Patient-reported outcomes in HCC: A scoping review by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

BACKGROUND AND AIMS: HCC is a leading cause of mortality in patients with advanced liver disease and is associated with significant morbidity. Despite multiple available curative and palliative treatments, there is a lack of systematic evaluation of patient-reported outcomes (PROs) in HCC. APPROACH AND RESULTS: The American Association for the Study of Liver Diseases Practice Metrics Committee conducted a scoping review of PROs in HCC from 1990 to 2021 to (1) synthesize the evidence on PROs in HCC and (2) provide recommendations on incorporating PROs into clinical practice and quality improvement efforts. A total of 63 studies met inclusion criteria investigating factors associated with PROs, the relationship between PROs and survival, and associations between HCC therapy and PROs. Studies recruited heterogeneous populations, and most were cross-sectional. Poor PROs were associated with worse prognosis after adjusting for clinical factors and with more advanced disease stage, although some studies showed better PROs in patients with HCC compared to those with cirrhosis. Locoregional and systemic therapies were generally associated with a high symptom burden; however, some studies showed lower symptom burden for transarterial radiotherapy and radiation therapy. Qualitative studies identified additional symptoms not routinely assessed with structured questionnaires. Gaps in the literature include lack of integration of PROs into clinical care to guide HCC treatment decisions, unknown impact of HCC on caregivers, and the effect of palliative or supportive care quality of life and health outcomes. CONCLUSION: Evidence supports assessment of PROs in HCC; however, clinical implementation and the impact of PRO measurement on quality of care and longitudinal outcomes need future investigation.

Quality measures in HCC care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The burden of HCC is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process-based measures and patient-reported outcomes (PROs) along the HCC care continuum. We identified candidate process and outcomes measures for HCC care based on structured literature review. A 13-member panel with content expertise across the HCC care continuum evaluated candidate measures on importance and performance gap using a modified Delphi approach (two rounds of rating) to define the final set of measures. Candidate PROs based on a structured scoping review were ranked by 74 patients with HCC across 7 diverse institutions. Out of 135 measures, 29 measures made the final set. These covered surveillance (6 measures), diagnosis (6 measures), staging (2 measures), treatment (10 measures), and outcomes (5 measures). Examples included the use of ultrasound (± alpha-fetoprotein [AFP]) every 6 months, need for surveillance in high-risk populations, diagnostic testing for patients with a new AFP elevation, multidisciplinary liver tumor board (MLTB) review of Liver Imaging-Reporting and Data System 4 lesions, standard evaluation at diagnosis, treatment recommendations based on Barcelona Clinic Liver Cancer staging, MLTB discussion of treatment options, appropriate referral for evaluation of liver transplantation candidacy, and role of palliative therapy. PROs include those related to pain, anxiety, fear of treatment, and uncertainty about the best individual treatment and the future. The AASLD PMC has developed a set of explicit quality measures in HCC care to help bridge the gap between guideline recommendations and measurable processes and outcomes. Measurement and subsequent implementation of these metrics could be a central step in the improvement of patient care and outcomes in this high-risk population.

Hepatitis C in the era of direct-acting antivirals: real-world costs of untreated chronic hepatitis C; a cross-sectional study.

BACKGROUND: Recent advances in Hepatitis C therapeutics offer the possibility of cure but will be expensive. The cost of treatment may be partially offset by the avoidance of advanced liver disease. We performed a micro-costing study of the ambulatory healthcare utilisation of patients with Hepatitis C supplemented with inpatient diagnosis related group costs. METHODS: The staff utilisation costs associated with a Hepatitis C ambulatory visit were measured and combined with the costs of investigations to establish a mean cost per consultation. An annualised estimate of cost was produced by multiplying this by the number of consultations accessed, stratified by degree of liver impairment. Inpatient costs were established by identifying the number of inpatient episodes and multiplying by Irish diagnosis related group costs. Non-parametric bootstrapping was performed to derive mean and 95%CI values. RESULTS: Two hundred and twenty-five patients were identified. The cost of an outpatient medical review was €136 (€3.60 SD). The cost of a Hepatitis C nursing review was €128 (€7.30 SD). The annual mean costs of care were as follows (95%CI): Mild €398 (€336, €482), Moderate €417(€335, €503), Compensated cirrhosis €1790 (€990, €3164), Decompensated cirrhosis €8302 (€3945, €14,637), Transplantation Year 1 €137,176 (€136,024, €138,306), Transplantation after Year 1 €5337 (€4942, €5799), Hepatocellular carcinoma €21,992 (€15,222, €29,467), Sustained virological response €44 (€16, €73). CONCLUSIONS: The direct medical cost associated with Hepatitis C care in Ireland is substantial and increases exponentially with progression of liver disease. The follow-up costs of patients with a sustained virological response in this cohort were low in comparison to patients with chronic infection.

