1. Hepatitis A

Sven Pischke, Heiner Wedemeyer

Epidemiology

Virology and diagnostics

Natural process and surveillance

Therapy

References

2. Hepatitis B – treatment

Heinrich Rodemerk, Thomas Berg, Florian van Bömmel

Introduction

Treatment goals (Why treat?)

Forms of cure and therapeutic endpoints

Indication for antiviral therapy (Who to treat?)

Acute hepatitis B

Chronic hepatitis B

Treatment of HBV infections in special populations

Treatment options and choice (How to treat?)

Interferons

Nucleoside and nucleotide analogues

Choosing the right treatment option

Combination therapy

Management of HBV resistance

Treatment Monitoring
(How to monitor treatment?)

Baseline

Under therapy

HCC risk

Prognostic factors and treatment response

Treatment cessation (When to stop?)

Treatment duration and stopping rules

Patients with HBsAg loss

HBeAg seroconversion

HBeAg-negative patients with detectable HBsAg

Who is eligible for a stopping NA?

PEG-IFN

Outlook

New parameters for treatment monitoring

New therapeutic strategies

References

3. Hepatitis C

Christoph Sarrazin, Christiana Graf

Epidemiology

Global occurrence

Transmission

Clinical presentation and natural history of HCV infection

Recently acquired HCV infection

Chronic HCV infection

Diagnosis

Management of HCV infection

Indications for treatment: who should be treated?

Endpoint of HCV therapy

Pretherapeutic assessment of patients

Direct-acting antiviral therapy

Management of HCV in special epidemiological groups

HCV treatment in children and adolescents

HCV treatment in pregnancy

HCV treatment in people with hepatocellular carcinoma

Post-treatment surveillance

Remaining challenges

Treatment of patients with virological failure after pan-genotypic DAA therapy

Treatment of patients with decompensated liver disease

Treatment of patients with rare HCV subtypes

References

4. Hepatitis D – diagnosis and treatment

Lisa Sandmann, Heiner Wedemeyer, Markus Cornberg

Introduction

Virology of HDV

Epidemiology of HDV

Pathogenesis of HDV

Clinical course of HDV

Acute HBV/HDV coinfection

Chronic HDV infection

Diagnosis of HDV

Treatment of HDV

Bulevirtide

Pegylated interferon alfa

Nucleoside and nucleotide analogues

New drugs against HDV in clinical development

Liver transplantation for HDV

Summary and outlook

References

5. Hepatitis E

Sven Pischke, Katja Dinkelborg, Patrick Behrendt

Epidemiology

Diagnostic

Acute hepatitis E in immunocompetent individuals

Acute and chronic HEV infections in organ transplant recipients

Hepatitis E in patients with HIV infection or other immunological deficiencies

Extrahepatic manifestations of hepatitis E

Therapy and prevention

Conclusions and recommendations

Key Messages

References

6. Viral hepatitis and HIV coinfection

6.1 Management of HBV/HIV coinfection

Stefan Mauss, Kathrin van Bremen

Abstract

Introduction

Treatment of chronic hepatitis B in HBV/HIV coinfected patients on antiretroviral therapy

Conclusion

Key messages

References

6.2 Hepatitis C virus and HIV coinfection

Stefan Mauss, Jürgen Kurt Rockstroh, Christoph Boesecke

Short history of HCV/HIV-coinfection

Specifics of the clinical course of hepatitis C in HIV coinfected patients

Treatment of hepatitis C in patients with HIV coinfection

Aspects to be considered before the start of therapy

Treatment of HCV in HIV coinfection

Treatment of recently acquired HCV in HIV

Management of liver cirrhosis and liver transplantation in people with HCV/HIV coinfection

