Kidney after liver transplantation does not have an increased risk of rejection compared to liver alone.

BACKGROUND: Simultaneous liver kidney (SLK) transplant protects against acute cellular rejection. In 2017, UNOS implemented a "safety net" policy to allow patients with renal recovery to avoid renal transplantation. Whether kidney after liver transplantation (KALT) increases the risk of rejection is unknown. METHODS: We performed a retrospective analysis of the Organ Procurement and Transplantation Network (OPTN) database of adult patients who received liver transplant, SLK or KALT between 2010 and 2020. We examined rejection of the liver within 6 months and 1 year of the liver transplant, as well as rejection of the kidney within 6 months and 1 year of receiving the kidney, as well as patient and graft loss. RESULTS: Sixty-six thousand seventy-nine patients were transplanted; 60 168 with liver transplant alone, 5627 with SLK, and 284 with KALT. Acute or chronic liver rejection rates within 6 or 12 months were statistically higher in the KALT group (10.0% and 10.9%) compared to the SLK group (6.1% and 7.5%), but comparable to the LTA group (9.3% and 11.1%). Kidney rejection and graft survival rates were not different. Liver graft survival was worse in KALT than SLK or LTA (Kaplan-Meier estimates .61 vs. .89 and .90), but these patients were more ill at the time of transplantation. KDPI and LDRI scores were notably lower in the SLK than KALT group. Patient survival was not clinically different between the groups. CONCLUSION: KALT does not increase the risk of acute or chronic kidney rejection. SLK has a lower risk of early liver rejection, but this effect diminishes by one year to being not clinically different compared to KALT. Given that KALT is immunologically safe, and potentially avoids unnecessary renal graft use, it should be preferred over SLK. BRIEF SUMMARY: Patients undergoing sequential kidney after liver transplant do not have an increased risk of liver or kidney rejection when compared to liver transplant alone or simultaneous liver and kidney transplant.

Improved outcomes of kidney after liver transplantation after the implementation of the safety net policy.

The number of kidney after liver transplants (KALT) increased after the implementation of the United Network of Organ Sharing (UNOS) safety net policy, but the effects of the policy on KALT outcomes remain unknown. Using the UNOS database, we identified KALT between 60 and 365 days from liver transplant from January 1, 2010, to December 31, 2020. The main outcome was 1- and 3-year patient, liver, and kidney graft survival. Secondary outcomes included 6-month and 1-year acute rejection (AR) of liver and kidney, and 1-year kidney allograft function. Of the 256 KALT, 90 were pre-policy and 166 post-policy. Compared to pre-policy, post-policy 1- and 3-year liver graft survival was higher (54% and 54% vs. 86% and 81%, respectively, p <0.001), while 1- and 3-year kidney graft survival (99% and 75% vs. 92% and 79%, respectively, p =0.19), and 1- and 3-year patient survival (99% and 99% vs. 95% and 89%, respectively, p =0.11) were not significantly different. Subgroup analysis revealed similar trends in patients with and without renal failure at liver transplant. Liver AR at 6 months was lower post-policy (6.3% vs. 18.3%, p =0.006) but was similar (10.5% vs. 13%, p =0.63) at 1 year. Kidney AR was unchanged post-policy at 6 months and 1 year. Creatinine at 1 year did not differ post-policy versus pre-policy (1.4 vs. 1.3 mg/dL, p =0.07) despite a higher proportion of deceased donors, higher Kidney Donor Profile Index, and longer kidney cold ischemia time post-policy ( p <0.05 for all). This 3-year follow-up after the 2017 UNOS policy revision demonstrated that the safety net implementation has resulted in improved liver outcomes for patients who underwent KALT with no increased AR of the liver or the kidney allografts.

Nonalcoholic Fatty Liver Disease and the Development of Metabolic Comorbid Conditions in Patients With Human Immunodeficiency Virus Infection.

