Patients Underwent Liver Biopsy Research Articles

Non‐invasive assessment of liver fibrosis by stiffness measurement in patients with chronic hepatitis B

The need for new non-invasive tools to assess liver fibrosis in chronic liver diseases has been largely advocated. Liver stiffness measurement (LSM) using transient elastography (FibroScan), Echosens) has been shown to be correlated to liver fibrosis in various chronic liver diseases. This study aims to assess its diagnosis accuracy in patients with chronic hepatitis B. We prospectively enrolled 202 patients with chronic hepatitis B in a multicentre study. Patients underwent liver biopsy (LB) and LSM. METAVIR and Ishak liver fibrosis stages were assessed by two pathologists. LSM or LB was considered unreliable in 29 patients. Statistical analysis was conducted in 173 patients. LSM was significantly (P<0.001) correlated with METAVIR (r=0.65) and Ishak fibrosis stage (0.65). The area under receiver-operating characteristic curves were 0.81 (95% confidence intervals, 0.73-0.86) for F>/=2, 0.93 (0.88-0.96) for F>/=3 and 0.93 (0.82-0.98) for F=4. Optimal LSM cut-off values were 7.2 and 11.0 kPa for F>/=2 and F=4, respectively, by maximizing the sum D of sensitivity and specificity, and 7.2 and 18.2 kPa by maximizing the diagnosis accuracy. In conclusion, LSM appears to be reliable for detection of significant fibrosis or cirrhosis in HBV patients and cut-off values are only slightly different from those observed in HCV patients.

Incidence of hepatocellular carcinoma in hepatitis C carriers with normal alanine aminotransferase levels

This study sought to identify the independent risk factors involved in the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection who have normal alanine aminotransferase (ALT) levels. A total of 519 patients with average ALT integration values less than or equal to 40 IU/L over 10 years were included. Baseline ultrasound was done in all patients and 68 patients underwent liver biopsy at the start of this study. Factors associated with the cumulative incidence of HCC were determined. HCC occurred in 48 of 519 patients (9.2%). The following factors were significantly associated with the incidence of HCC: age>65 years (adjusted hazard ratio: 2.006 [95% confidence interval: 1.078-3.733]), ALT>20 IU/L (6.242 [1.499-25.987]), platelet count<15.0x10(4)/m(3) (2.675 [1.407-5.085]), total bilirubin>1.2mg/dL (2.798 [1.257-6.228]), ALP>338 IU/L (2.486 [1.327-4.657]), and total albumin<3.5g/dl (2.707 [1.177-6.223]). The 5- and 10-year cumulative incidences of HCC were 4.4% and 26.5% in patients with ALT>20 IU/L and platelet count<15.0x10(4)/m(3), respectively. High ALT level and low platelet count are closely associated with the development of hepatocarcinogenesis. Therefore, individuals within this group are candidates for antiviral therapy.

Alanine aminotransferase‐based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B

The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.

Clinical trial: pilot study of metformin for the treatment of non‐alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH. To assess the effects of metformin on insulin sensitivity, body composition, serum alanine aminotransferase (ALT) levels and liver histology in patients with NASH. Patients underwent liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint was a three-point improvement in the histological NASH activity index. Of 28 patients enrolled, 26 (13 females; average age 44 years) completed 48 weeks of treatment and underwent repeat metabolic studies, imaging and liver biopsy. Thirty per cent achieved a histological response. Most patients lost weight, the average being 6 kg. There was a marked association between weight loss and improvements in NASH activity index and ALT levels (both, P < 0.01). Insulin sensitivity also improved, but the degree of change did not correlate with histological improvement. Metformin leads to improvements in liver histology and ALT levels in 30% of patients with NASH, probably by its effects in causing weight loss.

