Liver transplantation in patients with chronic viral hepatitis

Liver transplantation (LT) for end-stage liver disease secondary to hepatitis viruses has evolved rapidly during the last two decades. Currently, due to significant improvements in immunosuppressive therapy and surgical techniques, excellent survival rates and quality of life can be achieved. Among several circumstances that may pose a threat to long-term survival, the greatest is likely the recurrence of the original liver disease. Recurrence of viral infection and hepatitis is a common problem for patients undergoing LT for hepatitis B or hepatitis C. In the early 1980s, results of LT for chronic hepatitis B virus (HBV) infection were hampered by recurrent infection and subsequent allograft failure. However, following the introduction of passive immunoprophylaxis with hepatitis B immunoglobulin (HBIg) and treatment with potent oral nucleoside analogs, there has been a resurgence in the interest for this indication. HCV-related end-stage liver disease virus accounts for approximately 50% of LT in the United States and Europe. Despite the decrease in the number of new HCV infections, the prevalence of advanced HCV-related liver disease is steadily increasing. In light of the near universal recurrence of posttransplantation HCV infection and our limited ability to treat recurrent disease, transplantation is in danger of being overrun by viral hepatitis, unless effective strategies can be used to treat disease. This review summarizes available data and highlights appropriate strategies to improve outcomes.     

Pulmonary dysfunction in non-cirrhotic patients with chronic viral hepatitis

Background: Hepatopulmonary syndrome (HPS), defined as hypoxemia and functional intrapulmonary right-to-left shunts in the presence of chronic liver disease, is a frequent complication of end-stage liver disease. The aim of this study was to determine the extent of pulmonary dysfunction and the prevalence of HPS in non-cirrhotic patients with chronic viral hepatitis. Methods: Lung function tests were carried out in 178 patients with chronic viral hepatitis (mean age 43.2 years, 95 smokers). To demonstrate intrapulmonary shunting, contrast echocardiography was performed in all patients with hypoxemia (paO(2)<70 mmHg) or a reduced diffusion capacity (DLCO<70% predicted). Results: The median results of lung function parameters (FVC, FEV(1), FEV(1)/FVC, TLC, DLCO, and blood gas analysis) were normal. Despite normal lung function, hypoxemia and/or DLCO reduction were observed in 17 of 178 patients (9.6%). A correlation with inflammatory activity, extent of fibrosis, or etiology was not found. Intrapulmonary shunting was observed in three of 17 patients. Two of these patients fulfilled the diagnostic criteria of HPS. Conclusions: Impaired gas exchange is a common finding even in non-cirrhotic patients with chronic viral hepatitis. HPS, however, was present in 1.1% of patients with chronic viral hepatitis and is thus not restricted to patients with liver cirrhosis, portal hypertension, or acute liver failure.     

Antiplatelet antibodies in patients with chronic viral hepatitis receiving interferon-alpha

BACKGROUND/AIMS: The aim of this study was to investigate the possible role of interferon-alpha in the development of antiplatelet IgG antibodies in patients with chronic viral hepatitis B or C. METHODOLOGY: Ninety-one consecutive patients with chronic viral hepatitis (51 with chronic hepatitis B and 40 with chronic hepatitis C) were investigated for the presence of antiplatelet IgG antibodies in their serum immediately prior to IFN-alpha therapy and after six months of therapy. The method used was the solid phase red cell adherence test (Immucor, Norcross, USA), which is a sensitive tracer of antiplatelet antibodies. Some of the results were confirmed using an indirect immunofluorescence test for the detection of antiplatelet antibodies RESULTS: Overall, we found that antiplatelet antibodies were present in 37.54% (19/51) of patients with chronic hepatitis B before IFN-alpha therapy and in 35.29% (18/51) after therapy. Moreover, antiplatelet antibodies were found in 20% (8/40) of patients with chronic hepatitis C before and after IFN-alpha therapy. CONCLUSIONS: Therapy with IFN-alpha did not induce antiplatelet antibodies in patients with chronic viral hepatitis B or C. Thrombocytopenia observed during IFN-alpha therapy in our study was not due to the development of antiplatelet antibodies.     

Sperm DNA damage in patients with chronic viral C hepatitis

Introduction

The aim of this study was to evaluate the conventional and biofunctional parameters of sperm in young infertile patients with Hepatitis C (HCV) infection.

Methods

Forty HCV patients with primary infertility, aged 27 to 42 years (mean 36.4 years) and twenty HCV patients with secondary infertility aged 28 to 45 years (mean 35.0 ± 2.8 years), underwent hormonal and sperm analysis in addition to the determination of reactive oxygen species (ROS) concentrations in the sperm and flow-cytometric evaluation. The following biofunctional sperm parameters were evaluated by flow cytometry: DNA fragmentation, mitochondrial membrane potential, chromatin condensation, and the rate of early apoptosis.

