Background & Aims
Porphyria cutanea tarda (PCT) is an iron-related disorder caused by reduced activity of hepatic uroporphyrinogen decarboxylase (UROD); it can be treated by phlebotomy or low doses of hydroxychloroquine. We performed a prospective pilot study to compare the efficacy and safety of these therapies.
Methods
We analyzed data from 48 consecutive patients with well-documented PCT to characterize susceptibility factors; patients were treated with phlebotomy (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low-dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month after they had normal plasma levels of porphyrin). We compared the time required to achieve a normal plasma porphyrin concentration (remission, the primary outcome) for 17 patients treated with phlebotomy and 13 treated with hydroxychloroquine.
Results
The time to remission was a median 6.9 months for patients that received phlebotomy and 6.1 months for patients treated with hydroxychloroquine treatment (6.7 and 6.5 months for randomized patients), a difference that was not significant (Log Rank P=.06 and P=.95, respectively). The sample size was insufficient to confirm noninferiority of hydroxychloroquine treatment (hazard ratio [HR], 2.19; 95% confidence interval [CI], 0.95–5.06) for all patients. Patients that received hydroxychloroquine had substantially better compliance. There were no significant side effects of either treatment.
Conclusions
Hydroxychloroquine, 100 mg twice weekly, is as effective and safe as phlebotomy in patients with PCT, although noninferiority was not established. Given these results, higher-dose regimens of hydroxychloroquine, which have more side effects, do not seem justified. Compliance was better and projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long-term studies are needed to compare durability of response.
Porphyria cutanea tarda (PCT) is a cutaneous porphyria with sporadic (type 1) and familial (type 2) subtypes, both resulting from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. Environmental and genetic factors are involved in the development of PCT, and genetic variants in the cytochrome P450 (CYP ) genes, CYP1A1 and CYP1A2, have been implicated. We investigated the association between PCT and variants in CYP1A1, CYP1A2 and CYP2E1, and the glutathione-S-transferase (GST ) genes, GSTM1 and GSTT1. PCT diagnosis was based on urinary or plasma porphyrin profiles. Patients were classified as type 1 or 2 PCT based on UROD mutation analysis. The CYP1A2*1F promoter A allele frequency was significantly higher (P < 0.022) and the A/A genotype frequency marginally higher in PCT patients overall (P < 0.057), with the A/A genotype significantly more common in type 1 PCT (P < 0.043). The presence of the wild-type GSTM1 allele also was associated significantly with PCT (P < 0.019). Neither hemochromatosis (HFE) mutations, tobacco smoking, hepatitis C and HIV infection, ethanol consumption, nor estrogen use were associated with these allelic variants. Age at onset was significantly lower in type 2 PCT patients (P < 0.001), as observed previously. Thus, positive associations between PCT and the CYP1A2*1F promoter A allele and A/A genotype and the wild-type GSTM1 allele indicates that these functional hepatic biotransformation enzymes are risk factors for the development of this disease.
guidelines were followed (Figure). The meta-analysis was performed using RevMan software on studies for hospital length of stay. Mean differences were generated to describe the overall effect size using random effect models. Results: A total of 4,381 patients from eight studies were included in the qualitative analysis. A total of 909 patients in the NAFLD group and 3472 patients in the Non-NAFLD group. A qualitative synthesis showed that the mean difference in the hospital length of stay was 2.49 days between the NAFLD and NON-NAFLD groups and a 95% Confidence interval (95%CI) of 0.96-4.02. (Figure ) I2 5 61%.This denotes on an average ;2.5 days additional hospital stay among NAFLD/MAFLD patients with COVID-19. Conclusion: Our meta-analysis suggests that NAFLD patients remain in the hospital for a longer period than NON-NAFLD patients. Fatty Liver disease is a risk factor that leads to increased severity of COVID-19 infection.[1361] Figure 1. PRISMA Flowchart outlining the study search and Forest Plot, meta-analysis of Hospital length of stay in COVID-19 with Fatty Liver disease.
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