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| 2. |
- Castedal, Maria, 1964, et al.
(författare)
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INF-free sofosbuvir-based treatment of post-transplant hepatitis C relapse - a Swedish real life experience
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:5, s. 585-588
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Relapse of hepatitis C virus (HCV) infection after liver transplantation has been universal, and the fibrosis progression faster than in non-transplanted patients. Interferon (IFN)-free treatment with direct antiviral agents (DAA) has improved the treatment outcome dramatically. We here report on the outcome of IFN-free treatment for HCV relapse after liver transplantation in a real life setting in Sweden. MATERIAL: In total, 93 patients with a mean age of 60 years (range 32-80) with HCV relapse after liver transplantation were given sofosbuvir-based treatment in combination with a protease inhibitor (simeprevir) or a NS5A inhibitor (daclatasvir or ledipasvir) with or without addition of ribavirin (RBV), or sofosbuvir and RBV only. Treatment was generally given during 24 weeks for advanced fibrosis or cirrhosis cases and 12 weeks for mild fibrosis with fibrosis stage 2 or less. The distribution of genotype 1, 2, 3, 4 in our patients was 58, 7.5, 26.5 and 7.5%, respectively. RESULTS: All recipients reached end-of-treatment response (ETR) with HCV RNA <15 IU/mL. Sustained viral response 12 weeks after treatment cessation (SVR12) was achieved in 91/93 (97.8%) recipients. The SVR12 rates for genotype 1, 2, 3 and 4 were the SVR12 rate were 96, 100, 100 and 100%, respectively (p = .04). CONCLUSION: It is concluded that IFN-free treatment with DAAs for HCV relapse after liver transplantation is highly effective also in a real life setting and offers cure for most recipients.
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| 3. |
- Castedal, Maria, 1964, et al.
(författare)
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Steroid-free immunosuppression with low-dose tacrolimus is safe and significantly reduces the incidence of new-onset diabetes mellitus following liver transplantation.
- 2018
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 53:6, s. 741-747
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Tidskriftsartikel (refereegranskat)abstract
- Corticosteroids (CS) are traditionally used as part of the basal immunosuppression (IS) following liver transplantation (LT) but are known to be associated with an increased risk of new-onset diabetes mellitus (NODM), cardiovascular morbidity and mortality. The aim of this study was to retrospectively compare the incidence of transient as well as persistent NODM, rejection rate and patient- and graft survival between patients receiving steroid-based and steroid-free maintenance IS.A total of 238 patients liver transplanted (2008-2011) with deceased donor livers were divided into two groups, one group that received steroid-based IS (tacrolimus (TAC), corticosteroids (CS),±mycophenolate mofetil (MMF); n=155) (2008-2011) and another group of non-autoimmune recipients that received steroid-free IS (TAC, MMF; n=83) according to our new maintenance IS-protocol starting January 2010. The primary and secondary end-points were patient- and graft survival, rejection rates and the incidence of NODM. The median follow-up times were 1248 days and 681 days, respectively.The one-year patient- and graft survival in the steroid-based and steroid-free group was 92.7% and 93.3% (ns) and 87.6% and 84.9% (ns), respectively. The incidence of biopsy proven acute rejection (BPAR) was 27.7% in both groups (ns) during follow-up. The overall incidence of persistent NODM in the two groups were 16.8% and 2.9%, respectively (p<.01).The results show that steroid-free low-dose tacrolimus-based IS following LT is safe and decreases the incidence of NODM significantly.
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| 4. |
- Frankal, Miriam, 1983, et al.
