Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease that causes progressive hepatic fibrosis, often leading to liver failure. The severity of PBC is typically determined by grading the extent of fibrosis in a liver biopsy using a 4-point histological scale: 0 = no fibrosis, 1 = non-bridging fibrosis, 2 = bridging fibrosis, and 3 = cirrhosis. However, liver biopsy is prone to sampling error, and it is sometimes a painful and dangerous procedure. The utility of serial liver biopsies to detect disease progression has not been studied, but it is a critical issue for clinical investigators and physicians.
Null Hypothesis
The average change of fibrosis in serial liver biopsies in patients with PBC is not a reliable indicator of clinical progression.
Methods
Serial liver biopsies were collected every 2 years on 265 subjects with PBC as part of a multicenter double-blind randomized controlled study, which demonstrated that methotrexate, when added to ursodiol treatment, had no effect on PBC. Mean follow-up was 7.4 years, and 935 samples were collected. Four pathologists, who were blinded to the sample order, graded each biopsy. A mean fibrosis score was calculated for each biopsy. Clinical decompensation was defined as development of one or more of the following: varices, ascites, encephalopathy, variceal bleed, liver transplant or liver death. The rate of change of fibrosis over time was compared between the patients who experienced clinical decompensation (n = 83) and those who did not (n = 162) using the Wilcoxon rank sum test.
Results
Fibrosis increased an average of 0.05 stages per year in the group who developed clinical decompensation and decreased 0.01 stages per year in the group who did not. This difference was statistically significant (p<.01). However, a cumulative proportions analysis revealed that fibrosis changed no more than 0.25 stages per year in 86% of individuals with clinical events and in 92% without events.
Conclusion
In a large group of PBC patients, serial liver biopsies can detect a statistical difference in the change of fibrosis between patients who develop clinical decompensation versus patients who do not. However, the average rate of change in fibrosis associated with clinical decompensation is too small to be appreciated in an individual patient. Thus serial liver biopsies are not useful clinical tools to assess disease progression in individuals with PBC taking ursodiol.
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a hypersensitivity reaction with rash, fever and multiorgan dysfunction potentially lethal in up to 10% of cases. It often affects liver function, but it can also affect kidney, lungs, and heart. Severe gastrointestinal involvement is rare. We present a case of a 31-year-old hispanic woman with pseudomembranous colitis associated with lamotrigine-induced DRESS syndrome. To the best of our knowledge, this is the fourth reported case of severe involvement of the gastrointestinal tract and the first to report pseudomembranous colitis in the setting of DRESS syndrome.
Pemphigoid gestationis is a rare autoimmune vesiculobullous disease that occurs during pregnancy or postpartum. It is caused by circulating IgG autoantibodies that target the extracellular non-collagenous domain of the hemidesmosomal protein BP180. Urticarial papules and plaques with posterior development of tense vesicles and bullae with an erythematous background are the hallmark of the disease. It affects both primigravidas and multigravidas and can occur in any trimester or postpartum but presents most often in the second or third trimester
Abstract Pruritus is frequently the most debilitating symptom of cholestatic liver diseases. Moreover, existing therapies are often ineffective. Recent small, retrospective case series reports suggest that serotonin reuptake inhibitors can improve pruritus. This study was undertaken to establish the dose of sertraline and to evaluate its efficacy for cholestatic pruritus. Twenty one subjects with chronic pruritus due to liver disease (including primary biliary cirrhosis, primary sclerosing cholangitis, chronic hepatitis C, and postnecrotic cirrhosis) initially underwent an open-label, dose escalation to determine the dose with optimal efficacy and tolerability. After a washout period, 12 of the subjects entered a randomized, double-blind, placebo-controlled trial. Participants quantified their pruritus using a 0-10 visual analog scale, and pruritus was assessed for distribution, timing, degree of disability, and physical evidence of scratching. The optimum sertraline dose (75-100 mg/day) was well tolerated. In the controlled portion of the study, itch scores improved in patients taking sertraline, but worsened in patients taking placebo ( P = 0.009). Changes in itch distribution, duration, direction, and physical evidence of scratching paralleled changes in the visual analog pruritus score. Conclusion: Sertraline seems to be an effective, well-tolerated treatment for pruritus due to chronic liver disease. These results suggest that serotonergic pathways are important in the perception of itch. (Hepatology 2007;45:666–674.)
Abstract Primary biliary cirrhosis (PBC) is sometimes diagnosed based on a positive antimitochondrial antibody in the appropriate clinical setting without a liver biopsy. Although a liver biopsy can assess the extent of liver fibrosis and provide prognostic information, serum fibrosis markers avoid biopsy complications and sampling error and provide results as a continuous variable, which may be more precise than categorical histological stages. The current study was undertaken to evaluate serum fibrosis markers as predictors of clinical progression in a large cohort of PBC patients. Serial liver biopsy specimens and serum samples were collected every 2 years in 161 PBC subjects for a median of 7.3 years. Clinical progression was defined as development of one or more of the following events: varices, variceal bleed, ascites, encephalopathy, liver transplantation, or liver-related death. Serum hyaluronic acid, tissue inhibitor of metalloproteinase 1, and procollagen III aminopeptide were measured and entered into the previously validated enhanced liver fibrosis (ELF) algorithm. The ability of ELF, histological fibrosis, bilirubin, Model for End-Stage Liver Disease (MELD), and Mayo Risk Score to differentiate between individuals who would experience a clinical event from those who would not was evaluated at different time points. Event-free survival was significantly lower in those with high baseline ELF. Each 1-point increase in ELF was associated with a threefold increase in future complications. The prognostic performance of all tests was similar when performed close to the time of the first event. However, at earlier times in the disease process (4 and 6 years before the first event), the prognostic performance of ELF was significantly better than MELD or Mayo R score. Conclusion: The ELF algorithm is a highly accurate noninvasive measure of PBC disease severity that provides useful long-term prognostic information. (Hepatology 2008.)
Eruptive pseudoangiomatosis is a cutaneous disease of unknown origin, characterized by the sudden appearance of small, asymptomatic angioma-like erythematous papules surrounded by a pale halo that resolves spontaneously. It occurs due to transitory dermal blood vessel dilation and has been associated with viral infections and hematologic disorders. To this day, it remains a disease that affects mostly the lower spectrum of life. Most of the cases have been reported in children and few reports have described its association with immune system disorders. The diagnosis is based upon clinical presentation. Histopathological analysis has no pathognomonic findings and can include dilated dermal blood vessels, perivascular lymphocytic infiltration and plump endothelial cells. We report a 21-years-old female diagnosed with HIV in AIDS stage and a 19- years-old male diagnosed with non- Hodgkin’s lymphoma.