The Increasing Pace of Progress in Hepatology
The Increasing Pace of Progress in Hepatology
Distinguishing subtypes. Among the various subtypes of autoimmune liver disease, two received particular attention at this year's DDW.
Immunoglobulin (Ig) G4-related sclerosing cholangitis is a unique subtype that presents as biliary strictures that mimic biliary involvement in primary sclerosing cholangitis (PSC), cholangiocarcinoma, or pancreatic cancer. Although uncommon, IgG4-related sclerosing cholangitis is a steroid-responsive disorder that, if left untreated, can rapidly progress to biliary cirrhosis. Therefore, it is imperative to identify and differentiate IgG4-related sclerosing cholangitis from PSC.
Ahmed and colleagues looked at a large cohort of patients considered to have PSC to determine whether those with elevated serum IgG4 levels were more likely than those with typical PSC to have other organ involvement and a different outcome. Of 803 patients, 13% had elevated serum IgG4 levels; the frequency of progression to liver transplantation was similar to that in patients with normal IgG4 levels. Among the seropositive patients who had initial imaging (MRI or CT), 20% had evidence of pancreatic or renal manifestations of IgG4-related disease. In contrast, the prevalence of renal manifestation was 3%, with no pancreatic manifestations, among an age- and sex- matched sample of seronegative patients with PSC.
Minocycline-associated autoimmune hepatitis (AIH) was the second subtype for which interesting new data were presented. Minocycline, a semisynthetic tetracycline derivative commonly used for the treatment of acne, has been linked to various clinical and serologic autoimmune conditions, including AIH.
Vo and colleagues described the clinical, laboratory, histologic features, and treatment outcome of minocycline-induced AIH compared with idiopathic AIH. Patients with minocycline-induced AIH more frequently had symptoms of arthralgia and displayed serologic markers of type 1 AIH only, but they had excellent treatment outcomes. Durable immunosuppression withdrawal was possible in all patients with minocycline-induced AIH.
Outcomes. Normalization or reduction of serum alkaline phosphatase (ALP) levels correlates with improved outcomes in patients with PSC.
Levy and colleagues sought to investigate whether a reduction of serum ALP to < 1.5 times the upper limit of normal (ULN) after at least 1 year of follow-up would correlate with outcome. Patients who maintained a serum ALP level > 1.5 times the ULN were more likely to die or receive a liver transplant than patients with an ALP level < 1.5 times the ULN (43% vs 14%, respectively). The relative risk for death or liver transplant among patients with an ALP level > 1.5 times the ULN was 3.1.
The median time to death or liver transplantation was 49 months for patients with elevated ALP levels compared with 94 months for those with lower ALP levels. This difference was not statistically significant, possibly because of the small number of events in those with lower ALP levels.
Treatment. Obeticholic acid (OCA), a modified bile acid, functions as a farnesoid X receptor agonist, and has been proposed as a therapeutic option for a wide variety of liver diseases.
Kowdley and colleagues reviewed three studies of OCA efficacy (doses ranging from 5 to 50 mg over 3-12 months of treatment) in patients with primary biliary cirrhosis. Across all three studies, OCA treatment was consistently associated with statistically significant decreases in ALP levels and other liver enzymes, including gamma-glutamyltransferase, alanine aminotransferase, and aspartate aminotransferase. Although the patients in the OCA monotherapy group had higher ALP values at baseline than the OCA plus ursodeoxycholic acid (UDCA) group, the two groups reached similar ALP levels by the end of the double-blind period. Pruritus was the most common adverse event associated with OCA administration, with a dose-related increase in incidence.
A significantly larger percentage of patients treated with OCA, with or without UDCA, achieved both lower ALP values and a composite endpoint shown to correlate with long-term, transplant-free survival compared with placebo-treated patients.
Autoimmune Liver Disease
Distinguishing subtypes. Among the various subtypes of autoimmune liver disease, two received particular attention at this year's DDW.
Immunoglobulin (Ig) G4-related sclerosing cholangitis is a unique subtype that presents as biliary strictures that mimic biliary involvement in primary sclerosing cholangitis (PSC), cholangiocarcinoma, or pancreatic cancer. Although uncommon, IgG4-related sclerosing cholangitis is a steroid-responsive disorder that, if left untreated, can rapidly progress to biliary cirrhosis. Therefore, it is imperative to identify and differentiate IgG4-related sclerosing cholangitis from PSC.
Ahmed and colleagues looked at a large cohort of patients considered to have PSC to determine whether those with elevated serum IgG4 levels were more likely than those with typical PSC to have other organ involvement and a different outcome. Of 803 patients, 13% had elevated serum IgG4 levels; the frequency of progression to liver transplantation was similar to that in patients with normal IgG4 levels. Among the seropositive patients who had initial imaging (MRI or CT), 20% had evidence of pancreatic or renal manifestations of IgG4-related disease. In contrast, the prevalence of renal manifestation was 3%, with no pancreatic manifestations, among an age- and sex- matched sample of seronegative patients with PSC.
Minocycline-associated autoimmune hepatitis (AIH) was the second subtype for which interesting new data were presented. Minocycline, a semisynthetic tetracycline derivative commonly used for the treatment of acne, has been linked to various clinical and serologic autoimmune conditions, including AIH.
Vo and colleagues described the clinical, laboratory, histologic features, and treatment outcome of minocycline-induced AIH compared with idiopathic AIH. Patients with minocycline-induced AIH more frequently had symptoms of arthralgia and displayed serologic markers of type 1 AIH only, but they had excellent treatment outcomes. Durable immunosuppression withdrawal was possible in all patients with minocycline-induced AIH.
Outcomes. Normalization or reduction of serum alkaline phosphatase (ALP) levels correlates with improved outcomes in patients with PSC.
Levy and colleagues sought to investigate whether a reduction of serum ALP to < 1.5 times the upper limit of normal (ULN) after at least 1 year of follow-up would correlate with outcome. Patients who maintained a serum ALP level > 1.5 times the ULN were more likely to die or receive a liver transplant than patients with an ALP level < 1.5 times the ULN (43% vs 14%, respectively). The relative risk for death or liver transplant among patients with an ALP level > 1.5 times the ULN was 3.1.
The median time to death or liver transplantation was 49 months for patients with elevated ALP levels compared with 94 months for those with lower ALP levels. This difference was not statistically significant, possibly because of the small number of events in those with lower ALP levels.
Treatment. Obeticholic acid (OCA), a modified bile acid, functions as a farnesoid X receptor agonist, and has been proposed as a therapeutic option for a wide variety of liver diseases.
Kowdley and colleagues reviewed three studies of OCA efficacy (doses ranging from 5 to 50 mg over 3-12 months of treatment) in patients with primary biliary cirrhosis. Across all three studies, OCA treatment was consistently associated with statistically significant decreases in ALP levels and other liver enzymes, including gamma-glutamyltransferase, alanine aminotransferase, and aspartate aminotransferase. Although the patients in the OCA monotherapy group had higher ALP values at baseline than the OCA plus ursodeoxycholic acid (UDCA) group, the two groups reached similar ALP levels by the end of the double-blind period. Pruritus was the most common adverse event associated with OCA administration, with a dose-related increase in incidence.
A significantly larger percentage of patients treated with OCA, with or without UDCA, achieved both lower ALP values and a composite endpoint shown to correlate with long-term, transplant-free survival compared with placebo-treated patients.