Functional Hepatic Mass Research Articles

Portal vein stenosis preconditioning of living donor liver in swine: early mechanisms of liver regeneration and gain of hepatic functional mass

To reduce the morbidity and mortality risk for the donor in living donor liver transplantation (LDLT), we previously identified 20% left portal vein (LPV) stenosis as an effective preconditioning method to induce cell proliferation in the contralateral lobe without downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours after preconditioning and investigate the changes in liver volume and function. Fourteen pigs were used this study. Five pigs were used to study the genetic, cellular and molecular mechanisms set up in the early hours following the establishment of our preconditioning. The remaining nine pigs were equally divided into three groups: sham-operated animals, 20% LPV stenosis, and 100% LPV stenosis. Volumetric scanning and 99 mTc-Mebrofenin hepatobiliary scintigraphy were performed before preconditioning and 14 days after to study morphological and functional changes in the liver. We demonstrated that liver regeneration triggered by 20% LPV stenosis in the contralateral lobe involves TNF-α, IL-6, and inducible nitric oxide synthase 2 by means of STAT3 and hepatocyte growth factor. We confirmed that our preconditioning was responsible for an increase in the total liver volume. Finally, we demonstrated that this volumetric gain was associated with an increase in hepatic functional capacity. NEW & NOTEWORTHY We describe a new preconditioning method for major hepatectomy that is applicable to hepatectomy for donation. We identified 20% left portal vein stenosis as effective preconditioning that is capable of inducing cell proliferation in the contralateral lobe without the downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours following preconditioning, and we confirm that 20% left portal vein stenosis is responsible for an increase in the functional capacity and total liver volume in a porcine model.

Dynamic and accurate assessment of acetaminophen-induced hepatotoxicity by integrated photoacoustic imaging and mechanistic biomarkers in vivo

The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational non-invasive photoacoustic imaging of liver function with mechanistic circulating biomarkers of hepatotoxicity with histological assessment to facilitate the more accurate and precise characterization of APAP-ILI and the efficacy of therapeutic intervention.Perturbation of liver function and cellular viability was assessed in C57BL/6J male mice by Indocyanine green (ICG) clearance (Multispectral Optoacoustic Tomography (MSOT)) and by measurement of mechanistic (miR-122, HMGB1) and established (ALT, bilirubin) circulating biomarkers in response to the acetaminophen and its treatment with acetylcysteine (NAC) in vivo. We utilised a 60% partial hepatectomy model as a situation of defined hepatic functional mass loss to compared acetaminophen-induced changes to.Integration of these mechanistic markers correlated with histological features of APAP hepatotoxicity in a time-dependent manner. They accurately reflected the onset and recovery from hepatotoxicity compared to traditional biomarkers and also reported the efficacy of NAC with high sensitivity. ICG clearance kinetics correlated with histological scores for acute liver damage for APAP (i.e. 3h timepoint; r=0.90, P<0.0001) and elevations in both of the mechanistic biomarkers, miR-122 (e.g. 6h timepoint; r=0.70, P=0.005) and HMGB1 (e.g. 6h timepoint; r=0.56, P=0.04).For the first time we report the utility of this non-invasive longitudinal imaging approach to provide direct visualisation of the liver function coupled with mechanistic biomarkers, in the same animal, allowing the investigation of the toxicological and pharmacological aspects of APAP-ILI and hepatic regeneration.

Small-for-Size Syndrome: Bridging the Gap Between Liver Transplantation and Graft Recovery.

In living donor liver transplantation, optimal graft size is estimated from values like graft volume/standard liver volume and graft/recipient body weight ratio but the final functional hepatic mass is influenced by other donor and recipient factors. Grafts with insufficient functional hepatic mass can produce a life-threatening condition with rapidly progressive liver failure called small-for-size syndrome (SFSS). Diagnosis of SFSS requires careful surveillance for signs of inadequate hepatocellular function, residual portal hypertension, and systemic inflammation that suggest rapidly progressive liver failure. Early diagnosis, symptom control, and addressing the cause of SFSS may prevent the need for retransplantation. With increased attention to avoiding donor risk, intensivists will be confronted with more SFSS recipients. In this review, we aim to outline a systematic approach to the medical management of patients with SFSS by providing a concise synopsis of general supportive care-neurological, cardiovascular, and renal support, mechanical ventilation, nutritional support, infection control, and tailored immunosuppression-with an aim to avoid end-organ damage or death and a review of current interventions including liver support devices, portal flow modulating drugs, and other experimental interventions that aim to preserve existing hepatic mass and improve conditions for hepatic regeneration. We examine evidence for SFSS interventions to provide the reader with information that may assist in clinical decision making. Points of controversy in care are purposefully highlighted to identify areas where additional experimental work is still needed. A full understanding of the pathophysiology of SFSS and measures to support liver regeneration will guide effective management.

