型内毒素抗体与肝病患者的关系

为研究IgA型内毒素抗体与各型肝炎的关系,我们采用EIA法对慢性重型肝炎、肝硬变、慢性肝炎和急性肝炎患者各10例血清进行了IgA型内毒素抗体浓度的检测(均呈HBV-M阳性)。结果如下:慢性重型肝炎组、肝硬变组和慢性肝炎组阳性率分别为70％、60％和30％,急性肝炎组和正常人组一样均为0％。慢性重型肝炎组与急性肝炎组和正常     

Hepatitis C infection in potential recipients with normal liver biochemistry does not preclude renal transplantation

The hepatitis C virus (HCV) may be an important cause of chronic liver disease in renal transplant recipients. We investigated retrospectively the incidence and outcome of HCV infection in long-term renal transplant recipients and patients on hemodialysis. Stored, pretransplant sera of transplant recipients with normal liver biochemistry at surgery were tested for hepatitis C by a second-generation enzyme immunoassay. Hemodialysis patients were tested by a first-generation enzyme-linked immunosorbent assay (ELISA) against c100-3. We studied 252 renal transplant recipients and 58 hemodialysis patients followed for 65±10 months and 26±6 months, respectively. Fifteen percent (38/252) of the transplant recipients were HCV positive as were 3/58 (5%) of the hemodialysis patients. Over liver disease occurred in 22/252 (8.7%) transplant recipients and none in the hemodialysis group. Thirty-six percent (8/22) of transplant recipients with overt liver disease were HCV positive. No HCV-positive patients died of liver failure. Of six biopsies in the HCV-positive transplant group, two had histological evidence of CAH. CAH was seen in six of eight biopsies in the HCV-negative transplants and two of these latter patients progressed to cirrhosis. No hemodialysis patients had clinical or histological evidence of chronic liver disease. Two HCV-negative transplant patients died of liver failure, while no deaths related to liver disease occurred in hemodialysis patients regardless of HCV status. We conclude that hepatitis C may cause chronic hepatitis in renal transplant patients. However, chronic liver disease in HCV-positive renal transplant recipients appears to be a clinically and histologically benign entity. HCV-positive potential renal allograft recipients with normal liver biochemistry should not be excluded from renal transplantation.     

Characteristics of hepatitis C in renal transplant candidates

GOALS: To characterize hepatitis C in renal transplant candidates and to compare hepatitis C-related liver disease between patients with end-stage renal disease (ESRD) and well-matched control subjects without renal disease. BACKGROUND: Hepatitis C is common in dialysis patients and can cause morbidity and mortality in renal transplant recipients. Patients with advanced hepatitis C often are excluded from renal transplantation. STUDY: Forty-six renal transplant candidates and 46 control subjects matched for age, sex, and race without renal disease were included. Demographic, laboratory, and histologic data were compared between patients with ESRD and control subjects. RESULTS: Alanine aminotransferase levels were significantly lower in patients with ESRD (p < 0.001). Hepatitis C virus RNA levels were similar between groups. Patients with ESRD had less inflammatory activity (p < 0.001) and a lower proportion of bridging fibrosis or cirrhosis (13%) than control subjects (30%, p = 0.043). Clinical and laboratory features did not predict histologic grade or stage of hepatitis C in patients with ESRD. Two complications of percutaneous liver biopsy occurred per three diagnoses of cirrhosis in patients with ESRD. No complications occurred with transjugular liver biopsy in this group. CONCLUSIONS: Patients with ESRD had less severe hepatitis C than did control subjects. Clinical measurements did not predict histologic findings in renal transplant candidates. Transjugular liver biopsy should be considered to stage hepatitis C in renal transplant candidates due to the risk of percutaneous biopsy in uremic patients.     

High prevalence of antibodies to calreticulin of the IgA class in primary biliary cirrhosis: a possible role of gut-derived bacterial antigens in its aetiology?

