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Cancers Jun 2022Acute porphyrias are a group of metabolic disorders resulting in defective porphyrin synthesis and reduced heme production, which carries a risk of malignancy.... (Review)
Review
Acute porphyrias are a group of metabolic disorders resulting in defective porphyrin synthesis and reduced heme production, which carries a risk of malignancy. Porphyrias are inborn defects in the heme biosynthesis pathway resulting in neurovisceral manifestations and cutaneous photosensitivity attacks with multi-systemic involvement. Its estimated prevalence nears 5 per 100,000 patients worldwide. Subclinical liver disease is common, which can progress into transaminitis, fibrosis, cirrhosis, and malignancy. However, data on the incidence of primary liver cancer are lacking. We aim to determine the risk of hepatocellular carcinoma (HCC) in patients with porphyria. A systematic review and pooled analysis were conducted through 2021 on studies assessing blood tests, imaging, cancer development, liver transplant, surgical resection, and outcomes in porphyria. In total, 19 studies, which included 7381 patients with porphyria (3476 females), were considered for the final review. In eight studies, alpha-fetoprotein levels were elevated between 200 and 1000 IU/mL. Of the total cohort of patients with porphyria, primary liver cancer was diagnosed in 351 patients (4.8%), of whom 243 (3.3% of the total) were found to have HCC. A subset of patients was found to have cholangiocarcinoma ( = 18; 0.3% of the total). Interestingly, advanced liver disease or cirrhosis was not a prerequisite for the formation of HCC in a small group of patients. Of the total cohort, 30 patients underwent liver resection, 48 patients underwent liver transplantation, and 327 patients died. Patients with porphyria are at risk of developing primary liver malignancy. Further studies should aim to develop diagnostic and prognostic models aimed at the early detection of HCC in porphyria.
PubMed: 35740611
DOI: 10.3390/cancers14122947 -
BMC Gastroenterology Oct 2022Liver diseases post-COVID-19 vaccination is extremely rare but can occur. A growing body of evidence has indicated that portal vein thrombosis, autoimmune hepatitis,...
BACKGROUND
Liver diseases post-COVID-19 vaccination is extremely rare but can occur. A growing body of evidence has indicated that portal vein thrombosis, autoimmune hepatitis, raised liver enzymes and liver injuries, etc., may be potential consequence of COVID-19 vaccines.
OBJECTIVES
To describe the results of a systematic review for new-onset and relapsed liver disease following COVID-19 vaccination.
METHODS
For this systematic review, we searched Proquest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses PRISMA guideline for studies on the incidence of new onset or relapsed liver diseases post-COVID-19 vaccination, published from December 1, 2020 to July 31, 2022, with English language restriction.
RESULTS
Two hundred seventy-five cases from one hundred and eighteen articles were included in the qualitative synthesis of this systematic review. Autoimmune hepatitis (138 cases) was the most frequent pathology observed post-COVID-19 vaccination, followed by portal vein thrombosis (52 cases), raised liver enzymes (26 cases) and liver injury (21 cases). Other cases include splanchnic vein thrombosis, acute cellular rejection of the liver, jaundice, hepatomegaly, acute hepatic failure and hepatic porphyria. Mortality was reported in any of the included cases for acute hepatic failure (n = 4, 50%), portal vein thrombosis (n = 25, 48.1%), splanchnic vein thrombosis (n = 6, 42.8%), jaundice (n = 1, 12.5%), raised liver enzymes (n = 2, 7.7%), and autoimmune hepatitis (n = 3, 2.2%). Most patients were easily treated without any serious complications, recovered and did not require long-term hepatic therapy.
CONCLUSION
Reported evidence of liver diseases post-COIVD-19 vaccination should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively very small in relation to the hundreds of millions of vaccinations that have occurred and the protective benefits offered by COVID-19 vaccination far outweigh the risks.
Topics: Humans; Chronic Disease; COVID-19; COVID-19 Vaccines; Hepatitis, Autoimmune; Liver Failure, Acute; Vaccination; Venous Thrombosis
PubMed: 36229799
DOI: 10.1186/s12876-022-02507-3 -
Cardiovascular & Hematological Agents... 2021Acute porphyrias cause life-threatening attacks of neurovisceral non-specific symptoms, so this condition mimics many acute medical and psychiatric diseases. The disease... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Acute porphyrias cause life-threatening attacks of neurovisceral non-specific symptoms, so this condition mimics many acute medical and psychiatric diseases. The disease is very misdiagnosed, probably due to its low incidence and non-pathognomonic symptoms, this delays the effective treatment onset. Early diagnosis and treatment highly improve the prognosis and can prevent the development of neuropathic manifestations.