Homozygosity for HLA group 2 alleles predicts treatment failure with interferon-α and ribavirin in chronic hepatitis C virus genotype 1 infection.

Host genetic factors influence treatment responses to antiviral therapy in chronic hepatitis C virus (HCV) infection. We retrospectively investigated associations between host genetic markers and treatment-induced virologic responses to dual therapy with interferon-α and ribavirin in chronically infected HCV genotype 1 (g1)- and genotype 3 (g3)-infected individuals. A total of 171 patients (89 HCV g1 and 82 HCV g3 infected) were investigated for genetic markers influencing treatment-induced sustained virologic response (SVR). Overall, SVR was observed for 46/89 (52%) HCV g1- and 57/82 (70%) HCV g3-infected patients. Of the 4 interleukin 28B (IL28B) single-nucleotide polymorphisms (SNPs), rs12979860 was the host genetic marker most significantly associated with failure to achieve an SVR in HCV g1-infected individuals [P=3.83×10(-4); odds ratio (OR)=5.61; confidence interval (CI)=2.07-15.18] and gave a positive predictive value for treatment failure of 81.3% for minor homozygotes (TT). Using additive (P=3.54×10(-4)) and dominant models (P=3.83×10(-4)), a dosage effect of the T allele was observed, with the dominance term not significant for this SNP. Logistic regression showed an association between HLA-C1/C1 and rapid virologic response in HCV g1 infections with an OR relative to the heterozygote of 10.0 (95% CI: 1.6-62.5, P=0.014). HLA-C2 homozygosity was a significant predictor of nonresponse to treatment in HCV g1-infected individuals (P=0.023).

Coeliac-like duodenal pathology in orthotopic liver transplant patients on mycophenolic acid therapy.

AIMS: Diarrhoea following orthotopic liver transplantation (OLT) is a significant clinical problem associated with mycophenolic acid (MPA). The histological injury pattern associated with MPA in the large bowel is well documented in the literature; however, that in the duodenum is less extensively documented. The aim of this study was to investigate the histological spectrum of duodenal injury specifically in symptomatic OLT patients on MPA, and to compare this with the spectrum in patients with coeliac disease and in normal controls. METHODS AND RESULTS: We reviewed our pathology database for all duodenal biopsies from patients on the OLT list over a period of 19 years. Medical records, anti-tissue transglutaminase IgA serology and histology were reviewed. Of the 667 patients who underwent endoscopy, 127 had duodenal biopsies (152 biopsies). Of these, 87.5% were normal. Sixteen showed abnormal histology, and seven (43.8%) of these were on MPA at the time of biopsy. Significant features included coeliac-like changes (shortened villi and increased intraepithelial lymphocyte counts), and novel findings included increased endocrine cell counts, apoptotic counts and lamina propria eosinophil counts in comparison with normal duodenal biopsies. CONCLUSIONS: Pathologists should be aware of the features of MPA-associated duodenal injury, including coeliac-like changes and increased apoptotic counts. In those with abnormal histology, discontinuation or a reduction in the dose of MPA should be discussed.

Clinical and histological determinants of nonalcoholic steatohepatitis and advanced fibrosis in elderly patients.

