Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated. Protocol liver biopsy is generally recommended in HCV+ LT recipients, and antiviral therapy can be considered in those with severe/progressive HCV recurrence. Sustained virological response (SVR) can be achieved in approximately 30% of LT recipients with pegylated interferon/ribavirin (PEG-IFN/RBV) with survival benefit, but adverse effects are common. Favorable patient characteristics for response to therapy include non-1 genotype, previously untreated, low baseline HCV-RNA, and donor IL28B genotype CC. Direct acting antiviral (DAA)-based triple therapy is associated with higher rates of SVR, but with similar or slightly higher rates of side effects, and immunosuppressive regimens need to be closely monitored and adjusted during the treatment period. Notably, the safety and efficacy of HCV treatment are very likely to improve with newer generation DAA. The benefit of immunosuppressive strategy on the natural history HCV recurrence has not been well elucidated. Based upon available evidence, cyclosporine A (CSA), mycophenolate mofetil (MMF), and sirolimus appear to have a neutral or small beneficial impact on HCV recurrence. Donor interleukin 28 B (IL28B) polymorphisms appear to impact the course and treatment outcomes in recurrent HCV. Retransplantation should be considered for patients with reasonable survival probability.     

Pruritus in chronic cholestatic liver disease

Pruritus is a troublesome complication in patients with cholestatic liver disease. Several links to its pathogenesis have been proposed, including the role of bile acids, endogenous opioid and serotonins, and lysophosphatidic acid. The management of pruritus in cholestasis is challenging. Medical treatment of the underlying cholestatic condition may provide benefit. Extracorporeal albumin dialysis can be pursued for those who have a poor quality of life and failed the various therapeutic interventions, while awaiting liver transplantation. Experimental interventions, and the management of pruritus in certain conditions such as intrahepatic cholestasis of pregnancy and benign recurrent intrahepatic cholestasis, are also briefly reviewed.     

Hepatitis C genotype 6: A concise review and response-guided therapy proposal

Hepatitis C genotype 6 is endemic in Southeast Asia [prevalence varies between 10%-60% among all hepatitis C virus (HCV) infection], as well as also sporadically reported outside the area among immigrations. The diagnosis of HCV genotype can be inaccurate with earlier methods of genotyping due to identical 5’-UTR between genotype 6 and 1b, hence the newer genotyping methods with core sequencing are preferred. Risk factors and clinical course of HCV genotype 6 do not differ considerably from other genotypes. Treatment outcome of HCV genotype 6 with a combination of pegylated interferon and ribavirin is superior to genotype 1, and nearly comparable to genotype 3, with expected sustained virological response (SVR) rates of 60%-90%. Emerging data suggests that a shorter course 24-wk treatment is equally effective as a standard 48-wk treatment, particularly for those patients who attained undetectable HCV RNA at week 4 (RVR). In addition, baseline and on-treatment predictors of response used for other HCV genotypes appear effective with genotype 6. Although some pan-genotypic direct-acting antivirals have completed phase II/III studies (sofosbuvir and simeprevir) with clinical benefit demonstrated in small number of patients with genotype 6, broad availability of these agents in Southeast Asia may not be expected in the near future. While awaiting the newer therapy, response-guided therapy seems appropriate for patients with HCV genotype 6. Patients with RVR (representing > 70% of patients) are suitable for 24-wk treatment with expected SVR rates > 80%. Patients without RVR and/or those with poor response predictors may benefit from 48 wk of therapy, and a detectable HCV RNA at week 12 (with no early virological response) serves as a stopping rule. This treatment scheme is likely to have a major economic impact on HCV therapy, particularly in Southeast Asia, wherein treatment can be truncated securely in the majority of patients with HCV genotype 6.     

Clinical features and natural history of hepatocellular adenomas: the impact of obesity

Aliment Pharmacol Ther 2011; 34: 664–674

Summary

Background Hepatocellular adenoma is a benign tumour associated with bleeding and malignant transformation. Obesity has been linked to hepatic tumourigenesis. Aim To evaluate the presentation of hepatocellular adenoma in obesity, and the impact of obesity on the clinical course. Methods Records of 60 consecutive patients (between 2005 and 2010) with a diagnosis of hepatocellular adenoma from a single tertiary centre were analysed. Results Fifty six of 60 patients were women, median age was 36 years, 75% had history of contraceptive use, 18% were overweight and 55% were obese (BMI ≥30 kg/m²). Majority (63%) were asymptomatic; seven patients presented with bleeding. Single (28%) and multiple adenomas (72%) were encountered; size ranged from 1 to 19.7 cm. Obesity was more often associated with multiple adenomas (85% vs. 48%, P = 0.005), bilobar distribution (67% vs. 33%, P = 0.01), lower serum albumin (P = 0.007) and co‐morbidities of fatty liver (P = 0.006), diabetes (P = 0.003), hypertension (P = 0.006) and dyslipidemia (P = 0.03). During median follow‐up of 2.6 years, there were no instances of bleeding, malignant transformation or death. Thirty four patients underwent therapeutic intervention (17 surgical resection, nine transarterial embolization and eight both interventions sequentially). The rate of complete resection of adenoma(s) was significantly lower in obese patients (8% vs. 69%, P = 0.004). In the 26 patients without intervention, tumour size progression was more frequently observed in obese patients (33% vs. 0%, P = 0.05). Three of 15 obese patients (20%) lost ≥5% body weight and there was no progression in the liver lesions. Conclusions  Obesity and features of metabolic syndrome were frequently observed in hepatocellular adenoma. Multiple and bilobar adenomas were more frequent in obese patients. Among patients who were conservatively managed, tumour progression was more often associated with obesity.     

COVID-19 and the Liver: Lessons Learnt from the EAST and the WEST,A Year Later

Globally, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) has been a major cause for significant morbidity and mortality. Since the start of the pandemic, several hepato-biliary manifestations in coronavirus disease 2019 (COVID-19) have been described and unique considerations raised. The review aims to summarize the pathogenesis and hepato-biliary manifestations in COVID-19 and discuss the similarities, contrasting features and disease-specific management across a range of hepato-biliary diseases from the EAST and the WEST. Published studies and regional society guidelines from the EAST and the WEST were comprehensively reviewed and summarized. A wide range of hepato-biliary manifestations, including the infrequent and chronic manifestation of cholangiopathy, has been observed in COVID-19. The pathogenesis of liver injury is multifactorial and with scant evidence for a direct SARS-CoV-2 infection of the liver. Patients with non-alcoholic fatty liver disease, cirrhosis, and liver cancer are potentially at increased risk for severe COVID-19, and there are unique considerations in chronic hepatitis B or C, hepatocellular carcinoma, and in those immunosuppressed such as autoimmune hepatitis or liver transplant recipients. With the surges in SARS-CoV-2 infection, liver transplant activity has variably been impacted. Preliminarily, SARS-CoV-2 vaccines appear to be safe in those with chronic liver disease and in transplant recipients, while emerging data suggest the need for a third dose in immunosuppressed patients. In conclusion, patients with chronic liver disease, particularly cirrhosis, and liver transplant recipients, are vulnerable to severe COVID-19. Over the past year, several unique considerations have been highlighted across a spectrum of hepato-biliary diseases. Vaccination is strongly recommended for those with chronic liver disease and liver transplant recipients.