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Hepatic encephalopathy is a complex neurophysiological syndrome that follows a critical loss of functional hepatic mass. It can be challenging to diagnose and treat.

Drug-induced Liver Disease in Patients with Diabetes Mellitus.

The study presented here was accomplished to assess the course of drug-induced liver diseases in patient’s rheumatoid arthritis receiving long-term methotrexate therapy. Diabetes mellitus was revealed as the most significant risk factor. The combination of diabetes mellitus with other risk factors (female sex) resulted in increased hepatic fibrosis, degree of hepatic encephalopathy and reduction of hepatic functions. The effectiveness and safety of ursodeoxycholic acid and cytolytic type-with S-Adenosyl methionine was also evaluated.Abbreviations13C-MBT: 13C-methacetin breath test; ALT: alanine aminotransferase; AP: alkaline phosphatase; AST: aspartic transaminase; DILD: drug-induced liver disease; DM: diabetes mellitus; HE: hepatic encephalopathy; HFM: hepatic functional mass; SAMe: S-Adenosyl methionine; UDCA: ursodeoxycholic acid.How to cite this articleIryna K, Helen M, Elena S. Drug-induced Liver Disease in Patients with Diabetes Mellitus. Euroasian J Hepato-Gastroenterol 2015;5(2):83-86.

Long-term and short-term effects of hemodialysis on liver function evaluated using the galactose single-point test.

Aim. The galactose single-point (GSP) test assesses functioning liver mass by measuring the galactose concentration in the blood 1 hour after its administration. The purpose of this study was to investigate the impact of hemodialysis (HD) on short-term and long-term liver function by use of GSP test. Methods. Seventy-four patients on maintenance HD (46 males and 28 females, 60.38 ± 11.86 years) with a mean time on HD of 60.77 ± 48.31 months were studied. The GSP values were compared in two groups: (1) before and after single session HD, and (2) after one year of maintenance HD. Results. Among the 74 HD patient, only the post-HD Cr levels and years on dialysis were significantly correlated with GSP values (r = 0.280, P < 0.05 and r = −0.240, P < 0.05, resp.). 14 of 74 patients were selected for GSP evaluation before and after a single HD session, and the hepatic clearance of galactose was similar (pre-HD 410 ± 254 g/mL, post-HD 439 ± 298 g/mL, P = 0.49). GSP values decreased from 420.20 ± 175.26 g/mL to 383.40 ± 153.97 g/mL after 1 year maintenance HD in other 15 patients (mean difference: 19.00 ± 37.66 g/mL, P < 0.05). Conclusions. Patients on maintenance HD for several years may experience improvement of their liver function. However, a single HD session does not affect liver function significantly as assessed by the GSP test. Since the metabolism of galactose is dependent on liver blood flow and hepatic functional mass, further studies are needed.

The utility of uric acid assay in dogs as an indicator of functional hepatic mass

Uric acid was used as a test for liver disease before the advent of enzymology. Three old studies criticised uric acid as a test of liver function. Uric acid, as an end-product of purine metabolism in the liver, deserved re-evaluation as a liver function test. Serum totalbile acids are widely accepted as the most reliable liver function test. This study compared the ability of serum uric acid concentration to assess liver function with that of serum pre-prandial bile acids in dogs. In addition, due to the renal excretion of uric acid the 2 assays were also compared in a renal disease group. Using a control group of healthy dogs, a group of dogs with congenital vascular liver disease, a group of dogs with non-vascular parenchymal liver diseases and a renal disease group, the ability of uric acid and pre-prandial bile acids was compared to detect reduced functional hepatic mass overall and in the vascular or parenchymal liver disease groups separately. Sensitivities, specificities and predictive value parameters were calculated for each test. The medians of uric acid concentration did not differ significantly between any of the groups, whereas pre-prandial bile acids medians were significantly higher in the liver disease groups compared with the normal and renal disease group of dogs. The sensitivity of uric acid in detecting liver disease overall was 65% while the specificity of uric acid in detecting liver disease overall was 59%. The sensitivity and specificity of uric acid in detecting congenital vascular liver disease was 68% and 59%, respectively. The sensitivity and specificity of uric acid in detecting parenchymal liver disease was 63% and 60%, respectively. The overall positive and negative predictive values for uric acid in detecting liver disease were poor and the data in this study indicated uric acid to be an unreliable test of liver function. In dogs suffering from renal compromise serum uric acid concentrations may increase into the abnormal range due to its renal route of excretion.