BACKGROUND: Cardiovascular and liver disease are main causes of death in people with human immunodeficiency virus (HIV) (PWH). In HIV-uninfected patients, nonalcoholic fatty liver disease (NAFLD) is associated with incident metabolic complications. We investigated the effect of NAFLD on development of metabolic comorbid conditions in PWH. METHODS: We included PWH undergoing a screening program for NAFLD using transient elastography. NAFLD was defined as a controlled attenuation parameter ≥248 dB/m with exclusion of other liver diseases. Incident diabetes, hypertension, dyslipidemia, and chronic kidney disease were investigated using survival analysis and Cox proportional hazards. RESULTS: The study included 485 HIV-monoinfected patients. During a median follow-up of 40.1 months (interquartile range, 26.5-50.7 months), patients with NAFLD had higher incidences of diabetes (4.74 [95% confidence interval, 3.09-7.27] vs 0.87 [.42-1.83] per 100 person-years) and dyslipidemia (8.16 [5.42-12.27] vs 3.99 [2.67-5.95] per 100 person-years) than those without NAFLD. With multivariable analysis, NAFLD was an independent predictor of diabetes (adjusted hazard ratio, 5.13; 95% confidence interval, 2.14-12.31) and dyslipidemia (2.35; 1.34-4.14) development. CONCLUSIONS: HIV-monoinfected patients with NAFLD are at higher risk of incident diabetes and dyslipidemia. Early referral strategies and timely management of metabolic risk may improve outcomes.

Prediction of Esophageal Varices by Liver Stiffness and Platelets in Persons With Human Immunodeficiency Virus Infection and Compensated Advanced Chronic Liver Disease.

BACKGROUND: People living with human immunodeficiency virus (PLWH) are at increased risk of cirrhosis and esophageal varices. Baveno VI criteria, based on liver stiffness measurement (LSM) and platelet count, have been proposed to avoid unnecessary esophagogastroduodenoscopy (EGD) screening for esophageal varices needing treatment (EVNT). This approach has not been validated in PLWH. METHODS: PLWH from 8 prospective cohorts were included if they fulfilled the following criteria: (1) compensated advanced chronic liver disease (LSM >10 kPa); (2) availability of EGD within 6 months of reliable LSM. Baveno VI (LSM <20 kPa and platelets >150 000/µL), expanded Baveno VI (LSM <25 kPa and platelets >110 000/µL), and Estudio de las Hepatitis Víricas (HEPAVIR) criteria (LSM <21 kPa) were applied to identify patients not requiring EGD screening. Criteria optimization was based on the percentage of EGDs spared, while keeping the risk of missing EVNT <5%. RESULTS: Five hundred seven PLWH were divided into a training (n = 318) and a validation set (n = 189). EVNT were found in 7.5%. In the training set, Baveno VI, expanded Baveno VI, and HEPAVIR criteria spared 10.1%, 25.5%, and 28% of EGDs, while missing 0%, 1.2%, and 2.2% of EVNT, respectively. The best thresholds to rule out EVNT were platelets >110 000/µL and LSM <30 kPa (HIV cirrhosis criteria), with 34.6% of EGDs spared and 0% EVNT missed. In the validation set, HEPAVIR and HIV cirrhosis criteria spared 54% and 48.7% of EGDs, while missing 4.9% and 2.2% EVNT, respectively. CONCLUSIONS: Baveno VI criteria can be extended to HEPAVIR and HIV cirrhosis criteria while sparing a significant number of EGDs, thus improving resource utilization for PLWH with compensated advanced chronic liver disease.

Novel Inflammatory-Nutritional Biomarkers as Predictors of Histological Activity in Crohn's Disease.

