Clinics in Liver Disease

No abstract text is available yet for this article.

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The most common antibody associated with PBC is the anti-mitochondrial antibody (AMA), present in 90% to 95% of patients. For patients who are AMA-negative, novel biomarkers, such as antinuclear antibody-specific antibodies Sp100 and gp210 and anti-kelch-like-12 and anti-hexokinase-1 antibodies, may further aid in the diagnosis of PBC. Several laboratory methods, including immunofluorescence, enzyme-linked immunosorbent assay, immunoblotting, and bead-based assays, exist to evaluate for the presence of antibodies...

Primary biliary cholangitis (PBC) is the most common of the autoimmune liver diseases, in which there is chronic small bile duct inflammation. The pathophysiology of PBC is multifactorial, involving immune dysregulation and damage to biliary epithelial cells, with influences from genetic factors, epigenetics, the gut-liver axis, and environmental exposures.

Using ursodeoxycholic acid as a standard treatment and for its ability to test for antimitochondrial antibody to accelerate diagnosis, survival of primary biliary cholangitis patients has approached that of the general population, leading to a change in nomenclature from primary biliary cirrhosis to primary biliary cholangitis to more accurately describe the disease.

The goal of autoimmune hepatitis treatment is to achieve clinical and biochemical remission, which is associated with significantly improved outcomes. Induction treatment with corticosteroids and the subsequent addition of steroid-sparing therapy with gradual tapering of corticosteroids remains the standard of care. Several alternatives to azathioprine and second-line agents, such as mycophenolate mofetil, tacrolimus, cyclosporine, sirolimus, or rituximab, have been evaluated in those with intolerance or inadequate response to standard-of-care therapy...

Autoimmune hepatitis (AIH) presents a diagnostic challenge because it is relatively rare and heterogenous in presentation. This article presents the currently adopted approach to AIH diagnosis and explores the challenges with accurately identifying this disease entity. AIH offers no pathognomonic findings, instead relies on clinical presentation, serology, and histology to make the diagnosis. Diagnostic scoring systems support clinical judgment and serve as valuable tools in diagnosis and research. Histological analysis remains the cornerstone of diagnosis and to this day biopsy is essential to make the diagnosis...

Autoimmune liver diseases have unique post-transplant considerations. These recipients are at increased risk of rejection, and recurrent disease may also develop, which can progress to graft loss and increase mortality. Monitoring for and managing these complications is therefore important, though data on associated risk factors and immunosuppression strategies has in most cases been mixed. There are also other disease-specific complications that require management and may impact these decisions, including inflammatory bowel disease in PSC...

Cholangiocarcinoma (CCA) is a deadly complication observed in the setting of primary sclerosing cholangitis (PSC). When symptoms develop and CCA is diagnosed, it is usually at an advanced stage. Median survival is less than 12 months. Early identification of CCA leads to improved outcomes. Although diagnostic tests have excellent specificity, they are plagued by low sensitivity. No surveillance strategies have been widely agreed upon, but most societies recommend measurement of serum carbohydrate antigen 19-9 and MRCP every 6 to 12 months in patients with PSC...

Primary sclerosing cholangitis is a progressive cholestatic liver disease that causes stricturing of the intra and extrahepatic bile ducts that can lead to cirrhosis and end stage liver disease. Effective medical therapy has been elusive, but a course of ursodeoxycholic acid may be prescribed at doses of 17-23 mg/kg/day for up to a year to determine if a reduction in serum alkaline phosphatase is observed. A number of drugs are under investigation, including FXR agonists with choleretic and antimicrobial properties...

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the biliary tree leading to biliary strictures, cholangitis, and cirrhosis. Early in presentation, patients may have normal liver tests, though over time develop a cholestatic pattern of liver injury. Diagnosis is made radiographically with magnetic resonance or endoscopic cholangiography. While several autoantibodies are associated with PSC, none have proven to have adequate diagnostic utility...