UNLABELLED: The characteristics of nonalcoholic fatty liver disease (NAFLD) in elderly patients are unknown. Therefore, we aimed to examine the differences between elderly and nonelderly patients with NAFLD and to identify determinants of nonalcoholic steatohepatitis (NASH) and advanced fibrosis (bridging fibrosis or cirrhosis) in elderly patients. This is a cross-sectional analysis of adult participants who were prospectively enrolled in the NASH Clinical Research Network studies. Participants were included based on availability of the centrally reviewed liver histology data within 1 year of enrollment, resulting in 61 elderly (age ≥65 years) and 735 nonelderly (18-64 years) participants. The main outcomes were the presence of NASH and advanced fibrosis. Compared to nonelderly patients with NAFLD, elderly patients had a higher prevalence of NASH (56% versus 72%, P = 0.02), and advanced fibrosis (25% versus 44%, P = 0.002). Compared to nonelderly patients with NASH, elderly patients with NASH had higher rates of advanced fibrosis (35% versus 52%, P = 0.03), as well as other features of severe liver disease including the presence of ballooning degeneration, acidophil bodies, megamitochondria, and Mallory-Denk bodies (P ≤ 0.05 for each). In multiple logistic regression analyses, independent determinants of NASH in elderly patients included higher aspartate aminotransferase (AST) (odds ratio [OR] = 1.12, P = 0.007) and lower platelets (OR = 0.98, P = 0.02); and independent determinants of advanced fibrosis included higher AST (OR = 1.08, P = 0.007), lower alanine aminotransferase value (OR = 0.91, P = 0.002), and an increased odds of having low high-density lipoprotein (OR = 8.35, P = 0.02). CONCLUSION: Elderly patients are more likely to have NASH and advanced fibrosis than nonelderly patients with NAFLD. Liver biopsy may be considered in elderly patients and treatment should be initiated in those with NASH and advanced fibrosis.

Liver steatosis: concordance of MR imaging and MR spectroscopic data with histologic grade.

PURPOSE: To determine if the concordance of magnetic resonance (MR) imaging and MR spectroscopic data with histologic measures of steatosis is affected by histologic magnification level, tissue heterogeneity, or assessment of tissue area versus that of hepatocytes. MATERIALS AND METHODS: This study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. In- and out-of-phase MR imaging and MR spectroscopic measures of steatosis were compared in 33 patients with nonalcoholic fatty liver disease and in 15 healthy volunteers. Concordance of MR imaging and MR spectroscopic data with histologic findings was assessed for (a) histologic examination at standard (×40 and ×100) versus high magnification (×200 and ×400), (b) heterogeneity and homogeneity of livers, and (c) percentage of tissue and hepatocytes that contained lipids. Evaluations included linear regression and Fisher exact tests. RESULTS: In- and out-of-phase MR imaging and MR spectroscopic data were well correlated (R2=0.93) and generally concordant with histologic measures. Patients in whom MR fat fractions were higher than expected compared with steatosis grades at standard magnification histologic examination were upgraded significantly more often when high magnification was used than were the remaining patients (100% [10 of 10] vs 47% [7 of 15], P<.01). MR imaging and MR spectroscopic data of homogeneous livers were significantly more likely than those of heterogeneous livers to be concordant with steatosis grades when high magnification was used (81% [13 of 16] vs 47% [8 of 17], P<.05). For all patients, percentage of fat in tissue was lower than that in hepatocytes, which affected individual patients, but not the overall correlation. CONCLUSION: MR imaging and MR spectroscopic data were generally concordant with histologic measures of steatosis. Discordance between them may reflect differences in magnification at histologic examination and in liver heterogeneity.

MRI steatosis grading: development and initial validation of a color mapping system.

OBJECTIVE: The purpose of this article is to develop and validate a chemical-shift imaging-derived color mapping system for evaluation of liver steatosis. MATERIALS AND METHODS: Opposed phase MRI was evaluated for 85 subjects (51 with presumed nonalcoholic fatty liver disease and 34 healthy volunteers). Liver signal intensity loss was compared with histologic analysis for 52 subjects, assuming grade 0 steatosis for healthy volunteers, to determine signal-intensity-loss threshold points differentiating steatosis grades and subsequent Spearman correlation. Color scale grading was then applied for 78 subjects. Interpretation of color maps for steatosis severity and heterogeneity was performed by three readers. Analyses of agreement among readers and of color map steatosis grade with biopsy were performed using weighted kappa values. RESULTS: The numbers of subjects with steatosis grades 0, 1, 2, and 3 were 41, 12, 13, and 19, respectively. A correlation of 0.90 was obtained using selected threshold values of 5.9% or less, 6-26.1%, 26.2-36.8%, and greater than 36.8% for steatosis grades 0, 1, 2, and 3, respectively. Interobserver agreement for color map grading of steatosis was excellent (κ = 0.93-0.94). Color map interpretation for all readers also showed excellent agreement with histologic findings for whole liver (κ = 0.82-0.86) and estimated biopsy site location (κ = 0.81-0.86; anterior region of right lobe). Heterogeneous steatosis on color maps was identified in 56-60% of subjects with nonalcoholic fatty liver disease and in 7% of healthy volunteers and was associated with greater disagreement between color map and histology grading (61-74%) compared with the whole group (37-40%). CONCLUSION: MRI-derived color map estimation of liver steatosis grade appears to be reproducible and accurate.