METHODS
We assembled a systematic review, following the PRISMA guidelines and using Pubmed as our database. Our aim was to show some peculiarities among patients that present neurological manifestations in acute porphyria attack. We obtained the patients' age, sex, clinical presentation, eurological manifestations and porphyria type of 16 patients. We also evaluated the time between symptoms onset and neurological manifestations. The average age was 28,4 ± 11,1; 50% of patients were male.
RESULTS
AIP was the most prevalent porphyria type. The average time between symptoms onset and neurological manifestations was of 9,53 ± 11,6 days. Abdominal pain; nausea and vomiting and psychiatric manifestations were the most common symptoms preceding neurological attacks. Seizures and consciousness disturbance were the most prevalent findings within an attack. We also presenting a case to illustrate how difficult this diagnosis can be.
Topics: Abdominal Pain; Adult; Animals; Female; Humans; Male; Mental Disorders; Nervous System Diseases; Porphyria, Acute Intermittent; Porphyrias; Prognosis; Vomiting; Young Adult
PubMed: 32914723
DOI: 10.2174/1871525718666200910162000 -
Journal of Cancer 2024There remains a scarcity of published data on the clinical significance of paraneoplastic cutaneous manifestations in hepatocellular carcinoma (HCC). A systematic... (Review)
Review
There remains a scarcity of published data on the clinical significance of paraneoplastic cutaneous manifestations in hepatocellular carcinoma (HCC). A systematic search of MEDLINE was performed in December 2022. Inclusion criteria comprised studies reporting on patients with HCC, who had paraneoplastic cutaneous manifestations. Outcomes of interests comprise survival and response to cancer-directed and/or skin directed therapy. A total of 48 studies comprising 60 HCC patients were included in the analysis. The most frequent reported skin abnormalities were dermatomyositis, pityriasis rotunda, and porphyria. Most patients presented with dermatomyositis had underlying viral hepatitis, while all reported porphyria and acanthosis cases were associated with metabolic causes of HCC, such as steatosis. Paraneoplastic skin changes were more common in patients with metastatic disease. Pityriasis Rotunda was associated with the lowest risk of death, (OR: 0.05, 95% CI: 0.003 to 0.89; p = 0.04), while dermatomyositis had a statistically significant higher risk of death (OR: 3.37, 95% CI: 1.01-12.1; p = 0.03). Most patients showed an improvement in their cutaneous abnormalities, following cancer-directed therapy. Paraneoplastic cutaneous manifestations are reported more frequently in patients with a higher burden of disease, especially presence of metastases. Certain cutaneous manifestations have prognostic implication.
PubMed: 38230223
DOI: 10.7150/jca.88931 -
Medicine Sep 2023Acute intermittent porphyria (AIP) is caused by a partial deficiency of hydroxymethylbilane synthase and affects heme biosynthesis. Mutations in the HMBS gene result in...
BACKGROUND
Acute intermittent porphyria (AIP) is caused by a partial deficiency of hydroxymethylbilane synthase and affects heme biosynthesis. Mutations in the HMBS gene result in HMBS deficiency. AIP is a rare disease, and there been insufficient studies on it. This report describes the molecular epidemiology of HMBS gene defects and hydroxymethylbilane synthase activity levels in classical AIP.
METHODS
Databases of PubMed, CNKI, and Wang Fang Database were searched for eligible studies to investigate HMBS gene mutations in peripheral blood samples and HMBS activity in erythrocytes of patients with classical AIP. Relevant studies published up to July 15, 2023, from several databases were independently searched and selected by 2 reviewers. Accuracy data and relevant information were extracted from each eligible study by 2 independent researchers and analyzed using statistical software.
RESULTS
After pooling the accuracy data from 232 patients of the 15 eligible studies, 90.5% (210/232) of AIP patients had decreased erythrocyte hydroxymethylbilane synthase activity (<70%), and 96 different mutations were identified in 232 patients, including 33 missense (34.4%), 27 splice (28.1%), 19 deletion (19.8%), 8 nonsense (8.3%), 9 insertion (9.4%) mutations. Residual enzyme activities (%) for different groups of type were expressed using mean and 95% confidence interval (95% CI): missense (51.2, 48.5-53.9), splice (57.5, 52.0-59.1), deletion (54.9, 50.7-59.1), nonsense (52.2, 44.4-60.0), insertion (53.2, 47.4-59.0), group analysis P = .17. Subgroups of missense mutations, domain 1 (50.2, 46.0-54.4), domain 2 (52.8, 49.1-56.4), and domain 3 (49.2, 38.3-60.0), Subgroup analysis, P = .62.
