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BACKGROUND Chronic hepatitis B (CHB) infection remains a significant public health issue for Indigenous Australians, in particular for remote communities. AIM This study aimed to evaluate the spectrum of hepatitis B virus (HBV) care provided to a remote Aboriginal community. Measures studied included screening, seroprevalence, vaccination rates and efficacy, and HCC risk and surveillance adherence. METHODS A retrospective audit of HBV care received by all permanent residents currently attending a remote Aboriginal Health service. This study was endorsed by both the local Aboriginal Health service and the Aboriginal Health Council of South Australia. RESULTS A total of 208 patients attended the clinic, of whom 52% (109) were screened for HBV. Of these, 12% (13) had CHB and 20% (22) had evidence of past infection. Similarly, of the 208 attending patients, complete vaccination was documented in 48% (99). Of the 33 patients with post-vaccination serology, 24% (8) had sub-therapeutic (

OBJECTIVE Liver cirrhosis is a chronic disease complicated by recurrent hospital admissions. Self-management skills could facilitate optimal disease management. Currently there is no validated instrument for measuring self-management in these patients. Hence, we evaluated the internal reliability and construct validity of the Partners in Health (PIH) scale, a chronic condition self-management tool in cirrhotic patients. METHODS In this prospective cohort study, the PIH scale was administered to 133 consenting patients within a Chronic Liver Failure Program of a tertiary hospital from February 2017 to May 2018. A Bayesian confirmatory factor analysis (BCFA) was used to evaluate an a priori 4-factor structure. Omega coefficients and 95% credible intervals (CrI) were used to assess internal reliability. Known-group validity was assessed in patients receiving active case management (n = 60) versus those without (n = 73). RESULTS The mean (± standard deviation; SD) age of the participants was 62 (±11) years. Model fit for the hypothesised model was adequate (posterior predictive p-value = 0.073) and all hypothesised factor loadings were substantial (>0.6) and significant (p

Background & aims A unique model of care was adopted in Australia following introduction of universal subsidised direct-acting antiviral (DAA) access in 2016 in order to encourage rapid scale-up of treatment. Community-based medical practitioners and integrated hepatitis nurses initiated DAA treatment with remote hepatitis specialist approval of the planned treatment without physical review. We aimed to evaluate outcomes of community-based treatment of hepatitis C (HCV) through this remote consultation process in the first 12 months of this model of care. Methods A retrospective chart review of patients undergoing community-based HCV treatment from general practitioners and integrated hepatitis nurse consultants through the remote consultation model in three state jurisdictions in Australia from 1 March 2016 to 28 February 2017. Results SVR12 was confirmed in 383/588 (65.1%) subjects intended for treatment with a median follow-up time of 12 months (IQR 9-14 months). The SVR12 test was not performed in 159/588 (27.0%) and 307/588 (52.2%) did not have liver biochemistry rechecked following treatment. Subjects who completed follow-up exhibited high SVR12 rates (383/392,97.7%). Nurse-led treatment was associated with higher confirmation of SVR12 (73.7% v 62.4%, p = 0.01) and liver biochemistry testing post treatment (57.5% v 45.0%, p = 0.01). Conclusions Community-based management of HCV through remote specialist consultation may be an effective model of care. Failure to check SVR12, recheck liver biochemistry and appropriate surveillance in patients with cirrhosis may emerge as significant issues requiring further support, education and refinement of the model to maximise effectiveness of future elimination efforts. This article is protected by copyright. All rights reserved.

A nurse-led cirrhosis clinic model for management of stable, compensated cirrhotic patients is practised in our unit since 2013, wherein these patients are reviewed every six months by specialist nurses in community clinics under remote supervision of hepatologists. We evaluated the experiences of patients and healthcare providers involved in the model to understand the acceptability, strengths, and limitations of the model and obtain suggestions to improve. A qualitative design using in-depth interviews was employed, followed by thematic analysis of eight patients, one attending physician both nurse and hospital clinics, four hepatologists, and three experienced specialist nurses running the nurse-led cirrhosis clinic. Patients expressed satisfaction and a good understanding of the nurse-led cirrhosis clinic, preferring it to hospital clinics for better accessibility and the unique nurse-patient relationship. Upskilling and provision of professional care in a holistic manner were appreciated by specialist nurses. The hepatologists expressed confidence and satisfaction, although they acknowledged the difference between the medical training of specialist nurses and hepatologists. The greater availability of hospital clinic time for sick patients was welcomed. Increased specialist nurse staffing, regular forums to promote specialist nurse learning, and formalization of the referral process were suggested. No adverse experiences were reported by patients or staff. The nurse-led cirrhosis clinic model for compensated liver cirrhosis was well received by patients, hepatologists, and specialist nurses. Wider implementation of the model could be considered after further investigations in other settings.

INTRODUCTION Transjugular intrahepatic portosystemic shunt (TIPSS) is an effective modality in reducing portal pressure, and its current main indications are for the management of recurrent ascites and variceal bleeding. The demand and indications for TIPSS are growing. However, it is a complicated and technically demanding procedure with poorer outcomes associated with low volume centres. The aim of this study was, therefore, to review the outcomes of TIPSS at a 'low volume' single centre. Outcomes assessed included indications, safety, efficacy and survival. METHODS A retrospective study was undertaken of all patients who underwent a TIPSS procedure over 10 years at tertiary referral centre for complex liver disease and transplantation. Kaplan-Meier method was used to calculate actuarial survival and log-rank analysis was used to determine significant differences in survival. RESULTS Thirty-eight patients underwent the TIPSS procedure between January 2008 and December 2018. Technical, haemodynamic and clinical success were 95%, 92% and 92% respectively. Cumulative survival at one month, one year and five years were 86.8%, 72% and 44.7% respectively. Results achieved standards published in practice parameters to evaluate TIPSS safety and efficacy. CONCLUSION At a low volume centre, TIPSS usage was associated with high rates of technical, haemodynamic (HPVG reduction) and clinical success. Low volume should not be a contraindication to providing a TIPSS service; however, auditing outcomes and understanding specific institutional factors that influence quality are important requirements for low volume centres.