BACKGROUND: There has increasingly been an interest in histological remission as a therapeutic endpoint in inflammatory bowel disease. The aim of this study was to evaluate the utility of a variety of inflammatory - nutritional markers for predicting histological disease activity in patients diagnosed with Crohn's disease. METHODS: Patients with Crohn's disease that had requisite endoscopic, pathological, and laboratory data were retrospectively enrolled in the study. Relevant clinical, laboratory, endoscopic, and pathological data were abstracted. The neutrophil:lymphocyte ratio (NLR), lymphocyte:monocyte ratio (LMR), platelet:lymphocyte ratio (PLR), red blood cell distribution width (RDW), modified Glasgow Prognostic score (mGPS), Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk index (GNRI), CRP/Albumin ratio (CAR), Iron:Ferritin ratio (Fe:F) and the Systemic immune inflammation index (SII) were calculated. The cohort was stratified by presence of histological disease on colonoscopy, and groups were compared with appropriate statistical methods. RESULTS: When comparing patients without histological disease to those with disease, there was a statistically significant difference in CAR (2.9 ± 1.5 vs. 4.2 ± 2, p = 0.001), RDW (13.4 ± 1.3 vs. 14.5 ± 1.8, p = 0.008), PNI (52.4 ± 6.2 vs. 47.4 ± 9.3, p = 0.03), and mGPS (0.2 ± 0.4 vs. 0.6 ± 0.7, p = 0.01). For predicting histological activity, ROC analyses indicated an optimal cutoff of 0.3 for CAR (AUC 0.8, PPV 90.5%), 13.5 for RDW (AUC 0.7, PPV 84.1), 86.1 for PNI (AUC 0.7, PPV 86.1) and > 0 for mGPS (AUC 0.6, PPV 85.2%). The NLR, LMR, PLR, GNRI, Fe: F, and SII did not meet statistical significance (p = 0.4, 0.08, 0.2, 0.5, 0.6, and 0.3, respectively). CONCLUSIONS: We report on ten biomarkers, many of them never studied in Crohn's disease, which can help in predicting the presence of active histological disease. Larger prospective studies are needed to investigate the utility of these biomarkers alone and in combination.

Liver-related Events in Human Immunodeficiency Virus-infected Persons With Occult Cirrhosis.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients are at increased risk of liver-related mortality. The effect of occult cirrhosis (OcC), defined as preclinical compensated cirrhosis without any clinical findings, on liver-related events is unknown. METHODS: HIV-infected patients from 2 Canadian cohorts underwent transient elastography (TE) examination and were classified as (1) OcC (TE ≥13 kPa with no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (2) overt cirrhosis (OvC) (TE ≥13 kPa with signs of cirrhosis); or (3) noncirrhotic patients (TE <13 kPa). Incidence and risk factors of liver-related events were investigated through Kaplan-Meier and Cox regression analyses, respectively. We estimated monitoring rates according to screening guidelines for hepatocellular carcinoma (HCC) by OcC and OvC status. RESULTS: A total of 1092 HIV-infected patients (51% coinfected with hepatitis C virus) were included. Prevalence of OcC and OvC at baseline was 2.7% and 10.7%, respectively. During a median follow-up of 1.8 (interquartile range, 1.5-2.8) years, the incidence of liver-related events in noncirrhosis, OcC, and OvC was 3.4 (95% confidence interval [CI], 1.2-7.3), 34.0 (95% CI, 6.0-104.0), and 37.0 (95% CI, 17.0-69.1) per 1000 person-years, respectively. Baseline OcC (adjusted hazard ratio [aHR], 7.1 [95% CI, 1.3-38.0]) and OvC (aHR, 8.5 [95% CI, 2.8-26.0]) were independently associated with liver-related events. Monitoring rates for HCC were lower in patients with OcC (24%) compared to those with OvC (40%). CONCLUSIONS: HIV-infected patients with OcC have a high incidence of liver-related events. Greater surveillance and earlier recognition with appropriate screening strategies are necessary for improved outcomes.

Ledipasvir/sofosbuvir for treatment of hepatitis C virus in sofosbuvir-experienced, NS5A treatment-naïve patients: Findings from two randomized trials.