Liver diffusivity in healthy volunteers and patients with chronic liver disease: comparison of breathhold and free-breathing techniques.

PURPOSE: To compare liver ADC obtained with breathhold and free-breathing diffusion weighted imaging (DWI) in healthy volunteers and patients with liver disease. MATERIALS AND METHODS: Twenty-eight subjects, 12 healthy volunteers and 16 patients (9 NAFLD, 7 chronic active HCV), underwent breathhold (BH) and free-breathing (FB) DWI MRI at 1.5 Tesla. Pearson's correlation coefficient was used to determine correlation while paired t-tests assessed differences between BH and FB ADC. Estimated bias was calculated using the Bland-Altman method. RESULTS: Liver ADC (×10(-3) mm(2) /s) was lower on BH for all groups (mean difference 0.36 ± 0.20; P < 0.01). ADC was higher in healthy volunteers (BH 1.80 ± 0.18; FB 2.24 ± 0.20) compared with NAFLD patients (BH 1.43 ± 0.27; FB 1.78 ± 0.28) (P < 0.001) and HCV patients (BH 1.63 ± 0.191; FB 1.88 ± 0.12). Overall correlation between BH and FB ADC was (r = 0.75), greatest in NAFLD (r = 0.90) compared with the correlation in HCV (r = 0.24) and healthy subjects (r = 0.34). Bland-Altman plots did not show agreement in mean absolute difference and estimated bias between subjects. CONCLUSION: Correlation between BH and FB liver ADC is moderate indicating that BH and FB should not be used interchangeably. Additionally, the lower ADC values in BH versus FB should be accounted for when comparing different liver DWI studies.

Weight loss after Roux-en-Y gastric bypass in obese patients heterozygous for MC4R mutations.

BACKGROUND: Heterozygous mutations in melanocortin-4 receptor (MC4R) are the most frequent genetic cause of obesity. Bariatric surgery is a successful treatment for severe obesity. The mechanisms of weight loss after bariatric surgery are not well understood. METHODS: Ninety-two patients who had Roux-en-Y gastric bypass (RYGB) surgery were screened for MC4R mutations. We compared percent excess weight loss (%EWL) in the four MC4R mutation carriers with that of two control groups: 8 matched controls and with the remaining 80 patients who underwent RYGB. RESULTS: Four patients were heterozygous for functionally significant MC4R mutations. In patients with MC4R mutations, the %EWL after RYGB (66% EWL) was not significantly different compared to matched controls (70% EWL) and non-matched controls (60% EWL) after 1 year of follow-up. CONCLUSIONS: This study suggests that patients with heterozygous MC4R mutations also benefit from RYGB and that weight loss may be independent of the presence of such mutations.

Respiratory motion-corrected proton magnetic resonance spectroscopy of the liver.