13C-methacetin Breath Test Shortened: 2-point-measurements After 15 Minutes Reliably Indicate the Presence of Liver Cirrhosis

The 13C-methacetin breath test (MBT) measures the activity of the cytochrome P450 dependent enzyme system and has been developed to assess the functional hepatic mass. We evaluated simple modifications of the 13C-MBT to further increase its practicability and therefore clinical acceptance. One hundred and four patients with different chronic liver diseases (including 35 patients with histologically proven cirrhosis) and 65 healthy controls underwent the 13C-MBT. Breath test results of 2-point measurements were compared with conventional breath test results (cumulative recovery after 30 min) and liver histology. The 2-point-measurement at 0 and 15 minutes (with a cut-off <14.6 per thousand delta over baseline) had 92.6% sensitivity and 94.1% specificity in identifying the presence of cirrhosis compared with liver histology. The 2-point-measurements at 5 and 10 minutes also provided good discrimination between cirrhotic and noncirrhotic patients. The 13C-MBT using 2-point-measurement of breath samples at baseline and after 15 minutes reliably indicates decreased liver function in liver cirrhosis. This simplification of the 13C-MBT will increase practicability and cost efficiency, thus facilitating its clinical acceptability.

Morphological Regeneration and Hepatic Functional Mass after Right Hemihepatectomy

Background/Aims: Liver has a remarkable ability to regenerate after major resection. However, little is known about the process of morphological regeneration and hepatic functional recovery in human. Methods: Sixteen donors who underwent right hemihepatectomy were enrolled in this prospective clinical study. The preoperative liver volume and remnant liver volume on postoperative days 5, 12 and 28 were calculated from serial transverse computed tomography images. Liver function was evaluated by measuring the intrinsic clearance of antipyrine before and on postoperative days 5 and 12 days, as well as the biochemical and coagulation assay. Results: A smaller residual liver tended to regenerate faster in 28 days. Operative factors, including intraoperative blood loss, inflow occlusion time, liver transection time and duration of operation were not significantly correlated with postoperative liver regeneration. The intrinsic clearances of antipyrine on postoperative days 5 and 12 days were significantly reduced compared to the respective values before the operation (p < 0.001 and p < 0.05, respectively). On the contrary, the intrinsic clearance values per unit liver volume significantly increased on postoperative 12 days (p < 0.05). Conclusion: The microsomal function of individual hepatocytes may be upregulated after right liver resection perhaps in order to compensate for the reduced functional mass of the liver.

Age-related changes in liver, gall bladder and pancreas

The suggestion from post-mortem studies that there is an age-related fall in liver weight has been confirmed by in vivo studies, employing ultrasound or CT scanning. These demonstrate an estimated 28% lower volume in individuals above the age of 65 compared with those under 40 years of age. The functional significance of the fall in liver size with age is confirmed by the highly significant correlation between age, liver volume estimated by ultrasound and galactose elimination, the clearance of which is determined by functional hepatic mass this fall in mass of functional hepatocytes is also illustrated by an age-related reduction in binding of radiolabelled galactosyl-albumin. Liver blood flow, estimated by pulsed echo-doppler, or functional hepatic flow measured by the hepatic clearance of D-sorbitol or indocyanine green, falls significantly with aging, with around a 33% fall between youth and old age., The thickening of the sinusoidal endothelial lining with collagen, and fall in endothelial cell fenestrations, noted with increasing age in human liver, is likely to impair blood flow through liver sinusoids and hepatic perfusion, and reduce oxygen-dependent hepatocyte function, such as uptake of macromolecules. This may contribute to the link between the aging process and disease susceptibility.