HCV Treatment with Pegylated Interferon and Ribavirin in Patients with Haemophilia and HIV/HCV Coinfection: A Retrospective Review

Background: Adult patients with haemophilia are frequently coinfected with HIV and HCV, usually due to blood and plasma factor transfusion prior to effective screening programs. The current standard therapy for HCV is pegylated interferon and ribavirin (PEG+RBV), which has been investigated in HCVmonoinfection and HIV/HCV coinfection. Little data exists regarding the effectiveness of HCV therapy in coinfected patients with haemophilia. We reviewed HCV treatment outcomes in our cohort of patients with haemophilia and HIV/HCV coinfection. Methods: We performed a retrospective review of all patients with haemophilia and HIV/HCV co-infection treated with PEG+RBV at the Alfred Hospital between 2001—2007 (n = 13). Patient histories and medical records were reviewed for demographics, adverse events and effectiveness, including early, end of treatment and sustained virological response (EVR, EOTR and SVR, defined as undetectable HCV viral load/PCR at 12, 48 and 72 weeks respectively) of HCV Results: All patients were male with haemophilia A, and a median age of 43 (range 27—62) at initiation of HCV therapy. Nine of thirteen (69%) patients had genotype (gt1) 1 HCV (gt3 = 3, gt4 = 1). Due to bleeding tendencies, only 1/13 patients underwent liver biopsy prior to HCV therapy. Twelve of 13 (92%) were receiving ART, with a mean CD4 count of 428 cells/uL (range 175—928 cells/ L) at initiation of HCV therapy. Six of 11 (55%) patients achieved EVR (3× gt1, 2× gt3) at 12 weeks, 4/13 (31%) had EOTR (2× gt1, 2× gt3) and 1/13 (8%) achieved SVR (gt1). 7/11 (64%) patients normalised ALT during therapy wherein mean ALT fell from 101 to 76U/L. Only 1/13 (8%) patients prematurely stopped therapy prematurely due to side effects. CD4 cell counts and HIV viral load remained stable during HCV treatment, with a mean 437 cells/uL and <50 copies/mL at 48 weeks, respectively Conclusions: Treatment responses in patients with haemophilia and HIV/HCV coinfection were significantly lower from that reported in other coinfected populations. This is despite a low drop out rate and suggests that haemophilia is an independent risk factor for poor treatment response. Risk factors in this cohort for poor response may include long duration of coinfection, advanced liver disease and unfavourable genotype profile. Prospective studies in this patient population are needed to further evaluate HCV treatment efficacy.

Hepcidin Suppression Relative to Iron Status in Patients with Chronic Hepatitis C.

Patients with chronic hepatitis C (CHC) often have increased liver iron deposits, a condition associated with reduced sustained response to antiviral therapy, more rapid progression to cirrhosis, and development of hepatocellular carcinoma. The hepatic hormone hepcidin is a major regulator of iron metabolism that inhibits iron absorption and recycling from erythrophagocytosis. Hepcidin decrease is a possible pathophysiological mechanism of iron overload in CHC, but studies in humans have been hampered so far by the lack of reliable quantitative assays for the 25-amino acid bioactive peptide in serum (s-hepcidin). Using a recently validated immunoassay (Ganz T, Blood 2008, epub Aug 8), we measured s-hepcidin levels in 82 CHC naïve patients and 57 sex-matched healthy controls with rigorous definition of normal iron status. All CHC patients underwent liver biopsy with histological iron score (according to Deugnier YM, Gastroenterology 1992). S-hepcidin was much lower in CHC than in controls (geometric means with 95% CIs: 33.7, 21.5–52.9 versus 90.9, 76.1–108.4 ng/ml, respectively; P<0.001), while both serum ferritin and transferrin saturation were significantly higher in CHC than in controls, as expected. S-hepcidin strongly correlated with serum ferritin in both controls (r=0.741; P<0.001) and CHC patients (r = 0.718; P<0.001). In CHC patients, s-hepcidin also correlated with histological total iron score (r = 0.46; P<0.001), but not with serum interleukin-6 (r = −0.042; P = n.s.). After stratification for serum ferritin quartiles, s-hepcidin levels increased significantly across quartiles in both controls and CHC patients (chi for trend, P<0.001). However, in the latter group s-hepcidin levels were significantly lower than in controls for each corresponding quartile (ANOVA, P<0.001). In the lowest ferritin quartile, s-hepcidin was significantly inversely correlated with viral loading (e.g. serum HCV-RNA IU/ml; r = −0.526; P=0.036), while this association gradually disappeared with increasing ferritin quartiles. These results, together with very recent studies in animal and cellular models (Nishina S, Gastroenterology 2008; Miura K, Hepatology 2008), indicate that though hepcidin regulation by iron stores is maintained in CHC, the suppression of this hormone by HCV is likely an important factor in liver iron accumulation in this condition.