BACKGROUND & AIMS: We report data from two similarly designed studies that evaluated the efficacy, safety, and optimal duration of ledipasvir/sofosbuvir (LDV/SOF) ± ribavirin (RBV) for retreatment of chronic hepatitis C virus (HCV) in individuals who failed to achieve sustained virological response (SVR) with prior SOF-based, non-NS5A inhibitor-containing regimens. METHODS: The RESCUE study enrolled HCV mono-infected adults with genotype (GT) 1 or 4. Non-cirrhotic participants were randomized to 12 weeks of LDV/SOF or LDV/SOF + RBV. Compensated cirrhotic participants were randomized to LDV/SOF + RBV (12 weeks) or LDV/SOF (24 weeks). The AIDS Clinical Trials Group A5348 study randomized genotype 1 adults with HCV/HIV co-infection to LDV/SOF + RBV (12 weeks) or LDV/SOF (24 weeks). Both studies used SVR at 12 weeks post-treatment (SVR12) as the primary endpoint. RESULTS: In the RESCUE study, 82 participants were randomized and treated, and all completed treatment. Overall, SVR12 was 88% (72/82); 81-100% in non-cirrhotic participants treated with LDV/SOF or LDV/SOF + RBV for 12 weeks and 80-92% in cirrhotic participants treated with LDV/SOF + RBV for 12 weeks or LDV/SOF for 24 weeks. Adverse events (AEs), mostly mild-to-moderate in severity, were experienced by 78% of participants, with headache and fatigue most frequently reported. One serious AE, not related to treatment, was observed. No premature discontinuations of study drug, or deaths occurred. In the A5348 study, seven participants were randomized (cirrhotic n = 1; GT1a n = 5) and all attained SVR12, with no serious AEs or premature discontinuations. CONCLUSIONS: In this SOF-experienced, NS5A inhibitor-naïve population, which included participants with cirrhosis or HCV/HIV co-infection, high SVR12 rates were achieved.

Proposal of a novel MELD exception point system for hepatocellular carcinoma based on tumor characteristics and dynamics.

BACKGROUND & AIMS: Patients listed with exception points for hepatocellular carcinoma (HCC) have been more likely to be transplanted than those listed for chronic liver failure (LF) based on the model for end-stage liver disease (MELD) score. The aim of this study was to determine outcomes in the 5-year experience of a scoring system designed to reflect heterogeneity of tumor load of patients listed for HCC. METHODS: A novel MELD exception point system based on size and number of HCC was implemented in July 2009. This system allows stratification of patients based on risk of dropping out from the waiting list according to Milan criteria. LF patients were listed according to biological MELD sodium score; HCC patients were reassigned points every three months upon repeat imaging. RESULTS: Among 624 patients listed for liver transplant (LT), 505 were eligible. 94 (18.6%) were assigned MELD HCC points. Only 24.7% required changes in allocated points over time. Transplantation rates (HCC 83% vs. LF 73%, p=0.04) and waiting time in days (HCC 258 vs. LF 325; p=0.07) were similar. The method of competing risk analysis revealed that HCC patients were more likely to be transplanted than LF during the 5-year period preceding implementation, whereas transplant rates became equivalent for HCC and non-HCC in 2009-2014. One- and two-year survivals were similar between the two groups. CONCLUSIONS: Our study demonstrates that a novel MELD point system for HCC, taking into account dynamics in tumor size and number, allows for equitable liver allocation without compromising graft and patient survival. LAY SUMMARY: It has historically been difficult to achieve equitable liver allocation for liver cancer and chronic liver failure with the allocation systems currently in place in many countries worldwide. We designed a new system to help improve access to organs for liver failure patients in Québec, Canada. Our 5-year experience demonstrates that this unique system renders access to transplant similar for both liver cancer and liver failure indications.

Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis.

BACKGROUND & AIMS: Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear. METHODS: The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP >292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM] >7.1kPa), or transition to cirrhosis (LSM >12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression. RESULTS: A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection. CONCLUSION: HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to frequent metabolic disorders and the long-term effects of antiretroviral therapy. However, due to the invasiveness of liver biopsy, the traditional method of diagnosing fatty liver, there are few data regarding its frequency in people living with HIV. In this study, we used a non-invasive diagnostic tool to analyze the epidemiology of fatty liver in 726 HIV+ patients. We found that fatty liver affects over one-third of people living with HIV. When followed over time, we found that HIV+ patients without HCV co-infection develop fatty liver more frequently than those co-infected with HCV.