Teste respiratório da 13C-metacetina na doença hepática crônica pelo vírus C

RACIONAL: O teste respiratório da metacetina marcada com carbono 13 (13C-metacetina) é método não-invasivo que permite examinar a função hepática microssomal, permitindo avaliação quantitativa da massa hepática funcional. OBJETIVO: Avaliar a utilidade clinica do teste respiratório da 13C-metacetina na avaliação de pacientes com doença crônica do fígado pelo vírus da hepatite C. CASUÍSTICA E MÉTODOS: Setenta e oito pacientes com hepatite crônica C e 13 indivíduos saudáveis pareados por sexo e idade foram estudados. Pacientes infectados cronicamente pelo vírus C foram classificados como portadores de hepatite crônica (n = 51) ou cirrose hepática (n = 27, sendo 7 deles classificados como descompensados pela presença de ascite, icterícia e/ou encefalopatia). Pacientes co-infectados HbsAg/HIV, em uso crônico de álcool, com outras doenças crônicas ou em uso de medicamentos que pudessem interferir com a atividade do citocromo P450, foram excluídos. O estádio e a atividade da doença nos fragmentos de biopsia foram determinados de acordo com os critérios da Sociedade Brasileira de Hepatologia. O teste respiratório da 13C-metacetina foi realizado com 75 mg de 13C-metacetina e a concentração de 13CO2 no ar expirado foi medido através de espectrometria infravermelha não dispersiva. Foram calculados o "delta over baseline" e o percentual de recuperação cumulativo do 13CO2 aos 40 (teste respiratório da 13C-metacetina 40 min) e aos 120 minutos (teste respiratório da 13C-metacetina 120 min). RESULTADOS: Os parâmetros do teste respiratório da 13C-metacetina se correlacionaram com avaliação estrutural histológica, mas não com a atividade necroinflamatória no tecido hepático, sendo que a melhor correlação foi obtida entre o grau de estádio e o teste respiratório da 13C-metacetina 120 min. Os valores médios do teste respiratório da 13C-metacetina 120 min foram significantemente mais reduzidos nos grupos cirróticos (19,2 ± 7,1% para cirróticos compensados e 14,7 ± 4,0% para os cirróticos descompensados) que nos grupos controle (29,9 ± 4,5%) e com hepatite crônica (27,8 ± 6,1%). A melhor acurácia no diagnóstico de cirrose entre os portadores de hepatite crônica C foi encontrada para o teste respiratório da 13C-metacetina 120 min com 81% de sensibilidade e 77% de especificidade. CONCLUSÃO: O teste respiratório da 13C-metacetina se correlaciona com alterações estruturais encontradas na hepatite crônica pelo vírus C e o percentual de recuperação de 13CO2 aos 120 minutos é um sensível parâmetro para identificar a presença de cirrose nesses pacientes.

Factors Affecting the Quantitative Liver?Spleen Scan in Normal Individuals

The quantitative liver-spleen scan (QLSS) can estimate the functional hepatic mass and the organ volumes by precise measurement of sulfur colloid (SC) distribution. The normal range determined in prior studies was estimated from patients with absence of chronic liver disease in which intense fasting appeared to produce slightly abnormal values. This study was to determine the effect of fasting or fed status and colloid particle size on quantitative measurements from the QLSS in a small cohort of normal individuals. Twelve persons without any medical problems had QLSS taken twice, 2 weeks apart, one fasting and one postprandial. Patients were scanned after injection of 5-6 mCi of SC; six patients were given solution A (5- to 12-microm particle size) and six patients solution B (2- to 12-microm particle size). SPECT and planar analysis were performed. SC distribution of total counts between the liver and the spleen {[L/(L + S)]t ratio}, liver-spleen index (LSI), and liver-bone marrow index (LBI) were calculated. The perfused hepatic mass (PHM) is the average of the LSI and LBI. Spleen and liver volumes are expressed as milliliters per pound ideal body weight (IBW). Results showed that the liver and spleen volumes (solution B postprandial, 9.27 +/- 2.48 and 1.47 +/- 0.57 ml/lb IBW, respectively) and LBI were not affected by the type of SC solution or by ingestion status. L/(L + S) total and pixel count ratios were significantly higher for solution B and postprandial studies. [L/(L + S)]t, LSI, and PHM increased significantly (P < 0.05) from fasting to postprandial for solution A (0.71 +/- 0.13 vs 0.79 +/- 0.08, 80 +/- 14 vs 91 +/- 8, and 102 +/- 10 vs 106 +/- 8, respectively) and for solution B (0.81 +/- 0.05 vs 0.90 +/- 0.02, 86 +/- 4 vs 95 +/- 3, and 101 +/- 5 vs 110 +/- 3). Neither fasting nor postprandial LSI and PHM were significantly different between solution A and solution B. We conclude the following. (1) The QLSS functional indices in "true" normal patients fall within the previously reported normal range. (2) Calculated liver and spleen volumes are not altered by fasting or sulfur colloid particle size. (3) Fasting significantly decreased the [L/(L + S)]t, LSI, and PHM. (4) A postprandial scan may be preferable since the normal values for [L/(L + S)]t, LSI, and PHM are greater, with a narrower range, than fasting values.

