Stage Of Chronic Liver Disease Research Articles

Antibody to the Human T-Lymphotropic Virus Type 1 (HTLV-1) Envelope Protein Gp46 in Patients Co-infected with HCV and HTLV-1

Human T-lymphotropic virus type 1 (HTLV-1) infection is known to affect hepatitis C virus (HCV) clearance and to accelerate the development of hepatocellular carcinoma in HCV-infected patients. In this study, we found the prevalence and titer of an antibody recognizing the central region of the HTLV-1 Gp46 protein to be associated with the severity of chronic liver disease. The antibody prevalence was significantly correlated with the stage of chronic liver disease (P < 0.0001): 3 (14.3%) of 21 patients with minimal-mild chronic hepatitis, 12 (24%) of 50 with moderate-severe chronic hepatitis, 7 (87.5%) of 8 with liver cirrhosis, and 13 (100%) of 13 with hepatocellular carcinoma. These results indicate that the antibody may be a useful marker of the deterioration of liver disease in patients co-infected with HCV and HTLV-1. This antibody may be useful for the diagnosis of liver diseases and the development of more effective treatments.

A non-invasive diagnostic algorithm for the diagnosis of chronic liver disease: The role of echography and APRI test

Background. Diagnosis and staging of chronic liver disease is mainly based on liver biopsy (LB). Many attempts were made in order to replace LB with non-invasive markers of disease activity. Our study focuses on the role of ultrasound examination (US) associated to AST/platelets ratio index (APRI test) on the differential diagnosis between chronic active hepatitis (CAH) and liver cirrhosis (LC).

Application of the AbrioTM Imaging System to the Analysis of Liver Fibrosis

Fibrosis is a histological stage of chronic liver disease and in certain cases is difficult to quantify. The quantification of fibrosis, and thus determination of fibrosis stage, can be used as a predictive determinant of the progression to cirrhosis and also to objectively make decisions regarding the initiation or continuation of therapeutic intervention. A practical approach to better manage fibrosis and therapeutic intervention would be an imaging system capable of the early detection and determination of the orientation of collagen strand formation in liver biopsy specimens. We describe the application of a birefringence-based polarized light imaging system for this purpose. Birefringence imaging allows highly sensitive visualization and analysis of collagen strands without the need of a collagen-specific stain. We demonstrate that the Abrio system (CRi, Woburn, MA) is capable of providing measurable parameters representative of the structural density, and the underlying molecular order and orientation of collagen strands in liver fibrosis. This would be useful not only to quantitatively stage fibrosis, and subsequently chronic liver disease, but also to determine when to initiate or continue therapy. The capability demonstrated by the Abrio imaging system in this pilot study provides a new technique that can be used to improve the overall management of chronic liver disease.

Factors influencing health-related quality of life in chronic liver disease

To investigate the factors contributing to health-related quality of life (HRQL) in chronic liver disease (CLD). Patients with CLD and age- and sex-matched normal subjects performed the validated Thai versions of the short-form 36 (SF-36) by health survey and chronic liver disease questionnaire (CLDQ). Stepwise multiple regression analysis was used to assess the impact of disease severity, demography, causes of CLD, socioeconomic factors, and self-rating health perception on HRQL. Two-hundred and fifty patients with CLD and fifty normal subjects were enrolled into the study. Mean age and the numbers of low educated, unemployed, blue-collar career and poor health perception increased significantly from chronic hepatitis to Child's Classes A to B to C. Advanced stage of CLD was related to deterioration of HRQL. Increasing age and female reduced physical health area. Low socioeconomic factors and financial burden affected multiple areas of HRQL. In overall, the positive impact of self-rating health perception on HRQL was consistently showed. Advanced stages of chronic liver disease, old age, female sex, low socioeconomic status and financial burden are important factors reducing HRQL. Good health perception improves HRQL regardless of stages of liver disease.