The prognostic role of cardiac dysfunction in cirrhotic patients is increasingly recognized. We studied its impact on morbidity and mortality before and after liver transplantation (LT) including development of post-transplant cardiovascular disease (CVD). In this retrospective study, cirrhotic patients who underwent LT assessment from January 2010 to December 2020 were reviewed. Demographics, cardiac investigations and clinical courses were analyzed to identify the prevalence of cardiac dysfunction and its role in LT outcomes. Survival analysis was performed using Cox proportional hazard regression modelling, with LT as a time-varying covariate and as an interaction variable with cardiac dysfunction. Three hundred and eight patients (70% male) were studied. The median (interquartile range) age at LT assessment was 56 (12) years. Cardiac dysfunction was found in 178 (58%) patients (diastolic, 169; systolic, 26; both, 17) and was significantly associated with hepatorenal syndrome/acute kidney injury and peri- and post-transplant morbidity (adjusted odds ratio [aOR] 1.94, 95% CI 1.06-3.52, P .001; aOR 2.01, 95% CI 1.06-3.82, P = .033; aOR 1.9, 95% CI 1.01-3.65, P = .023, respectively). Cardiac dysfunction was not associated with mortality before (adjusted hazard ratio [aHR] 1.01, 95% CI .99-1.01) or after LT (aHR .74, 95% CI .4-1.05. Post-transplant CVD (61% cardiac failure) occurred in 36 patients, and there was no significant association with cardiac dysfunction (P = .11). Cardiac dysfunction was common in LT candidates and was significantly associated with morbidity before and after LT. Studies on the role of advanced echocardiographic parameters to improve diagnosis of cardiac dysfunction and optimize LT outcomes are needed.

This study investigated the effect of recipient and donor genetic variability on dose‐adjusted steady‐state tacrolimus concentrations (C(ss)) and clinical outcomes 3 and 6 months after liver transplant. Twenty‐nine recipients and matched donor blood samples were genotyped for 27 single nucleotide polymorphisms including CYP3A5*3 (rs776746), ABCB1 haplotype and immune genes. Associations between genetic variability and clinical parameters and C(ss) and the occurrence of rejection and nephrotoxicity were analysed by multivariate and multinomial logistic regression modelling and Jonckheere–Terpstra tests examined the impact of combined donor/recipient CYP3A5 expression on C(ss). At 3 months post‐transplant modelling revealed an association between tacrolimus C(ss) and recipient CASP1 rs580523 genotype (P = 0.005), accounting for 52% C(ss) variance. Jonckheere–Terpstra tests revealed that as combined donor/recipient CYP3A5 expression increased, C(ss) decreased (P = 0.010 [3 months], 0.018 [6 months]). As this is the first report of CASP1 genetic variability influencing tacrolimus C(ss), further validation in larger cohorts is required.

Screening and treatment for hepatitis C virus (HCV) infection were not prioritised in psychiatric patients due to adverse neuropsychiatric effects of interferon therapy despite reports of high prevalence. However, with the safe new antiviral drugs, HCV eradication has become a reality in these patients. The aim of this study was to report HCV seroprevalence, risk factors and treatment model in an Australian cohort. This prospective study involved patients admitted to four inpatient psychiatric units, from December 2016 to December 2017. After pretest counselling and consent, HCV testing was done; information on risk factors collected. A total of 260 patients (70% male), median age 44 years (IQR 24), were studied. The HCV seroprevalence was 10.8% (28/260) with 95% CI 7-15. Independent predictors of HCV positivity were injection drug use (P < 0.001, OR 44.05, 95% CI 7.9-245.5), exposure to custodial stay (P = 0.011, OR 7.34, 95% CI 1.6-33.9) and age (P = 0.011, OR 1.09, 95% CI 1.02-1.16). Eight of the 16 HCV RNA-positive patients were treated. Hepatitis nurses liaised with community mental health teams for treatment initiation and follow-up under supervision of hepatologists. Seven patients achieved sustained viral response, one achieved end of treatment response. The remaining eight patients were difficult to engage with. In conclusion, HCV prevalence was high in our cohort of psychiatric inpatients. Although treatment uptake was achieved only in 50% patients, it was successfully completed in all, with innovative models of care. These findings highlight the need to integrate HCV screening with treatment linkage in psychiatry practice.

Aim of the study To study the prevalence of risk factors for nonalcoholic fatty liver disease (NAFLD) in middle-aged (40–59 years) and elderly patients (≥60 years) with cryptogenic cirrhosis as compared to those with hepatitis B or C virus (HBV or HCV) related cirrhosis. Methods and materials Between August 2013 and December 2014, cases (cryptogenic cirrhosis) and controls (HBV/HCV cirrhosis) above 40 years of age were prospectively recruited and assessed for the cause and prevalence of risk factors for NAFLD. Results One hundred eighteen cases (male-74%; age 55 (40–74) years; median (range); Child's class A:B:C-46:38:16) and 59 controls (male-80%; age 55.5 (40–69) years; Child's class A:B:C-56:30:14) were enrolled. Obesity (53% v/s 39%, p-0.081), diabetes mellitus (DM) (52% v/s 27%; p-0.002), family history of DM (30% v/s 13%; p-0.016), family history of Obesity (21% v/s 3.5%; p-0.002) and metabolic syndrome (65% v/s 44%; p-0.01) were more among cases than controls. Lifetime weight as obese was also longer in cases than in controls (5.9 ± 6.2 years v/s 3.2 ± 5.1 years, p-0.002). On subgroup analysis, in elderly age group, DM (55% v/s 17%, p-0.006), family history of DM (40% v/s 11%, p-0.025), metabolic syndrome (76% v/s 44%, p-0.017) and family history of obesity (19% v/s 0, p-0.047) were more common in cases as compared to controls, where as in the middle-age group, family history of obesity was the only significant factor (22% v/s 5%, p-0.025). Lifetime weight as obese was longer in cases than controls in both middle and elderly age groups. Conclusion Among middle-aged and elderly patients with cirrhosis, there was a higher prevalence of risk factors for NAFLD in those with cryptogenic cirrhosis, compared to those with HBV or HCV cirrhosis.