Serum fibrosis biomarkers predict death and graft loss in liver transplantation recipients.

Noninvasive serum fibrosis biomarkers predict clinical outcomes in pretransplant patients with chronic liver disease. We investigated the role of serum fibrosis biomarkers and of changes in biomarkers in predicting death and graft loss after liver transplantation (LT). We included 547 patients who underwent LT between 1991 and 2012 and who met the following criteria: patient and graft survival > 12 months; serum fibrosis biomarkers aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis score 4 (FIB-4), and nonalcoholic fatty liver disease (NAFLD) fibrosis score available at 1 year after LT; and a minimum follow-up of 1 year. Delta of fibrosis biomarkers was defined as (end of follow-up score--baseline score)/follow-up duration. Baseline and delta fibrosis biomarkers were associated with death: APRI > 1.5 (adjusted hazard ratio [aHR], 2.2; 95% confidence interval [CI], 1.4-3.3; P < 0.001) and delta APRI > 0.5 (aHR, 5.3; 95% CI, 3.4-8.2; P < 0.001); FIB-4 > 3.3 (aHR, 1.9; 95% CI, 1.3-2.8; P = 0.002) and delta FIB-4 > 1.4 (aHR, 2.4; 95% CI, 1.4-4.1; P = 0.001); and NAFLD fibrosis score > 0.7 (aHR, 1.9; 95% CI, 1.3-2.9; P = 0.002) and delta NAFLD fibrosis score (aHR, 3.7; 95% CI, 2.6-5.4; P < 0.001). Baseline and delta fibrosis biomarkers were associated also with graft loss. In conclusion, serum fibrosis biomarkers 1 year after LT and changes in serum fibrosis biomarkers predict death and graft loss in LT recipients. They may help in risk stratification of LT recipients and identify patients requiring closer monitoring.

Occult cirrhosis diagnosed by transient elastography is a frequent and under-monitored clinical entity.

BACKGROUND & AIMS: Diagnosis of preclinical compensated cirrhosis (occult cirrhosis, OC) is challenging due to lack of clinical findings. We evaluated prevalence and outcomes of OC by transient elastography (TE, Fibroscan(®)). METHODS: Eight hundred and seventy-one patients with compensated chronic liver disease (CLD) and TE examination were divided into: (i) OC (TE ≥ 13 kPa and no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (ii) clinically evident cirrhosis (TE ≥ 13 kPa with signs of cirrhosis); (iii) non-cirrhotic CLD (TE < 13 kPa). Outcomes included hepatocellular carcinoma (HCC), esophageal varices and ascites. Late diagnosis of outcomes was defined as HCC stage ≥intermediate by BCLC or variceal bleeding. RESULTS: Occult cirrhosis represented 12% of the cohort and 37% of cirrhotic patients. Independent predictors of OC were age [odds ratio (OR) 1.15; 95% confidence interval (CI), 1.04-1.26], HIV co-infection (OR 3.53; 95% CI, 1.85-6.76) and APRI (OR 2.63; 95 CI, 1.87-3.71). During a median follow-up of 24 (interquartile range 20-37) months, OC received less surveillance than clinically evident cirrhosis, with fewer ultrasounds (2.7 ± 1.5 vs 3.6 ± 2; P < 0.001) and gastroscopies (2 ± 0.8 vs 2.6 ± 1.4; P < 0.001). Incidence of outcomes was 3.5/100 per person-years (PY) (95% CI, 0.1-6.9) in OC, 0 in non-cirrhotic CLD and 9.8/100 PY (95% CI, 0.3-19.3) in clinically evident cirrhosis (P < 0.001). Late diagnosis occurred more in OC than clinically evident cirrhosis (60 vs 15%, P = 0.01). CONCLUSIONS: Occult cirrhosis is a frequent and under-monitored clinical entity associated with short-term risk of outcomes. TE may help early diagnosis, prompt initiation of surveillance and specific therapy for an otherwise unrecognized condition.