Results

Overall, patients with HCV showed significantly worse median values of conventional and biofunctional sperm parameters than control subjects, including sperm density (31.7 vs. 80.4 million/ml), forward motility (9.4 vs. 25%), normal forms (15.4 vs. 24.8%), DNA fragmentation (6.6 vs. 2.2%), low MMP (45.5 vs. 8%), an early apoptosis rate (5 vs. 2.7%), and abnormal chromatin (18.9 vs. 13.9%). Finally, HCV patients had significantly higher basal (250 vs. 75 × 10³/cpm) and stimulated (550 vs. 120 × 10³/cpm) ROS levels in semen compared to control subjects. None of the examined parameters (sperm, hormonal, biofunctional and assessment of oxidative status in the semen) was significantly different between HCV patients with primary and secondary infertilities.

Discussion

These results confirm that HCV infection has a negative impact on sperm parameters. The overlap of the results observed in the two groups of HCV patients supports the hypothesis that HCV infection may cause to alterations in sperm parameters.     

Treatment of chronic viral hepatitis in patients with renal disease

In the last several years, numerous studies on the natural history and outcomes of viral hepatitis in dialysis and transplantation have been reported. Despite these, the management of hepatitis C virus or hepatitis B virus-related liver disease in end-stage renal disease continues to be an area of controversy. This article aims to address the current therapeutic options for patients with renal disease and chronic viral hepatitis.     

Serum matrix metalloproteinase-1 in patients with chronic viral hepatitis

BACKGROUND AND AIMS: Previously we found that serum matrix metalloproteinase (MMP)-1 activity decreased with progression of chronic liver disease. Our objectives in the present study were to observe the change in the serum MMP-1 protein concentration using recently developed specific enzyme immunoassays for MMP-1 and MMP-1 complexed with tissue inhibitor of metalloproteinases (TIMP)-1 and to elucidate the clinical usefulness of the serum MMP-1 test in chronic viral hepatitis. We measured the serum concentrations of MMP-1 and MMP-1/TIMP-1 complex using these immunoassays in 64 patients with histologically characterized chronic viral hepatitis. RESULTS: Serum MMP-1 concentration was inversely related to the histological severity of chronic hepatitis (P< 0.0001). It was closely associated with the histological degree of periportal necrosis (P< 0.0001), intralobular necrosis (P< 0.005), portal inflammation (P<0.0001) and liver fibrosis (P< 0.05). The serum concentration of MMP-1/TIMP-1 complex was also related to the histological severity of chronic hepatitis (P< 0.0001). It was associated with the degree of portal inflammation (P< 0.05), but not with the degree of periportal necrosis, intralobular necrosis or liver fibrosis. As serum MMP-1 level was closely associated with the histological degree of necroinflammation, we examined the ability of the serum MMP-1 test to differentiate active and inactive forms of hepatitis with a receiver operating curve. The results were compared with those of serum procollagen type III N-peptide (PIIINP) test. We found that the serum MMP-1 test was superior to the serum PIIINP test in assessing liver necroinflammation. CONCLUSIONS: In addition to the previously reported changes in enzyme activity, MMP-1 proteins in serum decreased during histological progression of chronic hepatitis. The serum MMP-1 test may be useful clinically to differentiate active and inactive types of hepatitis in patients with chronic viral hepatitis.     

Clearance of hepatitis C virus in HIV-infected patients with multiple chronic viral hepatitis

Viral interferences between hepatitis C (HCV) and hepatitis B (HBV) viruses were investigated in a case-control study conducted in 107 human immunodeficiency virus (HIV)-infected patients with HCV antibodies. Overall, 15 (68%) of 22 hepatitis B surface antigen (HBsAg)-positive patients had negative serum HCV-RNA while it occurred in only nine (10%) of 85 HBsAg-negative counterparts (P = 0.02). After adjusting for age, antiretroviral therapy, plasma HIV-RNA and CD4 counts, being HBsAg-positive was strongly associated with having negative serum HCV-RNA (odds ratio: 23; 95% confidence interval: 6-59; P < 0.001). Thus, HBV may favour the elimination of HCV in HIV-infected patients, which may influence liver disease and therapeutic decisions.     