Aim The objective was to study the long-term (lifetime) cost effectiveness of four different hepatitis C virus (HCV) treatment models of care (MOC) with directly acting antiviral drugs. Methods A cohort Markov model-based probabilistic cost-effectiveness analysis (CEA) was undertaken extrapolating to up to 30 years from cost and outcome data collected from a primary study involving a real-life Australian cohort. In this study, noncirrhotic patients treated for HCV from 1 March 2016 to 28 February 2017 at four major public hospitals and liaising sites in South Australia were studied retrospectively. The MOC were classified depending on the person providing patient workup, treatment and monitoring into MOC1 (specialist), MOC2 (mixed specialist and hepatitis nurse), MOC3 (hepatitis nurse) and MOC4 (general practitioner, GP). Incremental costs were estimated from the Medicare perspective. Incremental outcomes were estimated based on the quality-adjusted life years (QALY) gained by achieving a sustained virological response. A cost-effectiveness threshold of Australian dollar 50 000 per QALY gained, the implicit criterion used for assessing the cost-effectiveness of new pharmaceuticals and medical services in Australia was assumed. Net monetary benefit (NMB) estimates based on this threshold were calculated. Results A total of 1373 patients, 64% males, mean age 50 (SD ±11) years, were studied. In the CEA, MOC4 and MOC2 clearly dominated MOC1 over 30 years with lower costs and higher QALYs. Similarly, NMB was the highest in MOC4, followed by MOC2. Conclusion Decentralized care using GP and mixed consultant nurse models were cost-effective ways of promoting HCV treatment uptake in the setting of unrestricted access to new antivirals.

OBJECTIVES To compare the incidence of liver-related emergency admissions and survival of patients after hospitalisation for decompensated cirrhosis at two major hospitals, one applying a coordinated chronic disease management model (U1), the other standard care (U2); to examine predictors of mortality for these patients. DESIGN Retrospective observational cohort study. SETTING Two major tertiary hospitals in an Australian capital city. PARTICIPANTS Patients admitted with a diagnosis of decompensated cirrhosis during October 2013 - October 2014, identified on the basis of International Classification of Diseases (ICD-10) codes. MAIN OUTCOME MEASURES Incident rates of liver-related emergency admissions; survival (to 3 years). RESULTS Sixty-nine patients from U1 and 54 from U2 were eligible for inclusion; the median follow-up time was 530 days (range, 21-1105 days). The incidence of liver-related emergency admissions was lower for U1 (mean, 1.14 admissions per person-year; 95% CI, 0.95-1.36) than for U2 (mean, 1.55 admissions per person-year; 95% CI, 1.28-1.85; adjusted incidence rate ratio [U1 v U2], 0.52; 95% CI, 0.28-0.98; P = 0.042). The adjusted probabilities of transplantation-free survival at 3 years were 67.7% (U1) and 37.2% (U2) (P = 0.009). Independent predictors of reduced transplantation-free free survival were Charlson comorbidity index score (per point: hazard ratio [HR], 1.27; 95% CI, 1.05-1.54, P = 0.014), liver-related emergency admissions within 90 days of discharge (HR, 3.60; 95% CI, 1.87-6.92; P < 0.001), and unit (U2 v U1: HR, 2.54, 95% CI, 1.26-5.09; P = 0.009). CONCLUSIONS A coordinated care model for managing patients with decompensated cirrhosis was associated with improved survival and fewer liver-related emergency admissions than standard care.

The role of vasoactive chemicals in the pathogenesis of hepatopulmonary syndrome (HPS), a disorder characterized by intrapulmonary vascular dilation (IPVD), is only vaguely elucidated. We aimed to study the association between plasma H2S, nitrate levels, and presence and severity of IPVD and HPS. Consecutive adult patients with cryptogenic cirrhosis were evaluated for IPVD (by contrast echocardiography) and for hypoxemia (by arterial blood gas analysis). Plasma H2S and nitrate levels were measured in these patients. Fifty-eight patients with cryptogenic cirrhosis (male, 45; median age, range, 45, 16–74 years; Child’s class; A, 30; B, 18; C, 10) were enrolled in this study. Thirty-four of the 58 (59%) patients had IPVD and 13 (22%) had HPS (mild, 4; moderate, 5; severe, 2; very severe, 2). Plasma H2S levels were significantly higher in patients with IPVD (19.6, 5.7–83 μmol/L) as compared to patients who had no IPVD (12.3, 0–47 μmol/L; p-value 0.03) with an area under receiver operating characteristic curve of 0.68 (95% CI 0.53–0.84). Plasma H2S levels were higher in patients with IPVD irrespective of liver disease severity. There was a trend for higher plasma nitrate levels in patients with IPVD (47, 15.8–126.4 nmol/mL) as compared to patients who had no IPVD (32.3, 6.9–51.4 nmol/mL; p-value 0.1). Raised plasma H2S and nitrate levels had an additive effect on the presence of IPVD. Neither plasma H2S nor plasma nitrate levels correlated with the degree of hypoxemia. Raised plasma H2S and nitrate levels predict the presence of IPVD in patients with cryptogenic cirrhosis.