References

7. Prophylaxis and vaccination against viral hepatitis

Heiner Wedemeyer, Lea Marie Bartsch

Abstract

Introduction

Prophylaxis of hepatitis viruses

Hepatitis A and E virus

Hepatitis B and D virus

Vaccination against HAV

Vaccination against HBV

Efficacy of vaccination against HBV

Post-exposure prophylaxis

Safety of HBV vaccines

Long-term immunogenicity of HBV vaccination

Prevention of vertical HBV transmission

Vaccine development

Vaccination against HCV

Vaccination against HEV

Outlook

References

8. Grading and staging of liver diseases

Mireen Friedrich-Rust, Frank Grünhage

9. MAFLD / MASH

Andreas Geier, Elke Roeb

Summary

Introduction

Prevalence

Demographics and risk factors

Pathogenesis

Human genetic factors

Microbiome

Natural history

Screening

Diagnosis

Therapy

a) Diet, physical exercise and lifestyle recommendations

b) Alcohol and coffee, stimulants

c) Pharmacological treatment

d) Novel pharmacological approaches

e) Modification of the intestinal microbiome

f) Bariatric Surgery

g) Liver transplantation for MASH

Follow-up of MASLD and MASH patients

References

10. Genetic liver diseases

10.1 Haemochromatosis

Claus Niederau

Abstract

Definition and classification of iron overload diseases

Type 1 HFE haemochromatosis

History

Epidemiology

Aetiology and pathogenesis

Diagnosis

Early diagnosis and screening

Complications of iron overload

Therapy

Prognosis

Juvenile hereditary haemochromatosis

Transferrin receptor 2 (TFR2)-related type 3 haemochromatosis

Type 4 haemochromatosis – Ferroportin Disease

Secondary haemochromatosis

Pathophysiology

Use of blood from patients with HFE haemochromatosis (type 1) for blood donation

Key messages and future directions

References

10.2 Wilson disease

Uta Merle

Abstract

Introduction

Aetiology and pathogenesis

Clinical presentation

Hepatic presentation

Acute liver failure

Neuropsychiatric presentation

Other manifestations

Diagnostic findings

Kayser-Fleischer rings

Serum ceruloplasmin

Total serum copper and relative exchangeable serum copper

Urinary copper excretion

Liver biopsy

Genetic studies

Other diagnostic tests

Family screening

Prognosis

Treatment

Medical treatment

D-penicillamine

Triethylentetramine / Trientine

Zinc salts

Tetrathiomolybdate

Monitoring of treatment

Liver transplantation

Key messages

Future directions

References

10.3 Cholestatic syndroms

Verena Keitel

10.4 Alpha-1 antitrypsin deficiency

Michelle Walkenhaus, Pavel Strnad

Abstract

Background

Pi*ZZ

Adult liver

Paediatric liver

Lung

Others

Pi*MZ

Liver

Lung

Rare associations

Less common genotypes

Therapeutic approaches for AATD-related liver disease

Key messages

Future directions

References

11. AIH

Christian Strassburg

12. Primary sclerosing cholangitis

Tobias J. Weismüller

Introduction

Diagnosis of PSC

Variant Syndromes and secondary causes of sclerosing cholangitis

Clinical course of PSC and risk assessment

PSC and IBD

PSC as a risk factor for hepatobiliary malignancies

Role of surveillance strategies

Medical treatment

Endoscopic treatment

Liver transplantation for PSC

References

13. Primary biliary cholangitis

Heike Bantel, Andreas E. Kremer

Abstract

Introduction

Pathophysiology

Diagnosis of PBC

PBC-associated symptoms

Extrahepatic immune-mediated diseases in PBC

Risk factors of PBC progression and prognosis

Risk stratification of PBC patients by liver stiffness measurement

Hepatocellular carcinoma risk and surveillance in PBC

Therapeutic options in PBC

First-line therapy

Second-line therapy

Extrahepatic manifestations and quality of life

Pruritus

Fatigue

Sicca symptoms

Bone health: osteopenia and osteoporosis

Cholestasis and nutritional advice

Outlook

Key Messages

References

14. Alcohol-associated hepatitis

Julian Allgeier, Claus Niederau, Johannes Sauter, Christian M. Lange

Harmful alcohol use and its global burden

Pathogenesis of alcohol-related liver disease (ALD)

(1) Direct hepatic injury mediated by ethanol

(2) The gut-liver axis

(3) Genetic factors

Diagnosis

Criteria for diagnosis of alcoholic hepatitis

Predictive modeling and indication for therapy

ABIC uses the following equations for calculation:

Therapy

(1) Corticosteroids

(2) Pentoxifylline

(3) TNF-α inhibition

(4) N-acetyl cysteine (NAC) and other antioxidants

(5) G-CSF

(6) Nutrition and supportive therapy

(7) Liver transplantation (LT)