乙型肝炎病毒基因型与病毒复制的关系

检测慢性乙型肝炎患者血清乙型肝炎病毒(HBV)基因型和病毒载量(HBV-DNA定量),探讨它们之间的关系。用微板核酸杂交-ELISA方法对HBV进行基因分型,用PCR荧光定量检测血清HBV-DNA水平,共318例。检测到HBV B型111例(35％);C型128(40％);混合型(B+C,C+D,B+C+D)45例(14％);D型2例;F型2例;未分型30例(9.4％);没有发现A、E型。结果发现,C型和混合型HBV的血清DNA水平高于B型(1.14×107vs2.2×107vsl.60×106拷贝/ml,P<0.05);而混合型HBV的血清DNA水平与C型无差别(P=0.127)。研究提示,我国HBV以B,C两基因型为主,HBV基因型可能是影响HBV复制的重要因素之一。     

Histomorphological characteristics of liver tissue in patients with chronic viral hepatitis

OBJECTIVE : Chronic viral hepatitis and cirrhosis caused by hepatitis B virus (HBV), hepatitis C virus (HBC) or both constitute the majority of cases of liver diseases in China. Pathologists often need to differentiate between the morphological features of HBV and HCV. The aim of this study was to explore the differences in inflammatory activity, fibrosis and morphological characteristics in various types of chronic viral hepatitis. METHODS : Inflammatory activity and degree of fibrosis in liver biopsies taken from 224 patients with chronic hepatitis were determined according to the Diagnostic Criteria of Chronic Hepatitis, China, 1995. Each of hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and the hepatitis C virus nuclear core protein (CP₁₀) were detected on paraffin sections of the biopsies by using immunohistochemical methods. Patients were divided into HBV, HCV and HBV + HCV infection groups and the differences among these groups were assessed on the basis of histopathological characteristics including inflammatory activity, fibrosis, steatosis, intrahepatic cholestasis, Councilman bodies and ground‐glass hepatocytes. RESULTS : The HCV infection group had more severe inflammatory activity, fibrosis and intrahepatic cholestasis than did the HBV infection group. The degree of inflammatory activity and fibrosis in the HBV + HCV infection group was moderate, but the degree of intrahepatic cholestasis was the most severe of the three study groups. Ground‐glass hepatocytes were only noted in HBV‐infected specimens. There was no difference in the occurrences of steatosis and Councilman bodies among the three study groups. CONCLUSIONS : The degree of inflammatory activity and fibrosis induced by HCV in hepatocytes is more severe than that induced by HBV. The histological changes observed in liver infected by both HBV and HCV are no more severe than those observed in liver infected with either HBV or HCV. Intrahepatic cholestasis may play an important role in aggravating damage to hepatocytes.     

Autoantibodies and response to alpha-interferon in patients with chronic viral hepatitis

One hundred and fifteen patients with chronic type B, D and non-A, non-B hepatitis treated with recombinant alpha-interferon were tested for six different autoantibodies prior to or during therapy, and the course of treatment was compared in autoantibody-positive and -negative patients. Three out of 25 (12%) hepatitis B patients, 14 out of 30 (47%) hepatitis D patients and 19 out of 60 (32%) chronic non-A, non-B hepatitis carriers had baseline or post-therapy autoantibodies. The rate of response between patients with and without autoantibodies among B, D and non-A, non-B patients was, respectively, 67 vs. 79%, 23 vs. 25%, 70 vs. 61% (p = N.S.). No adverse reaction was observed in the 36 patients who had or developed nuclear, smooth muscle, parietal cells and thyroid autoantibodies during therapy. A patient with baseline antibodies against liver and kidney microsomes developed an icteric acute hepatitis at the fourth month of therapy, but five other patients with this reactivity responded to therapy uneventfully. The presence of autoantibodies before therapy or their induction following therapy is not a contraindication to the use of interferon in patients with chronic viral hepatitis.     

Association of erectile dysfunction with depression in patients with chronic viral hepatitis

AIM: To investigate the prevalence of erectile dysfunction(ED) and its association with depression in patients with chronic viral hepatitis.METHODS: This single center cross-sectional study was conducted from August 2013 through January 2014. All outpatients with chronic viral hepatitis in our liver clinic between 18 and 80 years of age were considered eligible for this study. The exclusion criteria included well-established causes of ED, such as diabetes, hypertension, hyperlipidemia, alcohol abuse, liver cirrhosis, ischemic heart disease, renal disease, neurologic disease, and malignancy. We also excluded the patients who had incompletely answered the questionnaires. ED was assessed using the validated Korean version of the International Index of Erectile Function(IIEF-5) scale. The Korean version of the self-administered Beck Depression Inventory(BDI) scale was used to assess depression in the patients. Demographic and medical data were obtained from the patients' medical records. Current or past history of psychiatric diagnosis and drug history including the use of an antiviral agent and an antidepressant were also recorded. RESULTS: A total of 727 patients met the initial eligibility criteria. Six hundred seventeen patients were excluded because their medical records contained one or more of the previously determined exclusion criteria. The remaining 110 patients were assessed based on the BDI and IIEF-5 questionnaires. Based on the IIEF-5 scale, the prevalence of ED among patients with chronic viral hepatitis was 40%. Compared with the non-ED group, patients in the ED group were older. The proportion of patients in the ED group who had a job or who were na?ve peg-interferon users was lower than that in patients in the non-ED group. Patients with ED had significantly lower scores on the IIEF-5 scale than patients without ED(11.75 ± 4.88 vs 21.33 ± 1.86, P = 0.000). Patients with ED rated significantly higher scores on the BDI scale compared with patients without ED(12.59 ± 7.08 vs 5.30 ± 4.00, P = 0.000). Also, the IIEF-5 scores were negatively correlated with age, employment, and BDI scores. In the multiple logistic regression analysis, age and depression were independently associated with erectile dysfunction(P =0.019 and 0.000,respectively).CONCLUSION:Patients with chronic viral hepatitis have a high prevalence of ED.Age and depression are independent factors for ED in male patients with chronic viral hepatitis.     