BACKGROUND AND AIMS In this follow-up study to a randomized controlled trial of a chronic disease management (CDM) model in cirrhosis, our aim was to assess the relative cost-effectiveness of this model compared with usual care during the 12-month study period, using incremental costs per death avoided as the primary outcome. METHODS Mean differences in hospitalization costs, deaths avoided, and change in Chronic Liver Disease Questionnaire (CLDQ) total scores were presented with 95% non-parametric bootstrapped confidence intervals. Results were also presented using a cost-effectiveness plane (CEP) and cost-effectiveness acceptability curve. RESULTS The CDM intervention was more expensive, by 18 521 AUD per participant, but more effective (% of deaths at 12 months: 10% vs 15% and 0.67 units increase per patient in CLDQ total scores). The resultant incremental cost-effectiveness ratios were 370 425 AUD per death avoided (95% confidence interval: -14 564 AUD to 2 059 373 AUD) and 27 547 AUD per unit improvement in the CLDQ total score (95% CI: 7455 AUD to 143 874 AUD). The CEPs demonstrated some uncertainty around cost-effectiveness. The cost-effectiveness acceptability curves demonstrated that at willingness to pay values of 400 000 AUD per additional death avoided and 40 000 AUD per unit improvement in the CLDQ, there was at least a 70% probability of CDM being more cost-effective than usual care. At 24 months, CDM was much more effective (12% less deaths but now also cheaper by 985 AUD per patient). CONCLUSIONS The analysis of data from a randomized controlled trial suggests that the CDM intervention used is likely to be cost-effective, relative to usual care, due to fewer patient deaths.

Experience with zinc in treating symptomatic hepatic Wilson’s disease (WD) is limited. To study the efficacy of Penicillamine followed by zinc in treating symptomatic hepatic Wilson’s disease. We retrospectively analyzed case records of 31 symptomatic hepatic WD patients for whom disease severity scores (Child’s, model for end-stage liver disease (MELD), Nazer’s, and New Wilson Index (NWI) score) and 24-h urinary copper were compared at 3-time points—baseline at presentation, at transition from penicillamine to zinc and at end of follow up. Thirty-one patients (median age 11 [5–24] years) with symptomatic hepatic WD were studied; ten had associated neuropsychiatric manifestations of WD. Penicillamine was changed to zinc sulfate either due to financial constraints (28 patients) or due to adverse effects of penicillamine (3 patients). At presentation (baseline), six patients belonged to Child’s class A, five to Child’s B, and 17 to Child’s C. Duration of initial penicillamine chelation therapy was 134 (2–320) weeks, and of subsequent zinc therapy was 363 (35–728) weeks. There was a significant improvement in liver function tests and disease severity scores (Child’s, MELD, Nazer’s, and NWI score) at the transition from penicillamine to zinc compared to baseline. This improvement was maintained until the end of study period with 90% survival at 10 (2–20) years. Fifteen of the 17 Child’s C cirrhotic patients showed significant improvement in disease severity scores from baseline until end of follow up. Penicillamine followed by zinc may be a safe and effective treatment in resource-constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Some patients with decompensated cirrhosis due to WD may be managed with medical treatment, avoiding liver transplantation.

Background & Aims There is no validated questionnaire to assess disease knowledge and self-management in patients with liver cirrhosis. We developed and validated a Cirrhosis Knowledge Questionnaire (CKQ). Methods We created a preliminary CKQ comprising 10 questions relevant to self-management of cirrhosis, based on publications and clinical experiences. The CKQ was given to a pilot sample of 17 patients with decompensated cirrhosis to assess its face validity. In consultation with experts, we developed a second version of CKQ, comprising 14 multiple choice questions, and administered it to 116 patients with cirrhosis participating in a Chronic Liver Failure Program. The dimensionality of the construct was assessed using exploratory factor analysis and internal consistency was assessed with Cronbach’s alpha. Known-group validity of the resulting instrument was assessed by comparing the performance of the CKQ in 69 patients with decompensated cirrhosis (mean age, 62 ± 13 years; 109 responses), with (n = 42) vs without (n = 67) case management. Results A 3-factor model with 7 questions related to variceal bleeding, ascites, and hepatic encephalopathy was considered the optimal dimensionality with excellent internal consistency (Cronbach’s alpha = 0.82). The mean knowledge score was higher in patients with case management (5.6 ± 1.1) than in patients without case management (4.3 ± 2.1) (P = .002). Conclusions We developed and validated a questionnaire with 7 questions on ascites, variceal bleeding, and hepatic encephalopathy to assess knowledge and self-management in patients with liver cirrhosis. Studies are needed to confirm its dimensionality and assess association of scores with patient outcomes.

BACKGROUND AND AIMS Screening for latent tuberculosis infection (LTBI) is recommended prior to solid organ transplantation. Interferon-gamma release assays (IGRAs) are the most widely used test for LTBI screening; however, assessment of IGRA performance in patients with end-stage liver disease is limited. The purpose of this study was to evaluate the prevalence and predictors of indeterminate (INDT) IGRA results in liver transplantation candidates. METHODS Between March 2011 and May 2018, we retrospectively analyzed 155 patients undergoing liver transplantation assessment, who underwent IGRA testing (Quantiferon-TB Gold, QFT-G) to exclude LTBI. Characteristics of patients, including age, gender, etiology of liver disease, MELD score, and absolute lymphocyte counts, were compared by QFT-G result (determinate vs INDT). RESULTS Of the 155 patients screened, the rate of positive, negative, and INDT results were 5.2%, 69.8%, and 25%, respectively. The only variable independently associated with an indeterminate test on multivariate analysis was MELD score (odds ratio = 1.07, 95% CI = 1.01-1.14 per unit increase; P = 0.014). In 95% of INDT tests, both TB antigen tube and the positive control tube were negative and repeat testing gave the same indeterminate result, suggestive of anergy rather than laboratory error. CONCLUSIONS Our study suggests a high rate of INDT IGRA results during screening of liver transplant candidates for LTBI, associated with severity of liver disease and anergy. Because of the high rate of INDT QFT-G testing in this setting, individualized risk assessment is required including a thorough assessment of clinical risk factors and knowledge of local TB prevalence.

