Broadening and strengthening the health providers caring for patients with chronic hepatitis C may improve continuity of care.

BACKGROUND: Direct-acting antiviral (DAA) therapies for hepatitis C virus infection (HCV) lead to excellent rates of sustained virological response (SVR). However, loss to follow-up (LTFU) for SVR testing remains a challenge. We examine factors associated with LTFU in a real-world setting. METHODS: Adults who received DAA therapy for HCV in one of 26 centers across Australia during 2016-2021 were followed up for 2 years. Data sources included the patient medical records and the national Pharmaceutical and Medicare Benefits Schemes. Linkage to Medicare provided utilization data of other health-care providers and re-treatment with DAAs. LTFU was defined as no clinic attendance for SVR testing by at least 52 weeks after DAA treatment commencement. Multivariable logistic regression assessed factors associated with LTFU. RESULTS: In 3619 patients included in the study (mean age 52.0 years; SD = 10.5), 33.6% had cirrhosis (69.4% Child-Pugh class B/C), and 19.3% had HCV treatment prior to the DAA era. Five hundred and fifteen patients (14.2%) were LTFU. HCV treatment initiation in 2017 or later (adj-OR = 2.82, 95% confidence interval [CI] 2.25-3.54), younger age (adj-OR = 2.63, 95% CI 1.80-3.84), Indigenous identification (adj-OR = 1.99, 95% CI 1.23-3.21), current injection drug use or opioid replacement therapy (adj-OR = 1.66, 95% CI 1.25-2.20), depression treatment (adj-OR = 1.49, 95% CI 1.17-1.90), and male gender (adj-OR = 1.31, 95% CI 1.04-1.66) were associated with LTFU. CONCLUSIONS: These findings stress the importance of strengthening the network of providers caring for patients with HCV. In particular, services targeting vulnerable groups of patients such as First Nations Peoples, youth health, and those with addiction and mental health disorders should be equipped to treat HCV.

Comparative Accuracy of Clinical Fibrosis Markers, Hepascore and Fibroscan® to Detect Advanced Fibrosis in Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Non-invasive tests are widely used to diagnose fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), however, the optimal method remains unclear. We compared the accuracy of simple serum models, a serum model incorporating direct measures of fibrogenesis (Hepascore), and Fibroscan®, for detecting fibrosis in NAFLD. METHODS: NAFLD patients undergoing liver biopsy were evaluated with Hepascore, NAFLD Fibrosis Score (NFS), FIB-4 and AST-platelet ratio index (APRI), with a subset (n = 131) undergoing Fibroscan®. Fibrosis on liver biopsy was categorized as advanced (F3-4) or cirrhosis (F4). Accuracy was determined by area under receiving operating characteristic curves (AUC). Indeterminate ranges were calculated using published cut-offs. RESULTS: In 271 NAFLD patients, 83 (31%) had F3-4 and 47 (17%) cirrhosis. 6/131 (4%) had an unreliable Fibroscan®. For the detection of advanced fibrosis, the accuracy of Hepascore (AUC 0.88) was higher than FIB-4 (0.73), NFS (0.72) and APRI (0.69) (p < 0.001 for all). Hepascore had similar accuracy to Fibroscan® (0.80) overall, but higher accuracy in obese individuals (0.91 vs 0.80, p = 0.001). Hepascore more accurately identified patients with cirrhosis than APRI (AUC 0.85 vs 0.71, p = 0.01) and NFS (AUC 0.73, p = 0.01) but performed similar to FIB-4 and Fibroscan®. For the determination of F3-4, the proportion of patients in indeterminate area was lower for Hepascore (4.8%), compared to FIB-4 (42%), NFS (36%) and APRI (44%) (p < 0.001 for all). CONCLUSIONS: Hepascore has greater accuracy and a lower indeterminate range than simple serum fibrosis tests for advanced fibrosis in NAFLD, and greater accuracy than Fibroscan® in obese individuals.

Liver Disease and Poor Adherence Limit Hepatitis C Cure: A Real-World Australian Treatment Cohort.