BACKGROUND: In a preliminary study we showed that antibodies to the endoplasmic reticulum protein calreticulin (CR) occur in primary biliary cirrhosis (PBC) and autoimmune hepatitis type 1 (AIH). Since anti-CR antibodies have also been found in patients with infectious diseases, we investigated their prevalence and immunoglobulin classes in patients with various hepatic and intestinal diseases, hoping to get some information on a possible relationship between an infectious trigger and the induction of a certain class of anti-CR antibodies. METHODS: Sera were tested for anti-CR antibodies of the IgA, IgG, and IgM class by Western blotting, using CR isolated from human liver: in autoimmune liver diseases (primary biliary cirrhosis (PBC) (n = 86) and autoimmune hepatitis (AIH) type 1 (n = 57)), alcoholic liver cirrhosis (ALC) (n = 32), viral liver infections (acute hepatitis A (n = 8), acute hepatitis B (n = 20), and chronic hepatitis C (n = 28)), and intestinal diseases (Crohn disease (CD) (n = 30), acute yersiniosis (n = 26)). Sera from 100 healthy individuals served as negative controls. RESULTS: The most prominent finding was the high prevalence of anti-CR antibodies of the IgA class and the similarity in the anti-CR antibody class pattern in PBC (IgA, 62%; IgG, 43%; IgM, 55%) and yersiniosis (IgA, 62%; IgG, 39%; IgM, 42%). Class IgA anti-CR antibodies also occurred frequently in ALC (IgA, 44%; IgG, 41%; IgM, 19%). In contrast, in AIH anti-CR antibodies were predominantly of class IgG (IgA, 28%; IgG, 60%; IgM, 33%). In hepatitis A anti-CR antibodies were absent. In the other diseases they had a low prevalence and were mostly of class IgG (acute hepatitis B: IgA, 0%; IgG, 15%; IgM, 0%; chronic hepatitis C: IgA, 7%; IgG, 21%; IgM, 0%; CD: IgA, 13%; IgG, 20%; IgM, 13%). Of the healthy individuals 7% had anti-CR antibodies exclusively of class IgG. CONCLUSIONS: The high prevalence of anti-CR antibodies of class IgA in patients with PBC and yersiniosis as well as in alcoholic liver disease reflects a reactivity of the gut-associated immune system and could imply that a still undefined gut-derived bacterial (?) agent may trigger PBC.     

Prevalence of diabetes mellitus in patients with end-stage liver cirrhosis due to hepatitis C, alcohol, or cholestatic disease

BACKGROUND/AIMS: The aims were to study: 1) the prevalence of diabetes mellitus in patients with end-stage liver cirrhosis due to hepatitis C, alcohol, or cholestatic liver disease, 2) viral and host immunogenetic factors that may predispose to diabetes, and 3) liver transplantation outcome in patients with or without diabetes. METHODS: Fasting blood glucose values of patients who underwent liver transplantation because of hepatitis C-related cirrhosis (73 patients) were compared with those of patients with cirrhosis due to cholestatic (78 patients) or alcoholic liver disease (53 patients) and to a general population. Data on diabetes prevalence in a population without liver cirrhosis was based on the prevalence of diabetes in Olmsted County, Minnesota, residents. HLA was determined using serologic assays. Hepatitis C virus genotypes were determined with polymerase chain reaction amplification and direct sequencing. Hepatitis G RNA was detected with polymerase chain reaction. Liver transplantation outcome in patients with or without diabetes was determined with rejection, retransplantation, or death at 1 year after transplantation as end points. RESULTS: Of 64 patients with hepatitis C alone, 16 (25%) had diabetes before transplantation compared with 1 of 78 (1.3%) with cholestatic liver disease (p= 0.0001) and 10 of 53 (19%) with alcoholic liver disease (p=0.36). Nine patients had hepatitis C plus cholestatic liver disease; one of these (11%) had diabetes. The prevalence of diabetes in patients with cholestatic liver cirrhosis was not different from that of the general population. The frequency of hepatitis G virus coinfection, HLA-DR3, or HLA-DR4 in hepatitis C and diabetes was not different from that of hepatitis C alone. The distribution of hepatitis C virus genotype was similar in those with and those without diabetes. Diabetes was not associated with increased risk of rejection, retransplantation, or death at 1 year after transplantation, and had no impact on overall survival after transplantation. CONCLUSIONS: 1) The risk of diabetes is not increased in patients with liver cirrhosis due to cholestatic liver disease but is in patients with liver cirrhosis due to hepatitis C or alcoholic liver disease; 2) cofactors (age, sex, body mass index, hepatitis G virus coinfection, hepatitis C virus genotype, or HLA-DR3/DR4) did not explain the increased risk of diabetes in patients with hepatitis C; 3) diabetes before liver transplantation did not change the outcome at 1 year after transplantation or survival.     

Prevalence of antibodies to hepatitis C virus among patients with cryptogenic chronic hepatitis and cirrhosis.