Increased Soluble Fas and Fas Ligand Levels in Patients with Nonalcoholic Steatohepatitis

Purpose: To test the association of death receptor proteins soluble FAS (sFAS) and soluble FAS Ligand (sFASL) with nonalcoholic steatohepatitis (NASH) independent of known confounders and their correlation with disease severity and insulin resistance. Methods: Plasma sFAS and sFASL were measured using a sandwich ELISA based immunoassay in 70 patients undergoing liver biopsy with clinical suspicion of NAFLD. Histology was assessed in a blinded manner and the NAFLD activity score was calculated for each sample. In parallel sFAS and FASL levels were measured in patients with Hepatitis C (validation set) and the levels in hepatitis C patients were compared with sFAS and sFASL levels in NASH patients. Results: Of the 70 study subjects,37 patients had NASH, 20 had steatosis and 13 normal liver biopsy. Mean age was 49 (±11) years, 45.7% were male and 84% Caucasians. The mean body mass index (BMI) was 31.7 (±4.9) kg/m2 and the median triglycerides and HOMA index were 158 (94–210) mg/dL and 3 (1–7.4) respectively. Patients with NASH had significantly higher levels of both sFAS and sFASL than patients with steatosis and normal liver biopsy (Table 1). NASH patients had significantly higher level of sFASL than Hepatitis C patients (Table 1). sFAS and sFASL showed strong positive correlation with degree of fibrosis (r = 0.499 and 0.315, P < .001 and P= .008 respectively). Positive correlation was also seen between sFAS and HOMA (r = 0.336, P= .007). On multivariate analyses, a 10 pg/ml increase in sFASL increased the odds of having NASH by 60% 1.6 (1.04–2.5, P= 0.034); a 1 ng/ml increase in sFAS levels increased the odds by 40% 1.4 (1.2–1.6, P= 0.003) and a 10 IU/L increase in liver enzymes showed only a 20% increase in the odds of having NASH 1.2 (1.00–1.4, P= 0.093) (Table 2).Table 2: Prognostic value of sFAS and sFASL in prediction of NASHTable 1: sFAS and sFASL levels are highest in patients with NASHConclusion: The data implicates a significant role for sFAS/sFASL interaction in NAFLD progression. This concept merits further investigation as a potential diagnostic and therapeutic strategy.

Magnetic Resonance Elastography for the Noninvasive Staging of Liver Fibrosis

The purpose of our study was to prospectively compare the success rate and diagnostic accuracy of magnetic resonance elastography, ultrasound elastography, and aspartate aminotransferase to platelets ratio index (APRI) measurements for the noninvasive staging of fibrosis in patients with chronic liver disease. We performed a prospective blind comparison of magnetic resonance elastography, ultrasound elastography, and APRI in a consecutive series of patients who underwent liver biopsy for chronic liver disease in a university-based hospital. Histopathologic staging of liver fibrosis according to the METAVIR scoring system served as the reference. A total of 141 patients were assessed. The technical success rate of magnetic resonance elastography was higher than that of ultrasound elastography (133/141 [94%] vs 118/141 [84%]; P = .016). Magnetic and ultrasound elastography, APRI measurements, and histopathologic analysis of liver biopsy specimens were technically successful in 96 patients. The areas under the receiver operating characteristic curves of magnetic resonance elasticity (0.994 for F >or= 2; 0.985 for F >or= 3; 0.998 for F = 4) were larger (P < .05) than those of ultrasound elasticity, APRI, and the combination of ultrasound elasticity and APRI (0.837, 0.709, and 0.849 for F >or= 2; 0.906, 0.816, and 0.936 for F >or= 3; 0.930, 0.820, and 0.944 for F = 4, respectively). Magnetic resonance elastography has a higher technical success rate than ultrasound elastography and a better diagnostic accuracy than ultrasound elastography and APRI for staging liver fibrosis.

