Viral hepatitis after liver transplantation: A brief overview

Table 1 Management of hepatitis B surface antigen positive recipients in setting of liver transplantation

Donor status	Recipient status	Management
HBsAg positive or anti-HBc positive	HBsAg positive	Lifelong antiviral treatment ± hepatitis B immunoglobulin1
	Anti-HBc positive	Lifelong antiviral treatment
	Anti-HBs titre ≥ 10 mIU/mL	No therapy required
	Anti-HBs titre < 10 mIU/mL	Booster dose and repeat titre after 1 month; Lifelong antiviral treatment if transplanted before achieving protective antibody titre

¹Detectable hepatitis B virus DNA levels at liver transplantation, hepatitis D virus co-infection, hepatocelular carcinoma liver transplantation, drug-resistant hepatitis B virus.

Anti-HBc: Hepatitis B core antibody; HBs: Hepatitis B surface; HBsAg: Hepatitis B surface antigen.

Table 2 Efficacy of directly acting antiviral based therapy in patients with hepatitis c virus related decompensated cirrhosis

Ref.	Patient population	SVR rates	Additional comments
Premkumar et al[44], 2024	1152 patients with DC (87% GT-3)	82%-90% with sofosbuvir + velpatasvir + ribavirin or sofosbuvir + daclatasvir + ribavirin	Probably the largest study showing effect of directly acting antivirals in DC and GT-3
Belperio et al[45], 2019	243 patients with GT-3 related DC	87.5%-100% in various arms with sofosbuvir + daclatasvir/velpatasvir with or without ribavirin	Higher SVR (up to 92%) in patients with compensated cirrhosis
Lim et al[46], 2018	667 patients with GT-1, 231 non-transplanted GT	87.5%-100% with ledipasvir + sofosbuvir with or without ribavirin	Higher SVR with compensated cirrhosis and in patients having normal bilirubin with high albumin
Manns et al[47], 2016	333 patients with DC, with GT-1 and 4	CTP-B: 87%-96%, CTP-C: 78%-85%	17 patients died during the study period
Poordad et al[48], 2016	60 patients with advanced cirrhosis	CTP-A: 93%, CTP-B: 93%, CTP-C: 56%, regimen used-sofosbuvir + daclatasvir + ribavirin	Presence of DC was a negative predictor of SVR
Reddy et al[49], 2017	240 patients with model for end stage liver disease score more than 10	35%-84% with sofosbuvir + simeprevir + ribavirin or sosfosbuvir + ribavirin	Low SVR rates with GT-1a; SVR only 35% with GT-3
Curry et al[50], 2015	267 patients with DC, GT-3: 13%, GT-1: 75%	Sofosbuvir + velpatasvir-24 weeks (86%), sofosbuvir + velpatasvir-12 weeks (83%), sofosbuvir + velpatasvir + ribavirin (94%)	Serious adverse events in 16%-19%
Charlton et al[51], 2015	337 DC patients with GT-1	86%-89% with sofosbuvir + ledipasvir + ribavirin for 12-24 weeks	All but 1 patient with GT-1

CTP: Child-Turcotte-Pugh; DC: Decompensated cirrhosis; GT: Genotype; SVR: Sustained viral response.

Table 3 Pros and cons of treatment of hepatitis C virus related decompensated cirrhosis with directly acting antivirals

Pros of treatment	Cons of treatment with directly acting antivirals
Improvement of liver function with survival till LT	Slight improvement in MELD score may not be sufficient enough overall functional improvement
Some patients may get delisted from LT waiting list	Due to lower MELD score patients may not get a liver timely
Only option of treatment for patients not opting for LT	Sustained viral response rate may be lower in patients with decompensated cirrhosis
Reduced rate of recurrence after LT	Some patients may die during therapy
Less risk of recurrent cirrhosis due to hepatitis C virus

LT: Liver transplantation; MELD: Model for end stage liver disease.

Table 4 Comparison of various genotypes of hepatitis E virus in the setting of liver transplantation

Characteristics	GT-1	GT-2	GT-3	GT-4
No of patients with LT	6 patients	None reported	Most commonly reported GT in post-LT setting	2 case reports
Mean age	42 years	NA	Mostly in 40 years; rarely in 20-30 years of age	68
Country of origin	India	NA	Europe/South America/United States/Japan	United States
Chronicity of illness	None	NA	Yes	Patients developed fibrosis/cirrhosis

GT: Genotype; LT: Liver transplantation; NA: Not available.

Table 5 Risk factors for cytomegalovirus infection in liver transplantation recipients

Risk factors of CMV infection in LT patients
CMV sero-negative status
High dose maintenance immunosuppression
Use of lymphocyte depleting agents like anti-thymocyte globulin, alemtuzumab and muromonab
LT recipients more than kidney transplant recipients
Donor/recipient advanced age
Human leukocyte antigen mismatch
Immediate graft rejection
Impaired humoral immunity
Co-infection with other herpes virus

CMV: Cytomegalovirus; LT: Liver transplantation.

Table 6 Evolution of classification system for post transplantation lymphoproliferative disorder

2017 World Health Organization Classification	2022 International consensus classification
Non-destructive PTLD	Hyperplasia arising at the time of immune deficiency/immune dysregulation
Polymorphic PTLD	Polymorphic lymphoproliferative disorder arising at the time of immune deficiency/dysregulation
Monomorphic PTLD	Lymphomas arising during immune-deficiency or dysregulation
Classic Hodgkin’s lymphoma PTLD

PTLD: Post-transplant lymphoproliferative disorders.