In March 2016, the Australian government offered unrestricted access to direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) to the entire population. This included prescription by any medical practitioner in consultation with specialists until sufficient experience was attained. We sought to determine the outcomes and experience over the first twelve months for the entire state of South Australia. We performed a prospective, observational study following outcomes of all treatments associated with the state's four main tertiary centres. A total of 1909 subjects initiating DAA therapy were included, representing an estimated 90% of all treatments in the state. Overall, SVR12 was 80.4% in all subjects intended for treatment and 95.7% in those completing treatment and follow-up. 14.2% were lost to follow-up (LTFU) and did not complete SVR12 testing. LTFU was independently associated with community treatment via remote consultation (OR 1.50, 95% CI 1.04-2.18, P = .03), prison-based treatment (OR 2.02, 95% CI 1.08-3.79, P = .03) and younger age (OR 0.98, 95% CI 0.97-0.99, P = .05). Of the 1534 subjects completing treatment and follow-up, decreased likelihood of SVR12 was associated with genotype 2 (OR 0.23, 95% CI 0.07-0.74, P = .01) and genotype 3 (OR 0.23, 95% CI 0.12-0.43, P ≤ .01). A significant decrease in treatment initiation was observed over the twelve-month period in conjunction with a shift from hospital to community-based treatment. Our findings support the high responses observed in clinical trials; however, a significant gap exists in SVR12 in our real-world cohort due to LTFU. A declining treatment initiation rate and shift to community-based treatment highlight the need to explore additional strategies to identify, treat and follow-up remaining patients in order to achieve elimination targets.

Background and aims: Treatment of hepatitis C virus (HCV) in patients with mental illness was previously hampered by the adverse neuropsychiatric effects of interferon therapy. The new era of directly acting antiviral (DAA) therapy has renewed interest in HCV treatment in this population due to its improved safety profile. The aims of this study were therefore to assess HCV prevalence and risk factors in psychiatric inpatients and to explore treatment models of care. Methods: This prospective study involved patients admitted to four inpatient psychiatric units, from December 2016 to December 2017. After consent HCV testing was performed, and information about HCV risk factors was obtained. Results: Two hundred and sixty patients (70% male), median age 44 years (IQR 24) participated in the study. The period prevalence of HCV antibody was 10·8% (95% CI 7-15). 80% of the study cohort had at least one risk factor for HCV. Independent predictors of HCV positive status were injection drug use (p

The role of vasoactive chemicals in the pathogenesis of hepatopulmonary syndrome (HPS), a disorder characterized by intrapulmonary vascular dilation (IPVD), is only vaguely elucidated. We aimed to study the association between plasma HConsecutive adult patients with cryptogenic cirrhosis were evaluated for IPVD (by contrast echocardiography) and for hypoxemia (by arterial blood gas analysis). Plasma HFifty-eight patients with cryptogenic cirrhosis (male, 45; median age, range, 45, 16-74 years; Child's class; A, 30; B, 18; C, 10) were enrolled in this study. Thirty-four of the 58 (59%) patients had IPVD and 13 (22%) had HPS (mild, 4; moderate, 5; severe, 2; very severe, 2). Plasma HRaised plasma H

In this follow-up study to a randomized controlled trial of a chronic disease management (CDM) model in cirrhosis, our aim was to assess the relative cost-effectiveness of this model compared with usual care during the 12-month study period, using incremental costs per death avoided as the primary outcome.Mean differences in hospitalization costs, deaths avoided, and change in Chronic Liver Disease Questionnaire (CLDQ) total scores were presented with 95% non-parametric bootstrapped confidence intervals. Results were also presented using a cost-effectiveness plane (CEP) and cost-effectiveness acceptability curve.The CDM intervention was more expensive, by 18 521 AUD per participant, but more effective (% of deaths at 12 months: 10% vs 15% and 0.67 units increase per patient in CLDQ total scores). The resultant incremental cost-effectiveness ratios were 370 425 AUD per death avoided (95% confidence interval: -14 564 AUD to 2 059 373 AUD) and 27 547 AUD per unit improvement in the CLDQ total score (95% CI: 7455 AUD to 143 874 AUD). The CEPs demonstrated some uncertainty around cost-effectiveness. The cost-effectiveness acceptability curves demonstrated that at willingness to pay values of 400 000 AUD per additional death avoided and 40 000 AUD per unit improvement in the CLDQ, there was at least a 70% probability of CDM being more cost-effective than usual care. At 24 months, CDM was much more effective (12% less deaths but now also cheaper by 985 AUD per patient).The analysis of data from a randomized controlled trial suggests that the CDM intervention used is likely to be cost-effective, relative to usual care, due to fewer patient deaths.

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality and healthcare expenditure in patients with chronic liver disease. There are no consensus guidelines on diagnosis and management of HCC in India. The Indian National Association for Study of the Liver (INASL) set up a Task-Force on HCC in 2011, with a mandate to develop consensus guidelines for diagnosis and management of HCC, relevant to disease patterns and clinical practices in India. The Task-Force first identified various contentious issues on various aspects of HCC and these issues were allotted to individual members of the Task-Force who reviewed them in detail. The Task-Force used the Oxford Center for Evidence Based Medicine—Levels of Evidence of 2009 for developing an evidence-based approach. A 2-day round table discussion was held on 9th and 10th February, 2013 at Puri, Odisha, to discuss, debate, and finalize the consensus statements. The members of the Task-Force reviewed and discussed the existing literature at this meeting and formulated the INASL consensus statements for each of the issues. We present here the INASL consensus guidelines (The Puri Recommendations) on prevention, diagnosis and management of HCC in India.