M1770 Serum Retinol-Binding Protein 4 (RBP4) Levels in Patients with Nonalcoholic Fatty Liver Disease

Introduction: Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome. Nonalcoholic steatohepatitis (NASH) is the most severe form. Insulin resistance (IR) is the pathophysiological hallmark of NAFLD. Recent data assigned RBP4 a key role in the pathogenesis of IR. Hepatocytes are the primary source of circulating RBP4 and adipose tissue has the second highest expression level. Changes in adipocyte derived RBP4 can have systemic effects on insulin sensitivity. Liver function may have a major impact on RBP4 levels. The aims of this study were to determine RBP4 levels in patients with biopsy proven NAFLD, and correlate these levels with histological features andmetabolic phenotypes.Methods: Our cohort consisted of consecutive patients undergoing liver biopsy for clinical suspicion of NAFLD. Patients were subsequently divided into 3 groups according to their histological findings: fatty liver (n=16), borderline NASH (n=2) and NASH (n=33). The stage of fibrosis was measured using a 4-point scale. Only 2 patients showed borderline NASH and were excluded as no comparisons could be made. A total of 49 patients with NAFLD were used for the final statistical analysis. RBP4 was measured in triplicates by an ELISA (ALPCO Diagnostics) in blood samples obtained from patients at the time of biopsy. Demographic, clinical, and laboratory data were collected. Fasting labs included insulin, glucose, and lipid profile. The degree of IR was determined by HOMA. Results: Patient age (49.0 +/11.0) and sex (51.1 % males) did not differ significantly between the groups, whereas BMI and HOMA were higher in NASH patients compared with fatty liver patients. Serum RBP4 levels did not significantly correlate to BMI, HOMA, fasting glucose, or insulin levels. Moreover, RBP4 levels were lower in patients with NASH compared to those with fatty liver (21.4 mg/L and 27.1 mg/L respectively) although the difference did not reach statistical significance. A stepwise decrease in RBP4 levels from patients without fibrosis (26.0 mg/L) to patients with cirrhosis (14.1 mg/L) was noted (p value=0.03) Conclusions: Our study demonstrated that RBP4 levels were not elevated in NAFLD patients despite the presence of IR (higher HOMA). RBP4 levels were lower in NASH patients compared to fatty liver patients. More importantly an inverse correlation was found between the stage of fibrosis and RBP4 levels. Our findings suggest that liver injury due to NASH may result in decreased levels of RBP4. Lower RBP4 levels in obese patients with IR could potentially be used as a screening tool to identify patients at higher risk for developing NASH.

Gray and Color Doppler Ultrasonography in Differentiation Between Chronic Viral Hepatitis and Compensated Early Stage Cirrhosis

To assess the value of Gray scale (GS) and Colour Doppler Ultrasonography (CDU) in differentiating the progression of chronic viral hepatitis (CVH) and compensated liver cirrhosis (CIR).Seventy-two patients and 32 normal individuals used as controls were studied. Forty-four patients suffered from CVH and 28 from CIR. All patients underwent liver biopsy. Multiple qualitative and quantitative variables were studied with GS and CDU in the Liver, Portal Vein (PV), Hepatic Artery (HA) and spleen. On the basis of the obtained Doppler data several known indexes were calculated. Alternative indexes [PV diameter (D)/time average maximum velocity (Vmax), PV diameter/time average mean velocity (VTAM), HA/PV VTAM ratio] derived from them were calculated.ROC analysis showed that PV Congestion Index, PV D/VTAM and HA/PV VTAM indexes had the best sensitivity and specificity in discriminating CVH from CIR. Stepwise discriminant analysis selected as significant predictors 3 qualitative and 4 quantitative variables that correctly classify 88.9% of the original grouped cases. In CVH patients that underwent biopsy we found statistically significant changes in those at fibrotic stage 5 compared to fibrotic stages 1-4.We found significant differences in haemodynamic parameters and indexes for CVH patients at fibrosis stage 5 compared to all other stages. Simple GS and CDU parameters may discriminate CVH from CIR. The alternative Doppler indexes suggested that accurate differentiation between CVH and CIR is possible. These indexes could be useful for monitoring CVH and avoiding unnecessary biopsies.