Diagnosis of Liver Cirrhosis

Liver cirrhosis, the final stage of chronic liver disease, is characterized by an unfavorable prognosis and an increased risk of hepatocellular carcinoma and also requires an appropriate management. Laparoscopy, the gold standard in the diagnosis of cirrhosis, is hampered by its invasiveness. Therefore, a noninvasive method for diagnosing liver cirrhosis would be of great benefit. A consecutive series of 100 patients, sent to our gastroenterological unit for diagnostic laparoscopy, underwent a standardized ultrasonographic examination prior to laparoscopy. Conventional ultrasonographic examination revealed a sensitivity of 55% and a specificity of 86% in the diagnosis of cirrhosis. Considering the assessment of the transmission of heart pulsation on the liver surface, the corresponding values improved by increasing to 85% and 93%. Evaluating the transmission of heart pulsation on the liver surface improves the ability of ultrasound to diagnose liver cirrhosis; therefore, it should be an integral part of routine sonographic examination of the liver.

Seroprevalence of hepatitis E virus (HEV) antibody and the possible association with chronic liver disease: a case-control study in Albania

A case-control study involving 109 in-patients with chronic liver disease and 190 in-patients with no apparent liver disease was conducted to evaluate the seroprevalence of anti-HEV antibodies and the possible association with chronic liver disease. Among cases, the anti-HEV prevalence was 36.6% which increased significantly by age; among controls, the prevalence was 12.1% (P<0.05) and was similar among age groups <60 years. Among cases, aged >50 years (OR 4.0, 95% CI 1.4-11) and the presence of end stage liver disease (ESLD) (OR 4.3, 95% CI 1.4-12.8) were associated independently with anti-HEV positivity. The mean optical density, determined by anti-HEV immunoenzymatic test, was significantly higher among patients with ESLD, compared to the other patients. These results indicate that there is a high seroprevalence of anti-HEV in patients with chronic liver disease and a possible association between HEV infection and/or anti-HEV production and advanced stage chronic liver disease.

Single-Pass Percutaneous Liver Biopsy for Diffuse Liver Disease Using an Automated Device: Experience in 154 Procedures

To describe our experience with ultrasound (US)-guided percutaneous liver biopsies using the INRAD 18 G Express core needle biopsy system. One hundred and fifty-four consecutive percutaneous core liver biopsy procedures were performed in 153 men in a single institution over 37 months. The medical charts, pathology reports, and radiology files were retrospectively reviewed. The number of needle passes, type of guidance, change in hematocrit level, and adequacy of specimens for histologic analysis were evaluated. All biopsies were performed for histologic staging of chronic liver diseases. The majority of patients had hepatitis C (134/153, 90.2%). All patients were discharged to home after 4 hr of post-procedural observation. In 145 of 154 (94%) biopsies, a single needle pass was sufficient for diagnosis. US guidance was utilized in all but one of the procedures (153/154, 99.4%). The mean hematocrit decrease was 1.2% (44.1--42.9%). Pain requiring narcotic analgesia, the most frequent complication, occurred in 28 of 154 procedures (18.2%). No major complications occurred. The specimens were diagnostic in 152 of 154 procedures (98.7%). Single-pass percutaneous US-guided liver biopsy with the INRAD 18 G Express core needle biopsy system is safe and provides definitive pathologic diagnosis of chronic liver disease. It can be performed on an outpatient basis. Routine post-biopsy monitoring of hematocrit level in stable, asymptomatic patients is probably not warranted.