Hepatocellular carcinoma (HCC) is a dreaded complication of cirrhosis as it is the commonest cause of mortality in these patients. The last few years have seen a dramatic improvement in the management of this tumor as nearly 50–70% of selected patients with early HCC survive for a median period of up to 5 years after liver transplantation, resection or local ablation. Surveillance has been found to be an effective tool to detect early tumors and expand the applicability of these curative treatment options. Semiannual ultrasonogram is recommended for surveillance by the American, European and Asia Pacific liver societies and is the standard of care in many countries. There is increasing evidence that this practice improves survival too. Since the only way to improve the outlook of HCC is its diagnosis prior to commencement of symptoms, providing surveillance becomes a major responsibility of physicians caring for patients with chronic liver disease. This review attempts to discuss the population at risk of HCC, modalities and frequency of surveillance tests, cost effectiveness and also the logistics of its delivery in the Indian context.

BACKGROUND Serum cholinesterase (ChE) is an enzyme synthesised by hepatocytes and its serum levels reflect the synthetic function of liver. METHODS In patients with cirrhosis, liver function tests, PT INR and serum ChE levels were done within a week of enrolment. We studied 178 cirrhosis patients and 154 healthy controls prospectively. Receiver operator characteristics (ROC) curve analysis was employed to compute an optimal cut-off level to distinguish these groups. Correlation between ChE activity and serum bilirubin, albumin, PT INR and MELD score (Model for End-Stage Liver Disease) was analysed. RESULTS Median serum ChE in cirrhotics was 1590 IU/L (110-8143) compared to controls 7886 IU/L (2022- 21673), p < 0.001. Serum ChE levels below 3506 had a 98.7% sensitivity and 80.3% specificity in predicting cirrhosis. Median serum ChE was higher (p < 0.001) in CC (n = 51) 4246 IU/L (680-8143) compared to DC (n = 127) 1324 IU/L (110-4550). ChE level less than 2385 IU/L had 80.1% sensitivity and 88.2% specificity in predicting DC. Follow-up levels in 25 patients showed good correlation with clinical course. The correlation coefficient between ChE and albumin was -0.67, 0.53 with PT INR and 0.59 with MELD score, (p < 0.001). CONCLUSIONS Serum ChE is an excellent biomarker of cirrhosis with good sensitivity and specificity. It shows good correlation with serum albumin, PT INR and MELD score. Since it distinguishes DC from CC well, low levels in cirrhosis may serve as a useful prognostic marker of advanced liver disease. Long-term follow-up studies are warranted to define its exact role in clinical practice.

Adefovir is one of the therapeutic options for the treatment of chronic hepatitis B. A total of 30 adefovir-experienced subjects with the median treatment duration of 12 (interquartile range (IQR) 6-18) months were studied. Virological response was measured by hepatitis B virus deoxyribonucleic acid (HBV DNA) levels. HBV reverse transcriptase (rt) domains were sequenced for the identification of resistance mutations. Among the 30 subjects, two (7%) showed virological response and 19 (63%) were non-responders. The virological response for the remaining nine (30%) subjects was not determined. On sequence analysis, two subjects were identified with rtI169L and rtA181V mutation after 9 months and 18 months of adefovir treatment, respectively. Though the frequencies of adefovir resistance mutations are low, a large majority of subjects showed non-response. Therefore, adefovir in the management of HBV should be used judiciously.

Patients with cirrhosis have increased morbidity from hepatitis A virus (HAV) and hepatitis B virus (HBV) infections, and vaccination against these infections is an important standard of care.1,2 However, vaccination in patients with cirrhosis is hindered by immune dysfunction and there is limited high-quality literature available. The aim of this work therefore was to compare immune responses of standard dose (SD) with high-dose accelerated (HDA) vaccination in cirrhotic patients.

Management of chronic hepatitis B is a global public health challenge. There are several updated guidelines proposed based on treatment outcome data from the respective study populations. In this study, we aim to characterize the antiviral resistance mutations to lamivudine monotherapy in patients diagnosed with chronic hepatitis B from the Indian subcontinent. A total of 147 lamivudine-treated patients with a median treatment duration of 13 (interquartile range 8–24) months were studied. Virological response was measured by hepatitis B virus (HBV) DNA levels. Antiviral resistance mutations were identified by sequencing HBV reverse transcriptase domains. Factors associated with virological response and antiviral resistance mutations were analyzed. Virological response was observed in 50 (35 %) patients while 84 (57 %) were non-responders. The virological response for the remaining 13 (9 %) patients was undetermined. Forty patients (27 %) developed lamivudine-resistant mutations. HBV genotypes, subgenotypes and hepatitis B surface antigen subtypes did not show significant association with virological response or lamivudine-resistant mutations. High HBV DNA levels and increased treatment duration were strongly associated with the development of lamivudine-resistant mutations (p = 0.002 and p

Conflicting data exist concerning the accuracy of esophageal capsule endoscopy (ECE) for the screening of varices. No study has examined the influence of operator factors on the accuracy of ECE reporting. The primary aims of this study were, therefore, to examine how operator experience with esophagogastroduodenoscopy (EGD) and operator reporting times of capsule videos influenced test accuracy. Twelve cirrhotic patients presenting for EGD had same-day ECE performed. The gold standard for variceal grade was determined using a panel of experienced endoscopists. Six novice capsule endoscopists, blinded to results of EGD, subsequently reported capsule videos for each of the 12 patients.Novice capsule endoscopists accurately identified high-risk varices. The mean area under the receiver operating characteristic curve for identifying high-risk varices for the six operators was 0.88 ±/-0.14. The mean sensitivity, specificity, positive, and negative predictive values for identifying high-risk varices for the six operators were 83%, 93%, 82%, and 97%, respectively. Years of prior EGD experience were not associated with accuracy of capsule reporting (OR = 0.9, 95% CI [0.74, 1.08]; p = .26). Time spent reporting capsule videos was associated with accuracy of capsule reporting for high-risk varices using British Society of Gastroenterology criteria (OR = 1.33, 95% CI [1.05, 1.08]; p = .018). Novice capsule endoscopists are able to accurately identify high-risk esophageal varices. Time taken to report capsule videos, but not amount of prior EGD experience, influenced capsule report accuracy. These findings may have implications for the design of further trials and the cost-effectiveness of ECE screening of varices.