Noninvasive means of diagnosing liver fibrosis in hepatitis C

Liver biopsy is still considered the gold standard for staging fibrosis in chronic liver diseases. However, liver biopsy is an invasive procedure, and complications occur in 0.6%-5% of patients [1,2]. In addition, to perform the procedure there is a need for additional resources such as ultrasonography. Therefore, as a rule, patients undergoing liver biopsy are hospitalized for at least 6 hours [3]. Recent studies involving patients with chronic hepatitis C showed that fragments of technically inadequate hepatic tissue frequently lead to the underestimation of the stage of liver fibrosis [4]. That rate of diagnostic error can vary from 10%-30% depending on the study [5]. In addition, in developed countries, there is greater patient resistance to undergoing biopsy. In Brazil, there is an additional factor, which is that patients are obligated to submit to liver biopsy for indication of treatment, except in clinically confirmed cases of hepatic cirrhosis according to the Ministry of Health guidelines. For all of these reasons, an increasing number of studies are being conducted in order to evaluate the effectiveness of noninvasive markers for staging liver fibrosis. The noninvasive methods used in the largest number of published studies are the calculation of two indices the aspartate aminotransferase (AST) to platelet ratio index (APRI) and the FibroTest index and the FibroScan test. The effectiveness of the various methods evaluated in various studies revealed quite heterogeneous results. The APRI method and the Forns index are unable to stage a large percentage of patients, and their accuracies do not exceed 80%-85%. Therefore, a considerable number of patients are required to undergo liver biopsy. Otherwise, approximately 20% would be incorrectly diagnosed. The efficacy of those methods encounters difficulty regarding standardization and the definition of cut-off values for each degree of fibrosis.

Evaluation of hepatic steatosis by ultrasound in patients with chronic hepatitis C virus infection

Objective: To compare two alternative ultrasound parameters, hepatic vein flow (HVF) pattern and presence of focal hypoechoic areas (FHA) within the liver hilus, as non-invasive predictors of liver steatosis in patients with chronic hepatitis C virus (HCV) infection. Design: In 122 consecutive patients with chronic HCV infection, the HVF pattern and presence of FHA within the liver hilus were assessed by Duplex–Doppler and B-mode sonography. All patients underwent liver biopsy and the sonographic results were compared with a histological score of steatosis used as the gold standard for this purpose. Association of fatty infiltrations with clinical and sonographic features were evaluated by a stepwise logistic regression analysis. Results: Reduced HVF and FHA, but not standard clinical and laboratory parameters, strongly correlated with steatosis on histology (P<0.001). Both sonographic parameters made excellent predictions for the subgroup of patients with severe steatosis, particularly when both tests were combined [sensitivity (SE) 95%, specificity (SP) 96%, positive predictive value (pPV) 93%, negative predictive value (nPV) 97%, and accuracy 96%]. However, the sensitivity and accuracy of HVF pattern analysis were markedly reduced when all degrees of steatosis were defined as positive (SE 71%, SP 76%, pPV 81%, nPV 64%, and accuracy 73%). In contrast, the dichotomous parameter FHA remained a powerful indicator even under the latter conditions (SE 74%, SP 100%, pPV 100%, nPV 72%, and accuracy 84%). The combination of both sonographic tests resulted in improved sensitivity (82%), but significant loss of specificity (76%) and accuracy (80%) for prediction of liver steatosis. Conclusion: Sonographic evaluation of reduced HVF and FHA within the liver hilum is easy to perform, non-invasive, and, when present, gives a high degree of confidence in the diagnosis of liver steatosis. However, the lack of sonographic evidence of steatosis cannot definitively exclude the presence of mild steatosis, as shown on biopsy.