Interstitial Lung Disease as an emerging contributor to mortality in patients with Inflammatory Bowel Disease: A population-based epidemiological study.

OBJECTIVES: We aim to investigate the contribution of Interstitial Lung Disease (ILD) to mortality in patients with Inflammatory Bowel Disease (IBD). METHODS: We carried out a comprehensive retrospective, population-based epidemiological study across the United States from 2001 to 2020, using the Wide-ranging Online Data for Epidemiologic Research (WONDER) database. Mortality data were classified according to the International Classification of Diseases, Tenth Revision, with the codes J84 for ILD, K50 for Crohn's Disease (CD), and K51 for Ulcerative Colitis (UC). To discern patterns, Age-adjusted Mortality Rates (AMR) were computed, stratified by gender, geographic census region, and racial/ethnic demographics. RESULTS: From 2001 to 2020, there were 57,967 reported deaths among IBD patients with an AMR per million significantly rising from 10.989 in 2001-2005 to 11.443 in 2016-2020 (p<0.0001). ILD was a contributor to death in 1.19% (692/57,967) of these cases, with AMR rising from 0.092 to 0.143 per million (p=0.010). The percentage of ILD-related deaths in the IBD population increased from 1.02% to 1.30% over two decades. ILD was a more common cause of death in patients with CD than with UC (54.6% vs. 45.4%), with a significant increase for both conditions from 2001 to 2020 (p<0.05). An upward trend in ILD-related mortality was observed in both sexes (p<0.05), and within the White population (p=0.010). CONCLUSIONS: The observed increase in mortality rates due to ILD among patients with IBD is concerning and highlights a critical need for systematic ILD screening protocols within the IBD patient population to facilitate early detection and management.

Characterization of hepatitis B virus genotypes and quantitative hepatitis B surface antigen titres in North American tertiary referral liver centres.

BACKGROUND & AIMS: Hepatitis B virus (HBV) genotype and quantitative hepatitis B surface antigen (qHBsAg) have been related to clinical outcome. In this nationwide cross-sectional study, we aimed to investigate the epidemiology and clinical significance of HBV genotype and qHBsAg in patients with chronic hepatitis B (CHB). METHODS: Six hundred and thirty patients with CHB were seen in four urban tertiary referral centres in Canada. HBV genotype was determined by line probe assay (INNO-LIPA) and HBV DNA quantified by commercial PCR (Roche TaqMan, sensitivity <55 IU/ml or AMPLICOR, sensitivity <60 IU/ml). Titres of qHBsAg were determined by an in-house assay based on the WHO standard (calibration range 0.24-62.5 IU/ml). RESULTS: In 630 patients (57% male, 69% Asian, median age 42 years), 21% were hepatitis B e antigen positive and the median alanine aminotransferase was 29 U/L. The HBV genotype distribution was A (16%), B (29%), C (31%), D (16%), E (6%). HBV genotype was strongly associated with ethnicity, but neither genotype nor qHBsAg correlated with the degree of fibrosis. In the treatment-naïve patients, the baseline qHBsAg levels correlated with HBV DNA (r = 0.2517, P < 0.0008). The median qHBsAg levels were lowest in patients with genotype B (P < 0.0001), but no significant correlation was noted with all other HBV genotypes. CONCLUSIONS: In this large North American HBV epidemiological study, genotypes B and C were the most common; however, all genotypes (A-E) were observed with varied distribution nationwide. Baseline qHBsAg significantly correlated with HBV DNA and with HBV genotype B, but not with liver fibrosis.

Association Between Helicobacter pylori and Steatosis Severity on Transient Elastography.