BACKGROUND AND AIMS: In 2016, direct-acting antiviral (DAA) treatment for hepatitis C (HCV) became available through Australia's universal health care system, with the aim of HCV elimination. We report real-world effectiveness of DAA HCV treatment in Australia from a clinically well-informed cohort, enriched for cirrhosis and prior HCV treatment. METHODS: 3413 patients were recruited from 26 hospital liver clinics across Australia from February 2016 to June 2020. Clinical history and sustained viral response (SVR) were obtained from medical records and data linkage to the Australian Pharmaceutical Benefits Scheme. Factors associated with SVR were assessed by multivariable logistic regression (MVR). RESULTS: At recruitment, 32.2% had cirrhosis (72.9% Child Pugh class B/C), and 19.9% were treatment experienced. Of the 2,939 with data, 93.3% confirmed SVR. 137 patients received second-line therapy. Patients with cirrhosis had lower SVR rate (88.4 vs. 95.8%; p < 0.001). On MVR, failure to achieve SVR was associated with Genotype 3 (adj-OR = 0.42, 95%CI 0.29-0.61), male gender (adj-OR = 0.49, 95%CI 0.31-0.77), fair/poor adherence (adj-OR = 0.52, 95%CI 0.28-0.94), cirrhosis (adj-OR = 0.57, 95%CI 0.36-0.88), FIB-4 > 3.25 (adj-OR = 0.52, 95%CI 0.33-0.83) and MELD score ≥ 20 (adj-OR = 0.25, 95%CI 0.08-0.80). Consistent results were seen in cirrhotic sub-analysis. CONCLUSIONS: Excellent SVR rates were achieved with DAAs in this real-world cohort of patients with chronic HCV infection. More advanced liver disease and clinician impression of poor adherence were associated with HCV treatment failure. Supports to improve liver fibrosis assessment skills for non-specialist DAA prescribers in the community and to optimize patient adherence are likely to enable more effective pursuit of HCV elimination in Australia.

Serum Fibrosis Tests Guide Prognosis in Metabolic Dysfunction-Associated Fatty Liver Disease Patients Referred From Primary Care.

BACKGROUND & AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is managed predominately in primary care, however, there is uncertainty regarding how to best identify patients for specialist referral. We examined the accuracy of noninvasive tests as screening tools for the prediction of outcomes in MAFLD patients referred from primary care. METHODS: Patients with MAFLD referred by primary care for specialist review to Sir Charles Gairdner Hospital (cohort 1, n = 626) or tertiary centers within Western Australia (cohort 2, n = 246) were examined. Hepascore, aspartate aminotransferase to platelet ratio, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score performed at baseline were examined for their accuracy in predicting liver-related death (LRD), decompensation, and hepatocellular carcinoma. Outcomes were collected from hospital records and data linkage. RESULTS: The median follow-up period was 5.0 years (range, 0.1-13.0 y) and 3.8 years (range, 0.1-10.0 y) in cohorts 1 and 2, respectively. In both cohorts, Hepascore and FIB-4 had the highest area under the curve for the prediction of LRD (0.90-0.95 and 0.83-0.94, respectively), decompensation (0.86-0.91 and 0.86-0.87, respectively), and hepatocellular carcinoma (0.75-0.90 and 0.67-0.85, respectively). The sensitivity and negative predictive values were high (>90%) for Hepascore (cut-off value, 0.60), FIB-4 (cut-off value, 1.30), and nonalcoholic fatty liver disease fibrosis score (cut-off value, -1.455) for all outcomes in cohort 1, and for predicting LRD in cohort 2. Hepascore had the highest specificity, classified the greatest proportion of patients as low risk, and was favored by decision curve analysis as providing the greatest net benefit. CONCLUSIONS: Serum noninvasive tests accurately stratify risk of liver-related outcomes in MAFLD patients and can be used as a screening tool for patients referred for specialist review by primary care.

Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up.