(författare)
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Hepatitis E Virus Infection, a Risk for Liver Transplant Recipients in Sweden
- 2022
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Ingår i: Transplantation Direct. - 2373-8731. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Background. Following exposure to hepatitis E virus (HEV), liver transplant (LT) recipients have an increased risk of developing chronic infection, which may rapidly progress to severe liver damage if not treated. The prevalence of HEV infection after LT is unclear and likely varies geographically. The aim of this study was to investigate the prevalence of acute and chronic HEV infection among LT recipients in an HEV endemic region. Methods. During 2013 to 2015, 109 of 152 prospectively enrolled patients listed for LT received a liver graft and completed the study protocol. They were evaluated for anti-HEV IgM, HEV IgG, and HEV RNA at the time of LT assessment and 3 and 12 mo post-LT. Medical records were reviewed. Results. Twelve (11%) LT recipients acquired markers of HEV infection during the study period. Seven patients (6%) had detectable HEV RNA, 1 before LT and 3 at the 3-mo and another 3 at the 12-mo follow-up post-LT. All resolved their infections without treatment and had undetectable HEV RNA at the succeeding follow-up. Another 5 (5%) patients developed anti-HEV antibodies without detectable HEV RNA as an indication of HEV infection during follow-up. Signs and symptoms of HEV infection were subtle‚ and none were diagnosed in routine clinical care. Conclusion. A substantial proportion of LT recipients in Sweden are at risk of acquiring HEV infection, both before and after LT. The results highlight the frequency of silent, spontaneously resolving HEV infections and do not support universal screening of LT recipients in Sweden, despite HEV being a potentially treatable infection.
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| 6. |
- Ringlander, Johan, et al.
(författare)
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Deep sequencing of liver explant transcriptomes reveals extensive expression from integrated hepatitis B virus DNA
- 2020
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 27:11, s. 1162-1170
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). Integration of HBV DNA into the human genome may contribute to oncogenesis and to the production of the hepatitis B surface antigen (HBsAg). Whether integrations contribute to HBsAg levels in the blood is poorly known. Here, we characterize the HBV RNA profile of HBV integrations in liver tissue in patients with chronic HBV infection, with or without concurrent hepatitis D infection, by transcriptome deep sequencing. Transcriptomes were determined in liver tissue by deep sequencing providing 200 million reads per sample. Integration points were identified using a bioinformatic pipeline. Explanted liver tissue from five patients with end-stage liver disease caused by HBV or HBV/HDV was studied along with publicly available transcriptomes from 21 patients. Almost all HBV RNA profiles were devoid of reads in the core and the 3 ' redundancy (nt 1830-1927) regions, and contained a large number of chimeric viral/human reads. Hence, HBV transcripts from integrated HBV DNA rather than from covalently closed circular HBV DNA (cccDNA) predominated in late-stage HBV infection, in particular in cases with hepatitis D virus co-infection. The findings support the suggestion that integrated HBV DNA can be a significant source of HBsAg in humans.
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| 7. |
- Ringlander, Johan, et al.
(författare)
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Enrichment Reveals Extensive Integration of Hepatitis B Virus DNA in Hepatitis Delta Virus-Infected Patients
- 2024
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Ingår i: JOURNAL OF INFECTIOUS DISEASES. - 0022-1899 .- 1537-6613.
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Tidskriftsartikel (refereegranskat)abstract
- Background. Hepatitis B virus (HBV) DNA may become integrated into the human genome of infected human hepatocytes. Expression of integrations can produce the surface antigen (HBsAg) that is required for synthesis of hepatitis D virus (HDV) particles and the abundant subviral particles in the blood of HBV- and HDV-infected subjects. Knowledge about the extent and variation of HBV integrations and impact on chronic HDV is still limited. Methods. We investigated 50 pieces of liver explant tissue from 5 patients with hepatitis D-induced cirrhosis, using a deep-sequencing strategy targeting HBV RNA. Results. We found that integrations were abundant and highly expressed, with large variation in the number of integration-derived (HBV/human chimeric) reads, both between and within patients. The median number of unique integrations for each patient correlated with serum levels of HBsAg. However, most of the HBV reads represented a few predominant integrations. Conclusions. The results suggest that HBV DNA integrates in a large proportion of hepatocytes, and that the HBsAg output from these integrations vary >100-fold depending on clone size and expression rate. A small proportion of the integrations seems to determine the serum levels of HBsAg and HDV RNA in HBV/HDV coinfected patients with liver cirrhosis.
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| 8. |
- Rydell, Gustaf E, et al.
(författare)
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Quantification of viral RNA in multiple pieces of explant liver tissue shows distinct focal differences of hepatitis B infection.