(8) Miscellaneous and emerging therapy options

(9) AUD and abstinence

Summary

References

15. Vascular liver disease

Matthias J. Bahr

Disorders of the hepatic sinusoid

Sinusoidal obstruction syndrome (Hepatic veno-occlusive disease)

Peliosis hepatis

Disorders of the hepatic artery

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)

Disorders of the portal vein

Portal vein thrombosis

Porto-sinusoidal vascular disease (PSVD)

Disorders of the hepatic veins

Budd-Chiari syndrome

References

16. Acute liver failure

Akif Altinbas, Josef Pospiech, Ali Canbay

Introduction

Epidemiology

General standard of care

Aetiology specific approach

Drug-induced

Viral hepatitis

Autoimmune related

Amanita intoxication

Wilson disease

Acute fatty liver of pregnancy

Budd- Chiari syndrome

Liver transplantation

References

17. Complications of liver cirrhosis

Jonel Trebicka, Ben Maasoumy

18. Diagnosis, prognosis & therapy of hepatocellular carcinoma

Ursula Ehmer, Jens U. Marquardt

Summary

Epidemiology, Screening and Prevention

Surveillance of patients at high risk

Diagnosis of hepatocellular carcinoma

Clinical presentation

Imaging-based diagnosis

Histology and biomarkers

Classification of HCC

Treatment allocation according to the BCLC staging system

Curative treatment approach in BCLC stages 0-A

Surgical resection

Liver transplantation

Ablation

Adjuvant therapy

Locoregional therapies in BCLC stages B and C

TACE and DEB-TACE

Transarterial Radioembolisation (TARE)

Stereotactic body radiation therapy (SBRT)

Systemic therapy in BCLC stage C

Historic view on systemic treatment options – the era of multi-tyrosine kinase inhibitorsSorafenib – The gold standard in first-line therapy for more than 10 years

Lenvatinib – REFLECT Trial

Compounds in first-line treatment with no therapeutic benefits in phase 3 trials

A new era of therapies – first-line immunotherapy with checkpoint inhibitor monotherapy and combination therapy.

Second-Line TherapiesRegorafenib – RESORCE Trial

Cabozantinib – CELESTIAL Trial

Ramucirumab – REACH-

Second-line checkpoint inhibitor monotherapy and combination therapy

Supportive therapy in end-stage liver disease – BCLC stage D

Key points

References

19. Transplant hepatology: a comprehensive update

S. Beckebaum, V. R. Cicinnati, A. Radtke

Abstract

Introduction

Timing and indications for liver transplantation

Patient evaluation

Pretransplant management issues

Waiting list monitoring of patients with ALD

Waiting list monitoring of hepatitis B liver transplant candidates

Waiting list monitoring and treatment of hepatitis C liver transplant candidates

Adjunct treatment and staging of HCC transplant candidates

Liver transplantation in autoimmune hepatitis and cholestatic liver diseases

Living donor liver transplantation: indications, donor evaluation, and outcome

Perioperative complications

Long-term complications after liver transplantation

Opportunistic infections

Hepatitis E

Chronic rejection (TCMR and AMR)

Calcineurin inhibitor-induced nephrotoxicity and alternative immunosuppressive protocols

Other side effects of CNI

Corticosteroid minimisation/avoidance protocols and additional strategies to reduce metabolic complications

De novo malignancies

Biliary complications

Metabolic bone disease

Recurrent diseases after liver transplantation

Pregnancy after liver transplantation

Experiences with liver transplantation in inherited metabolic liver diseases in adult patients

Outcome after liver transplantation for acute and acute-on-chronic liver failure

Conclusion

References

20. Nutrition and liver diseases

Katharina Hupa-Breier, Andrea Schneider

Abstract

Introduction

Screening and assessment of nutritional status

Screening and Baseline assessment for malnutrition and obesity

Nutrition Screening Tools

Expanded Nutritional Assessment

Nutritional Management

Therapy of malnutrition

Energy requirements

Nutrient requirements

Nutrition and liver transplantation

Before Liver transplantation

After liver transplantation

Immunosuppression

Conclusion

Nutrition associated liver injury, NALI

Liver damage caused by medical nutrition

Prevention and treatment of NALI

References