What’s New in Hepatology?

What’s New in
Hepatology
By
Prof. Sherif Mogawer
Cairo University

NAFLD 30%
Virus 30%
Alcohol 30%
Others 10%
Compensated C
Decompansated C
Encephalopathy
Infections / Bleeding
Ascites / Jaundice
50% in 5y 50% in 5y
Death
Liver Cancer

Hepatitis

HCV
- Can be cured
- Cured associated with disease
reversion
- Debatable points in follow up of cured
HCV

Disease Reversion & Point
of no Return
(Van de Meer & Berengeuer J Hepat 2016)

• 53 Chronic HCV naïve Egyptian patients
were treated in outpatient clinic with
Sofosbuvir 400 mg + Daclatasvir 60 mg +
weight based Ribavirin for 12 weeks
• 44% were male with average age 48y, 56 %
were female with average age 44 y.
• Patients were followed at 12 & 24 weeks
following end of treatment

• Fib 4: - 15 Patients were > 3.2 (F3-4)
- 38 patients were > 1.4 &

Cure Associated Benefits

3.1
0 12 w

Eradication of HCV can result in
real benefits
(Belli et al., J Hepatology 2016)

Fibrosis Regression among
Patients Achieving SVR
- 100 Patients followed twice/year with
Fibroscan for 2.5-3 years
- 82% of patients received DAAs, 45% Sofobased
therapy
- Overall Improvement in 60% of
patients achieving SVR
(Crissien et al., Abstract 108, AASLD 2015)

Improvement of Liver stiffness
values by successful INF-Free
Regimen: “Fibroscan”
(Deterding et al., Aliment Pharacol Therap 2016)

MELD Changes during INFfree
treatment & Follow up

SOLAR 2 study Ledi/Sofo/Riba
MELD changes from baseline to F.U 4
(Manns et al., Lancet Inf. Dis 2016)

Improvement of MELD score from
baseline to F.U 12
(Child B/C) n = 31
Point of no return
Future research
No=7
- 8 - 7 - 6 - 5 - 4 - 3 - 2 - 1 0 1 2
Including relapse patients documented at the time point of
relapse
(Deterding et al., Aliment Pharacol Therap 2015)

Sofo & Valpatsvir (ASTRAL 4 Study)
Improvement in MELD in
Decompansated Cirrhosis Patients
(Curry et al., N Engl J. Med 2015)

HCC is Left as a debatable
Point

HCC Development
Risk of HCC during INF-free
Therapy of HCV Infection
Untreated
De novo HCC vs. HCC Recurrence
INF-Free Therapy

HCC Recurrence
307 Patients treated for HCC occurring in 14,379
patients with past or active HCV
40 patients with progressive
or early recurrence of HCC
267 Patients with history of
treatment for HCC
DAA group
N= 189
Untreated group
N = 780
Recurrence 16
8.4%
No recurrence 165
Recurrence 16
20%
No recurrence
62
(Pol S et al., J Hepatol 2016)

De novo HCC 3-5%
Unexpected high rate of Recurrence 8%
“HCC developed after a median of 3.5
months”
(Reig et al., J Hepaol 2016)

Does Eradication of HCV increase
the risk of HCC
Yes…..

(J of Hepatology 2016)

NO……
(J of Hepatology 2016)

HEV

HEV
- Becoming a well recognized cause of
acute hepatitis
- Transmission from human to human by
both feco-roal & parenteral routes
- From animal to human

Emerging Epidemic of HEV
(Adlhoch et al., J of Virology 2016)

HBV
Strategies to develop cure

Aiming for Cure in HBV & HDV
Infections

Different Anti-HBV Drugs in
Different Phases

NASH

NASH
• Fibrosis is the determinant factor of
mortality in NAFLD
• Over-weight children are most likely to
develop NAFLD
• How to achieve an accurate diagnosis.
• Clinical trials & therapeutic targets
• Obeticholic acid succeeded in phase 2b
studies

Fibrosis Stage is the Main Predictor for
Disease Specific Mortality
2
(Mattias Ekstedi, Hepatology 2015)

Overweight in Late Adolescence
Predicts development of severe liver
disease later in life: A 39 years follow
up Study
(Hannes Hagstrom et al., J Hepatol 2016)

MRI & MRE for Non-invasive Quantitative
Assessment of Hepatic Steatosis & Fibrosis in
NAFLD & NASH: Clinical trials to Clinical
Practice
(Parambir S. Dulai et al., J Hepatol 2016)

Farnesoid X nuclear receptor Ligand Obeticholic
acid for non-Cirrhotic, NASH (FLINT): a
multicenter, randomized, placebo-controlled trial
(Lancet 2016)

Primary Biliary Cholangitis

Primary Biliary Cholangitis
• Primary biliary cirrhosis changes name to
Primary Biliary Cholangitis
• Obeticholic acid meets primary end point
in phase 2b studies & is approved

A Placebo Controlled Trial of
Obeticholic acid in Primary Biliary
Cholangitis
(New Engl J Med 2016)

Alcoholic Liver Disease

Alcoholic Liver Disease
• Genetic signature of patients likely to
develop alcoholic cirrhosis discovered

Identification of gene signature
determining risk of development of
alcoholic cirrhosis
• Why only a small
proportion of patients
that abuse alcohol
develop cirrhosis?
• A genome wide
association study
confirms PNPLA3
,TM6SF2 and MBOAT7
as risk loci for alcoholrelated
cirrhosis
(Buch et al., Nature Genetics 2015)

Cirrhosis

Cirrhosis
• Established diagnostic & Prognostic
criteria of acute on top of chronic liver
failure
• CLIF score validation
• Utilization of CLIF score for risk
stratification of patients with acute
deterioration

Acute on Chronic Liver Failure
(Jalan et al., Gastro 2014)

What is the Prognosis of
Individual Patients

How Can We Use the Score to help
patient Management?
Admission of cirrhotic patient with acute decompansation
Assess CLIF Score for diagnosis of ACLF
ACLF Present
CLIF-C ACLF Score (0-100)
ACLF Absent
CLIF-C AD Score (0-100)
CLIF AD score
≥ 60 High Risk
CLIF AD score>45

Hepatocellular Carcinoma

Hepatocellular Carcinoma
• Regorafenib: a new therapy for HCC
• HCC after HCV recurrence: a growing
concern & controversy

New Therapies for HCC

Resorce Trial for HCC
(Bruix et al., ECOS abstract 2016)

• 573 patients (BCLC) B or C randomized
from 21 countries
• On sorafenib ≥400 mg/day ≥20 days.
• Documented radiological progression.
• The primary endpoint was overall survival
(OS) was analyzed by intent-to-treat.

Death & Progression risk
• Regorafenib showed a 38% reduction in
death risk and a 54% reduction in
progression risk compared to placebo.
Median time to progression
• 3.1 months with Regorafenib and 1.5
months with placebo
Overall survival
• Median overall survival was 10.6 months
for Regorafenib and 7.8 months with
placebo.

The Microbiome
• The microbiome may dictate effects on
liver injury

Alteration of human gut
microbiome in liver cirrhosis
(Nature 2014)

How will you Eliminate the Virus?
(Feld and Foster J. Hepatol 2016)

Progression of patients with acute on
chronic liver failure: a prospective cohort
study
(Critical care 2012)