Measurement of hepatic functional mass by means of 13C-methacetin and 13C-phenylalanine breath tests in chronic liver disease: Comparison with Child-Pugh score and serum bile acid levels

To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels. One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated. Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test. Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.

Effect of aging on liver functions—an experimental study in a perfused rat liver model

Background. Aging is associated with marked changes in the physiology of many organs. Aging of the liver has been little studied and findings are inconclusive. The purpose of this work was to determine the effect of aging on transport and metabolic functions of the liver as assessed by extraction ratio of indocyanine green (ICG) and urea flux respectively. Bile flow was also recorded. As ICG is removed exclusively by the liver without bioconversion, its clearance reflects hepatic functional mass. Methods. Livers from adult (3-month old) or old (24-month old) rats were perfused in a recirculating system for 90 min. At time 30 min, a bolus of 0.125 mg of indocyanine green was introduced in the perfusion buffer. At least every 10 minutes, the perfusion buffer was sampled for the measurements of ICG and urea. Bile flow was closely monitored throughout the experiment. Results. Extraction ratio of ICG was increased in livers from old rats (9.49±2.84 vs 3.70±1.56% of ICG extracted), whereas urea flux was diminished (0.33±0.06 vs 1.33±0.65 μmol/min/% of ICG extracted) and bile flow was unchanged (4.03±1.02 vs 3.57±1.34 μl/min). Conclusions. Aging does not affect the different functions of the liver in the same way. It increases hepatocellular uptake function, but decreases the metabolic function of hepatocytes and does not change excretion function. These discrepancies are likely to be of some importance in the study of drug metabolism and action, and so we suggest that results should be corrected for ICG extraction.

Relationship between thrombopoietin serum levels and liver function in patients with chronic liver disease related to hepatitis C virus infection

Objectives Thrombopoietin (Tpo) is an important regulator of megakaryocyte maturation and platelet production, and is mainly produced by the liver. A decrease in Tpo production is partly responsible for the thrombocytopenia observed in patients with chronic liver disease (CLD). The aim of this study was to evaluate the relationship between Tpo serum levels and liver function in patients with CLD related to hepatitis C virus (HCV) infection. Methods We studied 37 patients with various degrees of HCV-related CLD. Of the patients, 17 had chronic hepatitis and 20 liver cirrhosis. Liver function was evaluated in all patients by the following hepatic blood flow dependent and independent tests that explore various hepatic metabolic functions: carbon-13 ( 13C)–aminopyrine breath test ( 13C-ABT), 13C-galactose breath test ( 13C-GBT), and monoethylglycinexylidide (MEGX) test. Liver function tests results were correlated with Tpo serum levels. Results Tpo serum levels were significantly lower in patients with liver cirrhosis (88 ± 23 pg/ml) as compared to those in patients with chronic hepatitis (128 ± 55 pg/ml, p = 0.0031). However, they did not correlate with serum albumin, bilirubin, or prothrombin activity. Tpo serum levels showed a significant positive correlation with 13C-ABT results (hourly dose at 30 min, r s = 0.489, p = 0.002; cumulative dose at 120 min, r s = 0.425, p = 0.008). Moreover, they showed a fair, positive correlation with 13C-GBT hourly dose at 30 min ( r s = 0.366, p = 0.028), and a trend toward a positive correlation with the various MEGX test sampling times (MEGX 15, r s = 0.314, p = 0.059; MEGX 30, r s = 0.284, p = 0.088; and MEGX 60, r s = 0.320, p = 0.059). Conclusions In this study we have shown that a progressive decline in liver function in patients with HCV-related CLD is paralleled by a decrease in Tpo production. The different correlations observed between Tpo and the various liver function tests suggests that this finding is mainly the result of a decrease in hepatic functional mass rather than dependent on alteration in splanchnic hemodynamic.

