The cholestatic hepatitis associated with acute viral hepatitis leads to prolonged jaundice and pruritus. While several treatment approaches have been proposed, there is a noticeable absence of agreement over the most effective course of action. The goal of this systematic review is to compile and assess the available data on treatment approaches for prolonged hepatitis associated with viral hepatitis.

We comprehensively searched for relevant studies in MEDLINE, Embase, and Scopus from their inception to May 2024. Studies reporting the treatment option for the management of the cholestatic phase associated with viral hepatitis were included.

A total of 28 studies describing 164 patients were included in the review, of which 18 were case reports, 8 were case series, and 2 were interventional studies. The benefit of ursodeoxycholic acid (UDCA) was reported in two case reports, with doses varying from 10 to 30 mg/kg/d in the included studies. The use of corticosteroids in adult patients was reported in 21 studies, with prednisolone doses varying from 30 to 60 mg/day in adults. Two studies used nasobiliary drain (NBD) for patients who failed to respond to conventional therapy. Lastly, three studies reported using plasma exchange (PLEX) in patients refractory to standard treatment.

Patients not responding to UDCA or cholestyramine may benefit from a short course of corticosteroids, suggesting an immune-mediated phenomenon. NBD placement or PLEX may be tried after analyzing the risk-to-benefit ratio for patients who are nonresponsive to corticosteroids. Further research is required to determine the optimal treatment strategy.

Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive liver disease, causing episodic cholestasis with intense pruritus. This case report highlights the effectiveness of early plasmapheresis as a therapeutic option for BRIC type 2, offering rapid symptom relief and early termination of cholestatic episodes. It contributes to the limited evidence supporting plasmapheresis as a treatment for BRIC flares resistant to conventional therapies.

A 43-year-old male with BRIC type 2 presented with fatigue, jaundice, and severe pruritus, triggered by a recent mild severe acute respiratory syndrome coronavirus 2 infection. Laboratory results confirmed cholestasis with elevated bilirubin and alkaline phosphatase. First-line pharmacological treatments, including cholestyramine and rifampicin, failed. Endoscopic nasobiliary drainage was ineffective, prompting initiation of plasmapheresis. This intervention rapidly relieved pruritus, with complete biochemical normalisation after 11 sessions. Two years later, a similar episode occurred, and early reinitiation of plasmapheresis led to symptom resolution within two sessions and biochemical recovery within two weeks. The patient tolerated the procedure well, with no adverse effects observed. Follow-up showed no signs of cholestasis recurrence.

Plasmapheresis is a safe and effective option for therapy-refractory BRIC type 2, particularly when initiated early in cholestasis.

Progressive Familial intrahepatic cholestasis (PFIC) are rare disorders of bile acid (BAs) secretion and transport with a genetic background. PFIC are paediatric manifestations, but the same variants causing PFIC can also cause cholestasis with a later paediatric onset or adult-onset cholestatic disease (AOCD). Pruritus is a symptom of cholestasis that can be so devastating that it requires a liver transplant (LT) in children; some PFIC types have been described as at risk of liver cancer development. Commonly prescribed medications for PFIC symptoms can partially relieve pruritus without changing the natural history of the disease. Recently, a therapy reducing the intestinal resorption of BAs has been approved; it is effective on both pruritus and cholestasis in PFIC, potentially being a disease-modifying intervention.

The clinical and genetic characteristics of different PFIC and AOCD are summarized to provide a common background for geneticists and paediatric and adult hepatologists in diagnosis and management.

Collaboration between paediatric and adult hepatologists and geneticists will become crucial for cholestatic disease research and patient treatment. Therefore, adult hepatologists will need to learn more about FIC. This might enable the implementation of individualized surveillance in FIC patients and the evaluation of patient family histories.