BACKGROUND: First Nations Peoples of Australia are disproportionally affected by hepatitis C (HCV) infection. Through a prospective study we evaluated the outcome of direct-acting antiviral (DAA) therapy among First Nations Peoples with HCV infection. METHODS: Adults who initiated DAA therapy at one of 26 hospitals across Australia, 2016-2019 were included in the study. Clinical data were obtained from medical records and the Pharmaceutical and Medicare Benefits Schemes. Outcomes included sustained virologic response (SVR) and loss to follow-up (LTFU). A multivariable analysis assessed factors associated with LTFU. RESULTS: Compared to non-Indigenous Australians (n = 3206), First Nations Peoples (n = 89) were younger (p < 0.001), morel likely to reside in most disadvantaged (p = 0.002) and in regional/remote areas (p < 0.001), and had similar liver disease severity. Medicines for mental health conditions were most commonly dispensed among First Nations Peoples (55.2% vs. 42.8%; p = 0.022). Of 2910 patients with follow-up data, both groups had high SVR rates (95.3% of First Nations Peoples vs. 93.2% of non-Indigenous patients; p = 0.51) and 'good' adherence (90.0% vs. 86.9%, respectively; p = 0.43). However, 28.1% of First Nations Peoples were LTFU vs. 11.2% of non-Indigenous patients (p < 0.001). Among First Nations Peoples, younger age (adj-OR = 0.93, 95% CI 0.87-0.99) and treatment initiation in 2018-2019 vs. 2016 (adj-OR = 5.14, 95% CI 1.23-21.36) predicted LTFU, while higher fibrosis score was associated with better engagement in HCV care (adj-OR = 0.71, 95% CI 0.50-0.99). CONCLUSIONS: Our data showed that First Nations Peoples have an equivalent HCV cure rate, but higher rates of LTFU. Better strategies to increase engagement of First Nations Peoples with HCV care are needed.

Efficacy and Safety of Sofosbuvir/Velpatasvir/Voxilaprevir for Hepatitis C Virus (HCV) NS5A-Inhibitor Experienced Patients With Difficult to Cure Characteristics.

BACKGROUND: In clinical trials, hepatitis C virus (HCV) salvage treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of >95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort. METHODS: We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE). FINDINGS: Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n = 46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A, and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n = 82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n = 18/18, GT1b n = 2/4), 89% in GT3 (n = 59/66) and 100% in GT6 (n = 3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were 4 serious AEs including 1 death and 3 hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12. CONCLUSIONS: This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most; however, serious AEs can occur in those with advanced liver disease.

Management, outcomes and survival of an Australian IgG4-SC cohort: The MOSAIC study.

BACKGROUND AND AIMS: IgG4 sclerosing cholangitis (IgG4-SC) is the biliary component of the multisystem IgG4-related disease. We aimed to investigate the clinical features, demographics, treatment response and outcomes of IgG4-SC in a large Australian cohort. METHODS: We conducted nationwide retrospective cohort via the Australian Liver Association Clinical Trials Network (ALA-CRN). 39 sites were invited to participate. IgG4-SC was defined by the clinical diagnostic criteria established by the Japanese Biliary Association in 2012. Data were collected on patient demographic, clinical and laboratory information, presenting features, response to therapy and clinical outcomes. RESULTS: 67 patients meet inclusion criteria from 22 sites. 76% were male with mean age of 63.3 ± 14.5 years and a median IgG4 level of 3.6 g/L [0.09-67.1]. The most frequent presenting symptom was jaundice (62%) and abdominal pain (42%) and Type 1 biliary stricturing (52%) at the distal common bile duct was the most frequent biliary tract finding. Prednisolone was used as a primary treatment in 61 (91%) and partial or complete response occurred in 95% of subjects. Relapse was common (42%) in those who ceased medical therapy. After a median follow up of 3.9 years there was one hepatocellular carcinoma and no cholangiocarcinomas. CONCLUSIONS: Our study confirms the preponderance of IgG4-SC in males and highlights the steroid response nature of this condition although relapse is common after steroid cessation. Progression to malignancy was uncommon.

Long-term Liver-related Outcomes of Patients With Chronic Liver Diseases in Australia.