Impairment of cytochrome P-450-dependent liver activity in cirrhotic patients with Helicobacter pylori infection.

Helicobacter pylori gastric infection has been associated with various digestive and extra-digestive diseases. The systemic influence of gastric H. pylori infection seems to be mediated by the release of various cytokines. In liver disease, bacterial infections have been associated with the impairment of liver metabolic function. To evaluate the influence of H. pylori infection on liver function as assessed by means of the monoethylglycinexylidide test, which depends upon liver blood flow and cytochrome P-450 activity, and the 13C-galactose breath test, which depends on cytosolic enzymatic activity and is correlated with hepatic functional mass. Moreover, to evaluate whether H. pylori-associated modifications of liver function may be related to tumour necrosis factor-alpha serum levels. Thirty-five patients with liver cirrhosis of various aetiologies, who underwent monoethylglycinexylidide and 13C-galactose breath tests, were retrospectively evaluated for H. pylori infection by means of anti-H. pylori immunoglobulin G. The main clinical, biochemical and functional characteristics of the patients as well as their tumour necrosis factor-alpha serum levels were then analysed on the basis of the presence of H. pylori infection. Twenty-one patients tested positive for H. pylori infection (60%), and 11 tested negative (31.4%). No clinical or biochemical differences were observed between H. pylori-infected and non-infected patients. H. pylori infection showed no difference in distribution according to Child-Pugh classes (A, 55%; B and C, 67%). The monoethylglycinexylidide test results were significantly lower at each sampling time in H. pylori-positive patients compared to H. pylori-negative patients (MEGX15, P=0.027; MEGX30, P=0.014; MEGX60, P=0.028), while 13C-galactose breath test showed no significant differences considering both cumulative percentage dose and percentage dose/h. The median tumour necrosis factor-alpha serum levels were no different between H. pylori-positive (16.1 pg/mL, 95% confidence interval, 8.7-28.7) and H. pylori-negative (12.3 pg/mL, 95% confidence interval, 8.7-23.4) patients. In cirrhotic patients, H. pylori infection seems to selectively affect cytochrome P-450 liver activity, while hepatic functional mass does not seem to be impaired. Tumour necrosis factor-alpha does not seem to be the mediator of this impairment. Further studies are needed to evaluate the impact of H. pylori eradication on parameters of liver function.

Functional hepatic mass variation in patients with chronic HCV hepatitis and small hepatocellular carcinoma tretated with interstitial laser photocoagulation

Functional hepatic mass variation in patients with chronic HCV hepatitis and small hepatocellular carcinoma tretated with interstitial laser photocoagulation

Impairment of metabolic function in chronic hepatitis C is related to factors associated with resistance to therapy.

Liver disease causes a loss of hepatic function, and remission is associated with improved functional hepatic mass. The object of the present study was to investigate whether liver metabolic function assessed by antipyrine clearance is related to other disease characteristics influencing response to therapy in chronic hepatitis C. Patients (n = 96) received three different treatment regimens: one group received interferon alfa-2b for 48 wk; in a second group with maintained positive hepatitis C virus (HCV) RNA after 12 wk, interferon was combined for 36 wk with oral ribavirin; and patients who were relapsers or nonresponders to a previous therapy with interferon alone received interferon alfa-2b plus ribavirin for 48 wk. Twenty-five patients (26%) showed sustained normalization of ALT levels and negative HCV RNA 6 months after therapy. The response was more likely to be sustained in patients with a genotype other than 1 (52.0% vs 15.5% in patients with genotype 1, p < 0.001), and the percentage of sustained responders was higher among patients who demonstrated negativity of HCV RNA at the end of 4 wk of treatment (64% vs 13% without negativity, p < 0.001). Sustained response was associated with significantly lower baseline serum ferritin (-46%, p < 0.01) and duration of infection (-33%, p < 0.01). Baseline antipyrine clearance was higher in sustained responders than in nonresponders (+19%, p < 0.05) and lower in genotype 1 patients than in those with a genotype other than 1 (-24%, p < 0.05). Antipyrine clearance increased by 12% at the end of the 48-wk course of treatment among sustained responders (+34% vs nonresponders, p < 0.001) and still remained elevated at the end of the follow-up (+35% vs nonresponders, p < 0.001). In summary, the present study shows that liver oxidative metabolism is related to antiviral response rates and suggests that much of the effect is explained by viral genotype.