Many cases of chronic hepatitis and cirrhosis cannot be attributed to a known cause and are collectively referred to as cryptogenic chronic liver disease. We have evaluated the role of the hepatitis C virus in the pathogenesis of this condition in a retrospective serum analysis for antibody to hepatitis C virus in 129 patients with cryptogenic liver disease. Other causes of chronic hepatitis and cirrhosis were ruled out by clinical, serum biochemical and serological techniques. All 129 patients were HBcAg negative, but 28 (22%) had antibody to HBcAg. Sera were tested by radioimmunoassays using recombinant peptides for antibodies to nonstructural (C100-3 and C33c) and structural regions (C22) of HCV. Among the 129 patients, 61 (47%) had antibody to C100-3, 76 (59%) had antibody to C33c and 74 (57%) had antibody to C22. Seventy-nine (61%) were reactive with at least one and 76 (59%) were reactive with at least two HCV peptides (this is the criterion used for hepatitis C virus antibody reactivity). A proportion of patients with chronic hepatitis and cirrhosis (55 of 91; 60%) similar to that of patients without cirrhosis (21 of 38; 55%) had hepatitis C virus antibody. No significant clinical, serum biochemical or histological differences were noted between the group of patients with hepatitis C virus antibody and those without this antibody reactivity. Thus more than half the patients with cryptogenic chronic liver disease had hepatitis C virus antibody, suggesting that chronic HCV infection plays a major role in the origin of cryptogenic chronic hepatitis and cirrhosis.     

Differences of liver membrane antibody frequency in alcoholic liver disease

The presence of liver membrane antibody in IgG and IgA was investigated by radioimmunoassay using isolated rabbit hepatocytes as target cells. This technique was more sensitive than the immunofluorescent method. IgG liver membrane antibodies were positive in 24% of patients with alcoholic liver disease. IgA liver membrane antibodies were detected in 58% of patients with alcoholic liver disease, whereas they were detected only in 21% of those with nonalcoholic liver disease, except for cases of autoimmune chronic active hepatitis. In alcoholic liver disease, IgA liver membrane antibodies were detected at a high frequency in a group of patients with alcoholic hepatitis and active cirrhosis (94%) as compared with that of fatty liver, hepatic fibrosis, and inactive cirrhosis (42%). These results suggest that alcoholic liver disease is characterized in part by a humoral immune response of IgA liver membrane antibodies.This study was supported in part by grants 59480207 and 60304058 from the Japanese Ministry of Education, Science and Culture.     

Simple blood tests can predict compensated liver cirrhosis in patients with chronic hepatitis C

BACKGROUND/AIMS: Twenty to fifty percent of patients with chronic hepatitis C virus infection will insidiously progress to cirrhosis after 10-20 years' follow-up. The aim of this study is to retrospectively evaluate the role of simple non-invasive blood tests in detecting the presence of compensated liver cirrhosis in Chinese patients with chronic hepatitis C. METHODOLOGY: One hundred and eleven biopsy-proven chronic hepatitis C patients were enrolled, 23 (20.7%) patients showed cirrhosis with class A in Child-Pugh's classification and were all asymptomatic. Liver biochemistry, complete blood count, and serum N-terminal propeptide of type III procollagen were determined and then compared between chronic hepatitis C patients with compensated cirrhosis and without cirrhosis. Multivariate logistic regression analysis was used to predict factors associated with compensated cirrhosis. RESULTS: Multivariate logistic regression analysis showed platelet count < or = 140,000/mm3 (odds ratio: 23.44, P < 0.001), globulin/albumin ratio > or = 1 (odds ratio: 31.47, P = 0.008), and AST/ALT ratio > or = (odds ratio: 6.58, P = 0.035) were significant predictors associated with hepatitis C virus-related compensated cirrhosis. Platelet count < or = 140,000/mm3 had 83% sensitivity and 85% specificity in detecting liver cirrhosis. Globulin/albumin ratio > or = 1 had 43% sensitivity, 98% specificity and AST/ALT ratio > or = 1 had 39% sensitivity, 92% specificity in detecting liver cirrhosis. Combined tests with AST/ALT > or = 1 and globulin/albumin > or = 1, platelet count < or = 140,000/mm3 and globulin/albumin > or = 1 had 100% specificity, 100% positive predictive value but lower sensitivity (22% and 39% respectively), lower negative predictive value (83% and 86%, respectively) in detecting hepatitis C virus-related compensated liver cirrhosis. CONCLUSIONS: Simple blood tests with platelet count < or = 140,000/mm3, globulin/albumin ratio > or = 1, and AST/ALT ratio > or = 1 can indicate liver cirrhosis in follow-up patients with chronic hepatitis C.     

Peg-IFNa-2a/RBV antiviral efficacy in cirrhotic hepatitis C patients after splenectomy or partial splenic embolization