CONCLUSION
Different mutation types and mutation positions are not associated with the level of hydroxymethylbilane synthase activity. Erythrocyte hydroxymethylbilane synthase activity is often reduced to half of normal in patients with AIP, and the enzyme activity assay has a high diagnostic value in AIP. AIP is highly molecularly heterogeneous, with missense mutations being the most common, followed by splice mutations. R173W and G111R are high-frequency mutations and have been found in multiple families from different countries.
Topics: Humans; Porphyria, Acute Intermittent; Hydroxymethylbilane Synthase; Mutation; Mutation, Missense
PubMed: 37773850
DOI: 10.1097/MD.0000000000035144 -
Cureus Jun 2023Acute intermittent porphyria (AIP) is a severe multiorgan dysfunction disorder that can be fatal if not treated promptly. The newest treatment modality involving small... (Review)
Review
Acute intermittent porphyria (AIP) is a severe multiorgan dysfunction disorder that can be fatal if not treated promptly. The newest treatment modality involving small interfering RNA (siRNA) molecules, givosiran, is administered for AIP. Although it has very beneficial effects in treating attacks of AIP, it comes with an extensive side effect profile that is not fully understood or studied. Hence, this novel drug model treatment's risk-benefit evaluation is still necessary. For relevant medical literature, we explored medical databases such as PubMed/Medline, PubMed Central, Cochrane Library, Internet Archive Scholar, Google Scholar, and Wiley Online Library. The selected papers were screened based on eligibility criteria and filtered through quality appraisal tools, and 13 finalized research papers were included in the study. Of the 13 identified papers, three were clinical trials, and 10 were review articles. The selected papers all discussed the effectiveness and side effects of givosiran in acute and recurrent attacks of AIP. The research papers showed decreased rates of acute attacks of AIP with givosiran and terminating recurrent attacks. But there are certain non-serious side effects, like fatigue and nausea. Also, there are some severe side effects, like pain. There is limited information on renal and liver function impairment using givosiran and the use of givosiran in patients with kidney and liver disease, for which further studies are required.
PubMed: 37469824
DOI: 10.7759/cureus.40585 -
Oral Diseases Oct 2010Hepatitis C virus (HCV) is one of the major causes of chronic liver disease worldwide but its morbidity is also due to a variety of extra-hepatic manifestations... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Hepatitis C virus (HCV) is one of the major causes of chronic liver disease worldwide but its morbidity is also due to a variety of extra-hepatic manifestations including mixed cryoglubulinemia, non-Hodgkin lymphoma, diabetes, porphyria cutanea tarda and lichen planus. The aims of this study were to conduct a systematic review and a meta-analysis on the prevalence of HCV in lichen planus patients and on the prevalence of lichen planus in chronic HCV infection.
MATERIALS AND METHOD
Bibliographic searches were conducted in several electronic databases. Pooled data were analysed by calculating odds ratios, using a random effects model.
RESULTS AND CONCLUSIONS
Thirty-three studies comparing the seroprevalence of HCV in lichen planus patients and six reporting the prevalence of lichen planus in patients with HCV infection were included in the meta-analysis. The summary estimate showed that LP patients have significantly higher risk (odds ratio 4.85; 95% confidence interval 3.58-6.56) than controls of being HCV seropositive. A similar odds ratio of having lichen planus was found among HCV patients (4.47; 95% confidence interval 1.84-10.86). Sub-analyses indicated that variability of HCV/lichen planus association seemed only partially depending on geographic effect.
Topics: Hepacivirus; Hepatitis C, Chronic; Humans; Lichen Planus; Risk Factors; Seroepidemiologic Studies; Viremia
PubMed: 20412447
DOI: 10.1111/j.1601-0825.2010.01670.x -
Frontiers in Genetics 2023Early detection and diagnosis are important crucial to prevent life-threatening acute attacks in patients with acute intermittent porphyria (AIP). We aim to provide...