Biotinidase is an enzyme synthesized predominantly by the liver. Serum activity of this enzyme has been shown to be low in chronic liver disease. In this study, we endeavored to assess the diagnostic value of serum biotinidase as a marker of hepatic biosynthetic function in acute and chronic liver dysfunction. Twenty-three patients with acute liver disease and 46 with chronic liver disease, as diagnosed by clinical examination, laboratory tests, histopathology and tests for viral markers, were inducted into the study. Forty-six healthy volunteers were selected as controls. Serum biotinidase activity was estimated in all the subjects. Biotinidase activity was found to be significantly lower in the serum of patients with acute (4.59 ± 1.26 IU/L vs 7.56 ± 0.82 IU/L in controls; P≤ 0.001) and chronic (2.98 ± 1.18 IU/L vs 7.56 ± 0.82 IU/L in controls; P≤ 0.001) liver disease. Using receiver–operator characteristic curves, serum biotinidase was found to have high values of sensitivity and specificity when applied as a diagnostic test in both acute and chronic liver disease. These results suggest that serum biotinidase may be a sensitive and specific diagnostic marker of hepatic biosynthetic function in both acute and chronic liver disease.

Background and Aims: The adverse effect of acute hepatitis A in chronic liver disease is well known. The outcome of acute hepatitis E in chronic liver disease has not been extensively studied. The present study aimed to examine the clinical profile and outcome of patients with chronic liver disease and hepatitis E virus (HEV) superinfection, and the seroprevalence of hepatitis A and E infections in patients with chronic liver disease and controls in India. Methods: A retrospective study of patients with chronic liver disease and acute icteric hepatitis E was performed. Acute hepatitis E was diagnosed by immunoglobulin (Ig)M ELISA. Seroprevalence studies were carried out using IgG ELISA in 100 patients with chronic liver disease and 79 age- and sex-matched controls. Results: From June 2001 to December 2002, nine patients with chronic liver disease were found to have superinfection with HEV. Out of these, six patients died of advanced liver failure. The etiology of liver disease was Wilson's disease in six, hepatitis B virus in one, autoimmune in one and cryptogenic in one case. The seroprevalence of hepatitis A was 99 and 100% and 56 and 21% for HEV in cases and controls, respectively. Conclusions: Acute HEV in patients with chronic liver disease has a grave prognosis. Wilson's disease was the most common cause of chronic liver disease complicated by acute HEV. Seroprevalence studies showed that 44% of patients with chronic liver disease were at risk of developing hepatitis E. Hepatitis E vaccine, when available, is indicated for use in this group.

BACKGROUND Severe autoimmune hepatitis is an entity which has been rarely reported in the Indian literature. We describe here the clinicopathological profile and treatment of severe autoimmune hepatitis (SAH) which is to the best of our knowledge the first report from India addressing this illness. METHODS AND RESULTS Between September 2010 and March 2013, 13 patients seeking treatment at our centre were diagnosed as SAH and treated with steroids. Jaundice along with coagulopathy was the presenting symptom in all these patients. Ascites was present in ten and encephalopathy in 6 patients. The median serum IgG was 2135 mg/dl (range: 1122-5490).Significant titers of autoantibodies were present in all patients except one. Transjugular liver biopsy in 9 patients showed characteristic features of SAH such as extensive bridging necrosis and moderate to dense portal inflammation. With corticosteroid therapy, 10 patients survived while three died. In those who survived, biochemical improvement was seen as early as seven days with excellent long-term remission. CONCLUSIONS Clinical suspicion supported by liver biopsy and autoimmune serology led to the diagnosis of SAH in a cohort of patients with unexplained liver failure. Corticosteroids were beneficial in majority of patients affording excellent results and this could be predicted by early reduction in serum bilirubin within 7-15 days.

Hepatitis C virus (HCV) infection is an important cause of liver-related morbidity and mortality in patients with end-stage renal disease (ESRD). Though indicated, antiviral therapy adds to the existing financial burden and is poorly tolerated in these patients. We studied HCV treatment outcomes in patients with moderate and severe chronic kidney disease (CKD) between June 2010 and June 2012. Out of 46 patients with CKD, only 16 (genotype 1:6, 3:9, indeterminate 1) received interferon treatment (conventional 9, pegylated 7; with low-dose ribavirin 5). End of treatment response was achieved in 50 % and sustained viral response in 44 %. Adverse effects such as tuberculosis, anemia, and cardiac failure resulting in discontinuation of therapy were seen in three. The dropout rate was 38 %. Though interferon therapy was efficacious and safe, it was received by only 35 % of patients with CKD. We suggest that antiviral therapy be offered under close monitoring in the absence of contraindications in patients with moderate and severe CKD.

The incidence of chronic kidney disease (CKD) and its impact on survival have not been widely studied in the Australian liver transplant (OLT) population. The aims of this study were to evaluate the prevalence of CKD stages at various time points, calculate the cumulative incidence of progression to severe CKD, and study the impact of CKD stages on patient survival and risk factors for severe CKD in a single-center post-OLT population. We studied retrospectively 130 patients who underwent OLT in South Australia with a minimum of 6 months of follow-up from 1992 to 2008. CKD was staged according to Kidney Diseases Outcome Quality Initiative Guidelines. Glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease equation. Multiple pre- and post-OLT variables were examined for their association with severe CKD. Log-rank tests and Cox regression analysis were performed to evaluate the survival data. The cumulative incidences of severe CKD (stages 4 and 5) at 2, 5, and 15 years were 3.8%, 12.7%, and 14.8%, respectively. Severe CKD was associated with an increased mortality (hazard ratio 6.5; 95% confidence interval = 2.5-17.0; P < .001). Mild and moderate CKD stages were not associated with increased mortality. Risk factors for severe CKD were: female gender, hepatitis C infection, pre-OLT diabetes, acute renal failure post-OLT, and low 1-year GFR. Mild and moderate CKD are common post-OLT. The development of severe CKD, which can be predicted early in the post-OLT period, is strongly associated with an increased mortality rate.