Hepatic steatosis in HIV‐HCV coinfected patients in France: comparison with HCV monoinfected patients matched for body mass index and HCV genotype

Significance of steatosis in HIV-HCV coinfection remains controversial. To compare the prevalence and predictors of hepatic steatosis between HIV-HCV and HCV patients matched for steatosis known determinants. A total of 564 HCV-naive patients undergoing liver biopsy were studied: 137 with HIV-HCV coinfection and 427 with HCV monoinfection, among whom 137 were matched for age, gender, body mass index and HCV genotype. Steatosis of any grade (67.1% vs. 41.6%, P < 0.0001), mixed steatosis (55.4% vs. 21.1%, P < 0.0001), severe histological activity (A2-A3: 78.1% vs. 55.5%, P < 0.0001) and severe fibrosis (F3-F4: 33.1% vs. 15.3%, P < 0.0001) were significantly more common in coinfected than in matched monoinfected patients. In multivariate analysis, steatosis was associated only with severe histological activity [odds ratio (OR): 3.1 (95% CI: 1.3-7.1)] in coinfected patients and with elevated body mass index [OR; 1.3 (1.1-1.5)], HCV genotype 3 [OR: 5.6 (2.3-13.9)], severe histological activity [OR: 3.1 (1.3-7.3)] and severe fibrosis [OR: 4.7 (1.3-17.3)] in monoinfected patients. Steatosis is significantly more common and severe in HIV-HCV coinfected than in HCV monoinfected French patients, even after matching for body mass index and HCV genotype. Steatosis is associated only with severe histological activity in coinfected patients and with previously reported factors in monoinfected patients, thus suggesting different underlying mechanisms.

Treatment Rates in Patients with Chronic Hepatitis B after Liver Biopsy

Purpose: Clinical practice concerns and recent updates of AASLD Guidelines (“guidelines”) and US algorithm (Keeffe et al., 2006) on treatment of chronic hepatitis B (CHB) (“algorithm”) have focused attention on the interpretation of ALT and HBV DNA levels with the utility of liver biopsy in CHB treatment decisions. Specifically, we focused on the use of liver biopsy in patients with high viral load having either ALT 1–2 × ULN or normal ALT. We also assessed the rates of treatment for CHB patients after the liver biopsy at our center. Methods: Charts of 159 patients with CHB seen in our ambulatory clinics between 1/07 and 5/07 have been reviewed. Patient demographics, laboratory, histology and clinical data were recorded. Results: 159 patients were seen (67% males, mean age of 52.4 years, 60% of Asian ethnicity), and 42 (26%) of them had a liver biopsy. A total of 34 (81%) patients were treated either before or after biopsy (see Table). Overall, 35 of 42 (83%) patients had liver biopsy prior to making initial therapeutic decisions, and 27 of the 35 (77%) patients started treatment. Among 47 patients with ALT 1–2 × ULN, 14 (30%) had a liver biopsy, including 6 subjects who had > stage 1 fibrosis on modified Ishak system. Similarly, among 37 patients with normal ALT and HBV DNA > 20,000 IU/mL (HBeAg-positive) or >2,000 IU/mL (for HBeAg-negative), 11 (30%) had a liver biopsy, including 4 subjects with > stage 1 fibrosis. The majority of liver biopsy was obtained from the group with ALT > 2 × ULN (24 patients). 14 (58%) of those 24 subjects demonstrated > stage 1 fibrosis. The overwhelming reasons for non-treatment were minimal fibrosis in 7 of 8 patients. The remaining one patient who had normal ALT and stage 2 fibrosis deferred treatment. Treatment was started in 13 patients with < stage 2 fibrosis, mainly due to increased ALT values or a family history of hepatocellular carcinoma. Conclusion: A liver biopsy was helpful in selecting treatment for patients with mild ALT elevation. A majority of patients with CHB undergoing liver biopsy received antiviral therapy afterwards. A large proportion of patients undergoing liver biopsy with normal ALT and high viral load had significant liver fibrosisTable

Separation of advanced from mild fibrosis in diffuse liver disease using 31P magnetic resonance spectroscopy