BACKGROUND & AIMS: Chronic liver disease is a major health burden that produces significant liver-related morbidity and mortality. We aimed to evaluate liver-related outcomes of patients with different causes of chronic liver disease in Australia. METHODS: We collected data from 10,933 patients with chronic liver disease assessed by Hepascore (a serum fibrosis model) in Western Australia from 2004 through 2015. We obtained records of liver-related death, transplantation, decompensation, and hepatocellular carcinoma from WA Data Linkage Unit databases. Competing risk analysis was used to calculate the cumulative risk of each clinical endpoint, and risks for clinical endpoints were compared among all causes of chronic liver disease. RESULTS: In our final cohort for analysis, 5566 patients had hepatitis C virus (HCV) infection, 1989 had HBV infection, 119 were infected with HBV and HCV, 955 had alcohol-associated liver disease, 1597 had non-alcoholic fatty liver disease (NAFLD), 123 had alcohol-associated liver disease and metabolic risk factors, 561 had autoimmune liver disease without overlap syndrome, and 23 autoimmune overlap syndrome. Significant differences among chronic liver diseases were observed in risk of all-cause death (P < .001), liver-related death (P < .001), liver transplantation (P < .001), and decompensation (P < .001) but not hepatocellular carcinoma (P=.095). Patients with alcohol-associated liver disease had the highest 5-year cumulative risk of liver-related death (17.1%) and the second-highest 5-year cumulative risk of decompensation (29.2%). Multivariate analysis found patients with alcohol-associated liver disease had significantly higher risks of liver-related death and decompensation than patients with HCV infection with hazard ratios (HRs) of 2.39 (95% CI, 1.88-3.03) and 3.42 (95% CI, 2.74-4.27), respectively. Patients with NAFLD had a significantly lower risk of liver related death and decompensation than patients with HCV infection, with HRs of 0.67 (95% CI, 0.48-0.95) and 0.70 (95% CI, 0.52-0.94) respectively. CONCLUSIONS: In an analysis of patients in Western Australia, we found patients with alcohol-associated liver disease to have significantly higher risk of decompensation and liver-related death than patients with HCV infection, whereas patients with NAFLD have significantly lower risks of either outcome.

Efficacy and safety profile of calcineurin inhibitor salvage therapy in autoimmune hepatitis.

BACKGROUND: As data is limited on the outcomes of calcineurin inhibitors (CNI) in autoimmune hepatitis (AIH), we evaluated the efficacy and safety of CNI in AIH patients who failed prior treatment(s). METHODS: A retrospective study was performed of AIH patients who received cyclosporine A (CsA) and/or tacrolimus (TAC) after prior treatment(s) failure. Records were reviewed for baseline demographic and clinical characteristics, and treatment outcomes. The primary outcome was biochemical remission.Results: Thirty-three AIH patients received CNI across seven liver centers:17 received CsA, 21 TAC and 5 TAC after CsA failure/intolerance. 82% received CNI for an insufficient response to treatment(s). Overall, 48% of CNI treated patients achieved biochemical remission including 41% in prior non-responders and 83% in treatment intolerant patients. Remission rates with CNI as second-line and third-line therapy were 63% and 29% respectively. There were no baseline predictors of response to CNI on multivariate analysis. Eighteen (55%) patients developed significant side effects and 8 (24%) discontinued due to intolerance. Three patients required liver transplantation for decompensated cirrhosis and 6 patients died including one from malignancy possibly related to CNI. CONCLUSION: CNI salvage therapy is well tolerated and moderately effective achieving remission in around 50% of AIH who failed standard therapy.

The MAAPE score in intermediate and advanced hepatocellular carcinoma treated with Yttrium-90 resin microsphere radioembolization.

BACKGROUND AND AIM: Yttrium-90 resin microsphere radioembolization (RE) is not recommended for routine use in intermediate or advanced hepatocellular carcinoma (HCC) by recent guidelines. This study aims to establish pre-treatment variables which predict survival in HCC patients treated with RE to identify those who will benefit most from it, and to inform patient selection for future trials. METHODS: Single center, retrospective study of consecutive patients with HCC treated with RE from 2007 to 2018. Patients included if undergoing their first RE treatment for intermediate or advanced HCC; a Child-Pugh score of B7 or less; and a performance status of 1 or less. Multivariable Cox regression identified variables that were significantly associated with survival. A predictive score was developed based upon coefficients from the fitted Cox regression model, and cubic spline regression was used to identify prognostic groups. RESULTS: One hundred thirteen patients with intermediate (53.1%) and advanced HCC (45.1%) followed for a median of 13.2 months were included. Variables associated with superior survival used to derive the MAAPE score were lower Model for End-Stage Liver Disease score (≤ 7), lower Alpha-fetoprotein (≤ 150 IU/L), higher serum Albumin (> 37 g/L), absence of Portal vein tumor thrombus, and better performance status (Eastern Cooperative Oncology Group = 0). Three survival prognostic groups were identified: good (median overall survival 25.0 months), average (15.3 months), and poor (6.3 months) (overall log-rank test, P < 0.001). CONCLUSION: The MAAPE score accurately identifies HCC patients in whom RE is safe and effective. This will allow for optimal patient selection for future trials of RE versus systemic therapy.