Background & objectives: There are only a few studies on aetiology of portal hypertension among adults presenting to tertiary care centres in India; hence we conducted this study to assess the aetiological reasons for portal hypertension in adult patients attending a tertiary care centre in southern India. Methods: Causes of portal hypertension were studied in consecutive new adult patients with portal hypertension attending department of Hepatatology at a tertiary care centre in south India during July 2009 to July 2010. Results: A total of 583 adult patients (>18 yr old) were enrolled in the study. After non-invasive testing, commonest causes of portal hypertension were cryptogenic chronic liver disease (35%), chronic liver disease due to alcohol (29%), hepatitis B (17%) or hepatitis C (9%). Of the 203 patients with cryptogenic chronic liver disease, 39 had liver biopsy - amongst the latter, idiopathic non cirrhotic intrahepatic portal hypertension (NCIPH) was seen in 16 patients (41%), while five patients had cirrhosis due to non alcoholic fatty liver disease. Fifty six (10%) adult patients with portal hypertension had vascular liver disorders. Predominant causes of portal hypertension in elderly (>60 yrs; n=83) were cryptogenic chronic liver disease (54%) and alcohol related chronic liver disease (16%). Interpretation & conclusions: Cryptogenic chronic liver disease was the commonest cause of portal hypertension in adults, followed by alcohol or hepatitis B related chronic liver disease. Of patients with cryptogenic chronic liver disease who had liver biopsy, NCIPH was the commonest cause identified. Vascular liver disorders caused portal hypertension in 10 per cent of adult patients. Cryptogenic chronic liver disease was also the commonest cause in elderly patients.

There is paucity of Indian data regarding serum HBsAg levels (qHBsAg) in treatment-naïve chronic hepatitis B (CHB). This study was done to determine correlation of qHBsAg with hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels and its ability to independently categorize subgroups of CHB.We studied 131 treatment-naive CHB patients and initially classified them based on HBeAg status. The HBeAg-positive group was further classified into immune tolerance (IT) and immune clearance (IC) phases based on serum alanine aminotransferase. HBeAg-negative patients were classified into low replicators (LR) and HBeAg-negative chronic hepatitis (ENH) based on DNA levels. HBsAg quantification was performed using the Architect chemiluminescence system.HBeAg-positive patients had higher DNA (7.89 vs. 2.69 log10 IU/mL) and higher qHBsAg (4.60 vs. 3.85 log10 IU/mL) compared to the HBeAg-negative group. Good correlation between qHBsAg and DNA was seen in HBeAg-positive (ρ = 0.6, p 0.001) but not in HBeAg-negative CHB (ρ = 0.2). A qHBsAg level greater than 4.39 log10 IU/mL predicted HBeAg-positive state with 81 % sensitivity and 85 % specificity. However, among HBeAg-negative CHB, qHBsAg failed to discriminate between LR and ENH.A single point estimation of qHBsAg in treatment-naïve patients could predict replicative HBeAg-positive CHB, but was not helpful in defining replicative status in the HBeAg-negative CHB.

Item does not contain fulltext Eosinophilic necrotizing granulomas in the liver, known as visceral larva migrans (VLM), are a rare cause of liver abscesses. The term VLM refers to infections in human tissues caused by the larval stages of ascarid worms of dogs and cats. We report two cases of VLM which presented with high grade fever and abdominal pain for 3-4 months. Marked peripheral eosinophilia, multiple confluent perivenous lesions in the right lobe of liver with characteristic migratory tracts on imaging and biopsy evidence of necrotizing eosinophilic granulomas led to the diagnosis. Complete recovery was achieved with repeated courses of a combination of anthelmintics.

Idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH) is often mis-diagnosed as cryptogenic cirrhosis. Serum vitamin B12 levels can be raised in cirrhosis, probably because of excess release or reduced clearance. Because NCIPH is characterised by long periods of preserved liver function, we examined whether serum B12 level could be used as a marker to differentiate NCIPH from cryptogenic cirrhosis.We analysed serum B12 levels in 45 NCIPH and 43 cryptogenic cirrhosis patients from January 2009 to September 2011.Serum B12 levels were significantly lower in NCIPH patients than in cryptogenic cirrhosis patients (p0.001) and were useful in differentiating the two disorders (area under ROC: 0.84; 95% C.I: 0.76-0.93). Low serum B12 level (≤250 pg/ml) was noted in 25/72 (35%) healthy controls, 14/42 (33%) NCIPH patients, and 1/38 (3 %) cryptogenic cirrhosis patients. In patients with intrahepatic portal hypertension of unknown cause, serum B12 level ≤ 250 pg/ml was useful for diagnosing NCIPH (positive predictive value: 93 %, positive likelihood ratio 12.7), and serum B12 level1,000 pg/ml was useful in ruling out NCIPH (negative predictive value: 86 %, negative likelihood ratio: 6.67). Low serum B12 levels (≤250 pg/ml) correlated with diagnosis of NCIPH after adjusting for possible confounders (O.R: 13.6; 95% C.I:1.5-126.2). Among patients in Child's class A, serum B12 level was ≤250 pg/ml in 14/35 NCIPH patients compared with 1/21 cryptogenic cirrhosis patients (O.R: 13.3; 95% C.I: 1.6-111).Serum vitamin B12 level seems to be a useful non-invasive marker for differentiation of NCIPH from cryptogenic cirrhosis.

Human T cell lymphotropic virus type 1 (HTLV-1) infection is a risk factor for Strongyloides stercoralis infection. HTLV-1 also predisposes to the development of T cell malignancies. We report a case of a patient with severe, treatment resistant Strongyloides infection and HTLV-1 infection who progressed to develop an advanced high grade T cell lymphoma of the intestine.