- 2022
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 226:6, s. 1036-1040
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV) DNA and RNA were quantified by digital PCR assays in 20-30 tissue pieces from each of four liver explants with cirrhosis caused by HBV. The within-patient variability of HBV RNA levels between pieces was up to thousand-fold. Core RNA and S RNA levels were similar and correlated strongly when replication was high, supporting transcription from cccDNA. By contrast, enhanced expression of S RNA relative to cccDNA and core RNA in patients with medium-high or low replication supports that HBV surface antigen (HBsAg) can be expressed mainly from integrated HBV DNA in such patients.
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| 9. |
- Skoglund, Charlotte, et al.
(författare)
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Factors Associated With Adherence to Methylphenidate Treatment in Adult Patients With Attention-Deficit/Hyperactivity Disorder and Substance Use Disorders
- 2016
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Ingår i: Journal of Clinical Psychopharmacology. - Philadelphia, USA : Lippincott Williams & Wilkins. - 0271-0749 .- 1533-712X. ; 36:3, s. 222-228
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Tidskriftsartikel (refereegranskat)abstract
- Adherence to treatment is one of the most consistent factors associated with a favorable addiction treatment outcome. Little is known about factors associated with treatment adherence in individuals affected with comorbid attention-deficit/hyperactivity disorder and substance use disorders (SUD). This study aimed to explore whether treatment-associated factors, such as the prescribing physician's (sub)specialty and methylphenidate (MPH) dose, or patient-related factors, such as sex, age, SUD subtype, and psychiatric comorbidity, were associated with adherence to MPH treatment. Swedish national registers were used to identify adult individuals with prescriptions of MPH and medications specifically used in the treatment of SUD or a diagnosis of SUD and/or coexisting psychiatric diagnoses. Primary outcome measure was days in active MPH treatment in stratified dose groups (≤36 mg, ≥37 mg to ≤54 mg, ≥55 mg to ≤72 mg, ≥73 mg to ≤90 mg, ≥91 mg to ≤108 mg, and ≥109 mg). Lower MPH doses (ie, ≤36 mg day 100) were associated with treatment discontinuation between days 101 and 830 (HR≤36 mg, 1.67; HR37-54mg, 1.37; HR55-72mg, 1.36; HR73-90mg, 1.19; HR≥108mg, 1.09). The results showed a linear trend (P < 0.0001) toward decreased risk of treatment discontinuation along with increase of MPH doses. In conclusion, this study shows that higher MPH doses were associated with long-term treatment adherence in individuals with attention-deficit/hyperactivity disorder and SUD.
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| 10. |
- Skoglund, Catarina, et al.
(författare)
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No need to discontinue hepatitis C virus therapy at the time of liver transplantation.
- 2019
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Direct antiviral agents (DAA) has dramatically improved the therapy outcome of hepatitis C-virus (HCV) infection, both on the waiting-list and post liver transplantation (LT). DAA are generally well-tolerated in patients with mild to moderate liver and kidney failure, but some DAAs are contraindicated in patients with severe dysfunction of these organs. Today there are few studies of peri-LT DAA use and treatment is commonly discontinued at the time of LT. We report here our experience of DAA therapy given continuously in the perioperative LT period in a real-life setting in Sweden.In total 10 patients with HCV-cirrhosis, with or without hepatocellular carcinoma, and a median age of 60.5 years (range, 52-65) were treated with DAAs on the waiting list for LT, and continued in the early postoperative period without any interruption, on the basis of not having reached a full treatment course at the time of LT. Sofosbuvir and a NS5A inhibitor with or without ribavirin, or sofosbuvir and ribavirin only, were given. The distribution of genotypes was genotype 1 and 3, in 4 and 6 patients, respectively. Six of the 10 patients had previously been treated with IFN-based therapy.There were no adverse events leading to premature DAA discontinuation. All recipients achieved a sustained viral response 12 weeks after end-of-treatment (SVR12). At the time of LT the median MELD-score was 16.5 (range 7-21), CTP-score 9.0 (range 5-10), creatinine 82.5 μmol/L (range 56-135, reference 60-105), bilirubin 33 μmol/L (range 16-79, reference 5-25) and PK-INR 1.5 (range 1.1-1.8). The median duration of DAA therapy was 60 days (range 18-132) pre-LT, 54 days post-LT (range 8-111 days) and in total 15.5 weeks (range 12-30 weeks).Interferon-free DAA therapy of HCV-infection given in the immediate pre- and post-operative LT period is safe, well-tolerated and yields high SVR rates.
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