The acute inflammatory milieu in patients with acute liver failure (ALF) results in 'toxic' blood in these patients. In vitro experiments have shown that the plasma obtained from ALF patients is toxic to rabbit hepatocytes and inhibits regeneration of rat hepatocytes. Treatments such as plasma exchange and continuous renal replacement therapy to cleanse the blood have improved survival in ALF patients. In the liver microcirculation, the exchange of fluid across fenestrae in liver sinusoidal endothelial cells (LSECs) is vital for proper functioning of hepatocytes. Clogging of the liver filter bed by inflammatory debris and cells ('traffic jam hypothesis') impeding blood flow in sinusoids may in turn reduce the exchange of fluid across LSEC fenestrae and cause dysfunction and necrosis of hepatocytes in ALF patients. In mouse model of paracetamol overdose, disturbances in microcirculation in the liver preceded the development of injury and necrosis of hepatocytes. This may represent a reversible pathophysiological mechanism in ALF which may be improved by the anti-inflammatory effect of plasma exchange. Wider access to urgent plasma exchange is a major advantage compared to urgent liver transplantation to treat ALF patients worldwide, especially so in resource constrained settings. Continuous hemo-filtration or dialysis is used to reduce ammonia levels and treat cerebral edema in ALF patients. In this review, we discuss the different modalities to cleanse the blood in ALF patients, with an emphasis on plasma exchange, from a hepatology perspective.

Primary biliary cholangitis (PBC), an immune-mediated disease characterised by destruction of intrahepatic bile ducts, results in progressive damage to the biliary tree, cholestasis and ultimately advanced liver disease. In the last decade, advances in practice have improved clinical care, driven novel therapeutic options and improved risk stratification tools.

To provide an overview of the disease characteristics of PBC and review a patient-centred management approach for the clinical team caring for those with PBC.

We reviewed the current literature and guidelines on PBC with a focus on management and therapies.

A confident diagnosis of PBC is usually made based on serum liver tests and immune serology. Management of PBC should focus on three main 'process' pillars: (a) treat and risk-stratify through use of biochemical and prognostic criteria; (b) manage concurrent symptoms and other associated diseases; and (c) stage disease, monitor progression and prevent complications. With ongoing complexities in management, including a newly licensed therapy (obeticholic acid) and alternative non-licensed treatments and ongoing clinical trials, discussion with PBC expert centres is encouraged.

PBC is a dynamic disease wherein current treatment goals have become appropriately ambitious. Goals of care should prioritise prevention of end-stage liver disease and amelioration of patient symptom burden for all.

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Eighth Edition of the JCA Special Issue continues to maintain this methodology and rigor in order to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Eighth Edition, like its predecessor, continues to apply the category and grading system definitions in fact sheets. The general layout and concept of a fact sheet that was introduced in the Fourth Edition, has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease entity or medical condition. The Eighth Edition comprises 84 fact sheets for relevant diseases and medical conditions, with 157 graded and categorized indications and/or TA modalities. The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.

Intrahepatic cholestasis of pregnancy is characterised by pruritus and elevated serum bile acids. The pruritus can be severe, and pharmacological options achieve inconsistent symptomatic improvement. Raised bile acids are linearly associated with adverse fetal outcomes, with existing management of limited benefit. We hypothesised that therapeutic plasma exchange removes pruritogens and lowers total bile acid concentrations, and improves symptoms and biochemical abnormalities in severe cases that have not responded to other treatments.

Four women with severe pruritus and hypercholanemia were managed with therapeutic plasma exchange. Serial blood biochemistry and visual analogue scores of itch severity were obtained. Blood and waste plasma samples were collected before and after exchange; individual bile acids and sulfated progesterone metabolites were measured with HPLC-MS, autotaxin activity and cytokine profiles with enzymatic methods. Results were analysed using segmental linear regression to describe longitudinal trends, and ratio t tests.

Total bile acids and visual analogue itch scores demonstrated trends to transiently improve following plasma exchange, with temporary symptomatic benefit reported. Individual bile acids (excluding the drug ursodeoxycholic acid), and the sulfated metabolites of progesterone reduced following exchange (P = .03 and P = .04, respectively), whilst analysis of waste plasma demonstrated removal of autotaxin and cytokines.

Therapeutic plasma exchange can lower potentially harmful bile acids and improve itch, likely secondary to the demonstrated removal of pruritogens. However, the limited current experience and potential complications, along with minimal sustained symptomatic benefit, restrict its current use to women with the most severe disease for whom other treatment options have been exhausted.