Melatonin prevents experimental liver cirrhosis induced by thioacetamide in rats

Liver cirrhosis is a critical stage of chronic liver diseases that can produce liver failure, portal hypertension and hepatocarcinoma. Sustained oxidative stress plays a key role in cell damage and fibrosis induced during liver cirrhosis. We evaluated the effect of oxidative stress regulation by melatonin on the development of parenchymal destruction and stellate cell activation in experimental liver cirrhosis. Melatonin was administered to rats with liver cirrhosis induced by thioacetamide (TAA) for 1 or 3 months. Liver injury was assessed by serological analysis, as well as hematoxylin-eosin staining and the in situ apoptosis detection assay in liver sections. Oxidative stress was evaluated by lipoperoxide and reduced glutathione levels, and by the measurement of catalase and superoxide dismutase activities in liver and serum respectively. The activation of stellate cells was evaluated by alpha-smooth muscle actin expression in liver sections. Our results showed that TAA induced oxidative stress with extensive tissue damage and enhanced alpha-smooth muscle actin expression in liver. Melatonin prevented the oxidative stress-related changes associated with TAA toxicity. In conclusion, the study showed that melatonin prevents the tissue damage and fibrosis associated with TAA-induced liver cirrhosis in rats.

The development of de novo hepatocellular carcinoma in patients on a liver transplant list: frequency, size, and assessment of current screening methods.

Chronic end stage liver disease is the most frequent indication for liver transplantation. Individuals with end stage cirrhosis, and therefore individuals on liver transplant lists, are at increased risk of developing a hepatic cancer. Those individuals on liver transplant lists also may represent the best group available for evaluating the current methods for screening and surveillance for the development of hepatic cancer as an examination of the explant liver provides a gold standard for tumor assessment. Assuming that only tumor free individuals were screened at the onset of this study, the data obtained enables one to determine the frequency of new hepatic cancers since listing and evaluate the positive and negative predictive values of each assessment method over the surveillance interval. All patients listed for liver transplantation with end stage chronic liver disease, who did not have a hepatoma at the time of transplant listing, were followed and assessed for the development of a hepatic cancer while on the waiting list. The screening techniques utilized included quarterly alpha fetoprotein (alpha FP) determinations and ultrasound (US) studies as well as semi-annual triple phase computed tomography (CT) scans of the liver. alpha FP failed to identify any cases of de novo hepatic cancer in patients waiting for a liver transplant. In contrast, US and especially CT scanning with intravenous contrast identified new hepatic masses. The later method, which identified early enhancing mass lesions, was the more valuable method at identifying masses that subsequently were shown by pathologic examination of the explant liver to be hepatic cancers. However, only 14 of 20 individuals found to have a de novo tumor were identified by this method. Once identified however, the treatments utilized for hepatic tumor ablation while waiting for a transplant appear to be effective with a mean of 57.8+/-8.3% necrosis of the treated masses being identified at the time of explant examination. In conclusion these data suggest that: 1. The development of a hepatocellular carcinoma (HCC) in an individual on a transplant list is not rare and occurs in as many as 20% of cases; 2. The most effective method for the detection of de novo HCC appears to be semi-annual triphasic CT scan with the identification of a new early enhancing lesion; and 3. Once recognized, the presence of the tumor enables the individual to move up on the waiting list as result of the additional model endstage liver disease (MELD) points allowed for individuals with HCCs.

Chronic liver disease in Lagos: a clinicopathological study

To evaluate the clinical features and stage of chronic liver disease at presentation in Lagos. Clinical features, hepatic functional reserve (Child-Pugh classification) and liver histopathology were evaluated in 74 patients with chronic liver disease (CLD). The average age of the patients was 44.1 +/- 14yr and most (57, 67% ) were male. Ascites, hepatomegaly and jaundice were noted in 66%, 51%, 47% respectively. Hepatocellular carcinoma, liver cirrhosis and chronic hepatitis were seen in 35, 29, and 10 patients respectively. Significant impairment of hepatic functional reserve was noted in most of the patients with liver cirrhosis (76% ) and carcinoma (68% ). Hepatitis B and C infections were identified in 58% and 12% of the patients respectively. The majority of clinically identified patients with CLD had severe impairment of hepatic function with underlying advanced liver cirrhosis or hepatocellular carcinoma at presentation. Viral hepatitis was associated with most CLD and thus is potentially preventable and treatable when detected early. Public enlightenment programmes on hepatitis, widespread implementation of HBV vaccination, and surveillance of individual at-risk are essential for the control of hepatitis infection and the early detection of compensated CLD.

