Sumant Arora

Hepatic porphyria: A narrative review

Porphyrias are a group of metabolic disorders, which result from a specific abnormality in one of the eight enzymes of the heme biosynthetic pathway. These have been subdivided based on the predominant site of enzyme defect into hepatic and erythropoietic types and based on clinical presentation into acute neurovisceral and cutaneous blistering porphyrias. This review focuses on hepatic porphyrias, which include acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), aminolevulinic acid dehydratase deficiency porphyria (ADP), and porphyria cutanea tarda (PCT). Of these, AIP and ADP are classified as acute porphyria, PCT as cutaneous, while VP and HCP present with both acute and cutaneous clinical manifestations. Porphobilinogen levels in a spot urine sample is the initial screening test for the diagnosis of acute hepatic porphyria, and plasma with spot urine porphyrin levels is the initial screening test to approach patients suspected of cutaneous porphyria. Specific biochemical porphyrin profile for each porphyria helps in determining the specific diagnosis. Pain relief and elimination of triggering agents are the initial steps in managing a patient presenting with an acute attack. Intravenous glucose administration terminates the mild episode of acute porphyria, with intravenous hemin needed for management of moderate to severe episodes. Liver transplantation is curative and may be needed for patients with a life-threatening acute porphyria attack or for patients with recurrent acute attacks refractory to prophylactic treatment. Of the cutaneous porphyrias, PCT is the most common and is frequently associated with a combination of multiple susceptibility factors such as alcohol use, smoking, hepatitis C virus infection, HIV infection, estrogen use, and mutations of the hemochromatosis gene. Regular phlebotomy schedule and low-dose hydroxychloroquine are effective and safe treatment options for management of PCT.

Rates of hospitalization among African American and Caucasian American patients with Crohn's disease seen at a tertiary care center

Abstract Background There is equivocal evidence regarding differences in the clinical course and outcomes of Crohn’s disease (CD) among African Americans compared with Caucasian Americans. We sought to analyze whether African Americans with CD are more likely to be hospitalized for CD-related complications when compared with Caucasian Americans with CD. Methods We conducted a retrospective cohort study including 909 African Americans and Caucasian Americans with CD who were seen at our tertiary care Inflammatory Bowel Disease (IBD) referral center between 2000 and 2013. We calculated the rate of hospitalization for CD-related complications among African Americans and Caucasian Americans separately. Zero-inflated Poisson regression models with robust variance estimates were used to estimate crude and multivariable adjusted rate ratios (RR) for CD-related hospitalizations. Multivariable adjusted models included adjustment for age, sex, duration of CD, smoking and CD therapy. Results The cumulative rate of CD-related hospital admissions was higher among African American patients compared with Caucasian American patients (395.6/1000 person-years in African Americans vs. 230.4/1000 person-years in Caucasian Americans). Unadjusted and multivariable adjusted rate ratios for CD-related hospitalization comparing African Americans and Caucasian Americans were 1.59 (95% confidence interval [95%CI]: 1.10–2.29; P=0.01) and 1.44 (95%CI: 1.02–2.03; P=0.04), respectively. Conclusions African Americans with CD followed at a tertiary IBD-referral center had a higher rate for CD-related hospitalizations compared with Caucasian Americans. Future studies should examine whether socioeconomic status and biologic markers of disease status could explain the higher risk observed among African Americans.

Reduced Impact of Renal Failure on the Outcome of Patients with Alcoholic Liver Disease Undergoing Liver Transplantation

Pretransplant renal failure is commonly reported to be a poor prognostic indicator affecting survival after liver transplantation (LT). However, whether the impact of renal failure on patient outcome varies according to the aetiology of the underlying liver disease is largely unknown.

