Association of circulating Z-polymer with adverse clinical outcomes and liver fibrosis in adults with alpha-1 antitrypsin deficiency.

BACKGROUND: Circulating polymerized mutant Z-alpha-1 antitrypsin (Z-polymer) constitutes a characteristic feature in alpha-1 antitrypsin deficiency (AATD), but there is limited knowledge about its association with adverse clinical outcomes and liver fibrosis. We explored this association using data from a large cohort of adults with AATD. METHODS: A total of 836 (431 PiZZ, 405 PiMZ) adults with AATD and 312 controls (PiMM) from the European Alpha-1 Liver Cohort (2015-2020) were included. Time-to-event analyses were conducted for adults with the PiZZ genotype followed for adverse clinical outcomes (earliest occurrence of liver-related hospitalization, liver transplant or all-cause mortality). Cox proportional hazard models were used to describe the association between binary circulating Z-polymer levels and adverse clinical outcomes. Correlations between baseline circulating Z-polymer levels and baseline liver fibrosis (liver stiffness measurement [LSM] determined by transient elastography [FibroScan®]) were evaluated. The analyses were stratified by augmentation therapy status. RESULTS: Of 324 adults with the PiZZ genotype and longitudinal follow-up data, 28 reported adverse clinical outcomes. Higher baseline circulating Z-polymer levels were associated with an increased risk of adverse clinical outcomes in both crude (hazard ratio [95% confidence interval, CI], 2.88 [1.21, 6.87]) and age-adjusted (1.96 [0.78, 4.94]) analyses. In adults with the PiZZ genotype, circulating Z-polymer levels were weakly positively correlated with baseline LSM (Spearman's rho [95% CI]: 0.21 [0.11, 0.31]). Similar results were observed after stratification by augmentation therapy status. CONCLUSIONS: In adults with the PiZZ genotype, higher circulating Z-polymer levels were associated with a shorter time to adverse clinical outcome, and positively correlated with baseline LSM. Circulating Z-polymer levels may be a prognostic biomarker of clinically relevant disease in AATD.

Liver transplant evaluation for fulminant liver failure due to acute hepatitis A infection: Case series and literature review.

Hepatitis A virus can cause liver damage ranging from mild illness to fulminant hepatic failure, constituting 0.35% of all cases of fulminant liver failure. While rates of spontaneous remission are higher for hepatitis A, recent outbreaks attributable to vaccine shortages in highly populated urban cities plagued by insufficient affordable housing and inaccessible sanitation, and changes in the epidemiology of viral strains have resulted in increased hospitalizations and deaths. While the prognosis for patients with FHF has improved since the introduction of transplantation, the decision to transplant is often difficult to reach. We present five patients with HAV and subsequent FHF, one of whom successfully received a liver transplant. We have reviewed all published cases of HAV FHF in the literature and report ten patients, seven of whom received liver transplantation. There are few predictive models that attempt to distinguish between fulminant hepatitis A and spontaneous recovery. Patients found to have positive hepatitis A IgM, encephalopathy, worsening LFT's and coagulation should be monitored closely and referred to transplant centers urgently for management.

Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma in Patients With Child-Pugh B or C Cirrhosis.

PURPOSE: Our purpose was to report outcomes in patients with Child-Pugh B or C (CP B/C) hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Patients with HCC suitable for SBRT were prospectively enrolled in the study from 2012 to 2018. Outcomes in patients with CP B/C were analyzed. Cox proportional hazard models were used to compare survival outcomes between baseline CP score and post-SBRT CP score. RESULTS: Twenty-three patients with CP B/C with a total of 29 HCC tumors were treated with SBRT. Eighty-seven percent of patients were CP B8-C10. Median tumor size was 3.1 cm (range, 1-10 cm). Median dose delivered was 40 Gy in a median of 5 fractions. Eighteen of 23 patients (78.3%) had been previously treated with transarterial chemoembolization. Median follow-up was 14.5 months. Rates of 6- and 12-month local control were 100% and 92.3%, respectively. Six- and 12-month survival rates were 73.9% and 56.5%, respectively. Median survival was 14.5 months overall and 9.2, 22.5, 14.5, and 14.4 months for patients with CP B7, B8, B9, and C10, respectively. No patients exhibited symptoms of classic radiation-induced liver disease. However, 10 patients had CP score progression, with 4 patients (17%) having a ≥2-point increase in CP score by 6 months (or time of censor). There were 7 liver-related deaths, and based on independent review by a hepatologist, 1 of these deaths may have been attributable to SBRT-related liver injury. Fifteen of 23 patients were listed for liver transplant (LT) at the time of SBRT and 9 went on to receive LT with a pathologic complete response rate of 63.6%. Median survival, excluding patients who received LT, was 7.3 months. CONCLUSIONS: SBRT is a reasonable treatment option for carefully selected patients with CP B7-C10. In our small cohort, there was no detectable difference between local control or overall survival and baseline CP score.

Sofosbuvir plus simeprevir treatment of recurrent genotype 1 hepatitis C after liver transplant.

BACKGROUND: Patients with recurrent hepatitis C (HCV) infection post-liver transplant can be difficult to treat safely and effectively. A prior (COSMOS) study in patients with non-transplant HCV, using sofosbuvir plus simeprevir, had high efficacy and tolerability in treating patients with HCV genotype 1, even prior non-responders to interferon therapy and those with cirrhosis. Our aim was to evaluate the efficacy of sofosbuvir and simeprevir in patients with genotype 1 HCV post-liver transplant. METHODS: In this prospective, observational study, patients received sofosbuvir 400 mg plus simeprevir 150 mg daily for 12 wk without ribavirin. The primary end point was a sustained virologic response 12 wk after the end of therapy. RESULTS: Forty-two patients completed the treatment. Twenty-six percent started the treatment ≤ 6 months post-liver transplant. Nineteen percent of the included patients had cirrhosis, 14% with decompensation. At week 4 on the treatment, 21% of patients had detectable virus but at the end of the treatment, 100% were undetectable. Twelve weeks after the end of the treatment, 95% of the patients had undetectable hepatitis C. The regimen was generally well tolerated. CONCLUSION: The oral regimen of sofosbuvir plus simeprevir without ribavirin is efficacious and well tolerated in the treatment of patients with genotype 1 hepatitis C post-liver transplant.

Methasteron-associated cholestatic liver injury: clinicopathologic findings in 5 cases.

BACKGROUND & AIMS: Methasteron is a nutritional supplement used to increase weight or accelerate the build-up of muscle mass. The aim of this study was to describe 5 cases of hepatotoxicity in patients using methasteron seen at tertiary-care medical centers. METHODS: A case report design was used. RESULTS: Five previously healthy patients who used methasteron developed jaundice 2 weeks after discontinuation; they presented to a tertiary-care medical center 2 weeks later. Within another 2 to 3 weeks, bilirubin levels peaked. About 12 weeks after initial presentation, all cases resolved with no identifiable residual hepatic dysfunction. CONCLUSIONS: Methasteron use can result in severe hepatotoxicity. Liver failure can worsen after initial presentation, especially within 2 weeks. With close observation and supportive care, acute hepatic injury should resolve.