Baseline and Post-treatment 18F-Fluorocholine PET/CT Predicts Outcomes in Hepatocellular Carcinoma Following Locoregional Therapy.

BACKGROUND AND AIMS: 18F-fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) is an emerging functional imaging technique in the diagnosis and management of hepatocellular carcinoma (HCC). The aim of this study was to assess the ability of a pre- and post-treatment 18F-FCH PET/CT to predict prognosis and treatment response in early-stage HCC. METHODS: Patients with early- or intermediate-stage HCC planned for locoregional therapy were prospectively enrolled. Baseline demographic and tumor information was collected and baseline and post-treatment 18F-FCH PET/CT performed. Maximum standardized uptake values (SUVmax) were determined for each HCC lesion, and the difference between baseline and post-treatment SUVmax values were compared with progression-free survival outcomes. RESULTS: A total of 29 patients with 39 confirmed HCC lesions were enrolled from a single clinical center. Patients were mostly men (89.7%) with hepatitis C or alcohol-related cirrhosis (65.5%) and early-stage disease (89.7%). Per-patient and per-lesion sensitivity of 18F-FCH PET/CT was 72.4% and 59.0%, respectively. A baseline SUVmax < 13 was associated with a superior median progression-free survival compared with an SUVmax of > 13 (17.7 vs. 5.1 months; p = 0.006). A > 45% decrease in SUVmax between baseline and post-treatment 18F-FCH PET/CT ("responders") was associated with a superior mean progression-free survival than a percentage decrease of < 45% ("non-responders," 36.1 vs. 11.6 months; p = 0.034). CONCLUSIONS: Baseline and post-treatment 18F-FCH PET/CT predicts outcomes in early-stage HCC undergoing locoregional therapy. This technique may identify patients with an objective response post-locoregional therapy who would benefit from further therapy.

Ad Libitum Mediterranean and Low-Fat Diets Both Significantly Reduce Hepatic Steatosis: A Randomized Controlled Trial.

Although diet-induced weight loss is first-line treatment for patients with nonalcoholic fatty liver disease (NAFLD), long-term maintenance is difficult. The optimal diet for improvement in either NAFLD or associated cardiometabolic risk factors, regardless of weight loss, is unknown. We examined the effect of two ad libitum isocaloric diets (Mediterranean [MD] or low fat [LF]) on hepatic steatosis (HS) and cardiometabolic risk factors. Subjects with NAFLD were randomized to a 12-week blinded dietary intervention (MD vs. LF). HS was determined by magnetic resonance spectroscopy (MRS). From a total of 56 subjects enrolled, 49 completed the intervention and 48 were included for analysis. During the intervention, subjects on the MD had significantly higher total and monounsaturated fat, but lower carbohydrate and sodium, intakes compared to LF subjects (P < 0.01). At week 12, HS had reduced significantly in both groups (P < 0.01), and there was no difference in liver fat reduction between groups (P = 0.32), with mean (SD) relative reductions of 25.0% (±25.3%) in LF and 32.4% (±25.5%) in MD. Liver enzymes also improved significantly in both groups. Weight loss was minimal and not different between groups (-1.6 [±2.1] kg in LF vs -2.1 [±2.5] kg in MD; P = 0.52). Within-group improvements in Framingham Risk Score (FRS), total cholesterol, serum triglyceride (TG), and glycated hemoglobin (HbA1c) were observed in the MD (all P < 0.05), but not with the LF diet. Adherence was higher for the MD compared to LF (88% vs. 64%; P = 0.048). Conclusion: Ad libitum low-fat and Mediterranean diets both improve HS to a similar degree.

Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy.

BACKGROUND & AIMS: Little is known about outcomes of patients with autoimmune hepatitis (AIH) who have a suboptimal outcome to standard therapy and are then given mycophenolate mofetil as rescue therapy. We evaluated the efficacy and safety of mycophenolate mofetil in patients failed by or intolerant to corticosteroids, with or without azathioprine. METHODS: We performed a retrospective study of 105 patients with AIH who received mycophenolate mofetil therapy after an inadequate response or intolerance to standard therapy (98% received combination therapy with corticosteroids plus thiopurines). Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network. We reviewed records for baseline demographic features and characteristics of liver disease, initial therapy, mycophenolate mofetil indications, treatment outcome, and side effects. The primary outcome was biochemical remission, defined as levels of alanine and aspartate transferase and IgG level within the normal reference range, with or without normal liver histology within the first 2 years of treatment. RESULTS: The indication for mycophenolate mofetil therapy was non-response to treatment for 40% of cases and intolerance to therapy for 60%. Overall, 63 patients (60%) achieved biochemical remission following a median 12 weeks treatment with mycophenolate mofetil. The proportion of patients who achieved biochemical remission was similar between patients receiving mycophenolate mofetil for non-response to standard therapy (57%) and patients with intolerance to standard therapy (62%). However, a lower proportion of patients with cirrhosis achieved biochemical remission (47%) than patients without cirrhosis (6%) (P = .07). Serious adverse events occurred in 3 patients (2.7%) including 1 death, and 10 patients (9.2%) discontinued mycophenolate mofetil because of adverse events. CONCLUSION: In this retrospective study of patients with AIH who received mycophenolate mofetil as a rescue therapy, we found the drug to be well tolerated and moderately effective, inducing biochemical remission in 60% of subjects. Rates of response are lower and rates of infection are higher in patients with AIH and cirrhosis. Prospective studies of mycophenolate mofetil are warranted for this population.

Type and Pattern of Alcohol Consumption is Associated With Liver Fibrosis in Patients With Non-alcoholic Fatty Liver Disease.

INTRODUCTION: It is unclear whether low levels of alcohol are harmful in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to determine whether quantity, binge pattern consumption, or type of alcohol was associated with liver fibrosis in patients with NAFLD. METHODS: Previous and current alcohol consumption was assessed in NAFLD patients undergoing liver biopsy. All subjects currently consumed <210 g per week (male) or <140 g per week (female). Binge consumption was defined as ≥4 standard drinks (female) or ≥5 standard drinks (male) in one sitting. Liver biopsies were scored according to the NASH CRN system with F3/4 fibrosis defined as advanced. RESULTS: Among 187 patients (24% with advanced fibrosis), the median weekly alcohol consumption was 20 (2.3-60) g over an average of 18 years. Modest consumption (1-70 g per week) was associated with lower mean fibrosis stage compared to lifetime abstainers (p < 0.05) and a decreased risk of advanced fibrosis (OR 0.33, 95% CI 0.14-0.78, p = 0.01). The association with reduced fibrosis was not seen in subjects drinking in a binge-type fashion. Exclusive wine drinkers but not exclusive beer drinkers, had lower mean fibrosis stage and lower odds of advanced fibrosis (OR 0.20, 95% CI 0.06-0.69, p = 0.01), compared to lifetime abstinent subjects. No interaction between gender and alcohol quantity, type, or binge consumption on fibrosis was observed. DISCUSSION: Modest (1-70 g per week) alcohol consumption, particularly wine in a non-binge pattern, is associated with lower fibrosis in patients with NAFLD. Prospective longitudinal studies into fibrosis progression, cardiovascular outcomes, and mortality are required before clinical recommendations can be made.