Genome-wide association analyses suggest that HLA genes including HLA-DRB*0301, HLA-DRB*0401, and HLA-B*3501 as well as non-HLA genes including CD28/CTLA4/ICOS and SYNPR increased AIH susceptibility. The destruction of hepatocytes is the result of the imbalance between proinflammatory cells and immunosuppressive cells, especially the imbalance between Tregs and Th17 cells. The microbiome in patients with AIH is decreased in diversity with a specific decline in Bifidobacterium and enrichment in Veillonella and Faecalibacterium...

Primary sclerosing cholangitis is a heterogenous immune-mediated disorder characterized by chronic inflammation and stricturing of the bile ducts. Though the driving pathophysiologic mechanisms remain elusive, there are several observed clinical phenotypes of the disease. The distribution of bile duct involvement, presence of concomitant inflammatory bowel disease, significant infiltration of IgG4-positive plasma cells, and overlapping features with other autoimmune disease has significant implications for prognosis and treatment...

Primary sclerosing cholangitis (PSC) is considered an immunologically mediated disease. However, some of its features are not consistent with the typical profile of autoimmune conditions. PSC is characterized by progressive biliary fibrosis that may ultimately result in the eventual development of cirrhosis. In recent years, multiple studies have reported that the incidence and prevalence of this disease are on the rise. Consequently, patients are often diagnosed without symptoms or signs of advanced liver disease, although many still present with signs of decompensated liver disease...

Chronic cholestasis is the hallmark clinical feature of primary biliary cholangitis. In addition to progressive liver damage, chronic cholestasis can lead to serious complications, many of which occur outside the liver. Bile acids are ligands for nuclear hormone receptors, and alterations in their concentration disrupt normal functioning of numerous different cell types. This article discusses the clinical presentation, pathophysiology, and management of pruritus (itching), fatigue, osteoporosis, hyperlipidemia, fat-soluble vitamin deficiencies, malignancies, cardiac dysfunction, bacterial cholangitis, cholemic (bile cast) nephropathy, and Sicca syndrome...

Ursodeoxycholic acid (UDCA) is the first-line treatment of primary biliary cholangitis (PBC). Long-term UDCA use significantly reduces progression to cirrhosis. UDCA improves liver enzymes and transplant-free survival rates. Despite the association between PBC and hyperlipidemia, treatment is indicated under specific circumstances with statins and fibrates being safe options. Osteoporosis, which is frequently seen, is usually managed based on data from postmenopausal women. Sicca syndrome is treated similarly to its standalone condition with the use of hydroxypropyl methylcellulose eye drops and anticholinergic drugs...

Autoimmune hepatitis (AIH) is a chronic immunologic disorder in which the immune system targets the liver. The disease has a genetic basis and this accounts for the epidemiologic variation observed in serologic testing and clinical presentation across different populations. The incidence of AIH increases with age into the 70s and seems to be increasing in prevalence. Most patients test positive for antinuclear antibody, ASMA, or anti-LKM but about 20% of patients do not have these serologic markers. At clinical presentation, patients may be asymptomatic, symptomatic, have acute liver failure, or decompensated cirrhosis...

No abstract text is available yet for this article.

Hepatitis B infection affects approximately 262 million people worldwide and is responsible for 900,000 deaths annually. This article reviews the major factors limiting HBV elimination, which includes limited linkage to care and complicated HBV testing and treatment guidelines. The article then provides solutions to these pressing issues.

HDV use the cell enzymes for its own replication, and the HBsAg as an envelope. There is an urgent need to develop new drugs for chronic hepatitis D (CHD). Pegylated interferon alpha (PEG-IFNα) (direct-antiviral and immune modulator) has been used and recommended by scientific guidelines, although not approved, with moderate efficacy and poor tolerability. There are several drugs in development which target the host: bulevirtide (BLV), lonafarnib (LNF), nucleic acid polymer, and others.

The disease burden of HDV is poorly understood. Our review identified multiple reasons: (1) HDV infection rates are overestimated in the general population due to limited sample sizes, sampling high-risk populations, and significant regional variations, (2) estimates are based on chronic HBV populations, but HBV burden itself is uncertain, (3) there is a lack of testing in at-risk populations, (4) prevalence testing is based on HDV antibody testing and not HDV RNA, which distinguishes between active infection versus prior exposure, (5) older studies used less reliable testing and (6) HBV vaccination programs have affected HDV prevalence, but is often not accounted for...