Liver micro-organs transcribe albumin and clotting factors and increase survival of 92% hepatectomized rats

Background/Aims: Currently there is no effective non-surgical therapy for most patients with fulminant or end stage chronic liver disease. Methods: We have prepared rat liver micro-organs (LMOs), which preserve the liver micro-architecture and ensure that no cell is more than 150 μm away from a source of nutrients and gases. The function of LMOs has been evaluated in vitro and in a new extra-corporeal liver device termed aLIVE in which LMOs are exposed to liver-like hemodynamic conditions. Results: In vitro LMOs maintain normal physiological and biochemical functions including oxygen consumption, glucose metabolism, conversion of ammonia to urea, secretion of albumin and de novo transcription of genes coding for albumin and clotting factors. Inside the aLIVE bioreactor, LMOs also display sustained oxygen consumption, glucose metabolism and transcription of albumin and clotting factors IX and X, when connected both to normal and to 92% hepatectomized rats. Survival of 92% hepatectomized rats was 40% longer following a single 4-h treatment with aLIVE, compared to untreated animals. Conclusions: An extra-corporeal liver device, aLIVE, which provides key liver functions, has been developed. When tested in 92% hepatectomized rats, aLIVE improved the clinical condition and significantly increased survival time of the treated rats.

GH-resistance in different stages of chronic liver disease

GH-resistance in different stages of chronic liver disease

Genotype B hepatitis B virus is associated with severe icteric flare-up of chronic hepatitis B virus infection in Hong Kong

OBJECTIVE: We aimed to investigate the association of viral genotype and the development of icteric flare-up (IF) in chronic hepatitis B virus (HBV) infection. METHODS: Twenty-one consecutive patients suffering from IF of chronic HBV infection, defined as elevation of ALT over five times the upper limit of normal, together with either bilirubin >50 IU/L or elevated bilirubin plus PT >3 s prolonged, were studied. Patients from three stages of HBV-related chronic liver disease were studied as controls: 1) asymptomatic carriers (31 patients), defined as persistent normal ALT for at least 2 yr; 2) active early cirrhosis (49 patients), defined as Child’s A liver cirrhosis plus HBV DNA >10 6 Eq/ml; and 3) decompensated cirrhosis (31 patients), defined as Child’s B or C liver cirrhosis with complications. Restriction fragment length polymorphism was used for genotyping. RESULTS: Only genotype B and C HBV were identified in our studied cohort. Ninety-one percent of patients suffering from IF were infected by genotype B HBV ( p <0.001 vs asymptomatic carriers, early cirrhosis patients, and decompensated cirrhosis patients). On the contrary, genotype C HBV was the predominant strain at different stages of chronic liver disease; no statistical difference was found on the relative prevalence of genotype B/C HBV among asymptomatic carriers, early cirrhosis patients, and decompensated cirrhosis patients. CONCLUSIONS: Genotype B HBV is associated with IF among chronic HBV-infected patients in Hong Kong, whereas genotype C HBV is more prevalent at all stages of chronic liver disease. Our findings suggested that the two different HBV genotypes might have different pathogenic mechanisms of liver damage.

Genotype B hepatitis B virus is associated with severe icteric flare-up of chronic hepatitis B virus infection in Hong Kong.

We aimed to investigate the association of viral genotype and the development of icteric flare-up (IF) in chronic hepatitis B virus (HBV) infection. Twenty-one consecutive patients suffering from IF of chronic HBV infection, defined as elevation of ALT over five times the upper limit of normal, together with either bilirubin > 50 IU/L or elevated bilirubin plus PT > 3 s prolonged, were studied. Patients from three stages of HBV-related chronic liver disease were studied as controls: 1) asymptomatic carriers (31 patients), defined as persistent normal ALT for at least 2 yr; 2) active early cirrhosis (49 patients), defined as Child's A liver cirrhosis plus HBV DNA > 106 Eq/ml; and 3) decompensated cirrhosis (31 patients), defined as Child's B or C liver cirrhosis with complications. Restriction fragment length polymorphism was used for genotyping. Only genotype B and C HBV were identified in our studied cohort. Ninety-one percent of patients suffering from IF were infected by genotype B HBV (p < 0.001 vs asymptomatic carriers, early cirrhosis patients, and decompensated cirrhosis patients). On the contrary, genotype C HBV was the predominant strain at different stages of chronic liver disease; no statistical difference was found on the relative prevalence of genotype B/C HBV among asymptomatic carriers, early cirrhosis patients, and decompensated cirrhosis patients. Genotype B HBV is associated with IF among chronic HBV-infected patients in Hong Kong, whereas genotype C HBV is more prevalent at all stages of chronic liver disease. Our findings suggested that the two different HBV genotypes might have different pathogenic mechanisms of liver damage.