Diabetes impacts prediction of cirrhosis and prognosis by non-invasive fibrosis models in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) patients with diabetes are at increased risk of cirrhosis and liver-related death, and thus accurate fibrosis assessment in these patients is important. We examined the ability of non-invasive fibrosis models to determine cirrhosis and outcomes in NAFLD patients with and without diabetes. METHODS: Non-alcoholic fatty liver disease patients diagnosed between 2006 and 2015 had Hepascore, NAFLD fibrosis score (NFS), APRI and FIB-4 scores calculated at baseline and were followed up for outcomes of overall and liver-related mortality/liver transplantation, hepatic decompensation and hepatocellular carcinoma (HCC). Model accuracy was determined by Harrell's C-index and by Kaplan-Meier analysis. RESULTS: A total of 284 patients (53% diabetic, 15% cirrhotic) were followed up for a median of 51.4 months, (range 6.1-146). During follow-up, diabetic patients had a greater risk of liver-related death/transplantation, HR 3.4 (95% CI 1.2-9.1) decompensation, HR 4.7 (95% CI 2.0-11.3) and HCC, HR 2.9 (95% CI 1.2-7.3). Among 241 subjects with a baseline liver biopsy, the accuracy of Hepascore, APRI and FIB-4 for predicting cirrhosis was lower amongst diabetics compared to non-diabetics (P < .005 for all). Model accuracy apart from Hepascore, was also significantly lower for predicting liver death/transplantation in patients with diabetes. No patient with a low fibrosis score and without diabetes developed liver decompensation or HCC, whereas up to 21% of diabetic patients with a low fibrosis score developed liver decompensation and up to 27% developed HCC at 5 years. CONCLUSIONS: Non-invasive scoring systems are less accurate at predicting cirrhosis and liver-related outcomes in patients with NAFLD and diabetes.

Rate of Nonsurveillance and Advanced Hepatocellular Carcinoma at Diagnosis in Chronic Liver Disease.

AIMS: Ultrasound surveillance for hepatocellular carcinoma (HCC) is recommended in cirrhotic patients to allow early diagnosis. This study investigated risk factors for nonsurveillance and advanced HCC at diagnosis and their effect on survival. MATERIALS AND METHODS: Two hundred seventy HCC patients were included. Clinical data were collected from hospital databases. RESULTS: One hundred twenty-eight (47.1%) patients had 6-monthly ultrasound surveillance before HCC diagnosis. Ninety-two (34.1%) patients had advanced HCC (multifocal or total diameter ≥6 cm) at diagnosis. The nonsurveillance rate was significantly higher in nonalcoholic fatty liver disease (NAFLD) (79%) compared with other causes of chronic liver disease (31.6% to 58.1%, P<0.001). Nonrecognition of NAFLD was significantly higher (68.4%) compared with other causes of chronic liver disease (0% to 23.2%, P<0.001). In NAFLD HCC patients, 23.7% were noncirrhotic and smoking was significantly associated HCC in this noncirrhotic group (P=0.041). No-surveillance for HCC was significantly associated with advanced HCC at diagnosis with an odds ratio (OR) of 8.1. Compared with nondrinkers, heavy alcohol consumption was significantly associated with advanced HCC (OR=7.6). In the surveillance group, diagnosis using computed tomography rather than magnetic resonance imaging was significantly associated with advanced HCC (OR=3.36). Patients without HCC surveillance had a significantly shorter median survival compared with those who had HCC surveillance (27.4 vs. 52.0 mo, P=0.0006). CONCLUSIONS: The lack of HCC surveillance is associated with advanced HCC at diagnosis and decreased survival. NAFLD patients with HCC have a significantly lower rate of diagnosis of chronic liver disease and HCC surveillance compared with the other causes of chronic liver disease.

The Prognostic Ability of Major Hepatocellular Carcinoma Staging Systems Is Improved by Including a Treatment Variable.

BACKGROUND AND AIMS: There has been significant debate regarding which hepatocellular carcinoma (HCC) staging system is best able to predict survival. We hypothesized that the prognostic ability of the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) systems would be improved with the addition of an explicit treatment variable. METHODS: We performed an analysis of a prospectively enrolled cohort of 292 patients undergoing 532 treatment episodes for HCC from 2006 to 2014. BCLC, standard nine-stage HKLC (HKLC9), and modified five-stage HKLC (HKLC5) for each treatment episode were assessed. Overall survival and time to disease progression were calculated for the initial treatment, re-treatment, and overall treatment cohorts. We compared the performance of various prognostic models including staging system alone, treatment alone, and staging system plus treatment using the corrected Akaike information criterion and Harrell's C statistic. RESULTS: The BCLC, HKLC5, and HKLC9 systems were significant predictors of survival and time to progression for all treatment cohorts (log rank test, p < 0.001). The addition of a treatment variable significantly improved (p < 0.01) the prognostic ability of the survival and time to progression models compared with those containing only the BCLC or HKLC stage across all treatment cohorts other than survival in re-treatment for BCLC (p = 0.094). CONCLUSIONS: Adding a treatment variable to major HCC staging systems improves their ability to predict survival and time to progression in initial treatment, re-treatment, and overall.