Background A possible association between Helicobacter pylori (HP) infection and liver diseases including steatosis is suspected. There is a lack of studies evaluating the association of HP and liver steatosis severity using transient elastography. Aim The aim of this study was to evaluate the frequency and risk factors for liver steatosis measured by transient elastography in patients with or without HP. Methods A total of 484 patients tested for liver steatosis and fibrosis using transient elastography from January 2017 to June 2018 were evaluated. Ninety-one patients who were also tested for H. pylori infection were included in the study. Transient elastography findings were compared between HP-positive patients and HP-negative patients. Demographic, clinical, and laboratory variables and the presence and severity of liver fibrosis and steatosis were analyzed. Results Patients with HP had a higher frequency of steatosis on transient elastography (86.8% vs. 60.7%, p =0.009). Patients with HP had increased steatosis severity compared to HP-negative patients (mild steatosis 15.8% vs. 7.1%, p=0.037; moderate to severe steatosis 71.1% vs. 53.6%, p=0.015, respectively). In the stepwise multivariate logistic regression analysis, HP infection remained an independent risk factor for steatosis (odds ratio: 4.36, 95% confidence interval: 1.09-14.78; p=0.037). Conclusion Patients with HP had an increased steatosis frequency, and patients with liver steatosis may warrant HP evaluation and treatment.

Smoking increases recurrent viral hepatitis after liver transplantation.

Smoking is a common behavior among transplant candidates. The aim of this study was to evaluate the effects of smoking on a range of complications after liver transplantation. We reviewed data about patient demographics and various complications after liver transplantation that were recorded in the McGill University Health Centre liver transplant database over a 14-year period. χ(2) and multivariate analyses were performed. Four hundred forty-four liver transplants were performed from 1990 to 2004, and 63 were repeat transplants. Only primary liver transplant recipients were included in our analysis. Smokers (ie, active or former smokers) were more likely to be male (77.9% versus 62.7%, P = 0.009) and Caucasian (88.4% versus 78.0%, P = 0.03). The median survival time was 13.23 years for smokers and was not estimable for nonsmokers because of censoring. The median recurrent viral hepatitis-free survival time was 0.87 years for smokers and 4.10 years for nonsmokers (P = 0.03). The following variables were not found to be associated with the smoking status: patient survival (P = 0.78), time to biliary complications after liver transplantation (P = 0.67), time to the first rejection episode after liver transplantation (P = 0.61), and time to depression after liver transplantation (P = 0.67). A Cox proportional hazards regression showed that recurrent viral hepatitis-free survival was still strongly associated with smoking [HR = 2.04, 95% confidence interval (CI) = 1.13-3.68, P = 0.018] and was marginally associated with East Asian race (HR = 0.26, 95% CI = 0.06-1.06, P = 0.06) and male sex (HR = 0.59, 95% CI = 0.34-1.02, P = 0.06). In conclusion, recurrent viral hepatitis-free survival was decreased for smokers after liver transplantation, likely because of the adverse effects of tobacco on immunological host defenses. Overall, the biliary complication-free, depression-free, and rejection-free survival rates were similar for smokers and nonsmokers. These findings suggest that smoking cessation should be encouraged, particularly in recipients undergoing transplantation for viral hepatitis.

Hepatitis B and the infected health care worker: public safety at what cost?

Public safety and the right of the health care worker to practise without prejudice based on underlying illness may be at odds for those affected by the hepatitis B virus (HBV). Nevertheless, HBV does not preclude entry into a health care profession, and the risk of transmission from health care worker to patient is not uniform across the spectrum of health care fields. In the present article, the authors present an overview of the literature regarding transmission of HBV from the health care worker to the patient, and the current recommendations that vary from province to province within Canada. The establishment of national guidelines to standardize monitoring of HBV infection among health care workers would improve health care workplace safety and patient care.

A meta-analysis of nutritional supplementation for management of hospitalized alcoholic hepatitis.