Interactions between metabolic disorders (diabetes, gallstones, and dyslipidaemial and the progression of chronic hepatitis C virus infection to cirrhosis and hepatocellular carcinoma. A cross-sectional multicentre survey

Background. Diabetes, gallstones and dyslipidaemia are widespread, metabolically related, disorders that can affect the liver, often in a clinically silent fashion. Aim. To investigate whether the presence of these disorders may worsen chronic viral disease by inducing additional liver damage, revealed by variations in serum increases of aminotransferase, alkaline phosphatase and gamma-glutamyl-transpeptidase activities. Patients and methods. This retrospective, cross-sectional study involved 1195 patients with chronic hepatitis C virus infection: 47.2% chronic hepatitis, 45.2% cirrhosis, and 7.6% hepatocellular carcinoma. 14.9% of patients had enzymatic cholestasis, defined as combined increase of alkaline phosphatase and gamma-glutamyl-transpeptidase. A Log-linear statistical model was applied to the following variables: stages of liver disease, diabetes, cholelithiasis, hypertriglyceridaemia, hypercholesterolaemia, and enzymatic cholestasis. Results. Log-linear analysis, applied to categorical variables, revealed, for the first time, a three-way interaction between the stages of chronic liver disease, diabetes, and enzymatic cholestasis. Two-way interactions demonstrated that liver disease stages correlated directly to the prevalence of cholelithiasis and inversely to hypercholesterolaemia. Irrespective of the liver disease stage, hypertriglyceridaemia correlated to hypercholesterolaemia. Conclusions. This study discloses a synergistic liver damaging effect of diabetes and hepatitis C virus. The three-way interaction obtained by our analysis suggests that diabetes is a risk factor for the progression of viral liver disease and that it contributes to disease evolution, at least in part, by induction of cholestasis.

The relation between the stage of chronic liver disease and thrombocyte functions

The relation between the stage of chronic liver disease and thrombocyte functions

Platelet count reflects stage of chronic hepatitis C

Since the classification of liver disease is firmly based on morphology, liver biopsy continues to hold a central place in diagnosis and disease management. It might be helpful in the outpatient clinic if the stage of the liver disease could be evaluated using routine biochemical tests. This study was conducted to assess the histological stage of chronic hepatitis C using parameters measured in routine laboratory blood tests. Correlation between blood biochemical parameters and histological stage of chronic liver disease was analyzed in 498 patients with chronic liver disease admitted to our hospital. Correlation of histological staging of liver biopsy specimens of chronic hepatitis C and ten blood parameters was analyzed, showing that platelet count, prothrombin time, AST, r-GTP, Al-P, LDH, total bilirubin and albumin were significant by Kruskal–Wallis test. An analysis using proportional odds model showed that platelet count, prothrombin time, Al-P, LDH and albumin levels were significant factors for fibrotic stage of the liver. As platelet count is easily determined by a routine laboratory test, it is one of the important parameters for evaluating the stage of chronic hepatitis C.

High prevalence of pulmonary diffusion abnormalities without interstitial changes in long-term survivors of liver transplantation.