Place of Liver Transplant in Alcoholic Hepatitis

In the United States and Europe, after viral hepatitis, alcoholic liver disease (ALD) is the second most commonly recognized indication for liver transplantation. Issues of conflicting data on six-month abstinence, eligibility criteria for selection of patients, and clarity of definition of post-transplant relapse are still under debate. Despite high early mortality, acute alcoholic hepatitis continues to be a contraindication to transplant despite data demonstrating the successful outcome of liver transplantation in these individuals. Disagreements arise due to the trepidation that these patients may relapse resulting in damage to the graft or non-compliance causing graft rejection. However, 1- year, 3-year, and 5-year patient and graft survival after transplant are comparable to transplantation for other etiologies. Studies have revealed that pre-OLT abstinence is a poor forecaster of post-OLT relapse. Life-threatening liver failure can potentially develop in this time frame, resulting in augmentation in waitlist mortality. Due to the paucity of available livers for donation, it is considered by many authorities to be obligatory to choose candidates with a lesser risk for relapse with the utilization of existing prophetic factors and mandatory clinical and psychological pre-transplant evaluations by substance abuse specialists and psychiatrists/psychologists. There is concern that if amendments in guidelines for liver transplantation are made for these patients, it may lead to a significant decline in willingness to donate. However, patients with fulminant hepatic failure due to intentional acetaminophen poisoning or due to intravenous-drug use-related acute hepatitis-B virus infection, did not come across this issue. Therefore, a further exploration into this field and these issues is needed.

Impact of vitamin D on the hospitalization rate of Crohn's disease patients seen at a tertiary care center

AIM To study the association between vitamin D level and hospitalization rate in Crohn’s disease (CD) patients. METHODS We designed a retrospective cohort study using adult patients (> 19 years) with CD followed for at least one year at our inflammatory bowel disease center. Vitamin D levels were divided into: low mean vitamin D level (< 30 ng/mL) vs appropriate mean vitamin D level (30-100 ng/mL). Generalized Poisson Regression Models (GPR) for Rate Data were used to estimate partially adjusted and fully adjusted incidence rate ratios (IRR) of hospitalization among CD patients. We also examined IRRs for vitamin D level as a continuous variable. RESULTS Of the 880 CD patients, 196 patients with vitamin D level during the observation period were included. Partially adjusted model demonstrated that CD patients with a low mean vitamin D level were almost twice more likely to be admitted (IRR = 1.76, 95%CI: 1.38-2.24) compared to those with an appropriate vitamin D level. The fully adjusted model confirmed this association (IRR = 1.44, 95%CI: 1.11-1.87). Partially adjusted model with vitamin D level as a continuous variable demonstrated, higher mean vitamin D level was associated with a 3% lower likelihood of admission with every unit (ng/mL) rise in mean vitamin D level (IRR = 0.97, 95%CI: 0.96-0.98). The fully adjusted model confirmed this association (IRR = 0.98, 95%CI: 0.97-0.99). CONCLUSION Normal or adequate vitamin D stores may be protective in the clinical course of CD. However, this role needs to be further characterized and understood.

Inflammatory Bowel Disease: Epidemiology

Inflammatory bowel disease (IBD) is characterized by two partially distinct alimentary disease processes, namely Crohn’s disease (CD) and ulcerative colitis (UC), affecting genetically predisposed individuals. CD and UC were first described in 1932 and 1859, respectively. It is estimated that 1.5 million in North America and 2.5 million persons in Europe have IBD. The peak incidence of CD and UC is between 20–30 years and 30–40 years of age, respectively. Both incidence and prevalence of CD and UC are similar across males and females. However, several studies suggest a female predominance in CD and a male predominance in UC. The pathogenesis of IBD is attributed to an uncontrolled immune-mediated inflammatory response to an unrecognized environmental trigger that interacts with the intestinal flora. Various determinants of IBD include the following: peculiar environmental triggers, intestinal immune mechanisms, heritable factors, gut flora, diet, mesenteric fat, medications, nicotine, infectious agents, immunization, hygiene, pregnancy, breastfeeding, stress and lifestyle. Predominant complications in IBD are surgery, malnutrition, disease exacerbations and cancer. Patients with CD have a higher mortality compared to general population. Epidemiological studies continue to expand our understanding of the distribution, determinants and mechanisms of IBD. This has enabled us to recognize safer and effective approaches to management.