PURPOSE: To develop a post-processing, respiratory-motion correction algorithm for magnetic resonance spectroscopy (MRS) of the liver and to determine the incidence and impact of respiratory motion in liver MRS. MATERIALS AND METHODS: One hundred thirty-two subjects (27 healthy, 31 with nonalcoholic fatty liver disease and 74 HIV-infected with or without hepatitis C) were scanned with free breathing MRS at 1.5 T. Two spectral time series were acquired on an 8-ml single voxel using TR/TE=2500 ms/30 ms and (1) water suppression, 128 acquisitions, and (2) no water suppression, 8 acquisitions. Individual spectra were phased and frequency aligned to correct for intrahepatic motion. Next, water peaks more than 50% different from the median water peak area were identified and removed, and remaining spectra averaged to correct for presumed extrahepatic motion. Total CH(2)+CH(3) lipids to unsuppressed water ratios were compared before and after corrections. RESULTS: Intrahepatic-motion correction increased the signal to noise ratio (S/N) in all cases (median=11-fold). Presumed extrahepatic motion was present in 41% (54/132) of the subjects. Its correction altered the lipids/water magnitude (magnitude change: median=2.6%, maximum=290%, and was >5% in 25% of these subjects). The incidence and effect of respiratory motion on lipids/water magnitude were similar among the three groups. CONCLUSION: Respiratory-motion correction of free breathing liver MRS greatly increased the S/N and, in a significant number of subjects, changed the lipids/water ratios, relevant for monitoring subjects.

Frequency and histopathologic basis of hepatic surface nodularity in patients with fulminant hepatic failure.

PURPOSE: To determine the frequency and histopathologic basis of hepatic surface nodularity at imaging in patients with fulminant hepatic failure. MATERIALS AND METHODS: The committee on human research approved this HIPAA-compliant study and waived written informed consent. Thirty-five consecutive patients [24 female [mean age, 38 years +/- 19 (standard deviation); range, 1-67 years] and 11 male [mean age, 29 years +/- 22; range, 2-61 years]] with a mean age of 35 years +/- 20 (range, 1-67 years) who underwent liver transplantation for fulminant hepatic failure at our institution during a 5-year period were retrospectively identified. Pretransplant ultrasonographic (n = 38; three patients each had two studies) and computed tomographic (n = 2) studies were retrospectively and independently reviewed for hepatic surface nodularity. Liver explant histopathologic findings (n = 33; slides unavailable in two patients) were reviewed for cirrhosis and for the combination of alternating foci of confluent regenerative nodules and necrosis. Differences among patients with nodular versus smooth liver surfaces in the proportion with the two histopathologic findings were compared with Fisher exact test. Differences in illness duration and maximum liver biochemical indices were compared with Mann-Whitney Rank Sum test. RESULTS: Fifteen of 35 patients (43%) demonstrated hepatic surface nodularity at pretransplant imaging, none of whom had cirrhosis at histopathologic examination. One patient with a smooth liver surface had cirrhosis. Compared with those who had a smooth liver surface, patients with hepatic surface nodularity had a significantly greater proportion with the histopathologic finding of a combination of alternating foci of confluent regenerative nodules and necrosis (12 of 14 vs one of 19, P < .001), longer illness duration (31 days +/- 32 vs 13 days +/- 13, P = .029), and lower maximum liver biochemical indices. CONCLUSION: Hepatic surface nodularity is commonly seen at imaging in fulminant hepatic failure and usually reflects a combination of alternating foci of confluent regenerative nodules and necrosis; this is important because an erroneous radiologic diagnosis of cirrhosis in this setting could adversely affect transplantation status.

Liver steatosis: investigation of opposed-phase T1-weighted liver MR signal intensity loss and visceral fat measurement as biomarkers.

PURPOSE: To investigate if opposed-phase T1-weighted and fat-suppressed T2-weighted liver signal intensity (SI) loss and visceral fat measurement at magnetic resonance (MR) imaging and body mass index (BMI) are correlated with grade of liver steatosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-related liver disease. MATERIALS AND METHODS: Committee on Human Research approval and patient consent were obtained for this HIPAA-compliant study. Fifty-two patients (15 men, 37 women) with NAFLD (n = 29) or HCV and HIV-related liver disease (n = 23) underwent prospective contemporaneous MR imaging and liver biopsy. Liver SI loss was measured on opposed-phase T1-weighted and fat-suppressed T2-weighted MR images. Visceral fat area was measured at three levels on water-suppressed T1-weighted MR images (n = 44). Spearman rank correlation coefficients and recursive partitioning were used to examine correlations. RESULTS: Histopathologic liver steatosis correlated well with liver SI loss on opposed-phase T1-weighted MR images (rho = 0.78), fat-suppressed T2-weighted MR images (rho = 0.75), and average visceral fat area (rho = 0.77) (all P < .01) but poorly with BMI (rho = 0.53, P < .01). Liver SI losses on opposed-phase T1-weighted MR imaging of less than 3%, at least 3% but less than 35%, at least 35% but less than 49%, and at least 49% corresponded to histopathologic steatosis grades of 0 (n = 16 of 17), 1 (n = 11 of 16), 2 (n = 7 of 13), and 3 (n = 5 of 6), respectively. A visceral fat area of greater than or equal to 73.8 cm(2) was associated with the presence of histopathologic steatosis in 41 of 44 patients. CONCLUSION: Liver SI loss on opposed-phase T1-weighted MR images and visceral fat area may be used as biomarkers for the presence of liver steatosis and appear to be superior to BMI.