31P-MRS using DRESS was used to compare absolute liver metabolite concentrations (PME, Pi, PDE, γATP, αATP, βATP) in two distinct groups of patients with chronic diffuse liver disorders, one group with steatosis (NAFLD) and none to moderate inflammation ( n = 13), and one group with severe fibrosis or cirrhosis ( n = 16). All patients underwent liver biopsy and extensive biochemical evaluation. A control group ( n = 13) was also included. Absolute concentrations and the anabolic charge, AC = {PME}/({PME} + {PDE}), were calculated. Comparing the control and cirrhosis groups, lower concentrations of PDE ( p = 0.025) and a higher AC ( p < 0.001) were found in the cirrhosis group. Also compared to the NAFLD group, the cirrhosis group had lower concentrations of PDE ( p = 0.01) and a higher AC ( p = 0.009). No significant differences were found between the control and NAFLD group. When the MRS findings were related to the fibrosis stage obtained at biopsy, there were significant differences in PDE between stage F0–1 and stage F4 and in AC between stage F0–1 and stage F2–3. Using a PDE concentration of 10.5 mM as a cut-off value to discriminate between mild, F0–2, and advanced, F3–4, fibrosis the sensitivity and specificity were 81% and 69%, respectively. An AC cut-off value of 0.27 showed a sensitivity of 93% and a specificity of 54%. In conclusion, the results suggest that PDE is a marker of liver fibrosis, and that AC is a potentially clinically useful parameter in discriminating mild fibrosis from advanced.

Antinuclear antibody is associated with a more advanced fibrosis and lower RNA levels of hepatitis C virus in patients with chronic hepatitis C

Aims:Positive serum antinuclear antibody (ANA) is present in a number of patients with chronic hepatitis C virus (HCV) infection. This study aimed to evaluate the prevalence of ANA in patients...

Evaluation of hepatic steatosis by ultrasound in patients with chronic hepatitis C virus infection

To compare two alternative ultrasound parameters, hepatic vein flow (HVF) pattern and presence of focal hypoechoic areas (FHA) within the liver hilus, as non-invasive predictors of liver steatosis in patients with chronic hepatitis C virus (HCV) infection. In 122 consecutive patients with chronic HCV infection, the HVF pattern and presence of FHA within the liver hilus were assessed by Duplex-Doppler and B-mode sonography. All patients underwent liver biopsy and the sonographic results were compared with a histological score of steatosis used as the gold standard for this purpose. Association of fatty infiltrations with clinical and sonographic features were evaluated by a stepwise logistic regression analysis. Reduced HVF and FHA, but not standard clinical and laboratory parameters, strongly correlated with steatosis on histology (P<0.001). Both sonographic parameters made excellent predictions for the subgroup of patients with severe steatosis, particularly when both tests were combined [sensitivity (SE) 95%, specificity (SP) 96%, positive predictive value (pPV) 93%, negative predictive value (nPV) 97%, and accuracy 96%]. However, the sensitivity and accuracy of HVF pattern analysis were markedly reduced when all degrees of steatosis were defined as positive (SE 71%, SP 76%, pPV 81%, nPV 64%, and accuracy 73%). In contrast, the dichotomous parameter FHA remained a powerful indicator even under the latter conditions (SE 74%, SP 100%, pPV 100%, nPV 72%, and accuracy 84%). The combination of both sonographic tests resulted in improved sensitivity (82%), but significant loss of specificity (76%) and accuracy (80%) for prediction of liver steatosis. Sonographic evaluation of reduced HVF and FHA within the liver hilum is easy to perform, non-invasive, and, when present, gives a high degree of confidence in the diagnosis of liver steatosis. However, the lack of sonographic evidence of steatosis cannot definitively exclude the presence of mild steatosis, as shown on biopsy.