To investigate the antiviral efficacy of combination therapy with peglyated-interferon alpha (peg-IFNa)-2a and ribavirin (RBV) in hepatitis C patients with liver cirrhosis after splenectomy or partial splenic embolization. Forty-nine hepatitis C patients with liver cirrhosis who were unable to use antiviral therapy because of hypersplenism were recruited for study and treated with splenectomy or partial splenic embolization. Three months later, a regimen of antiviral combination therapy was initiated with peg-IFNa-2a (once-weekly subcutaneous injection: 135 μg or 180 μg) and RBV (daily oral: 800 to 1200 mg), and was maintained for 48 weeks. The patients were followed up at treatment weeks 1, 2, 4, 6, 8, and 12. Thereafter, follow-up was conducted every four weeks. The patients were observed until 24 weeks after treatment discontinuation. Follow-up testing included liver function, blood chemistry, renal function, and HCV RNA level. Any adverse reactions were recorded. HLiver cirrhosis patients complicated by hypersplenism can be treated effectively with peg-IFNa-2a/RBV combination antiviral therapy after splenectomy or partial splenic embolization. The antiviral-induced sustained viral response rates was 65.00% in cirrhotic/hypersplenic hepatitis C patients receiving splenectomy and 58.62% in those receiving partial splenic embolization. Hypersplenism patients with hepatitis C-related cirrhosis achieved a good antiviral therapeutic effect with peg-IFNa-2a/RBV combination therapy following splenectomy or partial splenic embolization. This sequence of treatment may help to decrease incidences of chronic hepatitis C-induced liver failure and liver cancer in these patients.     

Liver biopsy performance and histological findings among patients with chronic viral hepatitis: a Danish database study

We investigated the variance of liver biopsy frequency and histological findings among patients with chronic viral hepatitis attending 10 medical centres in Denmark. Patients who tested positive for HBsAg or HCV- RNA were retrieved from a national clinical database (DANHEP) and demographic data, laboratory analyses and liver biopsy results were collected. A total of 1586 patients were identified of whom 69.7% had hepatitis C, 28.9% hepatitis B, and 1.5% were coinfected. In total, 771 (48.6%) had a biopsy performed (range 33.3-78.7%). According to the Metavir classification, 29.3% had septal fibrosis (> or =F2) and 13.9% had cirrhosis (F4). The frequency of cirrhosis varied from 8.3 to 18.6% among centres, and was independently associated with age, male gender, elevated alanine-aminotransferase (ALT) and non-Danish origin. Among 141 patients with hepatitis C and known duration of infection, cirrhosis had developed in 23% after 20 y of infection. Age above 40 y was a better predictor of cirrhosis than elevated ALT. National database comparison may identify factors of importance for improved management of patients with chronic viral hepatitis.     

Association of Helicobacter species with hepatitis C cirrhosis with or without hepatocellular carcinoma

BACKGROUND AND AIMS: Recent studies have suggested that bacterial coinfection with Helicobacter species in patients already infected with hepatitis C virus (HCV) could be involved in the development of cirrhosis and hepatocellular carcinoma (HCC). A retrospective cross sectional study was performed in order to explore the association between Helicobacter species and HCV associated liver diseases. METHODS: The presence of Helicobacter species was tested by polymerase chain reaction on liver samples from four groups of patients. RESULTS: Helicobacter 16S rDNA was found in only 4.2% of liver samples from control patients (n=24) and in 3.5% of liver samples from patients with non-cirrhotic chronic hepatitis C (n=29) while it was found in 68.0% of liver samples from patients with HCV positive cirrhosis without HCC (n=25) as well as in 61.3% of cirrhotic liver samples from patients with HCV positive cirrhosis and HCC (n=31). In addition, when the HCC tumour tissue was tested (n=21), 90.5% of samples were positive. DNA from Helicobacter pylori- and Helicobacter pullorum-like organisms was found. CONCLUSIONS: There is an association between the presence of Helicobacter species DNA in the liver and hepatitis C cirrhosis, with or without HCC. Indeed, the presence of these bacteria could be the result of structural changes in the liver. Alternatively, Helicobacter species could be a co-risk factor in HCV chronic liver diseases. This result warrants prospective studies to determine the possible causal role of these bacteria in the progression of chronic hepatitis C.     

Hepatitis C virus genotypes in patients with chronic liver disease and haemodialysis patients from Saudi Arabia

Summary. The genotypes of hepatitis C virus (HCV) were investigated in 28 Saudi patients (21 males, seven females; age range 23–68 years; mean 45.0 years) with histologically proven chronic hepatitis (13 chronic active hepatitis and 15 liver cirrhosis) and in 32 Saudi patients with chronic renal failure maintained on haemodialysis (22 males, 10 females; age range 18–60 years; mean 40.0 years) who also had liver disease due to HCV. Among the 28 patients with chronic liver disease genotype 4 was the predominant one (60.7%), followed by types 1b (21.4%), 1a (14.3%) and 2a (3.6%). The distribution of genotypes was similar in patients with chronic active hepatitis to those with liver cirrhosis. Among the 32 patients with chronic renal failure and maintained on haemodialysis, genotype 4 was also the dominant type (55.0%), followed by 1a (25.0%), 1b (21.9%) and 2a (3.1%). In all categories studied the prevalence of genotypes between males and females was the same. As our patients were selected from various regions of Saudi Arabia, we believe that genotype 4 is the predominant one throughout the whole kingdom.