Clinical and pathologic risk factors for atherosclerosis in cirrhosis: a comparison between NASH-related cirrhosis and cirrhosis due to other aetiologies.

BACKGROUND/AIMS: The precise prevalence of risk factors for atherosclerosis in NASH-related cirrhosis is unknown. The aims of this study were: (1) to compare the prevalence of major risk factors for atherosclerosis between subjects who underwent liver transplantation for NASH-related cirrhosis and those with cirrhosis of other aetiologies and (2) to compare pathologic changes of atherosclerosis within the explants hepatic hilar arteries between the groups. METHODS: Sixty subjects with NASH-related cirrhosis and 60 subjects with cirrhosis of other aetiologies were reviewed retrospectively. Demographic and clinical characteristics related to atherosclerosis were analyzed and compared. The hepatic hilar arteries of the explanted livers were examined for pathologic changes. RESULTS: The prevalence of all coronary artery disease (CAD) risk factors and the metabolic syndrome was significantly higher in NASH-related cirrhosis group compared to cirrhosis of other aetiologies. The proportion of patients with a diagnosis of CAD was also significantly higher in the NASH-related cirrhosis group (21.6% vs. 5%, p=0.005). Pathological examination of hilar arteries showed possible atherosclerotic changes in only 4 cases (3 NASH-related cirrhosis; 1 HCV). CONCLUSIONS: Major risk factors for atherosclerosis are significantly more prevalent in subjects with NASH-related cirrhosis than in subjects with cirrhosis of other aetiologies and are predictive of an increased prevalence of CAD. This study suggests that NASH-related cirrhosis is not protective against atherosclerosis.

A clinical scoring system for predicting nonalcoholic steatohepatitis in morbidly obese patients.

UNLABELLED: Nonalcoholic steatohepatitis (NASH) is common in morbidly obese persons. Liver biopsy is diagnostic but technically challenging in such individuals. This study was undertaken to develop a clinically useful scoring system to predict the probability of NASH in morbidly obese persons, thus assisting in the decision to perform liver biopsy. Consecutive subjects undergoing bariatric surgery without evidence of other liver disease underwent intraoperative liver biopsy. The outcome was pathologic diagnosis of NASH. Predictors evaluated were demographic, clinical, and laboratory variables. A clinical scoring system was constructed by rounding the estimated regression coefficients for the independent predictors in a multivariate logistic model for the diagnosis of NASH. Of 200 subjects studied, 64 (32%) had NASH. Median body mass index was 48 kg/m(2) (interquartile range, 43-55). Multivariate analysis identified six predictive factors for NASH: the diagnosis of hypertension (odds ratio [OR], 2.4; 95% confidence interval [CI], 1-5.6), type 2 diabetes (OR, 2.6; 95% CI, 1.1-6.3), sleep apnea (OR, 4.0; 95% CI, 1.3-12.2), AST > 27 IU/L (OR, 2.9; 95% CI, 1.2-7.0), alanine aminotransferase (ALT) > 27 IU/L (OR, 3.3; 95% CI, 1.4-8.0), and non-Black race (OR, 8.4; 95% CI, 1.9-37.1). A NASH Clinical Scoring System for Morbid Obesity was derived to predict the probability of NASH in four categories (low, intermediate, high, and very high). CONCLUSION: The proposed clinical scoring can predict NASH in morbidly obese persons with sufficient accuracy to be considered for clinical use, identifying a very high-risk group in whom liver biopsy would be very likely to detect NASH, as well as a low-risk group in whom biopsy can be safely delayed or avoided.