Prevalence of restless legs syndrome in a tertiary cohort of ambulant patients with chronic liver disease.

A cross-sectional survey of 188 ambulant patients with chronic liver disease was performed to determine the prevalence of restless legs syndrome (RLS) using a validated patient completed questionnaire. Patient responses were verified by standardised telephone interview. RLS was identified in 64 (34%) patients. Significantly, more patients with cirrhosis had RLS than patients without RLS (43.9 vs 23.3%, P = 0.003, respectively). Cirrhotic patients with a history of hepatic encephalopathy were also more likely to have RLS than patients without hepatic encephalopathy (odds ratio = 4.33, 95% confidence interval = 1.40-13.37, P = 0.011). Patients with chronic liver disease may be at risk for RLS; early detection and treatment may improve patient outcomes.

Transition to adult care for pediatric liver transplant recipients: the Western Australian experience.

Transition to adult care is a vulnerable period for pediatric transplant recipients and is associated with reduced medication compliance, graft loss, and increased mortality. Psychosocial outcomes in young adults differ between pediatric transplant recipients and their healthy peers. We conducted a single-center, retrospective cohort study of all pediatric liver transplant recipients who were transitioned through our center. This study aimed to assess the outcomes of transitioned pediatric liver transplant recipients at an Australian center, including mortality, adherence, and psychosocial morbidity. The 1- and 5-year survival rates following transition were 100% and 92%, respectively. There were no episodes of late rejection. In total, 66.7% of patients were compliant with immunosuppression and 61.1% of patients were compliant with clinic attendance. There was a significant relationship between medication compliance and clinic attendance, as well as presence of psychological issues with clinic non-attendance. Psychosocial outcomes were in keeping with age-matched data from the general population. All patients were employed or studying following transition. This is the first study of its kind in the Australian population, and outcomes were superior to published international data. Despite the demonstrated good outcomes, transition programs may improve healthcare engagement in this cohort.

HKLC Triages More Hepatocellular Carcinoma Patients to Curative Therapies Compared to BCLC and Is Associated with Better Survival.

BACKGROUND AND AIMS: The Hong Kong Liver Cancer (HKLC) system proposes to triage hepatocellular carcinoma (HCC) patients to more aggressive treatment and may be associated with superior survival compared with the Barcelona Clinic Liver Cancer (BCLC) system. We aimed to identify the influence of adherence to HKLC or BCLC treatment recommendations on survival and time to progression. METHODS: We examined a prospectively enrolled cohort of 292 patients undergoing 532 treatment episodes from a single clinical center. RESULTS: The BCLC and HKLC systems accurately predicted overall survival and time to progression after each treatment episode (BCLC: p < 0.001; HKLC: p < 0.001). Adherence to treatment recommendations was higher for HKLC than for BCLC (55.6 vs. 47.9%, p = 0.01). Survival was superior with adherence to HKLC recommendations compared to non-adherence (45.3 vs. 27.1 months, p < 0.001). There was no difference in survival in BCLC with adherence compared to non-adherence (34.6 vs. 32.3 months, p = 0.96). The survival benefit was limited to early- and very early stage disease for both HKLC (p < 0.001) and BCLC (p = 0.007). More patients were triaged to curative therapies by HKLC than BCLC (p = 0.004). The use of transarterial chemoembolization instead of ablation or resection in early- and very early stage disease for technical reasons was the major cause for non-recommended treatment and was associated with worse survival (p < 0.001). CONCLUSIONS: These data support the use of HKLC in early- and very early stage HCC. Efforts should be made to overcome technical reasons for not performing ablation in early- and very early stage disease.