Serum Concentrations of Insulin-Like Growth Factor-I (IGF-I) as a Marker of Liver Fibrosis in Patients With Chronic Hepatitis C

Liver biopsy was until recently the only way of evaluating liver fibrosis. Noninvasive tests for hepatic fibrosis, without potential risks, are desired by clinicians as well as patients. Insulin-like growth factor-I (IGF-I) synthesis is disturbed in liver fibrosis and reflects the severity of the clinical stage. We assessed serum IGF-I levels in patients with chronic hepatitis C (CHC) to correlate with liver fibrosis and antiviral therapy. Forty patients with CHC and persistently abnormal alanine aminotransferase values were enrolled and treated with peginterferon alpha-2a 180 microg per week plus ribavirin for 24 (n=20) or 48 (n=20) weeks. All patients underwent liver biopsy before treatment (METAVIR fibrosis stage F0, n=13; F1-F2, n=14; F3, n=7; F4, n=6). Serum IGF-I was measured at baseline, at the end of treatment period, and 24 weeks after finishing treatment. Mean IGF-I values were significantly lower in patients with advanced fibrosis (F4, 65.9+/-17.9 ng/mL) than in the others (F0, 145.2+/-47.1; F1-F2, 150.3+/-89.6; and F3, 121.4+/-35.2 ng/mL; P < .05). Serum IGF-I levels increased during combined therapy, being this increment markedly higher in patients with sustained virologic response. In conclusion, IGF-I synthesis is disturbed in CHC and reflects the severity of the liver fibrosis. Combined therapy improves serum IGF-I levels. IGF-I could represent a good, noninvasive marker of liver fibrosis.

Antiviral Therapy Decreases Hepatic Venous Pressure Gradient in Patients with Chronic Hepatitis C and Advanced Fibrosis

Antiviral therapy (AVT) may improve liver histology in patients with advanced viral hepatitis but its effect on portal pressure remains unknown. This study was aimed to evaluate the influence of antiviral therapy (AVT) on hepatic venous pressure gradient (HVPG) in hepatitis C virus infected patients with portal hypertension. Twenty compensated patients with chronic hepatitis C, fibrosis stage 3 or 4 and HVPG > 5 mmHg received PEG-IFN alpha2b plus ribavirin. Every patient underwent liver biopsy and portal pressure measurements before and immediately after AT. Biopsies were evaluated according to METAVIR score. HVPG significantly dropped in all but one treated patient, with a mean (SD) reduction of 28.2 (12)%[13.8 (5.6) Vs. 10.2 (3.8) mmHg, p = 0.005]. The percentage of HVPG decrease was significantly greater in patients who achieved a virological end of treatment response [26.2 (12.5)% Vs. 12.7 (8.5)%, p = 0.05] and in those with a decrease of at least 2 points in the grade of inflammation [35.7 (4.5)% Vs. 22.1 (9.5)%, p = 0.015]. Nine out of 11 patients with baseline HVPG > or = 12 mmHg showed a decrease greater than 20% (3/11) or under the 12 mmHg threshold (6/11). AVT reduces HVPG in compensated patients with advanced hepatitis C (fibrosis stage 3 or 4) and portal hypertension.

Outcomes of Donor Evaluations for Adult-to-Adult Right Hepatic Lobe Living Donor Liver Transplantation

The purpose of this study is to determine the role of liver biopsy and outcome of patients undergoing donor evaluation for adult-to-adult right hepatic lobe living donor liver transplantation (LDLT). Records of patients presenting for a comprehensive donor evaluation between 1997 and February 2005 were reviewed. Liver biopsy was performed only in patients with risk factors for abnormal histology. Two hundred and sixty patients underwent a comprehensive donor evaluation and 116 of 260 (45%) were suitable for donation, 14 of 260 (5.4%) did not complete evaluation and 130 of 260 (50%) were rejected. Four patients underwent unsuccessful hepatectomy surgery due to discovery of intraoperative abnormalities. Between 1997 and 2001, the acceptance rate of donor candidates (63%) was higher than 2002-2005 (36%), p < 0.0001. Sixty-six of the 150 eligible patients (44%) fulfilled criteria for liver biopsy and 28 of 66 (42%) had an abnormal finding. Less than half of the patients undergoing donor evaluation were suitable donors and the donor acceptance rate has declined over time. A large proportion of the patients undergoing liver biopsy have abnormal findings. Our evaluation process failed to identify 4 of 103 who had aborted donor surgeries.