Health-related fitness and physical activity in patients with nonalcoholic fatty liver disease.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) has been referred to as the hepatic manifestation of the metabolic syndrome. There is a lower prevalence of metabolic syndrome in individuals with higher health-related fitness (HRF) and physical activity (PA) participation. The relationship between NAFLD severity and HRF or PA is unknown. Our aim was to compare measures of HRF and PA in patients with a histological spectrum of NAFLD severity. Thirty-seven patients with liver biopsy-confirmed NAFLD (18 women/19 men; age = 45.9 +/- 12.7 years) completed assessment of cardiorespiratory fitness (CRF, VO(2peak)), muscle strength (quadriceps peak torque), body composition (%fat), and PA (current and historical questionnaire). Liver histology was used to classify severity by steatosis (mild, moderate, severe), fibrosis stage (stage 1 versus stage 2/3), necroinflammatory activity (NAFLD Activity Score; or=5 NAS2) and diagnosis of NASH by Brunt criteria (NASH versus NotNASH). Analysis of variance and independent t tests were used to determine the differences among groups. Fewer than 20% of patients met recommended guidelines for PA, and 97.3% were classified at increased risk of morbidity and mortality by %fat. No differences were detected in VO(2peak) (x = 26.8 +/- 7.4 mL/g/min) or %fat (x = 38.6 +/- 8.2%) among the steatosis or fibrosis groups. Peak VO(2) was significantly higher in NAS1 versus NAS2 (30.4 +/- 8.2 versus 24.4 +/- 5.7 mL/kg/min, P = 0.013) and NotNASH versus NASH (34.0 +/- 9.5 versus 25.1 +/- 5.7 mL/kg/min, P = 0.048). CONCLUSION: Patients with NAFLD of differing histological severity have suboptimal HRF. Lifestyle interventions to improve HRF and PA may be beneficial in reducing the associated risk factors and preventing progression of NAFLD.

Long-term follow-up of portopulmonary hypertension: effect of treatment with epoprostenol.

Moderate to severe portopulmonary hypertension (PPHTN) increases the risks of orthotopic liver transplantation (OLT). Epoprostenol is an effective treatment of PPHTN, but long-term effects on pulmonary hemodynamics or liver function in PPHTN are poorly defined. We sought to describe the long-term effects of treatment with or without epoprostenol on pulmonary hemodynamics, liver biochemistries, and survival in patients with moderate to severe PPHTN at a single center. A large retrospective cohort was identified with moderate to severe PPHTN diagnosed before OLT. Baseline and follow-up pulmonary hemodynamics and liver biochemistries were compared and outcomes assessed. Nineteen patients were treated with epoprostenol and 17 were not treated with epoprostenol. There were significant improvements in mean pulmonary artery pressure (MPAP, 48.4-36.1 mm Hg; P < 0.0001), pulmonary vascular resistance (PVR, 632-282 dynes . s . cm(-5); P < 0.0001), and cardiac output (5.7 to 7.7 L/min; P = 0.0009) with epoprostenol after a median of 15.4 months. Liver biochemistries did not change significantly, and survival did not seem to differ between the 2 groups (hazard ratio, 0.85; P = 0.77). In the epoprostenol group, patients who survived had greater absolute changes in MPAP, transpulmonary gradient, and PVR than those who died. Two patients in the epoprostenol group successfully underwent OLT. Long-term epoprostenol therapy greatly improves pulmonary hemodynamics in patients with PPHTN. Liver biochemistries are not greatly changed. Survival seemed not to differ between treatment groups. A minority of patients treated with epoprostenol will improve sufficiently to undergo OLT.

Medical treatment of non-alcoholic steatohepatitis.

There is no proven medical treatment of non-alcoholic steatohepatitis (NASH). Most prior therapeutic trials have had methodologic limitations. Insulin sensitizers are the more promising therapeutic candidates among categories that include antioxidants, lipid-lowering agents, and antiobesity drugs. The future will see the evaluation of novel agents and a comprehensive treatment strategy that addresses the risk factors for the metabolic syndrome. This article reviews the current status of medical management options for NASH.