BACKGROUND: Alcoholic liver disease (ALD) is associated with a high risk of morbidity and mortality. Malnutrition accompanies this condition and may be both a consequence of and contributor to the pathology. Many trials have investigated the benefits of providing supplemental nutrition in the management of patients with ALD. The present study is a meta-analysis of the available evidence. METHOD: A meta-analysis of randomized controlled studies comparing nutritional supplementation plus a normal hospital diet versus diet alone. RESULTS: Seven randomized controlled studies including 262 patients with ALD were identified. Pooled analysis revealed no statistical difference in mortality between groups given special nutritional therapy versus a normal balanced diet (OR 0.80 [95% CI 0.42 to 1.52]). In addition, nutrition did not significantly improve ascites (OR 1.29 [95% CI 0.52 to 3.20]) or any biochemical parameters. However, encephalopathy showed a significant improvement or resolution (OR 0.24 [95% CI 0.06 to 0.93]). CONCLUSION: Nutritional supplementation provided no mortality benefit in patients with ALD, and neither ascites nor biochemical parameters significantly improved. However, encephalopathy was significantly ameliorated and, therefore, nutritional supplementation should be encouraged in that setting.

The utility of Xenon-133 liver scan in the diagnosis and management of nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an important and common condition affecting approximately 20% of the general population. Given the limitation of radiological investigations, diagnosis often requires a liver biopsy. OBJECTIVE: To compare Xenon-133 (Xe-133) liver scanning with ultrasonography in the diagnosis of NAFLD. METHODS: From January 2003 to February 2007, 258 consecutive patients with suspected NAFLD underwent Xe-133 liver scanning at Royal Victoria Hospital (Montreal, Quebec). Of these, 43 patients underwent ultrasonography and liver biopsy for the evaluation of NAFLD. Patients with other liver diseases and significant alcohol consumption were excluded. Two nuclear medicine physicians assessed liver Xe-133 uptake and measured the grade of steatosis using a standardized protocol. The degree of steatosis was determined from biopsy specimens assessed by two hepatopathologists. RESULTS: NAFLD was identified by liver biopsy in 35 of 43 patients (81.4%). Xe-133 scan demonstrated 94.3% sensitivity (95% CI 81.4% to 98.4%) and 87.5% specificity (95% CI 52.9% to 99.4%) for the presence of NAFLD. The positive and negative predictive values for detection of steatosis by Xe-133 scan were 97.1% (95% CI 85.1% to 99.8%) and 77.8% (95% CI 45.3% to 93.7%), respectively. The positive and negative likelihood ratios were 7.54 (95% CI 1.20 to 47.26) and 0.07 (95% CI 0.02 to 0.26), respectively. Two patients with NAFLD (5.7%) who had a negative Xe-133 scan result had histologically mild steatosis (<10%). The grade of steatosis on liver biopsy was highly correlated with the results of the Xe-133 scan (r=0.87; P<0.001). The sensitivity and specificity of ultrasound in diagnosing steatosis were 62.9% and 75%, respectively. CONCLUSION: Xe-133 liver scan proved to be a safe, reliable, noninvasive method for diagnosing and quantifying hepatic steatosis, and was superior to ultrasound.

Current considerations for clinical management and care of non-alcoholic fatty liver disease: Insights from the 1st International Workshop of the Canadian NASH Network (CanNASH).

Non-alcoholic fatty liver disease (NAFLD) affects approximately 8 million Canadians. NAFLD refers to a disease spectrum ranging from bland steatosis to non-alcoholic steatohepatitis (NASH). Nearly 25% of patients with NAFLD develop NASH, which can progress to liver cirrhosis and related end-stage complications. Type 2 diabetes and obesity represent the main risk factors for the disease. The Canadian NASH Network is a national collaborative organization of health care professionals and researchers with a primary interest in enhancing understanding, care, education, and research around NAFLD, with a vision of best practices for this disease state. At the 1st International Workshop of the CanNASH network in April 2021, a joint event with the single topic conference of the Canadian Association for the Study of the Liver (CASL), clinicians, epidemiologists, basic scientists, and community members came together to share their work under the theme of NASH. This symposium also marked the initiation of collaborations between Canadian and other key opinion leaders in the field representative of international liver associations. The main objective is to develop a policy framework that outlines specific targets, suggested activities, and evidence-based best practices to guide provincial, territorial, and federal organizations in developing multidisciplinary models of care and strategies to address this epidemic.