Abnormalities in lung function are frequent findings in patients with terminal stage chronic liver disease. While spirometric parameters improve early after liver transplantation, a reduction in diffusion capacity has been reported up to 15 months after transplantation. It is unknown to what extent this disturbance in gas exchange occurs among long term survivors after liver transplantation. We assessed lung function in terms of spirometry, and gas exchange as well as pulmonary morphology by high resolution computed tomography (HRCT) in 40 patients 38 months (median, range 20-147 months) after liver transplantation. The prevalence of restrictive or obstructive changes was not different from predicted values. For the whole group of long-term survivors the carbon monoxide transfer coefficient (KCO) was reduced to 71.3 + 12.0% predicted (P < 0.05). HRCT revealed interstitial changes in only 2/40 (5.0%), emphysematous bullae in 2/40 (5.0%) and pleural thickening in 9/40 (22.5%). Diffusion abnormalities are prevalent in the majority of patients after liver transplantation, whereas spirometric abnormalities are absent also in the long term. The high prevalence of impaired gas exchange and the absence of interstitial lesions imply that changes in pulmonary blood vessels are the most likely cause.

Improvement of Pulmonary Hypertension After Liver Transplantation

Pulmonary hypertension at the end stage of chronic liver disease is not an uncommon situation. This association termed portopulmonary hypertension raises the question of the feasibility of performing orthotopic liver transplantation (OLT). In the case reported herein, there was a favorable outcome after OLT, even though the mean pulmonary artery pressure (MPAP) before transplantation was increased to 45 mm Hg. Before OLT, the cardiac index (CI) was considerably elevated (7.69 L/min/m2), giving evidence of a marked hyperdynamic circulatory state. The CI decreased significantly after OLT (3.38 L/min/m2), and this produced a significant decrease in the MPAP. Our observation suggests that portopulmonary hypertension due to a marked increase in the CI can be managed successfully by OLT.

Hepatocellular proliferation and development of hepatocellular carcinoma: A case-control study in chronic hepatitis C

Patients with hepatitis C have an increased risk of developing hepatocellular carcinoma (HCC). This is related to the stage of chronic liver disease, as characterized histologically by hepatic fibrosis and architectural distortion, but it is unclear whether histological markers can define the risk of developing HCC. We conducted a case-control immunohistochemical study of Ki-67, a marker for hepatocellular proliferation, in livers of 18 patients who had developed HCC more than 2 years after the biopsy specimen had been taken. Using conditional logistic regression analysis, the results were compared with 18 selected controls, who were age-matched patients with hepatitis C of similar histological stage who had not developed HCC. We also examined livers for cellular dysplasia, p53 mutations, and bcl-2 overexpression, and assessed whether the results could be correlated with demographic and disease-related variables, such as gender, region of birth, alcohol consumption, severity of liver disease, HCV genotype, and markers of hepatitis B virus (HBV) infection. Livers from patients who developed HCC were more often positive for Ki-67 (13 of 18 [72%] v 9 of 18 [50%]; P = .06) and tended to have higher mean Ki-67 scores (6 ± 7.5 v 3 ± 4.4; P = .10) compared with control cases. In the HCC-predisposed group, three livers showed large cell dysplasia, two were positive for p53 mutations, and two for bcl-2 overexpression. In contrast, in the non-HCC group, only one case had dysplasia, and none were positive for immunostaining for p53 or bcl-2 mutations. With the exception of one case, all livers with large cell dysplasia or p53 mutations and bcl-2 overexpression were also positive for Ki-67. Twelve (55%) of the 22 Ki-67-positive cases were anti-HBc-positive in the serum, in contrast to 2 of 14 (14%) patients in the Ki-67-negative group ( P = .01). Patients with evidence of past infection with HBV were more often Ki-67 positive than those who had no evidence of past infection (85% [11 of 13] v 45% [10 of 22]; P = .02). There were no other associations between demographic or disease-related variables and Ki-67 expression. Increased hepatocellular proliferative activity, as assessed by Ki-67 expression, may be one factor indicative of an increased risk of developing HCC among patients with chronic hepatitis C. Furthermore, past infection with HBV appears to be an important correlate of increased hepatocellular proliferation in hepatitis C.