Early detection and diagnosis are important crucial to prevent life-threatening acute attacks in patients with acute intermittent porphyria (AIP). We aim to provide comprehensive data on the clinical and gene variant characteristics and genotype-phenotype association of Chinese patients with AIP in order to improve clinicians' knowledge of AIP and reduce misdiagnosis and mistaken treatment. We searched the literature on Chinese patients with AIP in PubMed, Web of Science, Wiley Online Library, ScienceDirect and Chinese literature databases up to August 2023 in our analysis to explore the clinical and gene variant characteristics of Chinese patients with AIP. A total of 41 original articles associated with Chinese AIP patients were included for analysis: 97 variants were detected in 160 unrelated families, including 35 missense, 29 frameshift, 24 splicing and 9 nonsense variants, with c.517C>T being the most common variant. Clinical data were reported in 77 of 160 patients: Most of them were female (67/77) and the age was 28.8 ± 9.9 years. The most common symptom was abdominal pain (73/77, 94.8%), followed by central nervous system symptoms (45/77, 58.4%). 13.0% (10/77) of patients experienced psychiatric symptoms. Hyponatremia was the most common electrolyte abnormality (42/77). 31 patients received carbohydrate loading therapy, and 30 of them were improved. 6 patients were treated with carbohydrate loading combined with hemin therapy and 5 eventually improved. All variants causing premature stop codons, frameshifts or enzyme activity center may experience more severe clinical phenotypes such as seizures, respiratory paralysis, intracranial hemorrhage disorder or respiratory failure. The most common presenting symptom in Chinese AIP patients was abdominal pain, followed by central nervous system symptoms. The gene analysis in Chinese AIP patients revealed that the heterogeneity is strong and the most common variant was missense mutation, with c.517C>T being the most common variant. The genotype-phenotype association helps guide clinical diagnosis and treatment. However, the treatment for AIP in China is limited and monolithic, and more attention needs to be paid to the treatment.
PubMed: 38148975
DOI: 10.3389/fgene.2023.1291719 -
Journal of Addiction MedicineManagement of alcohol use disorder (AUD) is rarely used in patients with liver disease. We performed a systematic review to examine the impact of AUD management among... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Management of alcohol use disorder (AUD) is rarely used in patients with liver disease. We performed a systematic review to examine the impact of AUD management among patients with liver disease.
METHODS
Twenty studies fulfilling the inclusion and exclusion criteria on 38,329 patients (7072 receiving AUD intervention) with liver disease (15 with liver disease and 6 liver transplant [LT] recipients) were analyzed. One study was common to both groups. Variable follow-up period across studies was weighted for sample size and converting to person-years. Primary outcome was alcohol use, and secondary outcomes were liver decompensation and patient mortality.
RESULTS
Abstinence and alcohol relapse rates/person-year with AUD intervention among liver disease patients were 0.41 (0.27-0.55) and 0.42 (0.30-0.755), similar for integrated (colocated liver and addiction clinics) versus concomitant (separate hepatology and addiction clinics) intervention. Compared with standard of care, odds for decompensation with AUD intervention (n = 1), 30-day readmission (n = 1), and patient mortality (n = 2) were lower by 44%, 59%, and 58% respectively. Similar figures were 1.24 (0.86-1.80) for abstinence and 0.52 (0.24-0.14) for relapse. Among LT recipients, odds for alcohol relapse and mortality with follow-up integrated with addiction team versus hepatology alone were 0.48 (0.25-0.72) and 0.29 (0.08-0.99), respectively.
CONCLUSIONS
Follow-up of LT recipients in an integrated clinic with addiction team is associated with improved outcomes. Simultaneous management of AUD in patients with liver disease improves liver-related outcomes. Large prospective studies are needed to examine benefits of AUD intervention in patients with liver disease.
Topics: Humans; Alcoholism; Treatment Outcome; Liver Transplantation; Liver Diseases; Chronic Disease; Recurrence
PubMed: 36259647
DOI: 10.1097/ADM.0000000000001084 -
Journal of Hepatology Oct 2003To conduct a systematic review and meta-analysis on the prevalence of hepatitis C virus (HCV) infection in porphyria cutanea tarda (PCT). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
To conduct a systematic review and meta-analysis on the prevalence of hepatitis C virus (HCV) infection in porphyria cutanea tarda (PCT).
METHODS
Studies evaluating prevalence of HCV infection in patients with PCT were considered. Bibliographical searches were conducted in several electronic databases. Studies comparing HCV prevalence in PCT (cases) and in a reference group (controls) were included in the meta-analysis, combining the Odds Ratios (OR) of the individual studies.
RESULTS
Fifty studies including 2,167 patients were identified. Mean HCV prevalence by serology was 47%, and 50% with polymerase chain reaction (PCR). HCV prevalence markedly varied depending on the country and the type of PCT (57% in the sporadic and 26% in the familial form). Eight case-control studies were identified. Seven studies compared HCV prevalence in PCT vs. healthy controls: 40% vs. 0.24%, respectively (OR=275; 95% confidence interval=104-725). Heterogeneity disappeared when only studies evaluating HCV infection by PCR were included.
CONCLUSIONS
HCV prevalence in patients with PCT is approximately 50%, much higher than that reported in general population, suggesting a possible etiopathogenic role of HCV in PCT. The striking geographical variation in this association suggests that genetic and/or environmental factors may also be involved in the pathogenesis of this disorder.
Topics: Hepatitis C; Humans; Porphyria Cutanea Tarda; Prevalence
PubMed: 12971974
DOI: 10.1016/s0168-8278(03)00346-5