Impairment of metabolic function in chronic hepatitis C is related to factors associated with resistance to therapy

OBJECTIVE: Liver disease causes a loss of hepatic function, and remission is associated with improved functional hepatic mass. The object of the present study was to investigate whether liver metabolic function assessed by antipyrine clearance is related to other disease characteristics influencing response to therapy in chronic hepatitis C. METHODS: Patients (n = 96) received three different treatment regimens: one group received interferon alfa-2b for 48 wk; in a second group with maintained positive hepatitis C virus (HCV) RNA after 12 wk, interferon was combined for 36 wk with oral ribavirin; and patients who were relapsers or nonresponders to a previous therapy with interferon alone received interferon alfa-2b plus ribavirin for 48 wk. RESULTS: Twenty-five patients (26%) showed sustained normalization of ALT levels and negative HCV RNA 6 months after therapy. The response was more likely to be sustained in patients with a genotype other than 1 (52.0% vs 15.5% in patients with genotype 1, p < 0.001), and the percentage of sustained responders was higher among patients who demonstrated negativity of HCV RNA at the end of 4 wk of treatment (64% vs 13% without negativity, p < 0.001). Sustained response was associated with significantly lower baseline serum ferritin (−46%, p < 0.01) and duration of infection (−33%, p < 0.01). Baseline antipyrine clearance was higher in sustained responders than in nonresponders (+19%, p < 0.05) and lower in genotype 1 patients than in those with a genotype other than 1 (−24%, p < 0.05). Antipyrine clearance increased by 12% at the end of the 48-wk course of treatment among sustained responders (+34% vs nonresponders, p < 0.001) and still remained elevated at the end of the follow-up (+35% vs nonresponders, p < 0.001). CONCLUSION: In summary, the present study shows that liver oxidative metabolism is related to antiviral response rates and suggests that much of the effect is explained by viral genotype.

Assessment of Liver Function in Galahs (Eolophus roseicapillus) After Partial Hepatectomy: A Comparison of Plasma Enzyme Concentrations, Serum Bile Acid Levels, and Galactose Clearance Tests

The relative sensitivity of conventional assays of liver function was evaluated in com- parison with galactose clearance, a test of liver function used in humans since the 1960s. Results of galactose clearance tests were compared with plasma enzyme concentrations and serum bile acid levels in clinically normal galahs (Eolophus roseicapillus; n = 8), after celiotomy (n = 4), and after 6% or 18% hepatectomy (n = 8, respectively). Clearance tests and biochemical analyses were performed within 2-4 hours of surgery and at 4 and 7 days after surgery. Celiotomy and 6% and 18% hepatectomy resulted in changes in alkaline phosphatase, aspartate aminotransferase, and al- anine aminotransferase concentrations that were consistent with muscle trauma. Celiotomy and 6% hepatectomy did not significantly alter the results of galactose clearance tests; however, 18% hep- atectomy resulted in significant reduction in galactose clearance and galactose clearance as a func- tion of body surface area (GEC-SA). Galactose single-point concentrations were not significantly elevated at any time during the experiments; however, single-point concentrations were strongly correlated with galactose clearance and GEC-SA values, especially at 80 minutes after galactose injection. Serum bile acid levels were not significantly elevated after celiotomy or partial hepatec- tomy. Measurement of galactose single-point concentrations has the potential to be a simple, sen- sitive method of screening for reduced hepatic function in birds. Galactose clearance and GEC-SA have the potential to be sensitive assays of hepatic functional mass, for use as a noninvasive method of monitoring hepatic function.