慢性重型肝炎患者中性粒细胞超微结构的改变

目的观察慢性重型肝炎患者中性粒细胞超微结构的改变及其意义。方法采用透射电镜对１５例慢性重型肝炎患者中性粒细胞超微结构进行观察，并以１５例正常人为对照。结果慢性重型肝炎患者中性粒细胞有明显异常，表现为胞浆稀疏，吞噬空泡，细胞器及细胞颗粒明显减少，线粒体水肿、空化、退变，细胞核浓缩等，病情严重及继发严重感染者尤著。结论观察中性粒细胞的超微结构变化对判断慢性重型肝炎患者防御细菌感染能力以及肝衰竭程度有一定的参考价值。     

Pyridinoline collagen cross-links in patients with chronic viral hepatitis and cirrhosis

Background/Aims: The mature form of collagen cross-linking increases the resistance of collagen to degradative enzymes, and thus renders the protein in the fibrotic lesions extremely stable and the fibrosis virtually irreversible. It is crucial to elucidate the extent of cross-linking in fibrotic and cirrhotic livers if we are to control the subsequent removal of the excessive deposited collagen, whether by natural enzymes or induced by therapy. We aimed to quantitative pyridinoline, a mature form of the cross-linking, in normal control livers, viral fibrotic livers with various degrees of fibrosis and viral cirrhotic livers.Methods: Needle liver biopsy samples from 75 patients with chronic viral hepatitis and 13 patients with viral liver cirrhosis, and six normal control livers were analyzed. Collagen and pyridinoline contents were determined by high-performance liquid chromatography.Results: Significantly higher levels of pyridinoline cross-links per collagen molecule were found in the viral cirrhotic livers (0.60 [0.46, 0.65] pmol/pmol of collagen; median [25%, 75%]) compared with those in normal livers (0.39 [0.24, 0.43] pmol/pmol of collagen, p=0.03491). But no differences were found in levels between cirrhosis and chronic hepatits with various degrees of fibrosis. These data suggest that liver collagen may be susceptible to degradation to a similar degree in viral cirrhosis and in chronic viral hepatitis.Conclusion: The extent of the pyridinoline cross-linking of hepatic collagen does not seem to be responsible for the irreversibility of viral liver fibrosis.     

Treatment of chronic hepatitis B or C in HIV-infected patients with dual viral hepatitis

Dual chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are recognized in 3%-5% of human immunodeficiency virus (HIV)-infected individuals. More severe liver disease is seen in these patients. Viral interference may account for the fact that replication of one virus generally predominates over replication of the other. The impact that treatment of HBV or HCV infection has on this reciprocal inhibition is not well established. No evidence of reactivation of either HBV or HCV was seen when complete suppression of the other predominant virus was achieved with specific therapy in 21 subjects with HIV infection and dual HBV/HCV infections. This information has important pathogenic implications and may influence therapeutic decisions.     

Fas antigen (CD95) expression and apoptosis in hepatocytes of patients with chronic viral hepatitis

BACKGROUND: Apoptosis may be defined as programmed cell death. It is involved in the normal development and homeostasis of tissues in multicellular organisms. An increased or decreased rate of apoptosis may lead to a range of diseases. Fas antigen is a cell-surface receptor that induces apoptotic pathways when treated with Fas ligand or anti-Fas antibody. There is increasing evidence that apoptosis plays an important role in the immunopathogenesis of chronic viral hepatitis, in which the Fas antigen-Fas ligand pathway is particularly involved. METHODS: Fas antigen expression and apoptosis (apoptotic index) were assayed using flow cytometry in the hepatocytes of 27 patients with chronic viral hepatitis. Histopathological activity, scored by Knodell's histological activity index, other histopathological parameters, serum transaminase values and patient age were then compared with apoptotic index and Fas antigen expression. RESULTS: Apoptosis and Fas antigen expression in hepatocytes were correlated closely with histological activity (grade) of chronic viral hepatitis, but there were no correlations with histological stage, patient age or serum transaminase levels. CONCLUSION: Apoptosis and its triggering molecule, Fas antigen, induce mechanisms that appear to be associated with the pathogenesis of chronic viral hepatitis.